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This is to certify that the

dissertation entitled

DESIGN AND DEVELOPMENT OF A BEAM DEFIECI‘ION
TIME—OF—FLIGHT MASS SPECI'ROPETER:
APPLICATIONS IN GAS CHRWA'IWRAPHY/HASS SPFIITRGIETRY
AND POTASSIUM ION ION IZATION 0F DESORBED SPECIES

presented by

Gary Allen Schultz

has been accepted towards fulfillment
of the requirements for

Ph . D . degree in Chemistry

Major professor

/
Date October 8, 1991

MS U is an Affirmatiw Action/Equal Opportunity Institution 0-12771

 

 

 

 

 

 

 

 

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MSU In An Affirmetlve Action/Equal Opportunlty Indltutlon
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DESIGN AND DEVELOPMENT OF A BEAM DEFLECTION
TIME-OF-FLIGHT MASS SPECTROMETER:
APPLICATIONS IN GAS CHROMATOGRAPHY /MASS SPECTROMETRY
AND POTASSIUM ION IONIZATION OF DESORBED SPECIES

By

Gary Allen Schultz

A DISSERTATION
Submitted to
Michigan State University
in partial fulfillment of the requirements
for the degree of

DOCTOR OF PHILOSOPHY

Department of Chemistry
1991

ABSTRACT

DESIGN AND DEVELOPMENT OF A BEAM DEFLECTION
TIME-OF-FLIGHT MASS SPECTROMETER:
APPLICATIONS IN GAS CHROMATOGRAPHY /MASS SPECTROMETRY
AND POTASSIUM ION IONIZATION OF DESORBED SPECIES

By

Gary Allen Schultz

A beam deflection time-of-flight mass spectrometer (BDTOF-MS) has
been developed in conjunction with an integrating transient recorder (ITR)
to provide time array detection (TAD). This beam defection system is the
first to incorporate two pulses to form ion packets by applying a voltage
pulse to each of two parallel deflection plates. The pulses are held at two
different potentials, and by reversal of the potentials applied to each plate,
an ion packet is produced at the time during which the electric field
between the deflection plates is zero. This method of beam deflection
produces a resolving power of m/Am of 1400 at m/z 132 corresponding to the
nominal atomic mass of xenon. The resolving power achieved by this
procedure is better than unit resolution over the mass-to-charge ratio range

of20 to 749 11.

Gas Chromatography/Mass Spectrometry data were acquired during
the analysis of a trimethylsilyl derivatized mixture of urinary organic acids

at 1 and N 10 scans-per-second to show improvements in the

chromatographic information available from the reconstructed total ion
current (RTIC) chromatograms generated at higher mass spectral
acquisition rates. The RTIC chromatogram available from the mass
spectral acquisition rate of 10 mass spectra/second is shown to be
comparable to the profile obtained from a flame ionization detector in
representing the chromatography performed under identical experimental
parameters. The advantages of the higher mass spectral acquisition rate
in representing the chromatographic profile and in allowing mass spectral
data to be obtained for components in a complex ‘mixture that are

unresolved chromatographically are described.

The Desorption/Ionization technique, potassium ion ionization of
desorbed species (K+IDS), developed in this laboratory, uses thermionic
emitters as sources of alkali ions for attachment to thermally-desorbed
analyte molecules and fragments. This technique produces analyte ion
currents for periods of time ranging from one second to many seconds, with
the mass spectral information available rapidly changing due to the
temperature gradient produced by the heating of the sample by the
"potassium glass". A preliminary investigation of K+IDS has been
performed using the BDTOF mass spectrometer/1TB. Studies were
performed to determine the effects of the accelerating voltage penetration
into the ion volume of the ion source on the extent of conversion of gas phase
K+ to gas phase (analyte + K+) by placing a wire grid across the ion volume
exit slit. An increase in extent of conversion with the grid in the ion source

is shown to be approximately a factor of 15.

This dissertation is dedicated to my family,
especially my sister, Lori, who inspired me to achieve

iv

ACKNOWLEDGMENTS

I would like to thank Dr. John Allison for taking me on as a graduate
student. I am known as a stubborn person and know that advising me was
challenging if not outright difficult at times. John is a person that I admire
and respect as an advisor and a friend. Throughout this journey, he has
made himself available to me whenever I needed help and advice, both
professional and personal. I look forward to further interactions with him
throughout my professional career and life.

Dr. Watson has also been instrumental in my development as a
scientist and a person. He has opened my eyes to a greater understanding
to what it takes to be a professional. He would always politely correct any
errors in speech that I would utter, not to critize, but to make me aware of

them so that I may better myself as a person. For this, I am very greatful.

This project would not have been successful without the help of a very
good friend and colleague, Marty Rabb. Marty designed and built much of
the intricate and complex electronics and pulsing circuitry for this project.
I went to him with what appeared to be impossible requests and he always
came through with what I needed. This department will be at a great loss
when he retires. Over the years of close association with Marty, I have had
the opportunity to get to know him as a friend. We have had numerous
discussions about our experiences in life and I have learned much from

this man. Marty, I will indeed miss you!

I would like to thank the staff at the Mass Spectrometry Facility for
there help. Bev has been a friend and someone that I respect as a person.
She is one of the most genuinely nice persons that I have ever met or expect
to ever meet in my life and I will miss her. Mike has provided much
assistance and humor along the way. Mel, Betty and Melinda have all been
good friends. Kevin has been a friend and provided me with every program
that I have requested. He alone has been the life support for the TOF group.

Of course, I cannot forget all of the friends that I have met here at
Michigan State. My first two years here at MSU, living in the 'Chem
House' on Spartan Ave, were anything but boring. Halloween parties at the
Chem House were like no other. Jeff, Jim, Mike and I would be sitting
around the Chem House talking, wondering what we were going to do for
the evening and many times would end up at our favorite establishment at
the time, Mac's. We were persuaded many times by Mark and Kris to
make this trip. Here we met many friends, and for me, many good natured
people. Of course, Mac's attracted all types. My times playing pool with
Jeff T., singing every song on the jukebox, being excused from this fine
establishment, etc. will remain with me always. My friendship with Dan
has been close over the years. How two of the most stubborn people I know
could remain friends like we have, I don't know. This is a friendship that
will last a lifetime.

There are so many other friends that were gained in my later years,
Judy, Karen, Jon, Dave G., Laura, Ron, Dave W., Ed, Jason, Kurt, and
many, many more. All of them hold a special place in my heart and I will

remember them always. Remember, the world is a very small place.

TABLE OF CONTENTS

LIST OF TABLES ............................................................................. xi

LIST OF FIGURES ........................................................................... xii
Chapter 1 - Introduction .................................................................... 1

Chapter 2 - Developments In 'I‘ime-Of-Flight Mass Spectrometry ........... 19

Chapter 3 - Design of BDTOF Mass Spectrometer ................................. E

A. Ion Source .......................................................................... fl

1. Dupont 21-491B ion source ............................................ 11)

2. JEOL DM303 ion source ............................................... 31

B. Gas chromatography interface .............................................. 37

C. Beam Deflection Assembly .................................................... 37

1. Deflection Plate Geometries .......................................... 38

2. Beam Deflection Methods ............................................. 40

D. Detectors ............................................................................ 43

1. Galileo FTD-2003 ......................................................... 43

a. Standard multichannel plates ............................. 46

b. High output technology multichannel plates ......... 46

2. Becton Dickinson MM-l-lSG electron multiplier ............. 47

E. Detector Slit Assembly .......................................................... 48
F. Preamplifiers ...................................................................... 48
1. Comlinear .................................................................. 48

2. "in-house" .................................................................. 50

G. Ion Focus Assembly ............................................................ 51
H. Vacuum System .................................................................. 54
1. Integrating Transient Recorder ............................................. 56

J. Comparison of BEDER-TOF and BDTOF Mass
Spectrometers ......................................................................... 57

Chapter 4 - Gas Chromatography/Beam Deflection Time-Of-Flight

Mass Spectrometry ........................................................................... 61
A. Grob programmed test mixture ............................................ 62

1. Experimental .............................................................. &

2. Reconstructed Total Ion Current Chromatograms .......... 63

a. Comparison of 1 and 20 scans/second ................... 63

viii

b. Deconvolution of closely eluting components .......... 64
c. Limits of Detection .............................................. 70

B. Complex mixture analysis of TMS-derivatized organic acids

of urine .................................................................................. 71
1. Background ................................................................ 71
2. Experimental .............................................................. 72

3. Chromatographic Profiles from the GC/FID and

GC/BDTOF mass spectrometer/ITR .................................. 73
4. Mass Spectral Deconvolution ........................................ 79
5. Three-dimensional data presentation ............................ 91
6. Conclusions ................................................................ 93
Chapter 5 - Potassium Ion Ionization of Desorbed Species (K+IDS) .6 ........ %
A. Background ........................................................................ %
B. Experimental ...................................................................... 101
1. K+IDS probe design ..................................................... 101
2. Electronic circuit modifications .................................... 102
B. K+IDS by TOF-MS ................................................................ 103
1. Grided versus Gridless Ion Source ................................ 1(5

ix

Experimental ........................................................ 1(B

Results ................................................................. 107

2. MK+ abundance versus pressure .................................. 114

B. K+IDS spectra ..................................................................... 116

1. Polyethylene Glycol (PEG) 600 ....................................... 117

2. PEG 750 ...................................................................... 1%

C. Current limitations of K+IDS by BDTOF-MS ........................... 1%
Appendix I ...................................................................................... 13)

Mass spectra of selected compounds using the BDTOF mass
spectrometer ........................................................................... 130

Appendix II ..................................................................................... 138

"Beam Deflection for Temporal Encoding in Time-of-Flight
Mass Spectrometry", Yefchak, G. E., Schultz, G. A., Allison,
J ., Holland, J. F. and Enke, C. G., J. Am. Soc. Mass
Spectrum, 1, 440 (1990).

Appendix III ................................................................................... 146

"Renaissance of gas chromatography-time-of-flight mass
spectrometry", Watson, J. T., Schultz, G. A., Tecklenburg, R.
E., Jr. and Allison, J ., J. Chromatogr., 518, 283 (1990).

Table 3.1

Table 3.2

Table 3.3

Table 4. 1

Table 4.2

Table 5.1

Table 5.2

Table 5.3

LIST OF TABLES

Upper and lower electrical connections on Dupont ion
source housing for JEOL DM303 ion source.

Connector (amphenol) pin numbering for JEOL DM303
ion source voltages and ion source elements along with
those of the original Old Hirose connector used by JEOL.

Pin numbering on T-tube flange of flight tube for beam
defection assembly and ion focussing assembly.

Components in methylene chloride for the Grob
programmed test mixture in the order of elution.

TMS-derivatized urinary organic acids with a relative
response greater than 2 ug/mg creatinine.

Average intensity of K+ isotope at m/z 41 and (acetone +
K)+ at m/z 97 for various partial pressures of acetone in a
gridless ion source.

Average intensity of K+ isotope peak at m/z 41 and
(acetone 4» K)+ at m/z 97 for various partial pressures of
acetone in a grided ion source.

Extent of conversion of palmitic acid versus background
pressure of triethylamine.

xi

51

76

112

112

115

Figure 1.1

Figure 1.2

Figure 1.3

Figure 1.4

LIST OF FIGURES

The initial spatial distribution of neutrals upon ion
formation gives rise to ions that acquire difierent final
energies. Ions formed with some initial energy will
attain final energies equal to their initial energy 4-
accelerating potential. The turn-around time is a
special aspect of the initial energy distribution where
two isomass ions with the same initial energy, one with
initial direction towards the detector and the other with
direction away from the detector. Both will leave the ion
source with the same final kinetic energy, but at
different times.

a) Schematic of beam deflection assembly located in the
flight tube directly after the exit slit of the ion source.
The beam deflection spacing and plate dimensions are
also given. b) The repetition rate of mass spectral
transient formation is 5kHz with pulse rise and fall
times of 10ns. During time period 1, the ion beam is
deflected downward. As the voltages applied to VA and
VB change during time period 2, the beam is swept
across the detector surface, resulting in a mass spectral
transient available for acquisition. The continuous ion
beam is deflected upward during time period 3.

Mass spectrum of Xenon showing mass resolution with
new beam deflection assembly of the BDTOF mass
spectrometer.

The BDTOF mass spectrometer operates with a mass
spectral transient generation rate of 5000s'1. The
summation of consecutive 5000 mass spectral transients
by the ITR results in a mass spectral acquisition rate of 1
mass spectrum/second.

xii

8

14

Figure 1.5

Figure 2.1

Figure 2.2.

Figure 3.1

Figure 3.2
Figure 3.3
Figure 3.4

Figure 3.5

Figure 3.6

Figure 3.7

Figure 3.8

Figure 3.9

The BDTOF mass spectrometer operates with a mass
spectral transient generation rate of 50°08'1. The
summation of consecutive 250 mass spectral transients
by the ITR results in a mass spectral acquisition rate of
20 mass spectra/second.

Wiley-McLaren ion source showing two extraction
fields, Es +Ed.

Plot showing ion flight times versus initial position of ion
in region 3 of a Wiley-McLaren ion source for three
isomass ions with different initial velocities. By waiting
for a time t, after ion formation and before ion
extraction, the flight time of the two isomass ions with
the same initial velocities but opposite direction can be
made to arrive at the detector simultaneously.

Schematic diagram of GC/BDTOF mass spectrometer
(not to scale). Shown are the ion source, flight tube,
beam deflection assembly, ion focus plates, detector and
integrating transient recorder.

Dupont 21-491B ion source.
JEOL DM303 ion source.

Electronic diagram of duplicate circuit for JEOL DM303
ion source.

Voltage divider for JEOL DM303 ion source. Provides
VA and First Focus 1 (left and right) voltages.

Electronic diagram of :tZOOV power supplies for DM303
ion source X-Y deflection plates.

Electronic diagram of beam deflection circuit. This
circuit provides two output pulses that alternate between
0 and 63 V at 5 kHz. The rise and fall times for each
pulse are adjustable as is the relative time at which each
pulse changes potential with respect to the other.

Galileo FTD-2003 and Johnston MM-l detector mounting
flange for‘ Bendix flight tube.

Voltage divider network for Galileo FTD-2003
channelplate detector.

xiii

17

31

Figure 3.10

Figure 3.11

Figure 3.12
Figure 3.13

Figure 3.14

Figure 3.15

Figure 3.16

Figure 4.1

Figure 4.2

Figure 4.3
Figure 4.4

Detector slit assembly for Bendix flight tube. Provides
for adjustable ion beam widths up to 0.50". This
assembly also contains necessary holes and mounting

threads for the Allison-group beam Visualizer.

Electronic circuit diagram for "in-house" preamplifier
built around two CLC404 high-slew rate operational

amplifiers. Rf= 501 Q and RE = 47 0.
Electronic circuit diagram for ion focus assembly.

T-tube flange showing pin numbers. Table 3. 1 contains
a list of the electrical connections to this flange.

Five-pin Molex pin connector for quick disconnects to
flight tube steering plates and ion lens.

Mass spectrum of perfluorotributylamine obtained on
the BDTOF mass spectrometer. Also shown are the raw
data points for the peaks at m/z 69 and at m/z 502.

Comparison of mass resolving power of the BEDER-TOF
and BDTOF mass spectrometers for the major ions in
the mass spectrum of perfluorotributylamine. The

resolution is based upon Am (or its equivalent, 2At) being
the full width of the peak at half its maximum height
(FWHM). The BEDER-TOF data are from reference 13.

Reconstructed TIC chromatogram generated from the
data base acquired at 1 scan/second of standard Grob test
mixture.

a) Comparison of RTIC chromatograms reconstructed
from the data bases acquired at 1 and 20 mass
spectra/second over the region of the chromatogram
between the arrows in Figure 4.1. b) RTIC
chromatogram is shown along with the mass
chromatograms of m/z 57 and m/z 122 available from the
20 mass spectral second data base.

Mass spectrum in scan a) 192, b) 159, and c) 240.

Complex mixture analysis of TMS-derivatized urinary
organic acids. Comparison of a) GC-FID response to
reconstructed total ion current chromatograms
generated from mass spectral acquisition rates of b) l
and c) 10 mass spectra/second.

xiv

50

74

Figure 4.5

Figure 4.6

Figure 4.7

Figure 4.8

Figure 4.9

Figure 4.10

Selected region of RTIC chromatogram generated from
mass spectral acquisition rates of a) 1 and b) 10 mass
spectra/second showing improved representation of
chromatographic profile at a higher mass spectral
acquisition rate.

Comparison of RTIC chromatograms at mass spectral
acquisition rates of a) 1 and b) 10 mass spectra/second
for a chromatographic doublet. c) mass chromatograms
at m/z 180 and at m/z 227 identifying two components.

Figure 4.7a shows the mass spectrum in scan 1197 that
has mass spectral information for both of the
components eluting over the peak profile shown in
Figure 4.6c. Figure 4.7b shows the mass spectrum in
scan 1220. The mass spectrum shown in Figure 4.7c is
the result of subtracting 43 % of the ion currents in scan
1220 from the corresponding ones in scan 1197.

Figure 4.8a is a region of the RTIC chromatogram
generated from the 10 scans/second data base. Figure
4.8b shows the mass chromatograms at m/z 189 (solid
line) and at m/z 210 (broken line). The difference in the
maxima of the two peaks indicates the presence of two
components. ~

Comparison of mass spectral data (Figures 4.9a-c) in
scans 1551, 1555, and 1557 over the peak profile in Figure
4.8. The changes in the relative intensities at m/z 189
and m/z 210 indicates the presence of more than one
component. Figure 4.9d is the mass spectrum resulting
from averaging scans 1560 to 1570. Figure 4.9e is the
mass spectrum resulting from averaging scans 1540 to
1550.

Figure 4.10a is a region of the RTIC chromatogram
generated from the data base acquired at 10
scans/second. Figure 4.10b shows the mass
chromatograms at m/z 174 (broken line) and at m/z 247
(solid line). The difference in the maxima of the two
mass chromatograms indicates the presence of two
components.

Figure 4.11

Figure 4.12

Figure 5.1

Figure 5.2

Figure 5.3

Figure 5.4

Figure 5.5

Figure 5.6

Comparison of mass spectral data (Figures a-c) in scans
1883, 1890, and 1899 over the peak profile in Figure 4.10.
Comparison of the mass spectral data in each scan
shown indicates that Figure 4.11a (scan 1883) represents
the first component in the peak profile, Figure 4.11b
(scan 1890) contains mass spectral data for both
components, and Figure 4.11c (scan 1899) is the mass
spectrum of the second component represented by the
poorly resolved doublet in Figure 4.10b.

3-dimensional plot of scan range 1870 to 1910 of data base
acquired at 10 mass spectra/second.

Previous K+IDS probe designs used on HP 5985 mass
spectrometer. First design used by Bombick used the
potassium emitter as a sample holder. Later design of
Kassel used separate wire sample holder for better
temporal overlap of potassium emission and sample
desorption. A 30-fold improvement in detection limits
result from the separation of the wire sample holder and
potassium emitter.

Total ion current and desorption profiles at m/z 41 and
m/z 295 for the K+IDS analysis of palmitic acid. Bead
current was 2.7 A at a mass spectral acquisition rate of
10 mass spectra/second.

K+IDS mass spectrum of palmitic acid with MK+ at m/z
295. This mass spectrum is the sum of scans 42 to 47
from Figure 5.2. Bead current was 2.7 A with a mass
spectral acquisition rate of 10 mass spectra/second.

K+IDS probe designed for HV ion source of BDTOF mass
spectrometer.

SIMION model of Dupont ion source with a repeller
voltage of 3005 V, ion volume exit slit voltage of 3000 V,
and focus lens voltage of 1000 V. Each electric field line
represents a change of 1 V. A penetration of 20 V into
the ion volume of the ion source is evident.

Desorption profiles of (M + K)+ at m/z 97 and K+ isotope
at m/z 41 for gridless ion source at 1.6 x 10'4 torr partial
pressure of acetone and reconstructed from the data
base acquired at 10 mass spectra/second.

Q

102

106

108

Figure 5.7

Figure 5.8

Figure 5.9

Figure 5.10

Figure 5.11

Figure 5.12

Figure 5.13

Figure 5.14

Figure 5.15

Desorption profiles of (M + K)t at m/z 97 and K+ isotope
at m/z 41 for grided ion source at 1.2 x 10'4 torr partial
pressure of acetone and reconstructed from the data
base acquired at 10 mass spectra/second.

K+ CI mass spectrum of acetone in the gridless ion
source at 1.6 x 10‘4 torr and reconstructed from the data
base acquired at 10 mass spectra/second. Bead current
is 2.6A.

K+ CI mass spectrum of acetone in the grided ion source
at 1.2 x 10'4 torr and reconstructed from the data base
acquired at 10 mass spectra/second. Bead current is
2.6A.

Plot of adduct ion peak intensity versus partial pressure
of acetone in the grided ion source. Shown is the
intensity of the potassium isotope at m/z 41 along with
the intensity of the acetone adduct ions at m/z 97, 155, 213
and the sum of the acetone adduct ion intensities.

Comparison of acetone adduct ion peak intensity to
potassium isotope peak intensity at m/z 41 for the grided
and gridless ion source. A factor of 15 improvement is
adduct formation is gained by using a grid in the ion
source.

Desorption profiles for oligomers with n = 5, 8, 11, 13, 16
and 19 for PEG 600. The current was 2.7 A for the
potassium carbonate support wire. The mass spectral
acquisition rate was 10 mass spectra/second.

Mass spectrum of PEG 600 from the sum of scans 40 to
50. The current was 2.7 A for the potassium carbonate
support wire. The mass spectral acquisition rate was 10
mass spectra/second.

Mass spectrum of PEG 600 from the sum of scans 50 to
60. The current was 2.7 A for the potassium carbonate
support wire. The mass spectral acquisition rate was 10
mass spectra/second.

Mass spectrum of PEG 600 from the sum of scans 70 to
80. The current was 2.7 A for the potassium carbonate
support wire. The mass spectral acquisition rate was 10
mass spectra/second.

xvii

110

113

114

121

Figure 5.16

Figure 5.17

Figure 5.18

Figure 5.19

Figure A.1
Figure A.2

Figure A.3

Figure A.4

Figure A.5

Figure A.6

Figure A.7

Figure A.8

Mass spectrum of PEG 600 from the sum of scans 40 to
80. The current was 2.7 A for the potassium carbonate

support wire. The mass spectral acquisition rate was 10

mass spectra/second.

PEG 600 mass spectrum showing low mass ions. Scan
rate is 10 mass spectra/second. Bead current is 2.6 A.
Average of scans 20 to 100. Peaks are labeled based on
Scheme I.

Raw data collected at 5ns time bins in flight time region
of m/z 585 of PEG 600.

K+IDS mass spectrum of PEG 750 from average of scans
50 to 80. Bead current of 2.6 A was used at a mass
spectral acquisition rate of 10 mass spectra/second.

Mass spectrum of methyl stearate by GC/MS.

EI mass spectrum of xenon with VA of 1000 V. Beam

deflection d spacing is 25 mm with no detector slit
assembly.

EI mass spectrum of xenon with VA of 1500 V. Beam
deflection d spacing is 25 mm with no detector slit
assembly.

EI mass spectrum of xenon with VA of 2200 V. Beam
deflection d spacing is 25 mm with no detector slit
assembly.

EI mass spectrum of xenon with VA of 1000 V. Beam
deflection d spacing is 25 mm with the detector slit
assembly adjusted to 5 mm.

EI mass spectrum of xenon with VA of 1500 V. Beam
deflection d spacing is 25 mm with the detector slit
assembly adjusted to 5 mm.

EI mass spectrum of xenon with VA of 2200 V. Beam
deflection d spacing is 25 mm with the detector slit
assembly adjusted to 5 mm.

K+IDS mass spectrum of the hexapeptide VGVAPG
(MW = 498 u) at 10 mass spectra/second.

xviii

E

‘35

131

Chapter 1 - Introduction

The coupling of a gas chromatograph to a mass spectrometer was first
demonstrated by Gohlke1 in 1959 using a time-of-flight (TOF) mass
spectrometer. The mass spectrum for each of the compounds in a mixture
was recorded by photographing the mass spectrum as it appeared on an
oscilloscope connected to the detector of the mass spectrometer. Since the
first demonstration of gas chromatography/mass spectrometry (GC/MS),
this technique has been responsible for advancements in many fields of
science. The analysis of mixtures by GC/MS can provide qualitative and
quantitative information for each component. GC/MS has contributed
greatly to structural determinations of classes of compounds by the method
of electron ionization (EI), which provides reproducible fragmentation

patterns.

Column technology has advanced over the years where, today, GC
columns are available that can provide hundreds of thousands of
theoretical plates. Peak widths of components eluting from these high
efficiency capillary columns are typically 2 seconds or less in duration,
allowing for the analysis of complex mixtures containing hundreds of
components in less than an hour. The successful application of this new
technology to GC/MS is directly related to the mass spectral acquisition rate
of the mass spectrometer. Chromatographic profiles are reconstructed by

summing the ion current at each m/z value acquired in each scan by the

mass spectrometer data system. The temporal profile of the intensity of this
summed ion current (the total ion current) is an indication as to the
amount of sample in the ion source during the acquisition of the mass
spectrum. A plot of the total ion current for each scan versus scan number
displays a reconstructed total ion current (RTIC) chromatogram that can
be used to identify the retention times for each of the components in a
mixture. The greater the mass spectral acquisition rate, the more
accurately the "true" chromatographic profile can be represented by the
RTIC chromatogram. With the chromatographic peak widths ever
decreasing in width due to increased capillary column performance, the
mass spectrometers currently used for GC/MS may limit the usefulness of
this new technology.

In the early 19808, a review was written on mass spectral acquisition
rates2 available with mass spectrometers commonly used in GC/MS,
namely, quadrupole and magnetic sector mass spectrometers. At that
time, the fastest mass spectral acquisition rate for a quadrupole was 4-8 Hz.
Scan rates for quadrupole mass spectrometers are restricted by the transit
time of the ions through the quadrupole filter. The rf and d.c. voltages for a
given m/z value cannot change significantly during the ion's transit time
through the quadrupole without serious degradation of the ion
transmission efficiency and mass resolution. This will always be the
ultimate limit on the scan rate of a quadrupole mass spectrometer. For a
magnetic sector mass spectrometer (both single and double-focussing mass
spectrometers), mass spectral acquisition rates are limited by the rate at
which the magnetic field can be swept to focus each m/z value at the
detector. Scan rates for a magnetic sector mass spectrometers were limited

3
to 0.1s/decade with 0.2s to reset the magnetic field, thus limiting the rates to
34 Hz.

Recently, improvements in quadrupole and magnetic mass
spectrometers have led to the development of mass spectrometers that can
attain mass spectral acquisition rates as high as 10 scans/second.3 The
Hewlett-Packard 5970B GC/Mass Selective Detector (HP 5970B GC/MSD) is
the state-of-the-art in quadrupole mass spectrometers used for GC/MS.
This mass spectrometer provides scanning rates up to 1500 u/second4 with
a maximum scan rate of 8 Hz and a mass-to—charge ratio (m/z) range of 1 to
800 11. Typically, mass spectral acquisition rates for these devices are 1 to 2

scans-per-second due to low signal intensity at higher scan rates.

In many GC/MS analyses, mass spectral acquisition rates of 1 to 2
mass spectra-per-second are sufficient. However, for the analysis of
complex mixtures where there are regions of the chromatogram that have
unresolved components, these relatively slow mass spectral acquisition
rates are not sufficient to accurately represent the chromatography
available from the gas chromatograph and also provide useful mass
spectra for each component. An additional limitation resulting from these
typical mass spectral acquisition rates for quadrupole and magnetic sector
mass spectrometers is a misrepresentation of the relative ion currents at
m/z values due to changes in partial pressure of the analyte during the
time necessary to acquire a mass spectrum. The resulting mass spectra
show a skewing of the relative mass spectral peak intensities, making

mass spectral interpretation and library searches difficult.

4

The ion trap mass spectrometer has recently been introduced to the
GC/MS market as a fast scanning, highly sensitive mass spectrometer.
The ion trap is based on the Quadrupole Ion Storage Device (QUISTOR)
consisting of a hyperbolic ring electrode and two end caps. By applying an
rf potential to the central ring, ions once formed are stored in the device.
Ions are formed by pulsing electrons into this region. Increasing the rf
potential applied to the central ring destabilizes ion trajectories in the
device from low to high m/z. Detection of the destabilized ions produces a
mass spectrum. The pulsed nature of ion formation and subsequent
storage of all ions until detection in the ion trap eliminates mass spectral

skew.

Varian5 has introduced the Saturn II GC/MS based on this
technology. This ion trap scans at a constant rate of 5600 u/second up to 650
u with a maximum scan rate of 9 scans-per-second from 30 to 650 u. The
Saturn II averages 3 "micro-scans" resulting in a scan rate of 3 useable
mass spectra/second. This scan rate can be increased by decreasing the
mass range to be scanned. A comparison of mass spectral skew between
the Saturn II and a benchtop quadrupole mass spectrometer was made
using a capillary column and collecting 8 scans over the chromatographic
peak of decafluorotriphenylphosphine (DFTPP).6 Each of the mass
spectrometers was scanned from 50 to 450 u. The ratio of two major ions of
DFTPP, m/z 198 and m/z 442 was compared for each of the 8 scans acquired
across the chromatographic peak. The quadrupole had a variation of the
ratio of m/z 198/442 of 50% (from 80% to 30%) indicating the presence of
mass spectral skew in the data. The ion trap had a variation of the ratio of
m/z 198/442 of 15% due to random noise in the mass spectra.

5
Time-of-flight mass spectrometry (TOF-MS) is another viable
alternative for GC/MS because the mass spectral generation rate of TOF
mass spectrometers can be as high as 25 kHzl. Ions are typically formed in
a TOF ion source by collision with electrons of energies up to 70 electron
volts (eV) and then application of an extraction potential, pushing or
pulling the ions out of the source. The ions are commonly accelerated to a

given energy and have flight times, t, defined by the following equation:

‘11 - , =1, _m_
fligttimet ZzeV

where L = the length of the flight tube(meters), m = the mass of the ion in
kg, e = 1.609 x 10’19 C, and V = the accelerating potential (volts). The flight
time for a given ion is related to the square root of its m/z value. A transient
mass spectrum is defined as the resulting ion currents at each m/z value

that reach the detector after a single extraction pulse.

Collection of a mass spectrum from a TOF mass spectrometer has
historically been accomplished by time-slice detection (TSD). TSD is
accomplished by incrementing the delay time of a time window
synchronized with the extraction pulse of the transient mass spectrum. In
transients produced at 10 kHz, for unit mass resolution up to 500 u, this
time window should be as narrow as 5 ns. Using TSD, acquisition of a
complete mass spectrum can take from 1 to 2 seconds or longer. The major
shortcoming in using TSD is that most of the available data from each

6
transient mass spectrum is ignored (only a single 5 ns time window is

acquired from each transient mass spectrum).

A data collection system that utilizes all of the ion currents available in
each transient mass spectrum would greatly improve the sensitivity of
TOF-MS. This type of data collection has been termed time-array detection
(TAD) and has been implemented at MSU. The development of the
integrating transient recorder (ITR)7 that digitizes mass spectral data at
ZOO-MHz, allows the continuous acquisition of the information in every one
of the mass spectral transients generated, providing a data system that
makes use of all of the available information afi'orded by TOF-MS. Figures
1.4 and 1.5 illustrate the capabilities of the ITR. The mass spectral
acquisition rate of the TOF mass spectrometer is determined by the number
of consecutive transient mass spectra integrated by successive summation.
This mass spectral acquisition rate can be adjusted to meet the needs of the

experiment.

Conventional TOF-MS, where ions are formed from gas phase
molecules with a pulsed electron beam and a pulsed extraction voltage,
suffers from poor mass resolving power. The initial spatial and energy
distributions of the ions in the ion source upon formation result in a broad
distribution of arrival times at the detector for isomass ion packets. Figure
1.1 is an illustration of the effects of each of these phenomena and their
contribution to peak broadening. The initial spatial distribution gives rise
to ions that are accelerated through different dimensions of an accelerating
field resulting in a distribution of kinetic energies and ion flight times to
the detector. Ions that are formed with some initial energy are going to

maintain that energy distribution upon acceleration producing a

7
distribution of flight times. A special aspect of the initial energy
distribution considers two ions with the same initial kinetic energy with
one ion having its kinetic energy in the direction of the detector and the
other ion having its kinetic energy directly away fi'om the detector. Upon
acceleration, both ions will leave the ion source with the same kinetic
energy, but the ion with initial kinetic energy away from the detector will
leave the ion source later in time. This has been termed the tum-around
time and can be corrected by time-lag focussing for narrow m/z ranges, but

is mass-dependent.

Conventional TOF-MS, with its mass-dependent focussing, has limited
applicability with a time array detector, such as the ITR, because all of the
ion current at each m/z value is not optimally focussed at the detector for
each source extraction. TOF mass spectra of unit resolving power can be
obtained using TSD in conjunction with time-lag focussing by
synchronizing the time window with the time-lag optimized for that m/z
value collected, but not at mass spectral acquisition rates suited for GC/MS.
Erickson, et. al.,8 determined that three difi‘erent values of time-lag would
be necessary to sufficiently represent the mass spectral information
available over a mass range from m/z 50 to 575 u using a Wiley/McLaren-
type TOF mass spectrometer.

One of the primary research goals of the Michigan State
University/National Institutes of Health Mass Spectrometry Facility is to
take advantage of the high mass spectral acquisition rates available with
TOF-MS and develop a GC/MS instrument based on a TOF mass
spectrometer in conjunction with TAD. Improvements in the mass

resolving power of TOF mass spectrometers would be necessary to provide

Phenomena limiting resolution in time-of-flight mass spectrometry

ion
source detector
initial 0; o 0
spatial 0 i0 0
spread O

 

 

Figure 1.1 The initial spatial distribution of neutrals upon
ion formation gives rise to ions that acquire different final
energies. Ions formed with some initial energy will attain
final energies equal to their initial energy + accelerating
potential. The turn-around time is a special aspect of the
initial energy distribution where two isomass ions with the
same initial energy, one with initial direction towards the
detector and the other with direction away from the detector.
Both will leave‘ the ion source with the same final kinetic
energy, but at different times.

9
unit resolution over a mass range of m/z 20 to 600 u, for each transient
mass spectrum. Another goal was to develop a TOF mass spectrometer
capable of high pressure ionization techniques, in particular chemical
ionization, which is commonly used to complement GC/MS data collected
using EI. In order for high pressure ionization techniques to be
successfully implemented, a mass spectrometer that did not require source
extraction pulses to form transient mass spectra would be required due to

low and diverse ion mobilities in the ion source under CI pressures.

The successful development of beam-modulation techniques by
Bakker9-10 was the first demonstration of a TOF mass spectrometer that
provided mass-independent resolution. This TOF mass spectrometer
incorporates a continuous ion source for extraction of the ions.11 A 'slice'
of the continuous ion beam is selected by an electric gate to be mass
analyzed. The turn-around time no longer limits the resolving power of the
TOF mass spectrometer using beam-modulation techniques because the ion
source is operated in a continuous ion extraction mode. The major
contribution to mass spectral peak broadening in the beam modulation
technique is the energy distribution of the isomass ions in the continuous

ion beam and the temporal dimension of the excised slice.

Initial work towards the development of a beam modulation mass
spectrometer at MSU led to the design and development of the BEam
Deflection Energy-Resolved (BEDER) TOF mass spectrometer12-13 by David
Pinkston. This mass spectrometer incorporated an ion source with narrow
slits and an electric sector to provide energy-resolved ion beams. The ion
source was operated in a continuous ion extraction mode, which allowed

the use of high pressure ionization techniques, such as chemical ionization

10

(CI), to be successfully implemented on a TOF mass spectrometer. The
continuous ion beam passed through an energy filter that had an
adjustable exit slit to control the energy distribution of the ion beam
analyzed. The continuous ion beam was then time-encoded by beam
deflection producing a mass spectrum of much improved resolving power
compared to that of conventional source-pulsed TOF-MS, and having better
than unit mass resolution for each m/z value in the mass range of 20 to 600
u. The BEDER-TOF mass spectrometer also showed the capability of
MS/MS by time-resolved ion kinetic energy spectrometry (TRIKES)12.

Other developments in TOF-MS at MSU involve the development of
time-resolved ion momentum spectrometry (TRIMS)14. TRIMS originally
combined a pulsed ion source and magnetic sector to disperse ions based on
their momentum. Ions of a given momentum are selected to pass down a
tube with a detector at the end. The simultaneous measurement of the
magnetic field and flight time of an ion to the detector is used to determine
its m/z value. TRIMS later implemented beam deflection for improved
mass resolution.15 Mass spectrometry/mass spectrometry (MS/MS) is
achieved by scanning the magnetic field and collecting ion flight times for
each magnetic field setting.16v17. This mass spectrometer was the first to
demonstrate MS/MS on the chromatographic time-scale using a wide-bore
capillary column”.

My research began with an evaluation of the performance of the
BEDER-TOF mass spectrometer. An in-depth analysis of David Pinkston's
dissertation led to a number of conclusions that provided the impetus for
the development of the beam deflection TOF (BDTOF) mass spectrometer.
Figure 27 of David Pinkston's dissertation shows a plot of theoretical and

11
experimental resolution versus the exit slit width of the electric sector.
Adjustment of the exit slit width controls the energy distribution of the
continuous ion beam that is modulated to form a mass spectrum. In this
figure, the experimental data points do not correlate with the theoretical
data points. As the slit width was increased, i.e., allowing greater energy
distribution in the continuous ion beam, the resolving power did not
decrease accordingly. The experimental data suggest that the resolution of
the BEDER-TOF mass spectrometer was not limited by the energy
distribution of the continuous ion beam exiting the electric sector. The
conclusion was drawn that the resolution was limited by some factor after
the electric sector, namely, the mode of beam deflection implemented on the

BEDER-TOF mass spectrometer.

Modifications to the BEDER-TOF mass spectrometer were severe
enough to warrant the renaming of the mass spectrometer. The electric
sector was removed from the mass spectrometer due to the apparent
independence of the resolving power of the BEDER-TOF mass spectrometer
with the energy distribution in the continuous ion beam. A benefit of the
removal of the electric sector was an increase in total ion current of the
continuous ion beam since it wasn't being dispersed by the electric sector.
Of course, removal of the electric sector eliminated the capability of MS/MS
by TRIKES, but the main objective of this research was to develop a GC/TOF

mass spectrometer.

Much of the early work on the BDTOF mass spectrometer was directed
towards optimizing the method of beam deflection because it appeared that
this was limiting the mass resolving power of the mass spectrometer.

Experiments were performed utilizing a number of beam deflection

12
assemblies. A new set of deflection plates was designed with a factor of five
decrease in capacitance, improving pulse rise/fall times. The
pulsing/gating method used by Pinkston12 was discarded for a single gate
mode, operated at a 5 kHz rate. Figure 1.2 shows the final beam deflection
system and the pulse timing utilized. Two pulses were used to form ion
packets by applying a voltage pulse to each of two parallel deflection plates.

The pulses were held at two different potentials, and by reversal of the
potentials applied to each plate, an ion packet would be , produced at the time
during which the electric field between the deflection plates was zero. This
method of beam deflection proved quite successful, producing a resolving
power of m/Am of 1400 at m/z 132 corresponding to the nominal atomic
mass of xenon as shown in Figure 1.3. The resolving power achieved by
this procedure is better than unit resolution over the mass-to-charge ratio

range of20 to500 u.19

This is the first report of the use of two voltage pulses to form the ion
packet in beam deflection.20 Previous beam deflection methods utilized one
voltage pulse applied to one-half of the gate and a d.c. voltage applied to the
other half. Ion packet formation is accomplished by reversal of the electric
field between the deflection plates of the gate. The new beam deflection
circuitry provided control over the time when each pulse switched relative
to the other. By simply changing the time at which each pulse changed
magnitude (forming an ion packet), control of the efi'ective d.c. voltage of the
gate could also be optimized to focus the ion packet at the detector.

a) ion source deflection plates

 

exit slit 17" 3
I VF $6,927
6 ->
e -> ‘9 -> 1 3 e —>
9 +6 —> - cm
969-" e , ¢ 9 —> 2
1.5-3kV ions I ' .
1cm V O
B 9?‘
+1.4 cm" 6‘“ 1
b
) pulse rate = 5kHz
10 ns 10 ns 10 ns 10 ns

6,, w w w i

X X ‘5‘
av \ vB

1 2 3 2 1 2 3 2 1

“—100 ps—bld— 100 ps—DH—loo its—bl

Figure 1.2 a) Schematic of beam deflection assembly located
in the flight tube directly after the exit slit of the ion source.
The beam deflection spacing and plate dimensions are also
given. b) The repetition rate of mass spectral transient
formation is 5kHz with pulse rise and fall times of 10ns.
During time period 1, the ion beam is deflected downward. As
the voltage applied to VA and VB changes during time period 2,
the beam is swept across the detector surface, resulting in a
mass spectral transient available for acquisition. The
continuous ion beam is deflected upward during time period 3.

14

 

 

 

[ Xenon Isotopes
9000 . 132
I
R = m = 1388
e
n
s 5000 _
i I ‘- FWHM = 10 nsec
Y 3000 .
1000
27.20 27.40 27.60 27.80 28.00 28.20 28.40
Flight Time,
microseconds

Figure 1.3 Mass spectrum of Xenon showing mass
resolution with new beam deflection assembly of the BDTOF
mass spectrometer.

15

The high mass spectral acquisition rate of TOF-MS coupled with TAD
provided by the ITR is a powerful analytical combination that can be used to
study ionization methods where rapid changes in the abundance of analyte
ions occur in the ion source. Figures 1.4 and 1.5 demonstrate the
capabilities of TOF-MS coupled with the ITR. A gas chromatograph was
interfaced to the BDTOF mass spectrometer to show the capabilities of high
mass spectral acquisition rates of TOF mass spectrometers combined with
TAD in the context of complex mixture analyses. GC/MS data were
acquired during the analysis of a trimethylsilyl derivatized mixture of
urinary organic acids at 1 and 10 scans-per-second to show improvements
in the chromatographic information available from the reconstructed total
ion current (RTIC) chromatograms generated at higher mass spectral
acquisition rates. Chromatographic peak shapes and areas are more
accurately represented with the higher mass spectral acquisition rates due
to the greater number of mass spectra available. Mass spectra of closely
eluting components that are incompletely resolved chromatographically
are easily made available by mass spectral subtraction with the 10 mass
spectra/second data base. Regions of the chromatogram that contain
coeluting components are identified by a 3-dimensional display of the data
or by plotting mass chromatograms of selected ions.

There have been numerous accounts of time-dependent ion currents in
the desorption/ionization (D/I) techniques of fast atom bombardment2 1
(FAB) and secondary ion mass spectrometry22 (SIMS). The BDTOF mass
spectrometer/ITR may contribute to a greater understanding of the
mechanism of ion formation in these D/I techniques23 by utilization of the
high mass spectral acquisition rates of TOF-MS and the high mass spectral

16

1 second

IIIIIIIIIIIIIIIIIIIIIIIIIII IIIIIIIII II IIIIIIIIIIIIIIIIIIIIII

5000 transients

I—IIII

       
 

    
 

    

IIIII

1 mass spectrum/sec

Figure 1.4 The BDTOF mass spectrometer operates with a
mass spectral transient generation rate of 5000s'1. The
summation of consecutive 5000 mass spectral transients by the
ITR results in a mass spectral acquisition rate of 1 mass
spectrum/second.

17
Is encod

IIII— IIII

 

20 mass sscpectra/se

Figure 1. 5 The BDTiOF mass secp ectr oem ter oepr raest 1with a
mass spectral tr:en ent gen raiot rate of 50003 The
summation of con c1151}? e250 mass spectral tr rsan: ents 1by the
ITR results in a smca spec ecrt aal acquisi siiot rate of 20 mass

18
acquisition rates available with the ITR. It has been shown that it can take
many seconds to establish a "steady state" of matrix and analyte ion

currents upon primary beam bombardment“:25

Another D/I technique, developed in this laboratory, potassium ion
ionization of desorbed species (K+IDS)26, also, produces time-dependent ion
currents. This technique uses thermionic emitters27 as sources of alkali
ions for attachment to thermally-desorbed analyte molecules and
fragments. This technique produces analyte ion currents for periods of
time ranging from one second to many seconds. For the case of a one
second desorption profile, the mass spectral information available rapidly
changes due to the temperature gradient produced by the heating of the
sample by the "potassium glass". The high mass spectral acquisition rates
of TOF-MS may help elucidate the mechanisms of ion formation and a

better understanding of the processes occurring in this D/I technique.

A preliminary investigation of K+IDS has been performed using the
BDTOF mass spectrometer/ITR. Studies were performed to compare
K+IDS spectra obtained with the BDTOF mass spectrometer under K+
chemical ionization (K+ CI) conditions of acetone to those obtained using a
Hewlett Packard 5985 mass spectrometer under the same K+ CI conditions.
A comparative study was performed to determine the effects of the
accelerating voltage penetration into the ion volume of the ion source on the
extent of conversion of gas phase K+ to gas phase (analyte + Kt) by placing a
wire grid across the ion volume exit slit. Some preliminary spectra have

been collected on a number of samples.

Chapter 2 - Developments In 'l'lme-Ot-Fllght Mass Spectrometry

The first description of a "pulsed mass spectrometer with time
dispersion" was given in 1946 by Stephenszs. Cameron and Eggers29
deveIOped a TOF mass spectrometer that formed ions by E1 in an ion source
and accelerated them into an evacuated tube. The ion beam was allowed to
pass into the evacuated tube by deflecting plates for time periods close to 5 us
in duration, resulting in peak widths of 20-30 us. The mass resolving power
was limited by the design of the ion source and the large distribution of
energies for each ion with these early instruments. Later, TOF mass
spectrometers were designed using pulsed EI and pulsed acceleration from

the ion source.30:31

Time-offlight mass spectrometers are simple in design, consisting of
an ionization region (ion source) and dispersive region (flight tube), making
them easy to construct and maintain at low cost. Mass spectra can be
generated by a TOF mass spectrometer at high rates (up to 25 kHz) and is
limited by the transit time of the heaviest ion to the detector, which is
typically on the order of 100 us. The availability of transient recorders
(specifically the ITR) has allowed the acquisition of all of the transient mass
spectra produced each second, expanding the use of TOF mass

spectrometers.

Z)

Improvements in mass resolving power in TOF mass spectrometers
were accomplished by minimizing or correcting for the initial spatial and
energy distributions in the ions. Wiley and McLaren developed a
mathematical model for an ion source with two accelerating fields.32 The
Wiley and McLaren ion source was the first major advance in TOF-MS,
with the first commercially available TOF mass spectrometer based on this
instrument. This mass spectrometer demonstrated a mass resolving
power (m/Am) of better than 600 for the ionic isotopes of xenon. A
schematic of this mass spectrometer is shown in Figure 2.1. The first
accelerating region of the ion source is labeled as s. The ions are formed in
this region and then extracted by application of a positive voltage to the
source backing plate. An important feature of this ion source is that the
electric field, E5, in region s is held near zero during the ion formation
process to minimize the energy distribution in the ions. The region labeled
d is kept at a constant electric field strength, Ed. The ions are accelerated
into the field free region, D, separating into ion-packets of different m/z
value. Ions of a given m/z that are formed at different positions in region s
can be made to arrive simultaneously at the detector by varying the ratio of
Ed and E3, This has been termed space-focussing and is independent of the

m/z value of the ions.

Although this new TOF mass spectrometer had improved resolving
power over a single-extraction-field ion source, the focussing of each m/z
value was dependent upon ion source parameters. Wiley and McLaren
introduced a method for improved resolving power for narrow mass

windows called the-lag energy focussing of the ions. A delay time between

: ource backing plate
ionization region
acceleration region

 

 

 

 

 

 

 

ion collector

field free drift region

Figure 2.1. Wiley-McLaren ion source showing two extraction
fields, Es + Ed.

ion formation and application of an extraction pulse to the ion source
backing plate results in ions of a given m/z value and distribution of energy
to arrive simultaneously at the detector. This is more clearly understood by
referring to Figure 2.2. This figure shows a theoretical plot of ion flight
times versus initial ion position within region 8 of the ion source for three

isomass ions. One ion has no initial energy, while the other two have the

22
same initial energy but with velocities in opposite directions (one with a
velocity vector towards the detector, v0, and one away from the detector, -vo).
By allowing the ions to drift in region s fi'om their initial positions for a time
t, the final velocity given to each of the three ions after extraction is
dependent on their positions within region s. The ion with initial velocity
away from the detector, -vo, will acquire more energy upon extraction than
the ion with initial velocity towards the detector, v0, but will have a longer
flight path. The ion with initial velocity, v0, will acquire less energy upon
extraction and have a shorter flight path. The time-lag, t, is optimized for
each m/z value when the ions of initial velocity v0 and -v0 arrive
simultaneously at the detector. Energy-focussing is achieved when
isomass ions with different thermal velocities have flight times that are
independent of their velocity distributions. Using a linear drift path and
time-lag energy focussing, however, results in mass-dependent focussing
of the ions. This limits the usefulness of this mass spectrometer because
only a narrow range of m/z values is in optimum focus at the detector for
each ion source extraction pulse and time-lag. Stein33 showed that it was
mathematically impossible to have both space and velocity-focussing using
time independent, one-dimensional accelerating fields in TOF mass

spectrometers.

Bakker published a discussion of time-focussing in TOF-MS.34 Time
focussing involves making the flight time for an ion independent of an its
initial velocity or spatial distributions. Time-focussing is achieved when
isomass ions with initial space or velocity distributions can be made to
arrive at a point or line in space simultaneously. Mamyrin proposed the

use of an electrostatic mirror to provide energy-focussing.35

 

 

flight time

 

 

 

I
I
|
I
I
I
I

——_—————

 

‘V0 ‘5 V013

initial position of ion in region 8

Figure 2.2. Plot showing ion flight times versus initial position
of the ion in region 8 of a Wiley-McLaren ion source for three
isomass ions with different initial velocities. By waiting for a

time t, after ion formation and before ion extraction, the flight
time of the two isomass ions with the same initial velocities but
opposite direction can be made to arrive at the detector
simultaneously.

Poschenrieder derived a theoretical treatment of time-focussing using
a combination of linear drift spaces with magnetic and electric sectors.36:37
Using a combination of a magnetic sector with linear drift spaces and
constant momentum acceleration, the flight time for ions of a given m/z
value can be made to be independent of their initial thermal velocity
distribution. Likewise, combining one or more electric sectors with linear

drift spaces and constant energy acceleration provides ion flight times that

24
are independent of the initial energy distribution on the ions. Other TOF
mass spectrometers have since been proposed that use multiple electric

sectors and electrostatic mirrors to provide time-focussing.38»39

The use of time-dependent, or dynamic electric fields to improve the
mass resolving power has also received consideration. Time-dependent
extraction voltages can be applied to a lens in the ion source or to a separate
region in the ion flight path. Isomass ions with different initial velocities
can be made to arrive simultaneously at the detector by applying the

appropriate force to each isomass ion packet. In Impulse Field Focusing“),
the normal electric field, E3, applied to region s of the Wiley and McLaren

ion source is pulsed to a higher electric field strength, Er for a time, 1:. The
mass resolving power with impulse-field focusing has been theoretically
determined to be better than unit mass resolution up to m/z 2600.
Theoretical models for using post ion source time-dependent electric fields
have also been considered.41v42 Theoretical and experimental data to
support a post ion source time-dependent electric field has been

demonstrated by Johnston, et. al.4'3

Beam modulation techniques have been used in nuclear physics to
provide isomass ion packets of well defined energy.44v45 Anderson and
Swarm developed a theoretical description and experimental data of beam
chopping and bunching of a continuous ion beam for nuclear physics.46
Fowler and Good described two methods of beam modulation of a
mntinuous ion beam. Impulse sweeping involves deflecting a continuous
ion beam from its original path through an aperture using a set of
deflection plates. Ions that pass through the aperture are defined by the
time that the impulse is applied to the deflection plates. Differential

5
impulse sweeping forms ion packets using the rising and falling edges of a
waveform. The width and duration of each ion packet is defined by an
aperture placed in front of the detector.47

Beam modulation was only successfully demonstrated in TOF-MS
after the work of Bakker.6:7 Bakker developed a mathematical model of ion
trajectories based on the dimensions of beam deflection plates and
dimensions of the mass spectrometer such as length of the ion flight path
and aperture defining the ion packet width. This model determined that
the theoretical resolving power of a beam modulation TOF mass

spectrometer is given by the following equation:

= 14ng
ZDU(B + S)

 

L is the ion flight path, V0 is potential difference of the ion beam modulation
applied between the deflection gates, D is the deflection plate spacing, U is
the accelerating voltage, B is the ion beam width, and S is the aperture
width. This model was confirmed by development of a TOF mass
spectrometer that demonstrated that the mass resolving power varied by
the square of the ion flight path. Also, according to this theory the mass
resolving power is not dependent on m/z . A significant advantage to the
use of beam modulation is that the ion source is operated in a continuous
ion extraction mode. This removes the turn-around time as a limiting

aspect of the mass resolving power. The continuous ion source also allows

%
high pressure ionization techniques to be implemented in TOF-MS. These

were the main reasons for choosing beam modulation for this project.13

More recently there have been other developments of continuous ion
extraction TOF mass spectrometers.48 A TOF mass spectrometer has been
developed based on Fourier transform techniques.49 This FT-TOF mass
spectrometer modulates the continuous ion beam with a sinusoidal wave
and modulates the electron current of the detector in phase. The ion signal
is acquired as a function of the modulation frequency and a Fourier
transform of the ion signal yields the time-of-flight mass spectrum. This
mode of ion detection theoretically increases the duty cycle to 25 % which
would greatly enhance the sensitivity available with TOF mass
spectrometers. This work showed some preliminary data that reproduced
the mass spectral quality available with an instrument operating in the
normal pulsed ion extraction mode, however, the expected gain in

sensitivity, due to the increase in the duty cycle, has yet to be realized.

Another development of a continuous ion source in TOF-MS is the
orthogonal-acceleration TOF (oa-TOF) mass spectrometer.50 This mass
spectrometer accelerates ions from an ion source to 10 eV in one-axis and
then accelerates them to 3000 eV in an orthogonal direction (TOF-axis) to a
detector. The ion optics of the orthogonal accelerator are designed for
space-focussing. A key feature of this instrument is the use of a
collimating lens to make ion trajectories parallel. Variations from these
parallel trajectories mainly result from the translational energy
distributions in the ions. Ions entering the orthogonal accelerator are in
positions similar to those necessary for the optimum time-lag for each m/z
value in a conventional TOF mass spectrometer. For optimum resolving

27
power, the ion flight time between ion formation in the ion source and
extraction from the orthogonal accelerator must be equal to the optimum

time-lag necessary to focus the ions at the detector. A theoretical mass
resolving power at m/z 2000 of m/Am > 2000 (FWHM) is predicted.

Chapter 3 - Design at BDTOF Mass Spectrometer

A simplified schematic diagram of the BDTOF mass spectrometer is
shown in Figure 3.1. This figure shows the major components of the mass
spectrometer used for ion beam manipulation, focussing and detection.
The first part of this chapter provides a detailed description of these
different components either designed or modified for the mass spectrometer
along with the circuit diagrams of the circuits that supply the necessary
voltages. A discussion of the performance characteristics of the BDTOF
mass spectrometer will follow including mass resolving power and mass
range in suitable focus for each transient mass spectrum. A comparison of
mass spectrometer performance to the BEDER-TOF mass spectrometer will
round out this chapter.

A. Ion Source

Ion source design requirements are different for a TOF mass
spectrometer incorporating beam deflection methods compared to those of
the more common "pulsed extraction" ion source. Time encoding of the
ions formed in a commercially available TOF mass spectrometer is usually
accomplished by applying a voltage pulse to a repeller in the ion source.
Each of the source lenses in this type of ion source has a wide aperture (up
to 5 mm in diameter) to increase ion transmission efficiencies to the

detector. The utilization of beam deflection methods in a TOF mass

8

a)

spectrometer requires a narrowly-focussed, continuous ion beam exiting
the ion source to achieve adequate mass resolution. Also, successful
implementation of high pressure ionization techniques is possible only if
the ion source and flight tube regions of a TOF mass spectrometer are
differentially pumped. This is a necessary requirement to minimize ion

losses due to ion-neutral collisions in the flight tube.

 

 

 

gas continuous beam . . . 1
( Chromatograph ion source deflection ion focus Integratintg
EI/CI assembly plates detector tr ansien
* recorder
fl

im—g EDI

TI—III_ I

flight tube J

 

 

 

 

 

 

 

 

 

 

 

 

L

Figure 3.1 Schematic diagram of GC/BDTOF mass
spectrometer (not to scale). Shown are the ion source, flight
tube, beam deflection assembly, ion focus plates, detector and
integrating transient recorder.

The ion sources used in the BDTOF mass spectrometer were adapted
from mass spectrometers that used electrostatic and magnetic analyzers
because these mass spectrometers also require a narrowly-focussed ion
beam. During the course of these studies there were two different ion

sources used in this mass spectrometer. The Dupont 21-491B double-

30
focussing mass spectrometer ion source was the one originally used in the
BEDER-TOF mass spectrometer and also for the BDTOF mass
spectrometer. The JEOL DM303 double-focussing mass spectrometer ion
source was a gift from JEOL, U.S.A., Peabody, MA. This ion source was
adapted for the GC/MS research.

1. Dupont 21-49lB ion source

This ion source has been adapted from a Dupont 21-491B double-
focussing mass spectrometer. The ion source is simple in design,
consisting of two repellers in the ion volume and one set of focussing lenses
to collimate the ion beam exiting the ion source. Figure 3.2 is a drawing
showing the ion source. For a more descriptive drawing, see the Dupont 21-
491B operating manuals. The ion source did not have an electron trap and
therefore, the electron current of the electron filament could not be
regulated as ionization current, but only as total emission current from the
filament. Focussing the ion beam involved tuning of the two repeller
voltages and the focus right voltage. The ion source exit slit is held at
ground potential. A voltage divider provides the ion volume and focus left
voltages.

31

Dupont 21-49 13 ion source

ion source
exit slit

focus — — focus

left right

r exit slit I
31163:?th 3 ion volume g heater

LT—W”

repellers

 

Figure 3.2 Dupont 21-491B ion source.

2. JEOL DM303 ion source

This ion source was adapted to the Dupont 21-491B ion source housing.
A simple drawing of the components of this ion source is shown in Figure
3.3. This ion source consists of a repeller, two set of focussing lens, and X-
Y deflector plates for ion beam focussing. The electron current is regulated
on the ionization current measured on the. electron trap. High voltage is
supplied by a Bertan model 205A-05R high voltage power supply, Bertan
Assoc., Inc., 3 Aerial Way, Syosset, N.Y. 11791. The original JEOL
electronics were not available, so a duplicate of these electronics was

designed by M. Rabb of the electronics shop of the Chemistry Department.

32
A schematic of the duplicate electronics is shown in Figure 3.4. Table 3.1
contains information concerning connections to the upper and lower octal
sockets on the Dupont ion source housing for the ion source. Table 3.2

contains pin lettering for an amphenol connector that connects circuit

JEOL DM 303 ion source

ion source

—-I -_ exit slit

 

X-Y deflectors

   

 

l
_ — ground

left right
— — focus 2

_ — focusl

 

 

 

exit slit , I
electron } , :l electron
filament 1011 volume trap
I -|- I
repeller

Figure 3.3 JEOL DM303 ion source.

33

connections to the ion source elements. The filament voltage is variable
from 0 to -300V (relative to the ion volume). The electron trap voltage is
maintained at an ion source bias voltage of +11V. The voltages for the ion
volume and focus 1 (left and right) lens are derived from the voltage divider
in Figure 3.5. Focus 2 has the left and right electrodes connected and
derives its voltage from a separate voltage divider network. The voltage
applied to the focus 2 lens is variable from 0 to VA. A typical operating
voltage for focus 2 is a few hundred volts. The X-Y deflector plates have a
voltage range variable from 1:200 V derived from the power supply in Figure
3.6.

Table 3.1 and lower electrical connections on Dupont
for JEOL DM303 ion source.

    

upper

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

_ *2“, 4(A)
166 +450
RE‘D ’x 50v /7I_3il 11.17 (B)
30 :E , g .
RED -’ 450 ’ :I 337 I
U 5(0)
I *1 v map.24V
K
GRY 3 \/+220 100v l 1,,
GRY/ -’ 9(E) COM
WHT 1(F)
BRN J (G) CHAMBER
BRN
WHT 16(1)
BLU
BLU
BLU/WHT 15 (N)
-2ov
WHT
(ORN/WHJL:\ 50uF 350v '—’ 3“” "
WHT ___. 300mm Ag
(ORN) "’ 3 (R) § E
YEL/ 6 (S) E E
WHT _: 50ma +450 ". raw 3
7(U) g >
‘°“” ”a?“
H 14 (W) D a :4 A E

 

 

 

Figure 3.4 Electronic diagram of duplicate circuit for JEOL
DM303 ion source.

Table 3.2

35

Connector (amphenol) pin numbering for JEOL

DM303 ion source voltages and ion source elements along with

those of the o_riginal Old Hirose connector used by JEOL.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 3. 2
connector and/or Hirose connector and/or Hirose
connection conn nnector connection conn nnector
+24V 18t focus
1200V
(yellow)
B common 11,17 M 18f. foals
1000V
C -24V 5 N -20V 15
D ground , P +300V 8
(filament)
11V 9 R common 3
(electron (filament)
trap) J
F +24V 1 S 11V 6
(repeller)
G common (J) T common 12
L chamber (11V)
H -24V 2 U filament 7
(repeller)
I +20 16 , V filament 10 (H)
J VA I W 10052 CT. 14
K lst focus I X Tlament 13
800V (red) I control

 

 

 

 

 

 

 

 

 

:93 kV

9x100kQ

1200v ’1‘

$ 100 k!) -

1000 V b M 10 M
first

focus

100 k!) IOC3

800V

4x100kfl

 

>Dgnd

Figure 3.5 Voltage divider for J EOL DM303 ion source.
Provides VA and First Focus 1 (left and right) voltages.

 

 

 

 

 

 

 

 

 

 

 

 

+ _____0A
200V
112A -
B
115VAC °n ‘
+
200V
_ ~—o c

 

 

 

Figure 3.6 Electronic diagram of i200V power supplies for
DM303 ion source X-Y deflector plates.

B. Gas chromatography interface

The GC/MS interface is a modification of the aluminum block heater
used on the JEOL HX110 mass spectrometer. The aluminum block heated
the region from the gas chromatograph to the flange on the ion source
housing. The end of the aluminum block going into the HP 5790A gas
chromatograph was modified to fit through the oven wall insulation, flush
to the inner wall of the oven to maintain high interface temperatures
throughout the transfer line. Inside the ion source housing there is a
separate aluminum fitting machined to heat the capillary column from the
housing flange to the ion source. This aluminum piece was heated with a
Watlow ClE13 cartridge heater (HiWatt, 2130 Enterprise, Suite 104,
Kentwood, MI). These two heating blocks overlapped by approximately one
inch on the housing flange. The interface was wrapped in insulation to
maintain a constant temperature the length of the interface. The gas
chromatographic interface was tested for cold spots by injecting a standard
hydrocarbon mixture containing 09, 010-026 (even-numbered carbons)
hydrocarbons with a temperature program of 50 to 325°C at 20°C per
minute. A separate Variac controlled the heating of the aluminum block
and the aluminum fitting. The temperature of each component of the
interface was gradually increased until the peak shape for 026 showed no
evidence of chromatographic peak tailing.

C. Beam Deflection Assembly

Much time was spent developing a successful beam deflection
geometry and method. Successful beam ' deflection (with the BEDER-TOF
assembly) was only accomplished after tedious tuning of the pulse width

3
and delay time, along with the d.c. offset voltage of the ion packet
production gate. These parameters for the ion packet production gate had
to be synchronized to the select gate, which deflects one of the two ion
packets formed with the ion packet production gate from reaching the
detector. The select gate pulse was never successful in completely
deflecting the second ion packet from reaching the detector. Instead a d.c.
signal consisting of random ion events at the detector was observed on the
oscilloscope that changed in width and delay with changes made to the
select gate pulse. The grass signal was proportional to the intensity of the
continuous ion current at approximately 5-10% of the peak intensity.
Pinkston had to apply an unusually high voltage (close to 100 V!) to the
horizontal steering plate located half way down the flight tube to only
observe one transient mass spectrum on the oscilloscope. This "tuning" of
the mass spectrometer diminished the intensity of the transient mass

spectrum as well. All of these variables proved difficult to optimize.

1. Deflection Plate Geometries

The deflection plate geometry of the BEDER-TOF mass spectrometer
used 1 x 4 x 1.4 cm blocks of aluminum for the deflection plates (refer to
David Pinkston's Dissertation, Figure 20 for details). These blocks were
isolated from each other with teflon spacers. The size and design of this
assembly resulted in a capacitance between each set of plates of 39 pF at a
plate spacing of 2 mm. The capacitance between gates can affect pulse
rise/fall times and also induce a voltage on an adjacent gate when pulse

amplitudes are changing rapidly. The Avtec pulse generator used for beam

:9
deflection with the BEDER-TOF mass spectrometer was discarded (due to
failure of pulse integrity) along with the deflection plate geometry for better
designs.

The plate geometry used on the BEDER-TOF mass spectrometer was
replaced with a set of horizontal gates etched on a teflon circuit board. This
was done mainly to minimize capacitive effects between adjacent gates
affecting the voltage pulse applied each individual deflection plate. The
active area of the original BEDER-TOF mass spectrometer deflection plate
geometry was reduced to 1.4 cm in length by 2 cm in height with the same
deflection plate separation of 2 m. I The capacitance between gates

decreased to 7 pF.

Geometry studies of the deflection plates led to the conclusion that a
greater plate separation provided higher resolution than the 2 mm spacing
geometry for the same experimental conditions. Further improvements in
the plate geometry were made by eliminating one set of the deflection plates
(due to the problems mentioned previously). Eliminating one set of
deflection plates (the select gate) and lengthening the pulse time to 10011.8
improved the success of beam deflection (discussed in more detail in the
next section). Increasing the plate separation by a factor of 6.5 reduced the
effect of fringing electric fields on the ion beam and created a more uniform
electric field between the deflection plates. Also, the deflection plate
assembly alignment to the exit slit of the ion source was less critical with
the wider deflection plate spacing. The final deflection plate geometry and

position relative to the ion source exit slit is shown in Figure 1.2.

2. Beam Deflection Methods

The following is a chronological description of the beam deflection
methods implemented beginning on the BEDER-TOF mass spectrometer,
including deflection plate geometries and pulse characteristics, and ending
with the BD-TOF mass spectrometer.

Initial work on the BEDER-TOF mass spectrometer involved the Avtec
pulse generator and David Pinkston's deflection plate geometry. The
failure of the Avtec pulse integrity led to the design and construction of a
new pulsing circuit by M. Rabb. The specifications for this circuit were as

follows:

1. Output should consist of two independently controlled pulses
with variable delay of 0 - 20 us and variable width of 0 - 20 us.

2. The pulse amplitudes were fixed at 63 V (because this was a
typical operating voltage used by David Pinkston).

3. Pulse rate was variable from 1 to 10 kHz.
4. Pulse rise and fall times were less than 10 us.

A d.c. voltage offset, variable from 0 to 63 V, was applied to one of the
pulsing plates. The gate was "opened" by holding the gate pulse at 0 V and
grounding the other gate plate. The gate was "closed" after one of the ion
packets had passed through the gate by raising the gate pulse amplitude to
63 V. The mass resolution of the mass spectrometer with this new circuit
was approximately 100 (m/Am, with Am being the width of the peak at half

41
its maximum height, FWI-IM), with the baseline peak width for m/z 28 at
150ns.

At this point in time, the select gate of the beam deflection assembly
was eliminated and the beam deflection electronics were modified in the

following way:

1. The pulse width was changed to be variable from 5 us up to 100
us.

2. The pulsing circuitry would provide two voltage pulses. One
pulse would switch from 63 V to 0 V on "edge 1" and the other
pulse from 0 V to 63 V.

3. Variable delay of the rising and falling edges of each pulse from
0 to 5 us.

The electronic diagram of this pulsing circuit is shown in Figure 3.7.
This modification eliminated many of the drawbacks associated with the
two-gate pulsing assembly. First, the pulse rate was reduced from 10 kHz
to 5 kHz and the deflection pulse held for 100 us after "edge 1", in exchange
for the elimination of the select gate of the deflection assembly. Secondly,
the application of a dynamic voltage pulse to each plate in the beam
deflection assembly provided for both control over the efi'ective d.c. ofi'set
voltage that formed the ion packet, thus providing a focussing effect for the
ion packet, and also produced an electric field that changed magnitude
twice as quickly compared to that from the old method of using one dynamic
pulse and a d.c. ofi‘set voltage.

FIIST SWITCH

 

 

 

Figure 3.7 Electronic diagram of beam deflection circuit.
This circuit provides two output pulses that alternate between 0
and 63 V at 5 kHz. The rise and fall times for each pulse are
adjustable as is the relative time at which each pulse changes
potential with respect to the other.

D. Detectors

Descriptions of each of the detectors used in this mass spectrometer
are given along with the general performance characteristics of each. A
flange was designed and machined from stainless steel to fit on the Bendix
flight tube. The vacuum seal to the flight tube can be made with a silver
wire or 1/16" diameter Viton o-ring. The flange is shown in Figure 3.8.
There is a BNC feedthrough centered on the flange for mounting the
detectors. Four high voltage feedthroughs are available for any necessary
high voltage connections. The Galileo ETD-2003 channel plate detector
requires two high voltage feedthroughs and the Becton Dickinson MM-l-

ISG electron multiplier requires three.

1. Galileo FTD-2003

A microchannel plate (MCP) is a lead glass substrate containing many
channels that are coated with a secondary emissive material. An MCP
consists of up to 107 channels that operate independently as electron
multipliers. Primary ions or electrons that strike the wall of a channel will
form 1 or more secondary electrons. A bias voltage up to 1000 volts across
the channel will form a cascade of secondary electrons, multiplying the
primary ion or electron current up to 104. The schematic diagram of the

voltage divider used for this detector is shown in Figure 3.9.

3/32"

 

 

 

2.5000 " 1.7740 "

 

 

 

 

 

i __J k

8 holes (0.344") equally 2 alignment holes (0.261")
spaced on 4.080" circle on a 4.500" Circle

@ BNC anode

high voltage feedthrough

Figure 3.8 Galileo FTD-2003 and Johnston MM-l detector
mounting flange for Bendix flight tube.

-3250 V

1.1 MG

 

-2600 V D Vout front plate

1.1 M9

1.1 MI!

1.1 M!)

'600 V > vout back plate

 

1.1 MI)

Figure 3.9 Voltage divider network for Galileo FTD-2003
channelplate detector.

The bias voltage is controlled by adjusting the input voltage at the top of
the voltage divider. The channels are biased at an angle of 120 to minimize
ion feedback through the channels of the MCP. The Galileo FTD-2003
detector consists of two MCPs in series providing a linear output current up
to 10'7A. The output current of an MCP has a linear response to input

46
current provided that the output current does not exceed 10% of the bias
current of the MCP. After a primary ion or electron strikes the wall of a
channel and the cascade of secondary electrons leaves the channel, there is
a "dead time" during which the channel will not respond to any incoming
ions or electrons. This dead time can be related to the resistance and
capacitance of each channel and is on the order of 20 ms. Since each
channel operates independently, this does not limit the gain response of the
MCP provided that a primary ion or electron does not strike a dead channel
20 ms after the previous one. The detection efficiencies for primary
electrons and ions have been reported to be approximately the same“. For
primary electrons and ions with energy ranging from 02-2 kV, the

detection efficiencies ranges from 585%.

a. Standard multichannel plates

The standard MCP has a linear response of output current/input
current of 10'7A/10'11A. Typical bias currents are 10'5A per MCP, which
limits the linear response to output currents less than 10'7A. The dynamic
range of a standard MCP is limited to 104 and drops off at output currents
greater than 10'7A. The gain of the chevron assembly used in the Galileo
ETD-2003 detector is 106 at the maximum operating voltage of 2000 V.

b. High output technology multichannel plates

The high output technology (HOT) MCP is of the same construction as
a standard MOP, but constructed from a different lead formulation that can

47
maintain output currents up to 60 times that of a standard MCP while
providing a linear gain response. The HOT MCP has a linear response of
output current/input current of 10'4A/10‘3A. The dynamic range is the
same as the standard MCP, but has a linear response up to 104A of output

current.

2. Becton Dickinson MM- 1- 18G electron multiplier

This electron multiplier is a 20-stage Be-Cu dynode assembly available
from Becton Dickinson Diagnostic Instrument Systems, 7 Loveton Circle,
Sparks, MD 21152. A wire mesh is located in front of the first dynode to
deflect the primary ions towards the secondary emissive surface to increase
detection efficiency. Each stage has a resistance of 1M!) making a
combined resistance of 20M!) for the stack. The maximum voltage for the
stack is 5000V (250V/stage) with a typical operating voltage of 3000V. The
electron detection efficiency is reported at greater than 90% at 200eV, while
the ion detection efficiency is greater than 90% at 3000eV. The ion detection
efficiency decreases as the mass-to-charge ratio of the primary ion
increases while it is higher at greater ion energies. A typical gain response
has a linear output from 103 (at 1.5kV) to 109 (at 3.5kV).

The gain of the discrete dynode electron multipliers decreases over
time due to operation at high output currents or contamination. The
lifetime of the detector can be extended by increasing the voltage applied to
the stack up to 5000V. The detector can be reactivated to recover the original
gain characteristics of the detector when new as guaranteed by the

manufacturer.

E. Detector Slit Assembly

The detector slit assembly (Figure 3.10) is positioned 4 1/2" from the
end of the flight tube. This positions the slit assembly 1/2" in front of the
detector. It is machined from aluminum and designed to fill the entire
cross section of the flight tube to prevent stray ions and neutrals from
striking the detector surface. The assembly is held in position by 4 thumb
screws. A set of adjustable slits centered on the assembly allows a range of
slit widths from 0 to 1/2 inch. The assembly also was designed to hold the

Allison-group beam Visualizer52 for ion beam visualization.

F. Preamplifiers

Both the Comlinear and the "in-house" preamplifiers were powered

with a 115 V power supply 6 200 mA (SOLA Electric, Elk Grove, IL 66007
cat. no. 84-15-02120-E).

1. Comlinear

The preamp used for most of this work is the Comlinear E220 I BNC 50
50 30 preamplifier, Comlinear Corporation, 4800 Wheaton Dr., Fort Collins,
CO 80525, (303)226-0500. This preamplifier converts the input ion current
to a voltage, inverts the signal to produce a positive voltage, and provides a
gain of 30. This device provides control of the d.c. offset voltage of the output
signal with an adjustable resistor. The offset voltage of the A/D converter of
the ITR requires the input d.c. voltage to be set near -250 mV. The exact

49
value varies from day-to-day and is dependent on preamp and ITR warm-

up time. The preamp and ITR require approximately 1 hour to warm-up.

 

 

‘ 3.3750 " V

 

 

 

 

 

 

 

 

 

 

+l 0.50" '4-

drawn to scale

E 4-40 screw

O 6-32 threaded hole

0 0-80 threaded hole

Figure 3.10 Detector slit assembly for Bendix flight tube.
Provides for adjustable ion beam widths up to 0.50". This
assembly also contains necessary holes and mounting threads
for the Allison-group beam Visualizer.

2. "in-house"

An "in-house" preamplifier was designed and constructed based on
the Comlinear CLC404 wideband, high-slew rate, monolithic operational
amplifier. A schematic diagram of the circuit layout is shown in Figure
3.11. This preamp was designed to invert the input signal and provide a
gain of 81. Control of the output d.c. offset voltage also was provided with
this circuit to interface to the ITR.

 

 

 

 

 

 

 

 

Av=1+ % +5V Av=-%-f-
8
+5V g 3;?“
if --t
0.1uF
—-I
0.1uF 2 +> . Vouta
@- out Vin -4 RI '5 I
I 2 .. R
on?" '1
Rs éE —I IguF
—| -5V
6.8},LF
V -5v

Figure 3.11 Electronic circuit diagram for "in-house'
preamplifier built around two CLC404 high-slew rate

operational amplifiers. Rf = 501 Q and R3 = 47 Q.

51
G. Ion Focus Assembly

The ion focus assembly is a set of horizontal and vertical steering
plates and an einzel lens located at the midpoint of the flight tube. These
"steering plates" are used to deflect the ion packets toward the detector.
The voltage divider designed for the ion focus assembly is shown in Figure
3.12. The 2000 V is supplied by a Ferranti Venus LR-2 200-2000VDC 0
10mA d.c. to d.c. converter, Ferranti International 399 Smith Street,
Farmingdale, N.Y. 11735. The voltages go through the beam deflection
assembly circuit box that mounts on a flange located on the T-tube of the
flight tube. The pin numbering of the T-tube flange is given in Figure 3.13
and listed in Table 3.3. There is a 5-pin Molex pin connector located inside
the flight tube for the ion focus assembly that allows a quick disconnect to
the ion focus assembly when removal of the T-tube is necessary. The pin

numbering for the 5-pin Molex connector is given in Figure 3.14.

Table 3.3 Pin numbering on T-tube flange of flight tube for
beam defection assembl and ion assembl .

 

1) connection
number

 

 

 

 

 

 

 

 

2000 V
500m
249M! ‘ 249M!
249k!) 249k!)
mm 2491:!)
249k!) 249110
249 1:0 V 249m
Einaellens
249 k!) 249k!)
CCW
> 100 to F 100 he
CW CW
+ — + —
haizontal vertical
.stea-ingplate stea'hrgplate

Figure 3.12 Electronic circuit diagram for ion focus assembly.

T-tube flange pin numbering

 

Figure 3.13 T-tube flange showing pin numbers. Table 3.1
contains a list of the electrical connections to this flange.

5-pin molex pin connector

 

OOOOO

 

 

 

 

 

 

 

 

 

 

A A
L—@ ion lens
Q) horizontal steering plate (left)
{3) horizontal steering plate (right)
(1) vertical steering plate (top)
{5) vertical steering plate (bottom)

Figure 3.14 Five-pin Molex pin connector for quick
disconnects to flight tube steering plates and ion lens.

H. Vacuum System

The exit slit of the ion source serves as a limiting aperture for this
instrument that operates as a differentially-pumped mass spectrometer.
This allows high pressure ionization techniques in the ion source while
still maintaining flight tube pressures in the low 10'6 torr range. The ion
source is pumped by a National Research Corporation model M0012
diffusion pump backed by an Alcatel roughing pump. The flight tube is
pumped by a Varian model VHS-4 diffusion pump backed by an Alcatel
roughing pump. A gate valve (K.J. Lesker model VR9-LP68) is located

55
between each difiusion pump and the mass spectrometer. The gate valves
are air actuated, and are opened and closed by powering a Humphries
solenoid (model 062-4E1-36). For mass spectrometer safety, the power to the
solenoids is wired such that the gate valves will close due to power failure

or pressure surges.

Improvements in the vacuum system of the BEDER-TOF were
necessary before operation of the mass spectrometer could take place. The
base pressure of the ion source and flight tube was in the 10'5 torr range
when this project was begun. Many of the vacuum seals on the DuPont 21-
491B ion source housing and electric sector were gold or silver wire gasket
seals. These seals were leaking due to cross scratches on the flange
surfaces on which the wire gasket seals were to be seated. These scratches
provided channels through which air leaks were possible. The scratches
were removed from each flange by hand sanding the flange surfaces with
No. 220 sand paper to remove the major scratches; eventually, minor
scratches were removed with polishing paper. Sanding motion was in a
circular motion around the flange so that any fine scratches that remained
would be concentric with the wire gasket seals thus minimizing the

potential for further leaks.

The original adapter flange used to mate the Dupont electric sector to
the Bendix flight tube was machined from aluminum and designed to use
wire gasket seals. This particular area of the mass spectrometer was also
a major source of vacuum leaks due to the high amount of stress placed on
it by the design of the mass spectrometer frame supporting the source and
flight tube. This piece was redesigned out of stainless steel and designed to

use either wire gasket seals or rubber o-rings. The adapter flange was

56

designed to first mate to the source end of the mass spectrometer with
either a wire gasket or an o-ring. The o-ring was used due to its greater
tolerance during the process of connecting each half of the mass
spectrometer. After the entire source assembly is connected to the support
frame, the source and flight tube are connected by rolling the source frame
up to the flight tube and adjusting the height of the source frame with the
height adjustable table.

Further improvements in the vacuum system were made by
redesigning the roughing lines between the rough pumps and the diffusion
pumps. The roughing line on the flight tube was constructed from 1" o.d.
copper tubing. A separate roughing pump was connected to the direct

probe interface during the K+IDS experiments.

I. Integrating Transient Recorder

A brief description of the ITR is given here. For more descriptive
information concerning the ITR, refer to reference 5. The ITR is a data
collection system that digitizes data at 5 nsec resolution. This is
accomplished with a ZOO-MHz flash analog-to-digital converter. The
digitized data are passed to 16 high speed ECL (emitter coupled logic)
summer cards where transients are summed to form a mass spectral
scan. The integrated scans are passed across a VME bus to three Motorola
68020 parallel processors whereby time/mass calibration, and/or conversion
to reconstructed mass chromatograms and/or real-time conversion to
mass, intensity pairs occurs. The processed scans are written to a 300-

Mbyte Priam disk drive. Each transient can be up to 80 nsec in duration (or

5'7
16,000 data points). The BDTOF mass spectrometer generates 5000

transient mass spectra each second.

J. Comparison of BEDER-TOF and BDTOF Mass Spectrometers

The design goals for the TOF project were to develop a TOF mass
spectrometer that could provide sufficient mass resolving power over the
entire m/z range of a typical GC/MS experiment. Commercially available
GC/MS instruments have upper mass limits in the range of 650 to 800 u.
Successful implementation of beam deflection in TOF-MS would require
that the mass resolving power be better than unit mass resolution up to

some m/z value in this mass range.

Perfluorotributylamine (PFTBA) is a compound commonly used to
calibrate the m/z axis (or time axis in TOF-MS) since it has a number of
peaks in its mass spectrum over the mass range up to m/z 614 (the
molecular ion). Figure 3.15 shows the mass spectrum of PFTBA using the
BD-TOF mass spectrometer and TAD. The mass spectrum is the result of
integrating 5000 mass spectral transients over 1 second. Also shown in this
figure are the raw data points for m/z 69 and m/z 502 to show that each ion
is in focus at the detector for each mass spectral transient. This is a
requirement to take full advantage of the capabilities of the ITR. Figure
3.15 demonstrates that the beam deflection method implemented on the BD-
TOF mass spectrometer provides focussed mass spectral transients to the

ITR over the mass range of most GC/MS applications.

 

 

 

Mass spectrum of perfluorotributylamine

 

 

 

 

 

 

 

R m.
e
1 ”I.
3 so
P I
1 70‘
v .
e 60-
I 50.
n .
t 40-
e I
n m-
8 1
i 20«
t t
y 101
0"" v1!.l:1‘"lvf""livv!"
50 100 150 200 250 (I!) 350 400 450 500 550
m/z
m/z 69 m/z 502
1&0 '1
I . I 4
n ' n .
t 110‘” " t 1400 -I
e ‘ e I
n : n "
9 600° ‘ 8 1200 -
1 ‘ i
t I t
y 1a” g ' l fi I ' 1‘F y If“) 'I v r ' l '
28.950 28.960 28.970 28.980 65.57 65.59 65.61 65.63
flight time (us) flight time (us)

Figure 3.15 Mass spectrum of perfluorotributylamine obtained
on the BDTOF mass spectrometer. Also shown are the raw
data points for the peaks at m/z 69 and at m/z 502.

59

A comparison of the mass resolving power of the BD-TOF and BEDER-
TOF mass spectrometers for each of the major ions in the mass spectrum of
PFTBA is shown in Figure 3.16. The intensity of the peaks at m/z 502 and at
m/z 614 are relatively weak and may result in an underestimate of the peak
widths for these ions. The BD-TOF mass spectrometer provides better mass
resolution without the use of an energy filter to minimize the energy
distribution in the continuous ion beam than the BEDER-TOF mass
spectrometer. An advantage to operating the mass spectrometer without
the electric sector is the higher ion transmission efficiency, which

improves the sensitivity of the mass spectrometer.

A plot of baseline peak widths vs m for the major ions in the mass
spectrum of PFTBA in Figure 3.15 yields a slope of 3.7 x 1093 x {11172. This
slope can be used to calculate the upper m/z value that will have unit mass
resolution (50% valley definition) using beam deflection. The peak width at
half its maximum height can be approximated by one-half of the slope and
setting it equal to At in the following equation:

 

At=—2VTLVUm/z + 1 - Vm/z)

Using L = 2.1m, V = 3000V. and At = 1.85 x 1093 x Im/z. An upper m/z
value of 749 u is calculated to be resolved by this beam deflection method.

”50°” A BDTOF

O BEDER-TOF (data from ref. 13)

Resolution (FWHM) = m/ Am = U2 At

Resolution
(F WHM)

 

 

 

0 I ‘ l ' l ' 1 V I ' I fl I

m 131 219 $4 414 502 614
m/z

Figure 3.16 Comparison of mass resolving power of the
BEDER-TOF and BDTOF mass spectrometers for the major
ions in the mass spectrum of perfluorotributylamine. The

resolution is based upon Am (or its equivalent, 2At) being the
full width of the peak at half its maximum height (FWHM).
The BEDER-TOF data are from reference 13.

Chapter 4 - Gas Chromatography/Beam Detlectlon Tlme-Ot-Fllght

Mass Spectrometry

This chapter discusses developments in the area of GC/MS using the
BDTOF mass spectrometer. Two examples are shown using high-
resolution capillary column gas chromatography. The first is an analysis
of a simple 12-component mixture with a region of the RTIC chromatogram
having unresolved chromatographic profiles for three of the components.
The analysis of this sample mixture was performed at mass spectral
acquisition rates of 1 and 20 mass spectra/second to show the advantages of
higher mass spectral acquisition rates on representing the
chromatography available and providing mass spectral data even for
compounds that are represented by unresolved peaks in the
chromatographic profile. The second example is the analysis of the TMS-
derivatized urinary organic acids in a normal urine sample. This example
further demonstrates the advantages of acquiring the mass spectral data
base at higher rates by comparison of the RTIC chromatograms and data
available from mass spectral acquisition rates of 1 and 10 mass
spectra/second to that available from a gas chromatograph using a flame

ionization detector.

A. Grob programmed test mixture
1. Experimental

The gas chromatograph used is a Hitachi 663-30, fitted with an 18-m
(DB-1, 0.18 mm i.d.) capillary column. The ion source and ion source
housing from a double-focusing mass spectrometer, a DuPont 21-491B, is
used to provide a continuous, narrow, focussed beam of ions produced by
El. Ions formed in the ion source are accelerated to a kinetic energy of
approximately 3000 eV. Transient mass spectra are generated at a rate of

5,000 seC'l.

A 12-component programmed test mixture was obtained from Supelco,
Inc., Supelco Park, Bellefonte, PA 16823-0048, Cat. no. 4-7304. Table 4.1 lists
the components and their concentrations in methylene chloride. A 1.0-ul
injection of this mixture, split at 10:1 ratio, delivered approximately 50
ng/component to the column. A temperature program of 120°C - 200 °C at
20°C/min was used. The direct interface was maintained at a temperature
of 250°C. The GC interface was direct, with all of the effluent fi'om the gas

chromatograph passing into the mass spectrometer ionization chamber.

Table 4.1 Components in methylene chloride for the Grob
1n

 

63
2. Reconstructed Total Ion Current Chromatograms

a. Comparison of 1 and 20 scans/second

Figure 4.1 shows the reconstructed total ion current (RTIC)
chromatogram available with a mass spectrum acquisition rate of 1 mass
spectrum/second of a standard test mixture53 analyzed using the
GC/BDTOF mass spectrometer/ITR. Several questions must be addressed
concerning the results in Figure 4.1. 1 Does the RTIC chromatogram
generated from the data base acquired at 1 mass spectrum/second
adequately represent the chromatography? Also, it was known that the
mixture contained 12 components, but only 10 peaks are shown in the
RTIC. The portion of the chromatogram containing the solvent peak and
2,3 butanediol is not shown here (Figure 4.1), so there should be 11
components represented by the RTIC chromatogram. To answer these
questions, another aliquot of the test mixture was analyzed by the
GC/BDTOF mass spectrometer/ITR, summing every 250 transient mass
spectra, thereby generating 20 mass spectra/second. The RTIC
chromatogram, resulting from the 20 mass spectra/second data base at
approximately 2.5 minutes into the run, is shown in Figure 4.2a; the
corresponding segment of the RTIC in Figure 4.1 between the vertical
arrows, obtained from the 1 mass spectrum/second data base is shown for
comparison. There are two obvious advantages to the faster mass spectral
acquisition rate that can be seen upon comparing the RTIC
' chromatograms in Figure 4.2a. The 20 mass spectra/second data base
offers 20 points/second to reconstruct the chromatographic profile more
accurately in terms of peak shapes, relative heights, and relative areas.

This feature of the data provides better quantitation of the components in

64
the mixture. The other advantage is that the RTIC chromatogram
available from higher mass spectral acquisition rates more accurately
represents the true chromatographic profile. It is obvious from the RTIC
chromatogram generated from the data base acquired at 20 mass
spectra/second, presented in Figure 4.2a, that this region of the
chromatogram contains three components.

b. Deconvolution of closely eluting components

A common method of "resolving" chromatographically-unresolved
components in a GC/MS analysis is to plot the intensity at an m/z value
unique to each unresolved component versus scan number, generating
mass chromatograms for each ion. Mass chromatograms suggest which
scans would contain mass spectral information for particular components,
allowing for qualitative and quantitative information to be obtained, even for
overlapping components. The success of this approach depends on the
mass spectral acquisition rate of the mass spectrometer and the
identification of unique ions for each component. For example, a sufficient
number of mass spectra must be acquired during elution of a
chromatographic doublet for the mass spectral data base to be adequately
time-resolved for identifying and deconvoluting overlapping components.
The result of mass spectral interpretation is only as good as the quality of
the mass spectra, which can be compromised due to skewing of relative
peak intensities by scanning mass spectrometers, or due to spectral
interferences from co-eluting components. Because the BDTOF mass

spectrometer/ITR can generate many unskewed mass spectra each second,

65
mass spectral quality is superior and interferences are easier to identify

and remove.

The high mass spectral acquisition rate allows the presence of three
components to be recognized in this unresolved region of the RTIC
chromatogram in Figure 4.2b. Can the three components be identified from
the mass spectral data base even though the components coeluted? Because
the components in the test mixture are known, as well as the type of
column used for analysis, we were able to determine which components
were expected to be in this region of the chromatogram. One of the expected
components is 2,6-dimethylphenol. Instead of searching through the 200
mass spectra that contain mass spectral data for a match of the data to a
library mass spectrum of this compound, we can display the mass
chromatogram of one of the dominant ions in the mass spectrum of 2,6-
dimethylphenol. The library mass spectrum of 2,6-dimethylphenol
indicates that the molecular ion is represented by the base peak at m/z 122.
Figure 4.2b shows the mass chromatogram of m/z 122 and identifies the
middle component as 2,6-dimethylphenol. Another component expected to
be in this region of the RTIC chromatogram is undecane; the alkyl cation
C4H9+, m/z 57, was selected as a designate ion for this hydrocarbon. The
mass chromatogram at m/z 57 displayed in Figure 4.2b shows that the
mass spectra of both of the other two components contain this alkyl cation.

The mass chromatograms at m/z 57 and 122 available from the data
base acquired at 20 mass spectra/second provide information on the
chromatographic peak shapes of the three components and can be used to
identify scans from which mass spectra. for the three components can be

obtained. By choosing a mass spectrum that does not contain peaks at both

$
m/z 122 and m/z 57, one can obtain a pure mass spectrum for each of the
three components represented here. A visual inspection of the mass
chromatograms represented in Figure 4.2b shows a region (scans 190-200)
where the ion current at m/z 57 is minimal. Because the mass spectra of
the other two components have an intense peak at m/z 57, this is a region of
the data base that should provide a reasonably pure mass spectrum of the
middle component. The mass spectrum contained in scan 192 is shown in
Figure 4.3a and is identified as that of 2,6-dimethylphenol. A similar
procedure was used to obtain pure mass spectra of the other two
components by choosing mass spectra that do not contain ion current at
m/z 122. Ion current at m/z 122 is observed in scans 160-232. I'igure 4.3b
shows the mass spectrum in scan 159, which is identical with the library
spectrum of nonanal. Figure 4.3c shows the mass spectrum in scan 240,

which is identical with that of undecane.
c. Limits of Detection

The detection limit of the GC/BDTOF mass spectrometer/ITR at a
mass spectral acquisition rate of 20 mass spectra/second was compared to
that of the JEOL JMS-AX505H MS system, which is a commercially
available double-focussing sector mass spectrometer routinely used for GC-
MS analyses. The fastest scan rate available with the JEOL mass
spectrometer, 0.9 seconds/decade (e.g., m/z 50-500), which generates 1.1

scans/second, was used for the comparison.

Complete mass spectra were collected during the analysis of the
standard test mixture at various concentrations at the mass spectral

acquisition rate described above for each mass spectrometer. Mass

Total Ion Current Chromatogram of Test Mixture

40000- 4,5,6 11

N

 

 

 

 

Intensity
q

 

 

 

 

 

IN‘\ M

 

 

 

 

 

 

 

 

o .
(2”) IT m l 2!!) (65 ')
mm D 1' . mm

Figure 4.1 Reconstructed TIC chromatogram generated
from the data base acquired at 1 scan/second of standard Grob

test mixture.

a)

b)

as

A

0
O
1

l scan/sec
0-0—0

886‘
Lmlnl

20 scan/sec

.5
O
1

Relative Intensi
N
O

A

N
O
1

l

 

 

 

Retention time

2.6-dimcthylphcnol

nonanal
mlz 122

IIIIIIIIIIII
I’ll/III]!!!
III/I’ll]!!!
[I’ll/III!!!

aloooooooooo

undecanc

A I A l L l L A A I

Intensity

JLML‘AJA‘A‘A‘A

~ 5
I
I

 

0 100 200 300
scan number

Figure 4.2 a) Comparison of RTIC chromatograms
reconstructed from the data bases acquired at 1 and 20 mass
spectra/second over the region of the chromatogram between
the arrows in Figure 4.1. b) RTIC chromatogram is shown
along with the mass chromatograms of m/z 57 and m/z 122
available from the 20 mass spectra/second data base.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

I) 2.0-Dimethylphenol
100- ras
>1
E vs-
3
.5 so-
i’. m
E ...
0
D:
o 1 v 1 II t A Jr a A ' .a 1 v
20 40 60 80 100 120 140 160
m/z
5) Nonanal
1001 51
3‘
'5 75
I:
o
q.)
.5 so
(D
5
.9. 26
0
m 142
o- .-' - .l 41
20 40 60 80 100 120 140 160
m/z
c)
Undecane
100- 51
3‘
a 76-
t:
o
a.)
5 50. 11
O
2.
*3 25- as
.—
0
m I“
o ‘ v A A “I v4 v A u
20 40 60 80 100 120 140 160
m/z

Figure 4.3 Mass spectrum in scan a) 192, b) 159, and c) 240.

70

chromatograms were reconstructed from the corresponding data bases.
The area of the peak in the mass chromatogram at m/z 122 (corresponding
to the mass spectrum of 2,6-dimethylphenol) was plotted versus the amount
of analyte injected. The limit of detection was calculated using the method
of regression analysis on each data set. The y-intercept of each regression
line was used as an estimate of the blank signal, yb. The signal, y = yb 4-
38b, determines the limit of demction. The limit of detection calculated for
both the scanning mass spectrometer and the GC/BDTOF mass
spectrometer/ITR system was 0.6 i 0.2 ng of 2,6-dimethylphenol.

B. Complex mixture analysis of TMS-derivatized organic acids of urine

1. Background

The results of analyses using the GC/BDTOF-MS/ITR system in the
context of metabolic profiling of urinary organic acids is demonstrated.
Metabolic profiling is an analytical method for quantitative and qualitative
analysis of metabolites in complex mixtures extracted from physiological
fluids such as urine or plasma54. The metabolic profile, which is a
chromatogram of the components of the mixture, portrays the relative
amounts of these metabolites as derived from intermediary metabolism of
proteins, carbohydrates, and lipids in the individual. The coupling of gas
chromatography and mass spectrometry has played a crucial role in the
development of methodologies for such analyses. The metabolic profile of
urinary organic acids reflects metabolic status and allows for the
identification of genetic disorders that perturb homeostasis. Improvements
in metabolic profiling have been limited in the same way as have analyses

71
of other complex mixtures. Even with recent advances in capillary column
technology, chromatographic resolution is not sufficient to separate every
component in the mixture and, thus, some components in these complex

mixtures may go undetected.

This example compares the results of the GC-only analysis of a
urinary organic acid mixture using a flame ionization detector (FID) to
those obtained by the GC/BDTOF mass spectrometer/ITR system at mass
spectral acquisition rates of 1 and 10 mass spectra/second. The advantages
of the higher mass spectral acquisition rates are demonstrated, both in
terms of accurately representing the chromatographic profile and in
providing a data base from which mass spectra can be obtained for closely-

eluting components.

2. Experimental

The ion source was adapted from a JEOL DM303 mass spectrometer.
The GC is a Hewlett Packard model 5790. The GC and BDTOF mass
spectrometer are connected via a modified JEOL HX110 aluminum block
interface, heated to 260°C. The detector is a Galileo FTD-2003 (Galileo
Electra-Optics Corp., Sturbridge, MA) in which the standard multichannel
plates (MCP) were replaced with high output technology (HOT) MCPs. The
preamplifier was made “in-house”. The urinary organic acid mixture was
separated using a short capillary column, 6 m x 0.2 mm DB-5 (J &W
Scientific), 0.4um film thickness, using a column head pressure of 13 psig

with helium as the carrier gas, splitless injection with an injector

72
temperature of 275°C, and a temperature program of 50°C to 325°C, at a
rate of 20°C/min.

The urinary organic acid mixture also was analyzed on a Hewlett
Packard model 5890 gas chromatograph with a flame ionization detector.
The FID output was digitized by an HP 3392A printing integrator, with the
peak width response set to 0.01 min, which digitizes the data atthe highest
sampling rate available (20-Hz).

The number of theoretical plates for the capillary column used for
these analyses was determined on the GC/FID instrument. A two-
component hydrocarbon mixture containing nonane and decane was
analyzed isothermally at 120°C. The average value for the number of plates
as determined by measurements on each of the two peaks was 51,000 plates.

The method of urinary organic acid extraction has been reported
previously55 . The acidic metabolites isolated from 1 ml of a control urine
sample were derivatized by mixing 25111 of pyridine and 100111 of
bis(trimethylsilyl)-trifluoroacetamide/trimethylchlorosilane and heating at
80°C for 1 h. A 1.0-ul aliquot of the TMS-derivatized urinary organic acids
was analyzed by GC/MS with mass spectral acquisition at 1 and 10 mass

spectra/second, with the same column and GC conditions.

3. Chromatographic Profiles from the GC/FID and GC/BDTOF mass
spectrometer/ITR

A comparison of the chromatograms obtained from analysis of a

urinary organic acid mixture by GC-only with flame ionization detection

73

and by GC/MS with the reconstructed total ion current (RTIC) is shown in
Figure 4.4. The RTIC chromatograms represent the analysis of the same
quantity of this mixture and are generated from data acquired at 1 and 10
mass spectra/second on the GC/BDTOF mass spectrometer/ITR. A three-
minute delay between injection of the mixture and data acquisition was
used. The data base, obtained at 1 mass spectrum/second (providing only 1
RTIC point/second with which to reconstruct the chromatography), was
generated by summing 5000 consecutive mass spectral transients,
acquiring 600 mass spectra during the 10-minute analysis. Another data
base, obtained at 10 mass spectra/second, was generated by summing 500
consecutive mass spectral transients, acquiring 6000 mass spectra during
the lO-minute analysis. Table 4.2 lists several of the TMS-derivatized
organic acids identified from data acquired at 10 mass spectra/second, with
their retention times and relative amounts for each component. The
components in the mixture were identified by comparison of retention times
and mass spectra of each component to those in a reference library
previously compiled in our laboratory using another GC/MS instrument.56
Components yet to be identified have been labeled as unknowns.
Quantitation was achieved based on the area in the RTIC represented by 36
ng of the TMS-derivative of tropic acid (peak marked by an asterisk in
Figure 4.4c) which was used as a coinjected internal standard.

The goal of any analysis by GC/MS is to obtain useful information for
all of the components in a mixture represented by the RTIC chromatogram.
Ideally, the RTIC chromatogram would provide an accurate representation
of the chromatographic profile for retention times and quantitation of the
components in the mixture. The data base from which the RTIC

74

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

‘8 GC-FID
R
e
l
a
tTIFTIIIIIIIII'IIII[ITIIIIIIIII
i .
V b RTIClscans/s
e .
I
n t
t LII In,“
e IIIUIT IIIII'IIIjIIIII
n '0 RTIClOscans/s
s .
i
t
Y I
I I
1.1lull,1.uk_uci_. x _ _
4 6 8 10 12
Retentiontime(min)

Figure 4.4 Complex mixture analysis of TMS-derivatized
urinary organic acids. Comparison of a) GC-FID response to
reconstructed total ion current chromatograms generated
from mass spectral acquisition rates of b) 1 and c) 10 mass
spectra/second.

75

chromatogram is generated should provide information to distinguish
those components that are not fully resolved chromatographically. In
capillary GC/MS, it is difficult to meet these criteria when mass spectra are
generated at 1 mass spectrum/second or less. Mass spectral acquisition
rates of 10 or more mass spectra/second are necessary to generate RTIC
chromatograms that accurately represent the resolution achieved by the
capillary GC column57. The RTIC chromatogram in Figure 4.4c
accurately represents the chromatographic peak shapes and areas as

verified by comparison with the GC-FID chromatogram in Figure 4.4a.

Cram, et. al.,58 have investigated the relationship between the number
of data points required to represent the profile of a given chromatographic
peak and the characteristic features of that peak shape as described by s,
where 82 is the variance that can be related to the mathematical function
describing the profile. Mass spectral acquisition rates of 10 or more mass
spectra/second are necessary to generate RTIC chromatograms that
accurately represent the resolution achieved by the capillary GC column.59
Based on the chromatographic peak widths for this analysis, the minimum
number of data points that can accurately represent this profile is 10 mass
spectra/second.

Selected segments of the complete RTIC chromatograms (shown in
Figure 4.4) are shown in more detail in Figure 4.5. The RTIC
chromatogram from the data base collected at 1 mass spectrum/second
(Figure 4.5a) clearly does not accurately represent the chromatographic
profile when compared to either the GC-FID chromatogram or the
GC/BDTOF mass spectrometer/ITR RTIC chromatogram generated from

76

Table 4.2 TMS-derivatized urinary organic acids with a
relative than 2 creatinine.
Table 4.2. U c Acids in Mixture .

ten scan
time (min) number (or other compound) Response
(1' 0.002 min) ug/mg

creatinine

 

   

acid
succr
tn-

scan
time (min) number (or other compound) Response
(II: 0.002 min) ug/mg

creatinine

lactone
ucono

C
ucuromc
“CO C
1100 C
C
C

 

* Quantitative results assuming identical ionization

eficiencies for all compounds.

I” Table 4.2 contains information on compounds present at
greater than 2.0 ug/mg of creatinine.

78
the data base collected at 10 mass spectra/second (Figure 4.5b). Regions
where there are two or more closely eluting components are represented by
a single peak in the RTIC chromatogram in Figure 4.5a due to the small
number of data points available with which to reconstruct the
chromatographic peak profiles. For example, the segment marked “A” in
Figure 4.5a suggests the presence of 3 components, while the data in Figure
4.5b clearly show that at least 5 components are eluting in this time period.
Region “B” in Figure 4.5a may represent baseline noise; however, the data
in Figure 4.5b show a chromatographic peak in that time window (see
arrow). Similarly, region “C” becomes a chromatographic doublet (or
possibly a triplet) when the mass spectral data base allows for adequate
reconstruction of the chromatographic resolution (Figure 4.5b). If the
RTIC chromatogram in Figure 4.5a were the only one available, an analyst
would incorrectly interpret apparent “single peaks” as representing single
components. However, the mass spectrum obtained by averaging the mass
spectra across the peak, as is commonly done for data presumed to
represent a single component, would be the sum of mass spectra from two
or more components, thus making mass spectral interpretation difficult, if
not impossible. Minor components in the mixture are also difiicult to
distinguish from the baseline in Figure 4.5a, again due to the insufficient
number of data points (mass spectra) with which to reconstruct the

chromatographic peak profiles.

4. Mass Spectral Deconvolution

An important difference between the RTIC chromatogram (Figure
4.4c) and the GC-FID chromatogram (Figure 4.4a) is that with the RTIC
chromatogram additional dimensions of information are available in the
mass spectral data base. The mass spectral data base can be used in two
ways. Resolution of chromatographically-unresolved components is
possible by plotting the ion current at specified m/z values versus scan

number, generating a mass chromatogram.

One of the advantages of generating a mass spectral data base at 10
mass spectra/second rather than at 1 mass spectrum/second, is
demonstrated in Figure 4.6. A portion of the RTIC chromatogram
generated from the data base collected at 1 mass spectrum/second shown in
Figure 4.6a has one “peak” in the vicinity of scan 125 that appears to result
from a single component in the mixture. The 5-second peak width might be
interpreted as resulting from overloading the column, and the scans 123 to
128 of the RTIC chromatogram, would be averaged and the resulting mass
spectrum (mis)interpreted. In comparing Figure 4.6a to Figure 4.6b
(reconstructed from the data base collected at 10 mass spectra/second), it is
apparent that more than one component is eluting during this time period.

Differential comparison of adjacent mass spectra collected during a
GC peak may help to discern the number of components present. For
example, Figures 4.7a and 4.7b are the mass spectra in scans 1197 and
1220, respectively, from the region of the RTIC chromatogram in Figure
4.6b. The mass spectrum in Figure 4.7a has a number of peaks not

observed in Figure 4.7b; the most obvious are at m/z 165 and m/z 180.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

RTIC 1 scan/s

a
3. I
c:
H
0 L—l I._.l l_l
> A B C
E RTIC 10 scans/s
6'3 b

I
7.5 8I f ' 9 I 10 I

Retention time (min)

Figure 4.5 Selected region of RTIC chromatogram generated
from mass spectral acquisition rates of a) 1 and b) 10 mass
spectra/second showing improved representation of
chromatographic profile at a higher mass spectral acquisition
rate. .

 

 

RTIC 1 scan/s

 

 

 

 

115 1'20 1'25 no 135

 

 

b RTIC 10 scans/s

T Y I Y

 

 

j

 

scan 1220

 

 

‘ 10 scans/s
4— m/z 227

 

 

 

1300

 

Figure 4.6 Comparison of RTIC chromatograms at mass
spectral acquisition rates of a) 1 and b) 10 mass spectra/second
for a chromatographic doublet. c) mass chromatograms at
m/z 180 and at m/z 227 identifying two components.

&
Other peaks, such as those at m/z 73, m/z 147, and m/z 227 are found in both
mass spectra. Because there are peaks that are not found in both scans,
one can assume that there is more than one component represented by the
peak. in the RTIC chromatogram in Figure 4.6b. The relative intensity at
m/z 147 and m/z 227 in Figures 4.7a and 4.7b remains constant, which
indicates that both mass spectral peaks represent the same component.
Also, the mass chromatograms at each of these m/z values correlate with
each other. By plotting the signal intensifies at m/z 180 and m/z 227 versus
scan number, the elution profiles of the two components can be resolved,

and these individual profiles realized (Figure 4.6c).

Mass spectra can be obtained after identification of a unique ion for
each component. Ion current at m/z 180 is observed in scans 1180 to 1203.
Thus, the data in Figure 4.6c show that the mass spectrum in scan 1220 is
representative of the second component with no mass spectral interferences
from the first, and can be interpreted as such. The mass spectrum in scan
1197 contains mass spectral data from both of the components. A mass
spectrum representative of the first component can be obtained by mass
spectral subtraction. By subtracting the peak intensities at m/z values
representative of the second component found in scan 1220 from those in
scan 1197, a mass spectrum for the first component will result. The base
peak in scans 1197 and 1220 is at m/z 147, which represents only the second
component. The ion current at m/z 147 in scan 1220 is 34,384. arbitrary
units (AU) and 14,704 AU in scan 1197. Subtracting 43% ((14,704 AU/34,384
AU) x 100%) of the ion currents at all of the peaks in scan 1220 from those
peaks in scan 1197 will remove all of the ion current indicative of the second

component, leaving only peaks indicative of the first component.

 

 

 

 

 

 

 

 

 

 

 

 

 

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Figure 4.7 Figure 4.7a shows the mass spectrum in scan
1197 that has mass spectral information for both of the
components eluting over the peak profile shown in Figure 4.6c.
Figure 4.7b shows the mass spectrum in scan 1220. The mass
spectrum shown in Figure 4.7c is the result of subtracting 43 %
of the ion currents in scan 1220 from the corresponding ones in
scan 1197.

84
The mass spectrum resulting from this mass spectral subtraction is shown
in Figure 4.7c. This powerful operation is only possible with unskewed
mass spectra, such as those obtained by TOF-MS.

The first component represented in the RTIC segment in Figure 4.6c
has been identified as the TMS-derivative of p-cresol. The molecular ion,
M+-, is represented by the peak at m/z 180; the characteristic ion, (M-15)"',
due to the loss of a methyl group from the trimethylsilyl group, is
represented by the peak at m/z 165. The second component has been
identified as the bis-TMS-derivative of sulfuric acid. The molecular weight
of this compound is 242 u, and the mass spectrum shows a peak at m/z 227
for the characteristic ion corresponding to (M-15)+.

Another example is illustrated in Figure 4.8a, which exemplifies the
situation commonly encountered where two components elute so closely
that neither a conventional chromatogram nor the RTIC chromatogram
generated from a data base acquired at 10 scans/second shows clear
evidence for the presence of two components. The data in Figure 4.8
represents the 10-second portion of the chromatogram from 6.05 min to 6.22
min. The peak profile in Figure 4.8a gives no indication that there is more
than a single component eluting from the capillary column. However, the
mass spectra found in scans 1551, 1555, and 1557, as shown in Figures 4.9a-
c, show that more than one component could be eluting in this time
window, based on the fact that the relative intensities at m/z 189 and m/z
210 do not rise and fall together. Confirmation of this assumption is
provided by plotting mass chromatograms for each of these m/z values as

85
shown in Figure 4.8b, and noting that the maxima of the peaks in the two

profiles occur at different times.

Mass spectra for each of the two components represented in Figure
4.8b can be obtained from the mass spectral data base. Referring to Figure
4.8b, scans 1540 to 1550 only contain mass spectral data for the first
component. These scans were averaged to provide the mass spectrum
shown in Figure 4.9d. A mass spectrum for the second component in the
RTIC peak can be obtained by averaging the mass spectra in scans 1560 to
1570, shown in Figure 4.9e.

The first component represented by this peak profile has been
identified as bis-TMS—urea. The ion current at m/z 189 represents the
characteristic loss of a methyl group from the TMS ester of urea. The
second component represented by this peak profile has yet to be identified.
Based on its mass spectrum shown in Figure 4.9e, the molecular ion
appears to be at m/z 225 with an intense ion at m/z 210 representing the loss
of a methyl group. There is a peak at m/z 73 and at m/z 147 which
represent one and two TMS groups, respectively. Since the molecular
weight of this unknown is an odd mass, this compound has an odd number
of nitrogens. The weight of two TMS groups (73 u per TMS group) is
subtracted from the molecular weight determined by interpretation of the
mass spectrum, the molecular weight of the unknown is 81 u (Note that
each TMS group replaces a hydrogen so that the effective weight gain or
loss for each TMS group is 72 u.). The odd molecular weight for this

compound indicates one or three nitrogens. The most probable empirical
formula for this molecular weight is C5H7N.

 

‘ a RTIC

 

 

 

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‘<HH’mfl@€¥bH

 

 

 

1500 1550 1600

scan number

Figure 4.8 Figure 4.8a is a region of the RTIC chromatogram
generated from the 10 scans/second data base. Figure 4.8b
shows the mass chromatograms at m/z 189 (solid line) and at
m/z 210 (broken line). The difference in the maxima of the two
peaks indicates the presence of two components.

 

 

 

 

 

 

 

 

 

 

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Figure 4.9 Comparison of mass spectral data (Figures 4.9a-c)
in scans 1551, 1555, and 1557 over the peak profile in Figure 4.8.
The changes in the relative intensities at m/z 189 and m/z 210
indicates the presence of more than one component. Figure
4.9d is the mass spectrum resulting from averaging scans 1560
to 1570. Figure 4.9e is the mass spectrum resulting from

averaging scans 1540 to 1550.

88

A more dramatic example of a reconstructed chromatographic peak
profile, suggesting, incorrectly, the elution of a single component, is shown
in Figure 4.10a. The peak shape and width are consistent with elution of a
single component at this retention time. The mass spectral data in scans
1883, 1890, and 1899, are shown in Figures 4.11a-c, respectively. The most
obvious differences are the changes in relative intensities at m/z 147, m/z
174, and m/z 247 in the three mass spectra, suggesting the elution of at least
two different components. Mass chromatograms at m/z 174 and m/z 247
are shown in Figure 4.10b. Again, the mass chromatograms do not overlap
completely, indicating the presence of two components. By identifying a
mass spectral peak for each of the components in the chromatographic
peak profile, a mass spectrum for each component is obtained. A
comparison of the mass spectra shown in Figures 4.11a-c shows that scan

1883 only has ion currents indicative of one of the components.

Similarly, scan 1899 only has ion currents indicative of the other
component. Selection of these scans is more clear upon examination of the
overlapping mass chromatograms shown in Figure 4.10b. Note that at the
maximum intensities at m/z 174 and m/z 247, the retention times, shown in
Figure 4.10b, W, but one can still obtain a mass
spectrum for each of the components directly from the data base acquired at
a rate of 10 mass spectra/second. The two components represented in
Figure 4.10 have been identified as bis-TMS-succinic acid and tri-TMS-
glycine, respectively, The TMS ester of succinic acid has a molecular
weight of 262 u and its mass spectrum shows a peak for the characteristic
(M-15)+ ion at m/z 247.

 

RTIC

Intensi

 

 

 

 

Intensity

 

 

 

1830 1930

 

Figure 4.10 Figure 4.10a is a region of the RTIC
chromatogram generated from the data base acquired at 10
scans/second. Figure 4.10b shows the mass chromatograms at
m/z 174 (broken line) and at m/z 247 (solid line). The difi'erence
in the maxima of the two mass chromatograms indicates the
presence of two components.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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Figure 4.11 Comparison of mass spectral data (Figures a—c) in
scans 1883, 1890, and 1899 over the peak profile in Figure 4.10.
Comparison of the mass spectral data in each scan shown
indicates that Figure 4.11a (scan 1883) represents the first
component in the peak profile, Figure 4.11b (scan 1890)
contains mass spectral data for both components, and Figure
4.11c (scan 1899) is the mass spectrum of the second
comgonent represented by the poorly resolved doublet in Figure
4.10 .

91
5. Three-dimensional data presentation

Three-dimensional (3-D) plots of mass spectra versus scan number are
another useful means of displaying data consisting of a large number of
scans per chromatographic peak60. These 3-D plots are constructed by
plotting mass chromatograms for all m/z values in a given region of the
RTIC chromatogram. This allows the temporal profiles of each mass
chromatogram to be compared to indicate which chromatographic peaks
result from more than one component. An example of a 3-D plot is shown
in Figure 4.12 over the chromatographic peak in the metabolic profile
represented in Figure 4.10. The 3-D plot clearly shows evidence for the two
components over this region of the RTIC chromatogram. The two
components have peaks in common at m/z 73 and m/z 147, but there are a
number of peaks that are unique to one or the other component. The two
major peaks that are unique to each of the components occur at m/z 174 and
m/z 247 (as in Figure 4.10b). Chromatographic profiles for the two
components can be recognized by plotting mass chromatograms at m/z 174
and m/z 247. The mass spectrum of each component can be obtained by

examining the mass chromatograms as shown previously.

Relative Intensity

 

   

  
   

      
 

  
  
 

 

  
   
   

m/z 247
_ g 1910
.:.—.'72 Eff-F5— . _ :————.= 1m
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( “g". 3;; ‘ '- . ‘
2 ._ .~.=_—= '—-.~—-. ~ _ ———.—.— .—.—— number
40 100 200 270

Figure 4.12 3-dimensional plot of scan range 1870 to 1910 of
data base acquired at 10 mass spectra/second.

6. Conclusions

A GC/MS instrument based on beam deflection time-of-flight mass
spectrometry can perform complex mixture analyses by generating
complete mass spectra at a rate appropriate for specific chromatographic
conditions. The mass spectral acquisition rate for an analysis is dictated by
requirements to accurately represent the chromatography and provide data
with good signal-to-noise. The utility of this unique system is demonstrated
in the context of realistic problems encountered in the analysis of the
complex mixture of organic acids extracted from human urine. The
problems in such analyses frequently manifest themselves as components
that are chromatographically unresolved. It is further demonstrated that
long capillary columns, with high numbers of theoretical plates and peak
separation, are not necessary with this technology. Rather, an analysis
can be performed on a short capillary column giving the same analytical
information, but with reduced analysis time. The typical analysis time for
this metabolic profile was reduced from 1 hour to 15 minutes (this
particular analysis time was limited by the rate at which the GC
temperature could be increased). The success of these analyses is due to
the nature of the BDTOF-MS instrument combined with the ITR. In this
application, each of the 10 mass spectra acquired each second is the sum of
500 transient mass spectra. The high mass spectral acquisition rate
provides a data base that can be used to accurately represent the
chromatographic information and that facilitates the identification of each
of the components in a complex mixture. Quantitation of each of the
components is facilitated due to the greater number of points available with
which to determine peak shape, width and area. The "unskewed" nature of

 

94
the mass spectrum in each of the scans facilitates preparation of “pure”
mass spectra by deconvolution of nearly co-eluting components using mass
spectral subtraction. For the data presented here, compounds with
retention times differing by 0.1 sec, can be analyzed. The three-
dimensional presentation of the data allows the user to identify peaks that
are representative of poorly-resolved components, display the
corresponding mass chromatograms, and then choose scan and
background scans for subtraction to obtain mass spectra for closely eluting

components.

Chapter 5 - Potassium Ion ionization of Desorbed Species (K+IDS)

A. Background

Blewett and Jones61 developed the use of alumino-silicate glasses,
doped with metal oxides, as a source of gas phase metal ions. By heating a
mixture of 28i02:1A1203:1K20, copious amounts ‘of gas phase K+ are
produced. The development of K+IDS as a complementary ionization
technique to chemical ionization has been introduced in this laboratory.62
With K+IDS, samples are thermally desorbed into the gas phase by
radiative heating by the potassium emitter. The thermally desorbed
neutrals are "sampled" by gas phase K+ resulting in the formation of K+
adduct ions. The desorption products are dependent on the rate of heating
and final temperature of the potassium glass used in an analysis. The two
competing rates of decomposition and desorption of intact molecules
determine the mass spectrum obtained for an analysis. Desorption of intact
molecules is favored at high temperatures, while decomposition is favored

at lower temperatures.

Previous work on K+IDS was performed on a Hewlett Packard 5985
quadrupole mass spectrometer. This mass spectrometer operates with the
source at ground potential and a mass range up to 1000 u. The original
K+IDS probe shown in Figure 5.1 was designed with only a potassium glass
that also functioned as a sample holder. Sample analysis by thermal

desorption from the potassium glass was accomplished as the current

%

 

 

 

 

   

 

 

 

 

Potassium Bead
a) Current Supply
0 to 3.5 A
I I ' '—‘ a-
1 I
I I—\
Bead Bias
Voltage —
0 to 100 V T
relative
to ion
volume 1/4 " dia. 4-holed I? bead and
potential ceramic rod sample holder
Potassium Bead
b) Current Supply wire sample holder
0 to 3.5 A \
I E — ..'_fi
Bead Bias
Voltage —
0 to 100 V T
relative
to ion
volunae 1/4 " dia. 4-holed
potential ceramic rod

Figure 5.1 Previous K+IDS probe designs used on HP 5985
mass spectrometer. First design used by Bombick used the
potassium emitter as a sample holder. Later design of Kassel
used separate wire sample holder for better temporal overlap of
potassium emission and sample desorption. A 30-fold
improvement in detection limits result from the separation of
the wire sample holder and potassium emitter.

97

through the potassium glass was increased. This probe design did not take
full advantage of this desorption technique because most of the sample was
desorbed from the potassium glass before a suficient amount of potassium
ions were available for attachment to the desorbed sample. The overlap of
potassium ion desorption and sample desorption profiles was improved
with the separation of the sample from the potassium glass. Here, the
temporal overlap of the desorption profiles of both the potassium ions and
desorbed sample can be optimized by the spatial separation of the wire
sample holder and potassium bead in the ion source. The separation of the
wire sample holder and potassium emitter improved the detection limits of
101133 by 30401163

K+IDS is a useful method for obtaining molecular weight information
for a number of compound classifications63. Most often in the analysis of
thermally-labile compounds, molecular weight information is desired and
thus a high final potassium glass temperature is used. Structural
information is available with K+IDS by controlling the rate of heating and
final temperature of the potassium glass and/or sample. A slower rate of
heating induces more decomposition products that provide structurally
significant ions. K+IDS is useful in the analysis of polymers“ and complex
mixtures.65 The analysis of polymers by K+IDS is used to provide both
structural information on the oligomeric units and information on the

distribution of oligomers in the polymer66v67.

The KtIDS analysis of palmitic acid using the BDTOF mass
spectrometer is shown as an example in Figure 5.2. The K+IDS probe
design using a separate wire sample holder and potassium emitter was

used for this analysis. A l-ul solution of palmitic acid in methanol was

Q

placed on the wire sample, holder and the methanol was allowed to
evaporate. The probe was inserted into the mass spectrometer until the
probe tip was in the center of the ion volume of the ion source. The current
through the potassium emitter was ramped from 0 to 2.7 A in less than 2
seconds and mass spectral data was acquired at 10 mass spectra/second
from m/z 30 to m/z 350. Figure 5.2 shows the sum of the ion currents in
each scan versus scan number along with the desorption profiles at m/z 41
(K+ isotope ion) and at m/z 295 (MK+ ion of palmitic acid). The desorption
profile for the MK” of palmitic acid is approximately 0.8 seconds for this
analysis. A sum of the mass spectral data in the scans over the desorption
profile at m/z 295 is shown in Figure 5.3. This is the typical K+IDS mass
spectrum of palmitic acid with only an MK+ ion formed in the analysis.

 

1-1-

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20 30 40 50 60 70 80 90 100
Scan number

'UVVYIYVTVIVWYVIUVVV

Figure 5.2 Total ion current and desorption profiles at m/z 41
and m/z 295 for the K+IDS analysis of palmitic acid. Bead
current was 2.7 A at a mass spectral acquisition rate of 10
mass spectra/second.

 

x10

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A

 

 

 

QRH'UflOfiflt-t

"u.).-11H [[129 J 'l‘ ;H l‘lil [Ill Illiil‘l

40 80 120 160 200 240 280 320
m/z

   

Figure 5.3 K+IDS mass spectrum of palmitic acid with MK+
at m/z 295. This mass spectrum is the sum of scans 42 to 46
from Figure 5.2. Bead current was 2.7 A with a mass spectral
acquisition rate of 10 mass spectra/second.

The BDTOF mass spectrometer combined with TAD and the high
mass spectral acquisition rates of the ITR may have a greater utility than a
quadrupole mass spectrometer for K+IDS analyses. Figure 5.2 shows that a
K+IDS analysis can be less than a second in duration. High acquisition
rates of complete mass spectra are required when information on the rate
of formation of all the analyte ions is desired. The high mass spectral
acquisition rates will be useful in K+IDS applications that involve analyzing
mixtures where there are desorption profiles being generated for each

component in the mixture.

100

Rapid heating techniques have been used for the determination of the
heats of vaporization of thermally-labile compounds.68 Polyalcohols were
rapidly heated from a rhenium filament and the desorbed neutrals reacted
under CI conditions with methane and ammonia. The rate of appearance
of the protonated molecules can be used to determine their heats of
vaporization by plotting the rate of appearance versus the reciprocal of the
absolute temperature. The slope of the resulting Arrhenius plot was used
to obtain the heat of vaporization for each ion. Heats of vaporization for the
polyalcohols studied were correlated to the degree of hydrogen bonding in

each compound.

Light investigated the use of K+IDS as a rapid heating technique to
determine the heats of vaporization of palmitic acid and sucrose.69 The
rate of appearance of K+ adducts of the desorbed neutrals was used as an
approximation for the rate constant of the volatilization process. During a
K+IDS' analysis, the desorption of the sample was monitored versus
temperature of the sample using a thermocouple as the sample holder.
The temperature of the sample holder was calibrated for various final
currents through the potassium bead. The slope of an Arrhenius plot of log
of the rate of appearance of MK+ versus 1/T(K) yields the heat of
vaporization for the desorbed neutral. The high mass spectral acquisition
rates available with the ITR may provide more accurate determinations of
the heats of vaporization and may be used to determine the heats of

vaporization of several species in the same experiment.

101
B. Experimental

1. K+IDS probe design

When K+IDS was considered for study on the BDTOF mass
spectrometer, a probe had to be designed that could operate at high ion
source potentials (3-5 kV). Figure 5.4 shows the probe design and the
materials used for its construction. The vacuum-lock inlet of the Dupont
21-49lB ion source housing was designed for a 1/4 " diameter probe. High
voltage isolation for the K+IDS probe was achieved by using 1/4 " diameter
glass tubing. The two current supply leads for the potassium glass were
passed through the center of this glass tubing. One of the leads was also
passed through a second glass tube of 2 mm o.d. for electrical isolation from
the other lead. High voltage feedthroughs were also necessary for this
K+IDS probe. The base of the probe was machined from stainless steel to
weld the stainless steel high voltage feedthroughs to the base plate.
Electrical contact is made between the feedthroughs and the current supply
leads by a screw-type pinch connector. The base plate containing the two
high voltage feedthroughs was sealed to the base using a 1/16" o-ring seal.
The 1/4" glass capillary was sealed to the probe base using a Cajon fitting.
Probe disassembly was made possible by removing the probe base plate
screws, loosening the Cajon fitting and then sliding the probe base up the
length of the 1/4" glass tubing of the probe. The side of the base was also
fitted with an SGE fitting to allow a capillary column to pass through the
probe assembly up to the base of the sample holder. This setup allowed the
continuous leak of volatile samples into the ion source for mass calibration
of the time axis and performing K+ chemical ionization (Kt CI)

experiments.

102

11" x 0.029" stainless
steel spnng wire 9 1/2" x 1/4" pyrex tubing

high voltage .
/ 1/4" Cadon fitting
/ wire sample holder

feedthrough
F u

 

   
  
  

-r......—‘

——-——_—-—
, ———_—-—————_—

 

 

 

K+bead

  

glass tubing

4— ' 1/4 " dia. 4-h018d
. glass capillary ce 'c rod

~.~ valve

sample vial

Figure 5.4 K+IDS probe designed for HV ion source of BDTOF
mass spectrometer.

2. Electronic circuit modifications

The EI electron filament controls and electronics of the JEOL ion
source power supply were modified to control the current and bias voltage of
the potassium bead and sample holder. In Figure 3.4 there are two 0.50
resistors that are shaded. These resistors are used to control the current
supplied to the E1 electron filament. In the E1 mode, the minimum
unregulated current that the circuit can attain is 4 A. For a K+IDS
experiment, the current supplied to the. potassium bead typically ranges
from 2 to 3 A. Two 0.3!! resistors were added to each of the 0.59 resistors
for a total of 1.10. Adjusting the CURRENT LIMIT (1000 resistor) provided

103
a range of potassium bead currents from 1 to 3.5 A. The bias voltage
applied to the potassium bead is adjusted using the El filament voltage
(typically set to 70 V for E1). This voltage is typically set in the range fi'om 0
to 5 V above the accelerating voltage. Potassium ion emission reaches a

steady state condition within 3 s after the current supply is turned-on.

B. K+IDS by TOF-MS

Early work on K+IDS on the BDTOF mass spectrometer was directed at
creating a benchmark by which to compare to the previous K+IDS work
performed on the HP5985 quadrupole mass spectrometer. The best way to
compare the performance of the BDTOF to that of the HP mass
spectrometer is to compare the extent of conversion of K+ + M -> MK+ for
known conditions. Also, the ion transmission efficiency for a TOF mass
spectrometer utilizing a beam deflection system is not as high as that
available with other mass spectrometers (assuming that a 10 ns "slice" is
removed from a continuous ion beam for analysis using beam deflection,

99.995% of the continuous ion beam is not utilized).

In order to compare the extent of conversion of K+ + M —> MK+ of the
HP5985 and BDTOF, it was necessary to find some data acquired on the
HP5985 that showed both K+ and MK+ ions in the same mass spectrum.
From the previous work on K+IDS on the HP5985, the only mass spectra
reported that show the relative adduct ion intensities to the potassium ion
intensities for the two major isotopes of potassium (m/z 39 and 41) were in
Dan Bombick's dissertation (Figures 6-9). It is important to have both of the
potassium isotope peak intensities to determine whether the major isotope

104

peak at m/z 39 is saturating the detector. Bombick performed a number of
K+ CI experiments on different compound classes including aldehydes,
ethers, ketones, and amines to show their typical K+ CI mass spectra.
Experimental parameters included with the data in Figures 6.9 were the
ion source pressure for the samples and the current through the potassium
bead, but not the channelth electron multiplier (CEM) voltage used for
these K+ CI experiments. The voltage used determines the gain cf the CEM
detector and, therefore, it is an important parameter to determine the
feasibility of K+IDS on the BDTOF mass spectrometer.

The K+IDS mass spectrum of acetone under K+ CI conditions was
obtained on the HP5985 to determine the CEM voltage that would produce a
mass spectrum with both of the potassium isotope ion currents "on-scale"
with the acetone adduct of potassium at a partial pressure of 1 x 10'4 torr of
acetone. The CEM voltage was adjusted to 1200V to obtain this mass

spectrum. This provided a benchmark for a direct comparison of the extent
of conversion of K+ + M -) MK+ for the K+IDSIBDTOF experiments.

Bombick had reported that the energy of the potassium ions used in a
K+IDS experiment greatly affected the adduct ion intensities. An "addition
bias window" ranging from 0 to 5 V for the energy of the potassium ions
results in the best extent of conversion of K+ + M -9 MK". One of the major
difi‘erences between the HP5985 and the BDTOF mass spectrometers (other
than the mode of ion separation) is the accelerating potential used in each
instrument. The I-IP5985 mass spectrometer uses an accelerating potential
of approximately -(10 V + 100 mV/amu) compared to 1.5-3kV with the

BDTOF.

105

The electric fields in the ion volume of the Dupont 21-491B ion source
were modeled using SIMION70 to determine the penetration of the
accelerating potential into the ion volume. SIMION is a program that
allows a user to define electrode surfaces and the potentials applied to them
to determine the electric field lines for that geometry. A SIMION model of
the Dupont ion volume of the ion source used for the KtIDS experiments is
shown in Figure 5.5. Each potential field line in this figure represents a 1
volt change. The ion source voltage is 3000 V, the repeller is 3005 V and the
focus lens is at 1000 V (not shown). Figure 5.5 shows considerable
penetration (by as much as 20 V) of the accelerating field into the region of
the ion volume. The tip of the K+IDS probe containing the potassium glass
and sample holder is located midway between the repeller and ion source
exit slit of the ion source. The penetration of the accelerating potential into
the ion volume may contribute to a greater energy distribution of the
potassium ions emitted from the potassium bead than those in an ion
source in a quadrupole mass spectrometer operating with a lower

accelerating potential.

1. Grided versus Gridless Ion Source

The results of the SIMION modeling of the Dupont ion source led to a
series of experiments to compare the K+ CI extent of conversion of K+ + M
—> MK+ for an ion source with a wire mesh grid placed across the exit slit of
the ion volume relative to no grid in the ion source. A wire mesh grid
placed across the ion source exit slit will reduce the penetration of the

accelerating potential into the ion volume.

repeller ion volume
(3005V) 300W 300W 299W exitslit(3000V)

) 1

Figure 5.5 SIMION model of Dupont ion source with a
repeller voltage of 3005 V, ion volume exit slit voltage of 3000 V,
and focus lens voltage of 1000 V (not shown). Each electric field
line represents a change of 1 V. A penetration of 20 V into the
ion volume of the ion source is evident.

    
 

 

 

E

i

WW

 

 

 

 

Experimental

The experiments for the gridless and grided ion sources were
performed using the same probe assembly and potassium bead to minimize
systematic errors. The current through the potassium glass was set to

2.6A with a bias voltage less than 5V. The Kt CI mass spectrum of acetone

107
was collected at a number of pressures ranging from 3.6 x 10’5 torr to 1.6 x
10'4 torr as measured by the ionization gauge attached to the ion source
housing. Data collection was initiated and then the current supply to the
potassium bead was applied. Scan 0 is not necessarily 'time zero' because
everything is manually controlled and the time between starting data
collection with the ITR and flipping the switch for the current supply is not
constant. Data were recorded at 10 mass spectra/second for periods

ranging from 10 to 20 seconds in duration.

Results

The intensity of the ion current at m/z 39, an isotope of potassium,
saturates the preamplifier and A/D of the ITR at a potassium bead current
of 2.6 A. The ion current for the potassium isotope peak at m/z 41 did not
saturate the preamplifier and was used to compare the extent of conversion
for the grided and gridless ion source. Figure 5.7 shows the desorption
profiles at m/z 41 and at m/z 97 for the gridless ion source at 1.6 x 10‘4 torr of
acetone in the ion source. The information at the top of each figure
contains the file name, ion source pressure, mass spectral acquisition rate,
and whether there was a grid (w/ grid) or no grid (w/o grid) in the ion
source. Figure 5.7 shows the desorption profiles at m/z 41 and at m/z 97 for
the grided ion source at 1.2 x 10'4 torr of acetone in the ion source. A steady-
state ion current was established after a few seconds for each of these

experiments.

;100%=37048
:m/z97

wnH-mbmnbi—t

108

 

 

 
   

 

 

 

 

 

 

 

Figure 5.6 Desorption profiles of (M + K)+ at m/z 97 and K+

isotope at m/z 41 for gridless ion source at 1.6 x 10'4 torr partial
pressure of acetone and 10 mass spectra/second.

 

‘ 100%:
‘m/z97

 

 

.100%=4074
‘m/z41

VHH-mflwfl-Ui—i

 

 

 

0 100 200

V T V U I Y

Scan number

Figure 5.7 Desorption profiles of (M + K)+ at m/z 97 and K+
isotope at m/z 41 for grided ion source at 1.2 x 10'4 torr partial
pressure of acetone and 10 mass spectra/second.

109

Mass spectra for the gridless and grided ion source are shown in
Figures 5.8 and 5.9, respectively. The mass spectrum obtained with the
gridless ion source was at a higher pressure than the one with the grided
ion source, but the relative abundance of the (acetone + K)+ ion at m/z 97 to
that of K+ at m/z 41 is much less than that with the grided ion source. In
fact, the K+ CI mass spectrum for the grided ion source shows ion currents
at m/z 155 and at m/z 213 as well. These ions are the (2M + K)+ and (3M +
K)+ ions, where M is one acetone molecule. The increase in the extent of
conversion can be attributed to the increase in ion residence times in the ion
volume of the ion source due to the grid minimizing the drawout potential

of the accelerating voltage.

 

$

m<-nm~ow

 

 

 

 

 

 

A 1].: Annualunannnnnnnnnluflllnllnnallnllal llhunnuuuu

'40 ”so" 60 70 '8'0 '9'0 160'110
m/z

 

A A
"vv'vvv vvvvjvvfl'vvv

10 '250 30"

qnfl-mumapi—i

Figure 5.8 K+ CI mass spectrum of acetone in the gridless
ion source at 1.6 x 10'4 torr at 10 mass spectra/second. Bead
current is 2.6A.

110

 

ca<~w+m~¢tw

J

155

ll i 213
'i "-'r'r'*r"" "r'l'*"'1**'

20 40608010012014016018020220240260
m/z

 

 

 

 

wet-wmuoeo-pi—t

 

Figure 5.9 K+ CI mass spectrum of acetone in the grided ion
source at 1.2 x 10'4 torr at 10 mass spectra/second. Bead
current is 2.6A.

This result in an increase in conversion of gas phase Kt to (M + K)+
prompted data collection for the grided and gridless ion source at a number
of partial pressures of acetone in the ion source. Table 5.1 contains the
intensity at m/z 41 and at m/z 97 for the adduct ion of acetone for the
gridless ion source. The values reported for the intensity at m/z 41 and at
m/z 97 are the average of scans 60 to 100. Table 5.2 contains the intensity at
m/z 41 and the (Mn + K)+ ions at m/z 97, m/z 155 and m/z 213 for the grided
ion source. The data are the average of scans 100 to 200. The abundance of

111
the potassium isotope peak at m/z 41 decreases at higher pressures due to
"cooling" of the potassium bead by gas phase acetone molecules.

The grided ion source data are plotted in Figure 5.10 to show the
general trends in the adduct ion intensities with partial pressure of
acetone. The ITR data system can only sum up to 65,536 peak intensity
counts for each time bin in each scan; if the ion current for a particular
time bin "saturates" the ITR, the "excess" ion current is subtracted from
65,536 and that difference stored as the peak intensity. Based on the general
trend of the ion current at m/z 97 in Figure 5.10 up to 9.5 x 10'5 torr of
acetone, it is apparent that this ion current saturated the ITR data system.
At 1 x 10" torr of acetone in the ion source, the increase in extent of
conversion with the grid in the ion source is approximately a factor of 15.
This is more clearly shown in Figure 5.11, which compares the ratio of the
acetone adduct ion at m/z 97 to that at m/z 41 versus the partial pressure of
acetone for the grided and gridless ion source. Figure 5.11 also shows the
multiple acetone adduct ions to potassium for the grided ion source. The
remaining K+IDS data were collected with a grid in the ion source due to

the improved extent of conversion with the grided ion source.
2. MK+ abundance versus pressure

The mechanism of adduct ion formation in K+IDS has been considered
a termolecular process, at least for small analyte molecules. Previous work
by Bombick showed improved sensitivity (by a factor of 2) when a collision
gas at 1 x 10'4 torr N2 was used in a KtIDS analysis of polyphenyl ether.
Collisional stabilization of an excited MK" adduct ion can result from

collision with another gas phase molecule or with the walls of the ion

112
Table 5.1 Average intensity of K+ isotope peak at m/z 41 and
(acetone + K)+ at m/z 97 for various partial pressures of acetone

in a 'dless ion source.
I Table 5.1

 

 

   

     

 

 

 

 

 

 

 

Gridless ion source
Partial pressure of Intensity at m/z 41 Intensity at m/z 97
acetone (torr)

6e-05 2328 71

8e-05 3175 1226
1.1e-04 6677 4394
1 4e-04 coco ' 6437
1 6e-04 4303 6499
1.9e-04 5412 6&6

 

 

 

Table 5.2 Average intensity of K+ isotope peak at m/z 41 and
(acetone + K)+ at m/z 97 for various partial pressures of acetone
in a grided ion source.

I Table 5.2 l

Grided ion source

 

 
 
 

Source pressure Intensity at Intensity at Intensity at Intensity at
of acetone (in m/z 41 m/z 97 m/z 155 m/z 213
torr)

 
 

 

 

 

 

 

 

 

 

 

 

 

3.6e-05 51% 1010' 215 a
4.3a-05 8541 7436 592 $3
5.6605 9922 19707 2117 446
9.5e-05 7570 51923 15551 14%
1.29-04 5785 5752) $978 w
1.6e-04 4485 613:!)

 

Intensity

1W '

 

113

—9— fit/Z41
—D— iti/297
+ swam/2155

—O— ave mlz 213
—'I-— cum oi 97.155213

/‘ -

I V I 1 V U I I I i V V I '

 

3.0e-5 6.0e-5 9.0e-5 1.2e-4 1.5e-4

Pressure of acetone (torr)

Figure 5.10 Plot of adduct ion peak intensity versus partial
pressure of acetone in the grided ion source. Shown is the
intensity of the potassium isotope at m/z 41 along with the
intensity of the acetone adduct ions at m/z 97, 155, 213 and the
sum of the acetone adduct ion intensities.

114

 

 

 

m I
l —D— gridless ratio intensity (m/z 97/m/z 41)

c) 18 ‘ + grided ratio intensity (m/z 97/m/z 41)
3. g 16 ‘ —9— grided ratio intensity ((m/z 97 + 155 + 213)/m/z 41)
r -
.5 “a .. ‘4 "

In I: l
“a t: O 12 J
a3 a .
g E .5 m -
..... g i
g a *3 8-
8.2 3 6-
“.1
o '0 .
O 3 4 q
'5 8. .
.2 5 2..

0" I ' I
2.08-5 6.0e-5 1.094 1.484 1.88-4

Partial pressure of acetone (torr)

Figure 5.11 Comparison of acetone adduct ion peak intensity
to potassium isotope peak intensity at m/z 41 for the grided and
gridless ion source. A factor of 15 improvement is adduct
formation is gained by using a grid in the ion source.

volume. The effect of pressure on the extent of conversion was studied
using palmitic acid as the analyte and triethylamine as the steady state
background pressure (Triethylamine was conveniently available in the
sample vial used for mass calibration). A more appropriate collision gas
would be one that does not react with the potassium ions, but only serves to

absorb excess energy from excited K+ adduct ions.

Table 5.3 lists the results obtained at two different pressures of
triethylamine for the analysis of the same amount of palmitic acid. The
peak intensity for the MK+ of palmitic acid at m/z 295 is tabulated with the

115
peak intensity for the potassium isotope at mlz 39. The extent of conversion
of K+ + M —) MK+ is calculated by the following equation:

2 MKf
2 (11+ + MK“)

 

The number in parentheses in Table 5.3 is the percent of adduct ion formed
relative to potassium ions available. Note that at higher pressures there is
a "cooling" effect of the potassium bead due to the collision of the
triethylamine with the potassium bead causing fewer potassium ions to be
formed. An improvement by a factor of 6 in the extent of conversion results

at the higher pressure.

Table 5.3 Extent of conversion of palmitic acid versus

back ound pressure of triethylamine. ,
I Table 5.3 I

Peak intensity for MK+ of palmitic acid vs triethylamine partial
pressure

 

 

 
  
  

Peak intensity for
MK+ at mlz 295

Peak intensity for
K” at mlz 39

Triethylamine
partial pressure
(tort)

       

 

 

  
   

87(0.7%)
1.5e-04 I 3170 131(4.1%)

116
B. K+IDS spectra

During the course of these studies, the use of potassium carbonate as
the source of K+ was investigated. Upon heating, potassium carbonate
decomposes into K20 and C02. On a hot wire, the K20 produces 10‘. The
reasoning for the use of K2C03 is that the formation of K+ and C02 will
provide both the formation of potassium adduct ions and also a collision gas
to stabilize the adduct ions. Potassium carbonate was dissolved in water
and a In] drop of this solution placed on a bare rhenium wire (in place of
the rhenium wire with the potassium bead) and allowed to dry. Rapid
heating of the rhenium wire produces a large flux of potassium ions along
with an increase in the ion source pressure to 5 x 10'4 torr for
approximately 2 to 3 seconds. A steady state of K+ exists for several minutes
after the initial "burst" of K+ at approximately the same abundance as that
from a potassium glass. It was difficult to quantitate the improvement in
the sensitivity afforded from the use of K2CO3 compared to use of a
potassium bead due to the relatively large sample sizes needed for a K+IDS
analysis on the BDTOF mass spectrometer. The sensitivity did, however,
appear to be improved with the use of K2003.

1. Polyethylene Glycol (PEG) 600

Polyethylene glycols are liquid and solid polymers of the general
formula H(OCHzCH2)nOH. Polyethylene glycol 600 (PEG 600) has an
average value of n between 12.5 - 13.9, and a molecular weight range of 570 -
630 11. PEG 600 was analyzed by placing 1 pl of neat PEG 600 on the wire
sample holder and lul of a K2003 solution in H20 on the rhenium filament

wire and the H20 allowed to evaporate. The current in the rhenium wire

was set to 2.7 A and the data collected at 10 mass spectra/second from 250 to

117

930 u. The desorption profiles for the oligomers with n = 5,8,11,13,16,and 19
are shown in Figure 5.12. The desorption of PEG 600 is complete in
approximately 6 seconds with increasing desorption times with increasing
size of the oligomer. The 10 mass spectra/second acquisition rate allows an
accurate reconstruction of the desorption profiles for the MK+ ions
representing each of the oligomers in the mixture and provides a data base
that contains mass spectra during the early and late stages of the
desorption process. Figure 5.13 shows the mass spectrum resulting fi'om
the sum (scans 40 to 50) of the mass spectra early in the analysis; Figures
5.14 and 5.15 are the mass spectra that result from the sum of the mass
spectra in scans 50 to 60 and scans 70 to 80, respectively. The mass
spectrum in Figure 5.16 is the sum of all scans represented in Figures 5.13-
13 (scans 40 to 80).

m<-nmwaw

VHH-thbn-DH

118

: 100%: 4395 m/z 393
{ [H(OCH 2191310112) OH]

:100%= -7421 m/z 761
: [moon 201496 OHJK

:100%.-.3424 mlz 629
-‘ [H(OCH20H2) OHlK

: 13

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1 100% = 8360 mlz 541
‘ [H(OCHZCH2) 0H]K*
1 11
: 100% = 3734 m/z 409
[H(OCHZCH2) OHJK”
s
i 100%: 10328 mlz 277
i [H(OCHZCH2) OHlK+
.' 5
‘ , , A 4W...
1 100
Scan number

Figure 5.12 Desorption profiles for oligomers with n =
5,8,11,13,16,and 19 for PEG 600. A potassium bead current of
2.7 A and mass spectral acquisition rate of 10 mass
spectra/second were used.

 

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600 640 680 720 760 800 840 880 {9132/2

Figure 5.16 Mass spectrum of PEG 600 from the sum of scans
40 to 80. The current was 2.7 A for the potassium carbonate
support wire. The mass spectral acquisition rate was 10 mass
spectra/second.

Figure 5.16 shows the distribution of the oligomers in PEG 600 and can
be used to provide information on the number-average molecular weight
and weight-average molecular weight for this polymer.72 The number-
average molecular weight, Mn, is defined by Mn = ZNiMi/ZNi where Ni is
approximated by the peak intensity for each oligomer of molecular weight
Mi. The weight-average molecular weight, MW, is defined by MW =
ZNiMi3/2NiMi. The peak intensity at each Mi was corrected by subtraction
of the background intensity observed in Figure 5.16 at each mlz value. For
this particular analysis, Mn = 603 and Mw = 642.

123

The analysis of PEG 600 by K+IDS can also provide structural
information of the monomeric units of the polymer. The mechanism of
fragmentation for K+IDS is believed to be a 1.2-elimination followed by K+
adduct formation of neutral species in the gas phase.26 Figure 5.17 shows
the mass spectrum of the low mass ions of PEG 600. Scheme I shows the
fragmentation pathways and resulting ion series labeled as A,B,C, and D
for PEG polymers. The four series of fragment ions observed in the mass
spectra of PEG polymers are labeled in the mass spectrum in figure 5.17.
The fragmentation observed is sufficient to determine the structure of the
polymer for this analysis.

 

 

 

 

 

 

{B
R‘
a? 1:145 C
l. 83 C A D
:4 127 14.5 159
i1 A B
v.
ei
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1405060708090100110120130140150160
11.
t.
e4 A A A
:10 189 D 233 277
i‘171 i
t; B 203 ' D
y

 

 

17018019)Z'Xl2102m230240%030270$0fl)3n
mlz

Figure 5.17 PEG 600 mass spectrum showing low mass ions.
The scan rate is 10 mass spectra/second. Bead current is 2.6
A. Average of scans 20 to 100. Peaks are labeled based on
Scheme I.

124
Scheme I

[HOCHZCHZOCH20H2(OCHZCH2),,OH]K*

[HOCHch o

Iw‘i'
H CH20H2(OCH20H2),,0H]K”
l -HOCHZCH=O

CH30H2(OCH20H2),,0H1K+

[HO H

W |

CH2—CHOCHZCH2(OCH2CH2),,OH]K*
I
-1120

CH2 = CHOCHzCHz(OCH20H2)nOH]K+

mm

[11W CHZOCHZCH2(OCH2CH2),,OH]K+
l «mu.

CH3 OCH20H2(OCHZCH2),,OH1K*

125

The K+IDS analysis of PEG 600 with the BDTOF mass spectrometer
does not induce as much fragmentation as that previously shown using the
HP 5985 mass spectrometer. The BDTOF ion source was maintained at
room temperature except for heating of the ion source by the potassium
glass during each analysis by K+IDS. The mass spectra show fragment
ions in the oligomers from n = 1 to 4 with little to no fragmentation in the
larger oligomers. The temperature of the ion source used on the HP 5985
mass spectrometer is typically operated at 100°C and may contribute to the
increased fragmentation and the duration of the adduct ion currents

observed in K+IDS analyses using this instrument.

One observation from the mass spectrum of PEG 600 in Figure 5.16 is
the broad increase in the width of each peak as the m/z increases. Figure
5.18 shows a region of the PEG 600 mass spectrum collected as raw data,
with data points collected at 5 ns intervals. Peaks at m/z 581, m/z 585 and at
mlz 590 are labeled in the figure. The mass resolution appears to be greatly
reduced compared to that of the BDTOF mass spectrometer operated in the
El mode. This phenomenon is still under investigation, but is most likely
due to the energy distribution in the ions upon formation. If this is so,
installation of the electric sector between the ion source and the flight tube,
as in the BEDER-TOF mass spectrometer, may improve the mass

resolution.

585
m1 l
2000-
:? 581|
g 590
S l
lfll)‘ ‘

 

 

l I
98.0 99.0 100.0

Flight time in microseconds

Figure 5.18 Raw data collected at 5ns time bins in flight time
region of mlz 585 of PEG 600.

2.PEG750

Figure 5.19 shows the K+IDS mass spectrum of PEG 750 with a
potassium bead current of 2.6 A at a mass spectral acquisition rate of 10
mass spectra/second. A comparison of the mass spectra for PEG 600
(Figure 5.16) and PEG 750 show that the distribution of oligomers is shifted
to a higher value of n as expected. Again, the distribution of the oligomers

127

in PEG 750 can be used to determine the number-average molecular
weight, Mn, and the weight-average molecular weight, MW. The peak
intensity at each Mi was corrected by subtraction of the background
intensity observed in Figure 5.19 at each mlz value. The experimental
number-average and weight-average molecular weights are Mn = 633 and
Mw = 660, respectively. The low values for Mn and Mw may result from
approximating Ni by the peak intensity for each oligomer. The broad
increase in peak widths at the higher mlz values may be responsible for the
low peak intensities. Another factor that may contribute to the low values
for Mn and MW is the dependence of the detectors ion detection efliciency on
mlz value. This dependence would be diflicult to quantify.

 

 

 

 

 

     

 

 

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ed

1.

a:

t.

i.

v-r 321

el ,r‘l..‘..

1200 240 280 320

n

t.‘ 585 629 613

e. 717

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s< l 305

i- 849 891

t; | ' T ‘

y . I ' . m .. 11 J
.immleW . I‘M“ IN £11411!

560 600 640 680 720 760 800 840 880
mlz

Figure 5.19 K+IDS mass spectrum of PEG 750 from average of
scans 50 to 80. Bead current of 2.6 A was used at a mass
spectral acquisition rate of 10 mass spectra/second.

C. Current limitations of K+IDS by BDTOF-MS

There are a number of interesting conclusions that can be made from
this work. The relative extent of conversion of the HP and BDTOF mass
spectrometers are similar, if not the same, within experimental error.
This means that whatever the sample size, both mass spectrometers
produce the same relative amount of K+ adduct ions to potassium ions
available. A limitation of the BDTOF mass spectrometer is the low ion
current that is available for amplification compared to the HP 5985
quadrupole mass spectrometer. Also, the ion transmission efliciency of a
quadrupole with wide apertures is much higher than that of a TOF mass

spectrometer with narrow slits and beam deflection.

The comparison study of the HP 5985 and BDTOF mass spectrometers
for the K+IDS analysis of acetone under K+ CI conditions determined that
the HP 5985 mass spectrometer had similar detector output currents for the
4700 series CEM operating voltage of 1.2kV compared to the FTD-2003
operating at 2000 V. The Galileo FTD-2003 detector used in the BDTOF
mass spectrometer is always operated at its maximum gain setting of 106
due to the low ion transmission emciency of this instrument. The electron
gain for the 4700 series CEM at an operating voltage of 1.2kV is 1 x 104.73
Therefore, it appears that the available ion current for detection is a factor
of 100 higher for the HP 5985 compared to that in the BDTOF mass
spectrometer. With a maximum electron gain of 4 x 106 possible for the
4700 series channeltron detector, it is apparent that improvements in the

ion transmission efliciency or detector gain response is necessary for the

129
BDTOF mass spectrometer to utilize this instrument for further study of
K+IDS.

The Becton-Dickinson MM-l-lSG may meet the gain requirements of
the detector necessary for successful implementation of K+ IDS on the
BDTOF mass spectrometer. This detector can provide an electron gain up
to 109 when new or reactivated by the manufacturer. The detector gain for
this type of detector (Cu-Be discrete dynodes) diminishes over time due to
exposure to high currents and contamination due to exposure to the
atmosphere. This detector was used for some of the K+IDS studies, but was
not operating with its maximum gain characteristics because it was

installed in the instrument after many years of exposure to the atmosphere.

130

Appendix I

Mass spectra of selected compounds using the BDTOF mass spectrometer

‘E

 

iI
300
mlz

l
100120140160180200220240260280

 

143

 

 

74

 

Figure A.1 Mass spectrum of methyl stearate by GC/MS.

 

40mm

 

 

g‘e‘sré‘eZS'
m

Qmflddou>0 Hdumflmmah

131

 

5731 N

 

 

 

 

 

 

 

 

 

 

 

3250 83237 ' 8525 8662 8800
Time bins

Figure A.2 EI mass spectrum of xenon with VA of 1000 V.
Beam deflection d spacing is 25 mm with no detector slit
assembly.

 

10998

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Figure A.3 EI mass spectrum of xenon with VA of 1500 V.
Beam deflection d spacing is 25 mm with no detector slit
assembly.

 

 

 

 

 

 

 

 

 

 

 

 

 

UL.

6300 6400 ' 6500 séoo 6700
Time bins

Figure A.4 EI mass spectrum of xenon with VA of 2200 V.
Beam deflection d spacing is 25 mm with no detector slit
assembly.

 

12462‘ 1‘

”1960*

1457 ‘

9.. w V. W Z .
9800 9%0 10100 10250 10400
Time bins

 

 

 

 

 

 

 

 

 

 

 

 

Figure A.5 EI mass spectrum of xenon with VA of 1000 V.
Beam deflection d spacing is 25 mm with the detector slit
assembly adjusted to 5 mm.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

34%
I .
n29:32
t
e
:m‘ .
i
t I
y 1571*
1MW W -
947350 7950 8050 8150 8250

Figure A.6 EI mass spectrum of xenon with VA of 1500 V.
Beam deflection d spacing is 25 mm with the detector slit
assembly adjusted to 5 mm.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

4&1
I 3713'
n
t
e
11
32766'
i
t
y

1818‘

871M Z , , r . .

6200 6300 6400 6500 6600

Figure A.7 EI mass spectrum of xenon with VA of 2200 V.
Beam deflection d spacing is 25 mm with the detector slit
assembly adjusted to 5 mm.

m<-e+m—'cbv;u

‘(fifl‘mbmfiflhfl

 

vgvapg42.msu
vgvapg 20ug 108ps 8&0 grid em5000 5/2/91
Scans 42-52 : 481 peaks; 100%: 39757, TII= 908061, Ret time =0.068

 

537

 

381

 

 

 

Figure A.8 K+IDS mass spectrum of the hexapeptide
VGVAPG (MW = 498 u) at 10 mass spectra/second.

 

 

 

 

Beam Deflection for Temporal Encoding
in Time-of-Flight Mass Spectrometry

G. E. Yefchak, G. A. Schultz. J. Allison. and C. G. Enke
wam.wmum.huumwuu

I. P. Holland
wam.w5uuum.umwuu

 

The ionmrcesuaedinconventionaldnu-ot-flightmspmuyflOFMS)
doriotpmvideadeqtnumolvingpoweraaossuiemnngemiorappg
tiorumchasgaschromatogrephycombirwdwithoiassspectrometrfi
andexperirnentalaspectsotbeamdeflection .whichpronde tirneencodingtor
TOFMSwithcontirmousionssources. areexpioredhere. lnthisepprosch. ionsourcecondi-
tionsdonotatiectresol powerJllowirigtoragreetervarietyotioniutionmodestobe'

duapabflifiesofthbsystemancompuedtodmeotxammgmmum

‘
“

Schsa Spam 19”. I. “(l-“7)

 

 

llverietiesottime-ot-fliglitfionuassspec-

mmshareaneedioreynchrore'sedion
1 kpecsnproduction.Thedepamu-eotionpscko
etsironitheionsourceservestoindicatethestart-
irgtimestorionveloo’tyrneasureoientandthedi-
diamondthebnpadetdetermineemaseresolving
power. Although most TOF mass spectrometers malls
useotso-caliedpulsedionsourcee(i.e..ionsources
thstgerlnteionpsdtetsdirectly).thereareanumber
otcircumstancesinwhichitisdesirebletousesources
that produce ions continuously. Beans produced by
these‘ ‘contirmousionsources.’ 'whicharesimilarto
sourcesusedinmagneticsectorendquadrupoiemass
spectrometers. arespetiallymoduletedasdesaibed
belowtoa'eatethedeeiredionpschetstorTOFmass
anslyeis

Atheoreticelmdbesmuioduladontech-
mumphysicsappesred'oiIMULandin
1973 many theoretical considerstions for beam modu-
laticninTOl-‘massspecuornsoyflOl-‘Mfimelo
egsrelydesaibedbybaitlrsrRLShortlythereatter.
mnported thecorwtructionota beam modu-
lsthnTOFinass endsn '
mammm VerioueotherTOFin-
mmmmduhtionhavem
beenreported. dioeeotPinltmetal.[4l.
GlhhandGoeringertSl. andEdnnrodeetal. [6].A
beenimodulationionsourcewasalsodeveiopedfor
thesuiylendbrTOPWbyfirtreflandco-
WIZBLMMsWWM

Afl- reprnmCCltvep-Idm.”
“all”. Esau“).

©IMAmSoaeryiorMe-Specrnoieoy
toes-mm»

beenusedinatendeoiTOFoiaespmtose-
lectparereiompriortosseultdstageotoissearflysb
[9]. The ordiogonal-scceleretion TOFMSW
recentlydesaibedbyDewaonendGuilluusllOlirm
poreteebeem-deflectioninthebroedeetsense.butdie
operating pruicipleotorthogonalacaleretiondiflers
suflfientlytromconventionalbeam-otodulstsontedi-
niqueetoexdudeitsdiscussioninthiswork.
lonpacketproductionbymodulationotacon-
timousbeameliminatessooieottheditfhilt'neen-
counteredwithmoreconventionalpulsed-sotmtsdi-
niques. particularly when gaseous sunples such as
those encountered in gas chmuistog-ephy combirwd
withmassspeco'onietry(GCJMS)aretorused.With
pulsedionsources. threepatternsotionbehsviw
canleedtodeaeesedmassresolvingpowerm. 12].
fliedisu'ibutionotinitialpositiomotiomwithiidie
somee.espedallyimportantiorgaseoussamples.and
thedisu'ibutionotinitialionveiodiesbothlesdtos
spreedinfinalkineticenergyJ'hisspreadinm
energyleadstoadistributionotanivaltimesiorho-
maseionsandhencetothelossotresolvingpower.
Furthermore. thetliermaloiotionofiommwili
equalspeedstowerdandawsyirooithesmefl
prioetotheapplicstionottheatrsctionfieldresuts
ultimatelyhevingidenticalon-ardsenerp‘esJ'hedeb-
riorstionofresoivuigpowerduetothism
probieoihssnormsllybeenoiostsevere.nscsm
the use of high extraction field gradients disturbi-
miaethetum-aroundtimeinpulsedionm.Un-
fortunateleheuseotlergetieldgredieresmbetes
thespadalproblemthbincompeo'bilitybetweenspece

Mien-v3.1”
Willem!”

lA-SocllmhuI—MJJO-«i

focusing and energy focusing with gaseous samples
has been desaibed in the literature [11. 13]. Produc-
tion of ion packets by modulation of continuous beams
eliminates the turn-around problem because all ions
intheacceleratedbeamaremovinginthesamedirec-
tion. Furthermore. this elimination of the turn-around
effectpermitslowextractiongradientstobeused.
which significantly decrease the energy spread caused
by the initial spatial distribution. For these reasons.
studies of beam modulation have been undertaken in
an effort to achieve adequate mass resolving power in
GC/MS with TOF instrumentation. Both the theoretical
and experimental results reported here demonstrate
that beam deflection TOFMS is a viable technique for
GCIMS when used in combination with time-array de-
tection.

Methodology

The beam deflection TOFMS used for this study was
constructed by adapting the electron impact ion source
from a Dupont 214913 double-focusing mass spec-
trometer to a Bendix 12-101 TOFMS flight tube hav-
ing a 2.1 at length. The ion source was operated at an
accerati'ng potential of 3 IN in a continuous ion extrac-
tion mode. The ion beam enters the flight tube region
where beam modulation takes place. Die beam de-
flection assembly was constructed from copper-plated
cirniit boards and consists of two plates. 1.4 cm in
length it 2.0 cm in height. separated by a distance of
1.3 cm. This assembly was placed about 2 cm past the
source exit slit. A Galileo CEMA detector was used
to collect the ion current. The overall geometry of the
instrument is shown in Figure l.

Two dynamic voltages are used in tandem to mod-
ulate the continuous ion beam. Initially. the voltage
applied to one of the plates is held at +63 V. while
the voltage applied to the other plate is 0 V. When
beam modulation is desired. these voltage levels are
switched. in approuimately 10 ns. to 0 V and +63 V.
respectively. This is equivalent to the case in which
one plate is held at ground potential throughout the
experiment while the other plate is swept from -63

 

 

 

Fuel. Sdumaticdiagrmofthebeam-deflectionl‘OFMSin—
m.‘l‘heperariietersofiriterestmcludethebeamwidth.
8. the deflection plate separation. D. the flightopath length. L.
andthedetectorapernirewidth.$.lonsareacceleretedbythe
voltageV. appliedbetweentheeourceblochandthesourceean
slit. beamdeflectionisaccomplnhedbythevoltagell. applied
totheupperandlowerdeflsctionplatesaashovmlseeteat).

“WNW “I

Vto+63V(l.e..V, -63Vfortheequationsgiven
below). Thedualevoltageapproachisuaedsothatthe
magnitudeofthefieldreversalcanbetwiceasgreet.
forthesamerisetime.aswouldbepoesiblewithonly
oriepulsedvoltage.1‘lieriewvoltageappliedtoeach
plateismaintainedforlmas.wh°s:hallowsallofthe
ionpaciietstostriliethedetectorsurfacebeforethe
next ion modulation occurs. This modulation genr-
atesanewsetofionpachetmbutthesignalproduced
bytheseionsisignoredbythedetectionequipment
sotlutorflyfiansientsgenerutedbyeveryothermod-
ulationarecollected.Thisprocesa.whichallowsa5-
kstamplingraterusedinordertoswiddifficultiea
causedbyasymmetry betweentherisingandfalling
edges of the deflection pulses. The beam modulation
circuitry was designed in-house: schematic diagrams
for the circuits may be obtained from the authors.

Computer programs used for the simulations were
writtenin VAXollCand run onaDigitalEquipment
Corporation VAXstation 3200 computer (Mayo-d.
MA). The animation program waswritten in Microsoft
QuickC(Mia'oSoft. Redmond. WAlandrunonan
IBM-AT compatible computer.

Theory
Models for Beam Modulation Techniques

The ideal desired behavior of all beam modulation
techniques is illustrated in Figure 2; a packet having
an arbitrarily short temporal width is "chopped" out
of a continuous beam. Note that the packet retain
the kinetic energy distribution present in the original
beam and is finite in spatial and temporal width: these
are the only nonidealities if the fringing fields near
the ends of the deflection plates are ignored. All ions
depicted in Figure 2 and throughout this work have
the same mass-to-charge ratio. in actual operation. .t
course. an instrument would produce ions of van- as
masses. lon trajectories in a beam deflection item.
merit are independent of mass. though the velocities
of the different isomass packets are mass-dependent.

Modulation techniques have so far all relied upon
deflection of the beam by an electric field. generated by
some voltage function V(f). applied across a pair of de»
flection plates between which the ions pass. Some por-
tion of the beam is deflected across an aperture. caus-
inganionpacliettoemerge fromtheoppositeside.
Various V(t) functions may be used to generan ion
packetsvia atleastthreemodesofionbehavior.The
ion behavior patterns correspond“ to these modes

--°"_' ~33—~53;-

_

~- 2::-
Fig-rel. ldealionbehaviormbeammothheprocemes-
seruiallyyieldsaslicehomthecmbesnuAnowlergths

140

M2 WflAL

 

 

 

I F3

 

 

 

 

 

C

 

Flgmes.Threemodelaforbeammoduluuintechniquee. Iso-
massionaareshowntopassthmghaparrofdeflsctionplases
ariduiovetoward an aperture. Relative durationandpolaritvof
thedeflecrion voltage pulseisindcatedtoreachcase. lhedarker
shading indicates ions that will pass through the aperture and
form theionpacliet. la) Gate model; (bl Impulse Sweepmodel:
(c)DifferermallmpulseSweepmodel.

areillustratedinFigure 3. These includeapatternre-
feriedtohereastheGatemode.aswellasthelmpulse
Sweeping and Differential lrnpulse Sweeping modes
thatwereidentifiedbyfiowlerandcoodlll. lneach
ofthese modes. the "default" condition. whichexists
beforeand after applicationofthepacket-formi‘ngvolt-
agepulse.isthedeflectionoftheionbeamawayt'rom
theaperture. lntlieGateoiode(Figiire3a)tliefield
changestoallowthebeamtopassd'uectlythrough
theapertureforsomeper'kidoftime:attheendof
thistimethefieldieturmtoitsoriginalstateJnthis
iriodeV(t)servesmostcloeelyasa"gate."eithsrpre-
veruingorallowingpassageofionsthroughtheaper-
ture.The Sweepmode(Figure3b)issimilar
totheGatemodeinthatthefieldispulsed"on"fora
periodoftimeandthenreturnedtoitsoriginalvalue.
In Impulse Sweeping. however. the deflection voltage
pulseisshortmdurationcomparedtotheflighttime
throughtheplates.Thepulaeservestoaddaveloo‘ty

infill-hmi.“

componentperpendiculartothedlrsctionofionmo-
mmmmwmmdm
beamtobesweptintotlieaperture. Herethewidthd
theemergingionpacketisrelated.butnotequal.to
thedurationofthedeflectionpulse.‘l'hewidthand
iontraiectorieaarealsouussdependeruinthismode.
lmpulseSweepinghasbeendiff-inilttoamlhhbe-
caiiseitrequireaprec'negeometricaldesigr-uwd
asavoltageimpulseofprechelydefiiedamplitude.
Findiermore.itdoesiiotappeartohaveariyadvaruage
overtheothertwomodes. soitwillnotbedbcuaesd
furtherhere. lntheDifferentiallmpuheSweepmode
(Figure 3c). thedeflactionvoltageswflisspolarly.
causinga ‘kink" toformmthebeaml'heportbnof
thialiinkthatcontinuestomoveparafleltotheorigmd
beampassesthroughtheaperturetoformthepackst.
Arefereehaanotedthatatypeotlefereruiallmpibe
Sweepmgcouldalsobeaccomplishedwithuuqud
switchingvoltages.
TheGatemodeisthesimplestcaseJlerethewflth
oftheionpacketisessentiallyequaltotheduratbnof
the deflectionpulsemeglectingtheiruermediateion
behavior that occurs when the voltage change tabs
place). lonsthatpassthroughtheplateswhflethede-
flectionfieldisoffcontirmeonwardandpasstluough
theaperrurenhosethatpasathroughbeforeoraftsr
thispulaedonotJnthedesa'iptionofthismodmdie
transientionbehaviorcausedbythevoltagediangeit-
self is ignored: only the steady-state traysctor‘ns either
throughorawayfiomtheaperturearecomideredJon
packetsproducedinthecatemodearethcefoieal-
wayslongerindurationthantheflighttinlot'thebtl
through the deflection plate region. This '
mayperhapsbeoffsetbythefactthattheGatemoh
yields ionpacketsforwhichthetemporalwidthisin-
deperidentofmass.
Thetransientionbehaviorthatwasigmredinthe
Gatemodeisinfactreaponsibleforpackatformation
intheDifferennallmpulseSweepmode.Thismodeis
thereforecapableofproducingmuchshorterionpack-
ets.Considerionsthatenterthedeflectionplateregion
iustbeforetheswitchinthefielddirectionlflietime
under consideration here issomewhatearlierthanthat
ofthe"snap shot"showninFigure3c.)11ieseioruare
deflecteddownwardastheytravelthroughthereg'uin.
Whenthefieldchangespolarity.however.theybey’n
toexperiericeanupwardforce.1'hoeeioristhathave
traveledhalf-way throughtheplateregionwhenthe
pulseoccurswillexpenenceequaldurationsofdown-
wardandupwardforcesandthuseidttheregionmov-
ingparalleltotheiroriginaluapaaryTheapertureis
assumedheretobelocatedinlinewiththeinitidbsam
axis and the deflection plates. Some ions very nearto
theexacthalf-weypointofthedeflectionplateregbn
atthetimeotthefieldreversalwilldsoobiamtiml
trajectories that allow for their passage through the
aperture. The extent to which thisociurscontn'butes
tothetemporalwidthofthepadstandwilbedis-
cussedinthefollowingsection.

141

lA-SstMQSpeao-NUJ.“

lonPadirtQuali'ty
AsderivedbyBakker[2|,thetemporalbasewidthof
anionpachetresultingfromtheDifferentiallmpulse
Sweepprocessisgivenbytheexpression

(8 + $)D Van
"" " —’iv. \/ 7' 0’

wherebisthebeamwidth. Sistheaperturewidth. D
isthedeflectionplateseparation. Listhedistancebe-
tweentheplatesand the slit. and V. and V. aretheac-
celeration and deflection voltages. respectively. (That
is. the deflection voltage switches from -V, to +V,.)
Thesubacriptinw, ismeanttorepresent”ide "be-
cauaethisisthewidththatwouldbeobtainedifthe
ionbeamwereidealintermsofkineticenergyandan-
gulardispersion. Theprinn‘palassumptionsforeq 1
are that the rise time for the voltage change is neg-
liguile and. more importantly. that the distance from
the plates to the aperture. L. is much greater than the
length of the plates. (Note. however. that the actual
plate lengths do not appear in the expression.) This
latter assumption implies that the aperture should not
be placed near the deflection plates but rather at the
detector. In fact. it is possible for the detector surface
itseK to serve as the aperture.

In addition to the ideal width in. derived by Bakker.
thepacketisbroadenedbythekineticenergydistribuo
tion of ions within the packet. Two ions leaving an ini-
tialpositionx :- Osimultaneously. butwithdiffering
kineticenerp‘esUandu +B)U.willarriveataloca-
tion 2 - l. separated in time by At a: BLwn/Ulmlt.
Thus. an ion packet having negligible initial width but
with a normal kinetic energy distribution having stan-
dard deviation cu would be broadened. after traveling
distance L. to have a half-width given approximately
by

Tin-8L
wu - v; T (2)

whered -2.35¢u/U..
Athirdcauseforpacketbroadeningwasidentified
inthisstudyforionbeamshavingnonseroangular
divergence. Consider thetwoions showninFigure 4.
Thelowerioneriteuwithnooff-axiseriergyaridis
initiallyaccelerateddownwardbythedeflectionfield.
Ashreachespoirua.hafl-waythroughtheplatere-
gionthefleldreverseaandacceleratestheioninthe
upwarddirectionSincedownwardandupwardforce
are expel-irriced fwequal periods of time. the ion
leavesdieregbnwithmoffaaxisenergyandthus'u
iridudedinthsfinalpackst.‘l'heupperionentersthe
regbndlseoindsprkirtothelowerionandatanangle
Ofromthebeamaiiis.Duetoitsoff-axisenergy.this
ioncontinuestomoveupwardforaperiodoftimebut
iseventuallydeflecteddownwardbytheelectricfield.
Thlsionexperiencesthedownwardforcelongerthan

“WNW «3

 

 

 

 

 

Flutes. Twiorlenterugthedeflecrionplatsregi‘onwithdl-
fereretrayectoryangleeJieldreversalouawhenmelowuron
ismpouuaandtheuppcionoatpub.

theioweriondoesbecausetheuppaiontrevelsto
poiritbbeforethefieldreverses.1'liislorigerduration
of the applied downward force. followed by a slimter
durationofupwardforcelexperiemedfrompoirab
to the end of the deflection region). compensates for
the initial off-axis energy. The iontherefore leavesthe
regionparalleltothebeamaimandiaincludedlnthe
finalpacket.despitebemgot’fsetfromtheidealionby
atimedt.
Thevalueofuthatsatisfieetheeeconditiorlmay
berelatedtooffoaa'uangle.0.asfollowa.Comideran
”ide “ (i.e.. iiuti'ally on-asis)iontravelingwiththe
most-probablevelocityvo - (2V.e/rn)m. Anionen-
tering the deflection plate regionwith anotf-axisangle
Owillhaveavelocityvectorperpendiculartothebeam
axisgivenbyv.-vocosO.Whenleavingtheregion.
however.theperpendicularvelocityv',iszero.lfthe
ideal ion passes halfway through the plate region in
time tn. then the offoasis ion experiences downward
andupwardforcesfortimestm+uandtn-At.re-
spectively.ThefinaI ' velocityoftheoff-
axis ion is related to the initial value by theexpression

I

. V: V:
I), 80 . Donna-7‘00}; +N)+ gin-(ha-a“).

which rearrangestoAt - 2%msinefl'hhreprr
sentsthebroadeningot'thepeaktolowertlighttimes
dueto‘ionswith traiectoriesthatdhrergeintheup-
ward direction. (Only two-dimemional motioninthe
plane of Figuret isconsidered here.) Fotatrue beam
havingadivergencehalf-angleoftthoseiomhaving
trajectory anglesinthe downwardd'nectionwfllcause
similarbroadeningtohigherflighttimeaaswell.Thus
thequantitywcouldbeusedtoappraumatethebase
widthofapaclietbroadenedonlybythisat‘lilflef-
fect.yielding

D 2V.m .

EquationSyieldsanunderestimateofpeakbroaden-
ingduetotheangulareffect.however.becauseitis

142

m METAL

not necessary for ioru to be moving exactly parallel to
the beam axis as they leave the deflection region in
orderto pass through the aperture. Consider. forex-
ample. anionthatentersthedeflectionregionwiththe
same trajectory as the upper ion discussed above but
slightly ahead of it in time. This ion would experience
even more net downward force than the upper ion
piaiu'edinFiguretJndwouldthusleavetheregion
with a small downward velocity component. This final
traisctorycould. however. stillcarrytheionthrough
the aperture (at a position somewhat below the point
at which the pictured ion passes through). lons acting
inthisway. aswellasthe analogous ions havinginitial
downward motion. serve to further increase the find
packetwidth.Thougheq3cannotbeusedtoobtain
the complete magnitude of the peak broaderu'ng due
to angular divergence. the digital simulation described
belowcanbeusedtomeasurethiseifect.

Thebroaderungcausedbyionswithpositiveand
negativeinitialtraiectoryanglesneednotbesymmet-
ric because in both cases the forward velocity (in the
direction of the beam axis) of these off-axis ions is re-
ducedfromtheidealvelocitybyafactorofcostfor
ions having the same kinetic energy. The flight time
for ions haying an initial downward velocity compo-
nent is increased over that of the ideal ion both by
their lower velocity in the beam axis as well as the an.
gular effect described above. For the ions haying some
initial upward motion. however. flight times tend to be
deceased by the angular effect but inaeased by their
reduced velocity. The net result of this is that the peak
is skewed toward higher flight times

It is difficult to combine the expressions for w, . tau.
and in. directly to obtain an expression for true peak
width. but any of the expressions can be used alone
to approximate peak widths for cases in which one
effect (geometry. energy distribution. or angular di-
vergence) predominates. The combination of the three
effects was explored by means of digital simulations
as desaibed below: the individual expressions were
useful for checking the validity of these simulations as
well.

Simulations

In order to explore the combination of the energy
spread and angular divergence effects with the ideal
packetwidthgivenbyeql. computerprogramswere
developedtomodelionpacketbehavior. First. anani-
mationpiogrsmwasdevelopedthatillustratesionbe-
havicrinbeammodulationbymovingcoloieddots.

' individualbrmacrossthescreenofan
13M AT-oompstible computer. (Thisptogramwasused
toascertsinthepstternofionmotionshowninFigure
4.)Thenasimuletionprogamwaswrittentogener-
ate psi shapes for beam modulation TOFMS. The
triethodusedforthissimulationwillbeexplainedwith
theaidofFigure5.Theprogrammodelsthemotionof
variousions.chosensystematicallyfromtheregionin-

Insult-”Ml.”

51.—

 

Flg-es. Minimum-Whit!”
progrsmlseetexti.

dicated. by rneansof Runge-Kutta inugramnthrough
thedeflectionplatereg‘ionandonwardtothsapsr-
ture.l-1lghttimesforthoseionsfoundtopamthrough
theaperturearetabulatedintheformofahistogram
togeneratethepeakshape.Thethressolidregiorein
FlgureSaremeanttoindicatethelocusofpoiresoccu-
piedbytheseioruatthreeinstantsintimmpriortoen-
tering the deflection region. part-wayalongthsflight
path. andiustafterpassagethroughtheaperture.(§ss
ref2foracompletedescriptionoftheshapesofthese
ream.)
Anexamplsoftheoutputfromthisprogram‘u
giveninFigurefifortheparametersshowanablel.
Thepeak widthsobtainedbythissimulationmethod
maybeapproximatedbymeansofeqsl-Ilbyusingcal-
culated values of w), um, and to. toobtainestimams
ofpeakvariances. Thevarianceoftheoverallpeak'o
then givenbythesumofthecontributingvanances.
Examples of this process and ' with the
simulated peaks are summarized in Table 2. Values
forvsriancesshowninparenthesesweiealculatsdu
thedifferencebetweentheothersimulatedvalussun-
der the additivity-of-variances assumption. The peak

OJ 1

 

 

I. J

ioo'so itess

shape for ms 1“. -—-I&II
etfsctonlv: ------ -Bakkereffectwithenergydisperuon. -------
with diam -----alleflscta

14.3

”.thth

Table 1. Parametersussdforsimulatsd beam
deflectionpeskshape

 

 

lMu
V, soc. V
V. 1%. V
l. 1.5“ m
0 aces m
S QM m
I 0.”: m
0 0.1“
d

elk. 712l- 0.0215 sV

 

shapeobtainedbythebakkereffectalonemaybeap-
proximatedasatriangle.(1'hiswasfoundtoyieldmore
accurate results than a rectangular peak shape.) The
variancsofanisoscelestriangle havingabasewidthrr,
is given by Elf/2‘. Similarly. the variance contributed
by the angular effect may be approximated by tai/12;
a rectangular peak shape is assumed here to model
cases in which all values of 0 within the limits given
are equally likely. If the peak shape corresponding to
theenergyet'fect isassumedtobe normalwithastan-
dard deviation of tau/2.35. the variance contributed by
the energy effect is then (mu/235?. The accuracy of
the simulated peak variances cannot be well character-
izsd without. for example. detailed Monte Carlo anal-
ysis. but these widths are believed to fall within a few
percent of the true values. Note that the prediction of
peak widths from variance calculation is unreliable.
in particular for the angular divergence effect. This is
due to the variety of peak shapes (nearly rectangular
to nearly Gaussian) that can occur as the various pa-
rametersarealtered. Forcasesinwhich the
divergence is very small (e.g., o < 001°). the predic-
tion can be quite accurate: this was the case in the
experimental study desorbed below.

Experimental Results

A spectrum of perfluorotributylamine (PFTBA). ob-
taindbydiiectinletintroducu'onwithanionsource
temperatureof150°C.isshowninFigure7.'l'hese
dataresultfromtheintegrationofmuanientscol-

mammalian- 46

lectedin 1 sandsummedbythelrugrstlr'tran-
sienttecorder(l'l'll)[14].Acompu-‘uonofpsakbus-
widthsfoririaiorionirithisspscmimtothosspro-
duadbydlgitalsiniulationisaliowniristls3.l‘or
thesimulated data. parametersmachingthephysi-
caldimensionandvoltagesoftheintrumeruwere
used.namelyl. -2.1m.5 -6.35uun.8 -0.13
mD- 13mm.V. -3llllV.andV¢ -63V.
Thestandarddeviationofthekinetkenrgydisu'bu-
tion.:ru. wasapprurimatedasOJeVbassdonths
‘ ofthebesmwasneglscted.Thealopeof
base-width vs. (hit/r forthesxperi‘merual valussb
calculated tobe3.7:i:0.2 ns. andthatforthesirmilated
datais4.0:i:0.1n.de thattheintmmeru
performsncefollowsthetheorydesuibedabove.An
"expscted"slopecanbeobtainedbysumrningeqa1
andlthenfactoringoutnTh'nprocedureyieldsa
valueof3.9nsif0isassigisdavalueof6eu/u.to
reptesentbase-widths.Thissimplemethodisnotap-
proprietswhentheangulardlvergenceislsrge.butit
isquiteadequateforthiscase.

Practical Consideration

Mass Resolving Porter

Thel’Fl'BAspscti-umshownabovewssobtainedwith
unitorbettermassresolutionuptoatleastsi/sm
Anestimateoftheuppermasalimitforurutmamre-
solvingpowerwiththisintrumerucsnbefoundas
follows. Theflighttimeseparationbetweenionoftwo
adiacent Ill/Z valuesisgivenby

At - fih/m/z +1- V375) (4)

whereuistheatomicmassunit.5quation4msybe
approximatedbythefirsttermoftheTaylorseriesas

Ala ("a (5)

2 Julia /2

lnthepreviousaectioruthepeakbssewidthwasfound
tobe given approximately by3.9‘/ni/r n. (Eitherths
experimental slopeorthevalusfoundvia simulstain

Tablsz. Comperisonofpeskvariancesobtsinedfromcalculationusmgeqsl-Jand

 

 

 

fromdlgitalpsskshapssi‘mulatisn

cm cm 3m
Sci-net basswidth vsnsnos yeti-tes
be. hen-wig x 10" s‘ x 10‘" s' x 10'" s'
mother 13.! I 9
m 7.7 11 l‘lll
Am 0.! 7 lidl
but. 0 energy 19 20
M e any. 15 25
Idler 4- energy 0 angle 26 35

 

m METAL.

 

 

 

 

 

JAP4:

Infield-Smut.“

 

 

1..
O.
'0‘
"l 30°"- as
l
ges‘ gasses-J
I.
. Item
in
g. .
o 1 °‘
a: ao‘ so son sea so:
4 “its“
3“
1"
s l -1 I ll .1.1 I I
g '90.'lflrldefl‘rlO‘rlafli'efl‘vdavm'f,
mlz

Flgere7. MauspscnumofPFTlAcolhctedbvbesordeflsctionTOFMSJypicflpsakflupss-e

shownintlieinsetforin!1219and mm.

could also be used.) For simplicity. the width at half-
height (seconds) may be approximated as half of this
value. thus
w. ., z 2.0 x 10" (fin—[z (6)
Setting At awn yields the nu: value at which peak
separation rust equals peak width at half-height. and
heme the approximate upper ni/z limit for unit mass
resolving power. For the parameters in this example.
thisupperlimitisanni/z valueof710.
Animprovementcouldbemadeifanionmirror
were incorporated into the instrument. The ion mirror
would remove the effect of the energy dispersion and.
inadditiottincreasstheeffsctiveflightpathlength

Tables. Compsr‘uonofmsasuredandsimulatsdpeak

 

 

 

l . l I

m Misfire) SlmulsrulsSns)
69 40. as.

mo 30. 42.

131 51. 46.

219 64. 51.

264 67. as.

502 u. 92.

 

byafactoroffour.('l'hedecreasedflighttimeinthe
minor contributes a factor of two. while the travel in
the forward and reverse direction through the flight
path contributes another factor of two.) in this case. the
expected slop: is obtained from eq 1 alone and has the
value 2.5 v’m 12 ns. Using this value. and replacing L by
4L in eq 5. the upper m: limit increases to «no. This
is certainly adequate for most GCIMS application.

Signol-to-Noise Considerations

it would appear that beam modulation in TOT-MS
would experience greatly reduced detectability and
sensitivity due to the very small portion or the ion
beam that is selected for detection. In addition. it
would appear that the beam dimensions required for
beam deflection. which are much smaller than those
in conventional TOFMS. would further contribute to
poor ion statistics. It is important to realize. however.
that during the time an ion packet is striking the detec-
tor. the measured ion flux is the same as that seen from
a continuous beam. The advantage of the continuous
beamlies inthe possibilityofaveragingtheioninten-
sity measurements over a longer period of time. This
advantage results in an improvement in signal-to-noise
ratio (SIN)equaltothesquars-rootoftheratioofthe
measurement times. A TOP instrumuit with a packet

145

lAmIseH-ipu—MJ.“

widthoflOnandanextrscthnrepetitionratsoflO
kl'lawouldhsveanSlNlmtimesworsedianacoruln-
uousbeamscsnninginsu-umerewhenussdtomoru‘tm
asinglern/rvalueanruct'Inscaruurgsectorm
spectrometersgenerallyhavemuchloweriontran-
missionefficiencissthanTOFinu'umeresduetothe
smallerspsrturesrequ'nedtluoughoutthefllghtpeth.
lnquadrupolemaasspsctrometsraiontranmission'u
alsolimitedbytheaoceptanceangleandapertureere-
quired.5ecausescarirungmassspecuometersactas
deaeasesasthemassresolvingpowerisincreassd.0n
theotherhand.aTOFMSsystemthatfocuses(rather
thanfiltersHheioncanintenifythepeakciureru
rstherthaniustreducingthepeakwidth.asresolv-
ingpowerisincrsued.3ecausetheionmmorisa
' deviceand.withoutgrida.canbemadewith
encellent(ca.90%)tranmittance[15].thepeakcurteru
inamittorTOl-‘instrumentcanbehiglierthanthesv-
erageinstantaneousbeamcurtentforthesamemass.
Thesefactorstendtocounterschtosomedegremthe
deacaseinS/Npredictedfromthedutycycleconid-
erationalone.
lnthepreviouaparagraph.theionintenityatthe
peakarrivaltimsforanionofaparticularnt/zina
TOFinstrumeruiscomparedwiththepeakioninten-
sityforthatsariiein/zinamassscaruiinginu'ument
thatisfixedattheoptimumsettingfortheni/rbeing
monitored(selectedion-moriitoring. or SIM. mode).
TocompareTOFandscanrungintrumentsformodes
inwhichfullspectraaregenerated.otherfactorsned
tobeconidered.lnscanningmode.thescanningin—
sounieruniorutorsssingleni/rwiridowatalirrie.1'lie
aversgetimespentateachwindowisequaltothe
scantimedividedbythenumberofmassvaluessam-
pled. assuming no dead time between values. With
TOFMS using boxcar mtegrator detection (sometimes
called time-slice detection). the output signal also rep-
resentstheintenityofonlyonearrivaltimewindow
atatime.Thedelaytimeforthesamplewindowof
theboxcarintegratorissteppedorscanndtoobtain
amassspectiumiustasinthescaiuungfiltermass
specttouieters.Forthistypeofdetection.therelative
Sleorbothscann'mgandTOFmassspscu'ometets
mldbeequaltothatdiscussedabovefortheSlM
mode. The dutycycledisadvantsgesofTOFareoff-
set.atleastpartially.howeyer.byitstraniiwanceand
focusingadvantagee
AveryWadyueapcanbsseenforl'OF.
however.whsntime-arrsydetsction'upsrformsdusp
liganl'l'RJ'heTTRacquiresJoralltiinesllmswithm
thecollsctionper'uid.thesamsinformstbnthebai-
carintegratordossforonlyonsJioraanRthatstores
8192samplesper transient. theeffectisanS/Nim-
provementofVBl92~91timesthatofthescaruiing
baicardatacollectlonsystem. Beousethe
boitcardatasystemhas.atworst.a1m-timeslower
SthlianuiescamigfiltertiristruniemtheTOl-‘spsc-
troowterwithanl'l'landmirtorshouldhaveanSIN

mammalian. m

atleutequaltoandpotsrulallyiruichbeturthana
“‘61qu “Thebe-
cresssddatarsteavaflsblswithTOl'MSwhhl'l'Rde-
tsclloncanbeussdtogrestadvareagewhenqsara
uetobecollsmdimdercondkiondrapfllychq-
ammmdismmchmmed
WM.

Conclusion

Besmdeflsctionisbscofingsmuunonlecluflusm
TONS. yetbsamdeflsctionsyu-Iueoftends-
aigndwiththea-umptkinthmrhsionbehavhso
prodiicedwillfolloivthecstemodd.fioropdmm
time-resolutionhoweverdhemorecooplexbfiuen-
tiallmpulseSweepmecharfln'urequindJ‘hhsMy
showedthatacuu'ate ofiiiribstiaviorunht
thlsmodelcanbeobtainedeithulwdmplelnpsc-
tionoftheequatbnsgivenorbydlgitalsiiiuilsm
ofionoiotiorLSuchpredictkincanbeof-m
inthsdesigiofbsamdeflsctbnTOl-‘MSlnslrum-ls.
Thestudyalsodemonstratedthatsbeamdeflscfln
TOFMSinstrumerumcorporatngannnmii-rwsndn
l'l'llwouldhavemassresolutionandsenitlvlysui-
ableformodernGClMSspplication.

Acknowledgments

fibwmkwasmppruudbyswhudwlhugyle-
s-chhowdtheNMWdMWU
MWtDflMJ‘hs‘mar-efldhh
mum-idll'scklsn-ghtt‘m

11. mantra-cc.- Menuhin-rp-
mummmrrm

lelley.W.C.;Mcluen.l.l-l.las.5ci.mm8.
1130.

u. saunter.iusunaiieerepmir.n

Appendix III

146

Journal of Chromatography. 518 (1990) 283-295
Elsevier Science Publishers B.V.. Amsterdam

CHROM. 22 656

Renaissance of gas chromatography—time—of-flight mass
spectrometry

Meeting the challenge of capillary columns with a beam
deflection instrument and time array detection

J. T. WATSON‘

Departments of C hernistry and Biochemistry. Michigan State University. East Lansing. MI 48824 (U.S.A.)
G. A. SCHULTZ

Department or C llt’MlSH‘)‘. Michigan State Universrti'. East Lartsing. Ml 48824 ( U.S.A.)

R. E. TECKLENBURG. Jr.

Department or chhcmrstria Michigan State University. East Lansing. MI 48824 / U.S.A./

and

J. ALLISON

Department or C Ilemu'lrl'. Michigan State University. East Lansing. MI 48824 (U.S.A.)

(First received November 51h. I989: revised manuscript received June 26th. I990)

 

ABSTRACT

This report describes the use ol‘a unique beam deflection time-of-fiight mass spectrometer to address
some of the demands made on mass spectrometry by new developments in high-resolution capillary col-
umn gas chromatography. An integrating transient recorder is used in combination with this beam deflec-
tion time-ol'-flight instrument to apply the concept of time array detection in capturing all of the mass
spectral information available from the ion source. thereby greatly enhancing the signal-to-noise ratio
quality of the mass spectral data. The applicability of the time array detection approach to gas chromato-
graphy-mass spectrometry is demonstrated in the context of an analysis of the standard Grob mixture for
assessing performance of capillary column chromatography. During analysis of the Grob mixture by gas
chromatography-mass spectrometry. mass spectra were recorded at a rate of 20 scan files per second. The
data indicate that this rate of mass spectral seen his generation is adequate to provide a suitable data base
for reconstruction of the chromatographic profile. In addition. the effective scan rate is high enough that
there is no distortion in the relative peak intensities throughout the individual mass spectra of components
regardless of the relatively high dynamic changes in partial pressure of the analyte as reflected by the sharp
peaks in the chromatographic profile. The experimental results indicate that the beam deflection time-of-
flight mass spectrometer can provide mass spectra at a scan file generation rate much higher than that
possible with the conventional quadrupole or magnetic sector mass spectrometer. but at comparable
detection limits.

 

INTRODUCTION

Gas chromatography (GO—mass spectrometry (MS) is a powerful technique
because it combines a separation technique with an identification technique. The
separation power of modern high-performance gas—liquid chromatography helps

DWI-96739050150 C‘ I990 Elsevicr Science Publishers B.V.

147

 

     
    
 

   

 

 

 

 

 

 

 

 

 

 

 

 

284 J. T. WATSON ei at.
CASE A
Sample introduced from reservoir
partial g g ‘ t
pressure 3 "m 'n
of 3
analyte E
in :
ion source 5
17$ V time —)
:1”
Lil.
ml: 9 ml: 9 ml: -)
scan tile I scan tile 2 scan tile 3

CASE 3
Sample introduction by gas chromatograph

   
  
 

partial
pressure I

ot
analyte

in
ion source

 

 

 

lli llHtltHiiiiiiiiiiiiiitiiiiiiittllllli

L'-

 

 

m/z—a m/Z—O mlz-d
scan tile I scan tile 2 scan tile 3

Fig. l. Graphical illustration of the influence of analyte partial pressure in the ion source of a mass
spectrometer on the resulting bar graph mass spectra. Case A: When analyte partial pressure is constant.
spectra iii scans l. 2 and 3 are identical in the relatitc intensities of the peaks representing this hypothetical
compound. Case 8: When the partial pressure of the hypothetical compound changes in the ion source
during scans . 2 and 3. the spectra are skewed as described in the text.

148

RENAISSANCE OF GC-TIMEoOF-FLIGHT MS 285

make available at least partially purified mixture components for analysis by mass
spectrometry for identification purposes. Paradoxically. the dynamic nature of sam-
ple concentrations at the outlet of a gas chromatograph. especially in capillary col-
umn chromatography. tends to violate one of the cardinal mics in MS [I]. That is. it is
important for the partial pressure of the analyte in the ionization chamber to remain
constant during the time interval in which the mass spectrometer is scanned to ac-
quire a mass spectrum: this condition ensures that the relative peak intensities repre-
sented in the mass spectrum are related to structural features of the molecule. and not
distorted due to changes in partial pressure of the analyte during acquisition of that
mass spectrum. .

The influence of a dynamic partial pressure of an analyte in a mass spectrom-
eter‘s ion source on the appearance of the acquired mass spectra is illustrated in Fig.
1. Case A in Fig. 1 represents the acquisition of three mass spectra of a hypothetical
analyte maintained at constant pressure in the ion source. Case Bin Fig. l represents
analysis of the same hypOthetical analyte when introduced to the mass spectrometer
ion source via a gas chromatograph. The partial pressure of analyte in the ion source
of the mass spectrometer rises and then falls as the analyte emerges from the gas
chromatographic column. Scans l and 3 were acquired as the analyte concentration
(partial pressure) was changing most rapidly in the ion source during mass spectral
acquisition. and these mass spectra show a distortion or skewing of relative peak
intensities. The relative peak intensities in each mass spectrum are indicative of the
partial pressure of the analyte in the ion source. as well as the inherent fragmentation
pattern of the compound. This situation complicates mass spectral interpretation.
and limits compound identification based on mass spectral matching approaches.

Problems in t‘apt'lary GC -M S

Problem I: The acquisition of true mass spectra. The very definition of a gas
chromatogram is. in fact. the temporal profile of partial pressures of analytes as they
emerge from the chromatographic column. Improvements in the resolving power of
capillary columns during the last decade. as reflected by the very sharp peaks (2—3 s in
duration) in the chromatograms [2.3]. have placed severe demands on the mass spec-
trometer to scan quickly enough to avoid distorting the mass spectra without sacri-
ficing other important mass spectral features such as resolving power and the signal-
to-noise ratio associated with the data. This problem is exacerbated during the com-
mon occurrence of poorly resolved components: in this case. the ion source may
contain the vapor of one component or the other for only a few milliseconds. and it is
imperative to capture an undistorted “pure“ spectrum during this brief interval. An
assessment [4] of the capacity for various mass analyzers to scan rapidly during
analyses by GC—MS indicates that present demands for high scan rates (approaching
ten scans per second over the mass range 50 to 500 daltons) made by high—resolution
GC has forced many of the common mass analyzers to their very limit of performance
as established by the physics underlying their operating principles. On the other hand.
the time-of-flight mass spectrometer. by virtue of its rapid cycle time. has the capacity
for generating complete mass spectra at a rate even higher than that presently de-
manded by GC-MS instruments that utilize the most efficient high-resolution GC
capillary columns.

149

286 J. T. WATSON et al.

Problem 2: The satisfactory reconstruction of the chromatographic profile from
mass spectral data. The problem resulting from the great disparity between the rate of
change in sample partial pressure in capillary GC and the data acquisition rate of
complete mass spectra is illustrated in Fig. 2. In each of the three panels in Fig. 2. the
true chromatographic profile is illustrated by the dashed line; the solid line in each of
the three panels is an attempt to reconstruct the chromatographic profile from data
points available from a data base consisting of consecutively-recorded mass spectra.
Each point represents the reconstructed total ion current (TIC) obtained by summing
the measured intensities of all of the mass spectral peaks in one mass spectrum. In
panels A and B. the rate of data acquisition yielded one scan file per second: thus. in
these two panels there is available only one TIC point per second for purposes of
reconstructing the chromatographic profile. The only difi’erence between panels A
and B is the synchrony between the repetitive scanning of the mass spectrometer and
initialization of the chromatographic process. As can be seen in panels A and B. such
utilization of mass spectral data for reconstruction of the true chromatographic pro-
file is severely limited. However. as shown in panel C. if three points per second are
available (due to scanning the mass spectrometer three times per second) from which
to reconstruct the chromatographic profile as indicated by the solid line in panel C.
the true chromatographic profile is more correctly described.

Problem 3: Limitations of “scanning” mass analyzers. Another major problem
in GC—MS is the sacrifice of considerable ion counting statistical information when
the technique of scanning of the mass spectrometer is used. As in most spectroscopic

 

 

 

 

 

 

- ---
"
0' V
‘-----------—---- - -—--—

5:4:‘3 0246.0 0240.0
sccoms sures secures
Fig. 2. Comparison of the true chromatographic profile (--) and attempts to reconstruct the chroma-
tographic profile (—) from I0 data points for cases A and B. and 30 data points for case C. as described in
the text (adapted from ref. 4 with permission of the American Chemical Society).

150

RENAISSANCE OF GC-TIME-OF-FLIGHT MS . 287

instruments which use the exclusive process of scanning, considerable information is
lost as some parameter is varied to allow resolution elements of the mass spectrum to
consecutively pass across the detector slits. Sweeley et al. [5]. Hammar et al. [6] and
other pioneers as reviewed by Falkner [7] solved this problem with selected-ion mon-
itoring (SIM) which dedicates the instrument to monitoring ion current at only a
selected resolution element (m/z value). Whereas the excellent sensitivity of SIM (fem-
tomoles) is achieved by integrating all of the ion current from the ion source at a
particular resolution element or m/z value of the mass spectrum. such good sensitivity
could be achieved. in principle. while acquiring complete mass spectra if it were
possible to integrate all ion current at all resolution elements or all m/z values across
the mass spectrum all of the time. Such a process is possible only through array
detection which measures all ion currents over a range of m/z values simultaneously.
It would be desirable to acquire the complete mass spectrum in consecutive scans at
the same high sensitivity otherwise available only by selected-ion monitoring. The key
features of repetitive scanning and its advantages and disadvantages are presented in
Fig. 3 in parallel with the key features of SIM together with its advantages and
disadvantages.

A solution
As indicated in the conclusion of Fig. 3. the beneficial aspects of repetitive
acquisition of mass spectra in the generation of a complete data field for a GC-MS

WWW SelectedlonMo'I‘tor'nq

ONO-UM“

Naturalism-
“We“

simmere-
nae-moon

I

alien-thaw”

A.,...

M83
h—o

elitism-flame
as

 

BOTH rem
tF Au. lat m
m ALL Tl-E Till
Fig. 3. Summary of operational features and mutually exclusive advantages of the technique of repetitive
scanning and selected ion monitoring (reprinted from ref. I with permission from Raven Press).

151

288 J. T. WATSON et al.

analysis can be combined with the high sensitivity of SIM only if array detection is
used to record the mass spectrum. The approach of using array detectors in mass
spectrometry was pioneered by Gifl'en et al. [8] at the Jet Propulsion Laboratory in
the I970s. This resulted in the development of a device called an electro-optical ion
detector which was evaluated subsequently in GC-MS by Hedfiall and Ryhage [9].
The technique of Fourier transform (FT) MS also provides array detection in that all
ions present in the device are detected simultaneously [IO], although the application
of this instrument in GC—MS has not been extensively pursued to date. While FT-MS
can obtain an impressive number of mass spectra per second. there are acquisition
rate/resolution trade-ofl's. To avoid problems with limited dynamic range and other
potential mechanical difficulties with these and other approaches to array detection.
the research efl’ort in the Michigan State University (MSU) Mass Spectrometry Facil-
ity has pursued developments in time-of-flight MS to conduct array detection in time.

Time-of-flight (TOF) MS. because of its pulsed nature and the very short time
required for producing any given transient mass spectrum. i.e.. an ion sampling time
ranging from 3 to l00 its. makes this technique an ideal method for sampling rapidly
changing partial pressures of analytes in the ion source. As explained in early reports
on this work [4.11]. time array detection is achieved in TOF-MS by digitizing the
output from the detector such that all information in all resolution elements of the
transient time-of-flight mass spectrum are collected following each extraction pulse
from the ion source. For this purpose. an integrating transient recorder (ITR) has
been designed and implemented. as described elsewhere [ [2]. Briefly the [TR digitizes
the ion detector output at 200 MHZ. is capable of producing up to 50 complete mass
spectra per second. and can sustain high data collection rates continuously for up to
one hour without loss of data. Another major requirement for proper utilization of
time array detection is the necessity of providing optimum ion focus for ions of all ml:
values from each ion packet so that each of the 5000—I0 000 transient mass spectra
reaching the detector per second have properly resolved mass spectral peaks. Conven-
tional techniques in TOF-MS such as time-lag focusing are mass-dependent and are
not generally useful in conjunction with time array detection. although we have ob-
tained preliminary results [13] using time array detection with mass collection over
narrow mass ranges which fall within the limits of acceptable focus by a fixed value of
the time-lag parameter. The MSU group also has pursued techniques of beam deflec-
tion TOF-MS for purposes of achieving mass-independentjpn focus and for improv-
ing the resolving power. in general. of TOF-MS by eliminating the aberration in
resolution caused by the "turn around time“ problem [14]. The technical details of a
most recent version of a beam deflection TOF-MS system will be described elsewhere
[15]. This report provides a preliminary assessment of the beam deflection TOF-MS
system developed at MSU with time array detection for purposes of gathering com-
plete mass spectra from a standard test mixture introduced via capillary column GC.

EXPERIMENTAL

Preliminary results from the GC—TOF-MS system based on beam deflection as
represented schematically in Fig. 4 are presented here. In brief. the gas chroma-
tograph used is a Hitachi 663-30. fitted with an 18 m (08.1. 0.18 mm ID.) capillary
column; the test sample described herein is the Cirob mixture (Supelco catalog No.

152

 

 

 

 

 

 

 

 

 

 

 

 

 

RENAISSANCE OF GC-TIMEOF-FLIGHT MS 289
o I e
t 8 b
030 V I P V. (top)
Capillary
BIS >o all
Chromotogrooh
-30 V '“ V. (bottom)
Intortoeo V, (too) time
flight time
3.
35
I s
V. (bottom) I
Integrating
Troooloot
Itoeor'oor

 

 

 

Fig. 4. Schematic diagram of the beam deflection TOF-MS system showing the gas chromatograph.
continuous ion source. beam deflection assembly. CEMA detector. and ITR.

4-7304). The GC—MS interface is a heated block design from JEOL. The time-of-
flight mass spectrometer is a highly modified Bendix IZ-lOl instrument. The source
and source housing from a double-focusing mass spectrometer. a DuPont 21-491. is
used to provide a continuous. narrow. focussed beam of ions produced by electron or
chemical ionization. Ions formed in the source are accelerated to a kinetic energy of
approximately 3000 eV. Ion packets are formed by beam deflection [I4]. To obtain a
rapidly changing electric field in the beam deflector for good mass spectral resolution.
dynamic voltages ("pulses“) of equal magnitude. but of opposite sign (designated as
V, in Fig. 4). are applied to each deflection plate yielding temporally narrow ion
packets. The time-dependent voltages used are generated from pulsing circuitry that
was developed in-house. Typically. the voltages V. applied are modulated between
+ 30 V and - 30 V. The circuitry provides a rise time of < IO ns and a fall time of < 20
ns. lon packets traverse a 2.0-m flight tube. and transient mass spectra are generated
at a rate of 5000 s‘ ‘. This beam deflection TOF-MS system provides better than unit
resolution for all ions in the m/z 2-1000 range. with all ions in optimal focus for each
ion packet. A resolving power of > I400 has been demonstrated for this instrument

[15].

An in-house designed and built integrating transient recorder [I2] was used to
continuously collect full mass range, mass spectra throughout the entire duration of
the GC-MS run (20 min). Data collection with the ITR is accomplished by a 200
MHz flash analog-to-digital converter. The digitized data are passed to 16 high speed
ECL (emitter coupled logic) summer cards where 5 to 5000 transients are summed to
form a mass spectral scan file. If 5000 transients are produced each second by the

153

290 J. r. WATSON er al.

TOF-MS system. summation of S to 5000 transients corresponds to mass spectral
generation rates of 1000 scan files per second to I scan file per second. respectively.
The integrated scan files are passed across a VME bus to three Motorola 68020
parallel processors whereby time/mass calibration. and/or conversion to reconstruct-
ed mass chromatograms and/or real-time conversion to mass. intensity pairs occurs.
Finally. the processed scan files are written to a 300 Mbyte Priam disk drive (typical
scan file sizes - SOD—2000 bytes).

RESULTS AND DISCUSSION

The principal goals of this paper are to demonstrate that beam deflection TOF-
MS is capable of producing good quality mass spectra and that these mass spectra are
well focussed and resolved over the complete mass range so that time array detection
can be implemented by means of an ITR. The importance of acquiring complete mass
spectra at a rate of 20 scan files per second in deconvoluting unresolved chroma-
tographic components is illustrated in the analysis of a capillary column test mixture.
As described elsewhere. the ITR is capable of generating up to 1000 complete
summed spectra per second [4.I 1.12]. This scan file generation rate would provide
1000 data points per second from which a chromatographic profile could be recon-
structed from a data base of consecutively-recorded mass spectra. However. such a
high frequency of scan file generation is not necessary to reconstruct the profiles
available from most high-resolution gas chromatographs at this time. In the prelimi-
nary assessment of time array detection described here. a scan file generation rate of
20 scan files per second has been found adequate to provide 20 data points per second
from which to reconstruct chromatographic profiles having peak widths on the order
of two seconds.

Representation of the chromatographic profile
Fig. 5 shows the reconstructed total ion current (RTIC) chromatogram of a
standard test mixture [16] analyzed using GC—beam deflection TOF-MS—ITR. repre-

12

 

 

 

 

 

 

6530

 

Fig. 5. Reconstructed TIC chromatogram (RTIC) of standard Grob test mixture as separated on a 20 m x
0.!8 mm ID. column containing DB-I. 0-0.4 um film thickness at a flow-rate of LS mI/min with a
temperature program of 20‘C.‘min from 120 to 200'C. Components (approx. 50 ng each) in the mixture:
I - 2.3-butanediol; 2 - decane; 3 - l-octanol; 4 - nonanal; 5 - 2.6-dimethylphenol; 6 - undecane;
7 - 2.6-dimethylaniline: 8 - 2-ethylhexanoicacid; 9 - C", acid methyl ester: I0 - Cu acidmethylester:
II - dicyclohexylamine: I2 - Cu acid methyl ester. Time in min:s.

154

RENAISSANCE OF GC-TIME-OF-FLIGHT MS 29I

senting approximately 50 ng of each component. A scan file generation rate of one
scan file per second offers one TIC point per second to reconstruct the chroma-
tographic profile. Generation of one TIC point per second is typical of most available
GC-MS instruments (e.g., quadrupoles and magnetic sector instruments) in use to-
day.

Several questions must be addressed concerning the results in Fig. 5. Does the
RTIC, reconstruCted from the one-scan-file-per-second data base. adequately repre-
sent the chromatography? Also. it was known that the mixture contained 12 compo-
nents. but only IO peaks are shown in the RTIC. The portion of the chromatogram
containing the solvent peak and 2.3-butanediol is not shown here (Fig. 5). so there
should be ll components represented by the RTIC. To answer these questions. an-'
other aliquot of the test mixture was analyzed by GC-beam deflection TOF-MS-
ITR. summing every 250 transient mass spectra. thereby generating 20 scan files per
second. The RTIC chromatogram, resulting from the 20-scan-files-per-second data
base at approximately 2.5 min into the run. is shown in Fig. 6b; for comparison. the
corresponding segment of the RTIC in Fig. 5 (between the vertical arrows). obtained
from the one-scan-fiIe-per-second data base is reproduced as Fig. 6a. There are two
obvious advantages to the greater scan file generation rate that can be seen upon
comparing Fig. 6a and b. Because the 20-scan-files-per-second data base offers 20
points per second to reconstruct the waveform (Fig. 6b). the chromatographic profile
is more accurately represented in terms of peak shapes. relative heights. and relative

 

 

 

 

 

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E
I
i
a
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\\\\\\\\\ \\\\\
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ttttd
I 200 400

scan file number

Fig. 6. (a—d) Data over a region of the chromatogram representing coeluting components. (a) RTIC
obtained from spectra collected at I scan file/s; it only shows evidence for two components. (bl RTIC
obtained from spectra collected at 20 scan files/s; it shows evidence for three components. (c) Mass chroma-
togram at mi: I22 representing the molecular ion of 2.6-dimethylphenol. (d) Mass chromatogram at int: 57
representing an alkyl cation. a characteristic ion of both nonanal and undecane.

292 J. T. WATSON et al.

areas. This feature of the data provides better quantification of the components in the
mixture. The other advantage is that the RTIC generated from higher scan file gener-
ation rates more accurately represents the true chromatographic profile. It is obvious
from the RTIC presented in Fig. 6b that this region of the chromatogram contains
three components.

Chester and Cram [17] have investigated the relationship between the number
of data points required to represent the profile of a given chromatographic peak and
the characteristic features of that peak shape as described by a. where a’ is the
variance that can be related to the mathematical function describing the profile. It has
been previously estimated that 10 data points (scan files) per standard deviation unit
are necessary to obtain an accurate representation of the chromatographic peak
height. area. and position assuming a Gaussian peak [18]. The minimum number of
data points which can accurately represent this profile is 10 scan files per second.
Most scanning mass analyzers would not be able to represent the chromatography in
this situation due to their scan file generation rate limitations.

The high scan file generation rates allow the presence of three components to be
recognized in this unresolved region of the reconstructed chromatogram in Fig. 6b.
Can the three components be identified from the mass spectral data base even though
the components are coeluting? Because the components in the test mixture are
known. as well as the type of column used for analysis. we were able to determine
which components were expected to be in this region of the chromatogram. One of
the expected components is 2.6-dimethylphenol. Instead of searching through the 200
scan files which contain mass spectral data for a match of the data to a library mass
spectrum of this compound. we can display the mass chromatogram of one of the
dominant ions in the mass spectrum of 2.6«dimethylphenol. A mass chromatogram is
a graphic display of the peak intensity at a specified mass-to-charge value versus scan
file number [19]. The library mass spectrum of 2.6-dimethylphenol indicates that the
molecular ion is represented by the base peak at m1: 122. Fig. 6c is the mass chroma-
togram of m/: 122 and identifies the middle component as 2.6-dimethylphenol. An-
other component expected to be in this region of the RTIC is undecane; the alkyl
cation C‘HJ . mi: 57. was selected as a designate ion for this hydrocarbon. The mass
chromatogram at m/: 57 displayed in Fig. 6d shows that the mass spectra of both of
the other two components contain this alkyl cation. The mass chromatograms at m/z
57 and 122 (Fig. 6d and c. respectively) provide information on the chromatographic
peak shapes of the three components. By choosing a scan file which does not contain
both m/: I22 and m/z 57. one can obtain a pure mass spectrum for each of the three
components represented here. A visual inspection of the mass chromatogram repre-
sented in Fig. 6d shows a region (scan files I90—200) where the ion current at m/z 57 is
minimal. Because the mass spectra of the other two components have an intense peak
at m/z 57. this is a region of the data base that should provide a reasonably pure mass
spectrum of the middle component. The mass spectrum contained in scan file 192 is
shown in Fig. 7a. A similar procedure was used to obtain pure mass spectra of the
other two components by choosing scan files which do not contain ion current at m/z
122. Ion current at m/z 122 is observed in scan files I60—232. Fig. 7b shows the mass
spectrum in scan file 159 which is identical with the library spectrum of nonanal. Fig.
7c shows the mass spectrum in scan file 240 which is identical with that of undecane.

156

 

 

 

 

 

 

 

 

 

 

RENAISSANCE OF GC-TIME-OF-FLIGHT MS 293

a

3‘ tool 2.6-Dimethylphenol 122

i ...

f not

§ 254 “3'1

3 o a . J. a JIF s .
as so so so too too 140 tee

m/a

b

3‘ mo. 5., Nonenal

3 ”a

3

5 604

é

a ”‘ l

a o .31-)? till if. 342, A.
so so so so too rzo 140 no

c m/a

:3 ‘°° ‘ s? Undoeane

c .

3 7s

.5

E “l 71

.... l ”l

3 o . . . h. . . ‘1‘
so so so so too m 140 toe

m/a

Fig. 7. Massspectra selected from theseveralhundred scanfilescollectedatZOscanfiles/sasrepresentedin
Figs. 5 and 6. (a) Mass spectrum of 2.6-dimerhylphenol obtained from scan file 192. (b) Mass spectrum of
nonanal obtained from scan file 159. (c) Mass spectrum of undecane obtained from scan file 240. These
spectra represent components 5. 4 and 6 in Fig. 5.

Limits of detection

The detection limit of the GC—beam deflection TOF-MS—ITR at 20 scan files
per second was compared to that of the JEOL J MS-AXSOSl-I MS system which is a
commercially available double-focusing sector instrument routinely used for GC-MS
analyses. The fastest scan rate available with the JEOL instrument is 0.9 s per decade
(e.g., m/z 50-500) which generates 1.1 scan files per second.

Complete mass spectra were collected during the analysis of the standard test
mixture at various concentrations at the scan file generation rate described above for
each mass spectrometer. Mass chromatograms were reconstructed from the corre-
sponding data bases. The area of the peak in the mass chromatogram at m/z 122
(corresponding to the base peak in the mass spectrum of 2.6-dimethylphenol) was
plotted versus the amount of analyte injected. The limit of detection was calculated
using the method of regression analysis [20] on each data set. The y-intercept of each
regression line was used as an estimate of the blank signal. y.. The signal. y 8 y. +
33.. determines the limit of detection. The limit of detection calculated for both the

157

294 J. T. WATSON er al.

JEOL instrument and the GC-beam deflection TOF-MS—ITR system was 0.6 t 0.2
ng of 2,6—dimethylphenol.

Quality of mass spectra

An important feature of the data obtained with GC-beam deflection TOF-MS-
ITR is the absence of mass spectral skew. due to the high sampling rate (5000 s‘ ‘) of
the continuous ion beam. Thus, the mass spectra of individual components obtained
at different scan file generation rates are identical. each having the same relative peak
intensities throughout the mass range. This feature of the data would have allowed
identification of the three components by use of available mass spectral deconvolu-
tion routines [21] to distinguish the coeluting components based on their character-
istic contributions to peak intensities among the adjacent scan files.

CONCLUSIONS

We have shown that the GC-beam deflection TOF-MS—ITR combination is
capable of providing good-quality GC—MS data. The GC-beam deflection TOF-
MS—ITR system can generate data files at a rate greater than those commonly avail-
able from quadrupole and magnetic sector instruments. The importance of the high
scan file generation rate was illustrated by comparison of reconstructed total ion
current chromatograms from data bases collected at 20 scan files per second and at
one scan file per second. the latter being representative of the performance of most
magnetic or quadrupole instruments (even though, in principle. these instruments can
generate data at higher rates. but at the expense of performance and data quality).
Here we have shown an example where one scan file per second is insufl‘icient to
reproduce the chromatographic profile; in this case. we reanalyzed the mixture by
GC-MS generating 20 scan files per second. Each mass spectral transient is free of
any skewing due to the changing partial pressure of the analyte in the ion source. thus
the summed spectra are free of the types of skew that would be imposed by other
scanning instruments.

This report describes one approach by which the MSU research group is at-
tempting to respond to the fact that developments (e.g., scan spwdSi in MS have not
progressed in a timely fashion commensurate with improvements in GC resolving
power. Chromatograms are now being reported with peak widths on the order of tens
of milliseconds [2]; further improvements in GC could make contemporary MS of
little use as a GC detector. While these preliminary results with the GC-beam c tiec-
tion TOF-MS-ITR system are not competitive from the standpoint of sensuivity
(because the source is designed for a magnetic sector instrument). they do illustrate
that developments in TOF-MS and its use with the IT R provide a mass spectrometer
that can “keep up" with the demands imposed by high-resolution QC on MS. These
developments provide the basis for sustaining the use of MS as a GC detector. the
data from which can be used to both adequately represent the chromatography and
identify eluting components of complex mixtures.

RENAISSANCE OF GC-TIME-OF-FLIGHT MS 295
ACKNOWLEDGEMENT

This work was funded through a Biomedical Research Technology Program
grant (NIH-DRR-OO480) from The National Institutes of Health. -

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