Antimicrobial resistance represents an imminent and growing threat to global health. It is estimated that antimicrobial resistance will cause 10 million deaths a year by 2050. The testing of clinical infections for susceptibility to antimicrobial drugs is therefore critical. However, current methods of susceptibility testing are prohibitively slow, and they require pathogen isolation and culture. This inability to rapidly screen infections causes serious problems including patient mortality by sepsis, over-prescription of broad-spectrum antibiotics, and the accelerated spread of antimicrobial resistance in human pathogens. Faster susceptibility testing is required to more effectively treat sepsis and prevent the unnecessary selection for resistant pathogenic strains more effectively. Quantifying drug susceptibility at the single-cell level on a multiphase chip platform will eliminate the need for culture and enable drug susceptibility screening within minutes. Antibiotics often alter extracellular levels of adenosine triphosphate (ATP) in susceptible microbial cells, while leaving resistant cells mostly unaffected. An individual microbial cell will contain ~1-5 attomoles of ATP, which is only detectable if confined to extremely small reaction volumes. Here we propose a multiphase (immiscible aqueous and ether) microfluidics platform combined with a microcapillary system (Chapters 2,3). This system will confine individual pathogens and challenge drugs inside droplets of nanoliter-scale volume to enable detection of drug-induced alteration of ATP release from susceptible cells. This system will enable more informed and specific prescription of drugs to both improve patient outcomes and relieve unnecessary selective pressure for the spread of antimicrobial resistance. The same 3D printing tools that apply well to multiphase fluidic devices are also leveraged to address biomedical challenges in tangent fields. Progress in the fields of organoid modeling and regenerative tissue printing are discussed (Chapter 4).
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