Implantable electrodes have gained popular attention in research and clinical settings to treat and study a variety of neurological conditions. Detection of electrical and chemical signals drive the performance of implanted microelectrodes used for sensing and/or stimulating brain activity. However, signal instability and device failure over time in the implanted brain inhibit the therapeutic and biomedical promise of such microelectrodes. As the field of neurotechnology moves towards next-generation probes and sophisticated methodologies to improve signal detection in the brain, detailed explorations of the inherent biological response to implanted electrodes are warranted. The foreign body reaction to implanted probes can change over acute and chronic durations while experiencing structural, functional and genetic changes at the tissue level. Further, mechanical factors (for example, device material, flexibility, dimensions, etc.) can exacerbate or mitigate the inflammatory response, signal detection and overall integration of the device-tissue interface. This dissertation recognizes the diverse nature of the tissue response to implanted microelectrodes and conducts a deeper investigation of two biological sources contributing to signal loss – (1) protein adsorption, or biofouling, and (2) cellular encapsulation. The findings expand on – (1) assessments of a novel all-diamond boron-doped diamond microelectrode to tackle signal instability influenced by protein adsorption, and (2) gene expression changes brought about by cellular encapsulation of implanted devices. The results discussed herein take an interdisciplinary approach to investigate the biological sources influencing signal detection and employ numerous techniques including fast-scan cyclic voltammetry, electrophysiology and spatial transcriptomics. Overall, this work adds to the growing body of literature reporting on the basic science understanding of the multifaceted biological response to implantable microelectrodes.
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