Neural Biosensor Probes for Simultaneous Electrophysiological Recordings, Neurochemical Measurements, and Drug Delivery with High Spatial and Temporal Resolution.

Abstract

The aim of this work is to develop and validate novel neural biosensor probes for simultaneous electrophysiological and neurochemical measurements with precise, localized drug delivery. This technology has been developed to interface with the complex environment of the brain for more advanced experimental investigations at the intersections of neurophysiology, neuropathology, and neuropharmacology. The validation experiments have been conducted using relevant in vivo testbeds as a foundation for future work to more fully understand and treat neurological disorders.

Chapter II presents a multimodal probe that enables concurrent detection of choline, recording of electrophysiology, and localized drug delivery. Central to this work is the development of selective electrodeposition methods for enzyme immobilization and polymerization on individual microelectrode sites that more closely approach the scale of neurons than currently reported neural biosensors.

Multiple neurotransmitter systems are implicated in the pathophysiology of schizophrenia, Alzheimer’s disease, Parkinson’s disease, and other neurological disorders, yet the direct relationships remain unclear. The ability to simultaneously monitor multiple chemical signals concurrently with electrophysiology and integrated pharmacological manipulation can serve as a useful tool to further these investigations. Chapter III further extends the probe capabilities to include glutamate sensing concurrent with choline sensing, electrophysiology recordings, and drug delivery.

Electrochemical biosensors are commonly used to record neurotransmitter dynamics, yet there remains no standard calibration media or procedure. Differences in calibration procedures can impact reported performance making the interpretation of in vivo difficult. Chapter IV aims to improve our ability to interpret in vivo neurochemical recordings by investigating the influence of calibration media on performance characteristics of amperometric biosensors.

Bridging the electrophysiological and neurochemical domains with sufficient fidelity, resolution, sensitivity, and selectivity can provide novel insights into neurophysiology that lead to improved therapeutic approaches for treating neurologicalvdisorders.