Microsystems For Real-Time Neurochemical Monitoring Using Fast-Scan Cyclic Voltammetry
Dorta Quinones, Carlos
Dopamine is an important neurotransmitter that plays a fundamental role in motor control and reward-seeking behaviors. Electrochemical detection of dopamine is accomplished through fast-scan cyclic voltammetry (FSCV), a neurochemical monitoring technique that can resolve rapid changes in dopamine concentration with subsecond temporal resolution and high selectivity. This dissertation describes the development of several microsystems for real-time monitoring of dopamine levels using FSCV, including a wide-range analog-todigital converter (ADC), a fully-integrated low-power wireless sensing system, and a scalable electrochemical detector array. The work described here tackles some of the challenges that exist in the field of neuroscience to advance two important applications: long-term in vivo monitoring in freely-behaving animals using carbon-fiber microelectrodes (CFMs) and high-throughput drug screening using planar microelectrode arrays (MEAs). In particular, a low-power two-step cyclic ADC for wide-range acquisition of neurochemical signals is demonstrated. The system was validated by recording flow-injection of 2-[MICRO SIGN]M dopamine at a CFM using 300-V/s FSCV. A 30-[MICRO SIGN]W wireless microsystem for real-time in vivo monitoring and a lightweight miniaturized device that can enable long-term behavioral studies in freely-behaving animals are also demonstrated. On-chip integration of analog background subtraction and UWB telemetry yields a 32-fold increase in resolution versus stan- dard Nyquist-rate conversion alone, near a four-fold decrease in the volume of uplink data versus single-bit, third-order, delta-sigma modulation, and more than a 20-fold reduction in transmit power versus narrowband transmission at low data rates. The system was validated by wirelessly recording flow-injection of dopamine with concentrations in the range of 250 nM to 2 [MICRO SIGN]M at a CFM using 300-V/s FSCV. Measurement results indicate an input-referred current noise of 92 pArms and an input current range of ±430 nA at a conversion rate of 10 kHz. A scalable 32 x 32 (1,024-electrode) CMOS VLSI potentiostat array for highthroughput drug screening applications is also presented. The core of the array is a high-precision bidirectional-current detector that enables both amperometry and FSCV using MEAs for massively-parallel detection of transmitter release as well as electrode impedance characterization.
neurochemical monitoring; fast-scan cyclic voltammetry; dopamine detection
Apsel, Alyssa B.
Molnar, Alyosha Christopher; Lindau, Manfred
Ph. D., Electrical Engineering
Doctor of Philosophy
dissertation or thesis