Surface Modified CMOS IC for Electrochemical Characterization of Living Cell Transmitter Release
Neurotransmitters are released to the extracellular space in packages by the fusion of vesicles with the cell membrane, a process known as exocytosis. Modulation of this process is a key target for the treatment of neurogenerative diseases, such as Parkinson’s disease and Alzheimer’s disease. Amperometry detects neurotransmitters released through exocytosis by their oxidation at a polarizable electrode. The resulting oxidation current or amperometric spike provides information about the number of released neurotransmitters from a single vesicle release event (quantal size) and the kinetics of exocytosis. Complementary metal-oxide-semiconductor (CMOS) technologies enable the design and fabrication of devices with hundreds or thousands of planar electrodes and amplifiers integrated on the same chip, offering high throughput measurement of exocytosis from living cells. In this dissertation, the development and application of CMOC IC devices with surface modified structures for electrochemical characterization of live cell exocytosis are introduced. In chapter 2, a surface modified CMOS integrated circuit (IC) is demonstrated for highly parallel amperometry measurement of live chromaffin cells. The surface modified structures with SU-8 microwells fabricated on the chip surface solved the two major issues for on-chip single cell measurement devices, the reliability and the single cell targeting efficiency. The surface modified CMOC IC was able to reliably measure 10-30 cells per time per chip with low noise levels, which was a significant increase in efficiency compared to conventional carbon fiber microelectrode measurement. In chapter 3, the surface modified CMOS IC was used to investigate the working mechanisms of the antidepressant drugs bupropion and citalopram. Bupropion was found to potentiate the quantal size and citalopram to increase the release frequency by increasing the readily releasable pool (RRP) size. In chapter 4, a bidirectional-current measurement CMOS IC was designed to enable on-chip cyclic voltammetry (CV) measurement. The new design was capable of measuring current within the range of ±1.5 nA at 10 kS/s. Finally, an improved CMOS IC for CV measurement is presented in chapter 5. The devices consumed less area for each detector and a sign binary output was implemented to identify the polarity of the output current. The devices were validated with on-chip dopamine injection test and potassium ferricyanide CV measurement.
Chromaffin Cells; Neurotransmitter Release; Biophysics; biosensor; amperometry; CMOS; Materials Science; Integrated Circuit
Van Dover, Robert B.
Lindau, Manfred; Ma, Minglin
Materials Science and Engineering
Ph.D., Materials Science and Engineering
Doctor of Philosophy
dissertation or thesis