Post-CMOS Fabrication of Working Electrodes for On-Chip Recordings of Transmitter Release

The release of neurotransmitters and hormones from secretory vesicles plays a fundamental role in the function of the nervous system including neuronal communication. High-throughput testing of drugs modulating transmitter release is becoming an increasingly important area in the fields of cell biology, neurobiology, and neurology. Carbon-fiber amperometry provides high-resolution measurements of amount and time course of the transmitter release from single vesicles, and their modulation by drugs and molecular manipulations. However, these methods do not enable the rapid collection of data from a large number of cells. To allow this testing, we have developed a complementary metal-oxide semiconductor (CMOS) potentiostat circuit that can be scaled to a large array. In this paper, we present two post-CMOS fabrication methods to incorporate the electrochemical electrode material. We demonstrate by proof of principle the feasibility of on-chip electrochemical measurements of dopamine, and catecholamine release from adrenal chromaffin cells. The measurement noise is consistent with the typical electrode noise in recordings with external amplifiers. The electronic noise of the potentiostat in recordings with 400-??s integration time is ~ 0.11 pA and is negligible compared to the inherent electrode noise.