A CMOS based Sensor Array Platform for Analysis of Exocytosis Events

Abstract

The release of neurotransmitters into the extracellular space is an important drug target and crucial for molecular manipulation. Amperometric measurements provide details about the amount and kinetics of transmitter release in single quantal events. However, amperometric spikes vary from cell to cell even under the same condition; therefore, a large number of release events must be analyzed to achieve the statistical significance. We present CMOS chips with 100 or 1,024 active electrodes with surface modifications for amperometry measurements. To enable amperometry measurements, polarizable electrodes such as platinum are patterned on the original aluminum metal contact on the chip. To prevent potential current leakage, a new shifted electrode design was used to enhance the reliability of post-fabrication. Platinum electrode material is deposited on the aluminum contact extending onto the periphery area and further insulated to redefine the openings of the active electrodes by lithography and sputtering. The insulation of the surface is performed by lithography using photoresist. The 100 sensor array was validated by simultaneous recording from all electrodes at 1MS/s using dopamine injection and recordings from live chromaffin cells cultured on-chip. A new chip with 1024 working electrodes capable of bi-directional current recordings was developed for fast scan cyclic voltammetry. Positive as well as negative currents are measured in the same working manner, and a current mirror and a biased cascode transistor ensure a gain error <1%. A sign detection function is implemented to report the polarity of the current input. Simulations of the circuit revealed reliable capacitive current recording and the linearity of the gain over a wide range of input with the correct sign-bit output. We anticipate that the chip will serve as a universal platform for characterizing various physiological events.