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Neurotransmitter release is modulated by many drugs and molecular manipulations. We present an active CMOS-based electrochemical biosensor array with high throughput capability (100 electrodes) for on-chip amperometric measurement of neurotransmitter release. The high-throughput of the biosensor array will accelerate the data collection needed to determine statistical significance of changes produced under varying conditions, from several weeks to a few hours. The biosensor is designed and fabricated using a combination of CMOS integrated circuit (IC) technology and a photolithography process to incorporate platinum working electrodes on-chip. We demonstrate the operation of an electrode array with integrated high-gain potentiostats and output time-division multiplexing with minimum dead time for readout. The on-chip working electrodes are patterned by conformal deposition of Pt and lift-off photolithography. The conformal deposition method protects the underlying electronic circuits from contact with the electrolyte that covers the electrode array during measurement. The biosensor was validated by simultaneous measurement of amperometric currents from 100 electrodes in response to dopamine injection, which revealed the time course of dopamine diffusion along the surface of the biosensor array. The biosensor simultaneously recorded neurotransmitter release successfully from multiple individual living chromaffin cells. The biosensor was capable of resolving small and fast amperometric spikes reporting release from individual vesicle secretions. We anticipate that this device will accelerate the characterization of the modulation of neurotransmitter secretion from neuronal and endocrine cells by pharmacological and molecular manipulations of the cells.

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High-throughput electrode arrays are required for advancing devices for testing the effect of drugs on cellular function. In this paper, we present design criteria for a potentiostat circuit that is capable of measuring transient amperometric oxidation currents at the surface of an electrode with submillisecond time resolution and picoampere current resolution. The potentiostat is a regulated cascode stage in which a high-gain amplifier maintains the electrode voltage through a negative feedback loop. The potentiostat uses a new shared amplifier structure in which all of the amplifiers in a given row of detectors share a common half circuit permitting us to use fewer transistors per detector. We also present measurements from a test chip that was fabricated in a 0.5-μm, 5-V CMOS process through MOSIS. Each detector occupied a layout area of 35μm × 15μm and contained eight transistors and a 50-fF integrating capacitor. The rms current noise at 2kHz bandwidth is ≈ 110fA. The maximum charge storage capacity at 2kHz is 1.26 × 10 6 electrons.

We have developed a bandpass floating-gate amplifier that uses tunneling and pFET hot-electron injection to set its dc operating point adaptively. Because the hot-electron injection is an inherent part of the pFET's behavior, we obtain this adaptation with no additional circuitry. Because the gate currents are small, the circuit exhibits a high-pass characteristic with a cutoff frequency less than 1 Hz. The high-frequency cutoff is controlled electronically, as is done in continuous-time filters. We have derived analytical models that completely characterize the amplifier and that are in good agreement with experimental data for a wide range of operating conditions and input waveforms. This autozeroing floating-gate amplifier demonstrates how to use continuous-time floating-gate adaptation in amplifier design.