This project has developed single-chip wireless microsystems fabricated using a 0.5-µm double-poly triple-metal n-well CMOS process that incorporate three powerful neuromonitoring techniques: fast-scan cyclic voltammetry (FSCV) for monitoring neurotransmitter concentrations, extracellular electrophysiology for single-unit recording, and time-share recordings of these two techniques for quasi-simultaneous measurements of chemical and electrical neural activity at a single brain site in vivo. These devices also support electrical stimulation for focal activation of neural circuits.
In particular, a 1.1-mW, 5-mm2, 4-channel integrated circuit has been developed that can be dynamically configured to perform neurochemical monitoring using 300-V/s FSCV and neuroelectrical recording using extracellular electrophysiology. The chip architecture uses a 76-µW, 3rd-order, continuous-time delta-sigma modulator per channel that achieves an rms input-referred noise of 56.7 pA (dc-5 kHz) and 3.5 µV (1.1-5 kHz) for chemical and electrical neuromonitoring, respectively. The chip architecture also incorporates monolithic circuitry for generating FSCV and biphasic constant-current stimulus waveforms. It has been externally interfaced with carbon-fiber microelectrodes implanted acutely in the caudate-putamen of an anesthetized rat, and enables chemically resolved monitoring of electrically evoked dopamine release and its postsynaptic bioelectrical response at the same recording site. The dopamine limit of detection corresponding to a signal-to-rms noise ratio of three is estimated to be 16.7 nM, which compares favorably with the amplitude of phasic dopamine transients that varies in the range of 40 nM-1 µM.
The chip has also been packaged on a miniature rigid-flex substrate to develop an implantable device for investigating brain-behavior relationships in an ambulatory rat. The device successfully captures the effect of high-dose amphetamine administration on electrically and non-electrically evoked dopamine neurotransmission in the brain, demonstrating that the technology developed throughout the course of this project can indeed be applied to conduct neurochemical measurements in the context of behavior.