Achieving stable and continuous monitoring of signals of numerous single neurons in the brain faces the conflicting challenge of increasing the microelectrode count while minimizing cross-sectional shank dimensions to reduce tissue damage, foreign-body-reaction and maintain signal quality. Passive probes need to route each microelectrode individually to external electronics, thus increasing shank size and tissue-damage as the number of electrodes grows. Active complementary metal-oxide-semiconductor (CMOS) probes overcome the limitation in electrode count and density with on-probe frontend, addressing and multiplexing circuits, but current probes have relatively large shank widths of 70 - 100 μm. Here we demonstrate the use of CMOS technology to overcome this conflicting challenge and realize chronically stable multielectrode probes with "microwire-like" cross-sectional shank dimensions. By optimizing the size of SiNAPS electrode-pixel circuits, we engineered a ChroMOS probe with 64 electrode-pixels on a compact 26 × 26 μm2 and 4 mm long shank. Electrical characterizations in saline show a noise level of 8.74 ± 1.11 μVRMS (AP-band, 15 μm electrode diameter). Recordings from six-month chronic implants in freely behaving mice show a signal-to-noise ratio (SNR) of ∼ 4 dB, mean-firing rate (MFR) of 3 spikes/s and the ability to track multiple single-units. Immunofluorescence quantifications show an average lesion size of 636 ± 360 μm2 comparable to the shank footprint (676 μm2), a confined tissue response (< 150 μm), and presence of post-mitotic neurons near the electrodes (< 80 μm). Altogether, these results establish a new class of minimally invasive, chronically implantable and stable CMOS probe that can be scaled to support higher electrode-channel counts.
Keywords: Active neural probe; Brain implant; Foreign body reaction; Freely behaving mice; Neural signals.
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