ChroMOS: a "microwire-like" CMOS neural probe for chronic neural recordings in mice.

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.