High-density, large-scale recording and stimulating neural probes with integrated ASIC

Ultraflexible probes offer a revolutionary approach to stable neural recording and stimulation by creating a glial scar-free neuronal interface utilizing biocompatible materials in compact cross-sectional areas. However, these probes don’t have an equivalent number of electrodes within the same invasive footprint as rigid probes have. This limitation stems from photolithography, which is used for fabricating ultraflexible probes, is not capable of yielding a similar high electrode density. Here, to record more neurons per implantation, we introduce a novel fabrication technique utilizing electron-beam lithography (EBL) to construct densely packed electrodes on the polyimide encapsulations. This method has enabled us to design and fabricate a 128-channel probe that presents the highest electrode density per cross-sectional area among flexible probes. The oversampling electrodes can isolate highly clustered single units both locally and across brain regions over extended period for up to 6 months in mice cortex and 2 months in rats hippocampus along with populational neuronal tracking. The intracortical microstimulation (ICMS) triggered by dispensed microelectrodes can modulate the neural circuity and connectivity with a lower threshold at 1µA. Further, we propose a comprehensive system incorporating a large-scale flexible microelectrode array with 5,376 simultaneously recording sites into a customized application-specific integrated circuit (ASIC) with 1,344 ADCs. Multiple prototypes include penetrating multi-shank electrodes with a density of 100 electrodes/ mm depth and surface electrodes of 70 electrodes / mm2. In summary, our work expands the toolkits for high-density, large-scale in vivo electrophysiology and advanced data acquisition technologies, providing unprecedented insights into studying brain functions.