Multi-shanks SiNAPS Active Pixel Sensor CMOS probe: 1024 simultaneously recording channels for high-density intracortical brain mapping

Abstract

The advent of implantable active dense CMOS neural probes opened a new era for electrophysiology in neuroscience. These single shank electrode arrays, and the emerging tailored analysis tools, provide for the first time to neuroscientists the neurotechnology means to spatiotemporally resolve the activity of hundreds of different single-neurons in multiple vertically aligned brain structures. However, while these unprecedented experimental capabilities to study columnar brain properties are a big leap forward in neuroscience, there is the need to spatially distribute electrodes also horizontally. Closely spacing and consistently placing in well-defined geometrical arrangement multiple isolated single-shank probes is methodologically and economically impractical. Here, we present the first high-density CMOS neural probe with multiple shanks integrating thousand's of closely spaced and simultaneously recording microelectrodes to map neural activity across 2D lattice. Taking advantage from the high-modularity of our electrode-pixels-based SiNAPS technology, we realized a four shanks active dense probe with 256 electrode-pixels/shank and a pitch of 28 µm, for a total of 1024 simultaneously recording channels. The achieved performances allow for full-band, whole-array read-outs at 25 kHz/channel, show a measured input referred noise in the action potential band (300-7000 Hz) of 6.5±2.1µV RM S , and a power consumption <6 µW/electrode-pixel. Preliminary recordings in awake behaving mice demonstrated the capability of multi-shanks SiNAPS probes to simultaneously record neural activity (both LFPs and spikes) from a brain area >6 mm 2 , spanning cortical, hippocampal and thalamic regions. High-density 2D array enables combining large population unit recording across distributed networks with precise intra-and interlaminar/nuclear mapping of the oscillatory dynamics. These results pave the way to a new generation of high-density and extremely compact multi-shanks CMOS-probes with tunable layouts for electrophysiological mapping of brain activity at the single-neurons resolution.

Electrophysiology Read-Out Tools for Brain-on-Chip Biotechnology

“…Typically, in fact, front-end amplifiers require a relatively large area to integrate a capacitive feedback architecture to achieve large AC gains and low-noise performances (both necessary to retrieve the small amplitude of extracellularly-recorded action potentials) while removing large DC offsets arising at the electrode–tissue interface [ 311 ]. Conversely, the DC-input architecture described in [ 312 ] for in vitro applications and in [ 281 , 313 ] for in vivo recordings were successfully demonstrated as a minimum area solution for highly-scalable neuroelectronic interfaces. In parallel, an important outcome of this research effort on front-end electronics for neural signals recording are low-power integrated circuit components that can be used in compact hybrid platforms to advance the interfacing of passive electrode arrays for a broad range of applications, including electroencephalography EEG recording systems [ 314 , 315 ] or BoC.…”

A 0.064 mm2 16-Channels In-Pixel Neural Front-End With Improved System Common-Mode Rejection Exploiting a Current-Mode Summing Approach

“…In turn, the number of individual neurons that can be simultaneously recorded has also experienced a steady rise [15]. At the forefront of neural recording, devices such as Neuropixels 2.0, Neuroseeker, and SiNAPS have produced groundbreaking results when applied to small mammals and non-humane primates [16][17][18][19][20].…”

Compression strategies for large-scale electrophysiology data

“…These probes have already been used to record spike trains from tens of thousands of neurons distributed across the entire brain (Steinmetz et al 2019, Siegle et al 2021, Chen et al 2023. Recently developed SiNAPS probes (Angotzi et al 2019, Boi et al 2020 increase the number of simultaneously recorded electrodes per probe to 1024. And even higher electrode counts have been achieved in CMOS-based micro-electrode arrays (MEAs) for in vitro experiments, such as the 3-Brain HyperCAM Alpha (6144 channels) 5 and the Maxwell Biosystems MaxTwo (26 400 channels) 6 .…”