SiNAPS: An implantable active pixel sensor CMOS-probe for simultaneous large-scale neural recordings

Angotzi, Gian Nicola; Boi, Fabio; Lecomte, Aziliz; Miele, Ermanno; Malerba, Mario; Zucca, Stefano; Casile, Antonino; Berdondini, Luca

doi:10.1016/j.bios.2018.10.032

Cited by 139 publications

(103 citation statements)

References 37 publications

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“…The 4-shanks SiNAPS probe solution builds on power efficient analog frontend module that was also used in our single shank device previously described in Angotzi et al (2019). As illustrated in Figure 1A, a single SiNAPS module comprises 32 electrode-pixel sites, each providing in situ amplification and low-pass filtering (Gain = 46 dB, f −3dB = 4 kHz).…”

Section: Sinaps 4-shanks Probementioning

confidence: 99%

“…Devices were delivered as single dies with size of (W×L×T = 3 mm×8.5 mm×250 µm) and were post processed in our clean room to make them compatible for brain implantation (final size of each shank W×L×T = 80 µm×5 mm×30 µm). The process flow involves a two-step lithography: a lift-off of Ti/Au on top of the native Al-Cu electrode-pixels to improve the neural interfaces with a noble metal of lower impedance, then the standard process flow established previously for shaping and thinning (Angotzi et al (2019)). Briefly, multiple single chips are fixed onto a single glass slide using water-dissoluble glue, and 80% of the steps in the process can be performed on several dies simultaneously.…”

Section: Cmos Post-processingmentioning

confidence: 99%

“…As previously described in Angotzi et al (2019) the back-end module (currently capable of simultaneous, real-time acquisition of 4096 channels with a 25 kHz sampling rate) comprises an interface board, an acquisition unit, and a data-acquisition software running on a PC equipped with a frame grabber. The interface board connects the headstage mounting the SiNAPS probe to the acquisition unit and integrates a bank of 32 analog to digital converters, one for each of the 32 electrode-pixels module of the SiNAPS probe (MAX11105, Maxim Integrated, USA) with 12-bit resolution each.…”

Section: Sinaps Acquisition Systemmentioning

confidence: 99%

“…Combining the two facets of multichannel extracellular recordings requires high-resolution, large-scale sensing devices capable of monitoring spiking and local field potentials (LFP) within and across widely distributed circuits (Alivisatos et al (2013); Buzsáki (2004); Lewis et al (2015)) and calling for radical scaling of the number of recorded electrodes to yield dense sampling across distributed circuits. Recent studies (Jun et al (2017b); Raducanu et al (2016);De Dorigo et al (2018); Angotzi et al (2019)) proposed micro-/nano fabricated implantable Complementary Metal-Oxide Semiconductor (CMOS) probes with hundreds to thousands recordings sites within small cross-sectional areas. By integrating into the same silicon substrate electrodes and active electronic circuits for signal amplification and filtering, such implantable CMOS probes can simultaneously record from multiple brain regions (Seymour et al (2017); Steinmetz et al (2018)) with an unprecedented spatial resolution.…”

Section: Introductionmentioning

confidence: 99%

“…Ability to densely sample extracellular signals for both single neuronal populations and oscillatory dynamics analysis with anatomical resolution requires precise geometrical scaling of the CMOS-based shafts. In order to address this and many other biological questions related to any type of brain circuits in which vertical and horizontal information needs to be simultaneously sampled, we present here a novel CMOS-probe that exploits the modularity of our SiNAPS (Simultaneous Neural Active Pixel Sensor) technology (see Angotzi et al (2019)) to integrate simultaneous sampling of 1024 electrode-pixels (electrode-pixel size 26×26 µm 2 , pitch 28 µm, electrode pad size 15×15 µm 2 ) arranged on four distinct shanks (80 µm wide x 5 mm long; incorporating 256 contacts/shank covering 3.6 mm; shank separation 560 µm). Preliminary in vivo acute recordings from the brain of behaving head fixed mice demonstrate how broadband neural signals can be acquired from all electrodes simultaneously, with low noise, 6.5±2.1µV RM S in the action potential and 8.5±2.7µV RM S in the LFP (local field potential) bands, and high temporal resolution (16 kHz sampling frequency).…”

Section: Introductionmentioning

confidence: 99%

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

Boi¹,

Perentos

Lecomte³

et al. 2019

Preprint

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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.

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Section: Sinaps 4-shanks Probementioning

confidence: 99%

Section: Cmos Post-processingmentioning

confidence: 99%

Section: Sinaps Acquisition Systemmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Boi¹,

Perentos

Lecomte³

et al. 2019

Preprint

Self Cite

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Surface‐Functionalized Self‐Standing Microdevices Exhibit Predictive Localization and Seamless Integration in 3D Neural Spheroids

et al. 2020

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diseases and develop potential cures. [1] Developments across the fields of biotechnology, tissue engineering, biomaterials, and microtechnology, have led to in vitro models ranging from multilayer 3D cell cultures [2] to small self-standing cell aggregates called spheroids, [3] up to complex brain organoids derived from human pluripotent stem (hPS) cells. [4] Albeit grown in an artificial in vitro environment, the shift from conventional 2D neural cultures to 3D models was shown to better mimic the complexity of intertwined 3D networks found in the brain. [5] hPS-derived brain organoids can indeed recapitulate several aspects specific to human brain development at the level of gene expression, [6] cell-type differentiation and network formation, [7] and can express phenotypes of human brain diseases when generated from patient-derived hPS-cells. [4a,8] Following these results, 3D neural cell assemblies have raised a large interest for the study of human brain diseases and therapies. Furthermore, these models can overcome certain limitations of currently used animal models, such as low experimental accessibility for functional studies, [9] low sample size, low reproducibility and, above all, poor translational relevance of screening results to humans. [5] The routine experimental use of 3D brain tissue models, however, remains largely unpractical for applications in drugdiscovery. On one side, intermodel variability and unmonitored cellular viability can affect the reliable generation of complex 3D brain tissue model systems. For instance, as 3D models become critically sized, the low diffusion of nutrients and oxygen tends to induce the formation of a necrotic core, [1b,4a,5] with consequent losses in cellular viability. On the other side, available biosensing technologies are not yet adapted for the routine monitoring of biosignals such as neural activity inside individual 3D models. This hinders studies aiming toward a better understanding of the emergence of spontaneous neural activity in these models as well as their optimization to reliably generate electrically active brain tissue models for functional assays. Over the last few years, researchers have been working on protocols for culturing organoids with minimal variability, mainly focusing on homogenizing morphologies. [4c] As far as monitoring brain organoids, current major biosensing Brain organoids is an exciting technology proposed to advance studies on human brain development, diseases, and possible therapies. Establishing and applying such models, however, is hindered by the lack of technologies to chronically monitor neural activity. A promising new approach comprising selfstanding biosensing microdevices capable of achieving seamless tissue integration during cell aggregation and culture. To date, there is little information on how to control the aggregation of such bioartificial 3D neural assemblies. Here, the growth of hybrid neurospheroids obtained by the aggregation of silicon sham microchips (100 × 100 × 50 μm 3) with primary cortical cells ...

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Combining PEDOT:PSS Polymer Coating with Metallic 3D Nanowires Electrodes to Achieve High Electrochemical Performances for Neuronal Interfacing Applications

et al. 2023

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This study presents a novel approach to improve the performance of microelectrode arrays (MEAs) used for electrophysiological studies of neuronal networks. The integration of 3D nanowires (NWs) with MEAs increases the surface‐to‐volume ratio, which enables subcellular interactions and high‐resolution neuronal signal recording. However, these devices suffer from high initial interface impedance and limited charge transfer capacity due to their small effective area. To overcome these limitations, the integration of conductive polymer coatings, poly(3,4‐ethylenedioxythiophene)‐poly(styrenesulfonate) (PEDOT:PSS) is investigated as a mean of improving the charge transfer capacity and biocompatibility of MEAs. The study combines platinum silicide‐based metallic 3D nanowires electrodes with electrodeposited PEDOT:PSS coatings to deposit ultra‐thin (<50 nm) layers of conductive polymer onto metallic electrodes with very high selectivity. The polymer‐coated electrodes were fully characterized electrochemically and morphologically to establish a direct relationship between synthesis conditions, morphology, and conductive features. Results show that PEDOT‐coated electrodes exhibit thickness‐dependent improved stimulation and recording performances, offering new perspectives for neuronal interfacing with optimal cell engulfment to enable the study of neuronal activity with acute spatial and signal resolution at the sub‐cellular level.

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SiNAPS: An implantable active pixel sensor CMOS-probe for simultaneous large-scale neural recordings

Cited by 139 publications

References 37 publications

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

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

Surface‐Functionalized Self‐Standing Microdevices Exhibit Predictive Localization and Seamless Integration in 3D Neural Spheroids

Combining PEDOT:PSS Polymer Coating with Metallic 3D Nanowires Electrodes to Achieve High Electrochemical Performances for Neuronal Interfacing Applications

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