Time Multiplexed Active Neural Probe with 1356 Parallel Recording Sites

We present a high electrode density and high channel count CMOS (complementary metal-oxide-semiconductor) active neural probe containing 1344 neuron sized recording pixels (20 µm × 20 µm) and 12 reference pixels (20 µm × 80 µm), densely packed on a 50 µm thick, 100 µm wide, and 8 mm long shank. The active electrodes or pixels consist of dedicated in-situ circuits for signal source amplification, which are directly located under each electrode. The probe supports the simultaneous recording of all 1356 electrodes with sufficient signal to noise ratio for typical neuroscience applications. For enhanced performance, further noise reduction can be achieved while using half of the electrodes (678). Both of these numbers considerably surpass the state-of-the art active neural probes in both electrode count and number of recording channels. The measured input referred noise in the action potential band is 12.4 µVrms, while using 678 electrodes, with just 3 µW power dissipation per pixel and 45 µW per read-out channel (including data transmission)

Time Multiplexed Active Neural Probe with 678 Parallel Recording Sites

We present a high density CMOS neural probe with active electrodes (pixels), consisting of dedicated in-situ circuits for signal source amplification. The complete probe contains 1356 neuron size (20x20 μm2) pixels densely packed on a 50 μm thick, 100 μm wide and 8 mm long shank. It allows simultaneous highperformance recording from 678 electrodes and a possibility to simultaneously observe all of the 1356 electrodes with increased noise. This considerably surpasses the state of the art active neural probes in electrode count and flexibility. The measured action potential band noise is 12.4 μVrms, with just 3 μW power dissipation per electrode amplifier and 45 μW per channel (including data transmission)

A neural probe with up to 966 electrodes and up to 384 configurable channels in 0.13 μm SOI CMOS

In vivo recording of neural action-potential and local-field-potential signals requires the use of high-resolution penetrating probes. Several international initiatives to better understand the brain are driving technology efforts towards maximizing the number of recording sites while minimizing the neural probe dimensions. We designed and fabricated (0.13-μm SOI Al CMOS) a 384-channel configurable neural probe for large-scale in vivo recording of neural signals. Up to 966 selectable active electrodes were integrated along an implantable shank (70 μm wide, 10 mm long, 20 μm thick), achieving a crosstalk of −64.4 dB. The probe base (5 × 9 mm2) implements dual-band recording and a 1

Challenges and opportunities for large-scale electrophysiology with Neuropixels probes

Electrophysiological methods are the gold standard in neuroscience because they reveal the activity of individual neurons at high temporal resolution and in arbitrary brain locations. Microelectrode arrays based on complementary metal-oxide semiconductor (CMOS) technology, such as Neuropixels probes, look set to transform these methods. Neuropixels probes provide ∼1000 recording sites on an extremely narrow shank, with on-board amplification, digitization, and multiplexing. They deliver low-noise recordings from hundreds of neurons, providing a step change in the type of data available to neuroscientists. Here we discuss the opportunities afforded by these probes for large-scale electrophysiology, the challenges associated with data processing and anatomical localization, and avenues for further improvements of the technology

Materials and neuroscience: validating tools for large-scale, high-density neural recording

Extracellular recording remains the only technique capable of measuring the activity of many neurons simultaneously with a sub-millisecond precision, in multiple brain areas, including deep structures. Nevertheless, many questions about the nature of the detected signal and the limitations/capabilities of this technique remain unanswered. The general goal of this work is to apply the methodology and concepts of materials science to answer some of the major questions surrounding extracellular recording, and thus take full advantage of this seminal technique. We start out by quantifying the effect of electrode impedance on the amplitude of measured extracellular spikes and background noise. Can we improve data quality by lowering electrode impedance? We demonstrate that if the proper recording system is used, then the impedance of a microelectrode, within the range typical of standard polytrodes (~ 0.1 to 2 MΩ), does not significantly affect a neural spike amplitude or the background noise, and therefore spike sorting. In addition to improving the performance of each electrode, increasing the number of electrodes in a single neural probe has also proven advantageous for simultaneously monitoring the activity of more neurons with better spatiotemporal resolution. How can we achieve large-scale, highdensity extracellular recordings without compromising brain tissue? Here we report the design and in vivo validation of a complementary metal–oxide–semiconductor (CMOS)-based scanning probe with 1356 electrodes arranged along approximately 8 mm of a thin shaft (50 μm thick and 100 μm wide). Additionally, given the ever-shrinking dimensions of CMOS technology, there is a drive to fabricate sub-cellular electrodes (< 10 μm). Therefore, to evaluate electrode configurations for future probe designs, several recordings from many different brain regions were performed with an ultra-dense probe containing 255 electrodes, each with a geometric area of 5 x 5 μm and a pitch of 6 μm. How can we validate neural probes with different electrode materials/configurations and different sorting algorithms? We describe a new procedure for precisely aligning two probes for in vivo “paired-recordings” such that the spiking activity of a single neuron is monitored with both a dense extracellular silicon polytrode and a juxtacellular micro-pipette. We gathered a dataset of paired-recordings, which is available online. The “ground truth” data, for which one knows exactly when a neuron in the vicinity of an extracellular probe generates an action potential, has been used for several groups to validate and quantify the performance of new algorithms to automatically detect/sort single-units

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

Abstract Large-scale neural recordings with high spatial and temporal accuracy are instrumental to understand how the brain works. To this end, it is of key importance to develop probes that can be conveniently scaled up to a high number of recording channels. Despite recent achievements in complementary metal-oxide semiconductor (CMOS) multi-electrode arrays probes, in current circuit architectures an increase in the number of simultaneously recording channels would significantly increase the total chip area. A promising approach for overcoming this scaling issue consists in the use of the modular Active Pixel Sensor (APS) concept, in which a small front-end circuit is located beneath each electrode. However, this approach imposes challenging constraints on the area of the in-pixel circuit, power consumption and noise. Here, we present an APS CMOS-probe technology for Simultaneous Neural recording that successfully addresses all these issues for whole-array read-outs at 25 kHz/channel from up to 1024 electrode-pixels. To assess the circuit performances, we realized in a 0.18  μ m CMOS technology an implantable single-shaft probe with a regular array of 512 electrode-pixels with a pitch of 28  μ m. Extensive bench tests showed an in-pixel gain of 45.4 ± 0.4 dB (low pass, F-3 dB = 4 kHz), an input referred noise of 7.5 ± 0.67 μVRMS (300 Hz to 7.5 kHz) and a power consumptio

Parylene Based Flexible Multifunctional Biomedical Probes And Their Applications

MEMS (Micro Electro Mechanical System) based flexible devices have been studied for decades, and they are rapidly being incorporated into modern society in various forms such as flexible electronics and wearable devices. Especially in neuroscience, flexible interfaces provide tremendous possibilities and opportunities to produce reliable, scalable and biocompatible instruments for better exploring neurotransmission and neurological disorders. Of all the types of biomedical instruments such as electroencephalography (EEG) and electrocorticography (ECoG), MEMS-based needle-shape probes have been actively studied in recent years due to their better spatial resolution, selectivity, and sensitivity in chronical invasive physiology monitoring. In order to address the inherent issue of invasiveness that causes tissue damage, research has been made on biocompatible materials, implanting methods and probe structural design. In this dissertation, different types of microfabricated probes for various applications are reviewed. General methods for some key fabrication steps include photolithography patterning, chemical vapor deposition, metal deposition and dry etching are covered in detail. Likewise, three major achievements, which aim to the tagets of flexibility, functionality and mechanical property are introduced and described in detail from chapter 3 to 5. The essential fabrication processes based on XeF2 isotropic silicon etching and parylene conformal deposition are covered in detail, and a set of characterization is summarized

Parylene Based Flexible Multifunctional Biomedical Probes And Their Applications

MEMS (Micro Electro Mechanical System) based flexible devices have been studied for decades, and they are rapidly being incorporated into modern society in various forms such as flexible electronics and wearable devices. Especially in neuroscience, flexible interfaces provide tremendous possibilities and opportunities to produce reliable, scalable and biocompatible instruments for better exploring neurotransmission and neurological disorders. Of all the types of biomedical instruments such as electroencephalography (EEG) and electrocorticography (ECoG), MEMS-based needle-shape probes have been actively studied in recent years due to their better spatial resolution, selectivity, and sensitivity in chronical invasive physiology monitoring. In order to address the inherent issue of invasiveness that causes tissue damage, research has been made on biocompatible materials, implanting methods and probe structural design. In this dissertation, different types of microfabricated probes for various applications are reviewed. General methods for some key fabrication steps include photolithography patterning, chemical vapor deposition, metal deposition and dry etching are covered in detail. Likewise, three major achievements, which aim to the tagets of flexibility, functionality and mechanical property are introduced and described in detail from chapter 3 to 5. The essential fabrication processes based on XeF2 isotropic silicon etching and parylene conformal deposition are covered in detail, and a set of characterization is summarized

Optogenetic stimulation probes with single-neuron resolution based on organic LEDs monolithically integrated on CMOS

Funding: This work was supported in part by the Defense Advanced Research Projects Agency (DARPA) under contract N6600117C4012, by the National Institutes of Health under grant U01NS090596, by the Leverhulme Trust (RPG-2017-231) and by the Alexander von Humboldt Stiftung (Humboldt-Professorship to M.C.G.). This work was performed in part at the Columbia Nano Initiative cleanroom facility, at the CUNY Advanced Science Research Center Nanofabrication Facility, and at the Singh Center for Nanotechnology, part of the National Nanotechnology Coordinated Infrastructure Program, which is supported by the National Science Foundation grant NNCI-2025608. C.-K.M. acknowledges funding from the European Commission through a Marie-Skłodowska Curie Individual Fellowship (101029807).The use of optogenetic stimulation to evoke neuronal activity in targeted neural populations—enabled by opsins with fast kinetics, high sensitivity and cell-type and subcellular specificity—is a powerful tool in neuroscience. However, to interface with the opsins, deep-brain light delivery systems are required that match the scale of the spatial and temporal control offered by the molecular actuators. Here we show that organic light-emitting diodes can be combined with complementary metal–oxide–semiconductor technology to create bright, actively multiplexed emissive elements. We create implantable shanks in which 1,024 individually addressable organic light-emitting diode pixels with a 24.5 µm pitch are integrated with active complementary metal–oxide–semiconductor drive and control circuitry. This integration is enabled by controlled electrode conditioning, monolithic deposition of the organic light-emitting diodes and optimized thin-film encapsulation. The resulting probes can be used to access brain regions as deep as 5 mm and selectively activate individual neurons with millisecond-level precision in mice.Publisher PDFPeer reviewe

Histological assessment of a chronically implanted cylindrically-shaped, polymer-based neural probe in the monkey

Objective. Previous studies demonstrated the possibility to fabricate stereo-electroencephalography probes with high channel count and great design freedom, which incorporate macro-electrodes as well as micro-electrodes offering potential benefits for the pre-surgical evaluation of drug resistant epileptic patients. These new polyimide probes allowed to record local field potentials, multi- and single-unit activity (SUA) in the macaque monkey as early as 1 h after implantation, and yielded stable SUA for up to 26 d after implantation. The findings opened new perspectives for investigating mechanisms underlying focal epilepsy and its treatment, but before moving to possible human application, safety data are needed. In the present study we evaluate the tissue response of this new neural interface by assessing post-mortem the reaction of brain tissue along and around the probe implantation site. Approach. Three probes were implanted, independently, in the brain of one monkey (Macaca mulatta) at different times. We used specific immunostaining methods for visualizing neuronal cells and astrocytes, for measuring the extent of damage caused by the probe and for relating it with the implantation time. Main results. The size of the region where neurons cannot be detected did not exceed the size of the probe, indicating that a complete loss of neuronal cells is only present where the probe was physically positioned in the brain. Furthermore, around the probe shank, we observed a slightly reduced number of neurons within a radius of 50 µm and a modest increase in the number of astrocytes within 100 µm. Significance. In the light of previous electrophysiological findings, the present data suggest the potential usefulness and safety of this probe for human applications