We present a waveguide-based optogenetics neural probe with 1,280 electrodes, 384 recording channels, and 88 emission sites enabled by dual-layer silicon photonics. Thermo-optic switches are controlled by a custom photonic driver IC, while integrated tap couplers with photodiodes and a temperature sensor provide on-chip calibration and thermal monitoring. The probe achieves a large number of recording and emission sites, enabling reliable large-scale, cell-type-specific optogenetic studies.

The brain orchestrates billions of neurons spanning hundreds of regions to drive behavior. High-density electrophysiology has provided insights into this process, but monitoring brain-wide patterns of spiking activity demands new tools. Here we present Neuropixels 2.0 Quad Base, a 1536-channel probe with four times the simultaneous recording capacity of state-of-art Neuropixels 2.0. Using two Quad Base probes, we performed 3072-channel recordings in mice trained to produce complex sequences of goal-directed licks. We decoded behavioral kinematics from neural populations across more than 20 brain regions and identified the spatiotemporal emergence of motor decision signals. The probes’ high channel count further revealed expanded inter-neuronal functional subnetworks and latent dynamics across multiple areas—features significantly undersampled when channels were subsampled to mimic standard Neuropixels 2.0. Neuropixels 2.0 Quad Base offers a powerful tool to explore neural encoding of cognition and behavior at grand scale.

High-density electrophysiological recording with Neuropixels probes enables single-unit resolution of human neural activity, but integration into routine clinical environments remains challenging and reported recordings have been limited to a few US centres. Here, we present a reproducible roadmap for human Neuropixels recordings under a nationally managed regulatory framework in the United Kingdom. Guided by the IDEAL Stage 2a (Development) framework, we established a frameless intraoperative workflow using manufacturer-sterilised probes and a commercially available, clinical-grade setup. We prospectively evaluated this workflow in six participants (mean age 62.5 years) undergoing elective ventriculoperitoneal shunt surgery, assessed across three predefined endpoints: clinical safety, procedural timing, and neural data yield. Iterative failure-mitigation cycles resolved key technical barriers, including neuronavigation interference and hardware instability. The workflow achieved zero research-related adverse events, maintained a 30-minute procedural extension, and progressively increased single-unit yield to 146 manually curated units.

High-density, integrated silicon electrodes have begun to transform systems neuroscience, by enabling large-scale neural population recordings with single cell resolution. Existing technologies, however, have provided limited functionality in nonhuman primate species such as macaques, which offer close models of human cognition and behavior. Here, we report the design, fabrication, and performance of Neuropixels 1.0-NHP, a high channel count linear electrode array designed to enable large-scale simultaneous recording in superficial and deep structures within the macaque or other large animal brain. These devices were fabricated in two versions: 4416 electrodes along a 45 mm shank, and 2496 along a 25 mm shank. For both versions, users can programmatically select 384 channels, enabling simultaneous multi-area recording with a single probe. We demonstrate recording from over 3000 single neurons within a session, and simultaneous recordings from over 1000 neurons using multiple probes. This technology represents a significant increase in recording access and scalability relative to existing technologies, and enables new classes of experiments involving fine-grained electrophysiological characterization of brain areas, functional connectivity between cells, and simultaneous brain-wide recording at scale.

OBJECTIVE:The Neuropixels probe, a high-density silicon microelectrode array, has been a transformative tool for extracellular recording of large numbers of single neurons across animal models. Traditional tungsten microelectrodes available for clinical neurophysiology typically only record 1-2 neurons at a given time. Human intraoperative Neuropixels recording increases access to single-neuron spiking by an order of magnitude and is poised for rapid adoption. The authors' objective was to determine the safety and yield of intraoperative Neuropixels for large-scale simultaneous neuronal recordings. METHODS:This study examined safety and the success rate from the authors' case series of 56 consecutive patients who participated in Neuropixels intraoperative recording at the authors' institution. All participants were undergoing craniotomy for resection for various pathologies (intractable epilepsy [n = 33], tumor [n = 19], and vascular lesion [n = 4]). Among these craniotomies for resection, the vast majority were done under monitored anesthesia care with awake mapping (50/56). In all cases, a Neuropixels probe was placed into tissue that was resected, allowing histology to be recovered from a subset of cases. All intraoperative probe fractures, cases that did not yield any putative single-neuron recordings, and postoperative complications are reported here. RESULTS:No medical or neurological complications, surgical complications, 30-day readmissions, or deaths were observed. Overall, probe fractures were rare (n = 3) and all occurred within the first 6 cases. All fractures occurred at the base of the probe shank and were easily recovered. In recovered acute histology from 1 case, the histological evidence of insertion was minimal and proportional to the 70 mm × 132 mm cross-sectional area. In terms of yield, most cases had good neuronal yield, with only 9 (16.1%) cases that did not result in at least 1 putative single-neuron recording, with the etiology of failure being attributable to either electrical noise (6/9) or there being no detectable spikes (3/9). All cases that did not result in at least 1 putative single-neuron recording occurred within the first 20 cases, suggesting significant improvements in the learning curve and techniques for high-yield and safe intraoperative recordings. CONCLUSIONS:Intraoperative Neuropixels recordings can be done safely for large-scale neuronal recordings. Over time, the authors experienced no probe fractures and improved success rate of microelectrode recording. Further measures to float the electrodes, limit forces on the probe, and prevent probe fracture during insertion may improve the yield. Neuropixels has tremendous potential for future applications in clinical functional mapping over traditional microelectrodes.

To understand the neural basis of behavior, it is essential to sensitively and accurately measure neural activity at single-neuron and single-spike resolution. Extracellular electrophysiology delivers this, but it has biases in the neurons it detects and it imperfectly resolves their action potentials. To minimize these limitations, we developed a silicon probe with much smaller and denser recording sites than previous designs, called Neuropixels Ultra (NP Ultra). Using NP Ultra, neuronal yield in mouse visual cortex recordings increased by more than 2-fold. With ultra-high spatial resolution, we discovered that a feature of extracellular waveforms, the spatial extent or “footprint,” distinguished axonal from somatic recordings. In addition, three genetically identified cortical cell types could be discriminated from one another with ∼80% accuracy and from other neurons with ∼85% accuracy. NP Ultra improves yield, detection of subcellular compartments, and cell type identification to enable a more powerful dissection of neural circuit activity during behavior.

We report on the progress in multimodal high resolution integrated neural interfaces with a focus on the Neuropixels probes. Historically, the number of neurons recorded simultaneously follows a Moore's law like behavior, with numbers doubling every 6.7 years. Traditional approaches to probe fabrication have failed to meet the needs of scaling needs of neural recording. The Neuropixels platform, is a custom 130nm/55nm CMOS wafer scale process technology that enables electrode counts beyond the 1000's, enabling system level simultaneous recording of tens of thousands of neurons with single neuron spatial precision and millisecond timing resolution. This required the utilization of multilevel BEOL technology and integrating analog and digital circuitry with the electrode array, making it a standalone integrated electrophysiological micro-system. Recently, we have added a switchable two-color visible photonics module that enables cell specific stimulation and responsive electro-physiology using opto-genetics. In addition, we have added 3D-integration modules which allows die-to-wafer attachment and have extended the platform to the 55nm node to enable higher electrode and recording density. These enable the recording of 10,000 neurons in a chronic freely moving animal and 40,000 neurons in an acute headfixed set-up.

We present a highly integrated neural probe for in vivo recordings, boasting a record of 1536 channels and 5120 TiN electrodes. The probe is optimally engineered with integrated capless LDOs and a low-power LVDS transmitter for energy-efficient data transfer, achieving a high level of integration and minimizing the number of external components. Innovative block-level optimization techniques result in a total area of 0.012mm2/ch, a total power of 19.34μW/ch, and the lowest total power-efficiency factor, while attaining excellent performance uniformity across channels. The probe is fabricated using a fab-compatible 300-mm post-CMOS process and fully validated in saline, demonstrating its ability to record full-band neural signals.

Co-integration of III-V and silicon on the same substrate can enable many applications in photonics, RF, imaging, and sensing. Wafer reconstitution (WARE) is an embedded multi-die integration platform that allows for the integration of heterogenous materials on 200/300 mm Si substrates. This paper describes an integration flow for InP dies attached to 200 mm silicon. Electrical measurements on InGaAs diodes fabricated on WARE wafers confirm that the performance is similar to devices on native InP substrates.

We present the development of a monolithically integrated CMOS and photonics platform, capable of supporting passive and active visible photonics with thermooptic switches. This platform is co-integrated with a 130-nm SOI-based 6-level Al-BEOL, enabling a range of bi-modal opto-electronic sensor applications. Through this platform, we demonstrate an implantable CMOS-based neural probe that integrates a high-density array of 960 selectable electrodes and 384 recording channels, along with 14 programmable optical emission sites for two visible wavelengths: 450 and 638 nm. The probe offers the neuroscience community a new technique for cell/circuit-specific activity and neural modulation monitoring through optogenetics-based optical tagging.

High-density, integrated silicon electrodes have begun to transform systems neuroscience, by enabling large-scale neural population recordings with single cell resolution. Existing technologies, however, have provided limited functionality in nonhuman primate species such as macaques, which offer close models of human cognition and behavior. Here, we report the design, fabrication, and performance of Neuropixels 1.0-NHP, a high channel count linear electrode array designed to enable large-scale simultaneous recording in superficial and deep structures within the macaque or other large animal brain. These devices were fabricated in two versions: 4416 electrodes along a 45 mm shank, and 2496 along a 25 mm shank. For both versions, users can programmably select 384 channels, enabling simultaneous multi-area recording with a single probe. We demonstrate recording from over 3000 single neurons within a session, and simultaneous recordings from over 1000 neurons using multiple probes. This technology represents a significant increase in recording access and scalability relative to existing technologies, and enables new classes of experiments involving fine-grained electrophysiological characterization of brain areas, functional connectivity between cells, and simultaneous brain-wide recording at scale.

Neuropixels are silicon-based electrophysiology-recording probes with high channel count and recording-site density. These probes offer a turnkey platform for measuring neural activity with single-cell resolution and at a scale that is beyond the capabilities of current clinically approved devices. Our team demonstrated the first-in-human use of these probes during resection surgery for epilepsy or tumors and deep brain stimulation electrode placement in patients with Parkinson's disease. Here, we provide a better understanding of the capabilities and challenges of using Neuropixels as a research tool to study human neurophysiology, with the hope that this information may inform future efforts toward regulatory approval of Neuropixels probes as research devices. In perioperative procedures, the major concerns are the initial sterility of the device, maintaining a sterile field during surgery, having multiple referencing and grounding schemes available to de-noise recordings (if necessary), protecting the silicon probe from accidental contact before insertion and obtaining high-quality action potential and local field potential recordings. The research team ensures that the device is fully operational while coordinating with the surgical team to remove sources of electrical noise that could otherwise substantially affect the signals recorded by the sensitive hardware. Prior preparation using the equipment and training in human clinical research and working in operating rooms maximize effective communication within and between the teams, ensuring high recording quality and minimizing the time added to the surgery. The perioperative procedure requires ~4 h, and the entire protocol requires multiple weeks.

Understanding the neural basis of speech perception requires that we study the human brain both at the scale of the fundamental computational unit of neurons and in their organization across the depth of cortex. Here we used high-density Neuropixels arrays 1 – 3 to record from 685 neurons across cortical layers at nine sites in a high-level auditory region that is critical for speech, the superior temporal gyrus 4 , 5 , while participants listened to spoken sentences. Single neurons encoded a wide range of speech sound cues, including features of consonants and vowels, relative vocal pitch, onsets, amplitude envelope and sequence statistics. Neurons at each cross-laminar recording exhibited dominant tuning to a primary speech feature while also containing a substantial proportion of neurons that encoded other features contributing to heterogeneous selectivity. Spatially, neurons at similar cortical depths tended to encode similar speech features. Activity across all cortical layers was predictive of high-frequency field potentials (electrocorticography), providing a neuronal origin for macroelectrode recordings from the cortical surface. Together, these results establish single-neuron tuning across the cortical laminae as an important dimension of speech encoding in human superior temporal gyrus.

Intra-cortical extracellular neural sensing is being rapidly and widely applied in several clinical research and brain-computer interfaces (BCIs), as the number of sensing channels continues to double every 6 years. By distributing multiple high-density extracellular micro-electrode arrays (MEAs) in vivo across the brain, each with 1000's of sensing channels, neuroscientists have begun to map the correlation of neuronal activity across different brain regions, with single-neuron precision [1]. Since each neural sensing channel typically samples at 20 to 50kS/s with a > 10b ADC, multiple MEAs demand a data transfer rate up to Gb/s [2]. However, these BCIs are severely hindered in many clinical uses due to the lack of a high-data-rate and miniature-wireless-telemetry solution that can be implanted below the scalp, i.e., transcutaneously (Fig. 24.2.1). The area of the wireless telemetry module should be miniaturized to ~3cm 2 due to neurosurgical implantation constraints. A transmission range up to 10cm is highly desirable, in order to improve the reliability of the wireless link against e.g., antenna misalignment, etc. Finally, the power consumption of the wireless telemetry should be limited to ~10mW to minimize thermal flux from the module's surface area, avoiding excessive tissue heating. Most of the conventional transcutaneous wireless telemetry systems adopt inductive coupling, but the data-rate is limited to a few Mb/s. A near-infrared (NIR) optical transcutaneous TX using a vertical-cavity-surface-emitting laser (VCSEL) [2] demonstrated a data-rate up to 300Mb/s but suffers from a limited transmission range (4mm) and requires a sub-mm precise alignment between the implant TX and a wearable RX. Impulse-radio UWB (IR-UWB) is promising for the targeted requirements [3]–[5].

The action potential is a fundamental unit of neural computation. Even though significant advances have been made in recording large numbers of individual neurons in animal models, translation of these methodologies to humans has been limited because of clinical constraints and electrode reliability. Here, we present a reliable method for intraoperative recording of dozens of neurons in humans using the Neuropixels probe, yielding up to ∼100 simultaneously recorded single units. Most single units were active within 1 min of reaching target depth. The motion of the electrode array had a strong inverse correlation with yield, identifying a major challenge and opportunity to further increase the probe utility. Cell pairs active close in time were spatially closer in most recordings, demonstrating the power to resolve complex cortical dynamics. Altogether, this approach provides access to population single-unit activity across the depth of human neocortex at scales previously only accessible in animal models.

Recent advances in multi-electrode array technology have made it possible to monitor large neuronal ensembles at cellular resolution in animal models. In humans, however, current approaches restrict recordings to a few neurons per penetrating electrode or combine the signals of thousands of neurons in local field potential (LFP) recordings. Here we describe a new probe variant and set of techniques that enable simultaneous recording from over 200 well-isolated cortical single units in human participants during intraoperative neurosurgical procedures using silicon Neuropixels probes. We characterized a diversity of extracellular waveforms with eight separable single-unit classes, with differing firing rates, locations along the length of the electrode array, waveform spatial spread and modulation by LFP events such as inter-ictal discharges and burst suppression. Although some challenges remain in creating a turnkey recording system, high-density silicon arrays provide a path for studying human-specific cognitive processes and their dysfunction at unprecedented spatiotemporal resolution.

Measuring the dynamics of neural processing across time scales requires following the spiking of thousands of individual neurons over milliseconds and months. To address this need, we introduce the Neuropixels 2.0 probe together with newly designed analysis algorithms. The probe has more than 5000 sites and is miniaturized to facilitate chronic implants in small mammals and recording during unrestrained behavior. High-quality recordings over long time scales were reliably obtained in mice and rats in six laboratories. Improved site density and arrangement combined with newly created data processing methods enable automatic post hoc correction for brain movements, allowing recording from the same neurons for more than 2 months. These probes and algorithms enable stable recordings from thousands of sites during free behavior, even in small animals such as mice.

We review recent progress in neural probes for brain recording, with a focus on the Neuropixels platform. Historically the number of neurons' recorded simultaneously, follows a Moore's law like behavior, with numbers doubling every 6.7 years. Using traditional techniques of probe fabrication, continuing to scale up electrode densities is very challenging. We describe a custom CMOS process technology that enables electrode counts well beyond 1000 electrodes; with the aim to characterize large neural populations with single neuron spatial precision and millisecond timing resolution. This required integrating analog and digital circuitry with the electrode array, making it a standalone integrated electrophysiology recording system. Input referred noise and power per channel is 7.5μV and <; 50μW respectively to ensure tissue heating <; 1°C. This approach enables doubling the number of measured neurons every 12 months.

New silicon probes known as Neuropixels are shown to record from hundreds of neurons simultaneously in awake and freely moving rodents. Sensory, motor and cognitive operations involve the coordinated action of large neuronal populations across multiple brain regions. Existing technologies reliably measure activity from a relatively small number of neurons with high spatial and temporal resolution, or from a large volume of neurons with low resolution. Timothy Harris and colleagues describe the design, fabrication and performance of Neuropixels, a silicon probe that can measure well-isolated neural activity from hundreds of neurons. They integrated these probes into a lightweight system that could record activity simultaneously and with high fidelity from hundreds of neurons in awake and freely moving rodents. Sensory, motor and cognitive operations involve the coordinated action of large neuronal populations across multiple brain regions in both superficial and deep structures1,2. Existing extracellular probes record neural activity with excellent spatial and temporal (sub-millisecond) resolution, but from only a few dozen neurons per shank. Optical Ca2+ imaging3,4,5 offers more coverage but lacks the temporal resolution needed to distinguish individual spikes reliably and does not measure local field potentials. Until now, no technology compatible with use in unrestrained animals has combined high spatiotemporal resolution with large volume coverage. Here we design, fabricate and test a new silicon probe known as Neuropixels to meet this need. Each probe has 384 recording channels that can programmably address 960 complementary metal–oxide–semiconductor (CMOS) processing-compatible low-impedance TiN6 sites that tile a single 10-mm long, 70 × 20-μm cross-section shank. The 6 × 9-mm probe base is fabricated with the shank on a single chip. Voltage signals are filtered, amplified, multiplexed and digitized on the base, allowing the direct transmission of noise-free digital data from the probe. The combination of dense recording sites and high channel count yielded well-isolated spiking activity from hundreds of neurons per probe implanted in mice and rats. Using two probes, more than 700 well-isolated single neurons were recorded simultaneously from five brain structures in an awake mouse. The fully integrated functionality and small size of Neuropixels probes allowed large populations of neurons from several brain structures to be recorded in freely moving animals. This combination of high-performance electrode technology and scalable chip fabrication methods opens a path towards recording of brain-wide neural activity during behaviour.