Carolina Mora Lopez

An implantable 455-active-electrode 52-channel CMOS neural probe

Several studies have demonstrated that understanding certain brain functions can only be achieved by simultaneously monitoring the electrical activity of many individual neurons in multiple brain areas [1]. Therefore, the main tradeoff in neural probe design is between minimizing the probe dimensions and achieving high spatial resolution using large arrays of small recording sites. Current state-of-the-art solutions are limited in the amount of simultaneous readout channels [2], contain a small number of electrodes [2,3] or use hybrid implementations to increase the number of readout channels [3,4].

Fully integrated silicon probes for high-density recording of neural activity

Sensory, motor and cognitive operations involve the coordinated action of large neuronal populations across multiple brain regions in both superficial and deep structures. 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+ imaging 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 TiN 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.

A Multichannel Integrated Circuit for Electrical Recording of Neural Activity, With Independent Channel Programmability

Since a few decades, micro-fabricated neural probes are being used, together with microelectronic interfaces, to get more insight in the activity of neuronal networks. The need for higher temporal and spatial recording resolutions imposes new challenges on the design of integrated neural interfaces with respect to power consumption, data handling and versatility. In this paper, we present an integrated acquisition system for in vitro and in vivo recording of neural activity. The ASIC consists of 16 low-noise, fully-differential input channels with independent programmability of its amplification (from 100 to 6000 V/V) and filtering (1-6000 Hz range) capabilities. Each channel is AC-coupled and implements a fourth-order band-pass filter in order to steeply attenuate out-of-band noise and DC input offsets. The system achieves an input-referred noise density of 37 nV/√Hz, a NEF of 5.1, a CMRR >; 60 dB, a THD <; 1% and a sampling rate of 30 kS/s per channel, while consuming a maximum of 70 μA per channel from a single 3.3 V. The ASIC was implemented in a 0.35 μm CMOS technology and has a total area of 5.6 × 4.5 mm2. The recording system was successfully validated in in vitro and in vivo experiments, achieving simultaneous multichannel recordings of cell activity with satisfactory signal-to-noise ratios.

Towards a noise prediction model for in vivo neural recording

The signal-to-noise ratio of in vivo extracellular neural recordings with microelectrodes is influenced by many factors including the impedance of the electrode-tissue interface, the noise of the recording equipment and biological background noise from distant neurons. In this work we study the different noise sources affecting the quality of neural signals. We propose a simplified noise model as an analytical tool to predict the noise of an electrode given its geometrical dimensions and impedance characteristics. With this tool we are able to quantify different noise sources, which is important to determine realistic noise specifications for the design of electronic neural recording interfaces.

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).

22.7 A 966-electrode neural probe with 384 configurable channels in 0.13µm SOI CMOS

In vivo recording of neural action-potential (AP) and local-field-potential (LFP) signals requires the use of high-resolution penetrating probes. Driven by the need for large-scale recording and minimal tissue damage, a technology roadmap has been defined for next-generation probes aiming to maximize the number of recording sites while minimizing the probe dimensions [1]. In this paper we present a 384-channel configurable active neural probe for high-density recording which implements in situ buffering under each electrode to minimize the crosstalk between adjacent metal lines along the shank and other parasitic effects inherent to traditional passive probes [2]. Up to 966 selectable, neuron-sized electrodes (12×12μm2) were densely packed along a narrow (70μm) and thin (20μm) implantable shank using integrated CMOS. With twice the number of electrodes compared to state-of-the-art neural probes [2], our design achieves the highest electrode count in a single shank reported so far.

24-channel dual-band wireless neural recorder with activity-dependent power consumption

Recording neural activity from freely behaving animals has become extremely important for basic research in neuroscience. One of the major limitations in this domain arises from the need of a low-power, lightweight, wireless recording unit that can be used on small animals for at least a couple of hours. To conserve power, it is essential to reduce the large data volume from tens or even hundreds of recording sites. Since it is widely considered that the primary information in neural recording is limited to the infrequent action potentials (AP or spike), the data can be considerably reduced by using a system based on AP activity [1]. This paper presents a complete activity-dependent wireless system that utilizes an ASIC for recording simultaneous AP and local field potential (LFP) signals, improving the state of the art in terms of performance-to-weight ratio. In spite of large data compression, we demonstrate a method to accurately preserve the AP shape, essential for further processing and spike sorting. Finally, this is the first system (see Fig. 16.4.6 comparison table) particularly designed to take advantage of tetrode (four closely placed electrodes) based neural recording units (Fig. 16.4.1).

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 sized (20×20 μm2) pixels densely packed on a 50 μm thick, 100 μm wide and 8 mm long shank. It allows simultaneous high-performance 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).

Ultra-high-density in-vivo neural probes.

The past decade has witnessed an explosive growth in our ability to observe and measure brain activity. Among different functional brain imaging techniques, the electrical measurement of neural activity using neural probes provides highest temporal resolution. Yet, the electrode density and the observability of currently available neural probe technologies fall short of the density of neurons in the brain by several orders of magnitude. This paper presents opportunities for neural probes to utilize advances in CMOS technology for increasing electrode density and observability of neural activity, while minimizing the tissue damage. The authors present opportunities for neural probes to adapt advanced CMOS technologies and discuss challenges in terms of maintaining the signal integrity and implementing data communication.

A 16-channel low-noise programmable system for the recording of neural signals

The current migration from passive to active neuroprobes, the increasing density in multielectrode arrays, as well as the introduction of new materials and processes for electrode fabrication, are imposing important challenges on the implementation of optimal integrated neural recording systems. In this paper, we present the design and implementation of an integrated neural acquisition system with 16 fully-differential input channels with individual channel programmability for the recording of neural activity in in vitro and in vivo experiments. Each channel consists of ac-coupled low-power, low-noise programmable amplification (from 100 to 6000 V/V) and programmable band-pass filtering, achieving 37nV/√Hz input-referred noise density while consuming a maximum of 70 µA per channel from a single 3.3V. The ASIC was implemented in a 0.35 µm CMOS technology and has a total area of 5.6 × 4.5 mm2. The system has been successfully tested in in vitro experiments, achieving simultaneous extracellular recordings of action potentials and showing satisfactory signal-to-noise ratios.