Multiplexed, High Density Electrophysiology with Nanofabricated Neural Probes

Extracellular electrode arrays can reveal the neuronal network correlates of behavior with single-cell, single-spike, and sub-millisecond resolution. However, implantable electrodes are inherently invasive, and efforts to scale up the number and density of recording sites must compromise on device size in order to connect the electrodes. Here, we report on silicon-based neural probes employing nanofabricated, high-density electrical leads. Furthermore, we address the challenge of reading out multichannel data with an application-specific integrated circuit (ASIC) performing signal amplification, band-pass filtering, and multiplexing functions. We demonstrate high spatial resolution extracellular measurements with a fully integrated, low noise 64-channel system weighing just 330 mg. The on-chip multiplexers make possible recordings with substantially fewer external wires than the number of input channels. By combining nanofabricated probes with ASICs we have implemented a system for performing large-scale, high-density electrophysiology in small, freely behaving animals that is both minimally invasive and highly scalable

Dual-side and three-dimensional microelectrode arrays fabricated from ultra-thin silicon substrates

A method for fabricating planar implantable microelectrode arrays was demonstrated using a process that relied on ultra-thin silicon substrates, which ranged in thickness from 25 to 50 µm. The challenge of handling these fragile materials was met via a temporary substrate support mechanism. In order to compensate for putative electrical shielding of extracellular neuronal fields, separately addressable electrode arrays were defined on each side of the silicon device. Deep reactive ion etching was employed to create sharp implantable shafts with lengths of up to 5 mm. The devices were flip-chip bonded onto printed circuit boards (PCBs) by means of an anisotropic conductive adhesive film. This scalable assembly technique enabled three-dimensional (3D) integration through formation of stacks of multiple silicon and PCB layers. Simulations and measurements of microelectrode noise appear to suggest that low impedance surfaces, which could be formed by electrodeposition of gold or other materials, are required to ensure an optimal signal-to-noise ratio as well a low level of interchannel crosstalk

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

Active C4 electrodes for local field potential recording applications

Extracellular neural recording, with multi-electrode arrays (MEAs), is a powerful method used to study neural function at the network level. However, in a high density array, it can be costly and time consuming to integrate the active circuit with the expensive electrodes. In this paper, we present a 4 mm × 4 mm neural recording integrated circuit (IC) chip, utilizing IBM C4 bumps as recording electrodes, which enable a seamless active chip and electrode integration. The IC chip was designed and fabricated in a 0.13 μm BiCMOS process for both in vitro and in vivo applications. It has an input-referred noise of 4.6 μV rms for the bandwidth of 10 Hz to 10 kHz and a power dissipation of 11.25 mW at 2.5 V, or 43.9 μW per input channel. This prototype is scalable for implementing larger number and higher density electrode arrays. To validate the functionality of the chip, electrical testing results and acute in vivo recordings from a rat barrel cortex are presented.R01 NS072385 - NINDS NIH HHS; 1R01 NS072385 - NINDS NIH HH

Effect on signal-to-noise ratio of splitting the continuous contacts of cuff electrodes into smaller recording areas.

BackgroundCuff electrodes have been widely used chronically in different clinical applications. This neural interface has been dominantly used for nerve stimulation while interfering noise is the major issue when employed for recording purposes. Advancements have been made in rejecting extra-neural interference by using continuous ring contacts in tripolar topologies. Ring contacts provide an average of the neural activity, and thus reduce the information retrieved. Splitting these contacts into smaller recording areas could potentially increase the information content. In this study, we investigate the impact of such discretization on the Signal-to-Noise Ratio (SNR). The effect of contacts positioning and an additional short circuited pair of electrodes were also addressed.MethodsDifferent recording configurations using ring, dot, and a mixed of both contacts were studied in vitro in a frog model. An interfering signal was induced in the medium to simulate myoelectric noise. The experimental setup was design in such a way that the only difference between recordings was the configuration used. The inter-session experimental differences were taken care of by a common configuration that allowed normalization between electrode designs.ResultsIt was found that splitting all contacts into small recording areas had negative effects on noise rejection. However, if this is only applied to the central contact creating a mixed tripole configuration, a considerable and statistically significant improvement was observed. Moreover, the signal to noise ratio was equal or larger than what can be achieved with the best known configuration, namely the short circuited tripole. This suggests that for recording purposes, any tripole topology would benefit from splitting the central contact into one or more discrete contacts.ConclusionsOur results showed that a mixed tripole configuration performs better than the configuration including only ring contacts. Therefore, splitting the central ring contact of a cuff electrode into a number of dot contacts not only provides additional information but also an improved SNR. In addition, the effect of an additional pair of short circuited electrodes and the "end effect" observed with the presented method are in line with previous findings by other authors

Circuits And Methods For Artifact Elimination

Disclosed are apparatus and methods that provide the ability to electrical stimulate a physical system, and actively eliminate interference with signal acquisition (artifacts) that arises from the stimulation. The technique implemented in the circuits and methods for eliminating interference connects a discharge path to a physical interface to the system to remove charge that is built-up during stimulation. By placing the discharge path in a feedback loop that includes a recording preamplifier and AC-coupling circuitry, the physical interface is brought back to its pre-stimulation offset voltage. The disclosed apparatus and methods may be used with piezoelectric transducers, ultrasound devices, optical diodes, and polarizable and non-polarizable electrodes. The disclosed apparatus can be employed in implantable devices, in vitro or in vivo setups with vertebrate and invertebrate neural tissue, muscle fibers, pancreatic islet cells, osteoblasts, osteoclasts, bacteria, algae, fungi, protists, and plants.Georgia Tech Research Corporatio

Recent Advances in Neural Recording Microsystems

The accelerating pace of research in neuroscience has created a considerable demand for neural interfacing microsystems capable of monitoring the activity of large groups of neurons. These emerging tools have revealed a tremendous potential for the advancement of knowledge in brain research and for the development of useful clinical applications. They can extract the relevant control signals directly from the brain enabling individuals with severe disabilities to communicate their intentions to other devices, like computers or various prostheses. Such microsystems are self-contained devices composed of a neural probe attached with an integrated circuit for extracting neural signals from multiple channels, and transferring the data outside the body. The greatest challenge facing development of such emerging devices into viable clinical systems involves addressing their small form factor and low-power consumption constraints, while providing superior resolution. In this paper, we survey the recent progress in the design and the implementation of multi-channel neural recording Microsystems, with particular emphasis on the design of recording and telemetry electronics. An overview of the numerous neural signal modalities is given and the existing microsystem topologies are covered. We present energy-efficient sensory circuits to retrieve weak signals from neural probes and we compare them. We cover data management and smart power scheduling approaches, and we review advances in low-power telemetry. Finally, we conclude by summarizing the remaining challenges and by highlighting the emerging trends in the field

A power efficient neural spike recording channel with data bandwidth reduction

This paper presents a mixed-signal neural spike recording channel which features, as an added value, a simple and low-power data compression mechanism. The channel uses a band-limited differential low noise amplifier and a binary search data converter, together with other digital and analog blocks for control, programming and spike characterization. The channel offers a self-calibration operation mode and it can be configured both for signal tracking (to raw digitize the acquired neural waveform) and feature extraction (to build a first-order PWL approximation of the spikes). The prototype has been fabricated in a standard CMOS 0.13μm and occupies 400μm×400μm. The overall power consumption of the channel during signal tracking is 2.8μW and increases to 3.0μW average when the feature extraction operation mode is programmed.Ministerio de Ciencia e Innovación TEC2009-08447Junta de Andalucía TIC-0281

Wiring Nanoscale Biosensors with Piezoelectric Nanomechanical Resonators

Nanoscale integrated circuits and sensors will require methods for unobtrusive interconnection with the macroscopic world to fully realize their potential. We report on a nanoelectromechanical system that may present a solution to the wiring problem by enabling information from multisite sensors to be multiplexed onto a single output line. The basis for this method is a mechanical Fourier transform mediated by piezoelectrically coupled nanoscale resonators. Our technique allows sensitive, linear, and real-time measurement of electrical potentials from conceivably any voltage-sensitive device. With this method, we demonstrate the direct transduction of neuronal action potentials from an extracellular microelectrode. This approach to wiring nanoscale devices could lead to minimally invasive implantable sensors with thousands of channels for in vivo neuronal recording, medical diagnostics, and electrochemical sensing