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

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

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

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

High-resolution three-dimensional extracellular recording of neuronal activity with microfabricated electrode arrays

Microelectrode array recordings of neuronal activity present significant opportunities for studying the brain with single-cell and spike-time precision. However, challenges in device manufacturing constrain dense multisite recordings to two spatial dimensions, whereas access to the three-dimensional (3D) structure of many brain regions appears to remain a challenge. To overcome this limitation, we present two novel recording modalities of silicon-based devices aimed at establishing 3D functionality. First, we fabricated a dual-side electrode array by patterning recording sites on both the front and back of an implantable microstructure. We found that the majority of single-unit spikes could not be simultaneously detected from both sides, suggesting that in addition to providing higher spatial resolution measurements than that of single-side devices, dual-side arrays also lead to increased recording yield. Second, we obtained recordings along three principal directions with a multilayer array and demonstrated 3D spike source localization within the enclosed measurement space. The large-scale integration of such dual-side and multilayer arrays is expected to provide massively parallel recording capabilities in the brain

Recruitment characteristics of nerve fascicles stimulated by a multi-groove electrode

The recruitment characteristics of fascicle-selective nerve stimulation by a multigroove electrode have been investigated both theoretically and in acute experiments. A three-dimensional (3-D) volume conductor model of fascicles in a multigroove device and a model of myelinated nerve fiber stimulation were used to calculate threshold stimuli of nerve fibers in these fascicles. After their exposition, fascicles from rat sciatic nerve were positioned in different grooves of appropriate sizes and stimulated separately. The device appeared to be suitable for fascicle-selective stimulation, because both computer simulations and acute animal experiments showed that crosstalk between neighboring fascicles is not a problem, even when monopolar stimulation was used. The threshold stimulus was lower for a small fascicle than for a large one. When the amount of (conducting) medium between contact and perineurium or its conductivity was reduced, threshold stimuli were lower. Moreover, simulations predict that the slopes of recruitment curves are smaller and inverse recruitment order is less pronounced. Simulations also showed that a small contact is preferable to a large one, because a small contact gives a slightly smaller slope of the recruitment curve. Both experimentally and theoretically a significantly smaller slope of recruitment curves was obtained by stimulation with a cathode and an anode at opposite sides of the fascicle, driven by two current sources giving simultaneous pulses with different, but linearly dependent amplitude

Characterization of concurrent stimulation in multi-electrode array for use in a vision prosthesis

Concurrent stimulation in a visual prosthesis is necessary in order to deliver sufficient phospenes (perceived spots of light) for effective vision. Major issues with concurrent stimulation are the effects of inter-electrode current distribution which lead to current leakage and issues with charge recovery which determines whether balanced charges being delivered are recovered at each electrode. This thesis investigates concurrent stimulation in multi-electrode arrays of different electrode configurations and orientations using platinum electrodes immersed in physiological saline bath along with results from computational modelling. Current waveforms were recorded to determine current interactions and charge recovery in each electrode. Current interaction was found to be highest when imbalanced stimuli were delivered. Current interaction and charge recovery were found to be minimal for combined current source and sink stimulation mode, especially in the tripolar configuration of the hexagonal orientation, indicating that the combination of appropriate electrode configuration, orientation and stimulus mode will aid in current focusing and avoiding current interaction. Simplified models were developed to mimic the experimental setup and used to fit multiple experimental current waveforms, based on the stimulus currents and electrode-electrolyte properties. The models were optimized to predict the electrode-electrolyte properties of electrode arrays as well as the current interactions and voltage distributions in different electrode configurations and orientations. The resistance and capacitance of the electrode-electrolyte interface were found to decrease and increase with stimulus current, respectively. The optimized models were able to reproduce current results from the experimental recordings in terms of the dynamic waveforms , with a goodness of fit between 53 % - 90 %, where the percentage reduces in more complex model with multi-electrode. To validate that the optimized model is appropriate to present concurrent stimulation of multi-electrode array, 3D models of the multi-electrode array were constructed to mimic and reproduce the experimental results and to validate the optimized model. The model was able to predict current and voltage distribution as well as the electrode-electrolyte interface voltages and voltages at each individual electrodes which is not possible to measure experimentally. Improved version of the model with additional parameters will be useful to predict the performance of the implant in various numerical settings which may not be possible to be conducted experimentally. The new methodology developed in this thesis shows a strong link between experimental and computational modeling of concurrent stimulation in multi-electrode arrays, allowing for prediction for specific electrode design simulations and also as a platform for neural prosthesis evaluation using multi-electrode arrays

Hard-wired epimysial recordings from normal and reinnervated muscle using a bone-anchored device

Background: A combined approach for prosthetic attachment and control using a transcutaneous bone-anchored device and implanted muscle electrodes can improve function for upper-limb amputees. The bone-anchor provides a transcutaneous feed-through for muscle signal recording. This approach can be combined with targeted muscle reinnervation (TMR) to further improve myoelectric control. Methods: A bone-anchored device was implanted trans-tibially in n = 8 sheep with a bipolar recording electrode secured epimysially to the peroneus tertius muscle. TMR was carried out in a single animal: the peroneus tertius was deinnervated and the distal portion of the transected nerve to the peroneus muscle was coapted to a transected nerve branch previously supplying the tibialis anterior muscle. For 12 weeks (TMR) or 19 weeks (standard procedure), epimysial muscle signals were recorded while animals walked at 2 km·h−1. Results: After 19 weeks implantation following standard procedure, epimysial recording signal-to-noise ratio (SNR) was 18.7 dB (± 6.4 dB, 95% CI) with typical recordings falling in the range 10–25 dB. Recoveries in gait and muscle signals were coincident 6 weeks post-TMR; initial muscle activity was identifiable 3 weeks post-TMR though with low signal amplitude and signal-to-noise ratio compared with normal muscle recordings. Conclusions: Following recovery, muscle signals were recorded reliably over 19 weeks following implantation. In this study, targeted reinnervation was successful in parallel with bone-anchor implantation, with recovery identified 6 weeks after surger

A 32-Channel Time-Multiplexed Artifact-Aware Neural Recording System

This paper presents a low-power, low-noise microsystem for the recording of neural local field potentials or intracranial electroencephalographic signals. It features 32 time-multiplexed channels at the electrode interface and offers the possibility to spatially delta encode data to take advantage of the large correlation of signals captured from nearby channels. The circuit also implements a mixed-signal voltage-triggered auto-ranging algorithm which allows to attenuate large interferers in digital domain while preserving neural information. This effectively increases the system dynamic range and avoids the onset of saturation. A prototype, fabricated in a standard 180 nm CMOS process, has been experimentally verified in-vitro with cellular cultures of primary cortical neurons from mice. The system shows an integrated input-referred noise in the 0.5–200 Hz band of 1.4 µVrms for a spot noise of about 85 nV / √Hz. The system draws 1.5 µW per channel from 1.2 V supply and obtains 71 dB + 26 dB dynamic range when the artifact-aware auto-ranging mechanism is enabled, without penalising other critical specifications such as crosstalk between channels or common-mode and power supply rejection ratios