Single-unit neural recording with active microelectrode arrays

This paper discusses the single-unit recording characteristics of microelectrode arrays containing on-chip signal processing circuitry. Probes buffered using on-chip unity-gain operational amplifiers provide an output resistance of 200 ohm with an input-referred noise of 11-muV root-mean-square (rms) (100 Hz-10 kHz). Simultaneous in vivo recordings from single neurons using buffered and unbuffered (passive) iridium recording sites separated by less than 20 microm have shown that the use of on-chip circuitry does not significantly degrade system noise. Single-unit neural activity has also been studied using probes containing closed-loop preamplifiers having a voltage gain of 40 dB and a bandwidth of 13 kHz, and several input dc-baseline stabilization techniques have been evaluated. Low-noise in vivo recordings with a multiplexed probe have been demonstrated for the first time using an external asymmetrical clock running at 200 kHz. The multiplexed system adds less than 8-muV rms of noise to the recorded signals, suppressing the 5-V clock transitions to less than 2 ppm.     

In vivo validation of custom-designed silicon-based microelectrode arrays for long-term neural recording and stimulation

We developed and validated silicon-based neural probes for neural stimulating and recording in long-term implantation in the brain. The probes combine the deep reactive ion etching process and mechanical shaping of their tip region, yielding a mechanically sturdy shank with a sharpened tip to reduce insertion force into the brain and spinal cord, particularly, with multiple shanks in the same array. The arrays' insertion forces have been quantified in vitro. Five consecutive chronically-implanted devices were fully functional from 3 to 18 months. The microelectrode sites were electroplated with iridium oxide, and the charge injection capacity measurements were performed both in vitro and after implantation in the adult feline brain. The functionality of the chronic array was validated by stimulating in the cochlear nucleus and recording the evoked neuronal activity in the central nucleus of the inferior colliculus. The arrays' recording quality has also been quantified in vivo with neuronal spike activity recorded up to 566 days after implantation. Histopathology evaluation of neurons and astrocytes using immunohistochemical stains indicated minimal alterations of tissue architecture after chronic implantation.     

Silicon-substrate microelectrode arrays for parallel recording ofneural activity in peripheral and cranial nerves

A new process for the fabrication of regeneration microelectrode arrays for peripheral and cranial nerve applications is presented. This type of array is implanted between the severed ends of nerves, the axons of which regenerate through via holes in the silicon and are thereafter held fixed with respect to the microelectrodes. The process described is designed for compatibility with industry-standard CMOS or BiCMOS processes (it does not involve high-temperature process steps nor heavily-doped etch-stop layers), and provides a thin membrane for the via holes, surrounded by a thick silicon supporting rim. Many basic questions remain regarding the optimum via hole and microelectrode geometries in terms of both biological and electrical performance of the implants, and therefore passive versions were fabricated as tools for addressing these issues in on-going work. Versions of the devices were implanted in the rat peroneal nerve and in the frog auditory nerve. In both cases, regeneration was verified histologically and it was observed that the regenerated nerves had reorganized into microfascicles containing both myelinated and unmyelinated axons and corresponding to the grid pattern of the via holes. These microelectrode arrays were shown to allow the recording of action potential signals in both the peripheral and cranial nerve settings, from several microelectrodes in parallel     

Two multichannel integrated circuits for neural recording and signal processing

We have developed, manufactured, and tested two analog CMOS integrated circuit "neurochips" for recording from arrays of densely packed neural electrodes. Device A is a 16-channel buffer consisting of parallel noninverting amplifiers with a gain of 2 V/V. Device B is a 16-channel two-stage analog signal processor with differential amplification and high-pass filtering. It features selectable gains of 250 and 500 V/V as well as reference channel selection. The resulting amplifiers on Device A had a mean gain of 1.99 V/V with an equivalent input noise of 10 microV(rms). Those on Device B had mean gains of 53.4 and 47.4 dB with a high-pass filter pole at 211 Hz and an equivalent input noise of 4.4 microV(rms). Both devices were tested in vivo with electrode arrays implanted in the somatosensory cortex.     

Chronic neural recording using silicon-substrate microelectrode arrays implanted in cerebral cortex

An important aspect of the development of cortical prostheses is the enhancement of suitable implantable microelectrode arrays for chronic neural recording. The objective of this study was to investigate the recording performance of silicon-substrate micromachined probes in terms of reliability and signal quality. These probes were found to consistently and reliably provide high-quality spike recordings over extended periods of time lasting up to 127 days. In a consecutive series of ten rodents involving 14 implanted probes, 13/14 (93%) of the devices remained functional throughout the assessment period. More than 90% of the probe sites consistently recorded spike activity with signal-to-noise ratios sufficient for amplitudes and waveform-based discrimination. Histological analysis of the tissue surrounding the probes generally indicated the development of a stable interface sufficient for sustained electrical contact. The results of this study demonstrate that these planar silicon probes are suitable for long-term recording in the cerebral cortex and provide an effective platform technology foundation for microscale intracortical neural interfaces for use in humans.     

Long-term stimulation and recording with a penetrating microelectrode array in cat sciatic nerve

We studied the consequences of long-term implantation of a penetrating microelectrode array in peripheral nerve over the time course of 4-6 mo. Electrode arrays without lead wires were implanted to test the ability of different containment systems to protect the array and nerve during contractions of surrounding muscles. Treadmill walking was monitored and the animals showed no functional deficits as a result of implantation. In a different set of experiments, electrodes with lead wires were implanted for up to 7 mo and the animals were tested at 2-4 week intervals at which time stimulation thresholds and recorded sensory activity were monitored for every electrode. It was shown that surgical technique highly affected the long-term stimulation results. Results between measurement sessions were compared, and in the best case, the stimulation properties stabilized in 80% of the electrodes over the course of the experiment (162 days). The recorded sensory signals, however, were not stable over time. A histological analysis performed on all implanted tissues indicated that the morphology and fiber density of the nerve around the electrodes were normal.     

Linear electrode arrays for stimulation and recording within cardiac tissue space constants

In this paper, we document a fabrication process that yields linear arrays of rectangular platinum black electrodes spaced 25 mum apart with edge-to-edge separation of 20 microm. The spatial arrangement is therefore sufficiently fine to insure stimulation and recording within cardiac tissue space constants, as six electrodes with dimensions of either 5 x 100 microm2, 5 x 250 microm2, or 5 x 500 microm2 were positioned in a 130-microm2 span in the arrays. Despite the small electrode sizes and available surface areas, favorable impedance characteristics were identifed. Averages ranged from 111 kOmega to 146 kOmega at 0.5 Hz and from 14 kOmega 39 kOmega at 500 Hz. Differences in impedances between the electrode sizes tested were small. Potential differences (deltaphis) recorded using the two central electrodes during stimulation with combinations at separations of only 75 microm, 100 microm, and 125 microm had low signal noise. As a preliminary test of the use of these arrays for possible application to impedance measurements in cardiac tissue, the deltaphis recorded during stimulation were compared to deltaphis obtained from finite-difference simulations using an isotropic volume conductor model. Anticipated decays in deltaphi with widening electrode separation identified in those simulations matched the decays in the recorded deltaphis closely. These findings are significant because they suggest intracellular and interstitial microimpedance mesurements in heart experiments will be straightforward.     

A high-yield microassembly structure for three-dimensional microelectrode arrays

This paper presents a practical microassembly process for three-dimensional (3-D) microelectrode arrays for recording and stimulation in the central nervous system (CNS). Orthogonal lead transfers between the micromachined two-dimensional probes and a cortical surface platform are formed by attaching gold beams on the probes to pads on the platform using wire-free ultrasonic bonding. The low-profile (150 microns) outrigger design of the probes allows the bonding of fully assembled high-density arrays. Micromachined assembly tools allow the formation of a full 3-D probe array within 30 min. Arrays having up to 8 x 16 shanks on 200-micron centers have been realized and used to record cortical single units successfully. Active 3-D probe arrays containing on-chip CMOS signal processing circuitry have also been created using the microassembly approach. In addition, a dynamic insertion technique has been explored to allow the implantation of high-density probe arrays into feline cortex at high-speed and with minimal traumatic injury.     

Thin-film circuits for scanning image-sensor arrays

Integrated circuits for scanning a photosensitive array at standard television scan rates have been fabricated by evaporated thin-film techniques. These include: 1) A 264-stage parallel-output complementary shift register with a driver stage at each output. 2) A 256-output transistor decoder with video coupling circuits for scanning an array with line storage. A single line of 256 photoconductordiode elements has been included on the same substrate with the decoder. The complementary shift register has been demonstrated to operate at clock frequencies up to 100 kHz. The integrated decoder and line sensor, when driven by two external 16-stage shift registers, has been operated successfully with line storage at frequencies up to 4.8 MHz.     

Silicide resistors for integrated circuits

Thin-film resistors are useful in monolithic integrated circuits whenever high sheet resistance (ρs> 1 kΩ/sq) or radiation hardness are required. Silicide resistive films (MoSi2, CrSi2, and Si-Cr) deposited by dc sputtering have been shown to be compatible with monolithic circuit production end require no protective overlayer. Si-Cr films 200-300 Å thick have ρs, and temperature coefficients of resistance (TCR) ranging from about 1 kΩ/sq and +150 ppm/°C (CrSi2) to 20 kΩ/sq and -1400 ppm/°C (17 at % Cr). MoSi2is best suited for resistor applications requiring 100-200Ω/sq. MoSi2films are about 700 Å thick at 200 Ω/sq, compared to < 100 Å for 200-Ω/sq Ni-Cr, and their TCR is -125 ppm/°C. Typical stability for unprotected silicide resistors in TO-5 packages at 200°C, no load, is < ±3 percent during the first 200 h and < ± 0.5 percent during the next 2000 h. The films are stable during short term exposure to high temperatures as encountered during monolithic or hybrid circuit ceramic package sealing.     

A novel simultaneous unipolar multispectral integrated technology approach for HgCdTe IR detectors and focal plane arrays

In the last few years Rockwell has developed a novel simultaneous unipolar multispectral integrated HgCdTe detector and focal plane array technology that is a natural and relatively straightforward derivative of our baseline double layer planar heterostructure (DLPH) molecular beam epitaxial (MBE) technology. Recently this technology was awarded a U.S. patent. This simultaneous unipolar multispectral integrated technology (SUMIT) shares the high performance characteristics of its DLPH antecedent. Two color focal plane arrays with low-10¹³ cm⁻²s⁻¹ background limited detectivity performance (BLIP D^*) have been obtained for mid-wave infrared (MWIR, 3–5 m) devices at T>130 K and for long-wave infrared (LWIR, 8–10 m) devices at T∼80 K.     

A low-noise front-end for multiplexed ENG recording using CMOS technology

Multi-electrode cuffs have been proposed as a means for the parallel recording of naturally-occurring neural signals. Compared to a conventional tripole cuff providing a single channel signal, additional information about the velocity and direction of nerve signals can be extracted from the multi-electrode recordings. Moreover, interference suppression is improved and overall power consumption reduced, as the analysis shows. In this paper a new recording system is proposed, each channel of which consists of a low-noise preamplifier employing lateral bipolar transistors to provide an impedance match to the tissue and a path to ground for the switching currents of a single high-gain amplifier, which is multiplexed between the channels. The proposed system provides low-noise, low-power operation and practically identical channel gains and is suitable for integration in a larger CMOS-based system.     

Logical circuits for use in iterative arrays

Two logical circuits are proposed, and some examples of iterative arrays formed using them are discussed.     

Magnetic resonance compatibility of multichannel silicon microelectrode systems for neural recording and stimulation: design criteria, tests, and recommendations

Magnetic resonance (MR) compatibility of biomedical implants and devices represents a challenge for designers and potential risks for users. This paper addresses these problems and presents the first MR-compatible multichannel silicon chronic microelectrode system, used for recording and electrical stimulation of the central nervous system for animal models. A standard chronic assembly, from the Center for Neural Communication Technology at the University of Michigan, was tested on a 2 Tesla magnet to detect forces, heating, and image distortions, and modified to minimize or eliminate susceptibility artifacts, tissue damage, and electrode displacement, maintaining good image quality and safety to the animals. Multiple commercial connectors were tested for MR compatibility and several options for the reference electrode were also tested to minimize image artifacts and provide a stable biocompatible reference for shortand long-term neural recordings. Different holding screws were tested to anchor the microelectrode assembly on the top of the skull. The final selection of this part was based on MR-compatibility, biocompatibility, durability, and mechanical and chemical stability. The required adaptor to interconnect the MR-compatible microelectrode with standard data acquisition systems was also designed and fabricated. The final design is fully MR-compatible and has been successfully tested on guinea pigs.     

Regeneration microelectrode array for peripheral nerve recordingand stimulation

A microelectrode array capable of recording from and stimulating peripheral nerves at prolonged intervals after surgical implantation has been demonstrated. The microelectrode array, fabricated on a silicon substrate perforated by multiple holes (referred to as via holes), is implanted between the ends of a surgically severed nerve. Regenerating tissue fixes the device in place to provide a stable mapping between the microelectrodes and the axons in the nerve. Processes were developed for the fabrication of thin-film iridium microelectrodes, micromachined via holes, and silicon nitride passivation layers. All fabrication methods were designed to be compatible with standard CMOS/BiCMOS processes to allow for on-chip signal processing circuits in future designs. Such arrays, implanted in the peroneal nerves of rats, were used to record from and stimulate the nerves at up to 13 months postoperatively.     

Integrating microelectromechanical systems with integrated circuits

From the very beginning, integration of microelectromechanical systems (MEMS) with integrated circuits (ICs) was a major attraction of silicon micromachining technology. Significant progress toward integrating MEMS with ICs technologies has been made over the last four decades. Many products have been introduced and the benefits of such integration have been demonstrated. One of the most attractive developments, during the period of time called the Optical Bubble, was the vertical MEMS-IC integration, pioneered by Transparent Networks. It enabled a short path to merging VLSI electronics with MEMS. This approach can be easily applied to capacitive sensors, such as pressure, acceleration, gyro, and vacuum sensors, as well as to a broad range of other products.     

Antennas and waveguides for far-infrared integrated circuits

Antennas and waveguides for the wavelength range 0.1-3 mm are considered. Emphasis is placed on those designs which lend themselves to integration with each other and with other components such as diodes. The general properties of FIR antennas are reviewed. A novel silicon waveguide antenna is discussed, and its design, simulation, fabrication, and performance at 119 μm are described. This antenna has a highly symmetrical, single-lobed beam with 3 dB beamwidths of 35 and 38° in theE- andH-planes, respectively. The gain (measured in microwave simulation) is 12.8 dB. This antenna is well suited for integration with Schottky diodes. The related subject of FIR waveguides is discussed. Experiments with metal transmission lines at 119 μm are described and dielectric guides related to the waveguide antenna are also considered. Using components such as these it may soon be possible to construct receiver front ends for this wavelength range in integrated-circuit form.     

Circulators for microwave and millimeter-wave integrated circuits

The requirements for circulators for use in combination with microwave and millimeter-wave integrated circuits are reviewed, with special emphasis on modules for phased-array antennas. Recent advances in broadbanding and in miniaturization are summarized. Novel types of circulators that are fabricated by attaching a ferrite disc and a suitable coupling structure to the surface of a dielectric of semiconductor substrate (quasimonolithic integration) are described. Methods for achieving complete monolithic integration are also discussed     

Frequency mixer with a frequency doubler for integrated circuits

We have developed a bipolar LSI, including a frequency mixer and a local oscillator frequency doubler. The local oscillator frequency doubler consists of two identical unbalanced emitter-coupled pairs with a different emitter area ratio, whose input terminals are connected cross-coupled and whose output terminals are connected in parallel, and is coupled with the frequency mixer directly in the LSI. The fabricated LSI operates on supply voltage as low as 2.7, and has been put into practical use for a cordless telephone system