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

Doctor of Philosophy

dissertationSince the late 1950s, scientists have been working toward realizing implantable devices that would directly monitor or even control the human body's internal activities. Sophisticated microsystems are used to improve our understanding of internal biological processes in animals and humans. The diversity of biomedical research dictates that microsystems must be developed and customized specifically for each new application. For advanced long-term experiments, a custom designed system-on-chip (SoC) is usually necessary to meet desired specifications. Custom SoCs, however, are often prohibitively expensive, preventing many new ideas from being explored. In this work, we have identified a set of sensors that are frequently used in biomedical research and developed a single-chip integrated microsystem that offers the most commonly used sensor interfaces, high computational power, and which requires minimum external components to operate. Included peripherals can also drive chemical reactions by setting the appropriate voltages or currents across electrodes. The SoC is highly modular and well suited for prototyping in and ex vivo experimental devices. The system runs from a primary or secondary battery that can be recharged via two inductively coupled coils. The SoC includes a 16-bit microprocessor with 32 kB of on chip SRAM. The digital core consumes 350 μW at 10 MHz and is capable of running at frequencies up to 200 MHz. The integrated microsystem has been fabricated in a 65 nm CMOS technology and the silicon has been fully tested. Integrated peripherals include two sigma-delta analog-to-digital converters, two 10-bit digital-to-analog converters, and a sleep mode timer. The system also includes a wireless ultra-wideband (UWB) transmitter. The fullydigital transmitter implementation occupies 68 x 68 μm2 of silicon area, consumes 0.72 μW static power, and achieves an energy efficiency of 19 pJ/pulse at 200 MHz pulse repetition frequency. An investigation of the suitability of the UWB technology for neural recording systems is also presented. Experimental data capturing the UWB signal transmission through an animal head are presented and a statistical model for large-scale signal fading is developed

700mV low power low noise implantable neural recording system design

This dissertation presents the work for design and implementation of a low power, low noise neural recording system consisting of Bandpass Amplifier and Pipelined Analog to Digital Converter (ADC) for recording neural signal activities. A low power, low noise two stage neural amplifier for use in an intelligent Radio-Frequency Identification (RFID) based on folded cascode Operational Transconductance Amplifier (OTA) is utilized to amplify the neural signals. The optimization of the number of amplifier stages is discussed to achieve the minimum power and area consumption. The amplifier power supply is 0.7V. The midband gain of amplifier is 58.4dB with a 3dB bandwidth from 0.71 to 8.26 kHz. Measured input-referred noise and total power consumption are 20.7 μVrms and 1.90 μW respectively. The measured result shows that the optimizing the number of stages can achieve lower power consumption and demonstrates the neural amplifier's suitability for instu neutral activity recording. The advantage of power consumption of Pipelined ADC over Successive Approximation Register (SAR) ADC and Delta-Sigma ADC is discussed. An 8 bit fully differential (FD) Pipeline ADC for use in a smart RFID is presented in this dissertation. The Multiplying Digital to Analog Converter (MDAC) utilizes a novel offset cancellation technique robust to device leakage to reduce the input drift voltage. Simulation results of static and dynamic performance show this low power Pipeline ADC is suitable for multi-channel neural recording applications. The performance of all proposed building blocks is verified through test chips fabricated in IBM 180nm CMOS process. Both bench-top and real animal test results demonstrate the system's capability of recording neural signals for neural spike detection

Improving the mechanistic study of neuromuscular diseases through the development of a fully wireless and implantable recording device

Neuromuscular diseases manifest by a handful of known phenotypes affecting the peripheral nerves, skeletal muscle fibers, and neuromuscular junction. Common signs of these diseases include demyelination, myasthenia, atrophy, and aberrant muscle activity—all of which may be tracked over time using one or more electrophysiological markers. Mice, which are the predominant mammalian model for most human diseases, have been used to study congenital neuromuscular diseases for decades. However, our understanding of the mechanisms underlying these pathologies is still incomplete. This is in part due to the lack of instrumentation available to easily collect longitudinal, in vivo electrophysiological activity from mice. There remains a need for a fully wireless, batteryless, and implantable recording system that can be adapted for a variety of electrophysiological measurements and also enable long-term, continuous data collection in very small animals. To meet this need a miniature, chronically implantable device has been developed that is capable of wirelessly coupling energy from electromagnetic fields while implanted within a body. This device can both record and trigger bioelectric events and may be chronically implanted in rodents as small as mice. This grants investigators the ability to continuously observe electrophysiological changes corresponding to disease progression in a single, freely behaving, untethered animal. The fully wireless closed-loop system is an adaptable solution for a range of long-term mechanistic and diagnostic studies in rodent disease models. Its high level of functionality, adjustable parameters, accessible building blocks, reprogrammable firmware, and modular electrode interface offer flexibility that is distinctive among fully implantable recording or stimulating devices. The key significance of this work is that it has generated novel instrumentation in the form of a fully implantable bioelectric recording device having a much higher level of functionality than any other fully wireless system available for mouse work. This has incidentally led to contributions in the areas of wireless power transfer and neural interfaces for upper-limb prosthesis control. Herein the solution space for wireless power transfer is examined including a close inspection of far-field power transfer to implanted bioelectric sensors. Methods of design and characterization for the iterative development of the device are detailed. Furthermore, its performance and utility in remote bioelectric sensing applications is demonstrated with humans, rats, healthy mice, and mouse models for degenerative neuromuscular and motoneuron diseases

Wireless Implantable ICs for Energy-Efficient Long-Term Ambulatory EEG Monitoring

This thesis presents the design, development, and experimental characterization of wireless subcutaneous implantable integrated circuits and systems for long-term ambulatory EEG monitoring. Application-, system- and circuit-level requirements for such a device are discussed and a critical review of the state-of-the-art academic and currently available commercial solutions are provided. Two prototypes are presented: The first prototype presented in Chapter 2 is an 8-channel wireless implantable device with a 2.5×1.5 mm2 custom-designed integrated circuit implemented using CMOS 180nm technology at its core. The microchip is fabricated and the measurement results showing its efficacy in EEG signal recording in terms of input-referred noise, voltage gain, signal-to-noise ratio, and power consumption are presented. The chip is implemented together with a BLE 5.0 module on the same platform. Our vision and discussions on biocompatible encapsulation of this system, as well as its integration with a microelectrode array as also provided. The second prototype, also implemented in CMOS 180nm technology and presented in Chapter 3, employs a novel EEG recording channel architecture that enables long-term implantation of EEG monitoring devices through significant improvement of their energy efficiency. The channel leverages the inherent sparsity of the EEG signals and conducts recording in an activity-dependent adaptive manner. Thanks to the proposed fully dynamic spectral-compressing architecture, the recording channels power consumption is drastically reduced. More importantly, the proposed architecture reduces the required wireless transmission throughput by more than an order of magnitude. Our test results on 10 different patients’ pre-recorded human EEG data shows an average of 12.6× improvement in the device’s energy efficiency

Bidirectional Neural Interface Circuits with On-Chip Stimulation Artifact Reduction Schemes

Bidirectional neural interfaces are tools designed to “communicate” with the brain via recording and modulation of neuronal activity. The bidirectional interface systems have been adopted for many applications. Neuroscientists employ them to map neuronal circuits through precise stimulation and recording. Medical doctors deploy them as adaptable medical devices which control therapeutic stimulation parameters based on monitoring real-time neural activity. Brain-machine-interface (BMI) researchers use neural interfaces to bypass the nervous system and directly control neuroprosthetics or brain-computer-interface (BCI) spellers. In bidirectional interfaces, the implantable transducers as well as the corresponding electronic circuits and systems face several challenges. A high channel count, low power consumption, and reduced system size are desirable for potential chronic deployment and wider applicability. Moreover, a neural interface designed for robust closed-loop operation requires the mitigation of stimulation artifacts which corrupt the recorded signals. This dissertation introduces several techniques targeting low power consumption, small size, and reduction of stimulation artifacts. These techniques are implemented for extracellular electrophysiological recording and two stimulation modalities: direct current stimulation for closed-loop control of seizure detection/quench and optical stimulation for optogenetic studies. While the two modalities differ in their mechanisms, hardware implementation, and applications, they share many crucial system-level challenges. The first method aims at solving the critical issue of stimulation artifacts saturating the preamplifier in the recording front-end. To prevent saturation, a novel mixed-signal stimulation artifact cancellation circuit is devised to subtract the artifact before amplification and maintain the standard input range of a power-hungry preamplifier. Additional novel techniques have been also implemented to lower the noise and power consumption. A common average referencing (CAR) front-end circuit eliminates the cross-channel common mode noise by averaging and subtracting it in analog domain. A range-adapting SAR ADC saves additional power by eliminating unnecessary conversion cycles when the input signal is small. Measurements of an integrated circuit (IC) prototype demonstrate the attenuation of stimulation artifacts by up to 42 dB and cross-channel noise suppression by up to 39.8 dB. The power consumption per channel is maintained at 330 nW, while the area per channel is only 0.17 mm2. The second system implements a compact headstage for closed-loop optogenetic stimulation and electrophysiological recording. This design targets a miniaturized form factor, high channel count, and high-precision stimulation control suitable for rodent in-vivo optogenetic studies. Monolithically integrated optoelectrodes (which include 12 µLEDs for optical stimulation and 12 electrical recording sites) are combined with an off-the-shelf recording IC and a custom-designed high-precision LED driver. 32 recording and 12 stimulation channels can be individually accessed and controlled on a small headstage with dimensions of 2.16 x 2.38 x 0.35 cm and mass of 1.9 g. A third system prototype improves the optogenetic headstage prototype by furthering system integration and improving power efficiency facilitating wireless operation. The custom application-specific integrated circuit (ASIC) combines recording and stimulation channels with a power management unit, allowing the system to be powered by an ultra-light Li-ion battery. Additionally, the µLED drivers include a high-resolution arbitrary waveform generation mode for shaping of µLED current pulses to preemptively reduce artifacts. A prototype IC occupies 7.66 mm2, consumes 3.04 mW under typical operating conditions, and the optical pulse shaping scheme can attenuate stimulation artifacts by up to 3x with a Gaussian-rise pulse rise time under 1 ms.PHDElectrical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/147674/1/mendrela_1.pd

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

Integrated Circuits and Systems for Smart Sensory Applications

Connected intelligent sensing reshapes our society by empowering people with increasing new ways of mutual interactions. As integration technologies keep their scaling roadmap, the horizon of sensory applications is rapidly widening, thanks to myriad light-weight low-power or, in same cases even self-powered, smart devices with high-connectivity capabilities. CMOS integrated circuits technology is the best candidate to supply the required smartness and to pioneer these emerging sensory systems. As a result, new challenges are arising around the design of these integrated circuits and systems for sensory applications in terms of low-power edge computing, power management strategies, low-range wireless communications, integration with sensing devices. In this Special Issue recent advances in application-specific integrated circuits (ASIC) and systems for smart sensory applications in the following five emerging topics: (I) dedicated short-range communications transceivers; (II) digital smart sensors, (III) implantable neural interfaces, (IV) Power Management Strategies in wireless sensor nodes and (V) neuromorphic hardware

Analog Signal Buffering and Reconstruction

Wireless sensor networks (WSNs) are capable of a myriad of tasks, from monitoring critical infrastructure such as bridges to monitoring a person\u27s vital signs in biomedical applications. However, their deployment is impractical for many applications due to their limited power budget. Sleep states are one method used to conserve power in resource-constrained systems, but they necessitate a wake-up circuit for detecting unpredictable events. In conventional wake-up-based systems, all information preceding a wake-up event will be forfeited. To avoid this data loss, it is necessary to include a buffer that can record prelude information without sacrificing the power savings garnered by the active use of sleep states.;Unfortunately, traditional memory buffer systems utilize digital electronics which are costly in terms of power. Instead of operating in the target signal\u27s native analog environment, a digital buffer must first expend a great deal of energy to convert the signal into a digital signal. This issue is further compounded by the use of traditional Nyquist sampling which does not adapt to the characteristics of a dynamically changing signal. These characteristics reveal why a digital buffer is not an appropriate choice for a WSN or other resource-constrained system.;This thesis documents the development of an analog pre-processing block that buffers an incoming signal using a new method of sampling. This method requires sampling only local maxima and minima (both amplitude and time), effectively approximating the instantaneous Nyquist rate throughout a time-varying signal. The use of this sampling method along with ultra-low-power analog electronics enables the entire system to operate in the muW power levels. In addition to these power saving techniques, a reconfigurable architecture will be explored as infrastructure for this system. This reconfigurable architecture will also be leveraged to explore wake-up circuits that can be used in parallel with the buffer system

Nano-Watt Modular Integrated Circuits for Wireless Neural Interface.

In this work, a nano-watt modular neural interface circuit is proposed for ECoG neuroprosthetics. The main purposes of this work are threefold: (1) optimizing the power-performance of the neural interface circuits based on ECoG signal characteristics, (2) equipping a stimulation capability, and (3) providing a modular system solution to expand functionality. To achieve these aims, the proposed system introduces the following contributions/innovations: (1) power-noise optimization based on the ECoG signal driven analysis, (2) extreme low-power analog front-ends, (3) Manchester clock-edge modulation clock data recovery, (4) power-efficient data compression, (5) integrated stimulator with fully programmable waveform, (6) wireless signal transmission through skin, and (7) modular expandable design. Towards these challenges and contributions, three different ECoG neural interface systems, ENI-1, ENI-16, and ENI-32, have been designed, fabricated, and tested. The first ENI system(ENI-1) is a one-channel analog front-end and fabricated in a 0.25µm CMOS process with chopper stabilized pseudo open-loop preamplifier and area-efficient SAR ADC. The measured channel power, noise and area are 1.68µW at 2.5V power-supply, 1.69µVrms (NEF=2.43), and 0.0694mm^2, respectively. The fabricated IC is packaged with customized miniaturized package. In-vivo human EEG is successfully measured with the fabricated ENI-1-IC. To demonstrate a system expandability and wireless link, ENI-16 IC is fabricated in 0.25µm CMOS process and has sixteen channels with a push-pull preamplifier, asynchronous SAR ADC, and intra-skin communication(ISCOM) which is a new way of transmitting the signal through skin. The measured channel power, noise and area are 780nW, 4.26µVrms (NEF=5.2), and 2.88mm^2, respectively. With the fabricated ENI-16-IC, in-vivo epidural ECoG from monkey is successfully measured. As a closed-loop system, ENI-32 focuses on optimizing the power performance based on a bio-signal property and integrating stimulator. ENI-32 is fabricated in 0.18µm CMOS process and has thirty-two recording channels and four stimulation channels with a cyclic preamplifier, data compression, asymmetric wireless transceiver (Tx/Rx). The measured channel power, noise and area are 140nW (680nW including ISCOM), 3.26µVrms (NEF=1.6), and 5.76mm^2, respectively. The ENI-32 achieves an order of magnitude power reduction while maintaining the system performance. The proposed nano-watt ENI-32 can be the first practical wireless closed-loop solution with a practically miniaturized implantable device.PhDElectrical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/98064/1/schang_1.pd