Noise Efficient Integrated Amplifier Designs for Biomedical Applications

The recording of neural signals with small monolithically integrated amplifiers is of high interest in research as well as in commercial applications, where it is common to acquire 100 or more channels in parallel. This paper reviews the recent developments in low-noise biomedical amplifier design based on CMOS technology, including lateral bipolar devices. Seven major circuit topology categories are identified and analyzed on a per-channel basis in terms of their noise-efficiency factor (NEF), input-referred absolute noise, current consumption, and area. A historical trend towards lower NEF is observed whilst absolute noise power and current consumption exhibit a widespread over more than five orders of magnitude. The performance of lateral bipolar transistors as amplifier input devices is examined by transistor-level simulations and measurements from five different prototype designs fabricated in 180 nm and 350 nm CMOS technology. The lowest measured noise floor is 9.9 nV/√Hz with a 10 µA bias current, which results in a NEF of 1.2

VLSI Circuits for Bidirectional Neural Interfaces

Medical devices that deliver electrical stimulation to neural tissue are important clinical tools that can augment or replace pharmacological therapies. The success of such devices has led to an explosion of interest in the field, termed neuromodulation, with a diverse set of disorders being targeted for device-based treatment. Nevertheless, a large degree of uncertainty surrounds how and why these devices are effective. This uncertainty limits the ability to optimize therapy and gives rise to deleterious side effects. An emerging approach to improve neuromodulation efficacy and to better understand its mechanisms is to record bioelectric activity during stimulation. Understanding how stimulation affects electrophysiology can provide insights into disease, and also provides a feedback signal to autonomously tune stimulation parameters to improve efficacy or decrease side-effects. The aims of this work were taken up to advance the state-of-the-art in neuro-interface technology to enable closed-loop neuromodulation therapies. Long term monitoring of neuronal activity in awake and behaving subjects can provide critical insights into brain dynamics that can inform system-level design of closed-loop neuromodulation systems. Thus, first we designed a system that wirelessly telemetered electrocorticography signals from awake-behaving rats. We hypothesized that such a system could be useful for detecting sporadic but clinically relevant electrophysiological events. In an 18-hour, overnight recording, seizure activity was detected in a pre-clinical rodent model of global ischemic brain injury. We subsequently turned to the design of neurostimulation circuits. Three critical features of neurostimulation devices are safety, programmability, and specificity. We conceived and implemented a neurostimulator architecture that utilizes a compact on-chip circuit for charge balancing (safety), digital-to-analog converter calibration (programmability) and current steering (specificity). Charge balancing accuracy was measured at better than 0.3%, the digital-to-analog converters achieved 8-bit resolution, and physiological effects of current steering stimulation were demonstrated in an anesthetized rat. Lastly, to implement a bidirectional neural interface, both the recording and stimulation circuits were fabricated on a single chip. In doing so, we implemented a low noise, ultra-low power recording front end with a high dynamic range. The recording circuits achieved a signal-to-noise ratio of 58 dB and a spurious-free dynamic range of better than 70 dB, while consuming 5.5 μW per channel. We demonstrated bidirectional operation of the chip by recording cardiac modulation induced through vagus nerve stimulation, and demonstrated closed-loop control of cardiac rhythm

Integrated circuit design for implantable neural interfaces

Progress in microfabrication technology has opened the way for new possibilities in neuroscience and medicine. Chronic, biocompatible brain implants with recording and stimulation capabilities provided by embedded electronics have been successfully demonstrated. However, more ambitious applications call for improvements in every aspect of existing implementations. This thesis proposes two prototypes that advance the field in significant ways. The first prototype is a neural recording front-end with spectral selectivity capabilities that implements a design strategy that leads to the lowest reported power consumption as compared to the state of the art. The second one is a bidirectional front-end for closed-loop neuromodulation that accounts for self-interference and impedance mismatch thus enabling simultaneous recording and stimulation. The design process and experimental verification of both prototypes is presented herein

Doctor of Philosophy

dissertationThis dissertation describes the use of cortical surface potentials, recorded with dense grids of microelectrodes, for brain-computer interfaces (BCIs). The work presented herein is an in-depth treatment of a broad and interdisciplinary topic, covering issues from electronics to electrodes, signals, and applications. Within the scope of this dissertation are several significant contributions. First, this work was the first to demonstrate that speech and arm movements could be decoded from surface local field potentials (LFPs) recorded in human subjects. Using surface LFPs recorded over face-motor cortex and Wernickes area, 150 trials comprising vocalized articulations of ten different words were classified on a trial-by-trial basis with 86% accuracy. Surface LFPs recorded over the hand and arm area of motor cortex were used to decode continuous hand movements, with correlation of 0.54 between the actual and predicted position over 70 seconds of movement. Second, this work is the first to make a detailed comparison of cortical field potentials recorded intracortically with microelectrodes and at the cortical surface with both micro- and macroelectrodes. Whereas coherence in macroelectrocorticography (ECoG) decayed to half its maximum at 5.1 mm separation in high frequencies, spatial constants of micro-ECoG signals were 530-700 ?m-much closer to the 110-160 ?m calculated for intracortical field potentials than to the macro-ECoG. These findings confirm that cortical surface potentials contain millimeter-scale dynamics. Moreover, these fine spatiotemporal features were important for the performance of speech and arm movement decoding. In addition to contributions in the areas of signals and applications, this dissertation includes a full characterization of the microelectrodes as well as collaborative work in which a custom, low-power microcontroller, with features optimized for biomedical implants, was taped out, fabricated in 65 nm CMOS technology, and tested. A new instruction was implemented in this microcontroller which reduced energy consumption when moving large amounts of data into memory by as much as 44%. This dissertation represents a comprehensive investigation of surface LFPs as an interfacing medium between man and machine. The nature of this work, in both the breadth of topics and depth of interdisciplinary effort, demonstrates an important and developing branch of engineering

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

Analog Compressive Sensing for Multi-Channel Neural Recording: Modeling and Circuit Level Implementation

RÉSUMÉ Dans cette thèse, nous présentons la conception d’un implant d’enregistrement neuronal multicanaux avec un échantillonnage compressé mis en oeuvre avec un procédé de fabrication CMOS à 65 nm. La réduction de la technologie a˙ecte à la baisse les paramètres des amplificateurs neuronaux couplés en AC, comme la fréquence de coupure basse, en raison de l’e˙et de canal court des transistors MOS. Nous analysons la fréquence de coupure basse et nous constatons que l’origine de ce problème, dans les technologies avancées, est la diminution de l’impédance d’entrée de l’amplificateur opérationnel de transconductance (OTA) en raison de la fuite d’oxyde de grille à l’entrée des OTA. Nous proposons deux solutions pour réduire la fréquence de coupure basse sans augmenter la valeur des condensateurs de rétroaction de l’étage d’entrée. La première solution est appelée rétroaction positive croisée et la deuxième solution utilise des PMOS à oxyde épais dans la paire de l’entrée di˙érentielle de l’OTA. Il est à noter que pour compresser le signal neuronal, nous utilisons le CS dans le domaine analogique. Pour la réalisation, un intégrateur à capacité commutée est requis. Les paramètres non idéaux de l’OTA utilisé dans cet intégrateur, tels que le gain fini, la bande passante, la vitesse de balayage et le changement rapide de la sortie. Toutes ces imperfections induisent des erreurs et réduisent le rapport signal sur bruit (SNR) total. Nous avons simulé ces imperfections sur Matlab et Simulink pour définir les spécifications de l’OTA requis. Aussi, pour concevoir les circuits analogiques correspondant aux interfaces neuronales requises, tels qu’un amplificateur neuronal, une référence de tension compacte et à faible consommation d’énergie est requise. Nous avons proposé une référence de tension de faible consommation d’énergie sans utiliser le transistor bipolaire parasite de la technologie CMOS pour diminuer la surface de silicium requise. Finalement, nous avons complété l’encodeur de CS et un convertisseur analogique-numérique à approximation successive (SAR ADC) requis pour la chaine d’enregistrement des signaux neuronaux dans ce projet.----------ABSTRACT In this thesis we present the design of a multi-channel neural recording implant with analog compressive sensing (CS) in 65 nm process. Scaling down technology demotes the parameters of AC-coupled neural amplifiers, such as increasing the low-cuto˙ frequency due to the short-channel e˙ects of MOS transistors. We analyze the low-cuto˙ frequency and find that the main reason of this problem in advanced technologies is decreasing the input resistance of the operational transconductance amplifier (OTA) due to the gate oxide static current leakage in the input of the OTA. In advanced technologies, the gate oxide is thin and some electrons can penetrate to the channel and cause DC current leakage. We proposed two solutions to reduce the low-cuto˙ frequency without increasing the value of the feedback capacitors of the front-end neural amplifier. The first solution is called cross-coupled positive feedback, and the second solution is utilizing thick-oxide PMOS transistors in the input di˙erential pair of the OTA. Compress the neural signal, we utilized the CS method in analog domain. For its implementation, a switched-capacitor integrator is required. Non-ideal specifications of OTA of CS integrator such as finite gain, bandwidth, slew rate and output swing induce error and reduce the total signal to noise ratio (SNR). We simulated these non-idealities in Matlab and Simulink and extracted the specification of the required OTA. Also, to design analog circuits such as neural amplifier a low power and compact voltage reference is required. We implemented a low-power band-gap reference without utilizing parasitic bipolar transis-tor to decrease the silicon area. At the end, we completed the CS encoder and successive approximation architecture analog-to-digital converter (SAR ADC)

Analog Front-End Circuits for Massive Parallel 3-D Neural Microsystems.

Understanding dynamics of the brain has tremendously improved due to the progress in neural recording techniques over the past five decades. The number of simultaneously recorded channels has actually doubled every 7 years, which implies that a recording system with a few thousand channels should be available in the next two decades. Nonetheless, a leap in the number of simultaneous channels has remained an unmet need due to many limitations, especially in the front-end recording integrated circuits (IC). This research has focused on increasing the number of simultaneously recorded channels and providing modular design approaches to improve the integration and expansion of 3-D recording microsystems. Three analog front-ends (AFE) have been developed using extremely low-power and small-area circuit techniques on both the circuit and system levels. The three prototypes have investigated some critical circuit challenges in power, area, interface, and modularity. The first AFE (16-channels) has optimized energy efficiency using techniques such as moderate inversion, minimized asynchronous interface for data acquisition, power-scalable sampling operation, and a wide configuration range of gain and bandwidth. Circuits in this part were designed in a 0.25μm CMOS process using a 0.9-V single supply and feature a power consumption of 4μW/channel and an energy-area efficiency of 7.51x10^15 in units of J^-1Vrms^-1mm^-2. The second AFE (128-channels) provides the next level of scaling using dc-coupled analog compression techniques to reject the electrode offset and reduce the implementation area further. Signal processing techniques were also explored to transfer some computational power outside the brain. Circuits in this part were designed in a 180nm CMOS process using a 0.5-V single supply and feature a power consumption of 2.5μW/channel, and energy-area efficiency of 30.2x10^15 J^-1Vrms^-1mm^-2. The last AFE (128-channels) shows another leap in neural recording using monolithic integration of recording circuits on the shanks of neural probes. Monolithic integration may be the most effective approach to allow simultaneous recording of more than 1,024 channels. The probe and circuits in this part were designed in a 150 nm SOI CMOS process using a 0.5-V single supply and feature a power consumption of only 1.4μW/channel and energy-area efficiency of 36.4x10^15 J^-1Vrms^-1mm^-2.PHDElectrical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/98070/1/ashmouny_1.pd

Study of soft materials, flexible electronics, and machine learning for fully portable and wireless brain-machine interfaces

Over 300,000 individuals in the United States are afflicted with some form of limited motor function from brainstem or spinal-cord related injury resulting in quadriplegia or some form of locked-in syndrome. Conventional brain-machine interfaces used to allow for communication or movement require heavy, rigid components, uncomfortable headgear, excessive numbers of electrodes, and bulky electronics with long wires that result in greater data artifacts and generally inadequate performance. Wireless, wearable electroencephalograms, along with dry non-invasive electrodes can be utilized to allow recording of brain activity on a mobile subject to allow for unrestricted movement. Additionally, multilayer microfabricated flexible circuits, when combined with a soft materials platform allows for imperceptible wearable data acquisition electronics for long term recording. This dissertation aims to introduce new electronics and training paradigms for brain-machine interfaces to provide remedies in the form of communication and movement for these individuals. Here, training is optimized by generating a virtual environment from which a subject can achieve immersion using a VR headset in order to train and familiarize with the system. Advances in hardware and implementation of convolutional neural networks allow for rapid classification and low-latency target control. Integration of materials, mechanics, circuit and electrode design results in an optimized brain-machine interface allowing for rehabilitation and overall improved quality of life.Ph.D

Toward Brain Area Sensor Wireless Network

RÉSUMÉ De nouvelles approches d'interfaçage neuronal de haute performance sont requises pour les interfaces cerveau-machine (BMI) actuelles. Cela nécessite des capacités d'enregistrement/stimulation performantes en termes de vitesse, qualité et quantité, c’est à dire une bande passante à fréquence plus élevée, une résolution spatiale, un signal sur bruit et une zone plus large pour l'interface avec le cortex cérébral. Dans ce mémoire, nous parlons de l'idée générale proposant une méthode d'interfaçage neuronal qui, en comparaison avec l'électroencéphalographie (EEG), l'électrocorticographie (ECoG) et les méthodes d'interfaçage intracortical conventionnelles à une seule unité, offre de meilleures caractéristiques pour implémenter des IMC plus performants. Les avantages de la nouvelle approche sont 1) une résolution spatiale plus élevée - en dessous dumillimètre, et une qualité de signal plus élevée - en termes de rapport signal sur bruit et de contenu fréquentiel - comparé aux méthodes EEG et ECoG; 2) un caractère moins invasif que l'ECoG où l'enlèvement du crâne sous une opération d'enregistrement / stimulation est nécessaire; 3) une plus grande faisabilité de la libre circulation du patient à l'étude - par rapport aux deux méthodes EEG et ECoG où de nombreux fils sont connectés au patient en cours d'opération; 4) une utilisation à long terme puisque l'interface implantable est sans fil - par rapport aux deux méthodes EEG et ECoG qui offrent des temps limités de fonctionnement. Nous présentons l'architecture d'un réseau sans fil de microsystèmes implantables, que nous appelons Brain Area Sensor NETwork (Brain-ASNET). Il y a deux défis principaux dans la réalisation du projet Brain-ASNET. 1) la conception et la mise en oeuvre d'un émetteur-récepteur RF de faible consommation compatible avec la puce de capteurs de réseau implantable, et, 2) la conception d'un protocole de réseau de capteurs sans fil (WSN) ad-hoc économe en énergie. Dans ce mémoire, nous présentons un protocole de réseau ad-hoc économe en énergie pour le réseau désiré, ainsi qu'un procédé pour surmonter le problème de la longueur de paquet variable causé par le processus de remplissage de bit dans le protocole HDLC standard. Le protocole adhoc proposé conçu pour Brain-ASNET présente une meilleure efficacité énergétique par rapport aux protocoles standards tels que ZigBee, Bluetooth et Wi-Fi ainsi que des protocoles ad-hoc de pointe. Le protocole a été conçu et testé par MATLAB et Simulink.----------ABSTRACT New high-performance neural interfacing approaches are demanded for today’s Brain-Machine Interfaces (BMI). This requires high-performance recording/stimulation capabilities in terms of speed, quality, and quantity, i.e. higher frequency bandwidth, spatial resolution, signal-to-noise, and wider area to interface with the cerebral cortex. In this thesis, we talk about the general proposed idea of a neural interfacing method which in comparison with Electroencephalography (EEG), Electrocorticography (ECoG), and, conventional Single-Unit Intracortical neural interfacing methods offers better features to implement higher-performance BMIs. The new approach advantages are 1) higher spatial resolution – down to sub-millimeter, and higher signal quality − in terms of signal-to-noise ratio and frequency content − compared to both EEG and ECoG methods. 2) being less invasive than ECoG where skull removal Under recording/stimulation surgery is required. 3) higher feasibility of freely movement of patient under study − compared to both EEG and ECoG methods where lots of wires are connected to the patient under operation. 4) long-term usage as the implantable interface is wireless − compared to both EEG and ECoG methods where it is practical for only a limited time under operation. We present the architecture of a wireless network of implantable microsystems, which we call it Brain Area Sensor NETwork (Brain-ASNET). There are two main challenges in realization of the proposed Brain-ASNET. 1) design and implementation of power-hungry RF transceiver of the implantable network sensors' chip, and, 2) design of an energy-efficient ad-hoc Wireless Sensor Network (WSN) protocol. In this thesis, we introduce an energy-efficient ad-hoc network protocol for the desired network, along with a method to overcome the issue of variable packet length caused by bit stuffing process in standard HDLC protocol. The proposed ad-hoc protocol designed for Brain-ASNET shows better energy-efficiency compared to standard protocols like ZigBee, Bluetooth, and Wi-Fi as well as state-of-the-art ad-hoc protocols. The protocol was designed and tested by MATLAB and Simulink

De animais a máquinas : humanos tecnicamente melhores nos imaginários de futuro da convergência tecnológica

Dissertação (mestrado)—Universidade de Brasília, Instituto de Ciências Sociais, Departamento de Sociologia, 2020.O tema desta investigação é discutir os imaginários sociais de ciência e tecnologia que emergem a partir da área da neuroengenharia, em sua relação com a Convergência Tecnológica de quatro disciplinas: Nanotecnologia, Biotecnologia, tecnologias da Informação e tecnologias Cognitivas - neurociências- (CT-NBIC). Estas áreas desenvolvem-se e são articuladas por meio de discursos que ressaltam o aprimoramento das capacidades físicas e cognitivas dos seres humanos, com o intuito de construir uma sociedade melhor por meio do progresso científico e tecnológico, nos limites das agendas de pesquisa e desenvolvimento (P&D). Objetivos: Os objetivos nesse cenário, são discutir as implicações éticas, econômicas, políticas e sociais deste modelo de sistema sociotécnico. Nos referimos, tanto as aplicações tecnológicas, quanto as consequências das mesmas na formação dos imaginários sociais, que tipo de relações se estabelecem e como são criadas dentro desse contexto. Conclusão: Concluímos na busca por refletir criticamente sobre as propostas de aprimoramento humano mediado pela tecnologia, que surgem enquanto parte da agenda da Convergência Tecnológica NBIC. No entanto, as propostas de melhoramento humano vão muito além de uma agenda de investigação. Há todo um quadro de referências filosóficas e políticas que defendem o aprimoramento da espécie, vertentes estas que se aliam a movimentos trans-humanistas e pós- humanistas, posições que são ao mesmo tempo éticas, políticas e econômicas. A partir de nossa análise, entendemos que ciência, tecnologia e política estão articuladas, em coprodução, em relação às expectativas de futuros que são esperados ou desejados. Ainda assim, acreditamos que há um espaço de diálogo possível, a partir do qual buscamos abrir propostas para o debate público sobre questões de ciência e tecnologia relacionadas ao aprimoramento da espécie humana.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)The subject of this research is to discuss the social imaginaries of science and technology that emerge from the area of neuroengineering in relation with the Technological Convergence of four disciplines: Nanotechnology, Biotechnology, Information technologies and Cognitive technologies -neurosciences- (CT-NBIC). These areas are developed and articulated through discourses that emphasize the enhancement of human physical and cognitive capacities, the intuition it is to build a better society, through the scientific and technological progress, at the limits of the research and development (R&D) agendas. Objectives: The objective in this scenery, is to discuss the ethic, economic, politic and social implications of this model of sociotechnical system. We refer about the technological applications and the consequences of them in the formation of social imaginaries as well as the kind of social relations that are created and established in this context. Conclusion: We conclude looking for critical reflections about the proposals of human enhancement mediated by the technology. That appear as a part of the NBIC technologies agenda. Even so, the proposals of human enhancement go beyond boundaries that an investigation agenda. There is a frame of philosophical and political references that defend the enhancement of the human beings. These currents that ally to the transhumanism and posthumanism movements, positions that are ethic, politic and economic at the same time. From our analysis, we understand that science, technology and politics are articulated, are in co-production, regarding the expected and desired futures. Even so, we believe that there is a space of possible dialog, from which we look to open proposals for the public discussion on questions of science and technology related to enhancement of human beings