Ultra-low-power circuits and systems for wearable and implantable medical devices

Thesis (Ph. D.)--Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science, 2013.Cataloged from PDF version of thesis.Includes bibliographical references (pages 219-231).Advances in circuits, sensors, and energy storage elements have opened up many new possibilities in the health industry. In the area of wearable devices, the miniaturization of electronics has spurred the rapid development of wearable vital signs, activity, and fitness monitors. Maximizing the time between battery recharge places stringent requirements on power consumption by the device. For implantable devices, the situation is exacerbated by the fact that energy storage capacity is limited by volume constraints, and frequent battery replacement via surgery is undesirable. In this case, the design of energy-efficient circuits and systems becomes even more crucial. This thesis explores the design of energy-efficient circuits and systems for two medical applications. The first half of the thesis focuses on the design and implementation of an ultra-low-power, mixed-signal front-end for a wearable ECG monitor in a 0.18pm CMOS process. A mixed-signal architecture together with analog circuit optimizations enable ultra-low-voltage operation at 0.6V which provides power savings through voltage scaling, and ensures compatibility with state-of-the-art DSPs. The fully-integrated front-end consumes just 2.9[mu]W, which is two orders of magnitude lower than commercially available parts. The second half of this thesis focuses on ultra-low-power system design and energy-efficient neural stimulation for a proof-of-concept fully-implantable cochlear implant. First, implantable acoustic sensing is demonstrated by sensing the motion of a human cadaveric middle ear with a piezoelectric sensor. Second, alternate energy-efficient electrical stimulation waveforms are investigated to reduce neural stimulation power when compared to the conventional rectangular waveform. The energy-optimal waveform is analyzed using a computational nerve fiber model, and validated with in-vivo ECAP recordings in the auditory nerve of two cats and with psychophysical tests in two human cochlear implant users. Preliminary human subject testing shows that charge and energy savings of 20-30% and 15-35% respectively are possible with alternative waveforms. A system-on-chip comprising the sensor interface, reconfigurable sound processor, and arbitrary-waveform neural stimulator is implemented in a 0.18[mu]m high-voltage CMOS process to demonstrate the feasibility of this system. The sensor interface and sound processor consume just 12[mu]W of power, representing just 2% of the overall system power which is dominated by stimulation. As a result, the energy savings from using alternative stimulation waveforms transfer directly to the system.by Marcus Yip.Ph.D

Implantable Micro-Device for Epilepsy Seizure Detection and Subsequent Treatment

RÉSUMÉ L’émergence des micro-dispositifs implantables est une voie prometteuse pour le traitement de troubles neurologiques. Ces systèmes biomédicaux ont été exploités comme traitements non-conventionnels sur des patients chez qui les remèdes habituels sont inefficaces. Les récents progrès qui ont été faits sur les interfaces neuronales directes ont permis aux chercheurs d’analyser l’activité EEG intracérébrale (icEEG) en temps réel pour des fins de traitements. Cette thèse présente un dispositif implantable à base de microsystèmes pouvant capter efficacement des signaux neuronaux, détecter des crises d’épilepsie et y apporter un traitement afin de l’arrêter. Les contributions principales présentées ici ont été rapportées dans cinq articles scientifiques, publiés ou acceptés pour publication dans les revues IEEE, et plusieurs autres tels que «Low Power Electronics» et «Emerging Technologies in Computing». Le microsystème proposé inclus un circuit intégré (CI) à faible consommation énergétique permettant la détection de crises d’épilepsie en temps réel. Cet CI comporte une pré-amplification initiale et un détecteur de crises d’épilepsie. Le pré-amplificateur est constitué d’une nouvelle topologie de stabilisateur d’hacheur réduisant le bruit et la puissance dissipée. Les CI fabriqués ont été testés sur des enregistrements d’icEEG provenant de sept patients épileptiques réfractaires au traitement antiépileptique. Le délai moyen de la détection d’une crise est de 13,5 secondes, soit avant le début des manifestations cliniques évidentes. La consommation totale d’énergie mesurée de cette puce est de 51 μW. Un neurostimulateur à boucle fermée (NSBF), quant à lui, détecte automatiquement les crises en se basant sur les signaux icEEG captés par des électrodes intracrâniennes et permet une rétroaction par une stimulation électrique au même endroit afin d’interrompre ces crises. La puce de détection de crises et le stimulateur électrique à base sur FPGA ont été assemblés à des électrodes afin de compléter la prothèse proposée. Ce NSBF a été validé en utilisant des enregistrements d’icEEG de dix patients souffrant d’épilepsie réfractaire. Les résultats révèlent une performance excellente pour la détection précoce de crises et pour l’auto-déclenchement subséquent d’une stimulation électrique. La consommation énergétique totale du NSBF est de 16 mW. Une autre alternative à la stimulation électrique est l’injection locale de médicaments, un traitement prometteur de l’épilepsie. Un système local de livraison de médicament basé sur un nouveau détecteur asynchrone des crises est présenté.----------ABSTRACT Emerging implantable microdevices hold great promise for the treatment of patients with neurological conditions. These biomedical systems have been exploited as unconventional treatment for the conventionally untreatable patients. Recent progress in brain-machine-interface activities has led the researchers to analyze the intracerebral EEG (icEEG) recording in real-time and deliver subsequent treatments. We present in this thesis a long-term safe and reliable low-power microsystem-based implantable device to perform efficient neural signal recording, seizure detection and subsequent treatment for epilepsy. The main contributions presented in this thesis are reported in five journal manuscripts, published or accepted for publication in IEEE Journals, and many others such as Low Power Electronics, and Emerging Technologies in Computing. The proposed microsystem includes a low-power integrated circuit (IC) intended for real-time epileptic seizure detection. This IC integrates a front-end preamplifier and epileptic seizure detector. The preamplifier is based on a new chopper stabilizer topology that reduces noise and power dissipation. The fabricated IC was tested using icEEG recordings from seven patients with drug-resistant epilepsy. The average seizure detection delay was 13.5 sec, well before the onset of clinical manifestations. The measured total power consumption of this chip is 51 µW. A closed-loop neurostimulator (CLNS) is next introduced, which is dedicated to automatically detect seizure based on icEEG recordings from intracranial electrode contacts and provide an electrical stimulation feedback to the same contacts in order to disrupt these seizures. The seizure detector chip and a dedicated FPGA-based electrical stimulator were assembled together with common recording electrodes to complete the proposed prosthesis. This CLNS was validated offline using recording from ten patients with refractory epilepsy, and showed excellent performance for early detection of seizures and subsequent self-triggering electrical stimulation. Total power consumption of the CLNS is 16 mW. Alternatively, focal drug injection is the promising treatment for epilepsy. A responsive focal drug delivery system based on a new asynchronous seizure detector is also presented. The later system with data-dependent computation reduces up to 49% power consumption compared to the previous synchronous neurostimulator

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

The utility of latency and spectral analysis methods in evoked potential recordings from patients with hepatic encephalopathy

Evoked potentials (EPs) are small phasic potentials that are elicited in conjunction with sensory, motor and cognitive events. EP variables have been assessed in patients with cirrhosis but in general, methods were inadequately standardized and study populations incompletely characterized, leading to some studies questioning the validity of EP’s in diagnosing and monitoring hepatic encephalopathy, while other studies indicated that there is only a low positive yield with these investigations. Few studies have attempted tri-modal sensory and cognitive recordings. Recorded waveforms may demonstrate altered morphology while possessing broadly normal latencies. Since EP analysis is usually performed solely in the time domain, latency measurements do not therefore highlight morphological changes to the waveform and so abnormalities may go unreported. The aim of this study was twofold (i) to measure sensory and cognitive EPs in patients with cirrhosis in relation to their neuropsychiatric status and (ii) to address frequency content in relation to neuropsychiatric status by examining EPs with two spectral techniques, the Fourier Transform (FT) and the Power Spectral Density Estimate (PSD). Seventy patients with biopsy–proven cirrhosis were classified using clinical, psychometric and EEG criteria as unimpaired or as having minimal or overt hepatic encephalopathy (HE). Forty-eight healthy individuals served as controls. Visual (VEPs), brainstem auditory (BAEPs) somatosensory (SSEPs) and cognitive auditory (P300) EPs were recorded under standardized conditions. Significant latency differences were observed in sensory EPs between patients and controls with patient subgroups differences being less significant. The cognitive auditory P300 however, distinguished the patient subpopulations from one another. Frequency shifts are observed in all EP modalities with significant differences also occurring between patient groups. The sensitivity and specificity of the frequency-domain is comparable to that of the time-domain. Paired EP investigations analysed by latency indicate BAEP and P300 best discriminate any degree of encephalopathy; in the frequency domain it is the VEP combined with SEP and in the time-frequency domain it is the SEP. These findings suggest that EPs, when performed as a bank of multimodal tests and with spectral analysis, could provide a sensitive and specific method for the diagnosis and monitoring of hepatic encephalopathy

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

Advanced sensors technology survey

This project assesses the state-of-the-art in advanced or 'smart' sensors technology for NASA Life Sciences research applications with an emphasis on those sensors with potential applications on the space station freedom (SSF). The objectives are: (1) to conduct literature reviews on relevant advanced sensor technology; (2) to interview various scientists and engineers in industry, academia, and government who are knowledgeable on this topic; (3) to provide viewpoints and opinions regarding the potential applications of this technology on the SSF; and (4) to provide summary charts of relevant technologies and centers where these technologies are being developed

Walking aids for stroke patients

SIGLEAvailable from British Library Document Supply Centre-DSC:DXN024350 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Microfluidics and Neural Interfaces Development for the Safe Direct Current Stimulator

Safety of commercial neural implants fundamentally limits its working to the use of charge-balanced, biphasic pulses to interact with target neurons using metal electrodes. Short biphasic pulses are used to avoid toxic electrochemical reactions at the electrode-tissue interfaces. Biphasic pulses are effective at exciting neurons, but quite limited in inhibiting their activity. In contrast, direct current can both excite and inhibit neurons, however it leads to the formation of harmful, Faradaic reactions at the metal electrode/tissue interface. To address this challenge of safety over chronic use, we are developing the Safe Direct Current Stimulator (SDCS) technology, that generates an ionic direct current (iDC) from a biphasic input signal using a network of microfluidic channels and mechanical valves. This rectified iDC is applied to the target neural tissue through an ionically conductive neural interface. A key enabler towards transforming the SDCS concept from a benchtop design to an implantable neural prosthesis is the design of a miniature valve. Several valve architectures and actuation mechanism were studied for the development of the microfluidics in SDCS technology, before settling on the plunger-membrane microvalve design. This thesis characterizes a miniature polydimethylsiloxane (PDMS) based elastomeric normally closed (NC) mechanical valve actuated using a shape-memory alloy (SMA) wire through distinct tests and examines its current capability for iDC delivery. The analysis of the test outputs confirmed the feasibility of using this design for rectifying the charge-balanced alternating current (AC) into iDC. As metal electrodes are unsuitable for delivering iDC to the neural tissue safely, an ionic conductive neural lead is built. These gel-based, PDMS electrodes should be designed within the acceptable pressure limits that a nerve can handle safely. Preliminary experiments were conducted to verify the design and conductivity of the lead. While the results suggest that the lead design maintains the pressure below the maximum limit, its high impedance raises concerns. Although this thesis forms a basis for development of the SDCS device, further experimentation and progress is required for a reliable, safe, chronic, and fully functional device

Conformable transistors for bioelectronics

The diversity of network disruptions that occur in patients with neuropsychiatric disorders creates a strong demand for personalized medicine. Such approaches often take the form of implantable bioelectronic devices that are capable of monitoring pathophysiological activity for identifying biomarkers to allow for local and responsive delivery of intervention. They are also required to transmit this data outside of the body for evaluation of the treatment’s efficacy. However, the ability to perform these demanding electronic functions in the complex physiological environment with minimum disruption to the biological tissue remains a big challenge. An optimal fully implantable bioelectronic device would require each component from the front-end to the data transmission to be conformable and biocompatible. For this reason, organic material-based conformable electronics are ideal candidates for components of bioelectronic circuits due to their inherent flexibility, and soft nature. In this work, first an organic mixed-conducting particulate composite material (MCP) able to form functional electronic components and non-invasively acquire high–spatiotemporal resolution electrophysiological signals by directly interfacing human skin is presented. Secondly, we introduce organic electrochemical internal ion-gated transistors (IGTs) as a high-density, high-amplification sensing component as well as a low leakage, high-speed processing unit. Finally, a novel wireless, battery-free strategy for electrophysiological signal acquisition, processing, and transmission that employs IGTs and an ionic communication circuit (IC) is introduced. We show that the wirelessly-powered IGTs are able to acquire and modulate neurophysiological data in-vivo and transmit them transdermally, eliminating the need for any hard Si-based electronics in the implant