Wired, wireless and wearable bioinstrumentation for high-precision recording of bioelectrical signals in bidirectional neural interfaces

It is widely accepted by the scientific community that bioelectrical signals, which can be used for the identification of neurophysiological biomarkers indicative of a diseased or pathological state, could direct patient treatment towards more effective therapeutic strategies. However, the design and realisation of an instrument that can precisely record weak bioelectrical signals in the presence of strong interference stemming from a noisy clinical environment is one of the most difficult challenges associated with the strategy of monitoring bioelectrical signals for diagnostic purposes. Moreover, since patients often have to cope with the problem of limited mobility being connected to bulky and mains-powered instruments, there is a growing demand for small-sized, high-performance and ambulatory biopotential acquisition systems in the Intensive Care Unit (ICU) and in High-dependency wards. Furthermore, electrical stimulation of specific target brain regions has been shown to alleviate symptoms of neurological disorders, such as Parkinson’s disease, essential tremor, dystonia, epilepsy etc. In recent years, the traditional practice of continuously stimulating the brain using static stimulation parameters has shifted to the use of disease biomarkers to determine the intensity and timing of stimulation. The main motivation behind closed-loop stimulation is minimization of treatment side effects by providing only the necessary stimulation required within a certain period of time, as determined from a guiding biomarker. Hence, it is clear that high-quality recording of local field potentials (LFPs) or electrocorticographic (ECoG) signals during deep brain stimulation (DBS) is necessary to investigate the instantaneous brain response to stimulation, minimize time delays for closed-loop neurostimulation and maximise the available neural data. To our knowledge, there are no commercial, small, battery-powered, wearable and wireless recording-only instruments that claim the capability of recording ECoG signals, which are of particular importance in closed-loop DBS and epilepsy DBS. In addition, existing recording systems lack the ability to provide artefact-free high-frequency (> 100 Hz) LFP recordings during DBS in real time primarily because of the contamination of the neural signals of interest by the stimulation artefacts. To address the problem of limited mobility often encountered by patients in the clinic and to provide a wide variety of high-precision sensor data to a closed-loop neurostimulation platform, a low-noise (8 nV/√Hz), eight-channel, battery-powered, wearable and wireless multi-instrument (55 × 80 mm2) was designed and developed. The performance of the realised instrument was assessed by conducting both ex vivo and in vivo experiments. The combination of desirable features and capabilities of this instrument, namely its small size (~one business card), its enhanced recording capabilities, its increased processing capabilities, its manufacturability (since it was designed using discrete off-the-shelf components), the wide bandwidth it offers (0.5 – 500 Hz) and the plurality of bioelectrical signals it can precisely record, render it a versatile tool to be utilized in a wide range of applications and environments. Moreover, in order to offer the capability of sensing and stimulating via the same electrode, novel real-time artefact suppression methods that could be used in bidirectional (recording and stimulation) system architectures are proposed and validated. More specifically, a novel, low-noise and versatile analog front-end (AFE), which uses a high-order (8th) analog Chebyshev notch filter to suppress the artefacts originating from the stimulation frequency, is presented. After defining the system requirements for concurrent LFP recording and DBS artefact suppression, the performance of the realised AFE is assessed by conducting both in vitro and in vivo experiments using unipolar and bipolar DBS (monophasic pulses, amplitude ranging from 3 to 6 V peak-to-peak, frequency 140 Hz and pulse width 100 µs). Under both in vitro and in vivo experimental conditions, the proposed AFE provided real-time, low-noise and artefact-free LFP recordings (in the frequency range 0.5 – 250 Hz) during stimulation. Finally, a family of tunable hardware filter designs and a novel method for real-time artefact suppression that enables wide-bandwidth biosignal recordings during stimulation are also presented. This work paves the way for the development of miniaturized research tools for closed-loop neuromodulation that use a wide variety of bioelectrical signals as control signals.Open Acces

A high-performance 8 nV/root Hz 8-channel wearable and wireless system for real-time monitoring of bioelectrical signals

Background: It is widely accepted by the scientific community that bioelectrical signals, which can be used for the identification of neurophysiological biomarkers indicative of a diseased or pathological state, could direct patient treatment towards more effective therapeutic strategies. However, the design and realisation of an instrument that can precisely record weak bioelectrical signals in the presence of strong interference stemming from a noisy clinical environment is one of the most difficult challenges associated with the strategy of monitoring bioelectrical signals for diagnostic purposes. Moreover, since patients often have to cope with the problem of limited mobility being connected to bulky and mains-powered instruments, there is a growing demand for small-sized, high-performance and ambulatory biopotential acquisition systems in the Intensive Care Unit (ICU) and in High-dependency wards. Finally, to the best of our knowledge, there are no commercial, small, battery-powered, wearable and wireless recording-only instruments that claim the capability of recording electrocorticographic (ECoG) signals. Methods: To address this problem, we designed and developed a low-noise (8 nV/√Hz), eight-channel, battery-powered, wearable and wireless instrument (55 × 80 mm2). The performance of the realised instrument was assessed by conducting both ex vivo and in vivo experiments. Results: To provide ex vivo proof-of-function, a wide variety of high-quality bioelectrical signal recordings are reported, including electroencephalographic (EEG), electromyographic (EMG), electrocardiographic (ECG), acceleration signals, and muscle fasciculations. Low-noise in vivo recordings of weak local field potentials (LFPs), which were wirelessly acquired in real time using segmented deep brain stimulation (DBS) electrodes implanted in the thalamus of a non-human primate, are also presented. Conclusions: The combination of desirable features and capabilities of this instrument, namely its small size (~one business card), its enhanced recording capabilities, its increased processing capabilities, its manufacturability (since it was designed using discrete off-the-shelf components), the wide bandwidth it offers (0.5 – 500 Hz) and the plurality of bioelectrical signals it can precisely record, render it a versatile and reliable tool to be utilized in a wide range of applications and environments

A Novel Power-Efficient Wireless Multi-channel Recording System for the Telemonitoring of Electroencephalography (EEG)

This research introduces the development of a novel EEG recording system that is modular, batteryless, and wireless (untethered) with the supporting theoretical foundation in wireless communications and related design elements and circuitry. Its modular construct overcomes the EEG scaling problem and makes it easier for reconfiguring the hardware design in terms of the number and placement of electrodes and type of standard EEG system contemplated for use. In this development, portability, lightweight, and applicability to other clinical applications that rely on EEG data are sought. Due to printer tolerance, the 3D printed cap consists of 61 electrode placements. This recording capacity can however extend from 21 (as in the international 10-20 systems) up to 61 EEG channels at sample rates ranging from 250 to 1000 Hz and the transfer of the raw EEG signal using a standard allocated frequency as a data carrier. The main objectives of this dissertation are to (1) eliminate the need for heavy mounted batteries, (2) overcome the requirement for bulky power systems, and (3) avoid the use of data cables to untether the EEG system from the subject for a more practical and less restrictive setting. Unpredictability and temporal variations of the EEG input make developing a battery-free and cable-free EEG reading device challenging. Professional high-quality and high-resolution analog front ends are required to capture non-stationary EEG signals at microvolt levels. The primary components of the proposed setup are the wireless power transmission unit, which consists of a power amplifier, highly efficient resonant-inductive link, rectification, regulation, and power management units, as well as the analog front end, which consists of an analog to digital converter, pre-amplification unit, filtering unit, host microprocessor, and the wireless communication unit. These must all be compatible with the rest of the system and must use the least amount of power possible while minimizing the presence of noise and the attenuation of the recorded signal A highly efficient resonant-inductive coupling link is developed to decrease power transmission dissipation. Magnetized materials were utilized to steer electromagnetic flux and decrease route and medium loss while transmitting the required energy with low dissipation. Signal pre-amplification is handled by the front-end active electrodes. Standard bio-amplifier design approaches are combined to accomplish this purpose, and a thorough investigation of the optimum ADC, microcontroller, and transceiver units has been carried out. We can minimize overall system weight and power consumption by employing battery-less and cable-free EEG readout system designs, consequently giving patients more comfort and freedom of movement. Similarly, the solutions are designed to match the performance of medical-grade equipment. The captured electrical impulses using the proposed setup can be stored for various uses, including classification, prediction, 3D source localization, and for monitoring and diagnosing different brain disorders. All the proposed designs and supporting mathematical derivations were validated through empirical and software-simulated experiments. Many of the proposed designs, including the 3D head cap, the wireless power transmission unit, and the pre-amplification unit, are already fabricated, and the schematic circuits and simulation results were based on Spice, Altium, and high-frequency structure simulator (HFSS) software. The fully integrated head cap to be fabricated would require embedding the active electrodes into the 3D headset and applying current technological advances to miniaturize some of the design elements developed in this dissertation

Network Electrophysiology Sensor-On-A- Chip

Electroencephalogram (EEG), Electrocardiogram (ECG), and Electromyogram (EMG) bio-potential signals are commonly recorded in clinical practice. Typically, patients are connected to a bulky and mains-powered instrument, which reduces their mobility and creates discomfort. This limits the acquisition time, prevents the continuous monitoring of patients, and can affect the diagnosis of illness. Therefore, there is a great demand for low-power, small-size, and ambulatory bio-potential signal acquisition systems. Recent work on instrumentation amplifier design for bio-potential signals can be broadly classified as using one or both of two popular techniques: In the first, an AC-coupled signal path with a MOS-Bipolar pseudo resistor is used to obtain a low-frequency cutoff that passes the signal of interest while rejecting large dc offsets. In the second, a chopper stabilization technique is designed to reduce 1/f noise at low frequencies. However, both of these existing techniques lack control of low-frequency cutoff. This thesis presents the design of a mixed- signal integrated circuit (IC) prototype to provide complete, programmable analog signal conditioning and analog-to-digital conversion of an electrophysiologic signal. A front-end amplifier is designed with low input referred noise of 1 uVrms, and common mode rejection ratio 102 dB. A novel second order sigma-delta analog- to-digital converter (ADC) with a feedback integrator from the sigma-delta output is presented to program the low-frequency cutoff, and to enable wide input common mode range of ¡Ãƒâ€œ0.3 V. The overall system is implemented in Jazz Semiconductor 0.18 um CMOS technology with power consumption 5.8 mW from ¡Ãƒâ€œ0.9V power supplies

Ultra-Low-Power Sensors and Receivers for IoT Applications

The combination of ultra-low power analog front-ends and CMOS-compatible transducers enable new applications, such as environmental monitors, household appliances, health trackers, etc. that are seamlessly integrated into our daily lives. Furthermore, wireless connectivity allows many of these sensors to operate both independently and collectively. These techniques collectively fulfil the recent surge of internet-of-things (IoT) applications that have the potential to fundamentally change daily life for millions of people.In this dissertation, the circuit and system design of wireless receivers and sensors is presented that explores the challenges of implementing long lifespan, high accuracy, and large coverage range IoT sensor networks. The first is a wake-up receiver (WuRX), which continuously monitors the RF environment to wake up a higher-power radio upon detection of a predetermined RF signature. This work both improves sensitivity and reduces power over prior art through a multi-faceted design featuring an impedance transformation network with large passive voltage gain, an active envelope detector with high input impedance to facilitate large passive voltage gain, a low-power precision comparator, and a low-leakage digital baseband correlator.Although pushing the prior WuRX performance boundary by orders of magnitude, the first work shows moderate sensitivity, inferior temperature robustness, and large area with external lumped components. Thus, the second work shows a miniaturized WuRX that is temperature-compensated, yet still consumes only nano-watt power and millimeter area while operating at 9 GHz. To further reduce the area, a global common-mode feedback is utilized across the envelope detector and baseband amplifier that eliminates the need for off-chip ac-coupling components. Multiple temperature-compensation techniques are proposed to maintain constant bandwidth of the signal path and constant clock frequency. Both WuRXs operate at 0.4 V supply, consume near-zero power and achieve ~-70 dBm sensitivity.Lastly, the first reported CMOS 2-in-1 relative humidity and temperature sensor is presented. A unified analog front-end interfaces on-chip transducers and converts the inputs into a frequency vis a high-linearity frequency-locked loop. An incomplete-settling switched-capacitor-based Wheatstone bridge is proposed to sense the inputs in a power-efficient fashion

Low Power Circuits for Smart Flexible ECG Sensors

Cardiovascular diseases (CVDs) are the world leading cause of death. In-home heart condition monitoring effectively reduced the CVD patient hospitalization rate. Flexible electrocardiogram (ECG) sensor provides an affordable, convenient and comfortable in-home monitoring solution. The three critical building blocks of the ECG sensor i.e., analog frontend (AFE), QRS detector, and cardiac arrhythmia classifier (CAC), are studied in this research. A fully differential difference amplifier (FDDA) based AFE that employs DC-coupled input stage increases the input impedance and improves CMRR. A parasitic capacitor reuse technique is proposed to improve the noise/area efficiency and CMRR. An on-body DC bias scheme is introduced to deal with the input DC offset. Implemented in 0.35m CMOS process with an area of 0.405mm2, the proposed AFE consumes 0.9W at 1.8V and shows excellent noise effective factor of 2.55, and CMRR of 76dB. Experiment shows the proposed AFE not only picks up clean ECG signal with electrodes placed as close as 2cm under both resting and walking conditions, but also obtains the distinct -wave after eye blink from EEG recording. A personalized QRS detection algorithm is proposed to achieve an average positive prediction rate of 99.39% and sensitivity rate of 99.21%. The user-specific template avoids the complicate models and parameters used in existing algorithms while covers most situations for practical applications. The detection is based on the comparison of the correlation coefficient of the user-specific template with the ECG segment under detection. The proposed one-target clustering reduced the required loops. A continuous-in-time discrete-in-amplitude (CTDA) artificial neural network (ANN) based CAC is proposed for the smart ECG sensor. The proposed CAC achieves over 98% classification accuracy for 4 types of beats defined by AAMI (Association for the Advancement of Medical Instrumentation). The CTDA scheme significantly reduces the input sample numbers and simplifies the sample representation to one bit. Thus, the number of arithmetic operations and the ANN structure are greatly simplified. The proposed CAC is verified by FPGA and implemented in 0.18m CMOS process. Simulation results show it can operate at clock frequencies from 10KHz to 50MHz. Average power for the patient with 75bpm heart rate is 13.34W

ULTRA LOW POWER CIRCUITS FOR WEARABLE BIOMEDICAL SENSORS

Ph.DDOCTOR OF PHILOSOPH

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

Low-Power Wireless Medical Systems and Circuits for Invasive and Non-Invasive Applications

Approximately 75% of the health care yearly budget of public health systems around the world is spent on the treatment of patients with chronic diseases. This, along with advances on the medical and technological fields has given rise to the use of preventive medicine, resulting on a high demand of wireless medical systems (WMS) for patient monitoring and drug safety research. In this dissertation, the main design challenges and solutions for designing a WMS are addressed from system-level, using off-the-shell components, to circuit implementation. Two low-power oriented WMS aiming to monitor blood pressure of small laboratory animals (implantable) and cardiac-activity (12-lead electrocardiogram) of patients with chronic diseases (wearable) are presented. A power consumption vs. lifetime analysis to estimate the monitoring unit lifetime for each application is included. For the invasive/non-invasive WMS, in-vitro test benches are used to verify their functionality showing successful communication up to 2.1 m/35 m with the monitoring unit consuming 0.572 mA/33 mA from a 3 V/4.5 V power supply, allowing a two-year/ 88-hour lifetime in periodic/continuous operation. This results in an improvement of more than 50% compared with the lifetime commercial products. Additionally, this dissertation proposes transistor-level implementations of an ultra-low-noise/low-power biopotential amplifier and the baseband section of a wireless receiver, consisting of a channel selection filter (CSF) and a variable gain amplifier (VGA). The proposed biopotential amplifier is intended for electrocardiogram (ECG)/ electroencephalogram (EEG)/ electromyogram (EMG) monitoring applications and its architecture was designed focused on improving its noise/power efficiency. It was implemented using the ON-SEMI 0.5 µm standard process with an effective area of 360 µm2. Experimental results show a pass-band gain of 40.2 dB (240 mHz - 170 Hz), input referred noise of 0.47 Vrms, minimum CMRR of 84.3 dBm, NEF of 1.88 and a power dissipation of 3.5 µW. The CSF was implemented using an active-RC 4th order inverse-chebyshev topology. The VGA provides 30 gain steps and includes a DC-cancellation loop to avoid saturation on the sub-sequent analog-to-digital converter block. Measurement results show a power consumption of 18.75 mW, IIP3 of 27.1 dBm, channel rejection better than 50 dB, gain variation of 0-60dB, cut-off frequency tuning of 1.1-2.29 MHz and noise figure of 33.25 dB. The circuit was implemented in the standard IBM 0.18 µm CMOS process with a total area of 1.45 x 1.4 mm^(2). The presented WMS can integrate the proposed biopotential amplifier and baseband section with small modifications depending on the target signal while using the low-power-oriented algorithm to obtain further power optimization

A HARDWARE-SOFTWARE CO-DESIGNED WEARABLE FOR REAL-TIME PHYSIOLOGICAL DATA COLLECTION AND SIGNAL QUALITY ASSESSMENT

In the future, Smart and Connected Communities (S&CC) will use distributed wireless sensors and embedded computing platforms to produce meaningful data that can help individuals, and communities. Here, we presented a scanner, a data reliability estimation algorithm and Electrocardiogram (ECG) beat classification algorithm which contributes to the S&CC framework .In part 1, we report the design, prototyping, and functional validation of a low-power, small, and portable signal acquisition device for these sensors. The scanner was fully tested, characterized, and validated in the lab, as well as through deployment to users homes. As a test case, we show results of the scanner measuring WRAP temperature sensors with relative error within the 0.01% range. The scanner measurement shows distinguish temperature of 1F difference and excellent linear dependence between actual and measured resistance (R2 = 0.998). This device hasdemonstrated the possibility of a small, low-power portable scanner for WRAP sensors.Additionally, we explored the statistical data reliability metric (DReM) to explain the quality of bio-signal quantitatively on a scale between 0.0 -1.0. As proof of concept, we analyzed the ECG signal. Our DReM prediction algorithm measures the reliability of the ECG signals effectively with low Root mean square error = 0.010 and Mean absolute error = 0.008 and coefficient of determination R2 value of 0.990. Finally, we tested our model against the opinions of three independent judges and presented R2 value to determine the agreement between judgments vs our prediction model.We concluded our contribution to the S&CC framework by analyzing ECG beat classification with a pipeline of classifiers that focuses on improving the models performance on identifying minority classes (ventricular ectopic beat, supraventricular ectopic beat). Moreover, we intended to minimize morphological distortion introduced due to indiscriminate use of filtering techniques on ECG signals. Our approach shows an average positive predictive value 95.21%, sensitivity of95.28%, and F-1 score 95.76% respectively