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

Ultra-low power mixed-signal frontend for wearable EEGs

Electronics circuits are ubiquitous in daily life, aided by advancements in the chip design industry, leading to miniaturised solutions for typical day to day problems. One of the critical healthcare areas helped by this advancement in technology is electroencephalography (EEG). EEG is a non-invasive method of tracking a person's brain waves, and a crucial tool in several healthcare contexts, including epilepsy and sleep disorders. Current ambulatory EEG systems still suffer from limitations that affect their usability. Furthermore, many patients admitted to emergency departments (ED) for a neurological disorder like altered mental status or seizures, would remain undiagnosed hours to days after admission, which leads to an elevated rate of death compared to other conditions. Conducting a thorough EEG monitoring in early-stage could prevent further damage to the brain and avoid high mortality. But lack of portability and ease of access results in a long wait time for the prescribed patients. All real signals are analogue in nature, including brainwaves sensed by EEG systems. For converting the EEG signal into digital for further processing, a truly wearable EEG has to have an analogue mixed-signal front-end (AFE). This research aims to define the specifications for building a custom AFE for the EEG recording and use that to review the suitability of the architectures available in the literature. Another critical task is to provide new architectures that can meet the developed specifications for EEG monitoring and can be used in epilepsy diagnosis, sleep monitoring, drowsiness detection and depression study. The thesis starts with a preview on EEG technology and available methods of brainwaves recording. It further expands to design requirements for the AFE, with a discussion about critical issues that need resolving. Three new continuous-time capacitive feedback chopped amplifier designs are proposed. A novel calibration loop for setting the accurate value for a pseudo-resistor, which is a crucial block in the proposed topology, is also discussed. This pseudoresistor calibration loop achieved the resistor variation of under 8.25%. The thesis also presents a new design of a curvature corrected bandgap, as well as a novel DDA based fourth-order Sallen-Key filter. A modified sensor frontend architecture is then proposed, along with a detailed analysis of its implementation. Measurement results of the AFE are finally presented. The AFE consumed a total power of 3.2A (including ADC, amplifier, filter, and current generation circuitry) with the overall integrated input-referred noise of 0.87V-rms in the frequency band of 0.5-50Hz. Measurement results confirmed that only the proposed AFE achieved all defined specifications for the wearable EEG system with the smallest power consumption than state-of-art architectures that meet few but not all specifications. The AFE also achieved a CMRR of 131.62dB, which is higher than any studied architectures.Open Acces

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

Modulaarinen kehitysalusta langattomille lääketieteellisille anturi-implanteille

Implanting medical sensor devices under skin improves the quality of the acquired measurement results, and can greatly increase the comfort for the patient in prolonged measurement. Design of such complex devices and related systems benefits from using a dedicated development platform that represents the functionalities and associated challenges. This work presents the design, implementation and verified performance of a modular platform that can be used in demonstration, development and testing of various functionalities of wireless medical sensor implants. The system is constructed using discrete components and consists of five inter connectable modules, each representing a specific function of the sensor implant system: bio potential measurement front-end module, wireless communication front-end module, clock and power management module, control logic module and external reader module. The implemented system has measurement front-end with an ENOB of 9 bits and configurable structure for the needs of various bio potentials. Wireless data transfer operates at 840-960 MHz with supported data rate up to 640 kbps. The system demonstrates dual carrier operation for separating the power and data transfers. Power can be harvested and clock extracted from 6.75 MHz or 865 MHz radio signals, both radio signals can be generated by the external reader. Control logic is provided with a high-end FPGA evaluation board. The completed platform can be used for developing and testing aspects for novel implanted devices, such as different radio communication schemes, radio antenna options, or controls and algorithms in digital logic.Lääketieteellisten anturien asettaminen ihon alle parantaa biopotentiaalimittauksien tulosten laatua ja pitkäaikaisten mittauksien mukavuutta potilaalle. Näiden monimutkaisten laitteiden suunnittelua voidaan tehostaa käyttämällä apuna sovelluskohtaista kehitysalustaa. Tässä työssä suunnitellaan ja toteutetaan modulaarinen, korkean suorituskyvyn kehitysalusta biopotentiaalia mittaavien langattomien anturi-implanttijärjestelmien eri toiminnallisuuksien esittelyyn, kehitykseen ja testaukseen. Diskreeteillä komponenteilla toteutettu järjestelmä koostuu viidestä moduulista: biopotentiaalien mittausmoduuli, langattoman tiedonvälityksen radiomoduuli, tehon ja kellosignaalin keräysmoduuli, ohjauslogiikkamoduuli, ja kehon ulkopuolinen lukijamoduuli. Kehitysalusta on muokattavissa eri biopotentiaalien mittauksien tarpeisiin. Mittausetupään tehollinen bittimäärä on 9 bittiä. Langatonta tiedonsiirtoa tuetaan 840 - 960 MHz taajuuskaistalla 640 kbps siirtonopeuksiin asti. Järjestelmällä voidaan demonstroida kahden kantoaallon yhtäaikaista käyttämistä, jolloin tehon- ja tiedonsiirto voidaan tarvittaessa erottaa toisistaan. Tehoa voidaan kerätä ja kellosignaaleja muodostaa 6,75 MHz ja 865 MHz taajuuksien radiosignaaleilta, jotka molemmat voidaan luoda hallitusti lukijamoduulilla. Ohjauslogiikka on toteutettu käyttäen ohjelmoitavaa porttimatriisipiiriä. Kehitysalustaa voidaan käyttää uusien implanttijärjestelmien suunnittelussa, esimerkiksi eri tiedonsiirtotapojen, antennirakenteiden, ohjauslogiikan ja digitaalisten algoritmien arvioinnissa

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

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

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

CMOS Hyperbolic Sine ELIN filters for low/audio frequency biomedical applications

Hyperbolic-Sine (Sinh) filters form a subclass of Externally-Linear-Internally-Non- Linear (ELIN) systems. They can handle large-signals in a low power environment under half the capacitor area required by the more popular ELIN Log-domain filters. Their inherent class-AB nature stems from the odd property of the sinh function at the heart of their companding operation. Despite this early realisation, the Sinh filtering paradigm has not attracted the interest it deserves to date probably due to its mathematical and circuit-level complexity. This Thesis presents an overview of the CMOS weak inversion Sinh filtering paradigm and explains how biomedical systems of low- to audio-frequency range could benefit from it. Its dual scope is to: consolidate the theory behind the synthesis and design of high order Sinh continuous–time filters and more importantly to confirm their micro-power consumption and 100+ dB of DR through measured results presented for the first time. Novel high order Sinh topologies are designed by means of a systematic mathematical framework introduced. They employ a recently proposed CMOS Sinh integrator comprising only p-type devices in its translinear loops. The performance of the high order topologies is evaluated both solely and in comparison with their Log domain counterparts. A 5th order Sinh Chebyshev low pass filter is compared head-to-head with a corresponding and also novel Log domain class-AB topology, confirming that Sinh filters constitute a solution of equally high DR (100+ dB) with half the capacitor area at the expense of higher complexity and power consumption. The theoretical findings are validated by means of measured results from an 8th order notch filter for 50/60Hz noise fabricated in a 0.35μm CMOS technology. Measured results confirm a DR of 102dB, a moderate SNR of ~60dB and 74μW power consumption from 2V power supply

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

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