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

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

Development and modelling of a versatile active micro-electrode array for high density in-vivo and in-vitro neural signal investigation

The electrophysiological observation of neurological cells has allowed much knowledge to be gathered regarding how living organisms are believed to acquire and process sensation. Although much has been learned about neurons in isolation, there is much more to be discovered in how these neurons communicate within large networks. The challenges of measuring neurological networks at the scale, density and chronic level of non invasiveness required to observe neurological processing and decision making are manifold, however methods have been suggested that have allowed small scale networks to be observed using arrays of micro-fabricated electrodes. These arrays transduce ionic perturbations local to the cell membrane in the extracellular fluid into small electrical signals within the metal that may be measured. A device was designed for optimal electrical matching to the electrode interface and maximal signal preservation of the received extracellular neural signals. Design parameters were developed from electrophysiological computer simulations and experimentally obtained empirical models of the electrode-electrolyte interface. From this information, a novel interface based signal filtering method was developed that enabled high density amplifier interface circuitry to be realised. A novel prototype monolithic active electrode was developed using CMOS microfabrication technology. The device uses the top metallization of a selected process to form the electrode substrate and compact amplification circuitry fabricated directly beneath the electrode to amplify and separate the neural signal from the baseline offsets and noise of the electrode interface. The signal is then buffered for high speed sampling and switched signal routing. Prototype 16 and 256 active electrode array with custom support circuitry is presented at the layout stage for a 20 μm diameter 100 μm pitch electrode array. Each device consumes 26.4 μW of power and contributes 4.509 μV (rms) of noise to the received signal over a controlled bandwidth of 10 Hz - 5 kHz. The research has provided a fundamental insight into the challenges of high density neural network observation, both in the passive and the active manner. The thesis concludes that power consumption is the fundamental limiting factor of high density integrated MEA circuitry; low power dissipation being crucial for the existence of the surface adhered cells under measurement. With transistor sizing, noise and signal slewing each being inversely proportional to the dc supply current and the large power requirements of desirable ancillary circuitry such as analogue-to-digital converters, a situation of compromise is approached that must be carefully considered for specific application design

Impedance Spectroscopy

This book covers new advances in the field of impedance spectroscopy including fundamentals, methods and applications. It releases selected extended and peer reviewed scientific contributions from the International Workshop on Impedance Spectroscopy (IWIS 2017) focussing on detailed information about recent scientific research results in electrochemistry and battery research, bioimpedance measurement, sensors, system design, signal processing

Biomedical Engineering

Biomedical engineering is currently relatively wide scientific area which has been constantly bringing innovations with an objective to support and improve all areas of medicine such as therapy, diagnostics and rehabilitation. It holds a strong position also in natural and biological sciences. In the terms of application, biomedical engineering is present at almost all technical universities where some of them are targeted for the research and development in this area. The presented book brings chosen outputs and results of research and development tasks, often supported by important world or European framework programs or grant agencies. The knowledge and findings from the area of biomaterials, bioelectronics, bioinformatics, biomedical devices and tools or computer support in the processes of diagnostics and therapy are defined in a way that they bring both basic information to a reader and also specific outputs with a possible further use in research and development

Ultra-thin and flexible CMOS technology: ISFET-based microsystem for biomedical applications

A new paradigm of silicon technology is the ultra-thin chip (UTC) technology and the emerging applications. Very thin integrated circuits (ICs) with through-silicon vias (TSVs) will allow the stacking and interconnection of multiple dies in a compact format allowing a migration towards three-dimensional ICs (3D-ICs). Also, extremely thin and therefore mechanically bendable silicon chips in conjunction with the emerging thin-film and organic semiconductor technologies will enhance the performance and functionality of large-area flexible electronic systems. However, UTC technology requires special attention related to the circuit design, fabrication, dicing and handling of ultra-thin chips as they have different physical properties compared to their bulky counterparts. Also, transistors and other active devices on UTCs experiencing variable bending stresses will suffer from the piezoresistive effect of silicon substrate which results in a shift of their operating point and therefore, an additional aspect should be considered during circuit design. This thesis tries to address some of these challenges related to UTC technology by focusing initially on modelling of transistors on mechanically bendable Si-UTCs. The developed behavioural models are a combination of mathematical equations and extracted parameters from BSIM4 and BSIM6 modified by a set of equations describing the bending-induced stresses on silicon. The transistor models are written in Verilog-A and compiled in Cadence Virtuoso environment where they were simulated at different bending conditions. To complement this, the verification of these models through experimental results is also presented. Two chips were designed using a 180 nm CMOS technology. The first chip includes nMOS and pMOS transistors with fixed channel width and two different channel lengths and two different channel orientations (0° and 90°) with respect to the wafer crystal orientation. The second chip includes inverter logic gates with different transistor sizes and orientations, as in the previous chip. Both chips were thinned down to ∼20m using dicing-before-grinding (DBG) prior to electrical characterisation at different bending conditions. Furthermore, this thesis presents the first reported fully integrated CMOS-based ISFET microsystem on UTC technology. The design of the integrated CMOS-based ISFET chip with 512 integrated on-chip ISFET sensors along with their read-out and digitisation scheme is presented. The integrated circuits (ICs) are thinned down to ∼30m and the bulky, as well as thinned ICs, are electrically and electrochemically characterised. Also, the thesis presents the first reported mechanically bendable CMOS-based ISFET device demonstrating that mechanical deformation of the die can result in drift compensation through the exploitation of the piezoresistive nature of silicon. Finally, this thesis presents the studies towards the development of on-chip reference electrodes and biodegradable and ultra-thin biosensors for the detection of neurotransmitters such as dopamine and serotonin

Inorganic micro/nanostructures-based high-performance flexible electronics for electronic skin application

Electronics in the future will be printed on diverse substrates, benefiting several emerging applications such as electronic skin (e-skin) for robotics/prosthetics, flexible displays, flexible/conformable biosensors, large area electronics, and implantable devices. For such applications, electronics based on inorganic micro/nanostructures (IMNSs) from high mobility materials such as single crystal silicon and compound semiconductors in the form of ultrathin chips, membranes, nanoribbons (NRs), nanowires (NWs) etc., offer promising high-performance solutions compared to conventional organic materials. This thesis presents an investigation of the various forms of IMNSs for high-performance electronics. Active components (from Silicon) and sensor components (from indium tin oxide (ITO), vanadium pentaoxide (V2O5), and zinc oxide (ZnO)) were realised based on the IMNS for application in artificial tactile skin for prosthetics/robotics. Inspired by human tactile sensing, a capacitive-piezoelectric tandem architecture was realised with indium tin oxide (ITO) on a flexible polymer sheet for achieving static (upto 0.25 kPa-1 sensitivity) and dynamic (2.28 kPa-1 sensitivity) tactile sensing. These passive tactile sensors were interfaced in extended gate mode with flexible high-performance metal oxide semiconductor field effect transistors (MOSFETs) fabricated through a scalable process. The developed process enabled wafer scale transfer of ultrathin chips (UTCs) of silicon with various devices (ultrathin chip resistive samples, metal oxide semiconductor (MOS) capacitors and n‐channel MOSFETs) on flexible substrates up to 4″ diameter. The devices were capable of bending upto 1.437 mm radius of curvature and exhibited surface mobility above 330 cm2/V-s, on-to-off current ratios above 4.32 decades, and a subthreshold slope above 0.98 V/decade, under various bending conditions. While UTCs are useful for realizing high-density high-performance micro-electronics on small areas, high-performance electronics on large area flexible substrates along with low-cost fabrication techniques are also important for realizing e-skin. In this regard, two other IMNS forms are investigated in this thesis, namely, NWs and NRs. The controlled selective source/drain doping needed to obtain transistors from such structure remains a bottleneck during post transfer printing. An attractive solution to address this challenge based on junctionless FETs (JLFETs), is investigated in this thesis via technology computer-aided design (TCAD) simulation and practical fabrication. The TCAD optimization implies a current of 3.36 mA for a 15 μm channel length, 40 μm channel width with an on-to-off ratio of 4.02x 107. Similar to the NRs, NWs are also suitable for realizing high performance e-skin. NWs of various sizes, distribution and length have been fabricated using various nano-patterning methods followed by metal assisted chemical etching (MACE). Synthesis of Si NWs of diameter as low as 10 nm and of aspect ratio more than 200:1 was achieved. Apart from Si NWs, V2O5 and ZnO NWs were also explored for sensor applications. Two approaches were investigated for printing NWs on flexible substrates namely (i) contact printing and (ii) large-area dielectrophoresis (DEP) assisted transfer printing. Both approaches were used to realize electronic layers with high NW density. The former approach resulted in 7 NWs/μm for bottom-up ZnO and 3 NWs/μm for top-down Si NWs while the latter approach resulted in 7 NWs/μm with simultaneous assembly on 30x30 electrode patterns in a 3 cm x 3 cm area. The contact-printing system was used to fabricate ZnO and Si NW-based ultraviolet (UV) photodetectors (PDs) with a Wheatstone bridge (WB) configuration. The assembled V2O5 NWs were used to realize temperature sensors with sensitivity of 0.03% /K. The sensor arrays are suitable for tactile e-skin application. While the above focuses on realizing conventional sensing and addressing elements for e-skin, processing of a large amount of data from e-skin has remained a challenge, especially in the case of large area skin. A Neural NW Field Effect Transistors (υ-NWFETs) based hardware-implementable neural network (HNN) approach for tactile data processing in e-skin is presented in the final part of this thesis. The concept is evaluated by interfacing with a fabricated kirigami-inspired e-skin. Apart from e-skin for prosthetics and robotics, the presented research will also be useful for obtaining high performance flexible circuits needed in many futuristic flexible electronics applications such as smart surgical tools, biosensors, implantable electronics/electroceuticals and flexible mobile phones