Low-Noise Micro-Power Amplifiers for Biosignal Acquisition

There are many different types of biopotential signals, such as action potentials (APs), local field potentials (LFPs), electromyography (EMG), electrocardiogram (ECG), electroencephalogram (EEG), etc. Nerve action potentials play an important role for the analysis of human cognition, such as perception, memory, language, emotions, and motor control. EMGs provide vital information about the patients which allow clinicians to diagnose and treat many neuromuscular diseases, which could result in muscle paralysis, motor problems, etc. EEGs is critical in diagnosing epilepsy, sleep disorders, as well as brain tumors. Biopotential signals are very weak, which requires the biopotential amplifier to exhibit low input-referred noise. For example, EEGs have amplitudes from 1 μV [microvolt] to 100 μV [microvolt] with much of the energy in the sub-Hz [hertz] to 100 Hz [hertz] band. APs have amplitudes up to 500 μV [microvolt] with much of the energy in the 100 Hz [hertz] to 7 kHz [hertz] band. In wearable/implantable systems, the low-power operation of the biopotential amplifier is critical to avoid thermal damage to surrounding tissues, preserve long battery life, and enable wirelessly-delivered or harvested energy supply. For an ideal thermal-noise-limited amplifier, the amplifier power is inversely proportional to the input-referred noise of the amplifier. Therefore, there is a noise-power trade-off which must be well-balanced by the designers. In this work I propose novel amplifier topologies, which are able to significantly improve the noise-power efficiency by increasing the effective transconductance at a given current. In order to reject the DC offsets generated at the tissue-electrode interface, energy-efficient techniques are employed to create a low-frequency high-pass cutoff. The noise contribution of the high-pass cutoff circuitry is minimized by using power-efficient configurations, and optimizing the biasing and dimension of the devices. Sufficient common-mode rejection ratio (CMRR) and power supply rejection ratio (PSRR) are achieved to suppress common-mode interferences and power supply noises. Our design are fabricated in standard CMOS processes. The amplifiers’ performance are measured on the bench, and also demonstrated with biopotential recordings

New Techniques for Multi-Channel Biosignal Acquisition and Low-Power, Low-Resistance-Measurement Systems

Dense electrical recording of biosignals has been developed to provide spatial resolution and precise temporal information for health monitoring, diagnostics, and clinical research. However, more electrodes require more wires, and wiring density quickly becomes a limiting factor. To break this bottleneck, we proposed a frequency-division multiplexing (FDM) based architecture for multi-channel acquisition systems. In this final exam, I present two applications that make use of this FDM technique. The first is an FDM-based multi-channel electromyography (EMG) acquisition system, which demonstrates that the FDM system not only reduces wire count, but also mitigates the effect of low frequency motion artifacts and 50/60 Hz mains interference introduced in the wire. An FDM-based four-channel EMG recording is demonstrated, while carrying all channels over a 3-wire interface, and the system achieves an attenuation of low-frequency cable motion artifacts by 15X an! d 60Hz mains noise coupled in the cable by 62X. A second application that forms the basis of my current research effort is an FDM-based neural recording system with multiple graphene active electrodes. We demonstrated a two-channel system including graphene FET electrodes, a custom integrated circuit (IC) analog front-end (AFE), and digital demodulation. In related multi-channel sensor work, a growing need for ultra-low-power sensors has driven continuous advancement in read-out circuits for temperature, humidity, and pressure. IC-integrated Wheatstone bridges, commonly used, are efficient for large sensor resistance (5k-500kohm), but measuring small resistance (30,000x smaller nominal sensor resistance

Optimized Biosignals Processing Algorithms for New Designs of Human Machine Interfaces on Parallel Ultra-Low Power Architectures

The aim of this dissertation is to explore Human Machine Interfaces (HMIs) in a variety of biomedical scenarios. The research addresses typical challenges in wearable and implantable devices for diagnostic, monitoring, and prosthetic purposes, suggesting a methodology for tailoring such applications to cutting edge embedded architectures. The main challenge is the enhancement of high-level applications, also introducing Machine Learning (ML) algorithms, using parallel programming and specialized hardware to improve the performance. The majority of these algorithms are computationally intensive, posing significant challenges for the deployment on embedded devices, which have several limitations in term of memory size, maximum operative frequency, and battery duration. The proposed solutions take advantage of a Parallel Ultra-Low Power (PULP) architecture, enhancing the elaboration on specific target architectures, heavily optimizing the execution, exploiting software and hardware resources. The thesis starts by describing a methodology that can be considered a guideline to efficiently implement algorithms on embedded architectures. This is followed by several case studies in the biomedical field, starting with the analysis of a Hand Gesture Recognition, based on the Hyperdimensional Computing algorithm, which allows performing a fast on-chip re-training, and a comparison with the state-of-the-art Support Vector Machine (SVM); then a Brain Machine Interface (BCI) to detect the respond of the brain to a visual stimulus follows in the manuscript. Furthermore, a seizure detection application is also presented, exploring different solutions for the dimensionality reduction of the input signals. The last part is dedicated to an exploration of typical modules for the development of optimized ECG-based applications

Current efficient integrated architecture for common mode rejection sensitive neural recordings

In the last decade we have seen a significant growth of research and potential applications of electronic circuits that interact with the nervous system, in a wide range of applications, from basic neuroscience research to medical clinic, or from the entertainment industry to transport services. The real time acquisition and analysis of brain signals, either through wearable electroencephalography (EEG) or invasive or implantable recordings, in order to perform actions (brain machine interface) or to understand aspects of brain operation, has become scientifically and technologically feasible. This thesis aims to support neural recording applications with low noise, currentefficiency and high common-mode rejection ratio (CMRR) as main features of the recording system. One emblematic example of these applications in the neuroscience domain is the weakly electric fish neural activity recording, where the interference produced by the discharge of the fish electric organ is a key factor. Another example, from the implantable devices domain, is the nerve activity recorded with cuff electrodes, where the desired signal is interfered by electromyographic potentials generated by muscles near the cuff. In these cases, the amplitude of the interfering signals, which mainly appear in common mode, is several orders of magnitude higher than the amplitude of the signals of interest. Therefore, this thesis introduces a novel integrated neural preamplifier architecture targeting CMRR sensitive neural recording applications. The architecture is presented and analyzed in depth, deriving the preamplifier transfer function and the main design equations. We present a detailed analysis of a technique for blocking the input dc component and setting the high-pass frequency without using MOS pseudo-resistors. One of the main contributions of this work is the overall architecture coupled with an efficient and simple single-stage circuit for the preamplifier main transconductor. A fully-integrated neural preamplifier, which performs well in line with the state-ofthe-art of the field while providing enhanced CMRR performance, was fabricated in a 0.5 um CMOS process. Results from measurements show that the measured gain is 49.5 dB, bandwidth ranges from 13 Hz to 9.8 kHz, CMRR is very high (greater than 87 dB), and it is achieved jointly with a remarkable low noise (1.88 uVrms) and current-efficiency (NEF = noise efficiency factor = 2.1). A second version of the preamplifier with one external capacitor achieves a high-pass frequency of 0.1 Hz while keeping the performance of the fully-integrated version. In addition, we present in-vivo measurements made with the proposed architecture in a weakly electric fish (Gymnotus omarorum), showing the ability of the preamplifier to acquire neural signals from high amplitude common mode interference in an unshielded environment. This was the first in-vivo testing of a neural recording integrated circuit designed in Uruguay done in a local lab. Furthermore, signals recorded with our unshielded low-power battery-powered preamplifier perfectly match with those of a shielded commercially-available amplifier (ac-plugged, without power restrictions). To the best of our knowledge, the proposed preamplifier is the best option for applications that simultaneously need low noise, high CMRR and current-efficiency. Furthermore, in this thesis we applied the aforementioned architecture to bandpass biquad filters, specially but not only, to those with differential input. The new architecture provides a significant reduction in consumption (up to 30%) and/or makes it possible to block a higher level of dc at the input (up to the double, without using decoupling capacitors). Next, we applied the novel architecture to the design of the different stages of an integrated programmable analog front-end. Results from simulations shows that the gain is programmable between 57 dB and 99 dB, the low-pass frequency is programmable between 116 Hz and 5.2 kHz, the maximum power consumption is 11.2 uA and the maximum equivalent input-referred noise voltage is 1.87 uVrms. The comparison between our front-end and other works in the state-of-the-art shows that our front-end presents the best results in terms of CMRR and noise, has the greatest value of gain and equals the best NEF reported. Finally, some system-level topics were addressed during this thesis, including the design and implementation of three prototypes of end-to-end wireless biopotentials recording systems based on off-the-shelf components. Developing and applying circuits, systems and methods, for synchronized largescale monitoring of neural activity, sensory images, and behavior, would produce a dynamic picture of the brain function, which is essential for understanding the brain in action. In this context, we hope that the present thesis become our first step to further contribute to this area

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

Roadmap on signal processing for next generation measurement systems

Signal processing is a fundamental component of almost any sensor-enabled system, with a wide range of applications across different scientific disciplines. Time series data, images, and video sequences comprise representative forms of signals that can be enhanced and analysed for information extraction and quantification. The recent advances in artificial intelligence and machine learning are shifting the research attention towards intelligent, data-driven, signal processing. This roadmap presents a critical overview of the state-of-the-art methods and applications aiming to highlight future challenges and research opportunities towards next generation measurement systems. It covers a broad spectrum of topics ranging from basic to industrial research, organized in concise thematic sections that reflect the trends and the impacts of current and future developments per research field. Furthermore, it offers guidance to researchers and funding agencies in identifying new prospects.AerodynamicsMicrowave Sensing, Signals & System

Organic electrochemical transistors for neurotechnology

The organic electrochemical transistor is a device that has proven to provide a comprehensive insight into physiological activity. The burden of brain-related illnesses and the potential societal impact of enhancing human interaction and communication with computers motivates the advancement of technologies to provide greater insights into neural activity. This research focuses on the intersection of these fields through developing organic electrochemical transistors for neurotechnology. As such, this research reports the fabrication, characterisation, and operation of the devices to demonstrate their applicability in providing an accurate description of neural activity. In turn, pathways are offered on the optimisation and enhancement of transistor performance, informing the field on methods to maximise the efficacy of biosensing devices. This thesis opens with the motivations to develop neurotechnology in society by considering the burden of neurological disorders and the enhancement of human-machine communication. The roles that bioelectronics and organic electrochemical transistors could take in achieving such goals are then described. The literature on organic electrochemical transistors and their applications in neurotechnology is then examined. Foundational to this research was the design and fabrication of novel transistor architectures. As such, fabrication methods are then described which provide micrometre-scale resolutions, facilitating the production of biocompatible, high-performance devices. The thesis then describes an investigation with the aim to optimise the performance of organic electrochemical transistors for the maximisation of the range of electrophysiological signals that the devices can resolve and amplify. Devices are demonstrated with high amplification factors and bandwidths sufficient for transducing the full bioelectric spectrum. The devices efficaciously resolve electrophysiological inputs with a wide range of voltage and frequency characteristics, demonstrated through measuring the device response to pre-recorded signals and supported through noise quantification. Research is then presented with aims to employ organic electrochemical transistors in a linear amplifier topology that provides precise amplification control. Circuit parameters are identified for stable amplifier operation, and the transistors are physically implemented into amplifier circuits. An equation is then formulated which models the transistor current in the linear, non-linear and saturation regimes, and this equation is used to simulate the amplifier response. Through experimentation and simulation, the amplifier is extensively characterised, providing quantitative measures on amplifier gain, linearity, bandwidth, and noise. The amplifier is then inputted with pre-recorded bioelectric signals and the linear gain of the amplifier is experimentally demonstrated. The thesis then presents an investigation with the aim to determine the effect of electrode architecture on organic electrochemical transistor characteristics and bioelectric performance. The impacts of varying the interconnect resistance on the steady-state and transient characteristics are examined. Then, arrays of devices are fabricated, and the effects of varying the interconnect resistance and the interdigitated electrode geometry on bioelectric performance are quantified. The electrode architecture at the measurement site is then varied for a fixed site area to determine an optimal configuration for resolving bioelectric inputs. The investigation presents a pathway for the optimisation of electrode architecture for a given application. Finally, the thesis describes research that aims to determine the relationships between the morphological properties of the organic layer and the electrical characteristics relevant to biosensing performance. Electrical characterisations and resonant Raman spectroscopy are carried out on organic electrochemical transistors that are immersed in an aqueous solution over a period of 50 days, and the temporal changes in the derived parameters are presented. Then, the effects of varying the applied voltages on the active layer morphology and the device noise are investigated, providing an insight into how the structural changes of organic polymers correlate to variations in noise.Open Acces