IEEE Trans Instrum Meas

This paper introduces a novel compact low-power amperometric instrumentation design with current-to-digital output for electrochemical sensors. By incorporating the double layer capacitance of an electrochemical sensor's impedance model, our new design can maintain performance while dramatically reducing circuit complexity and size. Electrochemical experiments with potassium ferricyanide, show that the circuit output is in good agreement with results obtained using commercial amperometric instrumentation. A high level of linearity (R| = 0.991) between the circuit output and the concentration of potassium ferricyanide was also demonstrated. Furthermore, we show that a CMOS implementation of the presented architecture could save 25.3% of area, and 47.6% of power compared to a traditional amperometric instrumentation structure. Thus, this new circuit structure is ideally suited for portable/wireless electrochemical sensing applications.20192021-05-01T00:00:00ZR01 ES022302/ES/NIEHS NIH HHS/United StatesR01 OH009644/OH/NIOSH CDC HHS/United States32292210PMC7156046759

Novel miniaturised and highly versatile biomechatronic platforms for the characterisation of melanoma cancer cells

There has been an increasing demand to acquire highly sensitive devices that are able to detect and characterize cancer at a single cell level. Despite the moderate progress in this field, the majority of approaches failed to reach cell characterization with optimal sensitivity and specificity. Accordingly, in this study highly sensitive, miniaturized-biomechatronic platforms have been modeled, designed, optimized, microfabricated, and characterized, which can be used to detect and differentiate various stages of melanoma cancer cells. The melanoma cell has been chosen as a legitimate cancer model, where electrophysiological and analytical expression of cell-membrane potential have been derived, and cellular contractile force has been obtained through a correlation with micromechanical deflections of a miniaturized cantilever beam. The main objectives of this study are in fourfold: (1) to quantify cell-membrane potential, (2) correlate cellular biophysics to respective contractile force of a cell in association with various stages of the melanoma disease, (3) examine the morphology of each stage of melanoma, and (4) arrive at a relation that would interrelate stage of the disease, cellular contractile force, and cellular electrophysiology based on conducted in vitro experimental findings. Various well-characterized melanoma cancer cell lines, with varying degrees of genetic complexities have been utilized. In this study, two-miniaturized-versatile-biomechatronic platforms have been developed to extract the electrophysiology of cells, and cellular mechanics (mechanobiology). The former platform consists of a microfluidic module, and stimulating and recording array of electrodes patterned on a glass substrate, forming multi-electrode arrays (MEAs), whereas the latter system consists of a microcantilever-based biosensor with an embedded Wheatstone bridge, and a microfluidic module. Furthermore, in support of this work main objectives, dedicated microelectronics together with customized software have been attained to functionalize, and empower the two-biomechatronic platforms. The bio-mechatronic system performance has been tested throughout a sufficient number of in vitro experiments.Open Acces

IEEE Trans Biomed Circuits Syst

Airborne pollutants are a leading cause of illness and mortality globally. Electrochemical gas sensors show great promise for personal air quality monitoring to address this worldwide health crisis. However, implementing miniaturized arrays of such sensors demands high performance instrumentation circuits that simultaneously meet challenging power, area, sensitivity, noise and dynamic range goals. This paper presents a new multi-channel CMOS amperometric ADC featuring pixel-level architecture for gas sensor arrays. The circuit combines digital modulation of input currents and an incremental \uce\ua3\ue2\u2c6\u2020 ADC to achieve wide dynamic range and high sensitivity with very high power efficiency and compact size. Fabricated in 0.5 [Formula: see text] CMOS, the circuit was measured to have 164 dB cross-scale dynamic range, 100 fA sensitivity while consuming only 241 [Formula: see text] and 0.157 [Formula: see text] active area per channel. Electrochemical experiments with liquid and gas targets demonstrate the circuit's real-time response to a wide range of analyte concentrations.R01 ES022302/ES/NIEHS NIH HHS/United StatesR01 OH009644/OH/NIOSH CDC HHS/United States2017-08-01T00:00:00Z27352395PMC505675

CMOS and MEMS Based Microsystems for Manipulation and Detection of Magnetic Beads for Biomedical Applications

RÉSUMÉ Les micro et nano billes magnétiques dédiées à l'étiquetage des bio-particules attirent de plus en plus d'intérêt dans de nombreuses applications environnementales et sanitaires, tels que l'analyse de gènes, le transport des médicaments, la purification et l'immunologie. Les dimensions réduites et la haute sensibilité des billes magnétiques rendent leurs manipulations à haute précision possibles. Leur simplicité de suivi dans le milieu biologique et leur biocompatibilité permettent d’effectuer des détections rapides et à haute sensibilité pour des applications in vivo et in vitro. L'utilisation traditionnelle des billes magnétiques prend place dans un laboratoire se servant du matériel encombrant et dispendieux. Avec le développement de la technologie de microfabrication, des billes magnétiques peuvent être traitées dans un microsystème, plus précisément, dans une structure laboratoire sur puce (LoC). La combinaison microfluidique et microélectronique offre des possibilités d’autoévaluation, ce qui peut augmenter l'efficacité du travail. Cette thèse est orientée vers de nouvelles approches pour la manipulation et la détection de bio-particules se servant de la technologie de microsystèmes basées sur des structures microelectroniques et microfluidiques et en utilisant des marqueurs de billes magnétiques. Basé sur un réseau de microbobines à la fois comme une source de champ magnétique et un capteur inductif, le microsystème proposé est réalisé grâce à l'efficacité de fabrication de structures CMOS-MEMS, ainsi que des circuits intégrés dédiés CMOS de haute performance afin d'obtenir un rendement élevé de manipulation et de détection de billes magnétiques. Plusieurs défis ont été analysés dans la mise en œuvre de ces microsystèmes et des solutions correspondantes fournies. Plus précisément, la conception et la mise en œuvre d'une plate-forme contrôlée en température en format portable sont d'abord présentées, dans un effort réalisé pour résoudre la question de la chaleur par effet Joule lors de l'application du réseau de microbobines comme une source de champ magnétique dédié à la manipulation de billes magnétiques. Une plateforme similaire à cette dernière a été améliorée pour effectuer une analyse magnétique immunologique, en ajoutant des circuits de détection par des billes magnétiques. De plus, des IgG et anti-IgG de souris ont été utilisés dans des expériences pour vérifier les performances de détection de la plateforme de microsystème proposé.----------ABSTRACT Magnetic micro/nano beads as labels of bio-particles have been attracting more and more interest in many environmental and health applications, such as gene and drug delivery, purification, and immunoassay. The miniature size and high sensitivity of magnetic bead allow accurate manipulation, whereas its high distinguishability from biological background and biocompatibility make fast and high sensitivity detection possible for in vitro and in vivo applications. Traditional employment of magnetic beads is done in laboratory environment with the assist of bulky and expensive equipment. Thanks to the development of microfabrication technology, magnetic beads therefore can be handled on a microsystem, more specifically, a Lab-on-Chip (LoC). The combination of microfluidics with microelectronics offers the possibility of automatic analyses, which can liberate the labor and increase the efficiency.This thesis focuses on new approaches for bio-particles manipulation and detection on microelectronic/microfluidic hybrid microsystems using magnetic beads as labels. Based on planar microcoil array as both magnetic field source and the front-end inductive sensor, the proposed microsystems can take advantage of the massive producible CMOS/MEMS fabrication process, as well as the customized high performance CMOS circuits, to achieve a high efficient magnetic beads manipulation and a quantitative detection. Several challenges in implementing such microsystems are analyzed and corresponding solutions are provided. Specifically, the design and implementation of a temperature controllable LoC platform in portable format is firstly presented, for the sake of resolving the Joule heat issue when applying microcoil array as magnetic field source in magnetic beads manipulation. The similar platform is then improved to be used for magnetic immunoassay, by adding magnetic beads sensing circuits. Mouse IgG and anti-mouse IgG are employed in experiments to verify the detection performance of the proposed microsystem platform. Additionally, a fully integrated silicon substrate MEMS chip which integrates both microfluidic channel and microcoil array on a single chip is designed and fabricated following the Finite Element Analysis (FEA) simulation results and tested using bio-particles attached magnetic beads. This monolithic chip has the potential to be applied for in vivo applications

A Label Free CMOS-Based Smart Petri Dish for Cellular Analysis

RÉSUMÉ Le dépistage de culture cellulaire à haut débit est le principal défi pour une variété d’applications des sciences de la vie, y compris la découverte de nouveaux médicaments et le suivi de la cytotoxicité. L’analyse classique de culture cellulaire est généralement réalisée à l’aide de techniques microscopiques non-intégrées avec le système de culture cellulaire. Celles-ci sont laborieuses spécialement dans le cas des données recueillies en temps réel ou à des fins de surveillance continue. Récemment, les micro-réseaux cellulaires in-vitro ont prouvé de nombreux avantages dans le domaine de surveillance des cellules en réduisant les coûts, le temps et la nécessité d’études sur des modèles animaux. Les microtechniques, y compris la microélectronique et la microfluidique,ont été récemment utilisé dans la biotechnologie pour la miniaturisation des systèmes biologiques et analytiques. Malgré les nombreux efforts consacrés au développement de dispositifs microfluidiques basés sur les techniques de microscopie optique, le développement de capteurs intégrés couplés à des micropuits pour le suivi des paramètres cellulaires tel que la viabilité, le taux de croissance et cytotoxicité a été limité. Parmi les différentes méthodes de détection disponibles, les techniques capacitives offrent une plateforme de faible complexité. Celles-ci ont été considérablement utilisées afin d’étudier l’interaction cellule-surface. Ce type d’interaction est le plus considéré dans la majorité des études biologiques. L’objectif de cette thèse est de trouver des nouvelles approches pour le suivi de la croissance cellulaire et la surveillance de la cytotoxicité à l’aide d’un réseau de capteurs capacitifs entièrement intégré. Une plateforme hybride combinant un circuit microélectronique et une structure microfluidique est proposée pour des applications de détection de cellules et de découverte de nouveaux médicaments. Les techniques biologiques et chimiques nécessaires au fonctionnement de cette plateforme sont aussi proposées. La technologie submicroniques Standard complementary metal-oxide-Semiconductor (CMOS) (TSMC 0.35 μm) est utilisée pour la conception du circuit microélectronique de cette plateforme. En outre, les électrodes sont fabriquées selon le processus CMOS standard sans la nécessité d’étapes de post-traitement supplémentaires. Ceci rend la plateforme proposée unique par rapport aux plateformes de dépistage de culture cellulaire à haut débit existantes. Plusieurs défis ont été identifiés durant le développement de cette plateforme comme la sensibilité, la bio-compatibilité et la stabilité et les solutions correspondantes sont fournies.----------ABSTRACT High throughput cell culture screening is a key challenge for a variety of life science applications, including drug discovery and cytotoxicity monitoring. Conventional cell culture analysis is widely performed using microscopic techniques that are not integrated into the target cell culture system. Additionally, these techniques are too laborious in particular to be used for real-time and continuous monitoring purposes. Recently, it has been proved that invitro cell microarrays offer great advantages for cell monitoring applications by reducing cost, time, and the need for animal model studies. Microtechnologies, including microelectronics and microfluidics, have been recently used in biotechnology for miniaturization of biological and analytical systems. Despite many efforts in developing microfluidic devices using optical microscopy techniques, less attention have been paid on developing fully integrated sensors for monitoring cell parameters such as viability, growth rate, and cytotoxicity. Among various available sensing methods, capacitive techniques offer low complexity platforms. This technique has significantly attracted attentions for the study of cell-surface interaction which is widely considered in biological studies. This thesis focuses on new approaches for cell growth and cytotoxicity monitoring using a fully integrated capacitive sensor array. A hybrid platform combining microelectronic circuitry and microfluidic structure is proposed along with other required biological and chemical techniques for single cell detection and drug discovery applications. Standard submicron complementary metal–oxide–semiconductor (CMOS) technology (TSMC 0.35 μm) is used to develop the microelectronic part of this platform. Also, the sensing electrodes are fabricated in standard CMOS process without the need for any additional post processing step, which makes the proposed platform unique compared to other state of the art high throughput cell assays. Several challenges in implementing this platform such as sensitivity, bio-compatibility, and stability are discussed and corresponding solutions are provided. Specifically, a new surface functionalization method based on polyelectrolyte multilayers deposition is proposed to enhance cell-electrode adherence and to increase sensing electrodes’ life time. In addition, a novel technique for microwell fabrication and its integration with the CMOS chip is proposed to allow parallel screening of cells. With the potential to perform inexpensive, fast, and real-time cell analyses, the proposed platform opens up the possibility to transform from passive traditional cell assays to a smart on-line monitoring system

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

Low-power Wearable Healthcare Sensors

Advances in technology have produced a range of on-body sensors and smartwatches that can be used to monitor a wearer’s health with the objective to keep the user healthy. However, the real potential of such devices not only lies in monitoring but also in interactive communication with expert-system-based cloud services to offer personalized and real-time healthcare advice that will enable the user to manage their health and, over time, to reduce expensive hospital admissions. To meet this goal, the research challenges for the next generation of wearable healthcare devices include the need to offer a wide range of sensing, computing, communication, and human–computer interaction methods, all within a tiny device with limited resources and electrical power. This Special Issue presents a collection of six papers on a wide range of research developments that highlight the specific challenges in creating the next generation of low-power wearable healthcare sensors

Multimodal Wearable Sensors for Human-Machine Interfaces

Certain areas of the body, such as the hands, eyes and organs of speech production, provide high-bandwidth information channels from the conscious mind to the outside world. The objective of this research was to develop an innovative wearable sensor device that records signals from these areas more conveniently than has previously been possible, so that they can be harnessed for communication. A novel bioelectrical and biomechanical sensing device, the wearable endogenous biosignal sensor (WEBS), was developed and tested in various communication and clinical measurement applications. One ground-breaking feature of the WEBS system is that it digitises biopotentials almost at the point of measurement. Its electrode connects directly to a high-resolution analog-to-digital converter. A second major advance is that, unlike previous active biopotential electrodes, the WEBS electrode connects to a shared data bus, allowing a large or small number of them to work together with relatively few physical interconnections. Another unique feature is its ability to switch dynamically between recording and signal source modes. An accelerometer within the device captures real-time information about its physical movement, not only facilitating the measurement of biomechanical signals of interest, but also allowing motion artefacts in the bioelectrical signal to be detected. Each of these innovative features has potentially far-reaching implications in biopotential measurement, both in clinical recording and in other applications. Weighing under 0.45 g and being remarkably low-cost, the WEBS is ideally suited for integration into disposable electrodes. Several such devices can be combined to form an inexpensive digital body sensor network, with shorter set-up time than conventional equipment, more flexible topology, and fewer physical interconnections. One phase of this study evaluated areas of the body as communication channels. The throat was selected for detailed study since it yields a range of voluntarily controllable signals, including laryngeal vibrations and gross movements associated with vocal tract articulation. A WEBS device recorded these signals and several novel methods of human-to-machine communication were demonstrated. To evaluate the performance of the WEBS system, recordings were validated against a high-end biopotential recording system for a number of biopotential signal types. To demonstrate an application for use by a clinician, the WEBS system was used to record 12‑lead electrocardiogram with augmented mechanical movement information