Soft microfluidic systems that capture, store, and perform biomarker analysis of microliter volumes of sweat, in situ, as it emerges from the surface of the skin, represent an emerging class of ...wearable technology with powerful capabilities that complement those of traditional biophysical sensing devices. Recent work establishes applications in the real-time characterization of sweat dynamics and sweat chemistry in the context of sports performance and healthcare diagnostics. This paper presents a collection of advances in biochemical sensors and microfluidic designs that support multimodal operation in the monitoring of physiological signatures directly correlated to physical and mental stresses. These wireless, battery-free, skin-interfaced devices combine lateral flow immunoassays for cortisol, fluorometric assays for glucose and ascorbic acid (vitamin C), and digital tracking of skin galvanic responses. Systematic benchtop evaluations and field studies on human subjects highlight the key features of this platform for the continuous, noninvasive monitoring of biochemical and biophysical correlates of the stress state.
Recently, wideband microwave spectroscopy (WBMS) has been applied for material characterization. Blood glucose sensing through microwave spectroscopy is usually done with resonant frequency-domain ...methods. Time-domain (TD) WBMS is a low-cost and convenient technique that can be used for glucose sensing of the aqueous solution. In this paper, early research for the implementation of a TD dielectric spectroscopy setup for glucose concentration measurement is presented. TD reflected signals from water with different glucose content are calculated using inverse Laplace transform. The proposed setup is a quasi-monostatic setup in which measurements are done with two different devices in the frequency range of 0.1 to 6 GHz to make a comparison between frequency domain (FD) and TD methods. Frequency domain (FD) measurement is performed with VNA and two Vivaldi antennas. Then, TD data is obtained using the transforming option of VNA. Direct TD measurement is operated with a maximum length sequence (m-sequence) transceiver. Measurement and numerical results follow the same trend and show good agreement with each other. A monotonic relation between peaks of TD signals and the corresponding glucose concentration is achieved. The variation of the height of the reflected signal's peak is 0.00002 and 0.0005 for each 50 mg/dL glucose concentration with FD measurements and direct TD measurements, respectively. The glucose concentration range of 25 mg/dL to 400 mg/dL is investigated, and the worst repeatability of this method is 3.65% for 300 mg/dL.
Impedance measurement of live biological cells is widely accepted as a label free, non-invasive and quantitative analytical method to assess cell status. This method is easy-to-use and flexible for ...device design and fabrication. In this review, three typical techniques for impedance measurement, i.e., electric cell-substrate impedance sensing, Impedance flow cytometry and electric impedance spectroscopy, are reviewed from the aspects of theory, to electrode design and fabrication, and applications. Benefiting from the integration of microelectronic and microfluidic techniques, impedance sensing methods have expanded their applications to nearly all aspects of biology, including living cell counting and analysis, cell biology research, cancer research, drug screening, and food and environmental safety monitoring. The integration with other techniques, the fabrication of devices for certain biological assays, and the development of point-of-need diagnosis devices is predicted to be future trend for impedance sensing techniques.
•Three typical impedance sensing techniques: ECIS, IFC and EIS, are reviewed.•The theory, electrode fabrication, and applications are introduced.•Applications of impedance sensing have been expanded to all aspects of cell biology.•The development of point-of-need diagnosis devices is predicted to be future trend.
Coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was classified as a pandemic by the World Health Organization and has caused over 550,000 deaths ...worldwide as of July 2020. Accurate and scalable point-of-care devices would increase screening, diagnosis, and monitoring of COVID-19 patients. Here, we demonstrate rapid label-free electrochemical detection of SARS-CoV-2 antibodies using a commercially available impedance sensing platform. A 16-well plate containing sensing electrodes was pre-coated with receptor binding domain (RBD) of SARS-CoV-2 spike protein, and subsequently tested with samples of anti-SARS-CoV-2 monoclonal antibody CR3022 (0.1 μg/ml, 1.0 μg/ml, 10 μg/ml). Subsequent blinded testing was performed on six serum specimens taken from COVID-19 and non-COVID-19 patients (1:100 dilution factor). The platform was able to differentiate spikes in impedance measurements from a negative control (1% milk solution) for all CR3022 samples. Further, successful differentiation and detection of all positive clinical samples from negative control was achieved. Measured impedance values were consistent when compared to standard ELISA test results showing a strong correlation between them (R2=0.9). Detection occurs in less than five minutes and the well-based platform provides a simplified and familiar testing interface that can be readily adaptable for use in clinical settings.
•Capacitive immunosensing of clinically relevant concentrations of SARS-CoV-2 antibodies.•Antigen/antibody association and dissociation occurs within few seconds.•Rapid, label free detection using commercially available equipment.•Impedance peaks correlated with CR3022 concentration levels and ELISA measurements.
Electrical assays potentially offer a highly sensitive, cheap, portable, automated, and multiplexed means of protein biomarker detection, characteristics with an ability to underpin both disease ...stratification and the development of point of care diagnostics. Most conveniently applied in a reagent free manner, all sensitive assays such as these suffer, however, from profound problems when applied in complex fluids such as blood serum. We report herein, the development, and clinical application, of a highly sensitive and selective electrical insulin biosensor based on a chemisorbed zwittorionic polymer support and a novel reagentless sensing technique based on phase monitoring electrochemical impedance spectroscopy. The polymer adlayer is exceptionally effective in both reducing background response and maintaining receptive antibody binding efficacy, while the non-Faradaic analysis avoids potential interference from background electro-active molecules. Applied to the detection of even a low molecular weight protein (here, insulin), a linear range from 0.1 to 200 pM and an unprecedented femtomolar detection limit are possible in undiluted blood serum.
Accurate, rapid, and low-cost molecular diagnostics is essential in managing outbreaks of infectious diseases, such as the pandemic of coronavirus disease 2019 (COVID-19). Accordingly, microfluidic ...paper-based analytical devices (μPADs) have emerged as promising diagnostic tools. Among the extensive efforts to improve the performance and usability of diagnostic tools, biosensing mechanisms based on electrochemical impedance spectroscopy (EIS) have shown great promise because of their label-free operation and high sensitivity. However, the method to improve EIS biosensing on μPADs is less explored. Here, we present an experimental approach to enhancing the performance of paper-based EIS biosensors featuring zinc oxide nanowires (ZnO NWs) directly grown on working electrodes (WEs). Through a comparison of different EIS settings and an examination of ZnO-NW effects on EIS measurements, we show that ZnO-NW-enhanced WEs function reliably with Faradaic processes utilizing iron-based electron mediators. We calibrate paper-based EIS biosensors with different morphologies of ZnO NWs and achieve a low limit of detection (0.4 pg ml−1) in detecting p24 antigen as a marker for human immunodeficiency virus (HIV). Through microscopic imaging and electrochemical characterization, we reveal that the morphological and the electrochemical surface areas of ZnO-NW-enhanced WEs indicate the sensitivities and sensing ranges of the EIS nanobiosensors. Finally, we report that the EIS nanobiosensors are capable of differentiating the concentrations (blank, 10 ng ml−1, 100 ng ml−1, and 1 μg ml−1) of IgG antibody (CR3022) to SARS-CoV-2 in human serum samples, demonstrating the efficacy of these devices for COVID-19 diagnosis. This work provides a methodology for the rational design of high-performance EIS μPADs and has the potential to facilitate diagnosis in pandemics.
•Paper-based electrochemical impedance biosensors for accurate, rapid, and low-cost diagnostics of infectious diseases.•Zinc oxide nanowires (ZnO NWs) were directly synthesized on paper electrodes through hydrothermal growth.•Morphological and electrochemical surface areas of ZnO NWs on a working electrode affect the sensitivity and detection range of the electrochemical impedance biosensors.•Serological testing of IgG antibody (CR3022) to COVID-19 was demonstrated.
Miniaturizing potentiostats, keeping their cost low and yet preserving full measurement characteristics (e.g. bandwidth, determination of capacitive/inductive contribution to sensor's impedance and ...parallel screening) is still an unresolved challenge in bioelectronics. In this work, the combination of simple analogue circuitry together with powerful microcontrollers and a digital filter implementation is presented as an alternative to complex and incomplete architectures reported in the literature. A low-cost acquisition electronic system fully integrated with a biosensors platform containing eight gold working microelectrodes and integrated reference and counter electrodes was developed and validated. The manufacturing cost of the prototype was kept below 300 USD. The performance of the proposed device was benchmarked against a commercial impedance analyzer through the electrochemical analysis of a highly sensitive biosensor for the detection of tumor necrosis factor α (TNF-α) within the randomly chosen range of 266pg/mL to 666ng/mL in physiological medium (PBS). A strong correlation between the outputs of both devices was found in a critical range of frequencies (1–10Hz), and several TNF-α cytokine concentrations were properly discriminated. These results are very promising for the development of low-cost, portable and miniaturized electrochemical systems for point-of-care and environmental diagnosis.
•There is an increasing demand for point-of-care miniaturized and low-cost devices.•A biosensor array integrated with a low-cost miniaturized potentiostat is presented.•A digital lock-in filter and a graphical user interface were developed in MATLAB.•Detection of TNF-α was performed by EIS as a proof of concept.
The use of dielectric spectroscopy to carry out real time observations of cells and to extract a wealth of information about their physiological properties has expanded in recent years. This ...popularity is due to the simple, easy to use, non-invasive and real time nature of dielectric spectroscopy. The ease of integrating dielectric spectroscopy with microfluidic devices has allowed the technology to further expand into biomedical research. Dielectric spectra are obtained by applying an electrical signal to cells, which is swept over a frequency range. This review covers the different methods of interpreting dielectric spectra and progress made in applications of impedance spectroscopy for cell observations. First, methods of obtaining specific electrical properties of cells (cell membrane capacitance and cytoplasm conductivity) are discussed. These electrical properties are obtained by fitting the dielectric spectra to different models and equations. Integrating models to reduce the effects of the electrical double layer are subsequently covered. Impedance platforms are then discussed including electrical cell substrate impedance sensing (ECIS). Categories of ECIS systems are divided into microelectrode arrays, interdigitated electrodes and those that allow differential ECIS measurements. Platforms that allow single cell and sub-single cell measurements are then discussed. Finally, applications of impedance spectroscopy in a range of cell observations are elaborated. These applications include observing cell differentiation, mitosis and the cell cycle and cytotoxicity/cell death. Future applications such as drug screening and in point of care applications are then covered.
Display omitted
•Dielectric spectroscopy for cell and tissue biosensing exploits the interfacial polarization, which occurs across cell membranes in response to an applied electric field.•Several electrical models can be applied to dielectric spectra to extract cell electrical parameters.•Dielectric spectroscopy setups include chamber macrosystems and electric cell substrate impedance sensing (ECIS).•ECIS platforms can be categorized into microelectrode arrays, interdigitated electrodes and differential ECIS and can obtain single cell and sub cell resolution.•Dielectric spectroscopy has uses in observation of cell differentiation, mitosis/cell cycle and cytotoxicity/cell death along with point of care applications and cytometry.
Bioimpedance spectroscopy measurements can be used for tissue characterization. These measurements can be performed in soft tissues by direct contact of a non-invasive probe consisting of two or four ...electrodes. The amount of force applied by users can be quite different, and the measurements can vary as a result. To compensate for this, we have built an electrical impedance probe (diameter 3.2 mm) with fibre optic contact-force and temperature sensors built in it. The different sensors of the probe were tested individually. The errors in magnitude and phase angle of the probe are <0.9% and <4°, respectively, for a 0.9% NaCl solution. The linear dynamic range of the force sensor was from 0 to 100 grams. An ex-vivo experiment on a section of proximal colon from a guinea-pig was performed. Twenty bioimpedance measurements were taken in a frequency range of 5 kHz to 1 MHz, while simultaneously recording the force applied. For an increase in contact pressure applied to tissue from 0 to 15.4 kPa, the maximum change in resistivity was 33% at 5 kHz and the minimum was 6.6% at 142 kHz. The probe is small enough to be introduced via the instrument port of an endoscope.
A simple bisphenol A (BPA) sensor was successfully fabricated based on ordered mesoporous carbon CMK-3 modified nano-carbon ionic liquid paste electrode (CMK-3/nano-CILPE). The nanostructure of CMK-3 ...and the surface morphologies of modified electrodes were characterized by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Electrochemical properties of the fabricated electrodes were investigated by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The fabricated sensor displayed excellent electroactivity towards bisphenol A using linear sweep voltammetry (LSV). Experimental conditions influencing the analytical performance of the modified electrode were optimized. Under optimal conditions, the oxidation peak current was proportional to BPA concentration in the range from 0.2μM to 150μM with a detection limit of 0.05μM (S/N=3). This method was successfully used for determination of BPA leached from drinking bottle and plastic bag with good recoveries.
Display omitted
•The CMK-3 modified nano-carbon ionic liquid paste electrode was fabricated.•The sensor showed good electrocatalytic activity to BPA.•The sensor displayed low resistance, ease of modification and renewability.
PDF
