A microfluidic biosensor architecture for the rapid detection of COVID-19

The lack of enough diagnostic capacity to detect severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) has been one of the major challenges in the control the 2019 COVID pandemic;this led to significant delay in prompt treatment of COVID-19 patients or accurately estimate disease situation. Current methods for the diagnosis of SARS-COV-2 infection on clinical specimens (e.g. nasal swabs) include polymerase chain reaction (PCR) based methods, such as real-time reverse transcription (rRT) PCR, real-time reverse transcription loop-mediated isothermal amplification (rRT-LAMP), and immunoassay based methods, such as rapid antigen test (RAT). These conventional PCR methods excel in sensitivity and specificity but require a laboratory setting and typically take up to six hours to obtain the results whereas RAT has a low sensitivity (typically at least 3000 TCID50/ml) although with the results with 15 mins. We have developed a robust micro-electro-mechanical system (MEMS) based impedance biosensor fit for rapid and accurate detection of SARS-COV-2 of clinical samples in the field with minimal training. The biosensor consisted of three regions that enabled concentrating, trapping, and sensing the virus present in low quantities with high selectivity and sensitivity in 40 minutes using an electrode coated with a specific SARS-COV-2 antibody cross-linker mixture. Changes in the impedance value due to the binding of the SARS-COV-2 antigen to the antibody will indicate positive or negative result. The testing results showed that the biosensor's limit of detection (LoD) for detection of inactivated SARS-COV-2 antigen in phosphate buffer saline (PBS) was as low as 50 TCID50/ml. The biosensor specificity was confirmed using the influenza virus while the selectivity was confirmed using influenza polyclonal sera. Overall, the results showed that the biosensor is able to detect SARS-COV-2 in clinical samples (swabs) in 40 min with a sensitivity of 26 TCID50/ml.

Coronavirus Label-Free Immunosensor: Preliminary Results

Real-time detection of airborne infection agents present in human breath and environmental airways, such as the human respiratory Coronavirus, is important for public health. For this, a model label-free immunosensor, based on multi-walled nanotubes (MWNT)-based screen-printed graphite electrodes (SPEs), was proposed and studied. For sensing applications, MWNTs have many advantages such as small size with larger surface area, excellent electron transfer promoting ability when used for antibody immobilization, with retention of its selectivity for potential immunosensors development. In order to verify the selectivity of the selected primary antibody (anti-CoV 229E antibody) and the effective immunocomplex formation (antigen-antibody), an in-depth voltammetric characterization of MWNT-SPEs interface was carried out during the multistep fabrication of CoV immunosensor using [Fe(CN)6]3−/4− as an electroactive probe.After that, the analytical robustness of the performances of these immunosensing platforms was estimated and verified. Indeed, a nanomolar range detection limit (180 TCID50/mL)g/mL) with excellent reproducibility (RSD% = 8%) was obtained. © The Author(s), under exclusive license to Springer Nature Switzerland AG 2023.

Organic Electrochemical Transistors (OECTs): Advancements and Exciting Prospects for Future Biosensing Applications

Over the past few decades, the field of organic electronics has depicted proliferated growth, due to the advantageous characteristics of organic semiconductors, such as tunability through synthetic chemistry, simplicity in processing, cost-effectiveness, and low-voltage operation, to cite a few. Organic electrochemical transistors (OECTs) have recently emerged as a highly promising technology in the area of biosensing and flexible electronics. OECT-based biosensors are capable of sensing brain activities, tissues, monitoring cells, hormones, DNAs, and glucose. Sensitivity, selectivity, and detection limit are the key parameters adopted for measuring the performance of OECT-based biosensors. This article highlights the advancements and exciting prospects of OECTs for future biosensing applications, such as cell-based biosensing, chemical sensing, DNA/ribonucleic acid (RNA) sensing, glucose sensing, immune sensing, ion sensing, and pH sensing. OECT-based biosensors outperform other conventional biosensors because of their excellent biocompatibility, high transconductance, and mixed electronic-ionic conductivity. At present, OECTs are fabricated and characterized in millimeter and micrometer dimensions, and miniaturizing their dimensions to nanoscale is the key challenge for utilizing them in the field of nanobioelectronics, nanomedicine, and nanobiosensing.

Carbon Nanomaterials-Based Screen-Printed Electrodes for Sensing Applications.

Electrochemical sensors consisting of screen-printed electrodes (SPEs) are recurrent devices in the recent literature for applications in different fields of interest and contribute to the expanding electroanalytical chemistry field. This is due to inherent characteristics that can be better (or only) achieved with the use of SPEs, including miniaturization, cost reduction, lower sample consumption, compatibility with portable equipment, and disposability. SPEs are also quite versatile; they can be manufactured using different formulations of conductive inks and substrates, and are of varied designs. Naturally, the analytical performance of SPEs is directly affected by the quality of the material used for printing and modifying the electrodes. In this sense, the most varied carbon nanomaterials have been explored for the preparation and modification of SPEs, providing devices with an enhanced electrochemical response and greater sensitivity, in addition to functionalized surfaces that can immobilize biological agents for the manufacture of biosensors. Considering the relevance and timeliness of the topic, this review aimed to provide an overview of the current scenario of the use of carbonaceous nanomaterials in the context of making electrochemical SPE sensors, from which different approaches will be presented, exploring materials traditionally investigated in electrochemistry, such as graphene, carbon nanotubes, carbon black, and those more recently investigated for this (carbon quantum dots, graphitic carbon nitride, and biochar). Perspectives on the use and expansion of these devices are also considered.

In Situ Electrochemical Trapping and Unraveling the Mechanism of the Toxic Intermediate Metabolite N-Acetyl-p-Benzoquinone Imine of the Acetaminophen Drug and Its Biomimetic Mediated NADH Oxidation Reaction

The integrative study of the pharmacokinetics and dynamics of a drug has been of great research interest due to its authentic description of the biomedical and clinical pros and cons. Acetaminophen (N-acetyl-4-aminophenol, AcAP) is a well-known analgesic having a high therapeutic value, including the Covid-19 treatment. However, an overdose of the drug (>200 mg/kg of men) can lead to liver toxicity. An intermediate, N-acetyl-p-benzoquinone imine (NAPQI), metabolite formation has been found to be responsible for the toxicity. For the detection of NAPQI, several ex situ techniques based on electrochemical methods followed by nuclear magnetic resonance, high-performance liquid chromatography, and LC-MS were stated. For the first time, we report an in situ electrochemical approach for AcAP oxidation and NAPQI intermediate (Mw = 149.1 g mol-1) trapping on a graphitic nanomaterial, carbon black (CB)-modified electrode in pH 7 phosphate buffer solution (CB@NAPQI). The NAPQI-trapped electrode exhibited a surface-confined redox peak at E°′ = 0.350 ± 0.05 V vs Ag/AgCl with a surface excess value of 3.52 n mol cm-2. Physicochemical characterizations by scanning electron microscopy, Raman, FTIR, and in situ electrochemical quartz crystal microbalance (EQCM) techniques supported the entrapment of the molecular species. Furthermore, the scanning electrochemical microscopy (SECM) technique has been adopted for surface-mapping the true active site of the NAPQI-trapped electrode. As a biomimetic study, the mediated oxidation reaction of NADH by CB@NAPQI was demonstrated, and the mechanistic and quantitative aspects were studied using cyclic voltammetry, rotating disc electrode, amperometry, and flow injection analysis techniques. © 2023 American Chemical Society.

RBD-Modified Polyaniline-Based Label-Free Immunosensor for Sensitive Impedimetric Detection of Anti-SARS-CoV-2 Antibodies

The emergence of the SARS-CoV-2 virus and the associated pandemic has affected the entire human population. Human susceptibility to the virus has highlighted a tremendous need for affordable diagnostic systems to manage the pandemic and monitor the effectiveness of vaccination. We have developed a simple and label-free electrochemical immunosensor for the detection of human anti-SARS-CoV-2 IgG antibodies, which consists of a supporting screen-printed carbon electrode (SPCE) modified with an electrodeposited polyaniline film and glutaraldehyde, allowing effective immobilization of the SARS-CoV-2 spike glycoprotein receptor-binding domain (RBD) as a biorecognition element. The impedimetric immunosensor showed a linear response over a wide concentration range of 0.01–10 μg mL−1, that is, 67 pM–6.7 nM, with a low detection limit of 25.9 pM. A dual working electrode configuration with a built-in negative control unit was demonstrated for practical field applications. The immunosensor was successfully used in a real serum sample from an infected patient and showed good reproducibility and fair agreement with ELISA. An optional amplification step with secondary goat anti-human IgG antibodies was demonstrated, resulting in an extended linear range and a detection limit as low as 0.93 pM.

A Low-cost Handheld Reconfigurable Impedimetric Readout System for Diagnostics of Viral Infections

This paper presents a portable impedimetric biosensor for detecting infectious diseases such as SARS-CoV-2 Infections. A bio-ready sensing electrode functionalized with SARS-CoV-2 nucleocapsid antibody was employed to quantitatively convert the concentration of nucleocapsid protein (N-protein) into impedance changes. In this paper, we proposed a readout system with a dynamic input range of 200 Ωto 1 MΩmagnitude and 0 to 180°phase. The resolution of this device is 1% and 6.5°for measuring the magnitude and phase, respectively. Herein we demonstrate and discuss the proposed system’s functionality, sensitivity, and selectivity using the clinical swab samples. As per these results, this readout system is suitable for the detection of N-protein ranging up to 10,000 pg/mL with a resolution of 56 fg/mL. The proposed impedimetric sensing system can be adopted for the detection of infectious diseases in the future. This low-cost (<$80) device using off-the-shelf is a unique candidate for batch production purposes during urgent pandemic situations. IEEE

Customizable Fabrication Process for Flexible Carbon-Based Electrochemical Biosensors

In recent research, 3D printing has become a powerful technique and has been applied in the last few years to carbon-based materials. A new generation of 3D-printed electrodes, more affordable and easier to obtain due to rapid prototyping techniques, has emerged. We propose a customizable fabrication process for flexible (and rigid) carbon-based biosensors, from biosensor design to printable conductive inks. The electrochemical biosensors were obtained on a 50 µm Kapton® (polyimide) substrate and transferred to a 500 µm PDMS substrate, using a 3D-extrusion-based printing method. The main features of our fabrication process consist of short-time customization implementation, fast small-to-medium batch production, ease of electrochemical spectroscopy measurements, and very good resolution for an extrusion-based printing method (100 µm). The sensors were designed for future integration into a smart wound dressing for wound monitoring and other biomedical applications. We increased their sensibility with electro-deposited gold nanoparticles. To assess the biosensors' functionality, we performed surface functionalization with specific anti-N-protein antibodies for SARS-CoV 2 virus, with promising preliminary results.

Influence of Nitrogen-Doped Carbon Dot and Silver Nanoparticle Modified Carbon Paste Electrodes on the Potentiometric Determination of Tobramycin Sulfate: A Comparative Study

Two inexpensive and simple methods for synthesis of carbon nanodots were applied and compared to each other, namely a hydrothermal and microwave-assisted method. The synthesized carbon nanodots were characterized using transmission electron microscopy (TEM), ultraviolet-visible (UV-Vis), photoluminescence (PL), Fourier transform-infrared spectroscopy (FTIR), and X-ray diffraction (XRD). The synthesized microwave carbon nanodots had smaller particle size and were thus chosen for better electrochemical performance. Therefore, they were used for our modification process. The proposed electrodes performance characteristics were evaluated according to the IUPAC guidelines, showing linear response in the concentration range 10−6–10−2, 10−7–10−2, and 10−8–10−2 M of tobramycin with a Nernstian slope of 52.60, 58.34, and 57.32 mV/decade for the bare, silver nanoparticle and carbon nanodots modified carbon paste electrodes, respectively. This developed potentiometric method was used for quantification of tobramycin in its co-formulated dosage form and spiked human plasma with good recovery percentages and without interference of the co-formulated drug loteprednol etabonate and excipients.

A Microfluidic Biosensor for Rapid Detection of Covid-19

We have designed, fabricated, and tested a MEMS-based impedance biosensor for accurate and rapid detection of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) using of clinical samples. The device consists of focusing region that concentrate low quantities of the virus present in the samples to a detectable threshold, trap region hat maximize the captured virus, and detection region to detect the virus with high selectivity and sensitivity, using an array of interdigitated electrodes (IDE) coated with a specific antibody. Changes in the impedance value due to the binding of the SARS-COV-2 antigen to the antibody will indicate positive or negative result. The device was able to detect inactivated SARS-COV-2 antigen present in phosphate buffer saline (PBS) with a concentration as low as 50 TCID50/ml in 30 minutes. In addition, the biosensor was able to detect SARS-COV-2 in clinical samples (swabs) with a sensitivity of 84 TCID50/ml, also in 30 minutes. © 2023 IEEE.

Virus Elimination Using High-Voltage Pulses in Aqueous Solutions

This article presents the results of the research conducted on bacteriophages inactivation using high-voltage (HV) short electric pulses. The bacteriophages are bacterial viruses, which share similar basic features in their structure to other viruses, so that they may be considered a first choice model for experimental studies on viral pathogens, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). The aqueous solution of bacteriophages was subjected to the influence of high electric-field pulses, provided by a Marx generator. It had been observed that the electric discharge was a two-stage process where the initial inrush charging current was followed by a formation of a discharge channel due to local charge trapping and a secondary burst of current. The possible explanation of inactivation of bacteriophages could be due to the formation of discharge plasma observed during the experiments, followed by likely creation of radical species. Other plausible additional mechanisms include irreversible electroporation. Two different electrode configurations with different electric-field spatial distributions were examined. A complete 100% inactivation of the bacteriophages was achieved in the system featuring the uniform field distribution. This article novelty lies in the fact that it demonstrates 100% effectiveness of the HV pulses treatment in elimination of viruses, and proposes a method of capturing these pathogens from air. IEEE

Deep Reinforcement Learning-Based Approach for Efficient and Reliable Droplet Routing on MEDA Biochips

The micro-electrode-dot-array (MEDA) architecture provides precise droplet control and real-time sensing in digital microfluidic biochips. Previous work has shown that trapped charge under microelectrodes (MCs) leads to droplets being stuck and failures in fluidic operations. A recent approach utilizes real-time sensing of MC health status, and attempts to avoid degraded electrodes during droplet routing. However, the problem with this solution is that the computational complexity is unacceptable for MEDA biochips of realistic size. Consequently, in this work, we introduce a deep reinforcement learning (DRL)-based approach to bypass degraded electrodes and enhance the reliability of routing. The DRL model utilizes the information of health sensing in real time to proactively reduce the likelihood of charge trapping and avoid using degraded MCs. Simulation results show that our approach provides effective routing strategies for COVID-19 testing protocols. We also validate our DRL-based approach using fabricated prototype biochips. Experimental results show that the developed DRL model completed the routing tasks using a fewer number of clock cycles and shorter total execution time, compared with a baseline routing method. Moreover, our DRL-based approach provides reliable routing strategies even in the presence of degraded electrodes. Our experimental results show that the proposed DRL-based routing is robust to occurrences of electrode faults, as well as increases the lifetime and usability of microfluidic biochips compared to existing strategies.

The performance evaluation of pleated electret filters enhanced by electrostatic enhanced method

The filtration efficiency deterioration over operating time due to exposure to particles, organic solvents and other factors is an obvious defect of electret filter, especially during the coronavirus pandemic. Electrostatic enhanced method has been proposed as a promising way to improve the filtration efficiency and service time of electret filters without increasing the pressure drop. In this work, the effect of discharge electrode structure and operation mode of the electrostatic enhanced structure(EES) on the filtration efficiency of commercial pleated electret filters were studied firstly, then the EES was installed in a special designed prototype air purifier, two key indicators of air purifiers(clean air delivery rate (CADR) and cumulate clean mass (CCM)) were tested to evaluate the actual performance improvement of electret filters by the electrostatic enhanced method. It was found that the discharge electrode structure had significant influence on the filtration efficiency and multi-wire array electrode was more suitable for the discharge electrode to pleated filter to ground mesh structure used in this paper. The decayed electrostatic charges of pleated electret filter cannot be recharged again through the EES in actual operation condition. The filtration efficiency improvement of the test pleated electret filters was dominantly contributed by particle charging. The filter polarizing induced by the external electric field was helpful in increasing the filtration efficiency when the particles were charged while its effect on uncharged particles was almost negligible. Besides, the actual performance of the prototype air purifier indicated that the EES can alleviate the filtration efficiency deterioration of test electret filters and extend the service life of H11 and H13 filters by more than 3 and 1.5 times respectively according to the CCM test results. © 2023 IOP Publishing Ltd.

Design of real-time ECG monitoring wearable equipment based on the Holter system

The COVID-19 epidemic has largely restricted the traditional offline medical treatment model. In this study, we designed ECG monitoring smart clothing based on the Holter system after identifying and analyzing the needs of patients and doctors. This clothing is a wearable device that integrates monitoring and remote diagnosis, building a general network platform to realize remote data transfer sharing and online interactive auxiliary diagnosis. Wearable clothing that can monitor ECG in real time is designed and developed by intelligently integrating limb lead wires, conductive fiber fabrics, lead interfaces, and electrode signal storage receivers by using the human body sensing conduction principle of real-time ECG monitoring. Wearable real-time ECG monitoring clothing can help patients achieve fast virtual medical care and auxiliary diagnosis, and solve the design issues with electrode signal storage receivers. © 2022 IEEE.

Continuous Glucose Monitoring in Hypoxic Environments Based on Water Splitting-Assisted Electrocatalysis

Conventional enzyme-based continuous glucose sensors in interstitial fluid usually rely on dissolved oxygen as the electron-transfer mediator to bring electrons from oxidase to electrode while generating hydrogen peroxide. This may lead to several problems. First, the sensor may provide biased detection results owing to fluctuation of oxygen in interstitial fluid. Second, the polymer coatings that regulate the glucose/oxygen ratio can affect the dynamic response of the sensor. Third, the glucose oxidation reaction continuously produces corrosive hydrogen peroxide, which may compromise the long-term stability of the sensor. Here, we introduce an oxygen-independent nonenzymatic glucose sensor based on water splitting-assisted electrocatalysis for continuous glucose monitoring. For the water splitting reaction (i.e., hydrogen evolution reaction), a negative pretreatment potential is applied to produce a localized alkaline condition at the surface of the working electrode for subsequent nonenzymatic electrocatalytic oxidation of glucose. The reaction process does not require the participation of oxygen;therefore, the problems caused by oxygen can be avoided. The nonenzymatic sensor exhibits acceptable sensitivity, reliability, and biocompatibility for continuous glucose monitoring in hypoxic environments, as shown by the in vitro and in vivo measurements. Therefore, we believe that it is a promising technique for continuous glucose monitoring, especially for clinically hypoxic patients.

Electrochemical Sensing Platform Based on Renewable Carbon Modified with Antimony Nanoparticles for Methylparaben Detection in Personal Care Products

This paper describes for the first time the surface modification of glassy carbon (GC) electrodes with bamboo-based renewable carbon (RC) and antimony nanoparticles (SbNPs) for the determination of methylparaben (MePa) in personal care products (PCPs). The synthesized RC-SbNP material was successfully characterized by scanning electron microcopy, energy-dispersive X-ray spectroscopy and cyclic voltammetry. The proposed sensor was applied in the detection of MePa using the optimized parameters by differential pulse voltammetry (DPV). The analytical range for detection of MePa was 0.2 to 9.0 µmol L−1, with limits of detection and quantification of 0.05 µmol L−1 and 0.16 µmol L−1, respectively. The determination of MePa in real PCP samples was performed using the proposed GC/RC-SbNP sensor by DPV and UV-vis spectrophotometry as comparative methodology. The use of RC-SbNP material for the development of electrochemical sensors brings a fresh approach to low-cost devices for MePa analysis.

Self-powered digital microfluidics driven by rotational triboelectric nanogenerator

Digital microfluidic (DMF) has emerged as one of the most popular microfluidic platforms for sample-preparation in biochemical analysis and lab-on-a-chip applications. Operated with electrowetting on dielectric (EWOD) mechanism, DMF conventionally requires an external power source to provide the actuation voltage, which limited its portability and broader applications in point-of-care testing (POCT) environment. Herein, a DMF device, self-powered by triboelectric nanogenerator (TENG) is presented. TENG possesses a number of unique characteristics, and is very attractive to be integrated with DMF. It only requires a simple configuration with low-cost fabrication that can improve the DMF portability, but it also provides high voltage, low current output characteristics that are consistent with the EWOD actuation requirements. Basic droplet manipulations, including transportation, split, merge, dispense, and even elongate to follow the electrode patterns of alphabets, on a DMF device powered with manually-rotated Disk-TENG are demonstrated for the first time. Further, droplets containing samples and reagents are transported and mixed on the programmed electrode patterns on the chip to conduct chemical reactions, including nucleic acid amplification and phenol red test, showing that Disk-TENG can serve as the power source for DMF chips in POCT applications. © 2023 Elsevier Ltd

Molecularly imprinted polymer-modified carbon paste electrodes (MIP-CPE): A review on sensitive electrochemical sensors for pharmaceutical determinations

Recent years have been associated with the development of various sensor-based technologies in response to the undeniable need for the rapid and precise analysis of an immense variety of pharmaceuticals. In this regard, special attention has been paid to the design and fabrication of sensing platforms based on electrochemical detection methods as they can offer many advantages, such as portability, ease of use, relatively cheap instruments, and fast response times. Carbon paste electrodes (CPEs) are among the most promising conductive electrodes due to their beneficial properties, including ease of electrode modification, facile surface renewability, low background currents, and the ability to modify with different analytes. However, their widespread use is affected by the lack of sufficient selectivity of CPEs. Molecularly imprinted polymers (MIPs) composed of tailor-made cavities for specific target molecules are appealing complementary additives that can overcome this limitation. Accordingly, adding MIP to the carbon paste matrix can contribute to the required selectivity of sensing platforms. This review aims to present a categorized report on the recent research and the outcomes in the combinatory fields of MIPs and CPEs for determining pharmaceuticals in complex and simple matrices. CPEs modified with MIPs of various pharmaceutical compounds, including analgesic drugs, antibiotics, antivirals, cardiovascular drugs, as well as therapeutic agents affecting the central nervous system (CNS), will be addressed in detail.Copyright © 2023 Elsevier B.V.

Study of the Process of Destruction of Harmful Microorganisms in Water

In this scientific work, the problem of studying the process of destruction of microorganisms in water by an Etro-03 device based on electric corona discharge is considered. In the research, a special Etro-03 ozonator device was developed for clearing water of biological pollutants. Testing of the installation was carried out in order to disinfect surface water in the Kapshagai reservoir. During the research, various harmful microorganisms were found in the composition of the primary water that did not meet the maximum permissible concentration (MPC). For example, coliphages, coli-indices, and the number of microbes in general came across in large numbers. During the technological process, various amounts of ozone (O3) were released into the water, the amount and effective economic indicators of which were determined. In the same way, the effective time of the decontamination process was determined. During the research process, an algorithm of theoretical calculations was developed, and a mathematical model was given to bring 1m3 of surface water as the indicator for which sanitary rules and norms are approved.

Duplex Electrochemical Microfluidic Sensor for COVID-19 Antibody Detection: Natural versus Vaccine-Induced Humoral Response.

The rapid transmission and resilience of coronavirus disease 2019 (COVID-19) have led to urgent demands in monitoring humoral response for effective vaccine development, thus a multiplex co-detection platform to discriminate infection-induced from vaccine-induced antibodies is needed. Here a duplex electrochemical immunosensor for co-detection of anti-nucleocapsid IgG (N-IgG) and anti-spike IgG (S-IgG) is developed by using a two-working electrode system, via an indirect immunoassay, with antibody quantification obtained by differential pulse voltammetry. The screen-printed electrodes (SPEs) are modified by carbon black and electrodeposited gold nanoflowers for maximized surface areas, enabling the construction of an immunological chain for S-IgG and N-IgG electrochemical detection with enhanced performance. Using an optimized immunoassay protocol, a wide linear range between 30-750 and 20-1000 ng mL-1 , and a limit of detection of 28 and 15 ng mL-1 are achieved to detect N-IgG and S-IgG simultaneously in serum samples. This duplex immunosensor is then integrated in a microfluidic device to obtain significantly reduced detection time (≤ 7 min) while maintaining its analytical performance. The duplex microfluidic immunosensor can be easily expanded into multiplex format to achieve high throughput screening for the sero-surveillance of COVID-19  and other infectious diseases.