Optical Biosensors for Diagnostics of Infectious Viral Disease: A Recent Update.

The design and development of biosensors, analytical devices used to detect various analytes in different matrices, has emerged. Biosensors indicate a biorecognition element with a physicochemical analyzer or detector, i.e., a transducer. In the present scenario, various types of biosensors have been deployed in healthcare and clinical research, for instance, biosensors for blood glucose monitoring. Pathogenic microbes are contributing mediators of numerous infectious diseases that are becoming extremely serious worldwide. The recent outbreak of COVID-19 is one of the most recent examples of such communal and deadly diseases. In efforts to work towards the efficacious treatment of pathogenic viral contagions, a fast and precise detection method is of the utmost importance in biomedical and healthcare sectors for early diagnostics and timely countermeasures. Among various available sensor systems, optical biosensors offer easy-to-use, fast, portable, handy, multiplexed, direct, real-time, and inexpensive diagnosis with the added advantages of specificity and sensitivity. Many progressive concepts and extremely multidisciplinary approaches, including microelectronics, microelectromechanical systems (MEMSs), nanotechnologies, molecular biology, and biotechnology with chemistry, are used to operate optical biosensors. A portable and handheld optical biosensing device would provide fast and reliable results for the identification and quantitation of pathogenic virus particles in each sample. In the modern day, the integration of intelligent nanomaterials in the developed devices provides much more sensitive and highly advanced sensors that may produce the results in no time and eventually help clinicians and doctors enormously. This review accentuates the existing challenges engaged in converting laboratory research to real-world device applications and optical diagnostics methods for virus infections. The review's background and progress are expected to be insightful to the researchers in the sensor field and facilitate the design and fabrication of optical sensors for life-threatening viruses with broader applicability to any desired pathogens.

Textile-based wearable solid-contact flexible fluoride sensor: Toward biodetection of G-type nerve agents.

Rising global concerns posed by chemical and biological threat agents highlight the critical need to develop reliable strategies for the real-time detection of such threats. While wearable sensing technology is well suited to fulfill this task, the use of on-body devices for rapid and selective field identification of chemical agents is relatively a new area. This work describes a flexible printed textile-based solid-contact potentiometric sensor for the selective detection of fluoride anions liberated by the biocatalytic hydrolysis of fluorine-containing G-type nerve agents (such as sarin or soman). The newly developed solid-contact textile fluoride sensor relies on a fluoride-selective bis(fluorodioctylstannyl)methane ionophore to provide attractive analytical performance with near-Nernstian sensitivity and effective discrimination against common anions, along with excellent reversibility and repeatability for dynamically changing fluoride concentrations. By using stress-enduring printed inks and serpentine structures along with stretchable textile substrates, the resulting textile-based fluoride sensor exhibits robust mechanical resiliency under severe mechanical strains. Such realization of an effective textile-based fluoride-selective electrode allowed biosensing of the nerve-agent simulant diisopropyl fluorophosphate (DFP), in connection to immobilized organophosphorus acid anhydrolylase (OPAA) or organophosphorus hydrolase (OPH) enzymes. A user-friendly portable electronic module transmits data from the new textile-based potentiometric biosensor wirelessly to a nearby smartphone for alerting the wearer instantaneously about potential chemical threats. While expanding the scope of wearable solid-contact anion sensors, such a textile-based potentiometric fluoride electrode transducer offers particular promise for effective discrimination of G-type neurotoxins from organophosphate (OP) pesticides, toward specific field detection of these agents in diverse defense settings.

Electrochemical diagnostics of infectious viral diseases: Trends and challenges.

Infectious diseases caused by viruses can elevate up to undesired pandemic conditions affecting the global population and normal life function. These in turn impact the established world economy, create jobless situations, physical, mental, emotional stress, and challenge the human survival. Therefore, timely detection, treatment, isolation and prevention of spreading the pandemic infectious diseases not beyond the originated town is critical to avoid global impairment of life (e.g., Corona virus disease - 2019, COVID-19). The objective of this review article is to emphasize the recent advancements in the electrochemical diagnostics of twelve life-threatening viruses namely - COVID-19, Middle east respiratory syndrome (MERS), Severe acute respiratory syndrome (SARS), Influenza, Hepatitis, Human immunodeficiency virus (HIV), Human papilloma virus (HPV), Zika virus, Herpes simplex virus, Chikungunya, Dengue, and Rotavirus. This review describes the design, principle, underlying rationale, receptor, and mechanistic aspects of sensor systems reported for such viruses. Electrochemical sensor systems which comprised either antibody or aptamers or direct/mediated electron transfer in the recognition matrix were explicitly segregated into separate sub-sections for critical comparison. This review emphasizes the current challenges involved in translating laboratory research to real-world device applications, future prospects and commercialization aspects of electrochemical diagnostic devices for virus detection. The background and overall progress provided in this review are expected to be insightful to the researchers in sensor field and facilitate the design and fabrication of electrochemical sensors for life-threatening viruses with broader applicability to any desired pathogens.

An integrated microcatheter-based dual-analyte sensor system for simultaneous, real-time measurement of propofol and fentanyl.

According to the American Society of Anesthesiologists Closed Claims Database, one of three drug-related errors is the result administrating an incorrect dose. Directly measuring drug concentration removes the uncertainty in the dose-concentration relationship and addresses inter- and intra-subject variabilities that affect the pharmacokinetics of anesthetics. Here we describe a dual-analyte microcatheter-based electrochemical sensor capable of simultaneous real-time continuous monitoring of fentanyl (FTN) and propofol (PPF) drugs simultaneously in the operating rooms. Such a dual PPF/FTN catheter sensor relies on embedding two different modified carbon paste (CP)-packed working electrodes along with Ag/AgCl microwire reference electrodes within a mm-wide Teflon tube, and uses a square wave voltammetric (SWV) technique. The composition of each working electrode was judiciously tailored to cover the concentration range of interest for each analyte. A polyvinyl chloride (PVC) organic polymer coating on the surface of CP electrode enabled selective and sensitive PPF measurements in µM range. The detection of nM FTN levels was achieved through a multilayered nanostructure-based surface modification protocol, including a CNT-incorporated CP transducer modified by a hybrid of electrodeposited Au nanoparticles and electrochemically reduced graphene oxide (erGO) and a PVC outer membrane. The long-term monitoring capability of the dual sensor was demonstrated in a protein-rich artificial plasma medium. The promising antibiofouling behavior of the catheter-based multiplexed sensor was also illustrated in whole blood samples. The new integrated dual-sensor microcatheter platform holds considerable promise towards real-time, in-vivo detection of the anesthetic drugs, propofol and fentanyl, during surgical procedures towards significantly improved safe delivery of anesthetic drugs.

Epidermal Enzymatic Biosensors for Sweat Vitamin C: Toward Personalized Nutrition.

Recent advances in wearable sensor technologies offer new opportunities for improving dietary adherence. However, despite their tremendous promise, the potential of wearable chemical sensors for guiding personalized nutrition solutions has not been reported. Herein, we present an epidermal biosensor aimed at following the dynamics of sweat vitamin C after the intake of vitamin C pills and fruit juices. Such skin-worn noninvasive electrochemical detection of sweat vitamin C has been realized by immobilizing the enzyme ascorbate oxidase (AAOx) on flexible printable tattoo electrodes and monitoring changes in the vitamin C level through changes in the reduction current of the oxygen cosubstrate. The flexible vitamin C tattoo patch was fabricated on a polyurethane substrate and combined with a localized iontophoretic sweat stimulation system along with amperometric cathodic detection of the oxygen depletion during the enzymatic reaction. The enzyme biosensor offers a highly selective response compared to the common direct (nonenzymatic) voltammetric measurements, with no effect on electroactive interfering species such as uric acid or acetaminophen. Temporal vitamin C profiles in sweat are demonstrated using different subjects taking varying amounts of commercial vitamin C pills or vitamin C-rich beverages. The dynamic rise and fall of such vitamin C sweat levels is thus demonstrated with no interference from other sweat constituents. Differences in such dynamics among the individual subjects indicate the potential of the epidermal biosensor for personalized nutrition solutions. The flexible tattoo patch displayed mechanical resiliency to multiple stretching and bending deformations. In addition, the AAOx biosensor is shown to be useful as a disposable strip for the rapid in vitro detection of vitamin C in untreated raw saliva and tears following pill or juice intake. These results demonstrate the potential of wearable chemical sensors for noninvasive nutrition status assessments and tracking of nutrient uptake toward detecting and correcting nutritional deficiencies, assessing adherence to vitamin intake, and supporting dietary behavior change.

Continuous Opioid Monitoring along with Nerve Agents on a Wearable Microneedle Sensor Array.

There are urgent needs for sensing devices capable of distinguishing between episodes of opioid overdose and nerve agent poisoning. This work presents a wearable microneedle sensor array for minimally invasive continuous electrochemical detection of opioid (OPi) and organophosphate (OP) nerve agents on a single patch platform. The new multimodal microneedle sensor array relies on unmodified and organophosphorus hydrolase (OPH) enzyme-modified carbon paste (CP) microneedle electrodes for square wave voltammetric (SWV) detection of the fentanyl and nerve agent targets, respectively. Such real-time simultaneous sensing provides distinct unique information, along with attractive analytical performance, including high sensitivity, selectivity, and stability, for real-time on-body OPi-OP analysis. The patch represents the first sensing device capable of continuously monitoring fentanyl down to the nanomolar level through a nanomaterial-based multilayered surface architecture. Applicability of the sensor array toward opioids screening is demonstrated for morphine and norfentanyl. Successful OPi-OP detection conducted in a skin-mimicking phantom gel demonstrates the suitability of the device for rapid on-body sensing. Such progress toward continuous minimally invasive transdermal analysis of drugs of abuse and nerve agents holds promise for rapid countermeasures for protecting soldiers, civilians, and healthcare personnel.

A review on recent developments in optical and electrochemical aptamer-based assays for mycotoxins using advanced nanomaterials.

This review (with 163 refs) covers the recent developments of nanomaterial-based optical and electrochemical sensors for mycotoxins. The review starts with a brief discussion on occurrence, distribution, toxicity of mycotoxins and the legislations in monitoring their levels. It further outlines the research methods, various recognition matrices and the strategies involved in the development of highly sensitive and selective sensor systems. It also points out the salient features and importance of aptasensors in the detection of mycotoxins along with the different immobilization methods of aptamers. The review meticulously discusses the performance of different optical and electrochemical sensors fabricated using aptamers coupled with nanomaterials (CNT, graphene, metal nanoparticles and metal oxide nanoparticles). The review addresses the limitations in the current developments as well as the future challenges involved in the successful construction of aptasensors with the functionalized nanomaterials. Graphical abstract Recent developments in nanomaterial based aptasensors for mycotoxins are summarized. Specifically, the efficiency of the nanomaterial coupled aptasensors (such as CNT, graphene, metal nanoparticles and metal oxide nanoparticles) in optical and electrochemical methods are discussed.

Polymer scaffold layers of screen-printed electrodes for homogeneous deposition of silver nanoparticles: application to the amperometric detection of hydrogen peroxide.

A method is described for electrochemical oxidation of polymers on the surface of screen-printed electrodes (SPCE). These act as scaffold layers for homogeneous deposition of silver nanoparticles (AgNPs). Hexamethylenediamine (HMDA) and poly(ethylene glycol) were immobilized on the SPCE surface via electrochemical oxidation. AgNPs were then electrodeposited on the scaffolds on the SPCE. This type of different carbon chain containing materials like PEG and HMDA act as big tunnels for electron mobility and are useful for the homogenous deposition of AgNPs on the SPCE surface without agglomeration. The resulting sensor was applied to the determination of hydrogen peroxide (H2O2) as a model analyte. It is found to display favorable catalytic and conductive properties towards the reduction of H2O2. Cyclic voltammetry and amperometry revealed that the modified electrode performs better than other modified SPCEs. Best operated at a potential of around -0.61 V (vs Ag|AgCl), the amperometric response is linear in the 10-180 µM H2O2 concentration range and the detection limit is 1.5 µM. The sensor is stable and reproducible. The resultant sensor was appplied to toothpaste analysis, and good recovery values were gained. Graphical abstractSchematic representation of electropolymerization of poly(ethylene glycol) and hexamethylenediamine scaffold layers on screen-printed electrodes for homogeneous electrodeposition of silver nanoparticles. This electrode was applied for the amperometric determination of hydrogen peroxide.

Wearable Electrochemical Microneedle Sensor for Continuous Monitoring of Levodopa: Toward Parkinson Management.

Levodopa is the most effective medication for treating Parkinson's disease (PD). However, because dose optimization is currently based on patients' report of symptoms, which are difficult for patients to describe, the management of PD is challenging. We report on a microneedle sensing platform for continuous minimally invasive orthogonal electrochemical monitoring of levodopa (L-Dopa). The new multimodal microneedle sensing platform relies on parallel simultaneous independent enzymatic-amperometric and nonenzymatic voltammetric detection of L-Dopa using different microneedles on the same sensor array patch. Such real-time orthogonal L-Dopa sensing offers a built-in redundancy and enhances the information content of the microneedle sensor arrays. This is accomplished by rapid detection of L-Dopa using square-wave voltammetry and chronoamperometry at unmodified and tyrosinase-modified carbon-paste microneedle electrodes, respectively. The new wearable microneedle sensor device displays an attractive analytical performance with the enzymatic and nonenzymatic L-Dopa microneedle sensors offering different dimensions of information while displaying high sensitivity (with a low detection limit), high selectivity in the presence of potential interferences, and good stability in artificial interstitial fluid (ISF). The attractive analytical performance and potential wearable applications of the microneedle sensor array have been demonstrated in a skin-mimicking phantom gel as well as upon penetration through mice skin. The design and attractive analytical performance of the new orthogonal wearable microneedle sensor array hold considerable promise for reliable, continuous, minimally invasive monitoring of L-Dopa in the ISF toward optimizing the dosing regimen of the drug and effective management of Parkinson disease.

Silver nanoparticles impregnated chitosan layered carbon nanotube as sensor interface for electrochemical detection of clopidogrel in-vitro.

Continuous periodical monitoring of clopidogrel in physiological body fluids is indispensable in medical diagnosis of heart ailments and cardiovascular diseases. A highly sensitive electrochemical sensor has been fabricated with silver nanoparticles embedded chitosan-carbon nanotube hybrid composite (AgChit-CNT) as sensor interface for detection of the important anti-platelet drug, clopidogrel (CLP). Synthesized AgChit-CNT nanocomposite is examined by x-ray diffraction, Raman spectroscopy and field emission scanning electron microscopy for its chemical and structural characteristics. Crystalline silver nanoparticles of about 35 nm are well distributed in the composite and have formed continuous chain like linkages with CNTs all throughout. Electrochemical responses of the fabricated AgChit-CNT nanocomposite electrode for the determination of CLP have been examined by cyclic voltammetry and electrochemical impedance spectroscopy. The nanoAg patterned CNT nanocomposite interface acts as an excellent electron transfer mediator towards the oxidation of clopidogrel. Electrochemical determination of CLP was investigated by differential pulse voltammetry (DPV) and amperometric analysis under optimized conditions. The limit of detection by DPV and amperometry were 30 nM and 10 nM, respectively, and the time of the analysis is as low as 10 s. Practical applicability for determination in artificially prepared urine and pharmaceutical formulation has been examined with good recovery limits of 95.2 to 102.6%.

Ionic Liquid-Modified Disposable Electrochemical Sensor Strip for Analysis of Fentanyl.

The increasing prevalence of fentanyl and its analogues as contaminating materials in illicit drug products presents a major hazard to first responder and law enforcement communities. Electrochemical techniques have the potential to provide critical information to these personnel via rapid, facile field detection of these materials. Here we demonstrate the use of cyclic square wave voltammetry (CSWV) with screen-printed carbon electrodes (SPCE), modified with the room temperature ionic liquid (RTIL) 1-butyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide [C4C1pyrr][NTf2], toward such rapid "on-the-spot" fentanyl detection. This CSWV-based disposable sensor strip system provides an information-rich electrochemical fingerprint of fentanyl, composed of an initial oxidation event at +0.556 V (vs Ag/AgCl) and a reversible reduction and oxidation reaction at -0.235 and -0.227 V, respectively. The combined current and potential characteristics of these anodic and cathodic fentanyl peaks, generated using two CSWV cycles, thus lead to a distinct electrochemical signature. This CSWV profile facilitates rapid (1 min) identification of the target opioid at micromolar concentrations in the presence of other cutting agents commonly found in illicit drug formulations. The new protocol thus holds considerable promise for rapid decentralized fentanyl detection at the "point of need".

Progress on nanostructured electrochemical sensors and their recognition elements for detection of mycotoxins: A review.

Nanomaterial-embedded sensors have been developed and applied to monitor various targets. Mycotoxins are fungal secondary metabolites that can exert carcinogenic, mutagenic, teratogenic, immunotoxic, and estrogenic effects on humans and animals. Consequently, the need for the proper regulation on foodstuff and feed materials has been recognized from times long past. This review provides an overview of recent developments in electrochemical sensors and biosensors employed for the detection of mycotoxins. Basic aspects of the toxicity of mycotoxins and the implications of their detection are comprehensively discussed. Furthermore, the development of different molecular recognition elements and nanomaterials required for the detection of mycotoxins (such as portable biosensing systems for point-of-care analysis) is described. The current capabilities, limitations, and future challenges in mycotoxin detection and analysis are also addressed.

Label free aptasensor for ochratoxin A detection using polythiophene-3-carboxylic acid.

This work demonstrates the development of electrochemical aptasensor using ochratoxin A (OTA) aptamers. Different aptamer coupling strategies were tested using polythiophene-carboxylic acid (PT3C) and polypyrrole-3-carboxylic acid (PP3C). The best sensitivity was recorded by polythiophene-3-carboxylic acid (PT3C) on screen-printed carbon electrode (SPCE) to attain the direct detection of OTA. The quantification of OTA was achieved by using electrochemical impedance spectroscopy. A good dynamic range 0.125-2.5 ng ml-1 was obtained for OTA with limit of detection (LOD) 0.125 ng ml-1 and Limit of quantification (LOQ) 0.3 ng ml-1 respectively. The good reproducibility was recorded with RSD% of 3.68. The obtained straight line equation was y = 0.4061 × + 1.03, r = 0.99. For real sample applications, the developed aptasensors were demonstrated in coffee samples. The aptasensor displayed good recovery values in the range 88-89%, thus exhibited the effectiveness of proposed aptasensor for such complex matrices.

Carboxylic group riched graphene oxide based disposable electrochemical immunosensor for cancer biomarker detection.

In this work, we have developed for the first time a carboxylic group riched graphene oxide based disposable electrochemical immunosensor for cancer biomarker detection using methylene blue (MB). The developed immunosensor is highly sensitive for detection of biomarker Mucin1 (MUC1) in human serum samples. Development of this disposable electrochemical immunosensor was premeditated by applying specific monoclonal antibodies against MUC1. In this method, we explored highly conductive surface of carboxylic group (-COOH-) rich graphene oxide (GO) on screen-printed carbon electrodes (SPCE). This modified GO-COOH-SPCE was employed for the detection of MUC1 protein based on the reaction with methylene blue (MB) redox probe using differential pulse voltammetry (DPV) technique. Developed immunosensor exhibited good detection range for MUC1 with excellent linearity (0.1 U/mL- 2 U/mL), with a limit of detection of 0.04 U/mL. Upon potential application of developed biosensor, good recoveries were recorded in the range of 96-96.67% with % R.S.D 4.2. Analytical performance of the developed immunosensor assures the applicability in clinical diagnostic applications.

Tetramethyl-6-carboxyrhodamine quenching-based aptasensing platform for aflatoxin B1: Analytical performance comparison of two aptamers.

In this study, a simple TAMRA (tetramethyl-6-carboxyrhodamine) quenching-based aptasensing platform was designed for the detection of aflatoxin B1 (AFB1). Here, we compared the analytical performance of two aptamer sequences: seqA and seqB. The AFB1 detection was based on the interactions of FAM (carboxyfluorescein)-labeled aptamer with TAMRA-labeled DNA complementary strand in the presence and absence of target analyte. Under optimized experimental conditions, TAMRA-labeled strand quenched the fluorescence response of FAM-labeled aptamer due to the noncovalent interaction between the two DNA strands. The binding of AFB1 induced the complex formation and weakened the interaction between FAM-labeled aptamer and TAMRA-labeled complementary strand, resulting in the fluorescence recovery. By using this principle concept, an assay was constructed for the detection of AFB1. The method exhibited good sensitivity, good selectivity with a limit of detection of 0.2 ng ml(-1), and a wide linear range from 0.25 to 32 ng ml(-1). For real sample application, the aptasensors were tested in beer and wine samples, with good recovery rates obtained for AFB1 detection.