Copper Nanoparticles and Reduced Graphene Oxide as an Electrode Modifier for the Development of an Electrochemical Sensing Platform for Chloroquine Phosphate Determination.

This study describes the use of copper nanoparticles (CuNPs) and reduced graphene oxide (rGO) as an electrode modifier for the determination of chloroquine phosphate (CQP). The synthetized rGO-CuNPs composite was morphologically characterized using scanning electron microscopy and electrochemically characterized using cyclic voltammetry. The parameters were optimized and the developed electrochemical sensor was applied in the determination of CQP using square-wave voltammetry (SWV). The analytical range for the determination of CQP was 0.5 to 110 µmol L-1 (one of the highest linear ranges for CQP considering electrochemical sensors), with limits of detection and quantification of 0.23 and 0.78 µmol L-1, respectively. Finally, the glassy carbon (GC) electrode modified with rGO-CuNPs was used for quantification of CQP in tap water; a study was carried out with interferents using SWV and obtained great results. The use of rGO-CuNP material as an electrode modifier was thus shown to be a good alternative for the development of low-cost devices for CQP analysis.

Automatic Analysis of Isothermal Amplification via Impedance Time-Constant-Domain Spectroscopy: A SARS-CoV-2 Case Study

The development of sensitive and affordable testing devices for infectious diseases is essential to preserve public health, especially in pandemic scenarios. In this work, we have developed an attractive analytical method to monitor products of genetic amplification, particularly the loop-mediated isothermal amplification reaction (RT-LAMP). The method is based on electrochemical impedance measurements and the distribution of relaxation times model, to provide the so-called time-constant-domain spectroscopy (TCDS). The proposed method is tested for the SARS-CoV-2 genome, since it has been of worldwide interest due to the COVID-19 pandemic. Particularly, once the method is calibrated, its performance is demonstrated using real wastewater samples. Moreover, we propose a simple classification algorithm based on TCDS data to discriminate among positive and negative samples. Results show how a TCDS-based method provides an alternative mechanism for label-free and automated assays, exhibiting robustness and specificity for genetic detection.

An ultrasensitive electrochemical sensor for detecting porcine epidemic diarrhea virus based on a Prussian blue-reduced graphene oxide modified glassy carbon electrode.

This study developed a novel, ultrasensitive sandwich-type electrochemical immunosensor for detecting the porcine epidemic diarrhea virus (PEDV). By electrochemical co-deposition of graphene and Prussian blue, a Prussian blue-reduced graphene oxide-modified glassy carbon electrode was made, further modified with PEDV-monoclonal antibodies (mAbs) to create a new PEDV immunosensor using the double antibody sandwich technique. The electrochemical characteristics of several modified electrodes were investigated using cyclic voltammetry (CV). We optimized the pH levels and scan rate. Additionally, we examined specificity, reproducibility, repeatability, accuracy, and stability. The study indicates that the immunosensor has good performance in the concentration range of 1 × 101.88 to 1 × 105.38 TCID50/mL of PEDV, with a detection limit of 1 × 101.93 TCID50/mL at a signal-to-noise ratio of 3σ. The composite membranes produced via co-deposition of graphene and Prussian blue effectively increased electron transport to the glassy carbon electrode, boosted response signals, and increased the sensitivity, specificity, and stability of the immunosensor. The immunosensor could accurately detect PEDV, with results comparable to real-time quantitative PCR. This technique was applied to PEDV detection and served as a model for developing additional immunosensors for detecting hazardous chemicals and pathogenic microbes.

Green ecofriendly electrochemical sensing platform for the sensitive determination of doxycycline.

The detection of pharmaceutical compounds in extremely low concentrations remains a challenge despite recent advancements in electrochemical sensing. In this study, a green hydrothermally synthesized nickel hydroxide-graphene hybrid material was used for the point-of-care determination of the antibiotic doxycycline (DOXY), which is a promising treatment for COVID-19 and other infections. The electrochemical sensor, based on a screen-printed electrode modified with the hybrid material, was able to detect DOXY in the range of 5.1 × 10-8 to 1.0 × 10-4 M, with a low detection limit of 9.6 × 10-9 M. This approach paves the way for eco-friendly and sustainable methods of nanomaterial synthesis for electrochemical analyses, particularly in point-of-care drug monitoring, and has the potential to improve access to testing platforms.

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.

Advances in Electrochemical Biosensors Based on Nanomaterials for Protein Biomarker Detection in Saliva.

The focus on precise medicine enhances the need for timely diagnosis and frequent monitoring of chronic diseases. Moreover, the recent pandemic of severe acute respiratory syndrome coronavirus 2 poses a great demand for rapid detection and surveillance of viral infections. The detection of protein biomarkers and antigens in the saliva allows rapid identification of diseases or disease changes in scenarios where and when the test response at the point of care is mandated. While traditional methods of protein testing fail to provide the desired fast results, electrochemical biosensors based on nanomaterials hold perfect characteristics for the detection of biomarkers in point-of-care settings. The recent advances in electrochemical sensors for salivary protein detection are critically reviewed in this work, with emphasis on the role of nanomaterials to boost the biosensor analytical performance and increase the reliability of the test in human saliva samples. Furthermore, this work identifies the critical factors for further modernization of the nanomaterial-based electrochemical sensors, envisaging the development and implementation of next-generation sample-in-answer-out systems.

Loop-mediated isothermal amplification-based electrochemical sensor for detecting SARS-CoV-2 in wastewater samples.

The current pandemic COVID-19 caused by the coronavirus SARS-CoV-2, has generated different economic, social and public health problems. Moreover, wastewater-based epidemiology could be a predictor of the virus rate of spread to alert on new outbreaks. To assist in epidemiological surveillance, this work introduces a simple, low-cost and affordable electrochemical sensor to specifically detect N and ORF1ab genes of the SARS-CoV-2 genome. The proposed sensor works based on screen-printed electrodes acting as a disposable test strip, where the reverse transcription loop-mediated isothermal amplification (RT-LAMP) reaction takes place. Electrochemical detection relies upon methylene blue as a redox intercalator probe, to provide a diffusion-controlled current encoding the presence and concentration of RT-LAMP products, namely amplicons or double-stranded DNA. We test the performance of the sensor by testing real wastewater samples using end-point and time course measurements. Results show the ability of the electrochemical test strip to specifically detect and quantify RT-LAMP amplicons below to ~ 2.5 × 10-6 ng/µL exhibiting high reproducibility. In this sense, our RT-LAMP electrochemical sensor is an attractive, efficient and powerful tool for rapid and reliable wastewater-based epidemiology studies.

A Comprehensive Overview of Sensors Applications for the Diagnosis of SARS-CoV-2 and of Drugs Used in its Treatment.

During the COVID-19 process, determination-based analytical chemistry studies have had a major place at every stage. Many analytical techniques have been used in both diagnostic studies and drug analysis. Among these, electrochemical sensors are frequently preferred due to their high sensitivity, selectivity, short analysis time, reliability, ease of sample preparation, and low use of organic solvents. For the determination of drugs used in the SARS-CoV-2, such as favipiravir, molnupiravir, ribavirin, etc., electrochemical (nano)sensors are widely used in both pharmaceutical and biological samples. Diagnosis is the most critical step in the management of the disease, and electrochemical sensor tools are widely preferred for this purpose. Diagnostic electrochemical sensor tools can be biosensor-, nano biosensor-, or MIP-based sensors and utilize a wide variety of analytes such as viral proteins, viral RNA, antibodies, etc. This review overviews the sensor applications in SARS-CoV-2 in terms of diagnosis and determination of drugs by evaluating the most recent studies in the literature. In this way, it is aimed to compile the developments so far by shedding light on the most recent studies and giving ideas to researchers for future studies.

Scheelite-type rare earth vanadates TVO4 (T = Ho, Y, Dy) electrocatalysts: Investigation and comparison of T site variations towards bifunctional electrochemical sensing application

In the wake of the recent COVID-19 pandemic, antibiotics are now being used in unprecedented quantities across the globe, raising major concerns regarding pharmaceutical pollution and antimicrobial resistance (AMR). In view of the incoming tide of alarming apprehensions regarding their aftermath, it is critical to investigate control strategies that can halt their spread. Rare earth vanadates notable for their fundamental and technological significance are increasingly being used as electrochemical probes for the precise quantification of various pharmaceutical compounds. However, a comprehensive study of the role of the cationic site in tailoring the response mechanism is relatively unexplored. Hence, in this work we present a facile hydrothermal synthesis route of rare earth vanadates TVO4 (T = Ho, Y, Dy) as efficient electrocatalyst for the simultaneous detection of nitrofurazone (NF) and roxarsone (RX). There appears to be a significant correlation between T site substitution, morphological and the electrochemical properties of rare earth metal based vanadates. Following a comparative study of the electrochemical activity, the three rare-earth vanadates were found to respond differently depending on their composition of T sites. The results demonstrate that Dy-based vanadate displays increased electrical conductivity and rapid charge transfer characteristics. Thus, under optimal reaction conditions DyVO4- based electrodes imparts outstanding selectivity towards the detection of NF and RX with an extensive detection window of NF = 0.01–264 µM & RX = 0.01–21 µM and 36–264 µM and low detection limit (0.002, 0.0009 µM for NF and RX, respectively). In real-time samples, the proposed sensor reveals itself to be a reliable electrode material capable of detecting residues such as NF and RX. © 2022 Elsevier B.V.

COVID-19 Chloroquine Drug Detection Using Novel, Highly Sensitive SnO2-Based Electrochemical Sensor

A highly sensitive, selective, stable, and cost-effective SnO2-based electrochemical sensor is reported for the detection of chloroquine phosphate (CQP). Hydrothermal synthesis is used to synthesize SnO2 nanoparticles, which are mixed with graphite and form a highly electrochemically active composite. The SnO2 nanoparticles and SnO2/graphite composite are fully characterized physico- and electrochemically. Using the optimal SnO2/graphite composite, an excellent analytical performance is demonstrated with an electrode sensitivity of 35.7 µA/µM.cm2, a linear range of 0.1-23.3 µM, and limits of detection and quantification of 0.01 µM and 0.04 µM, respectively. High CQP selectivity with minimal interference at 100 × concentration of interferents is shown. The sensor is also highly repeatable and reproducible with RSD of 2.46% and 1.86%, respectively, and can retain >85% of its activity upon storage. The validity of the new sensor for real sample analysis is shown by applying it to CQP tablets using the standard addition method, obtaining an excellent percentage recovery of ∼102%. The low cost, facile processing, and superior performance of the SnO2/graphite electrode make it an up-and-coming candidate for the commercial electrochemical detection of CQP and other small molecules.

Synthesis of active-site rich molybdenum-doped manganese tungstate nanocubes for effective electrochemical sensing of the antiviral drug (COVID-19) nitazoxanide.

Nitazoxanide (NTZ), a promising antiviral agent, is currently being tested in clinical trials as a potential treatment for novel coronavirus disease 2019 (COVID -19). This paper describes a one-pot hydrothermal synthesis to prepare molybdenum (Mo)-doped manganese tungstate nanocubes (Mo-MnWO4 NCs) for the electrochemical sensing of NTZ. The as-prepared Mo-MnWO4 NCs were characterized using various techniques such as XRD, Raman, FE-SEM, FE-TEM, and XPS to confirm the crystal structure, morphology, and elemental composition. The obtained results demonstrate that Mo doping on MnWO4 generates many vacancy sites, exhibiting remarkable electrochemical activity. The kinetic parameters of the electrode modified with Mo-MnWO4 NCs were calculated to be (Ks) 1.1 × 10-2 cm2 s-1 and (α) 0.97, respectively. Moreover, a novel electrochemical sensor using Mo-MnWO4 NCs was fabricated to detect NTZ, which is used as a primary antibiotic to control COVID-19. Under optimal conditions, the electrochemical reduction of NTZ was determined with a low detection limit of 3.7 nM for a linear range of 0.014-170.2 µM with a high sensitivity of 0.78 µA µM-1 cm-2 and negligible interference with other nitro group-containing drugs, cations, and anions. The electrochemical sensor was successfully used to detect NTZ in the blood serum and urine samples and achieved high recoveries in the range of 94-99.2% and 95.3-99.6%, respectively. This work opens a way to develop high-performance sensing materials by exploring the introduction of defect engineering on metal tungstates to detect drug molecules for practical applications.

Quantification of MicroRNAs or Viral RNAs with Microelectrode Sensors Enabled by Electrochemical Signal Amplification.

Quantification of circulating microRNAs (miRNAs) or viral RNAs is of great significance because of their broad relevance to human health. Currently, quantitative reverse transcription polymerase chain reaction (qRT-PCR), as well as microarray and gene sequencing, are considered mainstream techniques for miRNA identification and quantitation and the gold standard for SARS-CoV2 detection in the COVID-19 pandemic. However, these laboratory techniques are challenged by the low levels and wide dynamic range (from aM to nM) of miRNAs in a physiological sample, as well as the difficulty in the implementation in point-of-care settings. Here, we describe a one-step label-free electrochemical sensing technique by assembling self-folded multi-stem DNA-redox probe structure on gold microelectrodes and introducing a reductant, tris(2-carboxyethyl) phosphine hydrochloride (TCEP), in the detection buffer solution to achieve ultrasensitive detection with a detection limit of 0.1 fM that can be further improved if needed.

The Modeling for Anti-Covid-19 Drug Molnupiravir Electrochemical Sensing on C3N4

The cathodic electrochemical determination of molnupiravir on carbon nitride nanoparticles has been investigated for the first time. The electrochemical determination is given in neutral and mildly acidic media, and C3 N4 plays the role of proton and electron transfer mediator. The analysis of the correspondent model confirms that the electrochemical determination of molnupiravir may be efficiently given with the easy interpretation of the analytical signal. As for the oscillatory behavior, its probability is more expressed than in the similar systems. © 2022 by the authors.

One-step synthesis of nanosilver embedding laser-induced graphene for H2O2 sensor.

During the novel coronavirus pandemic, hydrogen peroxide (H2O2) played an important role as a disinfectant. However, high concentrations of H2O2 can also cause damage to the skin and eyes. Therefore, the quantitative and qualitative detection of H2O2 is an important research direction. In this work, we report a one-step laser-induced synthesis of graphene doped with Ag NPs composites. It directly trims screen printed electrodes (SPE). Firstly, we did the timekeeping current method (CA) test on H2O2 using a conventional platinum sheet as the counter electrode, and obtained linear ranges of 1-110 µM and 110-800 µM with a sensitivity of 118.7 and 96.3 µAmM-1cm-2 and a low detection limit of (LOD) 0.24 µM and 0.31 µM. On this basis we have also achieved a good result in CA testing using Screen printed carbon electrodes (SPCE), laying the foundation for portable testing. The sensor has excellent interference immunity and high selectivity.

Rapid quantitation of SARS-CoV-2 antibodies in clinical samples with an electrochemical sensor.

The current coronavirus disease 2019 (COVID-19) pandemic is caused by several variants of severe acute respiratory syndrome coronavirus-2 virus (SARS-CoV-2). With the roll-out of vaccines and development of new therapeutics that may be targeted to distinct viral molecules, there is a need to screen populations for viral antigen-specific SARS-CoV-2 antibodies. Here, we report a rapid, multiplexed, electrochemical (EC) device with on-chip control that enables detection of SARS-CoV-2 antibodies in less than 10 min using 1.5 µL of a patient sample. The EC biosensor demonstrated 100% sensitivity and specificity, and an area under the receiver operating characteristic curve of 1, when evaluated using 93 clinical samples, including plasma and dried blood spot samples from 54 SARS-CoV-2 positive and 39 negative patients. This EC biosensor platform enables simple, cost-effective, sensitive, and rapid detection of anti-SARS-CoV-2 antibodies in complex clinical samples, which is convenient for evaluating humoral-responses to vaccination or infection in population-wide testing, including applications in point-of-care settings. We also demonstrate the feasibility of using dried blood spot samples that can be collected locally and transported to distant clinical laboratories at ambient temperature for detection of anti-SARS-CoV-2 antibodies which may be utilized for serological surveillance and demonstrate the utility of remote sampling.

Sensitive electrochemical assay of acetaminophen based on 3D-hierarchical mesoporous carbon nanosheets.

Acetaminophen plays a key role in first-line Covid-19 cure as a supportive therapy of fever and pain. However, overdose of acetaminophen may give rise to severe adverse events such as acute liver failure in individual. In this work, 3D-hierarchical mesoporous carbon nanosheet (hMCNS) microspheres with superior properties were fabricated using simple and quick strategy and applied for sensitive quantification of acetaminophen in pharmaceutical formulation and rat plasmas after administration. The hMCNS microspheres are prepared via chemical etching of zinc oxide (ZnO) nanoparticles from a zinc-gallic acid precursor composite (Zn-GA) synthesized by high-temperature anaerobic pyrolysis. The obtained hMCNS could enhance analytes accessibility and accelerate proton transfer in the interface, hence increasing the electrochemical performance. Under optimized experimental conditions, the proposed electrochemical sensor achieves a detection limit of 3.5 nM for acetaminophen. The prepared electrochemical sensor has been successfully applied for quantification of acetaminophen in pharmaceutical formulations and the rat plasma samples before and after administration. Meanwhile, this sensor is compared with high-performance liquid chromatography (HPLC) as a reference technology, showing an excellent accuracy. Such an electrochemical sensor has great potential and economic benefits for applications in the fields of pharmaceutical assay and therapeutic drug monitoring (TDM).

Voltammetric determination of Molnupiravir used in treatment of the COVID-19 at magnetite nanoparticle modified carbon paste electrode.

To reduce the progression of the viral process in patients infected with COVID-19, new treatments and drug active substances are needed. One of these drugs is Molnupiravir (MNP) which has a direct antiviral effect and has also proven to be highly effective in reducing the azopharyngeal SARS-CoV-2 infectious virus and viral RNA. Due to the importance and frequent use of this drug in the treatment of COVID-19, its accurate, quick, and cheap detection in pharmaceutical or biological samples is crucial. In this work, electrochemical behavior and sensitive voltammetric determination of MNP are described using a magnetite nanoparticle modified carbon paste electrode (Fe3O4@CPE) for the first time. Fe3O4 nanoparticles (NPs) were characterized by recording their transmission electron microscopy (TEM) images, energy dispersive X-ray (EDX), and X-ray diffraction (XRD) spectra. Cyclic voltammetric measurements showed that MNP was irreversibly oxidized at Fe3O4@CPE at 760 mV in pH 2.0 Britton Robinson buffer solution (BRBS). The peak current of MNP was increased approximately threefold at Fe3O4@CPE compared to bare CPE due to a good electrocatalytic efficiency of Fe3O4 NPs. According to differential pulse voltammetric studies, the fabricated electrode exhibited a linear range (LR) between 0.25 and 750 µM with sensitivity and limit of detection (LOD) of 4591.0 µA mM-1 cm-2 and 0.05 µM, respectively. On the other hand, although lower sensitivity (327.3 µA mM-1 cm-2) was obtained from CV compared to DPV, a wider linear calibration curve between 0.25 and 1500 µM was obtained in CV. Studies performed in tablet samples confirmed that the Fe3O4@CPE exhibits high applicability for selective and accurate voltammetric determination of MNP in real samples.

Polylactic acid/tapioca starch/banana peel-based material for colorimetric and electrochemical biosensing applications.

The rapidly growing electronic and plastic waste has become a global environmental concern. Developing advanced and environmentally safe agro-based materials is an emerging field with an enormous potential for applications in sensors and devices. Here, an agro-based material as membrane has been developed by incorporating tapioca starch and banana peel powder in polylactic acid, with uniform dispersibility and amorphous nature. The material was used for the development of electrochemical sensor for S-gene of SARS-CoV-2. Further, the membrane was used for the development of a non-invasive, colorimetric skin patch for the detection of glucose and a sensor for the assessment of fruit juice quality. Using OECD-recommended model systems, the developed membrane was found to be non-toxic towards aquatic and terrestrial non-target organisms. The developed conductive material opens new avenues in various electrochemical, analytical, and biological applications.

Development and Clinical Validation of RT-LAMP-Based Lateral-Flow Devices and Electrochemical Sensor for Detecting Multigene Targets in SARS-CoV-2.

Consistently emerging variants and the life-threatening consequences of SARS-CoV-2 have prompted worldwide concern about human health, necessitating rapid and accurate point-of-care diagnostics to limit the spread of COVID-19. Still, However, the availability of such diagnostics for COVID-19 remains a major rate-limiting factor in containing the outbreaks. Apart from the conventional reverse transcription polymerase chain reaction, loop-mediated isothermal amplification-based (LAMP) assays have emerged as rapid and efficient systems to detect COVID-19. The present study aims to develop RT-LAMP-based assay system for detecting multiple targets in N, ORF1ab, E, and S genes of the SARS-CoV-2 genome, where the end-products were quantified using spectrophotometry, paper-based lateral-flow devices, and electrochemical sensors. The spectrophotometric method shows a LOD of 10 agµL-1 for N, ORF1ab, E genes and 100 agµL-1 for S gene in SARS-CoV-2. The developed lateral-flow devices showed an LOD of 10 agµL-1 for all four gene targets in SARS-CoV-2. An electrochemical sensor developed for N-gene showed an LOD and E-strip sensitivity of log 1.79 ± 0.427 pgµL-1 and log 0.067 µA/pg µL-1/mm2, respectively. The developed assay systems were validated with the clinical samples from COVID-19 outbreaks in 2020 and 2021. This multigene target approach can effectively detect emerging COVID-19 variants using combination of various analytical techniques at testing facilities and in point-of-care settings.

High enrichment and near real-time quantification of airborne viruses using a wet-paper-based electrochemical immunosensor under an electrostatic field

Conventional airborne virus measurement usually requires appreciable sampling and detection times. Viral aerosols should also be collected or prepared in a liquid medium whose volume typically ranges from milliliters to tens of milliliters;hence, many sampling and detection steps need to be taken with the unit horizontal or immobile. Moreover, viral aerosols need to be sufficiently enriched, which makes real-time monitoring difficult. Herein, we present a near real-time enrichment and quantification system of airborne viruses that consists of a wet-paper-based electrochemical immunosensor with a gel electrolyte and a modified electrostatic particle concentrator. A small amount of phosphate-buffered saline flowed on the electrode, which resulted in sensor electrodes that are barely wet (covered in a thin buffer film measuring several micrometers) to ensure anti-gen-antibody interaction and the removal of non-target particles on the electrode surface. This system ensures that airborne viruses are highly enriched on the working electrode of the immunosensor, and it is possible to measure the MS2 virus particle concentrations every 10 min for 60 min stably and selectively against non-target airborne viruses and bacteria at horizontal and tilted measurement configurations. This system thus has the potential to be used in the real-time mobile monitoring of airborne microorganisms.