Visual diagnosis of COVID-19 disease based on serum metabolites using a paper-based electronic tongue.

This study aims to use a paper-based sensor array for point-of-care detection of COVID-19 diseases. Various chemical compounds such as nanoparticles, organic dyes and metal ion complexes were employed as sensing elements in the array fabrication, capturing the metabolites of human serum samples. The viral infection caused the type and concentration of serum compositions to change, resulting in different color responses for the infected and control samples. For this purpose, 118 serum samples of COVID-19 patients and non-COVID controls both men and women with the age range of 14-88 years were collected. The serum samples were initially subjected to the sensor, followed by monitoring the variation in the color of sensing elements for 5 min using a scanner. By taking into consideration the statistical information, this method was capable of discriminating COVID-19 patients and control samples with 83.0% accuracy. The variation of age did not influence the colorimetric patterns. The desirable correlation was observed between the sensor responses and viral load values calculated by the PCR test, proposing a rapid and facile way to estimate the disease severity. Compared to other rapid detection methods, the developed assay is cost-effective and user-friendly, allowing for screening COVID-19 diseases reliably.

Mask assistance to colorimetric sniffers for detection of Covid-19 disease using exhaled breath metabolites.

According to World Health Organization reports, large numbers of people around the globe have been infected or died for Covid-19 due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Researchers are still trying to find a rapid and accurate diagnostic method for revealing infected people by low viral load with the overriding goal of effective diagnostic management. Monitoring the body metabolic changes is known as an effective and inexpensive approach for the evaluation of the infected people. Here, an optical sniffer is introduced to detect exhaled breath metabolites of patients with Covid-19 (60 samples), healthy humans (55 samples), and cured people (15 samples), providing a unique color pattern for differentiation between the studied samples. The sniffer device is installed on a thin face mask, and directly exposed to the exhaled breath stream. The interactions occurring between the volatile compounds and sensing components such as porphyrazines, modified organic dyes, porphyrins, inorganic complexes, and gold nanoparticles allowing for the change of the color, thus being tracked as the sensor responses. The assay accuracy for the differentiation between patient, healthy and cured samples is calculated to be in the range of 80%-84%. The changes in the color of the sensor have a linear correlation with the disease severity and viral load evaluated by rRT-PCR method. Interestingly, comorbidities such as kidney, lung, and diabetes diseases as well as being a smoker may be diagnosed by the proposed method. As a powerful detection device, the breath sniffer can replace the conventional rapid test kits for medical applications.

A colorimetric electronic tongue for point-of-care detection of COVID-19 using salivary metabolites.

The monitoring of profile concentrations of chemical markers in saliva samples can be used to diagnose COVID-19 patients, and differentiate them from healthy individuals. Here, this purpose is achieved by designing a paper-based colorimetric sensor with an origami structure, containing general receptors such as pH-sensitive organic dyes, Lewis donors or acceptors, functionalized nanoparticles, and ion metal complexes. The color changes taking place in the receptors in the presence of chemical markers are visually observed and recorded with a digital instrument. Different types and amounts of the chemical markers provide the sensor with a unique response for patients (60 samples) or healthy (55 samples) individuals. These two categories can be discriminated with 84.3% accuracy. This study evidences that the saliva composition of cured and healthy participants is different from each other with accuracy of 85.7%. Moreover, viral load values obtained from the rRT-PCR method can be estimated by the designed sensor. Besides COVID-19, it may possible to simultaneously identify smokers and people with kidney disease and diabetes using the specified electronic tongue. Due to its high efficiency, the prepared paper device can be employed as a rapid detection kit to detect COVID-19.

Wearable Potentiometric Sensor Based on Na0.44MnO2 for Non-invasive Monitoring of Sodium Ions in Sweat.

Here, we present a wearable potentiometric ion sensor for real-time monitoring of sodium ions (Na+) in human sweat samples using Na0.44MnO2 as the sensing material. Na0.44MnO2 is an attractive material for developing wearable electrochemical sensors due to its good Na+ incorporation ability, electrical conductivity, stability, and low fabrication cost. In the first step, the analytical performance of the electrode prepared using Na0.44MnO2 is presented. Then, a miniaturized potentiometric cell integrated into a wearable substrate is developed, which reveals a Nernstian response (58 mV dec-1). We achieved the detection of Na+ in the linear ranges of 0.21-24.54 mmol L-1, which is well within the physiological range of Na+. Finally, for on-body sweat analysis, the potentiometric sensor is fully integrated into a headband textile. This platform can be employed for non-invasive analysis of Na+ in human sweat for healthcare and disease diagnosis.

Enzymeless voltammetric sensor for simultaneous determination of parathion and paraoxon based on Nd-based metal-organic framework.

The aim of this work is to fabricate a sensitive and novel enzymeless electrochemical sensor for the simultaneous determination of parathion and paraoxon using the Nd-UiO-66@MWCNT nanocomposite. For this purpose, Neodymium (Nd) was introduced into a Universitetet i Oslo (UiO-66) structure to construct Nd-UiO-66 and then, adding multi-walled carbon nanotubes to the Nd-UiO-66 to increase the electrocatalytic activity and surface area of the obtained composite. The Nd-UiO-66@MWCNT has numerous advantages like excellent conductivity, tunable texture, and large surface area and can be used as a distinctive structure for the construction of modified glassy carbon electrode (GCE) to enhance the charge-transfer and the efficiency of electrochemical sensors. This modified electrode showed sensitive and selective determination of paraoxon and parathion over the linear ranges of 0.7-100 and 1-120 nM, with detection limits of 0.04 and 0.07 nM, respectively. The proposed Nd-UiO-66@MWCNT/GCE sensor in this study can be applied in environmental and toxicological laboratories and field tests to detect parathion and paraoxon levels.

Dual-template rectangular nanotube molecularly imprinted polypyrrole for label-free impedimetric sensing of AFP and CEA as lung cancer biomarkers.

A high-performance sensing layer based on dual-template molecularly imprinted polymer (DMIP) was fabricated and successfully applied for one-by-one detection of carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP) as lung cancer biomarkers. The plastic antibodies of AFP and CEA were created into the electropolymerized polypyrrole (PPy) on a fluorine-doped tin oxide (FTO) electrode. Raman spectroscopy, field emission scanning electron microscopy (FE-SEM), cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS) tests were performed to pursue the formation and characterization of the sensing layer. Methyl orange (MO) increased the conductivity of PPy and induced the formation of MO doped PPy (PPy-MO) rectangular-shaped nanotubes. Using impedimetric detection, the rebinding of the template antigens was evaluated, the charge transfer resistance increased as the concentration of AFP and CEA increased. The linear dynamic ranges of 5-104 and 10-104 pg mL-1 and detection limits of 1.6 and 3.3 pg mL-1 were obtained for CEA and AFP, respectively. Given satisfactory results in the determination of AFP and CEA in the human serum samples, high sensitivity, and good stability of DMIP sensor made it a promising method for sensing of AFP and CEA in serum samples.

Electrochemical sandwich-type immunosensor for the detection of PSA based on a trimetallic AgAuPt nanocomposite synthesized using the galvanic replacement reaction.

A sandwich-type electrochemical immunoassay was introduced for the determination of the prostate-specific antigen (PSA) biomarker. A direct and simple galvanic replacement reaction was performed between the Ag framework and metallic salts of tetrachloroauric(iii) acid trihydrate and chloroplatinic acid to produce a trimetallic composite of AgAuPt. The trimetallic composite of AgAuPt was applied to the preparation of the capture layer of the immunoassay for stabilizing the primary Ab at the surface of the prepared composite. The immunoassay detection layer was also prepared using a labeled antibody containing a bimetallic composite of AgPt as a label. The various procedures in the immunoassay fabrication were monitored step by step using cyclic voltammetry and electrochemical impedance spectroscopy. Also, the electrochemical determination of PSA was performed using differential pulse voltammetry in the presence of the ferrocene redox probe and H2O2. Furthermore, the effective parameters in the fabrication of the immunoassay included the drop volume of the AgAuPt trimetallic composite and the incubation time for the immobilization of biomolecules (i.e., Ab1, BSA, PSA, and labeled Ab2), and the concentration of H2O2 were optimized during the determination of PSA. Then, the determination of PSA was performed under optimized conditions. It could be seen that there was a linear relation between the PSA concentration and DPV responses in the concentration range of 50 pg mL-1 to 500 ng mL-1 and the limit of detection (LOD) for the proposed immunoassay was calculated as 17.0 pg mL-1. In the following investigation, the cross-reactivity of the proposed immunoassay was studied in the presence of BSA, CEA, IgG, and human hepatitis surface antigen, in which the results showed a negligible change in the performance of the immunoassay.

Dual-modality impedimetric immunosensor for early detection of prostate-specific antigen and myoglobin markers based on antibody-molecularly imprinted polymer.

A new dual-modality immunosensor based on molecularly imprinted polymer (MIP) and a nanostructured biosensing layer has fabricated for the simultaneous detection of two important markers including prostate-specific antigen (PSA) and myoglobin (Myo) in human serum and urine samples. In the first step, 3,3'-dithiodipropionic acid di(N-hydroxysuccinimide ester) (DSP) was self-assembled on a gold screen printed electrode (SPE). Then, the target proteins were attached covalently to the DSP-SPE. The imprinted cocktail polymer ((MIP(PSA, Myo)-SPE)) was synthesized at the SPE surface using acrylamide as monomer, N,N'-methylenebisacrylamide as a crosslinker, and PSA and Myo as the templates, respectively. The MIP-SPE was specific for the impedimetric sensing of PSA and Myo. After that, a nanocomposite (NCP) was synthesized based on the decorated magnetite nanoparticles with multi-walled carbon nanotube, graphene oxide and specific antibody for PSA (Ab). Then, NCP incubated with (MIP(PSA, Myo)-SPE. The modified electrodes and synthesized nanoparticles were characterized using electrochemical impedance spectroscopy, dynamic light scattering, surface plasmon resonance and scanning electron microscopy. The limits of detections were found to be 5.4 pg mL-1 and 0.83 ng mL-1 with the linear dynamic ranges of 0.01-100 and 1-20000 ng mL-1 for PSA and Myo, respectively. The ability of proposed biosensor to detect PSA and Myo simultaneously with high sensitivity and specificity offers a powerful opportunity for the new generation of biosensors. This dual-analyte specific receptors-based device is highly desired for the integration with lab-on-chip kits to measure a wide panel of biomarkers present at ultralow levels during early stages of diseases progress.

Reduced graphene oxide decorated on Cu/CuO-Ag nanocomposite as a high-performance material for the construction of a non-enzymatic sensor: Application to the determination of carbaryl and fenamiphos pesticides.

A novel electrochemical sensor based on the reduced graphene oxide-Cu/CuO-Ag nanocomposite modified glassy carbon electrode (rGO/Cu/CuO-Ag/GCE) has been applied for the simultaneous analysis of carbaryl and fenamiphos as two important pesticides. The electrochemical behavior of carbaryl and fenamiphos at rGO/Cu/CuO-Ag/GCE was studied by cyclic voltammetry and differential pulse voltammetry. The modified electrode exhibited two separated oxidation signals for the simultaneous determination of both carbaryl and fenamiphos with excellent sensitivity. The characteristics of the modified electrode were studied with transmission electron microscopy, X-ray diffraction and Fourier transform-infrared spectroscopy techniques. Under optimized conditions, the rGO/Cu/CuO-Ag/GCE detected carbaryl and fenamiphos with the wide linear ranges of 0.05-20 and 0.01-30 µM, and the detection limits were 0.005 and 0.003 µM, respectively. This developed electrochemical platform applied as a simple and cost-effective sensor for the detection of low levels of carbaryl and fenamiphos in fruit and vegetable samples successfully.

Colorimetric immunosensor for determination of prostate specific antigen using surface plasmon resonance band of colloidal triangular shape gold nanoparticles.

In this work, we demonstrated the development of a colorimetric immunosensor using surface plasmon resonance band of gold nanoparticles for the detection of prostate specific antigen (PSA). To develop this biosensing tool, triangular gold nanoparticles (AuNPs) were synthesized using Tween-20 as a nonionic surfactant and then, conjugated with PSA capture antibody (Ab1-AuNPs). When exposed to Ab1-AuNPs, PSA antigens were found to be successfully captured by nanosystem (PSA)-Ab1-AuNPs. Next, (PSA)-Ab1-AuNPs were incubated with second PSA antibody (2)-decorated magnetite (Fe3O4-Ab2) and separated by an external magnetic force to leave Ab1-AuNPs in the supernatant solution to be directly analyzed using UV-Vis spectroscopy. It was found that the absorption intensity was directly proportional to the PSA concentration. As a result, the linear range for PSA detection was found to be 0.01-20 ng mL-1 with a detection limit of 0.009 ng mL-1. Because of significant stability of the prepared Ab1-AuNPs and excellent selectivity to the PSA antigen, this simple and sensitive sensing system is proposed to be potentially effective in the fast and real-time analysis of clinical samples from prostate cancer patients. We believe that the simple platform of this immunosensor to be useful in the development of future point-of-care sensing tools, working on the quantification of biomarkers in a drop of blood.

Enhanced Visual Wireless Electrochemiluminescence Immunosensing of Prostate-Specific Antigen Based on the Luminol Loaded into MIL-53(Fe)-NH2 Accelerator and Hydrogen Evolution Reaction Mediation.

A sensitive prostate-specific antigen (PSA) detection method using a visual-readout closed bipolar electrode (BPE) system has been introduced by integration of hydrogen evolution reaction (HER) in cathodic pole and electrochemiluminescence (ECL) of luminol loaded within the MIL-53(Fe)-NH2 (L@MIL-53(Fe)-NH2) in the anodic pole. The cathode of the BPE was electrochemically synthesized by 3D porous copper foam, followed by decorating with nitrogen-doped graphene nanosheet and ruthenium nanoparticles. As an alternative, we employed carboxylate-modified magnetic nanoparticles (MNPs) for immobilization of the primary antibody (Ab1) and utilized the L@MIL-53(Fe)-NH2 conjugated to secondary antibody (Ab2) as a signaling probe and coreaction accelerator. After sandwiching the target PSA between Ab1 and Ab2, the MNP/Ab1-PSA-Ab2/L@MIL-53(Fe) were introduced to a gold anodic BPE. Finally, the resulting ECL of luminol and H2O2 at the anodic poles was monitored using a photomultiplier tube (PMT) or digital camera. The PMT and visual (camera)-based detections showed linear responses from 1 pg mL-1 to 300 ng mL-1 (limit of detection 0.2 pg mL-1) and 5 pg mL-1 to 200 ng mL-1 (limit of detection 0.1 pg mL-1), respectively. This strategy provides an effective method for high-performance bioanalysis and opens a new door toward the development of the highly sensitive and user-friendly device.

Nanomolar simultaneous determination of tryptophan and melatonin by a new ionic liquid carbon paste electrode modified with SnO2-Co3O4@rGO nanocomposite.

This work describes the development of a new sensor for simultaneous determination of tryptophan and melatonin. The proposed sensor was an ionic liquid carbon paste electrode modified with reduced graphene oxides decorated with SnO2-Co3O4 nanoparticles. The voltammetric oxidation of the analytes by the proposed sensor confirmed that the electrooxidation process undergoes a two-electron/one-proton reaction for melatonin and a two-electron/two-proton reaction for tryptophan in diffusion-controlled processes. Moreover, based on the excellent electrochemical properties of the modified electrode, a sensitive voltammetric method was used for individual and simultaneous determination of melatonin and tryptophan in the aqueous solutions. Under the optimized experimental conditions, a linear response obtained in the range of 0.02 to 6.00µmolL-1 with detection limits of 4.1 and 3.2nmolL-1 for melatonin and tryptophan, respectively. The prepared sensor possessed accurate and rapid response toward melatonin and tryptophan with a good sensitivity, selectivity, stability, and repeatability. Finally, the applicability of the proposed sensor was verified by evaluation of melatonin and tryptophan in various real samples including human serum and tablet samples.

Protein capped Cu nanoclusters-SWCNT nanocomposite as a novel candidate of high performance platform for organophosphates enzymeless biosensor.

A biocompatible nanocomposite including bovine serum albumin (BSA) template Cu nanoclusters (CuNCs@BSA) and single-walled carbon nanotubes (SWCNT) was synthesized to fabricate a highly sensitive electrochemical biosensor for paraoxon as a model of organophosphates. The UV-vis, fluorescence and Fourier transform infrared (FTIR) demonstrated that BSA entrapped in the nanocomposite film have been changed in its secondary structure so that it provided an enzyme like activity attributing to the high electrical conductivity of the entrapped copper nanoclusters. Also, the morphology and structure of prepared nanocomposites were investigated by transmission electronic microscopy (TEM) and scanning electron microscopy (SEM). In the prepared nanocomposite, the CuNCs@BSA found to play as a conductive holder as well as an accumulator of redox active centers on the surface of the electrode, and SWCNT improves the electrocatalytic activity along with conductivity of glassy carbon electrode (GCE) surface. The fabricated biosensor exhibited excellent sensitivity, acceptable stability, fast response, and high electrocatalytic activity toward the reduction of paraoxon. The reduction peak current vs paraoxon concentration was linear over the range 50nM to 0.5µM and 0.5-35µM, with a limit of detection of 12.8nM. Notable electrocatalytic properties of the developed electrode toward paraoxon indicated that the nanocomposite possesses a promising potential to fabricate the third generation enzyme-free electrochemical biosensors, bioelectronics and state-of-the-art biomedical devices in the future.

Simultaneous electrochemical sensing of thallium, lead and mercury using a novel ionic liquid/graphene modified electrode.

In the present manuscript, an electrochemical sensor for the sensitive detection of Tl(+), Pb(2+) and Hg(2+) is described. A new composite electrode has been fabricated using graphene, 1-n-octylpyridinum hexafluorophosphate (OPFP), and [2,4-Cl2C6H3C(O)CHPPh3] (L), as a new synthetic phosphorus ylide. The physicochemical and electrochemical characterizations of fabricated sensor were investigated in details. The advantages of the proposed composite electrode are its ability in simultaneous electrochemical detection of Tl(+), Pb(2+) and Hg(2+) with good selectivity, stability and no need for separating of the three species from complex mixtures prior to electrochemical measurements. The analytical performance of the proposed electrode was examined using square wave voltammetry. Tl(+), Pb(2+) and Hg(2+) can be determined in linear ranges from 1.25×10(-9) to 2.00×10(-7) mol L(-1). Low detection limits of 3.57×10(-10) mol L(-1) for Tl(+), 4.50×10(-10) mol L(-1) for Pb(2+) and 3.86×10(-10) mol L(-1) for Hg(2+) were achieved. Finally, the proposed electrochemical sensor was applied to detect trace analyte ions in various water and soil samples with satisfactory results.

Preparation of NiFe2O4/graphene nanocomposite and its application as a modifier for the fabrication of an electrochemical sensor for the simultaneous determination of tramadol and acetaminophen.

An effective electrochemical sensor for the rapid and simultaneous determination of tramadol and acetaminophen based on carbon paste electrode (CPE) modified with NiFe2O4/graphene nanoparticles was developed. The structures of the synthesized NiFe2O4/graphene nanocomposite and the electrode composition were confirmed by X-ray diffraction (XRD) spectrometry, Fourier transform infrared (FT-IR) spectrometry and scanning electron microscopy (SEM). The peak currents of square wave voltammetry of tramadol and acetaminophen increased linearly with their concentration in the range of 0.01-9 µmol L(-1). The detection limit for their determination was found to be 0.0036 and 0.0030 µmol L(-1), respectively. The results show that the combination of graphene and NiFe2O4 nanoparticles causes a dramatic enhancement in the sensitivity of the sensor. The fabricated sensor exhibited high sensitivity and good stability, and would be valuable for the clinical assay of tramadol and acetaminophen.

Facile stripping voltammetric determination of haloperidol using a high performance magnetite/carbon nanotube paste electrode in pharmaceutical and biological samples.

Multi-walled carbon nanotubes decorated with Fe3O4 nanoparticles were prepared to construct a novel sensor for the determination of haloperidol (Hp) by voltammetric methods. The morphology and properties of electrode surface were characterized by scanning electron microscopy (SEM) and electrochemical impedance spectroscopy. This modified sensor was used as a selective electrochemical sensor for the determination of trace amounts of Hp. The peak currents of differential pulse and square wave voltammograms of Hp increased linearly with its concentration in the ranges of 1.2×10(-3)-0.52 and 6.5×10(-4)-0.52µmol L(-1), respectively. The detection limits for Hp were 7.02×10(-4) and 1.33×10(-4)µmol L(-1) for differential pulse and square wave voltammetric methods, respectively. The results show that the combination of multi-walled carbon nanotubes and Fe3O4 nanoparticles causes a dramatic enhancement in the sensitivity of Hp quantification. This sensor was successfully applied to determine Hp in pharmaceutical samples and biological fluids. The fabricated electrode showed excellent reproducibility, repeatability and stability.

Construction of a carbon ionic liquid paste electrode based on multi-walled carbon nanotubes-synthesized Schiff base composite for trace electrochemical detection of cadmium.

A simple, highly sensitive and selective carbon nanocomposite electrode has been developed for the electrochemical trace determination of cadmium. This sensor was designed by incorporation of multi-walled carbon nanotubes (MWCNTs) and a new synthesized Schiff base into the carbon paste ionic liquid electrode (CPE(IL)) which provides remarkably improved sensitivity and selectivity for the electrochemical stripping assay of Cd(II). The detection limit of the method was found to be 0.08 µg L(-1) (S/N=3) that is lower than the maximum contaminant level of Cd(II) allowed by the Environmental Protection Agency (EPA) in standard drinking waters. The proposed electrode exhibits good applicability for monitoring Cd(II) in various real samples.

Simultaneous trace-levels determination of Hg(II) and Pb(II) ions in various samples using a modified carbon paste electrode based on multi-walled carbon nanotubes and a new synthesized Schiff base.

A modified carbon paste electrode based on multi-walled carbon nanotubes (MWCNTs) and 3-(4-methoxybenzylideneamino)-2-thioxothiazolodin-4-one as a new synthesized Schiff base was constructed for the simultaneous determination of trace amounts of Hg(II) and Pb(II) by square wave anodic stripping voltammetry. The modified electrode showed an excellent selectivity and stability for Hg(II) and Pb(II) determinations and for accelerated electron transfer between the electrode and the analytes. The electrochemical properties and applications of the modified electrode were studied. Operational parameters such as pH, deposition potential and deposition time were optimized for the purpose of determination of traces of metal ions at pH 3.0. Under optimal conditions the limits of detection, based on three times the background noise, were 9.0×10(-4) and 6.0×10(-4) µmol L(-1) for Hg(II) and Pb(II) with a 90 s preconcentration, respectively. In addition, the modified electrode displayed a good reproducibility and selectivity, making it suitable for the simultaneous determination of Hg(II) and Pb(II) in real samples such as sea water, waste water, tobacco, marine and human teeth samples.

Preparation and characterization of magnetic nanocomposite of Schiff base/silica/magnetite as a preconcentration phase for the trace determination of heavy metal ions in water, food and biological samples using atomic absorption spectrometry.

A versatile and robust solid phase with both magnetic property and a very high adsorption capacity is presented on the basis of modification of iron oxide-silica magnetic particles with a newly synthesized Schiff base (Fe(3)O(4)/SiO(2)/L). The structure of the resulting product was confirmed by Fourier transform infrared (FT-IR) spectra, X-ray diffraction (XRD) spectrometry and transmission electron microscopy (TEM). We developed an efficient and cost-effective method for the preconcentration of trace amounts of Pb(II), Cd(II) and Cu(II) in environmental and biological samples using this novel magnetic solid phase. Prepared magnetic solid phase is an ideal support because it has a large surface area, good selectivity and can be easily retrieved from large volumes of aqueous solutions. The possible parameters affecting the enrichment were optimized. Under the optimal conditions, the method detection limit was 0.14, 0.19 and 0.12 µg L(-1) for Pb(II), Cd(II) and Cu(II) ions, respectively. The established method has been successfully applied to analyze real samples, and satisfactory results were obtained. All these indicated that this magnetic phase had a great potential in environmental and biological fields.