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.

Simultaneous determination of BoNT/A and /E using an electrochemical sandwich immunoassay based on the nanomagnetic immunosensing platform.

Developing new ultrasensitive assays for the detection of the presence, and determination of the serotype of the most poisonous material known i.e. botulinum neurotoxin (BoNT) is vital to human health and the wellbeing of the surrounding environment. Here, an electrochemical sandwich immunoassay with high sensitivity is adopted to achieve simultaneous determination of BoNT serotypes A and E based on polystyrene@polydopamine/Cd2+ and Ag nanoparticles acting as monoclonal antibody labels. Two well-separated peaks with strong electrochemical signals are generated by the labels, allowing for the simultaneous detection of two analytes existing on the electrode. To obtain well-oriented polyclonal antibodies immobilization, boronic acid is directly attached to the magnetic core/metal-organic framework (MOF) shell nanoagent surfaces without the requirement of a long and flexible spacer. Accordingly, it is possible to directly detect the metal ion labels through square wave voltammetry without the metal pre-concentration step. This results in distinct and well-defined voltammetric peaks, pertaining to each sandwich-type immunocomplexes. The limits of detection of BoNT/A and BoNT/E analyses were found to be 0.04 and 0.16 pg mL-1 with the linear dynamic ranges of 0.1-1000 and 0.5-1000 pg mL-1, respectively. Based on the obtained results, this immunosensor has the wide linear ranges, while also exhibiting low limits of detection along with good stability and reproducibility.

Disposable Paper-Based Biosensors for the Point-of-Care Detection of Hazardous Contaminations-A Review.

The fast detection of trace amounts of hazardous contaminations can prevent serious damage to the environment. Paper-based sensors offer a new perspective on the world of analytical methods, overcoming previous limitations by fabricating a simple device with valuable benefits such as flexibility, biocompatibility, disposability, biodegradability, easy operation, large surface-to-volume ratio, and cost-effectiveness. Depending on the performance type, the device can be used to analyze the analyte in the liquid or vapor phase. For liquid samples, various structures (including a dipstick, as well as microfluidic and lateral flow) have been constructed. Paper-based 3D sensors are prepared by gluing and folding different layers of a piece of paper, being more user-friendly, due to the combination of several preparation methods, the integration of different sensor elements, and the connection between two methods of detection in a small set. Paper sensors can be used in chromatographic, electrochemical, and colorimetric processes, depending on the type of transducer. Additionally, in recent years, the applicability of these sensors has been investigated in various applications, such as food and water quality, environmental monitoring, disease diagnosis, and medical sciences. Here, we review the development (from 2010 to 2021) of paper methods in the field of the detection and determination of toxic substances.

Electrochemiluminescent biosensor for ultrasensitive detection of lymphoma at the early stage using CD20 markers as B cell-specific antigens.

Herein, by taking advantage of the special binding of an aptamer to the membrane surface of a B cell and accumulation of the positive charges of a nanocomposite, including luminol-chitosan-platinum nanoparticles (L-Cs-Pt NPs), on the negatively charge of the aptamer phosphate backbone, a sensitive, simple, selective and rapid strategy for the detection of lymphoma cells by a new label-free electrogenerated chemiluminescence (ECL) aptasensor has been introduced. With increasing concentrations of B lymphoma cells, the nanocomposite detaches from the aptamer, leading to a decrease in the ECL of a luminol and H2O2 system. With high loading of luminol and Pt NPs on a chitosan, together with the electrocatalytic effect of Pt NPs, enhanced sensitive detection of cancer cells with a limit of detection of 31 cells/mL was achieved. Step-by-step modification and biosensor response to cancer cells was monitored by electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV), and ECL. The aptasensor exhibited excellent specificity for lymphoma cells vs breast cancer (MCF-7) and human embryonic kidney (HEK293) cell lines as potential interferents. Finally, the performance of the aptasensor in blood samples was assessed against a commercial flow cytometric method. Satisfactory results confirmed the applicability of the proposed biosensing platform.

Well-Orientation Strategy for Direct Immobilization of Antibodies: Development of the Immunosensor Using the Boronic Acid-Modified Magnetic Graphene Nanoribbons for Ultrasensitive Detection of Lymphoma Cancer Cells.

This work presents an effective strategy for the well-oriented immobilization of antibodies in which boronic acid is directly attached to the surface and with no need of the long and flexible spacer. A magnetic graphene nanoribbon-boronic-acid-based immunosensor was developed and tested for the impedimetric detection of lymphoma cancer cells, a blood cancer biomarker. Magnetic graphene nanoribbons (MGNRs) were modified with boronic acid (BA) to create a supporting matrix that is utilized by immobilizing anti-CD20 antibodies with good orientation. The prepared biosensing layer (MGNR/BA/Ab) with well-oriented antibodies was premixed into whole blood samples to interact with lymphoma cancer cell receptors. In the presence of target cell receptors, an immunocomplex was formed between anti-CD20 antibodies and lymphoma cancer cell receptors. Then, the biosensing layer was magnetically collected on a screen-printed carbon electrode (SPCE) and placed in a homemade electrochemical cell configuration to measure impedimetric signals. The fabrication steps of the immunosensor were characterized by various techniques, such as resonance light scattering, fluorescence, electrochemical impedance spectroscopy, and cyclic voltammetry. The assay is highly sensitive: the calculated limit of detection of lymphoma cancer cells was as low as 38 cells/mL, and the detection was linear from 100 to 1 000 000 cells/mL. The specificity of the immunosensor is also very high, and there is no interference effect with several potential interferents, such as the breast cancer (MCF-7), human embryonic kidney (HEK293), and leukemia (HL-60 and KCL-22) cell lines. The performance of the immunosensor for lymphoma cancer cells in clinical blood samples is consistent with that of commercial flow cytometric assays.

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.

Graphene nanoribbon/FePt bimetallic nanoparticles/uric acid as a novel magnetic sensing layer of screen printed electrode for sensitive determination of ampyra.

A novel electrochemical sensor for sensitive determination of ampyra (Am) based on graphene nanoribbons modified by iron-platinum bimetallic nanoparticles and uric acid (SPCE/FePtGNR/UA) dropped on the screen-printed carbon electrode (SPCE) surface and magnetically captured onto an SPCE working electrode surface is reported in the present work. The modified nanocomposite and sensing layer was characterized by different techniques, including cyclic voltammetry (CV), linear sweep voltammetry (LSV), electrochemical impedance spectroscopy (EIS), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR) and X-ray powdered diffraction (XRD). Am determination by conventional electrochemical methods is not possible, because of its high redox overpotential. Therefore, the differential pulse voltammetry (DPV) signals of UA were used as a redox probe for indirect electrochemical determination of Am. The limit of detection (LOD) and linear concentration range were obtained as 0.028 and 0.08-9.0µmolL-1 (3Sb/m = 3), respectively. The feasibility of the proposed method was examined by the detection of Am in biological and pharmaceutical samples with satisfactory results. The constructed electrochemical sensor was applied for fast, simple and sensitive detection of Am in real environments.

Fabrication of a novel aptasensor based on three-dimensional reduced graphene oxide/polyaniline/gold nanoparticle composite as a novel platform for high sensitive and specific cocaine detection.

In the present research, we have developed a novel label free aptasensor based on screen printed carbon electrode (SPCE) modified with three-dimensional magnetic reduced graphene oxide(3D-MRGO)/polyaniline(PA)/gold nanoparticle(AuNP) nanocomposite for impedimetric determination of cocaine. To achieve this goal, a specific thiolated cocaine aptamer was immobilized onto the surface of synthesized nanocomposite. The signaling mechanism of the proposed aptasensor was based on increase in the [Fe(CN)6]3-/4- charge transfer resistance (RCT) as an electrochemical probe in the presence of target analyte. In order to collect of 3D-MRGO/PA/AuNP/aptamer on the surface of working electrode easily, a new electrochemical cell was fabricated. The advantages of the new electrochemical cell configuration can be counted as reusing SPCE for several times, obtaining repeatable responses, reducing required volume of electrolyte and probe solution and making proposed method more user-friendly. Cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FT-IR) were used for the characterization of synthesized nanocomposite and modified electrode surface. Under optimized condition, cocaine was determined in a linear concentration range from 0.09 to 85 nM with a detection limit of 0.029 nM by EIS. Also, in order to test applicability of the proposed aptasensor, it was applied to determine cocaine in urine and serum samples and satisfactory results were obtained.

Fabrication of a novel impedimetric sensor based on l-Cysteine/Cu(II) modified gold electrode for sensitive determination of ampyra.

This paper presents a novel impedimetric sensor for the sensitive determination of ampyra (Am) based on the l-Cysteine/Cu (II) modified gold electrode (Cu (II)/L-Cys/AuE). This novel sensing layer was characterized by different techniques, including atomic force microscopy (AFM), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Am determination by conventional electrochemical methods is not possible, because of its high redox overpotential. Therefore, [Fe(CN)6]3-/4- was used as a redox probe for the impedimetric determination of Am. Under the optimized conditions, the calibration curve for Am concentration was linear in the range 0.010-40.0 nM with a detection limit of 0.0028 nM. The practical applicability of the proposed sensor was examined by evaluating the detection of Am in biological fluids and pharmaceutical samples with satisfied recoveries. Therefore, the prepared sensor can hold great promise for fast, simple and sensitive detection of Am in various real samples.

Impedimetric immunosensor for the label-free and direct detection of botulinum neurotoxin serotype A using Au nanoparticles/graphene-chitosan composite.

In this work, a novel nanocomposite film consisting of the Au nanoparticles/graphene-chitosan has been designed to construct an impedimetric immunosensor for a rapid and sensitive immunoassay of botulinum neurotoxin A (BoNT/A). BoNT/A antibody was immobilized on glassy carbon electrode modified with Au nanoparticles/graphene-chitosan for the signal amplification. The fabrication of immunosensor was extensively characterized by using transmission electron microscopy (TEM), scanning electron microscopy (SEM), atomic force microscopy (AFM), X-ray diffraction (XRD), Fourier transform infrared (FTIR), cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS). The impedance changes, due to the specific immuno-interactions at the immunosensor surface that efficiently restricted the electron transfer of redox probe Fe(CN)64-/3- were utilized to detect BoNT/A. The measurements were highly targeted specific and linear with logarithmic BoNT/A concentrations in PBS, milk and human serum across a 0.27-268pgmL-1 range and associated with a detection limit of 0.11pgmL-1.