key: cord-0822746-3vplanox authors: Alireza Hashemi, Seyyed; Bahrani, Sonia; Mojtaba Mousavi, Seyyed; Omidifar, Navid; Ghaleh Golab Behbahan, Nader; Arjmand, Mohammad; Ramakrishna, Seeram; Bagheri Lankarani, Kamran; Moghadami, Mohsen; Shokripour, Mansoureh; Firoozsani, Mohammad; Chiang, Wei-Hung title: Ultra-Precise Label-Free Nanosensor Based on Integrated Graphene with Au Nanostars Toward Direct Detection of IgG Antibodies of SARS-CoV-2 in Blood date: 2021-05-08 journal: J Electroanal Chem (Lausanne) DOI: 10.1016/j.jelechem.2021.115341 sha: 034a7c39730894694e5689cb56bd44e50620662a doc_id: 822746 cord_uid: 3vplanox Rapid distribution of airborne contagious pathogenic viruses such as SRAS-CoV-2 and their severely adverse impacts on different aspects of the human society, along with significant weaknesses of traditional diagnostic platforms, raised the global requirement for the design/fabrication of precise, sensitive, and rapid nanosystems capable of specific detection of viral illnesses with almost negligible false-negative results. To address this indispensable requirement, we have developed an ultra-precise fast diagnostic platform capable of detecting the trace of monoclonal IgG antibody against S1 protein of SARS-CoV-2 within infected patients' blood specimens with COVID-19 in about 1 min. The as-developed electrochemical-based nanosensor consists of a highly activated graphene-based platform in conjunction with Au nanostars, which can detect SARS-CoV-2 antibodies with a fantastic detection limit (DL) and sensitivity of 0.18×10-19 % V/V and 2.14 μA.%V/V. cm-2, respectively, in human blood plasma specimens even upon the presence of a high amount of interfering compound/antibodies. The nanosensor also exhibited remarkable sensitivity/specificity compared with the gold standard (i.e., ELISA assay), which furtherly confirmed its superb performance. Rapid distribution of airborne pathogenic viruses throughout the world and their subsequent vast mortality in different countries raised global demand for the design/development of efficient, reliable, and rapid diagnostic kits to detect pathogenic viruses within biological fluids to stop their fast person-to-person transferring chain. Among these viruses, SARS-CoV-2, viz., severe acute respiratory syndrome coronavirus 2, is a nano-sized (about 100 nm) envelopedbased positively sense single genomic stranded RNA crown-shaped virus that can rapidly transfer among people through close interaction and spilled respirational compounds, e.g., sneeze or cough, which is also known as a highly infectious airborne virus from beta coronaviruses' family [1] [2] [3] [4] . Coronaviruses are a vast family of pathogenic viruses that contain different categories and cause mild/moderate upper respiratory tract illness, e.g., common cold [5] . So far, seven types of coronaviruses have been identified that can infect human being where four of them, i.e., 229E, NL63, OC43 and HKU1, are responsible for one-third of common flu throughout the world and can only cause mild illnesses, while the rest of them can cause severe sicknesses among which SARS-CoV, MERS-CoV, and SARS-CoV-2 can be mentioned [6] . Correspondingly, SARS-CoV-2 showed less mortality compared with SARS-CoV (10%) and MERS-CoV (35%); however, it showed superiorly higher infectivity and transmissibility [6, 7] . Moreover, SARS-CoV-2 exhibits different signs in people that range from mild symptoms to life-threatening situations [8] . In this regard, most people only show flu-like symptoms, while the rest of them experience more severe symptoms such as thrombophilic vasculitis in the lung and interstitial pneumonia [9] . Since the announcement of the SARS-CoV-2 pandemic [10] , the lack of specific, sensitive, and rapid diagnostic kits has become a significant pitfall toward stopping the transfer chain of SARS-CoV-2. The major point for controlling a viral pandemic is wise isolation of suspected or ill people via strict quarantine strategies, which require practical tools such as ultrasensitive/specific, rapid, and reliable diagnostic kits. In this matter, there are two main methods for the detection of viral infections, among which detection of nucleic acid (i.e., RNA or DNA) and viral biomarkers (i.e., antibodies and antigens) can be mentioned [11, 12] . Among the methods discussed above, RT-PCR and enzyme-linked immunosorbent assay (ELISA) is the most well-known procedures for direct detection of either nucleic acids or antigen/antibody within biological fluids. These traditional methods suffer some demerits such as the requirement for extraction, viral isolation, a sophisticated laboratory, high rate of false-negative, well-trained personnel and time-consuming processes, which are not compatible with the fast transferring rate of SARS-CoV-2 and cannot render the possibility for rapid isolation of infected people [13] . Therefore, developing a quick, precise, and sensitive sensor for specific detection of viruses within biological media is crucial. Biosensors are the key to this urgent demand. They could be considered a valid alternative instead of traditional flawful methods due to their excellent sensitivity/specificity that offers a rapid manner for detecting pathogenic viruses. Biosensors can be classified into several subgroups, including antigen/antibody-based, nucleic acid-based, enzymatic, and whole cellbased biosensors [14] . Owing to the urgency of COVID-19, researchers worldwide conducted great efforts to develop state-of-the-art biosensors for the fast identification of SARS-CoV-2 in biological specimens. Among recently developed platforms, field-effect transistor-based immunosensor coupled with SARS-CoV-2 spike antibody with a detection limit (DL) of 2.42×10 2 copies.mL -1 [15] , an electrochemical impedance-based immune biosensor for identification of SARS-CoV-2 antibody [16] , ACE-2 receptor-based lateral flow immunoassay (LFIA) for detection of Spike 1 protein of SARS-CoV-2 with DL of 1.86 × 10 5 copies.mL -1 [17] , an electrochemical assay based on decorated calixarene functionalized graphene oxide (GO) toward detecting SARS-CoV-2 RNA with DL of 200 copies.mL -1 [18] , detection of induced reactive oxygen species (ROS) related to lung/respiratory epithelium of infected people with COVID-19 [19] and immunosensor based on the carbon black integrated magnetic beads toward detection of S and N proteins of SARS-CoV-2 within saliva samples with DL of 19 and 8 ng.mL -1 , respectively [20] , can be mentioned. What is more, in a work by Torrente-Rodrı´guez et al. [21] , they developed a graphene-based multiplexed economic rapid diagnostic kit that can simultaneously detect nucleocapsid protein of viral antigen, IgG/IgM antibodies and C-reactive protein as an inflammatory biomarker; the developed platform can be used as an ultrasensitive and rapid detection approach for accurate identification of SARS-CoV-2 and its related biomarkers within biological fluids, which showed remarkable performance as a multiplex detection platform. These works highlight the superiority of the new generation of biosensors over traditional detection platforms, viz., RT-PCR and ELISA, toward fast and precise tracking of pathogenic viruses or their biomarkers within biological specimens. Despite all of the progress, developed biosensors use biological markers that provide them with limited sensitivity and DL, while a majority of them cannot identify infected people at either incubation or prodromal period of the disease. In our previous work, for the first time, we have developed a rapid label-free graphene-based nanosensor that can detect the trace of SARS-CoV-2 in about 1 min based on the applied step potential without any biological receptor within different biological fluids (i.e., swab, saliva and blood) with significantly low DL and great sensitivity of about 1.68×10 -22 µg.mL -1 and 0.0048 µA.µg.mL -1 .cm -2 , respectively. The asdeveloped nanosensor can also be used as a viral characterization approach and detect different viruses' fingerprints through their differentiable specific electrochemical patterns at vividly different voltage positions within any biological and non-biological fluids [22] . Correspondingly, developed nanosensors were well-characterized and used for enhancement of glassy carbon electrode (GCE) and working electrode of DRP C110 carbon-based screen-printed electrode. Then, the obtained data were compared with the ELISA assay as the gold standard to evaluate the performance of developed nanosensors toward label-free detection of monoclonal IgG antibodies against S1 glycoprotein of SARS-CoV-2 as confident COVID-19 detection metrics. In this study, produced nanomaterials were evaluated via different analyses to assess their quality and successful fabrication. Figure 1 (a) shows that low-angle XRD, i.e., X-ray diffractogram, of well-exfoliated GO is demonstrated. As depicts, obtained GO nanoflakes showed a well-resolved broad peak at 2ϴ of 22.8, which correspond to the (002) plane of GO, whereas the Raman spectrum ( Figure 1 (b)) of GO with D, G and D+G bands peaks at about 1341, 1592 and 2693 cm -1 along with I D /I G ratio of 0.92 furtherly confirmed the successful fabrication of GO along with its high quality [23] . Moreover, in Figure 1 (c) (I-III), the FTIR spectrum of GO, activated GO, and Au NS can be seen, respectively. As depicts within part (I), following XRD and Raman spectroscopy results, GO is successfully synthesized with main functional groups such as C-H sp 2 (802 cm -1 ), in-plane vibration of C-H (1011 cm -1 ), CO alkoxy (1084 cm -1 ), unoxidized C=C double bond carbon atoms, which is known as the primary fingerprint of graphene (1565 cm -1 ), viz., the fingerprint of the heterocyclic structure of graphene flake, carbonyl (i.e., C=O) functional groups (1695 cm -1 ) and dominant hydrophilic hydroxyl (i.e., -OH) functional groups (3077 cm -1 ) [22] [23] [24] . Correspondingly, in part (II) of Figure 1 , the FTIR spectrum of activated GO is demonstrated. As (3205 cm -1 ) [22] . The appearance of these peaks in the FTIR spectrum of the hybrid 2D platform of activated GO highlighted the successful decoration of well-exfoliated GO flakes with main/active functional groups of 8H, EDC and NHS, which considerably enhance the sensitivity of GO for precise detection of monoclonal IgG antibody against S1 glycoprotein of SARS-CoV-2 from its active domains. In Figure 1 (g), respectively. As shown in part (f), GO is perfectly exfoliated from pristine graphite and presents a wide/active surface area ideal for modification/activation with desirable functional groups toward detecting target compounds. Likewise, activated GO also exhibits a 2D planar structure ideal for interaction with antibodies owing to the well-distribution of functional groups of 8H, EDC and NHS all around its basal plane. In Figure 1 (h & i), TEM images of activated GO can be seen. As depicted, activated GO shows an excellent flake of GO that not only confirms the fantastic exfoliation of GO and formation of single-layer GO but also clearly demonstrates the homogenous distribution of 8H, EDC and NHS related functional groups all around the wide surface area of GO, providing abundant active sites for effective attraction/detection of monoclonal antibodies against S1 glycoproteins. The electrochemical performance of enhanced electrodes with developed nanomaterials was assessed in (Fe(CN) 6 ) 3−/4− as redox probes through cyclic voltammetry (CV) and EIS analyses, as performed in our previous work [25] . transfer rate within the solution [26] . EIS analyses were performed at a frequency ranging from 0.1 to 10 5 Hz toward assessing the overall performance of developed sensors in case of interfaces and conductivity [27] . The obtained results were in good agreement with CV measurements, as presented in Figure 2 Additionally, developed nanomaterials' performance toward evaluating their antibody loading capability was also assessed through EIS and DPV analyses in PBS with pH 7.4; in Figure 2 , a view of these data can be seen clearly. As shown within Figure 2 (c), the related EIS outcome for each modified GCE is approximated, and electron transfer kinetics parameters, including Rs, R ct , and C dl , were extracted and tabulated in Table 1 . As tabulated, the initial value of C dl for the bare GCE was considerably declined upon the decoration of GCE with activated GO and G-Au NS owing to coverage of active sites of GCE by compositions mentioned above, which could thence lead to an increase in the thickness of the final film. In this matter, the C dl and C ф parameters can be measured via the following formula: The "g" parameter, which indicates the surface inhomogeneity and the porosity of the surface, is close to unity upon the accumulation of antibodies on the active surface area of the electrode [28] . The surface concentration (г) of adsorbed antibodies on the modified GCE by G-Au NS can be estimated from the following equation [2] : where n is the electron transfer rate (in here the value is 1), F is the Faraday constant (96485.34 C.mol −1 ), г is the surface concentration, and A is the surface area of the electrode. In this matter, the г value of IgG antibody against S1 protein of SARS-CoV-2 was measured to be 1.56×10 -7 mol.cm -2 , indicating the successful absorption of the antibody with the modified GCE by G-Au NS. Moreover, as depicted in Figure 2 (c) and Table 1 (Figure 2 (c) ). In accord with EIS data, the DPV analysis confirmed the modified platform's superior performance toward detecting SARS-CoV-2 antibodies in PBS with pH 7.4. As shown in Figure 2 (d), activated GO noticed the antibody with an intensity of 0.6 µA with a wider twin peak. Simultaneously, the addition of Au NSs to the composition considerably intensified the peak by about 200 % and improved the pattern's quality. These data clearly showed the integrated nanosensor's fantastic performance toward accurate/direct detection of SARS-CoV-2 antibodies in biological fluids. They furtherly highlighted the amplifying role of Au NSs for better detection of IgG antibodies against S1 glycoprotein of SARS-CoV-2. Additionally, the effect of potential scan rate (υ) on the electrochemical properties of GCE-G-Au NS between the range of 30-300 mV.s -1 was studied by CV measurement in the probe solution (5mM Fe(CN) 6 3-/4-) ( Figure S1 ). According to the Randles-Sevcik equation (I p = 2.69×10 5 n 3/2 A eff D 1/2 ν 1/2 C) and the slope of Ip-ν 1/2 plot, the effective area of GCE-G-Au NS was estimated to be 5.24 mm 2 , which is considerably higher than other electrodes. In the Randles-Sevcik equation, I p is the current signal (A), n is electrons transfer rate, A eff is the effective surface area (cm 2 ), D is the diffusion coefficient of 5.0 mM K 3 Fe(CN) 6 (cm 2 .s -1 ), v is the scan rate (V.s -1 ), and C is related to the bulk concentration of redox probe (mol.mL -3 ). GCE-G-Au NS platform's electrocatalytic capability regarding the rapid detection of monoclonal antibodies against S1 glycoprotein of SARS-CoV-2 in biological and non-biological fluids was initially traced by DPV technique in PBS with pH 7.4. In Figure 3 showing similar patterns to the S1 glycoprotein of SARS-CoV-2, as mentioned in our previous study [22] . Correspondingly, the monoclonal antibody against S1 glycoprotein of SARS-CoV-2 shows a very similar pattern compared with its source antigen and exhibits an electrochemical pattern with twin peaks at -0.02 V and 0.06 V between voltage range of -0.15 V to 0.15 V. This evidence confirmed the specific attachment of monoclonal antibody against S1 glycoprotein of SARS-CoV-2 antigen to the nanosensor owing to considerable similarities between their DPV patterns that could be due to the similarities in their active functional groups for effective immunological interaction between the antibody and source antigen. In the next step, the quantitative analysis of antibody in PBS (pH 7.4) was conducted through the generation of differential pulse voltammograms of antibody through varying concentrations of antibody in the optimum assessment conditions; a view of these data can be seen in Figure 3 (b), while their related calibration curve can be seen in Figure S2 To check the capability of the developed nanosensor toward detection of SARS-CoV-2 antibody in biological fluids, the DPV pattern of monoclonal antibody against S1 glycoprotein of SARS-CoV-2 ( Figure 3 (c)) and its related calibration curve were obtained in human blood plasma as aqueous biological sample ( Figure S2 (b) ). The calibration curve of monoclonal antibodies was obtained in the range of 1.25×10 -19 -90×10 -19 %V/V, whereas the respective DL and sensitivity were estimated to be 0.18×10 -19 % V/V and 2.14 μA.%V/V. cm -2 , respectively, for received current signals in human blood plasma samples. Obtained data vividly showed that the developed nanosensor based on the G-Au NS exhibits a very low DL and superiorly high sensitivity toward detecting monoclonal antibodies against S1 glycoprotein within aquatic media. What is more, the antibody also appeared at the same position in both PBS and plasma samples, viz., -0.03 and 0.06 V, which furtherly confirm the repeatability of the nanosensor's response. The fantastic electrocatalytic performance of GCE-G-Au NS could be owing to the perfect adsorptive potential of activated GO in conjunction with Au NSs, in which the Au NS facilitates the overall electron transfer rate and the activated GO improves the specific active surface area and sensitivity of the integrated platform toward direct detection of S1 antibody through its electroactive functional groups. In this regard, the proposed electrocatalyst could provide more adsorptive ability for antibodies through diverse interactions, including hydrogen bonding between either amino or acidic functional groups of antibodies with active functional groups of nano electrocatalyst on the modified working electrode's surface. In addition, CV analysis as one of the most practical and common assessment approaches for the characterization of selected chemical compounds could be employed as an efficient tool for examining electrochemical mechanisms of diverse chemical reactions. In this regard, the possible mechanism for adsorption of monoclonal antibody against S1 glycoprotein on the modified electrode's surface was initially assessed through CV analyses. To evaluate the proposed technique's electrocatalytic mechanism, the effect of variable potential scan rate on the electrochemical detection mechanism of antibodies was first performed via the CV method. As demonstrated within Figure 3 (d), upon changing the scan rate from 0.01 to 0.2 V s -1 , a set of weak current signals were observed; the related calibration curve can also be seen in Figure S2 (c). Correspondingly, obtained data via variation of anodic currents over scan rates revealed that the reaction is controlled/governed via the surface-confined reactions and adsorption electron transfer mechanism on the active surface area of the working electrode, which exhibits that the process is based on the direct electron transfer mechanism. Furthermore, due to the inherent low resolution and sensitivity of the CV method, it is more desired to utilize DPV as a far more sensitive assay to improve the obtained results' resolution. Thereby, more accurate outcomes can be achieved by DPV analysis to recognize various mechanisms occurring on the electrode's surface. Accordingly, to probe the antibodies' detection mechanism against S1 glycoprotein, the forward and backward sweeping of potential related to the antibodies' voltammetric pattern was performed, and their respective current signals were carefully analyzed. Figure 3 (e) exhibits the obtained processes related to the antibody against S1 glycoprotein within a PBS solution with pH 7.4. The labelled signal of the redox peak traced at the voltage position of -0.03 V is attributed to the nanosensor's electrochemical response on the modified working electrode's surface. The outcome of the DPV essay illustrated a slightly weak peak separation, somewhat about ~20 mV between the cathodic and anodic peaks, which showed ipa/ipc~1, exhibiting a reversible process, and correspond to the adsorption and interaction of electroactive hydroxyl or amine functional groups of the monoclonal IgG antibody against S1 glycoprotein with NHS/EDC activated hydrogen-based groups on the surface of modified electrode. These outcomes clearly showed that the process is governed via the electrochemical (E) mechanism. What is more, the introduction of 8H to the composition could increase the total Table S1 . As tabulated, the developed nanosensor revealed a perfect agreement with obtained data from the ELISA assay. Accordingly, the nanosensor detected the fingerprint of antibody against S1 glycoprotein in 26 Furthermore, validation of achieved clinical data and correlation between the nanosensor and ELISA assay were assessed via plotting the related ROC curves ( Figure S3) ; accordingly, related evidence can be seen within Tables S2-S7 . As demonstrated within Figure S3 (a) and Tables S2 and S3, the developed nanosensor showed perfect outcomes with an area under the curve (AUC) of 0.995, standard error of 0.007 and lower bound/upper bound of 0.982/1.000, which revealed the superior accuracy of the sensor and compatibility of its outcomes with the obtained data from ELISA assay. Correspondingly, in Table S3 , the relation between a cutoff point and sensitivity/specificity of the test can be seen. As tabulated, at a cutoff point of 0.2185 µA, the sensor showed a sensitivity/specificity of 100%/85%. In comparison, at a cutoff point of 0.3265 µA, the sensitivity/specificity becomes 95%/100%. Obtained outcomes vividly showed that the sensor could be used as a diagnostic kit for the confident evaluation of ill people with the infectious disease of COVID-19. These outcomes exhibit the platform's flexibility for becoming a fast diagnostic setup for either screening (at high sensitivities) or confident detection of viral disease (at high specificities). What is more, in Figure S3 (b) and Tables S4-S7, the correlation between the intensity of nanosensor based on µA and optical density obtained via ELISA assay was assessed. As demonstrated, the nanosensor showed a strong correlation with ELISA assay data with an AUC of 0.995, revealing the nanosensor's fantastic accuracy compared with the gold standard. The detection mechanism of IgG antibodies by the nanosensor is also assessed to further highlight its label-free approach toward precise detection of antibodies. The developed nanosensor is perfectly beautified with exciting features that enable the rapid electrochemical detection of antibodies via their active functional groups. Accordingly, the GO provides wide active surface area along with active hydrophilic functional groups such as -OH and C=O that ease the interaction with considered modifiers and thereby lead to their homogeneous distribution and attachment throughout and on the surface of GO, respectively [30] [31] [32] [33] . Moreover, the addition of 8H to the GO improves the overall rate of -OH functional groups and boosts the platform's sensitivity through its quinoline structure. More importantly, the addition of the NHS/EDC complex to the GO and 8H leads to activation of carbonyl and hydrogen-based functional groups that improve the interaction of the developed nanosensor with -NH 2 , -OH and C=O functional groups and provides the possibility for efficient absorption of antibodies through their electroactive amine functional groups located on their F ab region at neutral pH values. This process leads to the absorption of antibodies via the nanosensor and subsequent generation of a unique electrochemical pattern for IgG antibodies' glycoprotein structure via DPV assay. Additionally, the addition of Au NSs to the complex of activated GO improves the intensity of the nanosensor's voltammetric response, detection limit and sensitivity toward detection of antibodies, which arises from the superior electrical conductivity, electrocatalytic activity and compatibility of the Au NS with the graphene-based substrate [22] . In Figure 4 , a general view of this process can be seen. Fast person-to-person transfer of pathogenic viruses such as SARS-CoV-2 throughout the world raised healthcare authorities' requirements for developing precise, rapid and sensitive diagnostic platforms capable of detecting SARS-CoV-2's biomarkers within biological samples. In this study, we have addressed this urgent requirement via developing a quick, ultra-high sensitive and precise nanosystem based on integrated Au NS with an activated graphene-based platform that can rapidly detect the trace/fingerprint of monoclonal IgG antibody of SARS-CoV-2's S1 protein within biological media with fantastic DL and sensitivity of 0.18×10 -19 % V/V and 2.14 μA.%V/V. cm -2 , respectively. The sensor also exhibited a strong correlation with obtained data from gold-standard (ELISA assay). In this matter, it showed perfect sensitivity/specificity of about 100%/85% and 95%/100% at cutoff points of 0.2185 µA and 0.3265 µA, respectively, along with AUC of 0.995 from ROC curves. These outcomes justified the fantastic performance of the developed diagnostic kit for precise, rapid, and confident detection of infected people with the infectious disease of COVID-19, which is a vital requirement for viral outbreaks. Validation and Resources Highlights: An activated graphene-based nanosystem was developed and coupled with gold nanostars The hybrid platform was used for activation of carbon-based screen-printed electrodes The developed diagnostic kit rapidly detected the monoclonal IgG antibody of SARS-CoV-2 The developed nanosensor showed superior detection limit and sensitivity Origin and evolution of pathogenic coronaviruses Epidemiology, genetic recombination, and pathogenesis of coronaviruses Reverse transcription loop-mediated isothermal amplification combined with nanoparticles-based biosensor for diagnosis of COVID-19 Recent biotechnological approaches for treatment of novel COVID-19: from bench to clinical trial Covid-19 and air conditioning-is there an environmental link? Developments in biosensors for CoV detection and future trends Detection of severe acute respiratory syndrome (SARS) coronavirus nucleocapsid protein in human serum using a localized surface plasmon coupled fluorescence fiber-optic biosensor Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study COVID-19 pulmonary involvement: is really an interstitial pneumonia? WHO Director-General's opening remarks at the media briefing on COVID-19 Methods in virus diagnostics: from ELISA to next generation sequencing Chemical and Biological Sensors for Viral Detection Nanoscale virus biosensors: state of the art Rapid detection of COVID-19 causative virus (SARS-CoV-2) in human nasopharyngeal swab specimens using field-effect transistor-based biosensor Rapid detection of SARS-CoV-2 antibodies using electrochemical impedance-based detector A novel rapid detection for SARS-CoV-2 spike 1 antigens using human angiotensin converting enzyme 2 (ACE2) Ultrasensitive supersandwich-type electrochemical sensor for SARS-CoV-2 from the infected COVID-19 patients using a smartphone Real-time diagnosis of reactive oxygen species (ROS) in fresh sputum by electrochemical tracing; correlation between COVID-19 and viral-induced ROS in lung/respiratory epithelium during this pandemic Magnetic beads combined with carbon black-based screenprinted electrodes for COVID-19: A reliable and miniaturized electrochemical immunosensor for SARS-CoV-2 detection in saliva SARS-CoV-2 RapidPlex: A Graphene-Based Multiplexed Telemedicine Platform for Rapid and Low-Cost COVID-19 Diagnosis and Monitoring Ultra-sensitive viral glycoprotein detection NanoSystem toward accurate tracing SARS-CoV-2 in biological/non-biological media Superior X-ray Radiation Shielding Effectiveness of Biocompatible Polyaniline Reinforced with Hybrid Graphene Oxide-Iron Tungsten Nitride Flakes Lead oxidedecorated graphene oxide/epoxy composite towards X-Ray radiation shielding Ultra-sensitive viral glycoprotein detection NanoSystem toward accurate tracing SARS-CoV-2 in biological/nonbiological media Ultrasound-accelerated synthesis of gold nanoparticles modified choline chloride functionalized graphene oxide as a novel sensitive bioelectrochemical sensor: Optimized meloxicam detection using CCD-RSM design and application for human plasma sample Selective Detection of Dopamine in the Presence of Ascorbic and Uric Acids through its Covalent Immobilization on Gold Mercaptopropionic Acid Self-assembled Monolayer Functionalization of gold mercaptopropionic acid self-assembled monolayer with 5-amino-1,10-phenanthroline: Interaction with iron(II) and application for selective recognition of guanine Coupled graphene oxide with hybrid metallic nanoparticles as potential electrochemical biosensors for precise detection of ascorbic acid within blood Reinforced Polypyrrole with 2D Graphene Flakes Decorated with Interconnected Nickel-Tungsten Metal Oxide Complex Toward Superiorly Stable Supercapacitor Graphene nano-ribbon based high potential and efficiency for DNA, cancer therapy and drug delivery applications Coupled graphene oxide with hybrid metallic nanoparticles as potential electrochemical biosensors for precise detection of ascorbic acid within blood Decorated graphene with aluminum fumarate metal organic framework as a superior non-toxic agent for efficient removal of Congo Red dye from wastewater Credit for Authors Statement: Seyyed Alireza Hashemi Software, Validation, Formal analysis, Investigation, Data Curation, Writing -Original Draft, Writing -Review & Editing, Visualization and Project administration The fabricated nanosystem showed perfect sensitivity/specificity compared with the gold standard