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

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          Abstract

          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.

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          Rapid and extraction-free detection of SARS-CoV-2 from saliva by colorimetric reverse-transcription loop-mediated isothermal amplification

          Abstract Background Rapid, reliable, and widespread testing is required to curtail the ongoing COVID-19 pandemic. Current gold standard nucleic acid tests are hampered by supply shortages in critical reagents including nasal swabs, RNA extraction kits, personal protective equipment, instrumentation, and labor. Methods To overcome these challenges, we developed a rapid colorimetric assay using reverse-transcription loop-mediated isothermal amplification (RT-LAMP) optimized on human saliva samples without an RNA purification step. We describe the optimization of saliva pretreatment protocols to enable analytically sensitive viral detection by RT-LAMP. We optimized the RT-LAMP reaction conditions and implemented high-throughput unbiased methods for assay interpretation. We tested whether saliva pretreatment could also enable viral detection by conventional reverse-transcription quantitative polymerase chain reaction (RT-qPCR). Finally, we validated these assays on clinical samples. Results The optimized saliva pretreatment protocol enabled analytically sensitive extraction-free detection of SARS-CoV-2 from saliva by colorimetric RT-LAMP or RT-qPCR. In simulated samples, the optimized RT-LAMP assay had a limit of detection of 59 (95% confidence interval: 44-104) particle copies per reaction. We highlighted the flexibility of LAMP assay implementation using three readouts: naked-eye colorimetry, spectrophotometry, and real-time fluorescence. In a set of 30 clinical saliva samples, colorimetric RT-LAMP and RT-qPCR assays performed directly on pretreated saliva samples without RNA extraction had accuracies greater than 90%. Conclusions Rapid and extraction-free detection of SARS-CoV-2 from saliva by colorimetric RT-LAMP is a simple, sensitive, and cost-effective approach with broad potential to expand diagnostic testing for the virus causing COVID-19.
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            Diagnostic potential of saliva: current state and future applications.

            Over the past 10 years, the use of saliva as a diagnostic fluid has gained attention and has become a translational research success story. Some of the current nanotechnologies have been demonstrated to have the analytical sensitivity required for the use of saliva as a diagnostic medium to detect and predict disease progression. However, these technologies have not yet been integrated into current clinical practice and work flow. As a diagnostic fluid, saliva offers advantages over serum because it can be collected noninvasively by individuals with modest training, and it offers a cost-effective approach for the screening of large populations. Gland-specific saliva can also be used for diagnosis of pathology specific to one of the major salivary glands. There is minimal risk of contracting infections during saliva collection, and saliva can be used in clinically challenging situations, such as obtaining samples from children or handicapped or anxious patients, in whom blood sampling could be a difficult act to perform. In this review we highlight the production of and secretion of saliva, the salivary proteome, transportation of biomolecules from blood capillaries to salivary glands, and the diagnostic potential of saliva for use in detection of cardiovascular disease and oral and breast cancers. We also highlight the barriers to application of saliva testing and its advancement in clinical settings. Saliva has the potential to become a first-line diagnostic sample of choice owing to the advancements in detection technologies coupled with combinations of biomolecules with clinical relevance.
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              Is Open Access

              Development of Point-of-Care Biosensors for COVID-19

              Jane Choi (2020)
              Coronavirus disease 2019 (COVID-19) outbreak has become a global pandemic. The deleterious effects of coronavirus have prompted the development of diagnostic tools to manage the spread of disease. While conventional technologies such as quantitative real time polymerase chain reaction (qRT-PCR) have been broadly used to detect COVID-19, they are time-consuming, labor-intensive and are unavailable in remote settings. Point-of-care (POC) biosensors, including chip-based and paper-based biosensors are typically low-cost and user-friendly, which offer tremendous potential for rapid medical diagnosis. This mini review article discusses the recent advances in POC biosensors for COVID-19. First, the development of POC biosensors which are made of polydimethylsiloxane (PDMS), papers, and other flexible materials such as textile, film, and carbon nanosheets are reviewed. The advantages of each biosensors along with the commercially available COVID-19 biosensors are highlighted. Lastly, the existing challenges and future perspectives of developing robust POC biosensors to rapidly identify and manage the spread of COVID-19 are briefly discussed.
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                Author and article information

                Journal
                Talanta
                Talanta
                Talanta
                Elsevier B.V.
                0039-9140
                1873-3573
                14 May 2022
                15 August 2022
                14 May 2022
                : 246
                : 123537
                Affiliations
                [a ]Chemical Injuries Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
                [b ]Department of Mechanical Engineering, Shohadaye Hoveizeh Campus of Technology, Shahid Chamran University of Ahvaz, Dashte Azadegan, Khuzestan, Iran
                [c ]Department of Chemistry, College of Sciences, Shiraz University, Shiraz, Iran
                [d ]Research and Development Department, Farin Behbood Tashkhis LTD, Tehran, Iran
                Author notes
                []Corresponding author.
                Article
                S0039-9140(22)00333-2 123537
                10.1016/j.talanta.2022.123537
                9107099
                35597231
                b092ecbd-94b6-4817-a382-afa07b4496cf
                © 2022 Elsevier B.V. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 29 April 2022
                : 8 May 2022
                : 8 May 2022
                Categories
                Article

                Analytical chemistry
                covid-19,colorimetric detection,metabolomics,paper-based device,sensor array,saliva

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