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      BIOSENSORS FOR THE DETECTION OF RESPIRATORY VIRUSES: A REVIEW

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          Highlights

          • A review containing the newest contributions of biosensors for respiratory viruses’ detection is presented;

          • Influenza virus, coronavirus and respiratory syncytial virus were extensively analyzed;

          • Tables containing biosensors information regarding the detection of the viruses are presented;

          • Discussion based on the new trends and authors accomplishments are applied;

          • SARS-CoV-2 biosensors already published were included and analyzed.

          Abstract

          The recent events of outbreaks related to different respiratory viruses in the past few years, exponentiated by the pandemic caused by the coronavirus disease 2019 (COVID-19), reported worldwide caused by SARS-CoV-2, raised a concern and increased the search for more information on viruses-based diseases. The detection of the virus with high specificity and sensitivity plays an important role for an accurate diagnosis. Despite the many efforts to identify the SARS-CoV-2, the diagnosis still relays on expensive and time-consuming analysis. A fast and reliable alternative is the use of low-cost biosensor for in loco detection. This review gathers important contributions in the biosensor area regarding the most current respiratory viruses, presents the advances in the assembly of the devices and figures of merit. All information is useful for further biosensor development for the detection of respiratory viruses, such as for the new coronavirus.

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          Most cited references158

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          SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients

          To the Editor: The 2019 novel coronavirus (SARS-CoV-2) epidemic, which was first reported in December 2019 in Wuhan, China, and has been declared a public health emergency of international concern by the World Health Organization, may progress to a pandemic associated with substantial morbidity and mortality. SARS-CoV-2 is genetically related to SARS-CoV, which caused a global epidemic with 8096 confirmed cases in more than 25 countries in 2002–2003. 1 The epidemic of SARS-CoV was successfully contained through public health interventions, including case detection and isolation. Transmission of SARS-CoV occurred mainly after days of illness 2 and was associated with modest viral loads in the respiratory tract early in the illness, with viral loads peaking approximately 10 days after symptom onset. 3 We monitored SARS-CoV-2 viral loads in upper respiratory specimens obtained from 18 patients (9 men and 9 women; median age, 59 years; range, 26 to 76) in Zhuhai, Guangdong, China, including 4 patients with secondary infections (1 of whom never had symptoms) within two family clusters (Table S1 in the Supplementary Appendix, available with the full text of this letter at NEJM.org). The patient who never had symptoms was a close contact of a patient with a known case and was therefore monitored. A total of 72 nasal swabs (sampled from the mid-turbinate and nasopharynx) (Figure 1A) and 72 throat swabs (Figure 1B) were analyzed, with 1 to 9 sequential samples obtained from each patient. Polyester flock swabs were used for all the patients. From January 7 through January 26, 2020, a total of 14 patients who had recently returned from Wuhan and had fever (≥37.3°C) received a diagnosis of Covid-19 (the illness caused by SARS-CoV-2) by means of reverse-transcriptase–polymerase-chain-reaction assay with primers and probes targeting the N and Orf1b genes of SARS-CoV-2; the assay was developed by the Chinese Center for Disease Control and Prevention. Samples were tested at the Guangdong Provincial Center for Disease Control and Prevention. Thirteen of 14 patients with imported cases had evidence of pneumonia on computed tomography (CT). None of them had visited the Huanan Seafood Wholesale Market in Wuhan within 14 days before symptom onset. Patients E, I, and P required admission to intensive care units, whereas the others had mild-to-moderate illness. Secondary infections were detected in close contacts of Patients E, I, and P. Patient E worked in Wuhan and visited his wife (Patient L), mother (Patient D), and a friend (Patient Z) in Zhuhai on January 17. Symptoms developed in Patients L and D on January 20 and January 22, respectively, with viral RNA detected in their nasal and throat swabs soon after symptom onset. Patient Z reported no clinical symptoms, but his nasal swabs (cycle threshold [Ct] values, 22 to 28) and throat swabs (Ct values, 30 to 32) tested positive on days 7, 10, and 11 after contact. A CT scan of Patient Z that was obtained on February 6 was unremarkable. Patients I and P lived in Wuhan and visited their daughter (Patient H) in Zhuhai on January 11 when their symptoms first developed. Fever developed in Patient H on January 17, with viral RNA detected in nasal and throat swabs on day 1 after symptom onset. We analyzed the viral load in nasal and throat swabs obtained from the 17 symptomatic patients in relation to day of onset of any symptoms (Figure 1C). Higher viral loads (inversely related to Ct value) were detected soon after symptom onset, with higher viral loads detected in the nose than in the throat. Our analysis suggests that the viral nucleic acid shedding pattern of patients infected with SARS-CoV-2 resembles that of patients with influenza 4 and appears different from that seen in patients infected with SARS-CoV. 3 The viral load that was detected in the asymptomatic patient was similar to that in the symptomatic patients, which suggests the transmission potential of asymptomatic or minimally symptomatic patients. These findings are in concordance with reports that transmission may occur early in the course of infection 5 and suggest that case detection and isolation may require strategies different from those required for the control of SARS-CoV. How SARS-CoV-2 viral load correlates with culturable virus needs to be determined. Identification of patients with few or no symptoms and with modest levels of detectable viral RNA in the oropharynx for at least 5 days suggests that we need better data to determine transmission dynamics and inform our screening practices.
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            Rapid Detection of COVID-19 Causative Virus (SARS-CoV-2) in Human Nasopharyngeal Swab Specimens Using Field-Effect Transistor-Based Biosensor

            Coronavirus disease 2019 (COVID-19) is a newly emerging human infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, previously called 2019-nCoV). Based on the rapid increase in the rate of human infection, the World Health Organization (WHO) has classified the COVID-19 outbreak as a pandemic. Because no specific drugs or vaccines for COVID-19 are yet available, early diagnosis and management are crucial for containing the outbreak. Here, we report a field-effect transistor (FET)-based biosensing device for detecting SARS-CoV-2 in clinical samples. The sensor was produced by coating graphene sheets of the FET with a specific antibody against SARS-CoV-2 spike protein. The performance of the sensor was determined using antigen protein, cultured virus, and nasopharyngeal swab specimens from COVID-19 patients. Our FET device could detect the SARS-CoV-2 spike protein at concentrations of 1 fg/mL in phosphate-buffered saline and 100 fg/mL clinical transport medium. In addition, the FET sensor successfully detected SARS-CoV-2 in culture medium (limit of detection [LOD]: 1.6 × 101 pfu/mL) and clinical samples (LOD: 2.42 × 102 copies/mL). Thus, we have successfully fabricated a promising FET biosensor for SARS-CoV-2; our device is a highly sensitive immunological diagnostic method for COVID-19 that requires no sample pretreatment or labeling.
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              Biosensors and their applications - A review.

              The various types of biosensors such as enzyme-based, tissue-based, immunosensors, DNA biosensors, thermal and piezoelectric biosensors have been deliberated here to highlight their indispensable applications in multitudinous fields. Some of the popular fields implementing the use of biosensors are food industry to keep a check on its quality and safety, to help distinguish between the natural and artificial; in the fermentation industry and in the saccharification process to detect precise glucose concentrations; in metabolic engineering to enable in vivo monitoring of cellular metabolism. Biosensors and their role in medical science including early stage detection of human interleukin-10 causing heart diseases, rapid detection of human papilloma virus, etc. are important aspects. Fluorescent biosensors play a vital role in drug discovery and in cancer. Biosensor applications are prevalent in the plant biology sector to find out the missing links required in metabolic processes. Other applications are involved in defence, clinical sector, and for marine applications.
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                Author and article information

                Contributors
                Journal
                Talanta Open
                Published by Elsevier B.V.
                2666-8319
                2666-8319
                16 August 2020
                16 August 2020
                : 100007
                Affiliations
                [a ]Group of Electrochemistry Applied to Polymers and Sensors - Multidisciplinary Group of Research, Science and Technology (RMPCT) – Laboratory of Electroanalytic Applied to Biotechnology and Food Engineering (LEABE) – Chemistry Institute – Federal University of Uberlândia – campus Patos de Minas – Av. Getúlio Vargas, 230, 38.700-128, Patos de Minas, Minas Gerais, Brazil
                [b ]Institute of Science and Technology, Laboratory of Electrochemistry and Applied Nanotechnology, Federal University of the Jequitinhonha and Mucuri Valleys, Diamantina, Minas Gerais, Brazil
                [c ]Laboratory of Microbiology (MICRO) – Biotechnology Institute – Federal University of Uberlândia – campus Patos de Minas – Av. Getúlio Vargas, 230, 38.700-128, Patos de Minas, Minas Gerais, Brazil
                Author notes
                [* ]Corresponding author: Tel: +55(34)3823174, Av. Getúlio Vargas, 230, Centro, Patos de Minas, Minas Gerais, Brazil, ZIP code: 38700-128, ORCID: 0000-0003-4675-971X diegoleoni@ 123456ufu.br
                Article
                S2666-8319(20)30007-2 100007
                10.1016/j.talo.2020.100007
                7428963
                34913046
                74a821bb-a2a5-4bc4-8598-c86a4fc10a49
                © 2020 Published by Elsevier B.V.

                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.

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                biosensors,respiratory virus,detection,diagnosis
                biosensors, respiratory virus, detection, diagnosis

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