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In this study, we designed a protein\u2010enzyme\u2010free nano\u2010construction, named four\u2010armed DNA machine (4DNM), that requires neither an amplification stage nor a high\u2010temperature annealing step for SARS\u2010CoV\u20102 detection. It uses a binary deoxyribozyme (BiDz) sensor incorporated in a DNA nanostructure equipped with a total of four RNA\u2010binding arms. Additional arms were found to improve the limit of detection at least 10\u2010fold. The sensor distinguished SARS\u2010CoV\u20102 from other respiratory viruses and correctly identified five positive and six negative clinical samples verified by quantitative polymerase chain reaction (RT\u2010qPCR). The strategy reported here can be used for the detection of long natural RNA and can become a basis for a point\u2010of\u2010care or home diagnostic test.<\/jats:p>","DOI":"10.1002\/cmdc.202200382","type":"journal-article","created":{"date-parts":[[2022,8,28]],"date-time":"2022-08-28T22:34:45Z","timestamp":1661726085000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Toward a Home Test for COVID\u201019 Diagnosis: DNA Machine for Amplification\u2010Free SARS\u2010CoV\u20102 Detection in Clinical Samples"],"prefix":"10.1002","volume":"17","author":[{"given":"Ahmed A.","family":"El\u2010Deeb","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Robotics and Biosensor Materials SCAMT Institute ITMO University  191002 Saint Petersburg Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia S.","family":"Zablotskaya","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Robotics and Biosensor Materials SCAMT Institute ITMO University  191002 Saint Petersburg Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria S.","family":"Rubel","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Robotics and Biosensor Materials SCAMT Institute ITMO University  191002 Saint Petersburg Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moustapha A. 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