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To enable routine surveillance and comprehensive diagnostic applications, there is a need for detection technologies that can scale to test many samples\n                    <jats:sup>1\u20133<\/jats:sup>\n                    while simultaneously testing for many pathogens\n                    <jats:sup>4\u20136<\/jats:sup>\n                    . Here, we develop Combinatorial Arrayed Reactions for Multiplexed Evaluation of Nucleic acids (CARMEN), a platform for scalable, multiplexed pathogen detection. In the CARMEN platform, nanolitre droplets containing CRISPR-based nucleic acid detection reagents\n                    <jats:sup>7<\/jats:sup>\n                    self-organize in a microwell array\n                    <jats:sup>8<\/jats:sup>\n                    to pair with droplets of amplified samples, testing each sample against each CRISPR RNA (crRNA) in replicate. The combination of CARMEN and Cas13 detection (CARMEN\u2013Cas13) enables robust testing of more than 4,500 crRNA\u2013target pairs on a single array. Using CARMEN\u2013Cas13, we developed a multiplexed assay that simultaneously differentiates all 169 human-associated viruses with at least 10 published genome sequences and rapidly incorporated an additional crRNA to detect the causative agent of the 2020 COVID-19 pandemic. CARMEN\u2013Cas13 further enables comprehensive subtyping of influenza A strains and multiplexed identification of dozens of HIV drug-resistance mutations. The intrinsic multiplexing and throughput capabilities of CARMEN make it practical to scale, as miniaturization decreases reagent cost per test by more than 300-fold. Scalable, highly multiplexed CRISPR-based nucleic acid detection shifts diagnostic and surveillance efforts from targeted testing of high-priority samples to comprehensive testing of large sample sets, greatly benefiting patients and public health\n                    <jats:sup>9\u201311<\/jats:sup>\n                    .\n                  <\/jats:p>","DOI":"10.1038\/s41586-020-2279-8","type":"journal-article","created":{"date-parts":[[2020,4,29]],"date-time":"2020-04-29T06:03:17Z","timestamp":1588140197000},"page":"277-282","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":816,"title":["Massively multiplexed nucleic acid detection with Cas13"],"prefix":"10.1038","volume":"582","author":[{"given":"Cheri M.","family":"Ackerman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8971-184X","authenticated-orcid":false,"given":"Cameron","family":"Myhrvold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sri Gowtham","family":"Thakku","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1939-3102","authenticated-orcid":false,"given":"Catherine A.","family":"Freije","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8871-2349","authenticated-orcid":false,"given":"Hayden C.","family":"Metsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9972-3035","authenticated-orcid":false,"given":"David K.","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon H.","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chloe K.","family":"Boehm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tinna-S\u00f3lveig F.","family":"Kosoko-Thoroddsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jared","family":"Kehe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tien G.","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amber","family":"Carter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Kulesa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Barnes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivien G.","family":"Dugan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah T.","family":"Hung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4889-8783","authenticated-orcid":false,"given":"Paul C.","family":"Blainey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pardis C.","family":"Sabeti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,4,29]]},"reference":[{"key":"2279_CR1","doi-asserted-by":"publisher","first-page":"eaan1589","DOI":"10.1126\/scitranslmed.aan1589","volume":"9","author":"I Bosch","year":"2017","unstructured":"Bosch, I. et al. Rapid antigen tests for dengue virus serotypes and Zika virus in patient serum. Sci. Transl. Med. 9, eaan1589 (2017). https:\/\/doi.org\/10.1126\/scitranslmed.aan1589.","journal-title":"Sci. Transl. Med."},{"key":"2279_CR2","doi-asserted-by":"publisher","first-page":"1528","DOI":"10.1128\/JCM.03368-12","volume":"51","author":"EB Popowitch","year":"2013","unstructured":"Popowitch, E. B., O\u2019Neill, S. S. & Miller, M. B. Comparison of the Biofire FilmArray RP, Genmark eSensor RVP, Luminex xTAG RVPv1, and Luminex xTAG RVP fast multiplex assays for detection of respiratory viruses. J. Clin. Microbiol. 51, 1528\u20131533 (2013). https:\/\/doi.org\/10.1128\/JCM.03368-12.","journal-title":"J. Clin. Microbiol."},{"key":"2279_CR3","doi-asserted-by":"publisher","first-page":"992","DOI":"10.1002\/anie.201609108","volume":"56","author":"Y Du","year":"2017","unstructured":"Du, Y. et al. Coupling sensitive nucleic acid amplification with commercial pregnancy test strips. Angew. Chem. Int. 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Additional related applications for intellectual property have been filed by the Broad Institute. P.C.S. is a co-founder of and consultant to Sherlock Biosciences and Board Member of Danaher Corporation, and holds equity in both companies. D.T.H. is also a co-founder of Sherlock Biosciences. In addition, P.C.B. is a consultant to and equity holder in companies in the microfluidics and life sciences industries including 10X Genomics, GALT, Celsius Therapeutics, and Next Generation Diagnostics.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}