{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T00:21:15Z","timestamp":1794356475793,"version":"4.9.0"},"reference-count":55,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2022,2,7]],"date-time":"2022-02-07T00:00:00Z","timestamp":1644192000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,2,7]],"date-time":"2022-02-07T00:00:00Z","timestamp":1644192000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Med"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The coronavirus disease 2019 (COVID-19) pandemic has demonstrated a clear need for high-throughput, multiplexed and sensitive assays for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other respiratory viruses and their emerging variants. Here, we present a cost-effective virus and variant detection platform, called microfluidic Combinatorial Arrayed Reactions for Multiplexed Evaluation of Nucleic acids (mCARMEN), which combines CRISPR-based diagnostics and microfluidics with a streamlined workflow for clinical use. We developed the mCARMEN respiratory virus panel to test for up to 21 viruses, including SARS-CoV-2, other coronaviruses and both influenza strains, and demonstrated its diagnostic-grade performance on 525 patient specimens in an academic setting and 166 specimens in a clinical setting. We further developed an mCARMEN panel to enable the identification of 6 SARS-CoV-2 variant lineages, including Delta and Omicron, and evaluated it on 2,088 patient specimens with near-perfect concordance to sequencing-based variant classification. Lastly, we implemented a combined Cas13 and Cas12 approach that enables quantitative measurement of SARS-CoV-2 and influenza A viral copies in samples. The mCARMEN platform enables high-throughput surveillance of multiple viruses and variants simultaneously, enabling rapid detection of SARS-CoV-2 variants.<\/jats:p>","DOI":"10.1038\/s41591-022-01734-1","type":"journal-article","created":{"date-parts":[[2022,2,7]],"date-time":"2022-02-07T07:03:01Z","timestamp":1644217381000},"page":"1083-1094","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":303,"title":["Multiplexed CRISPR-based microfluidic platform for clinical testing of respiratory viruses and identification of SARS-CoV-2 variants"],"prefix":"10.1038","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1163-7002","authenticated-orcid":false,"given":"Nicole L.","family":"Welch","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1302-4020","authenticated-orcid":false,"given":"Meilin","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0455-5364","authenticated-orcid":false,"given":"Catherine","family":"Hua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliane","family":"Weller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marzieh Ezzaty","family":"Mirhashemi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tien G.","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8834-1461","authenticated-orcid":false,"given":"Sreekar","family":"Mantena","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew R.","family":"Bauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bennett M.","family":"Shaw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheri M.","family":"Ackerman","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\/0000-0002-4968-7072","authenticated-orcid":false,"given":"Megan W.","family":"Tse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jared","family":"Kehe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Martine","family":"Uwera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline S.","family":"Eversley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek A.","family":"Bielwaski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graham","family":"McGrath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Braidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felecia","family":"Cerrato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gage K.","family":"Moreno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4163-706X","authenticated-orcid":false,"given":"Lydia A.","family":"Krasilnikova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2110-7475","authenticated-orcid":false,"given":"Brittany A.","family":"Petros","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabrielle L.","family":"Gionet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewa","family":"King","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard C.","family":"Huard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha K.","family":"Jalbert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael L.","family":"Cleary","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas A.","family":"Fitzgerald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacey B.","family":"Gabriel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6837-9473","authenticated-orcid":false,"given":"Glen R.","family":"Gallagher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra C.","family":"Smole","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2589-7777","authenticated-orcid":false,"given":"Lawrence C.","family":"Madoff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine M.","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5850-1698","authenticated-orcid":false,"given":"Matthew W.","family":"Keller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malania M.","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0859-9604","authenticated-orcid":false,"given":"Marie K.","family":"Kirby","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Barnes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7226-7781","authenticated-orcid":false,"given":"Daniel J.","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine J.","family":"Siddle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian T.","family":"Happi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah T.","family":"Hung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Springer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bronwyn L.","family":"MacInnis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob E.","family":"Lemieux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Rosenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A.","family":"Branda","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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9843-1890","authenticated-orcid":false,"given":"Pardis C.","family":"Sabeti","sequence":"additional","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"}]}],"member":"297","published-online":{"date-parts":[[2022,2,7]]},"reference":[{"key":"1734_CR1","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1126\/science.abe9187","volume":"371","author":"MJ Mina","year":"2021","unstructured":"Mina, M. J. & Andersen, K. G. COVID-19 testing: one size does not fit all. Science 371, 126\u2013127 (2021).","journal-title":"Science"},{"key":"1734_CR2","doi-asserted-by":"publisher","first-page":"1206","DOI":"10.1126\/science.abf9569","volume":"371","author":"AL Rasmussen","year":"2021","unstructured":"Rasmussen, A. L. & Popescu, S. V. SARS-CoV-2 transmission without symptoms. Science 371, 1206\u20131207 (2021).","journal-title":"Science"},{"key":"1734_CR3","doi-asserted-by":"publisher","first-page":"e00297-20","DOI":"10.1128\/JCM.00297-20","volume":"58","author":"P Winichakoon","year":"2020","unstructured":"Winichakoon, P. et al. Negative nasopharyngeal and oropharyngeal swabs do not rule out COVID-19. J. Clin. Microbiol. 58, e00297-20 (2020).","journal-title":"J. Clin. Microbiol."},{"key":"1734_CR4","doi-asserted-by":"publisher","first-page":"e38","DOI":"10.1056\/NEJMp2015897","volume":"383","author":"S Woloshin","year":"2020","unstructured":"Woloshin, S., Patel, N. & Kesselheim, A. S. False negative tests for SARS-CoV-2 infection\u2014challenges and implications. N. Engl. J. Med. 383, e38 (2020).","journal-title":"N. Engl. J. Med."},{"key":"1734_CR5","doi-asserted-by":"publisher","first-page":"eabe326","DOI":"10.1126\/science.abe3261","volume":"371","author":"JE Lemieux","year":"2021","unstructured":"Lemieux, J. E. et al. Phylogenetic analysis of SARS-CoV-2 in Boston highlights the impact of superspreading events. Science 371, eabe326 (2021).","journal-title":"Science"},{"key":"1734_CR6","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1038\/s41579-021-00573-0","volume":"19","author":"WT Harvey","year":"2021","unstructured":"Harvey, W. T. et al. SARS-CoV-2 variants, spike mutations and immune escape. Nat. Rev. Microbiol. 19, 409\u2013424 (2021).","journal-title":"Nat. Rev. Microbiol."},{"key":"1734_CR7","doi-asserted-by":"publisher","first-page":"5730","DOI":"10.1038\/s41467-021-25915-7","volume":"12","author":"L Dyson","year":"2021","unstructured":"Dyson, L. et al. Possible future waves of SARS-CoV-2 infection generated by variants of concern with a range of characteristics. Nat. Commun. 12, 5730 (2021).","journal-title":"Nat. Commun."},{"key":"1734_CR8","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.1056\/NEJMc2001737","volume":"382","author":"L Zou","year":"2020","unstructured":"Zou, L. et al. SARS-CoV-2 viral load in upper respiratory specimens of infected patients. N. Engl. J. Med. 382, 1177\u20131179 (2020).","journal-title":"N. Engl. J. Med."},{"key":"1734_CR9","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1038\/s41586-020-2196-x","volume":"581","author":"R W\u00f6lfel","year":"2020","unstructured":"W\u00f6lfel, R. et al. Virological assessment of hospitalized patients with COVID-2019. Nature 581, 465\u2013469 (2020).","journal-title":"Nature"},{"key":"1734_CR10","doi-asserted-by":"publisher","first-page":"e3001236","DOI":"10.1371\/journal.pbio.3001236","volume":"19","author":"CBF Vogels","year":"2021","unstructured":"Vogels, C. B. F. et al. Multiplex qPCR discriminates variants of concern to enhance global surveillance of SARS-CoV-2. PLoS Biol. 19, e3001236 (2021).","journal-title":"PLoS Biol."},{"key":"1734_CR11","doi-asserted-by":"publisher","first-page":"eabg4901","DOI":"10.1126\/sciadv.abg4901","volume":"7","author":"JT Heggestad","year":"2021","unstructured":"Heggestad, J. T. et al. Multiplexed, quantitative serological profiling of COVID-19 from blood by a point-of-care test. Sci. Adv. 7, eabg4901 (2021).","journal-title":"Sci. Adv."},{"key":"1734_CR12","doi-asserted-by":"publisher","first-page":"e01669-20","DOI":"10.1128\/JCM.01669-20","volume":"58","author":"J Pham","year":"2020","unstructured":"Pham, J. et al. Performance characteristics of a high-throughput automated transcription-mediated amplification test for SARS-CoV-2 detection. J. Clin. Microbiol. 58, e01669-20 (2020).","journal-title":"J. Clin. Microbiol."},{"key":"1734_CR13","doi-asserted-by":"publisher","first-page":"115260","DOI":"10.1016\/j.diagmicrobio.2020.115260","volume":"99","author":"EJ Eckbo","year":"2021","unstructured":"Eckbo, E. J. et al. Evaluation of the BioFire\u00ae COVID-19 test and Respiratory Panel 2.1 for rapid identification of SARS-CoV-2 in nasopharyngeal swab samples. Diagn. Microbiol. Infect. Dis. 99, 115260 (2021).","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"1734_CR14","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1038\/s41564-021-00932-w","volume":"6","author":"F Konings","year":"2021","unstructured":"Konings, F. et al. SARS-CoV-2 variants of interest and concern naming scheme conducive for global discourse. Nat. Microbiol. 6, 821\u2013823 (2021).","journal-title":"Nat. Microbiol."},{"key":"1734_CR15","doi-asserted-by":"publisher","first-page":"1055","DOI":"10.1016\/j.cmi.2017.11.018","volume":"24","author":"H-S Huang","year":"2018","unstructured":"Huang, H.-S. et al. Multiplex PCR system for the rapid diagnosis of respiratory virus infection: systematic review and meta-analysis. Clin. Microbiol. Infect. 24, 1055\u20131063 (2018).","journal-title":"Clin. Microbiol. Infect."},{"key":"1734_CR16","doi-asserted-by":"publisher","first-page":"4208","DOI":"10.1021\/acs.analchem.0c04626","volume":"93","author":"L Jacky","year":"2021","unstructured":"Jacky, L. et al. Robust multichannel encoding for highly multiplexed quantitative PCR. Anal. Chem. 93, 4208\u20134216 (2021).","journal-title":"Anal. Chem."},{"key":"1734_CR17","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1016\/S0140-6736(21)00298-1","volume":"397","author":"T Burki","year":"2021","unstructured":"Burki, T. Understanding variants of SARS-CoV-2. Lancet 397, 462 (2021).","journal-title":"Lancet"},{"key":"1734_CR18","doi-asserted-by":"publisher","first-page":"2100131","DOI":"10.2807\/1560-7917.ES.2021.26.10.2100130","volume":"26","author":"V Borges","year":"2021","unstructured":"Borges, V. & et al. Tracking SARS-CoV-2 lineage B.1.1.7 dissemination: insights from nationwide spike gene target failure (SGTF) and spike gene late detection (SGTL) data, Portugal, week 49 2020 to week 3 2021. Euro Surveill. 26, 2100131 (2021).","journal-title":"Euro Surveill."},{"key":"1734_CR19","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1016\/j.canlet.2012.11.025","volume":"340","author":"J Xuan","year":"2013","unstructured":"Xuan, J., Yu, Y., Qing, T., Guo, L. & Shi, L. Next-generation sequencing in the clinic: promises and challenges. Cancer Lett. 340, 284\u2013295 (2013).","journal-title":"Cancer Lett."},{"key":"1734_CR20","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1038\/nrmicro.2016.182","volume":"15","author":"CJ Houldcroft","year":"2017","unstructured":"Houldcroft, C. J., Beale, M. A. & Breuer, J. Clinical and biological insights from viral genome sequencing. Nat. Rev. Microbiol. 15, 183\u2013192 (2017).","journal-title":"Nat. Rev. Microbiol."},{"key":"1734_CR21","doi-asserted-by":"publisher","first-page":"966","DOI":"10.1093\/clinchem\/hvaa106","volume":"66","author":"V Peddu","year":"2020","unstructured":"Peddu, V. et al. Metagenomic analysis reveals clinical SARS-CoV-2 infection and bacterial or viral superinfection and colonization. Clin. Chem. 66, 966\u2013972 (2020).","journal-title":"Clin. Chem."},{"key":"1734_CR22","doi-asserted-by":"publisher","unstructured":"Brito, A. F. et al. Global disparities in SARS-CoV-2 genomic surveillance. Preprint at medRxiv https:\/\/doi.org\/10.1101\/2021.08.21.21262393 (2021).","DOI":"10.1101\/2021.08.21.21262393"},{"key":"1734_CR23","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1038\/s41551-021-00760-7","volume":"5","author":"MM Kaminski","year":"2021","unstructured":"Kaminski, M. M., Abudayyeh, O. O., Gootenberg, J. S., Zhang, F. & Collins, J. J. CRISPR-based diagnostics. Nat. Biomed. Eng. 5, 643\u2013656 (2021).","journal-title":"Nat. Biomed. Eng."},{"key":"1734_CR24","doi-asserted-by":"publisher","first-page":"941","DOI":"10.1126\/science.abe7106","volume":"372","author":"C Jiao","year":"2021","unstructured":"Jiao, C. et al. Noncanonical crRNAs derived from host transcripts enable multiplexable RNA detection by Cas9. Science 372, 941\u2013948 (2021).","journal-title":"Science"},{"key":"1734_CR25","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1126\/science.aaq0179","volume":"360","author":"JS Gootenberg","year":"2018","unstructured":"Gootenberg, J. S. et al. Multiplexed and portable nucleic acid detection platform with Cas13, Cas12a, and Csm6. Science 360, 439\u2013444 (2018).","journal-title":"Science"},{"key":"1734_CR26","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1126\/science.aar6245","volume":"360","author":"JS Chen","year":"2018","unstructured":"Chen, J. S. et al. CRISPR-Cas12a target binding unleashes indiscriminate single-stranded DNase activity. Science 360, 436\u2013439 (2018).","journal-title":"Science"},{"key":"1734_CR27","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1038\/s41421-018-0028-z","volume":"4","author":"S-Y Li","year":"2018","unstructured":"Li, S.-Y. et al. CRISPR-Cas12a-assisted nucleic acid detection. Cell Discov. 4, 20 (2018).","journal-title":"Cell Discov."},{"key":"1734_CR28","doi-asserted-by":"publisher","first-page":"aaf5573","DOI":"10.1126\/science.aaf5573","volume":"353","author":"OO Abudayyeh","year":"2016","unstructured":"Abudayyeh, O. O. et al. C2c2 is a single-component programmable RNA-guided RNA-targeting CRISPR effector. Science 353, aaf5573 (2016).","journal-title":"Science"},{"key":"1734_CR29","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1126\/science.aam9321","volume":"356","author":"JS Gootenberg","year":"2017","unstructured":"Gootenberg, J. S. et al. Nucleic acid detection with CRISPR-Cas13a\/C2c2. Science 356, 438\u2013442 (2017).","journal-title":"Science"},{"key":"1734_CR30","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1126\/science.aas8836","volume":"360","author":"C Myhrvold","year":"2018","unstructured":"Myhrvold, C. et al. Field-deployable viral diagnostics using CRISPR-Cas13. Science 360, 444\u2013448 (2018).","journal-title":"Science"},{"key":"1734_CR31","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19097-x","volume":"11","author":"J Arizti-Sanz","year":"2020","unstructured":"Arizti-Sanz, J. et al. Streamlined inactivation, amplification, and Cas13-based detection of SARS-CoV-2. Nat. Commun. 11, 5921 (2020).","journal-title":"Nat. Commun."},{"key":"1734_CR32","doi-asserted-by":"publisher","first-page":"870","DOI":"10.1038\/s41587-020-0513-4","volume":"38","author":"JP Broughton","year":"2020","unstructured":"Broughton, J. P. et al. CRISPR\u2013Cas12-based detection of SARS-CoV-2. Nat. Biotechnol. 38, 870\u2013874 (2020).","journal-title":"Nat. Biotechnol."},{"key":"1734_CR33","doi-asserted-by":"publisher","first-page":"1140","DOI":"10.1038\/s41551-020-00603-x","volume":"4","author":"M Patchsung","year":"2020","unstructured":"Patchsung, M. et al. Clinical validation of a Cas13-based assay for the detection of SARS-CoV-2 RNA. Nat. Biomed. Eng. 4, 1140\u20131149 (2020).","journal-title":"Nat. Biomed. Eng."},{"key":"1734_CR34","doi-asserted-by":"publisher","first-page":"982","DOI":"10.1038\/s41589-021-00842-2","volume":"17","author":"TY Liu","year":"2021","unstructured":"Liu, T. Y. et al. Accelerated RNA detection using tandem CRISPR nucleases. Nat. Chem. Biol. 17, 982\u2013988 (2021).","journal-title":"Nat. Chem. Biol."},{"key":"1734_CR35","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-022-01213-5","author":"HC Metsky","year":"2022","unstructured":"Metsky, H. C. et al. Designing sensitive viral diagnostics with machine learning. Nat. Biotech. https:\/\/doi.org\/10.1038\/s41587-022-01213-5 (2022).","journal-title":"Nat. Biotech."},{"key":"1734_CR36","doi-asserted-by":"publisher","first-page":"1492","DOI":"10.1056\/NEJMc2026172","volume":"383","author":"J Joung","year":"2020","unstructured":"Joung, J. et al. Detection of SARS-CoV-2 with SHERLOCK one-pot testing. N. Engl. J. Med. 383, 1492\u20131494 (2020).","journal-title":"N. Engl. J. Med."},{"key":"1734_CR37","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1016\/j.tibtech.2019.04.005","volume":"37","author":"R Bruch","year":"2019","unstructured":"Bruch, R., Urban, G. A. & Dincer, C. CRISPR\/Cas powered multiplexed biosensing. Trends Biotechnol. 37, 791\u2013792 (2019).","journal-title":"Trends Biotechnol."},{"key":"1734_CR38","doi-asserted-by":"publisher","first-page":"113701","DOI":"10.1016\/j.bios.2021.113701","volume":"196","author":"T Tian","year":"2022","unstructured":"Tian, T., Qiu, Z., Jiang, Y., Zhu, D. & Zhou, X. Exploiting the orthogonal CRISPR-Cas12a\/Cas13a trans-cleavage for dual-gene virus detection using a handheld device. Biosens. Bioelectron. 196, 113701 (2022).","journal-title":"Biosens. Bioelectron."},{"key":"1734_CR39","doi-asserted-by":"publisher","first-page":"112887","DOI":"10.1016\/j.bios.2020.112887","volume":"177","author":"R Bruch","year":"2021","unstructured":"Bruch, R. et al. CRISPR-powered electrochemical microfluidic multiplexed biosensor for target amplification-free miRNA diagnostics. Biosens. Bioelectron. 177, 112887 (2021).","journal-title":"Biosens. Bioelectron."},{"key":"1734_CR40","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1038\/s41586-020-2279-8","volume":"582","author":"CM Ackerman","year":"2020","unstructured":"Ackerman, C. M. et al. Massively multiplexed nucleic acid detection with Cas13. Nature 582, 277\u2013282 (2020).","journal-title":"Nature"},{"key":"1734_CR41","doi-asserted-by":"publisher","unstructured":"Crowe, J. E. Jr. Human respiratory viruses. Reference Module in Biomedical Sciences https:\/\/doi.org\/10.1016\/B978-0-12-801238-3.02600-3 (2014).","DOI":"10.1016\/B978-0-12-801238-3.02600-3"},{"key":"1734_CR42","doi-asserted-by":"crossref","unstructured":"Garc\u00eda Fern\u00e1ndez, X., \u00c1lvarez-Arg\u00fcelles, M. E., Rojo, S. & de-O\u00f1a, M. Stability of viral RNA in clinical specimens for viral diagnosis. Enferm. Infecc. Microbiol. Clin. (Engl. Ed.) 38, 297\u2013298 (2020).","DOI":"10.1016\/j.eimce.2019.09.007"},{"key":"1734_CR43","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1126\/science.1165557","volume":"324","author":"AC Palmenberg","year":"2009","unstructured":"Palmenberg, A. C. et al. Sequencing and analyses of all known human rhinovirus genomes reveal structure and evolution. Science 324, 55\u201359 (2009).","journal-title":"Science"},{"key":"1734_CR44","doi-asserted-by":"publisher","first-page":"1292","DOI":"10.1093\/nar\/30.6.1292","volume":"30","author":"IM Mackay","year":"2002","unstructured":"Mackay, I. M., Arden, K. E. & Nitsche, A. Real-time PCR in virology. Nucleic Acids Res. 30, 1292\u20131305 (2002).","journal-title":"Nucleic Acids Res."},{"key":"1734_CR45","doi-asserted-by":"publisher","unstructured":"Pulliam, J. R. C. et al. Increased risk of SARS-CoV-2 reinfection associated with emergence of the Omicron variant in South Africa. Preprint at medRxiv https:\/\/doi.org\/10.1101\/2021.11.11.21266068 (2021).","DOI":"10.1101\/2021.11.11.21266068"},{"key":"1734_CR46","doi-asserted-by":"publisher","first-page":"2101147","DOI":"10.2807\/1560-7917.ES.2021.26.50.2101147","volume":"26","author":"LT Brandal","year":"2021","unstructured":"Brandal, L. T. et al. Outbreak caused by the SARS-CoV-2 Omicron variant in Norway, November to December 2021. Euro. Surveill. 26, 2101147 (2021).","journal-title":"Euro. Surveill."},{"key":"1734_CR47","doi-asserted-by":"publisher","first-page":"1731","DOI":"10.15585\/mmwr.mm7050e1","volume":"70","author":"CDC COVID-19 Response Team","year":"2021","unstructured":"CDC COVID-19 Response Team SARS-CoV-2 B.1.1.529 (Omicron) Variant\u2014United States, December 1\u20138, 2021. MMWR Morb. Mortal. Wkly. Rep. 70, 1731\u20131734 (2021).","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"1734_CR48","doi-asserted-by":"publisher","unstructured":"Li, A., Maier, A., Carter, M. & Guan, T. H. Omicron and S-gene target failure cases in the highest COVID-19 case rate region in Canada\u2014December 2021. J. Med. Virol. https:\/\/doi.org\/10.1002\/jmv.27562 (2021).","DOI":"10.1002\/jmv.27562"},{"key":"1734_CR49","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1016\/j.pathol.2020.09.013","volume":"52","author":"PD Kirkland","year":"2020","unstructured":"Kirkland, P. D. & Frost, M. J. The impact of viral transport media on PCR assay results for the detection of nucleic acid from SARS-CoV-2. Pathology 52, 811\u2013814 (2020).","journal-title":"Pathology"},{"key":"1734_CR50","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1016\/j.cell.2020.12.001","volume":"184","author":"P Fozouni","year":"2021","unstructured":"Fozouni, P. et al. Amplification-free detection of SARS-CoV-2 with CRISPR\u2013Cas13a and mobile phone microscopy. Cell 184, 323\u2013333.e9 (2021).","journal-title":"Cell"},{"key":"1734_CR51","doi-asserted-by":"publisher","first-page":"102996","DOI":"10.1016\/j.isci.2021.102996","volume":"24","author":"EA Nalefski","year":"2021","unstructured":"Nalefski, E. A. et al. Kinetic analysis of Cas12a and Cas13a RNA-guided nucleases for development of improved CRISPR-based diagnostics. iScience 24, 102996 (2021).","journal-title":"iScience"},{"key":"1734_CR52","doi-asserted-by":"publisher","unstructured":"Thakku, S. G. et al. Multiplexed detection of bacterial nucleic acids using Cas13 in droplet microarrays. Preprint at bioRxiv https:\/\/doi.org\/10.1101\/2021.11.12.468388 (2021).","DOI":"10.1101\/2021.11.12.468388"},{"key":"1734_CR53","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17994-9","volume":"11","author":"KG Barnes","year":"2020","unstructured":"Barnes, K. G. et al. Deployable CRISPR-Cas13a diagnostic tools to detect and report Ebola and Lassa virus cases in real-time. Nat. Commun. 11, 4131 (2020).","journal-title":"Nat. Commun."},{"key":"1734_CR54","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1093\/molbev\/mst010","volume":"30","author":"K Katoh","year":"2013","unstructured":"Katoh, K. & Standley, D. M. MAFFT multiple sequence alignment software version 7: improvements in performance and usability. Mol. Biol. Evol. 30, 772\u2013780 (2013).","journal-title":"Mol. Biol. Evol."},{"key":"1734_CR55","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0519-7","volume":"15","author":"CB Matranga","year":"2014","unstructured":"Matranga, C. B. et al. Enhanced methods for unbiased deep sequencing of Lassa and Ebola RNA viruses from clinical and biological samples. Genome Biol. 15, 519 (2014).","journal-title":"Genome Biol."}],"updated-by":[{"DOI":"10.1038\/s41591-023-02684-y","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2023,11,9]],"date-time":"2023-11-09T00:00:00Z","timestamp":1699488000000}}],"container-title":["Nature Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41591-022-01734-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41591-022-01734-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41591-022-01734-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,10]],"date-time":"2023-11-10T03:04:54Z","timestamp":1699585494000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41591-022-01734-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,7]]},"references-count":55,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2022,5]]}},"alternative-id":["1734"],"URL":"https:\/\/doi.org\/10.1038\/s41591-022-01734-1","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.12.14.21267689","asserted-by":"object"}]},"ISSN":["1078-8956","1546-170X"],"issn-type":[{"value":"1078-8956","type":"print"},{"value":"1546-170X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,7]]},"assertion":[{"value":"22 November 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 February 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 February 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 November 2023","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1038\/s41591-023-02684-y","URL":"https:\/\/doi.org\/10.1038\/s41591-023-02684-y","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"N.L.W., S.G.T., C.M.A., D.T.H., P.C.B., P.C.S. and C.M. are coinventors on a patent related to this work. P.C.B is a coinventor on patent applications concerning droplet array technologies and serves as a consultant and equity holder of companies in the microfluidics and life sciences industries, including 10x Genomics, GALT, Celsius Therapeutics, Next Gen Diagnostics, Cache DNA and Concerto Biosciences. P.C.B.\u2019s laboratory receives funding from industry for unrelated work. J.E.L. has received consulting fees from Sherlock Biosciences. J.A.B. has received research support for other studies from Pfizer, Zeus, bioM\u00e9rieux, Immunetics, Abbott Rapid Diagnostics (formerly Alere), Diasorin and the Bay Area Lyme Foundation. P.C.S. is a cofounder of and consultant to Sherlock Biosciences and a board member of the Danaher Corporation, and holds equity in the companies. The other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}