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We present here LAMP\u2010MS, an innovative technology that integrates linear amplification with single\u2010base quantitative nucleic acid mass spectrometry on silicon chips. This approach overcomes several limitations in utilizing cfDNA 5\u2010methylcytosine (5\u2005mC) status for colorectal cancer (CRC) screening. LAMP\u2010MS enables unbiased amplification of as little as 1\u2005ng of cfDNA, site\u2010specifically quantify methylation levels of multiple 5\u2005mC sites, thereby facilitating cost\u2010effective, high\u2010resolution quantitative detection of cfDNA methylation markers. We have validated the accuracy of DNA methylation determination using DNA probes and cfDNA from patient plasma samples, confirmed by mass spectrometric peak areas. Additionally, we have further shown this Mass Array technology could be expanded to also quantify RNA m<jats:sup>6<\/jats:sup>A modification sites. Combining the ability to work with ultra\u2010low input materials and a visually interpretable output, LAMP\u2010MS stands out as a promising method for real\u2010world applications in clinics and laboratories for nucleic acid methylation detection and quantification.<\/jats:p>","DOI":"10.1002\/anie.202413872","type":"journal-article","created":{"date-parts":[[2024,11,4]],"date-time":"2024-11-04T03:21:06Z","timestamp":1730690466000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["LAMP\u2010MS for Locus\u2010Specific Visual Quantification of DNA 5\u2005mC and RNA m<sup>6<\/sup>A Using Ultra\u2010Low Input"],"prefix":"10.1002","volume":"64","author":[{"given":"Runyu","family":"Xie","sequence":"first","affiliation":[{"name":"Shanghai Cancer Center, Institutes of Biomedical Sciences, Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology) Shanghai Medical College of Fudan University  Shanghai China 200032"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaotong","family":"Yang","sequence":"additional","affiliation":[{"name":"Shanghai Cancer Center, Institutes of Biomedical Sciences, Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology) Shanghai Medical College of Fudan University  Shanghai China 200032"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weizhi","family":"He","sequence":"additional","affiliation":[{"name":"Shanghai Cancer Center, Institutes of Biomedical Sciences, Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology) Shanghai Medical College of Fudan University  Shanghai China 200032"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongguang","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Digestive Diseases, Huashan Hospital Fudan University  Shanghai China 200040"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenshuai","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Digestive Diseases, Huashan Hospital Fudan University  Shanghai China 200040"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chu","family":"Xu","sequence":"additional","affiliation":[{"name":"Shanghai Cancer Center, Institutes of Biomedical Sciences, Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology) Shanghai Medical College of Fudan University  Shanghai China 200032"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaolong","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Chemistry The University of Chicago  Chicago USA IL 60637"},{"name":"Institute for Biophysical Dynamics The University of Chicago  Chicago USA IL 60637"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine Northwestern University Feinberg School of Medicine  Chicago USA IL 60611"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ning","family":"Wei","sequence":"additional","affiliation":[{"name":"Bionova (Shanghai) Medical Technology Co., Ltd.  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