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In this study, we developed a versatile, multilayer, detachable MN administration system capable of simultaneous photocontrolled drug delivery therapy that operated based on real\u2010time in situ conditions monitored by droplet\u2010based PCR (dPCR). The detachable MN consisted of an innermost poly (ethylene glycol) diacrylate extraction layer, an outer gelatin methacryloyl drug\u2010loaded layer containing Vemurafenib and black phosphorus (BP), and a polyvinyl alcohol connection layer designed for thermal detachment. The outer layer enabled light\u2010responsive drug release through BP's photothermal properties, achieving 78% release within 24\u00a0h. Subsequently, the significant mechanical strength and swelling characteristics facilitated the effective extraction of approximately 26\u00a0\u00b5L of interstitial fluid within 10\u00a0min. Both in vitro and in vivo studies on melanoma demonstrated the platform's capability to enhance therapeutic efficacy while minimizing systemic toxicity. It enabled dPCR\u2010based monitoring of MCAM and BRAF genes, including the drug\u2010resistant V600E polymorphism, with detection limits of 223\u00a0copies\/\u00b5L, along with digital proximity ligation assay detection of the protein markers IL\u20106, VEGF, and Ki\u201067 at 0.64\u00a0pg\/mL. This well\u2010designed biosystem highlighted its capability to interact with the pathophysiological environment, providing a preclinical proof\u2010of\u2010concept for minimally invasive theranostics in superficial tumors.<\/jats:p>","DOI":"10.1002\/adhm.202503813","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T04:42:59Z","timestamp":1778560979000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Multilayer Detachable Microneedles for Therapeutic and Collaborative Digital PCR Monitoring"],"prefix":"10.1002","volume":"15","author":[{"given":"Yun","family":"Cheng","sequence":"first","affiliation":[{"name":"Key Laboratory of Structural Malformations in Children of Zhejiang Province The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou Zhejiang China"},{"name":"Zhejiang Key Laboratory of Soft Matter Biomedical Materials Wenzhou Institute University of Chinese Academy of Sciences  Wenzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Luan","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory of Soft Matter Biomedical Materials Wenzhou Institute University of Chinese Academy of Sciences  Wenzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rokshana","family":"Parvin","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory of Soft Matter Biomedical Materials Wenzhou Institute University of Chinese Academy of Sciences  Wenzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dingmeng","family":"Hu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Structural Malformations in Children of Zhejiang Province The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Wu","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory of Soft Matter Biomedical Materials Wenzhou Institute University of Chinese Academy of Sciences  Wenzhou Zhejiang China"},{"name":"Huanhu Hospital Affiliated to Tianjin Medical University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Lin","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory of Soft Matter Biomedical Materials Wenzhou Institute University of Chinese Academy of Sciences  Wenzhou Zhejiang China"},{"name":"Harbin Institute of Technology School of Medicine and Health  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gangling","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Structural Malformations in Children of Zhejiang Province The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huaqiong","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Structural Malformations in Children of Zhejiang Province The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou Zhejiang China"},{"name":"Zhejiang Key Laboratory of Soft Matter Biomedical Materials Wenzhou Institute University of Chinese Academy of Sciences  Wenzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0374-4382","authenticated-orcid":false,"given":"Lexiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Structural Malformations in Children of Zhejiang Province The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou Zhejiang China"},{"name":"Zhejiang Key Laboratory of Soft Matter Biomedical Materials Wenzhou Institute University of Chinese Academy of Sciences  Wenzhou Zhejiang China"},{"name":"Joint Centre of Translational Medicine The First Affiliated Hospital of Wenzhou Medical University  Wenzhou China"},{"name":"Zhejiang Baifei Dairy Co., Ltd.  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