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Microneedle platforms provide minimally invasive access to dermal interstitial fluid (ISF) and can couple transdermal sampling with on\u2010needle or in situ sensing. This review critically summarizes the microneedle diagnostic systems by comprehensively considering the microneedle architecture, material and polymer properties, mechanical design, sensing modality, disease\u2010specific biomarker requirements and translational performance. Solid, hollow, coated, dissolving, and hydrogel microneedles are discussed together with recent advances in polymer structure\u2013property engineering and 3D\u2010printed microneedle platforms. Electrical\/electrochemical, optical, and Raman\u2010based sensing strategies are comparatively evaluated, followed by their applications in metabolic, oncological, inflammatory, allergic, stress\u2010related, and renal disorders. Particular attention is given to the trade\u2010offs among mechanical reliability, ISF transport, analytical sensitivity, biofouling, signal stability, manufacturing reproducibility, and clinical validation. Finally, scalable manufacturing, regulatory translation, wearable integration, and artificial\u2010intelligence\u2010assisted analysis are discussed as key requirements for moving microneedle diagnostics from proof\u2010of\u2010concept devices toward reliable personalized and decentralized healthcare.<\/jats:p>","DOI":"10.1002\/mabi.70265","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T17:20:01Z","timestamp":1790184001000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Advances in Microneedle\u2010Based Technology for Disease Detection via Interstitial Fluid"],"prefix":"10.1002","volume":"26","author":[{"given":"Lan","family":"Yu","sequence":"first","affiliation":[{"name":"College of Medical Technology Gannan Health Vocational College  Ganzhou Jiangxi People's Republic of 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