Lan Yu, Guoxin Liu, Feng Ouyang, Weiqiang Han
Conventional blood-based diagnostics provide essential clinical information but can be less suitable for frequent or continuous biomarker monitoring because they generally require repeated invasive sampling and laboratory-based analysis. Microneedle platforms provide minimally invasive access to dermal interstitial fluid (ISF) and can couple transdermal sampling with on-needle 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-specific biomarker requirements and translational performance. Solid, hollow, coated, dissolving, and hydrogel microneedles are discussed together with recent advances in polymer structure-property engineering and 3D-printed microneedle platforms. Electrical/electrochemical, optical, and Raman-based sensing strategies are comparatively evaluated, followed by their applications in metabolic, oncological, inflammatory, allergic, stress-related, and renal disorders. Particular attention is given to the trade-offs among mechanical reliability, ISF transport, analytical sensitivity, biofouling, signal stability, manufacturing reproducibility, and clinical validation. Finally, scalable manufacturing, regulatory translation, wearable integration, and artificial-intelligence-assisted analysis are discussed as key requirements for moving microneedle diagnostics from proof-of-concept devices toward reliable personalized and decentralized healthcare.