Active detection of melanoma via a dual-extraction-driven flexible microneedles sensor.

Wearable microneedles (MNs) biosensors offer significant potential for minimally invasive biomarker detection in interstitial fluid (ISF). However, suboptimal fluid collection efficiency, dermal irritation due to rigid structural components, and inadequate long-term operational stability collectively represent critical barriers to their clinical translation for early disease diagnosis. Here, we propose a fully integrated dual-extraction-driven flexible microneedles (DFMN) sensor for active detection of melanoma-associated miRNA. The DFMN sensor comprises hydrogel MNs, hollow Au-Ag NPs functionalized flexible electrodes, and a miniaturized wireless module. The synergistic combination of passive diffusion driven by hydrogel MN swelling and active transport via reverse iontophoresis enhanced ISF extraction volume by 1.6-fold within 5 min. This dual-extraction mechanism enabled real-time wireless detection of miRNA-221 with an ultra-low limit of detection (LOD) of 43 aM. Furthermore, to enhance reliability in complex biological environments, an artificial neural network algorithm was implemented, achieving a correlation coefficient (R2) of 0.985. The DFMN sensor holds broad application prospects in interdisciplinary fields such as human-machine interaction, smart healthcare, and artificial intelligence, providing an innovative solution for real-time sensitive detection of wearable flexible sensors.