Digital Microneedles for Multiplexed Transdermal Sensing via Fluorescent QR Codes

Abstract

ABSTRACT Real‐time biochemical sensing is essential for precision medicine, yet current wearable and transdermal biosensors suffer from signal drift, calibration demands, and limited multiplexing capabilities in vivo. Here, we introduce digital fluorescent microneedles that translate analyte concentrations into scannable QR codes via threshold‐activated probes. Each microneedle functions as a fluorescent binary switch, turning “on” only above a defined analyte threshold, thereby eliminating the need for calibration and enhancing robustness against tissue heterogeneity and environmental noise. The microneedles feature a biodegradable, mechanically optimized “baby‐bottle” design that enables reliable skin penetration and controlled tip detachment. Central to this concept is the rational engineering of fluorescent probes with discrete activation thresholds, which—when embedded in microneedles—produce stepwise readouts spanning physiopathological ranges of pH (4.5–8.5) and glucose (1–10 mM). By tuning probe loading, we achieve reproducible threshold activation, enabling fully digital, multiplexed detection of pH and glucose in skin with classification accuracies of 93% and 85%. This digital encoding concept is broadly extensible to diverse probes and biomarkers, providing a scalable route to calibration‐free, multiplexed biosensing in vivo. The QR‐based output delivers a direct, quantitative representation of biochemical information, facilitating decentralized diagnostics and integration into digital health workflows. Together, these advances establish digital microneedles as a versatile and clinically relevant platform for transdermal biosensing.