Fluorescence‐Amplified Origami Microneedle Device for Quantitatively Monitoring Blood Glucose

Abstract Exploration of clinically acceptable blood glucose monitors has been engaging in the past decades, yet the ability to quantitatively detect blood glucose in a painless, accurate, and highly sensitive manner remains limited. Herein, a fluorescence‐amplified origami microneedle (FAOM) device is described that integrates tubular DNA‐origami nanostructures and glucose oxidase molecules into its inner network to quantitatively monitor blood glucose. The skin‐attached FAOM device can collect glucose molecules in situ and transfer the input into a proton signal after the oxidase's catalysis. The proton‐driven mechanical reconfiguration of DNA‐origami tubes separates fluorescent molecules and their quenchers, eventually amplifying the glucose‐correlated fluorescence signal. The function equation established on clinical examinees suggests that FAOM can report blood glucose in a highly sensitive and quantitative manner. In clinical blind tests, the FAOM achieves well‐matched accuracy (98.70 ± 4.77%) compared with a commercial blood biochemical analyzer, fully meeting the requirements of accurate blood glucose monitoring. The FAOM device can be inserted into skin tissue in a trivially painful manner and with minimal leakage of DNA origami, substantially improving the tolerance and compliance of the blood glucose test.