Nanostructured Bubbles‐Enhanced Fluorescence for Ultrasensitive Portable MicroRNA Detection

Abstract The unmet on‐site clinical diagnostics are increasingly demanding portable bioassays, but compromised by sensitivity and throughput. Herein, a nanostructured bubbles‐enhanced fluorescence (nBEF) assay is reported by interfacing with smartphone imaging system to enable portable, ultrasensitive, and specific miRNA detection in parallel. In nBEF, the high‐curvature bubbles allow physically enhancing optical propagation, chemically enhancing fluorescence, assembling more DNA probes, undergoing faster self‐suspension and more efficient self‐aggregation fluorescence enhancement relative to their smooth counterparts. By coupling with bubble‐driven signal amplification by a plug‐and‐play DNA concatemer, and with a smartphone imaging system, this nBEF assay achieves a portable and ultrasensitive fluorescent assay of miRNA at the femtomolar level with one‐base resolution in a single test, and is capable of monitoring drug‐induced miRNA dynamic expression and accurate cancer diagnosis (AUC = 1) through profiling 40 plasma samples after RNA extraction. This assay further integrates an R‐value analysis in RGB module with the smartphone to realize automated, on‐site miRNA readout. Such a high‐performance nBEF assay provides a low‐cost, portable, and highly sensitive tool to enable accurate clinical diagnosis.