A Dual-Signal Twinkling Probe for Fluorescence-SERS Dual Spectrum Imaging and Detection of miRNA in Single Living Cell via Absolute Value Coupling of Reciprocal Signals

Imaging and detecting microRNAs (miRNAs) is of central importance in tumor cell analysis. It stays challenging to establish simple, accurate, and sensitive analytical assays for imaging and detection of miRNA in a single living cell, because of intracellular complex environment and miRNA sequence similarity. Herein, we designed a dual-signal twinkling probe (DSTP) with triplex-stem structure which employed a fluorescence-SERS signal reciprocal switch. The spatiotemporal dynamics of the miRNA molecular and intracellular uptake of the probe are monitored by fluorescence-SERS signal switch of the DSTP. Meanwhile, using the surface-enhanced Raman scattering (SERS) signals of DSTP, the measure of absolute value coupling of reciprocal signals is first used to real-time detection of miRNA. Through simultaneous enhancing the target response signal value and reducing blank value, this work deducted the background effect, and showed high sensitivity and reproducibility. Moreover, the probe shows excellent reversibility and specificity in real quantitative detection of intracellular miRNA. miR-203 was successfully monitored in MCF-7, in accord with the results in vitro as well as in cell lysates. We anticipate that this new dual-signal twinkling and dual-spectrum switch method will be generally useful to image and detect various types of biomolecules in single living cell.