Ultra-stable and highly-bright CsPbBr3 perovskite/silica nanocomposites for miRNA detection based on digital single-nanoparticle counting

Single-nanoparticle counting (SNPC) based on fluorescent tag (FT) stands out for its capacity to achieve amplification-free and sensitive detection of biomarkers. The stability and luminescence of FT are important to the sensitivity and reliability of SPNC. In this work, we developed novel perovskite/silica nanocomposites by in-situ nanoconfined growth of CsPbBr 3 nanocrystals inside mesoporous structure of silica nanoparticles. PbBr(OH) was formed in an alkaline-assisted reaction triggered by water on the surface of CsPbBr 3 nanocrystals. The as-obtained nanocomposites, featuring dual protection from silica matrix and PbBr(OH), exhibited high absolute photoluminescence quantum yield (PLQY) of 86.5% and demonstrated outstanding PL stability confronting with water, heat, ultrasound and UV-irradiation, which is desired by SNPC-based biosensor. Thereafter, these nanocomposites were used to construct an operationally friendly SNPC assay for the amplification-free quantification of cancer-associated miRNA. Quantitative detection of miRNA could be accomplished by directly counting the number of nanocomposites using a flow cytometer in this assay. This strategy did not ask for multiple washing steps and demonstrated specific and sensitive detection of miRNA 21, which exhibited a dynamic range of 1–1000 pM and limit of detection of 79 amol. The employment of highly stable perovskite/silica nanocomposites improved the test reliability and stability of SNPC, revealing the vast potential of perovskites in biosensing.