Simultaneous ultrasensitive detection of two breast cancer microRNA biomarkers by using a dual nanoparticle/nanosheet fluorescence resonance energy transfer sensor

The ability to detect multiple microRNAs (miRNAs) as cancer biomarkers with high sensitivity and good compatibility is still challenging. Here, we showed an ultrasensitive sensing system based on the fluorescence resonance energy transfer (FRET) effect between green-emitting and blue-emitting core@shell upconversion nanoparticles (UCNPs) and MoS 2 nanosheets for simultaneously detecting two miRNAs. The core@shell UCNPs and MoS 2 nanosheets served as energy donors and quenchers, respectively. The green-emitting and blue-emitting core@shell UCNPs were modified with single-stranded DNAs complementary to two breast cancer miRNA biomarkers, miR-593 and miR-155, respectively. When the two target miRNAs were absent in the samples, the ssDNA-modified nanoparticles bound to the MoS 2 nanosheets directly through van der Waals forces, leading to the close proximity between the nanoparticles and nanosheets and thus the occurrence of FRET between them. When the two target miRNAs were present in the samples, each of the miRNAs hybridized with the complementary ssDNA on the nanoparticles, preventing the direct contact between the nanoparticles and the nanosheets and thereby causing miRNA concentration-dependent fluorescence recovery of the nanoparticles. Thus, monitoring the fluorescence recovery from the nanoparticles established a unique linear relationship between the fluorescence recovery and the target miRNA concentrations, allowing us to determine the concentration of the miRNAs by simply detecting the fluorescent signals. Our FRET sensor could reach an ultralow limit of detection (∼0.17 nM and ∼0.25 nM for miR-593 and miR-155, respectively). It could selectively detect the target miRNAs but not the non-target molecules. Our sensor can be extended to the ultrasensitive detection of other biomolecules and holds promise for the early diagnosis of diseases such as breast cancer.