Fluorescence in situ hybridization (FISH) is the gold standard technique for the detection of chromosomal abnormalities. However, due to the spectral overlap, the present FISH method can only imaging 3~4 gene targets at most. In this work, a novel FISH method based on upconverting nanoparticles (UCNPs) has been developed, which is called UCNP-RNA FISH, aiming to image genomic loci at large sale. A facile approach to prepare ssDNA-UCNP probe has been used, where poly-cytosine (poly-C) can serve as binding segment and tether the ssDNA on UCNP surface, and then the probe can be used in RNA FISH to image biomarker transcript.

Thereafter, RNA POLR2A, MALAT1, COL5A1 and CENPF, were imaged using UCNP-labeled probes. Potentially, the adjustable fluorescence lifetime of UCNPs can be measured, as one more dimension for gene loci imaging. By this way, the number of imaged gene targets can increase significantly.

Next, we are employing the novel UCNP-RNA FISH method, to image gastric cancer biomarker transcript KLK10, KRT17 and others. In total, this novel method can be very helpful in early cancer detection, thus holding great potential in cancer screening in clinics.