Nanopore-based detection of circulating microRNAs in lung cancer patients

MicroRNAs are short RNA molecules that regulate gene expression. They have been investigated as potential biomarkers because their expression levels are correlated with various diseases. However, the detection of microRNAs in the bloodstream remains difficult because current methods are not sufficiently selective or sensitive. Here, we show that a nanopore sensor based on the alpha-hemolysin protein selectively detected microRNAs at the single molecular level in plasma samples from lung cancer patients without the need for labelling or amplification. The sensor, which used a programmable oligonucleotide probe to generate a target-specific signature signal, was able to quantify sub-picomolar levels of cancer-associated microRNAs and to discriminate single nucleotide differences between microRNA family members. This approach could prove useful for quantitative microRNA detection, biomarker discovery, and the non-invasive early diagnosis of cancer.