A Nanopore Sensor for Single Molecule Detection of Circulating Micrornas in Lung Cancer Patients

Abstract

Developing new technologies for cancer screening and early diagnosis is a critical issue for saving cancer patients’ lives. Our recent effort has led to the first nanopore biosensor in clinical disease detection. The targets are microRNA (miRNAs), a class of short (∼18-24-nt) non-coding RNAs molecules that regulate gene expression at the post-transcriptional level. Aberrant expression of miRNAs has been found in all types of tumors. Thus miRNAs have been recognized as potential cancer biomarkers. Most notably, specific miRNAs are released from the primary tumor into blood circulation, making the detection of circulating miRNAs profile a powerful tool for noninvasive cancer detection, diagnosis, staging, and monitoring. Guided by designed programmable oligonucleotide probe, single miRNA molecules captured in the nanopore produce a signature current signal that function fingerprints, enabling us to identify a specific miRNA and quantify its concentration. The prototype of nanopore sensor has demonstrated the capability to discriminate single nucleotide difference between miRNAs (single nucleotide polymorphisms, SNPs). In clinical tests, the nanopore has shown the power to differentiate miRNA levels in blood from lung cancer patients and healthy people. This simple, sensitive, label-free technique requiring no amplification for miRNA detection as in the RT-PCR method, has the potential for noninvasive and cost-effective early diagnosis of lung cancer. If validated in clinical trial, the nanopore sensor will become a system available to monitor cancer patients and to screen high risk populations for early diagnosis of cancers which will potentially save the lives of millions.