The authors report on their development of a facile and affordable method to fabricate the paper-based FET/chemiresistor biosensor for the sensitive, specific and quick detection of miRNA-122a at attomolar level for potential point-of-care diagnosis of HCC; the methodology developed in this report showed its potential to be integrated with fully developed microfluidics and portable electronics to further improve the sensing procedure for point-of-care use.
Micro RNAs (miRNAs) are 19- to 23-nucleotides long, non-coding RNA which have been identified as important biomarkers for many diseases, including cancers. In this paper, the authors report an ultrasensitive, highly specific, label-free, and without nucleic acid amplification (NAA) detection of miRNAs using paper-based single-walled carbon nanotubes (SWNTs) field-effect transistor (FET) biosensors. The strategy involved a two-step protocol starting with direct hybridization of the target miRNA with a specific RNA probe immobilized on SWNTs networks deposited on the paper substrate to generate the first response, followed by the recognition of the resulting RNA/miRNA duplexes with the Carnation Italian ringspot virus p19 protein (p19) in a size-dependent manner, giving the second electrical response that magnified the biosensor sensitivity. As a demonstration, the authors detected the miRNA-122a, a promising biomarker for the diagnosis of early-stage hepatocellular carcinoma (HCC) in various sample matrices, including phosphate buffers, human serum, and synthetic saliva. They achieved the lowest detection of 0.1 aM and a wide dynamic range of 0.1 aM–1 fM, that demonstrated its potential for rapid, facile, low-cost, and point-of-care detection of miRNAs for early cancer diagnosis.