Noble-metal nanoparticle labelling multiplex miRNAs by ICP-MS readout with internal standard isotopes of 115In and 209Bi†
Inductively coupled plasma-mass spectrometry (ICP-MS) is one of the most powerful techniques for multiplex nucleotide assay owing to the virtue of the high resolution of multiple-elements’ mass to charge ratio, in a mass spectrum. Here, a small sized (less than 20 nm) noble-metal nanoparticle labelled ICP-MS (NP-ICP-MS) is proposed for high-throughput microRNA (miRNA) determination. Three miRNA targets – miR-486-5p, miR-221, and miR-21 – in serum, were distinguished by single-stranded DNA (ssDNA) probes labelled with a small sized noble-metal nanoparticle – silver nanoparticles (AgNPs), platinum nanoparticles (PtNPs), and gold nanoparticles (AuNPs). The counting isotopes ion intensity per second (CPS) of the noble-metal label versus internal standard isotope intensity of 115In and 209Bi, exhibited good linearity in the range 0.25 pM to 100 pM with correlation coefficients (R2) of 0.9680, 0.9305, and 0.9418. The specific sandwich-type miRNA assay using the sensitive NP-ICP-MS readout pushed the detection limits down to 0.18 pM for miR-221, 0.23 pM for miR-486-5p, and 0.22 pM for miR-21. And the relative standard deviations (RSDs) for 10 pM target miRNA were less than 3.7%. This work promises a potential ultrasensitive ICP-MS bioassay of multiplex miRNA biomarkers for clinical serum diagnosis.