Highly sensitive detection of miRNA-21 in human serum via adjustable circular dichroism from chiral helical gold nanorods

MicroRNAs (miRNAs) serve as critical biomarkers for early cancer diagnosis due to their disease-specific expression profiles, yet their low abundance and complex matrix interference pose significant challenges for conventional detection methods. To address these limitations, an innovative chiral biosensing platform that synergistically integrates helical gold nanorods (HGNRs) with hybridization chain reaction (HCR) amplification and magnetic beads (MBs)-assisted separation for highly sensitive and specific detection of miRNA-21 is developed. In this proposed method, target miRNA-21 initiates cDNA displacement on MB surfaces, triggering HCR to generate extended DNA polymers with multiple streptavidin-alkaline phosphatase (SA-ALP) conjugation sites. Subsequent ALP-mediated conversion of ascorbic acid 2-phosphate (AAP) to ascorbic acid induces structural change of HGNRs, leading to detectable circular dichroism (CD) signal reduction. This integrated approach demonstrates remarkable sensitivity as low as 3.025 pmol/L, and excellent selectivity with successful validation in diluted human serum matrices. The chiral CD transduction strategy pioneers a new paradigm for miRNA analysis by synergizing chiral nanomaterial and enhanced signal transduction with cascade amplification, offering significant potential for clinical liquid biopsy applications.