Hybridization chain reaction assisted terahertz metamaterial biosensor for highly sensitive detection of microRNAs

MicroRNA (miRNA) is closely related to the occurrence and development of cancer. Accurate determination of the miRNA concentration is of great significance for early cancer diagnosis. However, due to the short sequence and low concentration of miRNA, it is still a challenge to achieve low-concentration detection. In this work, we proposed a method for the highly sensitive detection of miRNA-21 using a terahertz (THz) metamaterial sensor combined with a Hybridization chain reaction (HCR). First, a capture hairpin probe was combined with gold nanoparticles (AuNPs), which were then modified to the surface of the sensor for specific binding of miRNA-21. Then the signal amplification technique of HCR is used to amplify the trace amount of miRNA, and the super-long dendritic DNA macromolecules are formed on the surface of the sensor. This changes the dielectric environment of the sensor surface, and the resonance frequency of the sensor is shifted. The method has good specificity and sensitivity, and the concentration of miRNA-21 in the range of 100 aM to 10 nM shows excellent linear relationship with frequency shift. Most importantly, it paves the way for low-cost, easy-to-operate and marker-free miRNA detection.