A new QCM signal enhancement strategy based on streptavidin@metal-organic framework complex for miRNA detection

Sensitive and selective detection of miRNA is of great significance for the early diagnosis of human diseases, especially for cancers. Quartz crystal microbalance (QCM) is an effective tool for detecting biological molecules; however, the application of QCM for miRNA detection is still very limited. One of the great needs for QCM detection is to further improve the QCM signal. Herein, for the first time, we promote a new signal enhancement strategy for the detection of miRNA by QCM. First, a hairpin biotin-modified DNA was used as a probe DNA, which exposes the biotin site when interacting with target miRNA. Then, a streptavidin@metal-organic framework (SA@MOF) complex formed by electrostatic attractions between SA and a MOF was introduced into the QCM detection system. The SA@MOF complexes serve as both a signal amplifier and a specific recognition element via specific biotin-SA interactions. The strategy was applied to the detection of a colorectal cancer marker, miR-221, by using a stable Zr(IV)-MOF, UiO-66-NH₂. The detection linear range was 10 fM-1 nM, the detection limit was 6.9 fM, and the relative standard deviation (RSD) (n = 5) was lower than 10% in both simulated conditions and the real serum environment. Furthermore, the detection limit reached 0.79 aM when coupled with the isothermal exponential amplification reaction (EXPAR).