DNA Logic-Integrated Quantum Nanosensor for MicroRNA Diagnostics
Weiming Lin, Tao Ding, Die He, Nan Zhang, Haodong Li, Wenjian Luo, Zhongxia Wei, Min Ke, Sisi Jia, Chunhai Fan, Le Liang
Abstract
Nanodiamonds (NDs) with nitrogen-vacancy (NV) centers are emerging as powerful quantum nanosensors (QNs) in biomedical applications due to their exceptional sensitivity. However, achieving optimal diagnostics performance necessitates both high sensitivity and selectivity; especially in practical biomedical settings, it remains challenging for QNs to provide quantitative analyses when multiple analytes are present. Here, we present a biosensing platform that integrates DNA logic gates (DLGs) with spin-based quantum sensing, termed DLG-QN for ultrasensitive and ultraselective diagnostics. Utilizing an AND DLG, both NDs and magnetic beads (MBs) are functionalized with hairpin DNA strands. In the presence of both miRNA-21 and miRNA-155key biomarkers overexpressed in cancerthe hairpin DNAs undergo conformational changes that facilitate DNA-guided self-assembly of NDs and MBs, enriching the target signal. Resonant microwave modulation of ND fluorescence emission allows for high signal-to-noise ratio (SNR) detection by separating the signal from background fluorescence via spin-enhanced analysis. This platform demonstrated ultrasensitive and ultraselective detection of miRNA-21 and miRNA-155 with a limit of detection of 19.8 fM, highlighting its potential as a general biosensing strategy for precision diagnostics involving multiple biomarkers.