DNA Logic-Integrated Quantum Nanosensor for MicroRNA Diagnostics

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-155─key biomarkers overexpressed in cancer─the 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.