Ultrasensitive, Amplification-Free RNA Detection Using Nanodiamond Quantum Sensors.

Abstract

Compact and ultrasensitive detection of viral RNA and cancer-associated biomarkers is essential for early diagnosis and disease management. Conventional lateral flow assays (LFA), however, often lack the sensitivity and quantitative reliability required for low-abundance nucleic acids in complex matrices without amplification. Here, we present a quantum-enabled, magnetically modulated fluorescent nanodiamond LFA (FND-LFA) for amplification-free RNA detection through nucleic acid hybridization. Fluorescent nanodiamonds provide photostable, spin-dependent fluorescence, while magnetic modulation separates target-associated signals from background. Pixel-wise contrast analysis with Gaussian modeling enables robust quantitative readout, and sequence-optimized probes selectively hybridize to low-secondary-structure RNA regions without denaturation. The platform achieves a 10 fM detection limit and a linear range of 10 fM to 10 pM for SARS-CoV-2 RNA, together with a 100 fM detection limit for cancer-associated miRNAs. This strategy offers a compact and generalizable route for sensitive, amplification-free RNA diagnostics.