Ultrasensitive Lateral-Flow Immunoassay Based on Magnetically Modulated Fluorescent Nanodiamonds and Machine Learning Enhancement

Fluorescent nanodiamonds (FNDs) now underlie cutting-edge quantum precision measurements, owing to the rigorous spin qubit out of their negative-charged nitrogen vacancies (NV⁻) that are manipulable and scalable at ambient conditions (the DiVincenzo criteria). Though the FND-based ODMR (optically detected magnetic resonance) technique has already achieved an ultimate sensitivity down to the subcellular organelle or even monomolecular levels, confocal microimaging as a benchmarked setup must cohere microwaves with the Zeeman-split ±1 states (³E in spectral terms) of a rare single particle in a programmed pulse sequence. It is not easy to integrate such intricate instrumentation into some transportable benchtop devices, and then adapt these devices for point-of-care testing (POCT) scenarios in dire needs, for instance, a PCR-free dipstick reader that can be used for inspection during the COVID-19 pandemic in a resource-limited community.

The individual quantized eigenvectors of multiple NV⁻ spins in an FND ensemble can actually be modulated in unison once subjected to a strong alternating magnetic field (≥50 mT in our case), which would provide not only a nanofabricated chip-set for microwave coherence, but also the lens group for feeble signal amplification. By surface chemistry, biotinylated FNDs of a uniform size (~10 nm) were tagged with the model SARS-CoV-2 N-protein antibodies as a probe upon the Conjugate Pad of a lateral flow test strip. Following the standard LFA protocol, well-dispersed FNDs mounted on the T line, where their blinking photoluminescence emissions (λ_em = 632 nm, excited at 543 nm) were routed out via an optical fiber, were recorded and further processed with machine learning quantum computation for lock-in enhancement of timelapse captures in a swift and streamlined fashion.