Quantum Biosensing of Small-Molecule Metabolites Using Nitrogen-Vacancy Centers in Diamond

Quantum sensors based on nitrogen-vacancy (NV) centers in diamond provide a promising platform for molecular diagnostics, but their implementation requires robust biointerfaces and efficient transduction mechanisms. Here we develop a scalable quantum biosensing architecture that combines subnanometer PEGylated diamond surfaces, high-density DNA microarrays, and Gd3+-based spin-label reporters. A rapid one-step silanization strategy enables multiplexed biomolecule immobilization while maintaining close proximity to near-surface NV centers. Using Gd3+-DOTA labels, we demonstrate a strand-displacement assay in which target recognition is converted into changes in the NV spin-lattice relaxation time (T_1). We further establish an analytical framework describing concentration-dependent T_1 transduction by surface-bound spin labels. Applying this approach to ATP and dopamine aptamer switches, we show that target-induced conformational changes modulate the position of Gd3+ reporters and generate reversible quantum signals. Surface immobilization preserves ATP affinity and enhances dopamine binding, while spin-label multiplicity provides a means to tune signal amplitude and apparent affinity. In contrast to fluorescence transduction, which is limited by photobleaching and self-quenching, spin-labels reporters remain functional at high label densities and enable distinct conformational responses. These results establish a chemically programmable quantum sensing platform for multiplexed and continuous detection of metabolites and other biomolecular targets in complex environments.