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Quantum relaxometry for detecting biomolecular interactions with single NV centers.


ABSTRACT: The investigation of biomolecular interactions at the single-molecule level has emerged as a pivotal research area in life science, particularly through optical, mechanical, and electrochemical approaches. Spins existing widely in biological systems offer a unique degree of freedom for detecting such interactions. However, most previous studies have been largely confined to ensemble-level detection in the spin degree. Here, we developed a molecular interaction analysis method approaching single-molecule level based on relaxometry using the quantum sensor, nitrogen-vacancy (NV) center in diamond. Experiments utilized an optimized diamond surface functionalized with a polyethylenimine nanogel layer, achieving [Formula: see text]10 nm average protein distance and mitigating interfacial steric hindrance. Then we measured the strong interaction between streptavidin and spin-labeled biotin complexes, as well as the weak interaction between bovine serum albumin and biotin complexes, at both the micrometer scale and nanoscale. For the micrometer-scale measurements using ensemble NV centers, we reexamined the often-neglected fast relaxation component and proposed a relaxation rate evaluation method, substantially enhancing the measurement sensitivity. Furthermore, we achieved nanoscale detection approaching single-molecule level using single NV centers. This methodology holds promise for applications in molecular screening, identification, and kinetic studies at the single-molecule level, offering critical insights into molecular function and activity mechanisms.

SUBMITTER: Li M 

PROVIDER: S-EPMC12415212 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature

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Quantum relaxometry for detecting biomolecular interactions with single NV centers.

Li Min M   Zhang Qi Q   Kong Xi X   Zhao Sheng S   Pan Bin-Bin BB   Sun Ziting Z   Yu Pei P   Wang Zhecheng Z   Wang Mengqi M   Ji Wentao W   Kong Fei F   Cheng Guanglei G   Wu Si S   Wang Ya Y   Chen Sanyou S   Su Xun-Cheng XC   Shi Fazhan F  

Proceedings of the National Academy of Sciences of the United States of America 20250825 35


The investigation of biomolecular interactions at the single-molecule level has emerged as a pivotal research area in life science, particularly through optical, mechanical, and electrochemical approaches. Spins existing widely in biological systems offer a unique degree of freedom for detecting such interactions. However, most previous studies have been largely confined to ensemble-level detection in the spin degree. Here, we developed a molecular interaction analysis method approaching single-  ...[more]

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