Quantum relaxometry for detecting biomolecular interactions with single NV centers

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.

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Publication Details

Journal
Proceedings of the National Academy of Sciences
Published
2025-08-25
DOI
https://doi.org/10.1073/pnas.2509102122
Citations
1
Primary Topic
Diamond and Carbon-based Materials Research
Type
article
Field-Weighted Citation Impact
0.52

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article

Quantum relaxometry for detecting biomolecular interactions with single NV centers

Sheng Zhao, Fei Kong, Fazhan Shi, Si Wu et al.
1 citations
Proceedings of the National Academy of Sciences
Diamond and Carbon-based Materials Research
0.52
article

Quantum relaxometry for detecting biomolecular interactions with single NV centers

Sheng Zhao, Fei Kong, Fazhan Shi, Si Wu, Xun‐Cheng Su, Sanyou Chen, Qi Zhang, Guanglei Cheng, Wentao Ji, Ziting Sun, Ya Wang, Mengqi Wang, Min Li, Pei Yu, Zhecheng Wang, Baishen Pan, Xi Kong
article en
1 citations

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.

Proceedings of the National Academy of SciencesVol. 122(35)
University of Science and Technology of China (CN), Nankai University (CN), Laboratoire de physique des Solides (FR), Suzhou University of Science and Technology (CN), Hefei University (CN), Hefei National Center for Physical Sciences at Nanoscale (CN), Zhejiang Lab (CN), Suzhou Research Institute (CN), Microscale (United States) (US), Collaborative Innovation Center of Advanced Microstructures (CN), Institute of Physical and Organic Chemistry (BY), Kementerian Pendidikan Malaysia (MY), Zhejiang University (CN), Nanjing University (CN)
National Natural Science Foundation of China, National Key Research and Development Program of China, Fundamental Research Funds for the Central Universities, Science and Technology Department of Zhejiang Province
Openalex Percentile: Top 34%
Diamond and Carbon-based Materials Research
0.52
DOIOpen Access PDFOpenAlex
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