Quantum relaxometry for detecting biomolecular interactions with single NV centers

• 成果类型: Article
• 署名作者: Li, Min; Zhang, Qi; Kong, Xi; Zhao, Sheng; Pan, Bin-Bin; Sun, Ziting; Yu, Pei; Wang, Zhecheng; Wang, Mengqi; Ji, Wentao; Kong, Fei; Cheng, Guanglei; Wu, Si; Wang, Ya; Chen, Sanyou; Su, Xun-Cheng; Shi, Fazhan
• 署名单位: Chinese Academy of Sciences; University of Science & Technology of China, CAS; Chinese Academy of Sciences; University of Science & Technology of China, CAS; Chinese Academy of Sciences; University of Science & Technology of China, CAS; Chinese Academy of Sciences; University of Science & Technology of China, CAS; Zhejiang University; Nanjing University; Nankai University; Nankai University; Chinese Academy of Sciences; University of Science & Technology of China, CAS; Hefei National Laboratory; Chinese Academy of Sciences; University of Science & Technology of China, CAS
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-11216
• DOI: 10.1073/pnas.2509102122
• 发表日期: 2025-09-02
• 关键词: optical tweezers; real-time; spectroscopy

摘要

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 similar to 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.