Quantum relaxometry for detecting biomolecular interactions with single NV centers
- Min Li
- Qi Zhang
- Xi Kong
- Sheng Zhao
- Bin-Bin Pan
- Ziting Sun
- Pei Yu
- Zhecheng Wang
- Mengqi Wang
- Wentao Ji
- Fei Kong
- Guanglei Cheng
- Si Wu
- Ya Wang
- Sanyou Chen
- Xun-Cheng Su
- Fazhan Shi
2025-08-25
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 ∼ 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.