Quantum relaxometry for detecting biomolecular interactions with single NV centers

TL;DR

This paper introduces a quantum relaxometry method using NV centers in diamond to detect and analyze biomolecular interactions at the single-molecule level, enhancing sensitivity and resolution over traditional ensemble techniques.

Contribution

The study develops a novel single-molecule detection approach based on relaxometry with NV centers, including an improved sensitivity method and nanoscale detection capabilities.

Findings

Enhanced measurement sensitivity by re-evaluating relaxation components.

Achieved nanoscale detection approaching single-molecule level.

Demonstrated detection of both strong and weak biomolecular interactions.

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 $\sim$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 re-examined 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.