Suzhou Institute of Advanced Research (SIAR) has made a leap forward toward quantum precision sensing for biomedical applications using nitrogen-Vacancy (NV) color centers in diamonds. Its MIRACLE Research Center pioneered a digital magnetic method to detect biomolecular interactions, making highly sensitive biomedical magnetic detection possible due to the digital detection mode, single molecule sensitivity, high signal stability, low background, high specificity, magnetic enrichment and magnetic purification, and low sample demand. The results were published in Nano Letters on March 27, 2023 under the title of "Digital Magnetic Detection of Biomolecular Interactions with Single Nanoparticles".

As basic elements of all living organisms, biomolecular interactions biologically underpin numerous biomedical tests. Among the many used to measure biomolecular interactions, there are biochemical detection, single molecule fluorescence, and surface plasmon resonance. However, most of them are based on optical signal detection and thus susceptible to optical background, signal stability and light scattering, leading to shortcomings in sensitivity and specificity.

Figure 1. Digital magnetic detection of biomolecular interactions.

The team developed a single particle magnetic detection technique by leveraging the nitrogen-vacancy color center in diamonds (an atomic defect in diamond single crystal, which is a newly-developing quantum magnetic sensor). Similar to single molecule fluorescence, the idea is replacing fluorescence detection with magnetic signal detection to effectively solve the above problems. Using a self-built magnetic imaging microscope, quantum precision measurement of individual spins, diamond and magnetic particle surface biofunctionalization, and immunomagnetic labeling, the team established a digital biomolecular interaction magnetic detection technology (Figure 1), and demonstrated its effectiveness in biotin-streptavidin interaction, DNA interaction, protein interaction, and virus-related antibody and nucleic acid detection. Specifically, molecular interaction detection was performed through magnetic imaging with single magnetic particle resolution. Magnetic nanoparticles were bound to the diamond surface by interacting biomolecular pairs, which could be achieved by single molecular interaction. Then, single particle magnetic imaging was used to qualitatively and quantitatively analyze the interactions.

In a nutshell, this study developed a general digital magnetic detection method for biomolecular interactions, with broad application prospects in various fields spanning from basic research of life science to clinical medicine.

Chen Sanyou, research fellow of USTC's School of Biomedical Engineering; Sun Ziting, Li Wanhe and Yu Pei, doctoral students of the Department of Physics, are the co-first authors, while CAS Academician Du Jiangfeng and Professor Shi Fazhan are the co-corresponding authors. The research was sponsored by the National Natural Science Foundation of China, the Ministry of Science and Technology, the Chinese Academy of Sciences, Anhui Province and University of Science and Technology of China.

Paper link: https://pubs.acs.org/doi/10.1021/acs.nanolett.2c04961

(CAS Key Laboratory of Microscopic Magnetic Resonance, Department of Physics, School of Biomedical Engineering, Suzhou Institute of Advanced Research, Chinese Academy of Sciences, and CAS Center for Excellence in Quantum Information and Quantum Physics)