Supporting data for “Development of Wide-field Quantum Diamond Microscope for Practical Applications”
Diamond-based quantum sensing technology has garnered widespread attention due to its extremely high sensitivity and nanoscale spatial resolution. Particularly, the nitrogen-vacancy (NV) center within diamond, which benefits from its unique energy level structure and excellent quantum spin properties, has become an ideal choice for quantum sensing. The quantum spin state of the NV center can be easily manipulated with microwaves and maintains a long coherence time at room temperature, coupled with its optical readout capabilities. This makes diamond quantum sensors based on NV centers highly promising for applications in biological detection and extreme environment monitoring. Despite significant advancements in the measurement of magnetic fields, temperature, and ion concentrations, current quantum sensing technologies are still limited by the time and spatial resolution constraints of traditional wide-field microscopes. This thesis aims to explore how to enhance the performance of wide-field quantum microscopes and expand their applications in the field of biology, such as developing the cellular force measurement techniques based on quantum sensing technology to enchance our understanding of bio-mechanics.
Firstly, by integrating structured illumination microscopy (SIM) into traditional wide-field quantum sensing technique, we have successfully developed a super-resolution wide-field quantum sensing technique. The feasibility of this approach was verified using optically detected magnetic resonance (ODMR) measurements on two unresolved fluorescent nanodiamonds under a traditional wide-field microscope, which demonstrates the SIM-based super-resolution technique can be integrated into the quantum measurement without interference. Furthermore, we have confirmed the significance of the programmable illumination patterns based on digital micromirror devices (DMD) in reducing phototoxicity to light-sensitive samples during extended exposure times. These achievements lay a solid foundation for the application of DMD-based super-resolution wide-field quantum sensing technology in the field of biology.
Traditional frame-based wide-field quantum sensing technologies are limited in temporal resolution, primarily due to the restricted transmission and data readout speeds of conventional cameras. To overcome this limitation, we have developed a quantum sensing method based on event cameras. This method leverages the unique operating mechanism of neuromorphic vision sensors, which allows it to directly convert continuous fluorescence changes into discrete signals and accurately extract the optically detected magnetic resonance (ODMR) resonant frequencies. Compared to frame-based ODMR measurement techniques, our event camera method significantly reduces the time required for measurement while maintaining similar precision, achieving low-latency and high-precision results.
Thirdly, the interaction between cells and their environment is crucial for understanding various biological processes. However, existing cellular force measurement technologies have inherent limitations, such as photobleaching of the fluorescent labels. To address these issues, we have developed a wide-field quantum sensing technology for cellular force measurements based on diamond. This innovative technique converts mechanical signals into magnetic signals that can be detected by NV centers, enabling highly sensitive and high-resolution measurements of cellular forces. Moreover, the sensors can be cleaned and reused, which enhances the accuracy of measurements across different groups. This breakthrough has the potential to revolutionize the way we study cellular interactions and will have a profound impact on the fields of biophysics and biomedical engineering. Additionally, the data obtained from the study of cellular adhesion forces will have practical value for the development of future force sensing and force transmission theories.
Lastly, although the cellular force measurement tool we previously developed offers excellent spatial resolution and sensitivity, it still has some limitations, such as only being able to measure cellular forces in the vertical direction. This restricts our in-depth understanding of the mechanisms behind cell-environment interactions. While other tools are available to supplement the measurement of lateral cellular forces, they are insufficient to fully reveal the complexity of cellular behavior. To address this issue, we have built upon our previous work by employing nanodiamonds (FND) as quantum sensors in place of traditional bulk diamonds. This innovation allows for the measurement of cellular forces in any direction. The measurement principle is similar to our previous work, both involving the conversion of mechanical signals into magnetic signals detectable by NV centers. Currently, we have conducted preliminary experiments that, by measuring the changes in the longitudinal relaxation time of FND before and after labeling with nano-magnetic beads, have provisionally verified the feasibility of this approach. These experimental results have laid a solid foundation for us to further implement and refine this technological solution.
