Development of wide-field quantum diamond microscope for practical applications

Abstract

Diamond-based quantum sensing, particularly using nitrogen-vacancy (NV) centers, is valued for its high sensitivity and nanoscale resolution. The spin state of the NV center, which is easily manipulated by microwaves and features long coherence time, along with its optical readout capabilities, gives it great potential applications across various fields. However, current quantum sensing technologies are constrained by the limitations in temporal and spatial resolution inherent to traditional wide-field microscopes. This thesis aims to enhance the performance of wide-field quantum microscope in time and space, and expand their applications in biology, such as cellular force measurement.

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.

Secondly, 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 ODMR resonant frequencies. Compared to frame-based ODMR measurement techniques, our event camera method significantly reduces the measurement time 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 NV centers in 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.

Lastly, although the developed cellular force measurement tool offers excellent spatial resolution and sensitivity, it still has some limitations, such as only being able to measure vertical cellular forces. This restricts our in-depth understanding of the mechanisms behind cell-environment interactions. To address this issue, we use fluorescent nanodiamonds (FND) instead of bulk diamonds, converting mechanical signals into measurable magnetic signals with the FND, enabling the measurement of cellular forces in any direction. We have laid a solid foundation for further implementing and refining our technological solution by testing its feasibility through measuring the longitudinal relaxation time of FND both with and without nanomagnetic beads.