QuSeC-TAQS: Nanodiamond Quantum Sensing for Four-Dimensional Live-Cell Imaging

该项目旨在通过利用纳米金刚石量子传感和先进显微镜的力量，彻底改变活细胞成像。通过开发具有卓越灵敏度的纳米金刚石量子传感器，该项目将以前所未有的细节研究生命过程的复杂性。这项研究符合美国国家科学基金会的使命，即通过促进对基本生物学机制的理解来促进科学进步，并为国家利益服务。传统的荧光显微镜提供了对细胞结构和功能的宝贵见解，而对局部电磁场具有超高灵敏度的纳米金刚石量子传感器提供了一个新的维度来透视活细胞并揭示生命过程的潜在物理机制。通过将纳米金刚石量子传感器与先进的成像技术相结合，该项目将捕获四维（4D）信息，包括三维空间数据和额外的时间维度。这具有广泛的意义，从通过监测T细胞活性来增强癌症免疫治疗到揭示心脏和神经元细胞膜电位的奥秘。此外，这个项目超出了科学发现的范畴。它包括全面的教育和推广计划，特别侧重于促进STEM领域的多样性。通过让代表性不足的少数群体参与量子相关研究，该团队旨在创建一个充满活力和包容性的量子科学家和工程师社区。该项目不仅支持教育，而且造福于整个社会，为生物医学研究和应用提供了新的途径。这项研究将包括制造可扩展的纳米金刚石传感器，该传感器具有生物相容的界面、均匀的尺寸和形状、可控的色中心密度和最小的杂质。通过将纳米金刚石量子传感器的光学检测磁共振（ODMR）光谱与光片显微镜（LSM）相结合，该团队将实现高时空分辨率和低光毒性，从而实现对活细胞的精确成像。技术方法包括利用机器学习算法和图像处理技术来分析获得的数据，并提取对活细胞动态的有价值的见解。特别是，该团队将应用开发的ODMR-LSM量子传感成像技术来研究T细胞在癌症免疫治疗中的活性和测量膜电位。纳米金刚石量子传感与先进成像技术之间的协同作用将加深对复杂生物过程的理解。所提出的纳米金刚石量子传感系统具有将ODMR光谱与LSM的时空成像相关联的能力，可以揭示以前未研究过的四维活细胞动力学。该项目将弥合基础量子科学与应用生物工程之间的差距，使量子传感在生物医学领域得到丰富的应用。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

This project aims to revolutionize live-cell imaging by harnessing the power of nanodiamond quantum sensing and advanced microscopy. By developing nanodiamond quantum sensors with exceptional sensitivity, this project will study intricacies of life processes with unprecedented detail. This research aligns with NSF's mission to promote the progress of science and serves the national interest by advancing the understanding of fundamental biological mechanisms. While traditional fluorescence microscopy provides valuable insights into cell structures and functions, nanodiamond quantum sensors with ultra-high sensitivity to local electromagnetic fields offer a new dimension to see through live cells and reveal the underlying physical mechanisms of life processes. By integrating nanodiamond quantum sensors with advanced imaging techniques, this project will capture four-dimensional (4D) information, encompassing three-dimensional spatial data and an additional temporal dimension. This has wide-ranging implications, from enhancing cancer immunotherapy through the monitoring of T cell activity to unraveling the mysteries of membrane potentials in cardiac and neuronal cells. Furthermore, this project extends beyond scientific discoveries. It encompasses comprehensive educational and outreach programs, with a particular focus on fostering diversity in STEM fields. By engaging underrepresented minorities in quantum-related studies, this team aims to create a vibrant and inclusive community of quantum scientists and engineers. This project not only supports education but also benefits society at large, offering new avenues for biomedical research and applications.The research will involve the fabrication of scalable nanodiamond sensors with biocompatible interfaces, uniform sizes and shapes, controlled color center densities, and minimal impurities. By integrating optically detected magnetic resonance (ODMR) spectroscopy of nanodiamond quantum sensors with light-sheet microscopy (LSM), this team will achieve high spatiotemporal resolution and low phototoxicity, enabling precise imaging of live cells. The technical approach includes the utilization of machine learning algorithms and image processing techniques to analyze the acquired data and extract valuable insights into the dynamics of live cells. Particularly, this team will apply the developed ODMR-LSM quantum sensing imaging technology to study T cell activity in cancer immunotherapy and measure membrane electrical potential. The synergy between nanodiamond quantum sensing and advanced imaging techniques will deepen the understanding of complex biological processes. The proposed nanodiamond quantum sensing system, with the ability for correlating the ODMR spectroscopy and the spatiotemporal imaging of LSM, allows for revealing 4D live-cell dynamics which have not been studied before. This project will bridge the gap between fundamental quantum science and applied bioengineering and bring quantum sensing into rich applications in biomedical fields.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.