Volumetric Chemical Imaging of Cell Metabolism by Stimulated Raman Projection

在化学系化学测量和成像计划以及分子和细胞生物科学系系统和合成生物学计划的支持下，波士顿大学的程教授正在开发一种成像工具，以微米分辨率、三维(3D)方式和高速检查化学物种。程教授设想，他开发的技术可以用于监测细胞中的微小生物分子，并在原位了解它们的新陈代谢。程教授计划，一旦开发出这项技术，就可以通过商业化向其他用户提供。除了与学生一起参与该项目外，程教授还为本科生提供暑期研究机会。他还组织了一个为期两天的研讨会，教授学生关于无标记光谱成像的知识，并开发了一个关于化学显微镜概念的实验室模块。体积成像使3D复杂系统的定量和全球测量成为可能。它可以量化整个样本体积中的分子，并已被证明在细胞新陈代谢、脑功能和发育生物学的研究中具有无价的价值。对体积成像的最简单方法是在轴向上进行光学切片。这种方法需要聚焦紧密的激光束和良好的轴向切割能力。体积成像的一种方法是通过层析成像，即从样品周围的许多不同角度收集图像。然后，可以使用角度相关图像重建3D信息。程教授开发了一种基于贝塞尔光束的受激拉曼投影(SRP)显微镜和层析成像技术，用于高速体积化学成像。SRP方法是基于这样的概念，即被检测的信号是沿输入贝塞尔光束的瑞利长度方向的受激拉曼散射强度的积分，这些受激拉曼散射强度沿轴向保持很长距离的焦点。与高斯束SRS显微镜相比，Bessel束SRP显微镜能够在2D扫描中量化3D体积的总化学成分。程教授计划将为期两天的无标记光谱成像研讨会与波士顿大学光子学中心的年度研讨会结合起来，向出席此次研讨会的约250名科学家介绍无标记化学成像的创新。此外，郑教授利用波士顿大学的城市实验室与初高中学生和教师建立联系。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

With support from the Chemical Measurement and Imaging Program in the Division of Chemistry and the Systems and Synthetic Biology program in the Division of Molecular and Cellular Biosciences, Professor Cheng at Boston University is developing an imaging tool to examine chemical species at a micron resolution, in a three-dimensional (3D) fashion, and at high speed. Professor Cheng envisions the technique he develops can be used to monitor small biomolecules in cells and understand their metabolism in situ. Professor Cheng plans to make the technique, once developed, available to other users through commercialization. In addition to working with students on the project, Professor Cheng also provides summer research opportunities to undergraduate students. He also organizes a 2-day workshop to teach students about label-free spectroscopic imaging and develops a lab module on the concept of chemical microscopy. Volumetric imaging enables quantitative and global measurements of a 3D complex system. It allows quantitation of molecules in the whole volume of a specimen, and has proven to be invaluable in the studies of cell metabolism, brain function, and developmental biology. The simplest way to image a volume is through optical sectioning in the axial direction. Such a method requires tightly focused laser beams and good axial sectioning capability. One approach for volumetric imaging is through tomography, in which images are collected from many different angles around the sample. The 3D information can be then reconstructed using the angle-dependent images. Professor Cheng develops a Bessel-beam-based stimulated Raman projection (SRP) microscopy and tomography for high-speed volumetric chemical imaging. The SRP method is built upon the concept that the detected signal is an integration of SRS intensity along the Rayleigh length of the input Bessel beams, which remain their focuses along axial direction for a long distance. Compared to the Gaussian beam SRS microscopy, the Bessel beam SRP microscopy is able to quantify the total chemical compositions of a 3D volume in a 2D scan. Professor Cheng plans to integrate a two-day workshop on label-free spectroscopic imaging with the annual symposium of the Boston University's Photonics Center to present innovations in label-free chemical imaging to ~250 scientists attending this symposium. Furthermore, Professor Cheng leverages Boston University's CityLab to connect with middle and high school students and teachers.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.