IDBR: TYPE A: Directly Integratable Photoacoustic Microscopy with Established Optical Microscopy for Comprehensive Sub-cellular Biological Imaging

点击翻译按钮获取中文摘要

An award is made to Northwestern University to develop a photoacoustic microscopy (PAM) technology platform that is compatible with commercial optical microscopes. PAM differs from other established optical microscopic technologies by directly sensing the physiologically-specific optical absorption properties in tissue rather than optical scattering or fluorescence properties. Hence, it holds promise to greatly enhance the imaging capability of current biological research by offering a new type of imaging contrast. Despite this great promise, however, PAM can be performed only by a very limited number of research groups in the US due to the lack of a commercially available system, which is mainly because the existing PAM systems are incompatible with commercial optical microscopes. Thus, researchers have to construct their own PAM systems, which is clearly beyond the capability of biological researchers and may not be economically feasible. To address this barrier, this project aims to make PAM more accessible to the vast majority of biological researchers who are already using advanced optical microscopy in their daily research. This project will benefit biological investigations that require quantitative imaging of, for example, tissue hemodynamics, interactions of a cell and its microenvironment, cell/tissue regeneration, and drug evaluation. The PAM system can either be used independently for label-free volumetric imaging or be integrated with confocal/two-photon microscopes for multimodal imaging. The key intellectual merit of this project comes from its novel designs that enable PAM to be broadly accessible by making PAM compatible with existing optical microscopy. Two incompatibility issues prevent existing PAM from being seamlessly integrated with modern optical microscopes: (1) PAM's slow and bulky mechanical scanning mechanism cannot match the high-speed optical scanning used in modern optical microscopy and (2) PAM's opaque and sizeable ultrasonic detectors cannot be easily fit into the extremely limited working space associated with high-power objective lenses. This project provides effective solutions to address these two issues.The key broader impact of this research is that it will, for the first time, lay a solid foundation for PAM to be broadly accessible by the vast majority of biological researchers rather than just a few optics research groups. Breakthroughs in biological research often follow technology advancement; however, developing a novel technology applicable to biological research is only the beginning. The key step to bringing a societal benefit is to make newly developed technologies approachable by users. Owing to the great strengths of PAM to offer unstained functional imaging in tissues and cells at high resolution in three dimensions, the integrated system has the potential to augment a wide range of biological research fields. This project requires active involvement of students at both the undergraduate and graduate levels. A unique aspect of this project is that students will gain interdisciplinary expertise across fields from physics, optics, chemistry, and engineering to medical sciences. Moreover, the large biological research user base of the Center for Advanced Molecular Imaging and the ability to draw wide-spread public attention by the Chemistry of Life Processes Institute will warrant the maximum dissemination of the technology being developed in this project.This award is being made jointly by two Programs- (1) Instrument Development for Biological Research, in the Division of Biological Infrastructure (Biological Sciences Directorate), and (2) Biophotonics, in the Division of Chemical, Bioengineering, Environmental and Transport Systems (Engineering Directorate).