Collaborative Research/IDBR: High-Throughput Measurement of Oxygen Consumption Rates of Single Cells Using Wide-Field Optical-Resolution Photoacoustic Microscopy

合作研究/IDBR：利用宽视场光分辨率光声显微镜高通量测量单细胞耗氧率圣路易斯的华盛顿大学获得了一个奖项，以开发一种新型宽视场光分辨率光声显微镜（OR-PAM）和一种新的高密度单细胞阵列基板，以实现对大量细胞的单细胞耗氧率（OCR）的同时和高通量测量。OCR是细胞功能的关键参数，与它们的代谢状态直接相关。到目前为止，OCR测量已经在大量细胞群上进行。最近的研究表明，越来越多的证据表明，细胞与细胞之间的异质性，以前假定同质群体。测量细胞群体对刺激的平均反应可能不能很好地反映单个细胞的反应。因此，对单个细胞进行OCR测量将提供关于细胞功能的更准确的信息，不仅针对单个细胞，而且针对整个细胞群体。OR-PAM能够以高灵敏度和空间分辨率对广泛的生化物质进行“无标记”检测。将宽视野OR-PAM与高密度单细胞阵列基质相结合，将首次实现大群体单细胞的高通量及时筛选，该项目将为开发一类新的研究细胞代谢异质性的科学仪器奠定坚实的技术基础。这些仪器将是准确的，高分辨率，高通量，易于使用，低成本。因此，它们将对生物学研究的许多领域产生重大影响。这项研究的多学科性质，预计将提供学习和培训的机会，研究生和本科生通过学习新的原则和方法跨越学科界限。来自代表性不足的学区的7-12年级教师和学生将参与其中。研究成果将纳入专业进修学院的本科和研究生课程发展中。还将通过纸质出版物和外联活动向研究界和一般公众传播。除了外联计划外，还制定了一项全面的传播计划。开发的方法，设备和系统将通过会议演示，邀请讲座和研讨会积极推广到生物研究界。将与生物仪器行业建立合作和伙伴关系，以探索进一步开发和商业化的潜在机会。

Collaborative Research/IDBR: High-Throughput Measurement of Oxygen Consumption Rates of Single Cells Using Wide-Field Optical-Resolution Photoacoustic MicroscopyAn award is made to the Washington University in St. Louis to develop a novel wide-field opticalresolution photoacoustic microscope (OR-PAM) and a new high-density single-cell array substrate to achieve simultaneous and high-throughput measurements of single-cell oxygen consumption rates (OCRs) for a large population of cells. OCR is a critical parameter of the functioning of the cells, which is directly linked to their metabolic state. So far, OCR measurements have been performed on bulk populations of cells. Recent studies have shown increasing evidence of cell-to-cell heterogeneity among previously assumed homogeneous populations. Measuring the average response of a cell population to a stimulus may not well reflect individual cell responses. Therefore, conducting OCR measurements on single cells will provide more accurate information on cellular functioning, not only for individual cells but also for the entire cell population. OR-PAM is capable of "label-free" detection of a wide range of biochemicals with high sensitivity and spatial resolution. Combining wide-field OR-PAM with high-density single-cell array substrates will enable high-throughput screening of a large population of single cells in a timely manner for the first time.This project will lay a solid technical foundation for developing a new class of scientific instruments to study heterogeneity in cellular metabolism. These instruments will be accurate, high-resolution, highthroughput, easy-to-use, and low-cost. Therefore, they will significantly impact many areas of biological research. The multidisciplinary nature of this research is expected to offer learning and training opportunities for graduate and undergraduate students to cross their discipline boundaries by learning new principles and methods. Grade 7-12 teachers and students from underrepresented school districts will be involved. Research results will be incorporated into the PIs' course development at both the undergraduate and graduate levels. They will be also disseminated through paper publications and outreach activities to the research community and general public. In addition to the outreach plans, a comprehensive dissemination plan has also been developed. The developed methods, devices and system will be actively promoted to the biological research community through conference presentations, invited talks and seminars. Collaborations and partnerships with bioinstrumentation industries will be established to explore potential opportunities for further development and commercialization.