Collaborative Research: Fast Spectrally-Encoded Photoacoustic Microscopy for Multi-Parameter Bioenergetic Characterization of Heterogeneous Cancer Cells

合作研究：快速光谱编码光声显微镜用于异质癌细胞的多参数生物能表征

• 批准号: 2036800
• 负责人: Lihong Wang
• 金额: $ 31.5万
• 依托单位: California Institute of Technology
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-15 至 2025-01-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2036800&HistoricalAwards=false
• 关键词: Collaborative; Research; Fast; Spectrally; Encoded

Compared to their normal counterparts, cancer cells have distinctive bioenergetic (energy generating) functions related to cell metabolism and tumorigenic (tumor causing) properties with significant cell-to-cell variations. Thus, bioenergetic characterization at the single-cell level is necessary to reveal the differing cancer cell energy producing pathways. Such understanding is important for not only fundamental cancer research but also for accurate cancer diagnosis and prognosis and for the development of personalized anti-cancer therapies. In this project, a new high-speed and high-resolution spectroscopic imaging technology and a high-density microwell array will be developed. If successful, this project will lay a solid foundation to achieve a significant method for studying cancer cell metabolism and heterogeneity. Learning and training opportunities will be provided for graduate and undergraduate students as well as Grade 7-12 teachers and students. Technical translation and product development will be explored through teaming with bioinstrumentation companies.The goal of this research is to achieve single-cell oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) characterization for a large population of cancer cells. OCR and ECAR are closely related to the two main metabolic pathways in cells, oxidative phosphorylation and glycolysis, and therefore serve as primary indicators of their bioenergetic phenotypes. To date, electrical or fluorescence methods have been developed to characterize the OCR of a small number of cells. However, it is difficult to scale these methods up for multi-parameter characterization of a large cell population. To accomplish this goal, a fast spectrally-encoded photoacoustic microscopy will be developed to enable high-throughput and simultaneous OCR andECAR characterization on a single measurement platform. Specifically, the Hadamard transformation and optical switching with digital micromirror device will be employed to enable fast tuning of the excitation wavelength. A new water-immersible micro scanning mirror will be developed to provide wide-field optical and acoustic co-scanning. Combining these two new techniques will allow high-speed photoacoustic data acquisition at multiple excitation wavelengths that are programmable or reconfigurable for a specific target.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.

与正常的对应物相比，癌细胞具有与细胞代谢和肿瘤的（肿瘤引起的）特性有关的独特生物能（能量产生）功能，具有显着的细胞对细胞变化。因此，必须在单细胞水平上进行生物能表征来揭示不同的癌细胞能量产生途径。这种理解不仅对于基本癌症研究，而且对于准确的癌症诊断和预后以及个性化抗癌疗法的发展也很重要。在这个项目中，将开发一种新的高速和高分辨率光谱成像技术和高密度的微孔阵列。如果成功，该项目将奠定坚实的基础，以实现研究癌细胞代谢和异质性的重要方法。将为研究生和本科生以及7至12年级的教师和学生提供学习和培训机会。技术翻译和产品开发将通过与生物启示公司的组合探索。该研究的目的是实现大量癌细胞群体的单细胞氧消耗率（OCR）和细胞外酸化率（ECAR）表征。 OCR和ECAR与细胞中的两个主要代谢途径密切相关，氧化磷酸化和糖酵解，因此是其生物能表型的主要指标。迄今为止，已经开发了电或荧光方法来表征少数细胞的OCR。但是，很难将这些方法扩展为大细胞种群的多参数表征。为了实现这一目标，将开发快速编码的光声显微镜，以在单个测量平台上启用高通量和同时的OCR和ECAR表征。具体而言，将采用数字微龙设备的Hadamard转换和光学切换来实现激发波长的快速调整。将开发出一种新的可易感微扫描镜，以提供宽场光学和声学共同扫描。结合这两种新技术将允许以多种激发波长为特定目标的多个激发波长进行高速光声数据获取。该奖项反映了NSF的法定任务，并被认为是值得通过基金会的知识分子和更广泛的影响来支持的。审查标准。

项目成果

Location-Dependent Spatiotemporal Antialiasing in Photoacoustic Computed Tomography

• DOI: 10.1109/tmi.2022.3225565
• 发表时间: 2022-11
• 期刊: IEEE Transactions on Medical Imaging
• 影响因子: 10.6
• 作者: Peng Hu;Lei Li;Lihong V. Wang

Optical-resolution photoacoustic microscopy with a needle-shaped beam

• DOI: 10.1038/s41566-022-01112-w
• 发表时间: 2022-12-01
• 期刊: NATURE PHOTONICS
• 影响因子: 35
• 作者: Cao, Rui;Zhao, Jingjing;Wang, Lihong, V
• 通讯作者: Wang, Lihong, V