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

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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.