Coherent Doppler Spectroscopy of Intracellular Transport in Living Tissue

Cancer cells crawl at slow speeds that can be challenging to detect. Even at slow speeds, cancer cells can reach blood vessels that carry them to distant locations in the body. This project will use lasers and biophotonics technology to build a sensitive cell ‘radar speed gun’ that can measure the speed of cells crawling through living tissues and find which drugs can prevent them from spreading. This approach will also be able to measure faster speeds at which immune cells move while patrolling tissues to find and eliminate wayward cancer cells. By measuring the speed and density of immune cells inside cancer tumors, this imaging system will be able to assess the benefits of immunotherapies to specific patients. This project exemplifies how fundamental principles from the science of light can deliver transformative advancements in cancer diagnosis and treatment. Biodynamic imaging will be extended to measure a broad range of frequencies to access a wider range of cellular functions, such as metastatic motion, by developing a compact common-path configuration and fast vesicle transport by implementing high-speed imaging without losing quantum efficiency. Quantitative phase imaging of thick tissues will measure the probability distribution functions of anomalous intracellular Levy transport and will explore the connections among Doppler spectral changes and drug action. Fundamental scientific studies will connect Doppler shifts to specific drug mechanisms of action, and computational models will provide predictive tools that explain spectral signatures in terms of biological mechanisms to improve assay interpretability. The long-term goal of this project is to establish biodynamic imaging as a reliable phenotyping technology for the rapid selection of personalized medical treatment when drug resistance is the principal barrier to effective treatment. 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.