EFRI-BSBA: Photonic Technique for Sensing and Understanding Subcellular Structures at Nanoscale

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ABSTRACT Photonic technique for sensing and understanding subcellular structures at nanoscale PI: Vadim Backman This project is at the interface of biophotonics, macromolecular biophysics, biology and medicine. The main focus of the project is the development of a photonics technique for sensing the complexity of cellular structure at the nanoscale and its use for understanding alterations in cell nanoarchitecture in early carcinogenesis with the potential impact to advance fundamental knowledge of the initial stage of carcinogenesis and enable, for the first time, population-wide screening for a wide range of major cancers. The project addresses the following two BSBA elements: i) "paradigm shift in practices and applications in engineering, health care, medicine, and biological research" and ii) "sensing at the nanoscale, novel photonic techniques for detecting, identifying, characterizing, and understanding subcellular structures and processes at nanoscale". The applicants have developed a novel optical technique, single-cell partial-wave spectroscopy (PWS), which quantifies the statistical properties of nanoscale cellular structure. Using PWS, we demonstrated that an increase in the disorder of cell nanoarchitecture is one of the earliest events in carcinogenesis which precedes any known microscale alterations. Importantly, the increased nanoscale disorder is not restricted to tumor cells but seen diffusely throughout the organ thus serving as a marker of field carcinogenesis. This provides the impetus to elucidate the mechanisms that determine these nanoscale changes and their role in cancer progression, which is the main goal of this project. Using PWS the following three key questions will be adressed: i) Is the increase in the disorder of cell nanoarchitecture a general phenomenon that takes place in essentially all types of epithelial cancers? ii) What is the origin of these changes? iii) What are the biological implications and possible role in carcinogenesis of the nanoscale disorder? In other words, is this alteration a "side-effect" of other genetic events or is it a necessary step in carcinogenesis? Although it is well accepted that early cancer screening would dramatically decrease cancer mortality, no test currently exists for accurate screening of the most lethal cancers. This is largely because the current state-of-the-art requires direct examination of an already formed precancerous lesion through interventional procedures such as colonoscopy, endoscopy, bronchoscopy, etc. These procedures are expensive, laborious, invasive and not well tolerated by patients, leading to very poor screening rates. This project may lead to a new general paradigm of cancer screening where the presence of neoplasia is detected by the non-invasive optical analysis of non-neoplastic tissue that might be located at a distance from the neoplastic focus in an easily accessible part of the organ. The vision is that this methodology may enable screening for the major types of cancer, for example, during an annual physical exam. Examples include identifying patients with colonic adenomas by analysis of rectal cells, lung cancer by analysis of buccal cells, pancreatic cancer by analysis of duodenal cells, ovarian cancer through analysis of uterine or cervical cells and esophageal adenocarcinoma through analysis of upper-esophageal squamous mucosa. From the educational perspective, the project will provide opportunities in truly interdisciplinary research at the interface of biophotonics, molecular biophysics and cancer biology for graduate, undergraduate and high school students with a particular focus on recruitment of women and minorities in science. The findings will be incorporated into two graduate classes directed by the PI's. The findings and data generated during the course of the project will be disseminated to the scientific community. The main findings will also be disseminated to the general public.