Molecular-Specific Sensing and Imaging of Biological Samples

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During the past three decades, optics-based sensing and imaging technologies have gained significant attention due to their safe non-ionizing nature and high sensitivity to detect tissue structural abnormalities. The source of contrast in these technologies is predominantly scattering of light from biological structures which frequently fails to detect the difference between healthy and malignant tissue at the early stages of diseases. This limitation is due to induced changes typically initiating at the molecular level rather than structural level at early disease stages. This proposed research program aims to employ a combination of various light-matter interactions mechanisms (e.g., scattering and absorption of light) to generate new knowledge and technologies for concurrent sensing/imaging of structure and molecular contrast of biological samples to enable more accurate diagnosis of diseases and conditions at early stages. Target applications covers a broad range of biological samples, spanning from biomolecules to microorganisms to tissue: Photothermal sensing of biomolecules. We will develop knowledge and low-cost technologies for the extraction, concentration, and isolation of biomolecules from fluidic biosamples (e.g., COVID-19 virus or THC/psychoactive element of cannabis) and then utilize absorption of light to accurately detect and quantify the concentration of the biomolecules. These innovations will enable low-cost detection of biomolecules at the points-of-need, but with accuracy offered by costly and time-consuming laboratory techniques (e.g., PCR). High-throughput high-content microscopy of worms. C. elegans worms are model organism frequently used for studying the underlying mechanisms of human diseases (e.g., Parkinson's disease). We will develop artificial-intelligence-guided optofluidic solutions for continuous imaging of both structure and fluorescent expression of C. elegans populations at high resolution and with an unprecedented high speed. These platforms are expected to significantly enhance the efficiency of biological studies aimed at revealing disease mechanisms or discovery of new drugs. Co-registered tomography of tissue structure and chemistry. We will perform fundamental and applied research to enable quantitative photothermal optical coherence tomography of tissue. Co-registered structural and molecular characterization of tissue in 3D and at high resolution will enable earlier detection of diseases and conditions (e.g., identification of rupture-prone cardiac plaques). This program will train 22 undergraduate students and 7 postgraduates over 5 years. They will gain interdisciplinary skills at the interface of physics, engineering, biology, and medicine and interact with our collaborators from industry, academia, and government. Trainees will also be trained on professional dissemination of research findings via writing papers and giving talks at conferences.