IDBR: In vivo multifunctional photothermal cytometry

University Of Arkansas Medical Sciences Campus, Little Rock AR

Investigators

Abstract

Two methodologies have dominated in biological studies: Laboratory experiments at the subcellular levels, and experiments examining populations of cells in living organisms. This leaves a persistent and recurrent gap in our understanding of biological phenomena. It is not possible to adequately replicate in a test tube the full repertoire of environmental factors that are important in living organisms, and whole-animal studies currently are limited with regards to studying the structure and activities of individual cells with sufficient resolution and sensitivity, especially in a bioflow context. This award will fill this gap by developing a multiparameter photothermal cytometer for real-time study of individual cells in living organisms, in both static and flow conditions with molecular specificity, based upon intrinsic vibrational spectroscopic contrast. The advanced technical platform with a spectrally tunable near-infrared nanosecond pulse laser will be built for non-invasive, rapid (millisecond scale) detection and imaging of single cells with high optical resolution, enhanced absorption sensitivity (four orders better than in convention absorption spectroscopy), and accurate cell positioning. The instrument can be applicable to studies of various living animal models, including mouse ear and mesentery or C. elegans. The project outcomes encompass an almost unexplored area of biological research associated with the use of weakly fluorescent, light-absorbing cellular micro- and nanostructures as intrinsic cell-specific photothermal markers for the non-invasive real-time study in living organisms of various biological processes such as programmed cell death (apoptosis), metabolic activity, and the influence of environmental factors (e.g., oxidative stress) on homeostasis, immunity, and longevity. Long-term goals include enhancing the photothermal cytometer for use in three-dimensional imaging, developing photothermal multiphoton microscopy, and potentially integrating photothermal, fluorescence, and light scattering techniques. This interdisciplinary research involves mathematicians, physicists, electrical engineers, chemists and biologists, and will include developing a training program and new coursework on advanced optical imaging, animal models, and cell study in vivo to benefit the education of undergraduate, graduate, and postgraduate students at University of Arkansas for Medical Sciences and University of Arkansas at Fayetteville at Little Rock. Students from different ethnic groups from University at Pine Bluff, and disabilities (through Arkansas School for the Deaf) will be mentored.