Brillouin Microscope for Biomedical Research
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abstract
This proposal is motivated by the need to assess microscopic viscoelastic properties, which have emerged asa powerful biomarker for a number of diseases, such as cancer, atherosclerosis, sickle cell disease, etc., butalso have been identified as a driving force for many biological processes, such as carcinogenesis,angiogenesis, morphogenesis, etc. The emergence of novel biomaterials for regenerative medicine also callsfor a better understanding of biomechanical cellular-level interactions.In the past, assessment of elastic properties of tissues was mostly limited to large-scale imaging usingultrasound and magnetic resonant imaging and to nanoscopic contact assessment using either opticaltweezers or atomic force microscopy instruments, which paved the way to our better understanding ofviscoelastic properties of cells and tissues and their importance for biomedical research. In the same time, it isnow realized that there is a substantial technology gap in instrumentation capable of assessing non-invasivelyviscoelastic properties on a microscopic scale with high enough spatial resolution, high sensitivity and highspeed. Recently, optical coherence elastography was successfully developed to assess elastic properties oftissues on the scale of 15-100 ðœ‡ð‘š. Ideally, such an instrument should be fully compatible with existinginstrumentation using fluorescence and Raman microscopy systems to provide an additional capability tothose. Brillouin microscopy is emerging as a powerful tool for non-invasive biomedical imaging. Developing itinto a powerful instrument for biomedical research and, potentially, clinical applications is considered to be theoverarching goal of this proposal.Two strategies will be pursued through this grant application. The first approach is relying on spontaneousBrillouin microscopy, which is simpler in use, and, with relatively minor modifications, can be implemented asan option in already existing commercial fluorescent or Raman microscopes for a large biomedical community.The second strategy is to utilize nonlinear Brillouin spectroscopy and microscopy to boost the efficiency of thesignal and data acquisition rate by astonishing 5 orders of magnitude. This methodology utilizes ultrashortpulse excitation and is fully compatible with multiphoton fluorescence microscopy, second- and third-harmonicmicroscopies and coherent anti-Stokes Raman microscopy. An additional benefit of nonlinear Brillouinmicroscopy is improved sectioning capabilities. The overall strategy is to design, construct and characterizeboth microscopes in parallel, since each of those offers distinct advantages for a particular set of applications,and to demonstrate their imaging capabilities for biologically relevant systems to image cells growth anddevelopment in response to a local viscoelastic environment and image developing zebrafish embryo duringthe first 72 hours post fertilization.
