SBIR Phase I: Development of a Microscope to Detect Cellular Motion in Three-dimensional Tissue

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project is to develop a new microscope that integrates biodynamic imaging with conventional phase contrast microscopy for use in drug development and other research applications. Accurately capturing the signatures of three-dimensional (3D) biological systems provides more realistic measures of drug efficacy and response heterogeneity - two critical aspects of the drug-development process that help find the right drug doses and combinations to kill cancer cells with minimal toxic side effects. This tool will extract functional information at greater tissue depths than conventional microscopies by using cellular motions inside living tissue. The motion is detected by reflected light that carries with it important information about the action of drugs inside 3D tissue, allowing drug evaluations in heterogeneous three-dimensional tissues systems, and providing new insights for pharmaceutical development. This SBIR project aims to develop and test a bio-dynamic microscope that provides a new research tool capable of extracting high information content from three-dimensional tissue cultures and tumor biopsies. The project goals are to construct a new type of microscope based on the detection of cellular motions, and to integrate the microscope with a software platform that is easy to use by customers. The software modules to be developed drive the user interface and provide data visualization. The bio-dynamic microscope extracts functional information at greater tissue depths than conventional microscopes by using Doppler tags on light reflected from intracellular motions inside living tissue. These Doppler tags carry phenotypic profiling information about the action of drugs inside 3D tissue, a critical step towards functional characterization of tumors as targets in personalized cancer therapy.