IIBR Instrumentation: Optomagnetic twisting cytometry (OMTC) for high throghpout mapping of viscoelastic properties of live tis

University Of California-Los Angeles, Los Angeles CA

Investigators

Abstract

The mechanical properties of cells play a crucial role in various biological processes, including cell adhesion, migration, and differentiation, and are essential for understanding disease progression. This project aims to develop an innovative OptoMagnetic Twisting Cytometry (OMTC) system to quantify the dynamic viscoelastic properties of 3D tissue samples. The OMTC system enables simultaneous measurements over a large field-of-view, advancing our understanding of the mechanical properties of live tissues. This groundbreaking technology has the potential to significantly impact disease diagnosis, treatment monitoring, and tissue engineering. By bridging the technological gap in current methodologies, the project aligns with NSF's mission to promote the progress of science and contribute to the national interest. The broader impacts of the project include advancing healthcare and biological research and disseminating knowledge through social media, conferences, publications, and courses. The OMTC system quantifies the local dynamic viscoelastic properties inside a 3D tissue sample by detecting the rotational movement of microparticles embedded within the tissue. This detection is achieved by capturing orientation-dependent light scattering and fluorescence signals from anisotropic microparticles. An optical scanning system that utilizes the focal plane scanning emission (FPSE) concept will be constructed to provide a collimated light beam with uniform intensity distribution for large volume directional illumination. This method eliminates the need for high numerical aperture optics for precision measurement and allows for simultaneous measurements of hundreds of thousands of microparticles within a large field-of-view using low-magnification objective lenses. The OMTC system can detect both the 3D positions and 3D orientations of microparticles. By analyzing the orientation changes before and after magnetic actuation, the local viscoelastic properties near each microparticle can be determined. Integrating data from microparticles randomly distributed within the tissue allows for mapping the dynamic viscoelastic properties of a 3D tissue sample. The developed OMTC system will be applied to study the dynamic processes of antitumor immunity by CAR-T cells in 3D tumor spheroid models. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.