Innovative Imaging Techniques: A Conceptual Exploration of Multi-Modal Raman Light Sheet Microscopy

Abstract

Advances in imaging of microscopic structures are supported and complemented by adaptive visualization tools. These tools enable researchers to precisely capture and analyze complex three-dimensional structures of different kinds such as crystals, microchannels and electronic or biological material. In this contribution, we focus on 3D cell cultures. The new possibilities can play a particularly important role in biomedical research, especially here in the study of 3D cell cultures such as spheroids in the field of histology. By applying advanced imaging techniques, detailed information about the spatial arrangement and interactions between cells can be obtained. These insights help to gain a better understanding of cellular organization and function and have potential implications for the development of new therapies and drugs. In this context, this study presents a multi-modal light sheet microscope designed for the detection of elastic and inelastic light scattering, particularly Rayleigh scattering as well as the Stokes Raman effect and fluorescence for imaging purposes. By combining multiple modalities and stitching their individual results, three-dimensional objects are created combining complementary information for greater insight into spatial and molecular information. The individual components of the microscope are specifically selected to this end. Both Rayleigh and Stokes Raman scattering are inherent molecule properties and accordingly facilitate marker-free imaging. Consequently, altering influences on the sample by external factors are minimized. Furthermore, this article will give an outlook on possible future applications of the prototype microscope.