Refractive Index Imaging of Cellular Structures

Abstract

Label free microscopic approaches have become a necessity to explore, image, and understand, complex biological systems with minimal sample modifications [1]. These innovative microscopes exploit the native photophysical processes present when light interacts with matter, presenting a plethora of options not only for introducing image contrast, but in providing information unobtainable with traditional approaches [2]. When paired with the recent and significant advances in computational approaches, label free imaging is a profoundly powerful tool to image biological systems in innovative ways. In particular, the way in which light is slowed when passing through a sample, known as it's phase shift, is a label-free paradigm particularly useful for biological samples. This is because the refractive index is essentially a relation of the different chemical or physical properties of the sample, and if obtained quantitatively can be used to characterize the contents and distribution of cellular contents [3]. In this work the phase information from our custom ptychographic microscope is compared and combined with traditional fluorescent images, as well as advanced label-free techniques [4], to extract refractive index information of healthy and unhealthy cells. Our results showcase the ability of ptychography to not only provide high quality images of samples, but to also deliver complimentary information about the processes within a cell, currently not able to be captured with standard high-resolution approaches.