Ultralarge-scale spinning time-stretch quantitative phase imaging system for label-free cell and tissue imaging

Abstract

Continuing development of image-based bioassay is mainly hampered by the lack of throughput to systematically screen a large cell/tissue population under extensive experimental conditions; and the overwhelming reliance on biochemical markers, which are not always effective, especially when there is poor prior knowledge of the markers. Here we demonstrate ultralarge-scale, high-resolution “on-the-fly” quantitative phase imaging (QPI) of single-cells and whole-tissue-slide on a spinning-disk assay platform at an imaging rate of at least 100-times faster than current assays – mitigating the imaging throughput limitation hindered by the fundamental space-bandwidth-product limit of classical optical imaging. The concept takes advantage of the high-speed spinning motion, which naturally provides imaging at an ultrafast rate (<10MHz) that can only be made possible with time-stretch imaging. To demonstrate the capability of the system, we imaged both label-free adherent cells and tissue slices, prepared on the functionalized digital versatile discs (DVDs), across a giga-pixel-FOV exceeding 10mm2 at a resolution of ~ 1μm. Both bright-field and QPI images are generated in real-time with this FOV at a spinning speed of <1,000 rpm. In contrast to the vast majority of current QPI modalities, our platform requires no interferometry and no computationally-intensive iterative method for phase retrieval, favouring continuous high-speed QPI operation in real-time. More importantly, this spinning imaging platform allows generation of a catalogue of label-free biophysical phenotypes of cells/tissues, e.g. cell size, dry mass density, morphology as well as light scattering properties, which could enable a new generation of large-scale in-depth label-free image-based bioassays.