We developed a large-scale single-cell intrinsic morphological profiling strategy using ultrahigh-throughput quantitative phase imaging (QPI) combined with a novel spinning on-the-fly cell-based assay platform. This integrated system demonstrates the unprecedented functional assay capability of QPI in not only scaling up the assay throughput, but also empowering new cytometric power to perform multiplexed live-cell drug screening (96 conditions in a single run) and genetic perturbation assay (by CRISPR). This platform thus allows generation of large cellular QPI datasets (4.85 TByte in this study) that could spearhead cost-effective label-free solutions for identifying disease-or gene-related cellular morphological phenotypes in therapeutics screening.
We report an arrayed optofluidic imaging platform that allows multiplexed image-based cell assay at ultrahigh imaging throughput. The assay platform, consisting of 96 fluidic sample chambers arranged in a circular symmetry, operates in a reconfigurable spinning motion synchronized with an ultrafast laser-scanning microscope (a line-scan rate >10 MHz). Based on a stable through-focus spinning mechanism, the assay platform allows ultralarge field-of-view imaging (18.8 cm2, >160 Gpixels) with high image fidelity and subcellular resolution (in both the bright-field and quantitative phase image contrasts). We further validated that the continuous spinning operation has minimal impact on the cell morphology and viability.
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