High-throughput quantitative phase imaging enabled by a large field-of-view machine vision camera

High-throughput microscopy has expanded our ability to study large cellular libraries, enabling experiments involving millions of single-cell measurements. However, optical readouts in such large-scale studies are often limited to brightfield or fluorescence imaging, which provide only limited information about intrinsic biophysical properties. Quantitative phase imaging offers a powerful label-free alternative by reporting on cell size, shape, refractive-index distribution, and dry mass, but has traditionally lacked the throughput required for large-scale studies due to trade-offs between spatial resolution, field-of-view, and acquisition speed. Here, we present a high-throughput quantitative phase imaging platform that overcomes these limitations by combining illumination-based differential phase contrast microscopy with a large field-of-view machine vision camera. This approach enables sub-micron resolution quantitative phase imaging across millimeter-scale regions, allowing thousands of individual cells to be imaged simultaneously in a single exposure. By relaxing the traditional resolution–throughput trade-off, the platform enables quantitative phase measurements at scales not accessible with conventional implementations. The system is broadly applicable to biological samples and can be readily integrated with structured environments such as microfluidic devices. As a demonstration, we apply the platform to single bacterial cells in a mother-machine microfluidic device, showing robust, high-resolution quantitative phase imaging. While the platform can be extended to incorporate complementary modalities for validation or additional contrast, its primary contribution is establishing quantitative phase imaging as a scalable, high-throughput quantitative imaging modality for large-scale single-cell studies.