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Ptychography is an enabling microscopy technique for both fundamental and applied sciences. In the past decade, it has become an indispensable imaging tool in most X-ray synchrotrons and national laboratories worldwide. However, ptychography’s limited resolution and throughput in the visible light regime have prevented its wide adoption in biomedical research. Recent developments in this technique have resolved these issues and offer turnkey solutions for high-throughput optical imaging with minimum hardware modifications. The demonstrated imaging throughput is now greater than that of a high-end whole slide scanner. In this review, we discuss the basic principle of ptychography and summarize the main milestones of its development. Different ptychographic implementations are categorized into four groups based on their lensless/lens-based configurations and coded-illumination/coded-detection operations. We also highlight the related biomedical applications, including digital pathology, drug screening, urinalysis, blood analysis, cytometric analysis, rare cell screening, cell culture monitoring, cell and tissue imaging in 2D and 3D, polarimetric analysis, among others. Ptychography for high-throughput optical imaging, currently in its early stages, will continue to improve in performance and expand in its applications. We conclude this review article by pointing out several directions for its future development. 

The recent advent of whole slide imaging (WSI) systems has moved digital pathology closer to diagnostic applications and clinical practices. Integrating WSI with machine learning promises the growth of this field in upcoming years. Here we report the design and implementation of a handheld, colour-multiplexed, and AI-powered ptychographic whole slide scanner for digital pathology applications. This handheld scanner is built using low-cost and off-the-shelf components, including red, green, and blue laser diodes for sample illumination, a modified stage for programmable sample positioning, and a synchronized image sensor pair for data acquisition. We smear a monolayer of goat blood cells on the main sensor for high-resolution lensless coded ptychographic imaging. The synchronized secondary sensor acts as a non-contact encoder for precisely tracking the absolute object position for ptychographic reconstruction. For WSI, we introduce a new phase-contrast-based focus metric for post-acquisition autofocusing of both stained and unstained specimens. We show that the scanner can resolve the 388-nm linewidth on the resolution target and acquire gigapixel images with a 14 mm × 11 mm area in ∼70 seconds. The imaging performance is validated with regular stained pathology slides, unstained thyroid smears, and malaria-infected blood smears. The deep neural network developed in this study further enables high-throughput cytometric analysis using the recovered complex amplitude. The reported do-it-yourself scanner offers a portable solution to transform the high-end WSI system into one that can be made widely available at a low cost. The capability of high-throughput quantitative phase imaging may also find applications in rapid on-site evaluations.