Deep learning extended depth-of-field microscope for fast and slide-free histology

Significance Traditional microscopy suffers from a fixed trade-off between depth-of-field (DOF) and spatial resolution—the higher the desired spatial resolution, the narrower the DOF. We present DeepDOF, a computational microscope that allows us to break free from this constraint and achieve >5× larger DOF while retaining cellular-resolution imaging—obviating the need for z-scanning and significantly reducing the time needed for imaging. The key ingredients that allow this advance are 1) an optimized phase mask placed at the microscope aperture; and 2) a deep-learning-based algorithm that turns sensor data into high-resolution, large-DOF images. DeepDOF offers an inexpensive means for fast and slide-free histology, suited for improving tissue sampling during intraoperative assessment and in resource-constrained settings.