Resolution-enhanced Fourier ptychographic microscopy based on high-numerical-aperture illuminations

High-resolution and wide field-of-view (FOV) microscopic imaging plays a central role in diverse applications such as high-throughput screening and digital pathology. However, conventional microscopes face inherent trade-offs between the spatial resolution and FOV, which are fundamental limited by the space-bandwidth product (SBP) of the optical system. The resolution-FOV tradeoff can be effectively decoupled in Fourier ptychography microscopy (FPM), however, to date, the effective imaging NA achievable with a typical FPM system is still limited to the range of 0.4-0.7. Herein, we report, for the first time, a high-NA illumination based resolution-enhanced FPM (REFPM) platform, in which a LED-array-based digital oil-immersion condenser is used to create high-angle programmable plane-wave illuminations, endowing a 10x, 0.4 NA objective lens with final effective imaging performance of 1.6 NA. With REFPM, we present the highest-resolution results with a unprecedented half-pitch resolution of 154 nm at a wavelength of 435 nm across a wide FOV of 2.34 mm(2), corresponding to an SBP of 98.5 megapixels (similar to 50 times higher than that of the conventional incoherent microscope with the same resolution). Our work provides an important step of FPM towards high-resolution large-NA imaging applications, generating comparable resolution performance but significantly broadening the FOV of conventional oil-immersion microscopes.