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

Abstract

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 10×, 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 mm2, corresponding to an SBP of 98.5 megapixels (∼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.