Sub-diffraction Multi-Modal Microscopy using Two-Dimensional Microlens Arrays

Optical microscopy is central to biomedical research, enabling the visualization of pathogens, cells and tissues amongst others. Yet, high-resolution microscopy systems often remain confined to specialized labs due to cost and complexity. Recently, portable, low-cost microscopes have been developed for resource-limited settings, but they usually rely on a single low numerical aperture (NA) objective, which significantly restricts resolution and reduces diagnostic sensitivity. Here, we demonstrate a two-dimensional microlens array placed directly in close contact with the specimen, creating magnified virtual images that exceed the diffraction limit with minimal hardware requirements. Utilizing dark field, phase contrast, and fluorescence modes, our approach achieves sub-400 nm resolution with a 0.25 NA lens. We validated it by imaging nanoparticle uptake in BT-20 breast cancer cells. Furthermore, we then applied this technique to image mammalian cells and tissues, including sickle cells. This cost effective, and simple microlens substrate boosts resolution of low-resolution microscopes, bringing high-performance imaging capabilities to a broad spectrum of clinical diagnostics, research, and educational applications.