Microsphere-assisted quantitative phase microscopy: a review

Light microscopes are the most widely used devices in life and material sciences that allow the study of the interaction of light with matter at a resolution better than that of the naked eye. Conventional microscopes translate the spatial differences in the intensity of the reflected or transmitted light from an object to pixel brightness differences in the digital image. However, a phase microscope converts the spatial differences in the phase of the light from or through an object to differences in pixel brightness. Interference microscopy, a phase-based approach, has found application in various disciplines. While interferometry has brought nanometric axial resolution, the lateral resolution in quantitative phase microscopy (QPM) has still remained limited by diffraction, similar to other traditional microscopy systems. Enhancing the resolution has been the subject of intense investigation since the invention of the microscope in the 17th century. During the past decade, microsphere-assisted microscopy (MAM) has emerged as a simple and effective approach to enhance the resolution in light microscopy. MAM can be integrated with QPM for 3D label-free imaging with enhanced resolution. Here, we review the integration of microspheres with coherence scanning interference and digital holographic microscopies, discussing the associated open questions, challenges, and opportunities.