Inversion interferometry for resolving point sources in real microscopes*

Modal imaging can provide unprecedented resolution for imaging point sources, such as single-molecule fluorescent tags that are used to study biological samples. Theoretical work has shown that modal imaging can approach the quantum limits in optical resolution [1],  albeit assuming highly idealized measurements described by complex quantum operators. To make the potential of quantum measurements available for super-resolution microscopy it is imperative to understand the critical parameters in optical systems for realizing such quantum measurements under realistic conditions. Our efforts focus on understanding these critical parameters and developing an optical system for super-resolving two incoherent point sources (i.e. fluorophore tags) for the study of biological samples. We use a Mach-Zehnder interferometer with optical field inversion to realize image inversion interferometry, in principle allowing for near-optimal imaging of point sources.  We use laser light collimated with a microscope objective to mimic point sources imaged in a microscope. We investigate different methods for image inversion and the effects of aberrations and source bandwidth in the interference visibility.  In a second stage will use this setup with a fluorescence microscope, allowing measurements of sub-diffraction limit sized fluorescent beads, single-molecule fluorescence and finally, protein organization and dynamics in biological samples.

[1] M. Tsang, et al., Phys. Rev. X 6, 031033 (2016)