Diffusion Models to Enhance the Resolution of Microscopy Images: A Tutorial

Over a century ago, the microscopist Ernst Abbe devised an equation showing how the resolution of an optical microscope is limited by the wavelength of the illumination light [1]. This critical limitation, known as the Abbe's diffraction limit, implies that it is not possible to resolve objects smaller than 200 nanometers using an optical microscope. For scale, the diameter of a DNA molecule is about 2.5 nanometers--approximately one hundred times smaller. Since then, the quest to overcome this limit and to develop techniques for highresolution imaging of cellular and subcellular structures has led to significant advancements in biomedical research [2, 3, 4, 5, 6, 7] paving the way for super-resolution microscopy. The super-resolution techniques that have revolutionized the field include structured illumination microscopy (SIM) [6, 7], stimulated emission depletion (STED) [2, 3], stochastic optical reconstruction microscopy (STORM) [5], and photoactivated localization microscopy (PALM) [4]. However, these techniques require complex and expensive instrumentation, limiting their widespread availability.