Label-Free Super-Resolution Imaging Techniques

Biological and material samples contain nanoscale heterogeneities that are unresolvable with conventional microscopy techniques. Super-resolution fluorescence methods can break the optical diffraction limit to observe these features, but they require samples to be fluorescently labeled. Over the past decade, progress has been made toward developing super-resolution techniques that do not require the use of labels. These label-free techniques span a variety of different approaches, including structured illumination, transient absorption, infrared absorption, and coherent Raman spectroscopies. Many draw inspiration from widely successful fluorescence-based techniques such as stimulated emission depletion (STED) microscopy, photoactivated localization microscopy (PALM), and stochastic optical reconstruction microscopy (STORM). In this review, we discuss the progress made in these fields along with the current challenges and prospects in reaching resolutions comparable to those achieved with fluorescence-based methods.