The advancement of optical microscopy technologies has achieved imaging of nanoscale objects, including nanomaterials, virions, organelles, and biological molecules, at the single entity level. Recently developed plasmonic and scattering based optical microscopy technologies have enabled label-free imaging of single entities with high spatial and temporal resolutions. These label-free methods eliminate the complexity of sample labeling and minimize the perturbation of the analyte native state. Additionally, these imaging-based methods can noninvasively probe the dynamics and functions of single entities with sufficient throughput for heterogeneity analysis. This perspective will review label-free single entity imaging technologies and discuss their principles, applications, and key challenges.
Keywords: evanescent scattering; interferometric scattering; label-free optical microscopy; nanofluidic scattering; nanoscale single entities; plasmonic scattering; single molecules; surface plasmon resonance.