Illuminated up close: near-field optical microscopy of cell surfaces

Invented in the 1990s, near-field optical microscopy (NSOM) was the first optical microscopy method to hold the promise of finally breaking the diffraction barrier in studies of biological samples. This promise, though, failed to materialize at that time, largely owing to the inability to image soft samples, such as cell surfaces, without damage. However, steady technical improvements have now produced NSOM devices that can routinely achieve images of cell surfaces with sub-100nm resolution in aqueous solution. Further, beyond just optical information, these instruments can also provide simultaneous topographic, mechanical, and/or chemical details of the sample, an ability not yet matched by any other optics-based methodology. With the long recognized important roles of many biological processes at cell surfaces in human health and disease, near-field probing of cell surfaces is indeed now well poised to directly illume in biomedicine what has, until recently, been unknowable with classic light microscopy.