Atomic-Force Microscopy techniques for imaging cells and biological macromolecules in solution

The Atomic Force Microscope (AFM) is increasingly being used in the Life-Sciences field. With this increase in usage there has occurred a concomitant increase in the need for both better developed specimen preparation techniques and better defined operational parameters for the AFM instrument. Life-Science AFM methodology can be divided in to three main areas: Support substrate for the Specimen, Immobilization techniques for attaching the specimen to the support substrate, and Optimum instrument scan parameters to ensure reliable transfer of data from the specimen to the image. Of central importance to Life-Science AFM is the nature of the substrate to be used. The most reliable substrates are those with a well documented surface, whose features are at least an order of magnitude smaller than the specimens of interest. Furthermore, the material should be transparent so that other forms of microscopy can be used (i.e. light, fluorescence, near-field scanning optical, etc.) and the surface chemistry should be both well documented and susceptible to chemical derivitization.