The atomic force microscope (AFM) measures surface topography and properties at the nanoscale. It is a bread-and-butter characterization tool for research on nanostructured materials, nanoparticles, and nanoscale lithography. It has been used to measure interaction and conformational forces with piconewton sensitivity in nucleic acids, proteins, and coordination compounds.

Confocal laser scanning fluorescence microscopy (confocal) is widely used in the life sciences. As with widefield epifluorescence microscopy, it uses multiple channels to distinguish different functional labels at different wavelengths, typically with a combination of dyes, antibody labeling, and expression of fluorescent proteins. In addition, confocal provides rejection of out-of-focus light, or optical sectioning. This improves the signal-to-background ratio for all samples, but is especially important for samples with fluorescent media and environment-sensitive (e.g. Ca²⁺) dyes. Laser-scanned confocals also can be equipped with spectral detection for independent resolution of similar fluorophores.

Combining these techniques, we arrive at an integrated microscope in which the AFM provides nanoscale resolution and quantitative force measurements, while the confocal provides functional labeling and spectral characterization. Current results will be discussed, along with a practical perspective on implementation.