All investigations in biology - including imaging - begin with an experiment that modifies the function of a molecule, cell, or tissue. Usually, a foreign gene is introduced into the cell or the function of a resident gene is knocked out. Alternatively, the actions of proteins in cells are modulated by chemicals or the physical environment of the cells. How the samples to be imaged are manipulated depends largely on the molecules and cells being studied, the probes for tagging molecules, the microscopy method used, and the goal of the research. Cell and tissue samples may be chemically "fixed" or imaged "live" and in environmentally controlled conditions, based on the nature of a particular investigation.

Examples of samples

In cryoelectron microscopy, protein samples and entire cells are frozen in order to immobilize and visualize systems that are in dynamic motion at more normal temperatures. In light microscopy, individual proteins may be tagged with a fluorescent tag to make them stand out. Samples may also be imaged in microfabricated devices to ensure controlled and reproducible 3D environments, and subjected to various drugs or changes in environmental conditions.