The central idea is SWITCH -- a reaction control strategy that allows for uniform tissue processing. Basically, you allow chemicals to diffuse into the tissue first without reacting with the tissue (this is called SWITCH-Off). Then, when they are fully dispersed, you let them react (this is called SWITCH-On).


For example, imagine you were doing whole brain antibody labeling. You incubate the brain in antibody solution for a week, hoping that it's enough. But when you image, you will find that only the surface and regions close to the surface are stained, while the core is not stained very well.

The illustration above compares conventional labeling to SWITCH labeling. As you can see, if you do the SWITCH approach and give enough time for antibodies to diffuse throughout the tissue, you will get a uniform staining throughout the tissue.

This concept applies to fixation as well. It turns out that fixation is very similar. The surface always reacts first, then the core. But SWITCH protocol allows you to do uniform fixation. This becomes very useful when, for example, you are working with tissues that you can't perfuse (perfusion bypasses the diffusion step because it disperses chemicals through vasculature) or tissues from tissue banks.