A number of our users have been testing out the low-fluorescence DMEM from Life Technologies, Fluorobrite DMEM, and many have found that it substantially improves the signal-to-background of their experiments, particularly for imaging dim samples. Recently we tried it when doing sptPALM of PA-GFP, and found that it made a substantial difference in image quality. Below are two movies, taken under identical conditions, and scaled identically, of single PA-GFP labeled receptors diffusing in the membrane of a cell. They are illuminated with modest 488 nm excitation and weak 405 nm excitation to switch PA-GFP on. The movies were acquired by TIRF, and are shown in real time. The top movie is of cells in conventional DMEM-based media; the bottom, cells in Fluorobrite DMEM. The Fluorobrite media substantially improves the image contrast; there’s also a noticeable reduction in background events outside of the cell.
If you’re doing low-signal imaging, particularly in the GFP channel, I think the Fluorobrite media is well worth trying out.