In cell imaging, the most often used proteins are the Fluorescent proteins like (Green Fluorescent Protein}, GFP or many other fluorescent proteins like Yellow-FP, Blue-FP. They are popular because it is possible to express a labeled protein directly inside the cell. Before the discovery of fluorescent proteins, the only method was to express the protein, purify it and then label it. Then, you had to figure out a method to inject into the cell. That had been done by microinjection.
Luminscence based methods could also be used but they never gained popularity since they always required a substrate and the enzyme to catalyze the substrates were not very good and the light that was released was never enough to image.
Takeharu Nagai’s group at Osaka University has come up with a more efficient luminescent protein called nano-lantern by combining the Renilla luciferase with the yellow fluorescent protein, Venus. This has enabled real time imaging in cells for its intensity as well as specific localization. The technology is rugged enough that it can be used in mice.
The really interesting thing is that the team has engineered various domains into this 2-protein combination that enables it to act as a sensor for Calcium, cyclic AMP and ATP. Interestingly, even though the power density of emitted light for Nanolantern is hundred fold lower than that of Fluorescence (about 100-microwatts per cm2 ) the signal to noise is significantly better.
Its deficiency is that it requires the addition of the substrate that is catalyzed by the luciferase enzyme, however, in vivo applications for the technology may be its sweet spot for the very high signal to noise ratio’s.