A Whole New Level

Other than for cell biologists, who are the most important users, there are also several areas of application that could be of great interest to developmental biologists. The product manager believes that the market’s requirements are clear: “Everyone wants to show more sensitivity, so they inspect their samples more quickly and at a higher resolution.” For a long time, improving one of the three parameters – sensitivity, speed and resolution – was detrimental to the other two (see diagram). For instance, in the past, if you wanted to keep an eye on processes in the millisecond range, it was not possible to depict this in high resolution. Or you had to increase the light intensity to a degree that either damages the cell or significantly impacts the process. “In order to prevent this, you have to disrupt system dependencies. That’s exactly what we were able to achieve by integrating Lattice SIM into the ZEISS ELYRA 7,” says Weisshart.

The new microscope system allows you to work with much less laser light. If the phototoxicity, i.e. the destructive impact of light on the cell sample, is reduced, processes can be observed for a bit longer. This way, you can achieve high-res images with less damage to the sample. This works because a checkered pattern is used instead of a grid pattern. In the past you had to rotate the sample in order to show the frequency signal – thanks to Lattice SIM, this is no longer necessary. Suddenly, you see something you’ve never noticed before. This means you can observe the processes at different levels, which makes the microscope system incredibly fast.

ZEISS has been working on developing new microscope systems for many years together with Professor Eric Betzig, the US physicist and recipient of the Nobel Prize in Chemistry (see interview on p. 35). The idea to use Lattice SIM for structured illumination came from ZEISS. “Everyone involved was determined to get the system to market without delay,” says project manager Dr. Ingo Kleppe. Development was completed in record time: it took less than a year to go from the initial idea to the market launch. “It’s a tremendous help for us in the market when a key opinion leader acts as an ambassador for our brand”, says Weisshart.

Betzig holds several patents for superresolution, photo-activated localization microscopy (PALM). Scientists are now in a position to view processes in living cells and tissues down to the molecular level. His work has led to the development of the first commercially available super-resolution microscope based on PALM technology. In 2007, ZEISS obtained the exclusive rights to market PALM, and this served as the basis for the development of the ZEISS ELYRA microscope system in 2012. The Sales staff was impressed by the ZEISS ELYRA 7 from the get-go. Additional customer demos have already been held. The system continues to be very well-received.

RESOLVING MOLECULAR STRUCTURES SMLM (single molecule localization microscopy) enables individual proteins to be localized and mapped with great precision. Eightfold symmetry of the nuclear pore complex in A6 cells. Gp210 was labeled with Alexa Fluor 647. Widefield image, SMLM and magnified image section.