Once the diffraction limit in microscopy was discovered by Carl Zeiss and Ernst Abbe in the late 19th century, the basic function of the microscope didn’t change for the next 100 years, said Eric Betzig, the 2014 co-winner of the Nobel Prize in physics. But thanks to the development of technologies such as brightfield microscopy and the use of fluorescent tags, the microscope was able to play a role in some of the most significant advances in molecular biology in the last 30 years, he said. BiOS Plenary: Eric Betzig, 2014 winner of the Nobel Prize for physics, delivered the BiOS Sunday Plenary to close out the weekend at Photonics West 2020. Courtesy of École Polytechnique Université Paris-Saclay. Betzig, a professor of molecular and cell biology at the University of California, Berkeley, who left Bell Labs in 1996, developed photo-activated localization microscopy (PALM) with Harald Haas and has since moved on to work with such techniques such as correlation microscopy and high-pressure freezing microscopy, where a specimen is kept in a natural state. Betzig gave the Sunday Plenary talk titled, “Spying on the Secret Lives of Cells” to close out the BiOS exhibition during Photonics West 2020 in San Francisco on Sunday, Feb. 2. “Every type of microscopy has its advantages and limitations, because there are always trade-offs with spatial resolution, photo toxicity, imaging depth, and temporal resolution,” he said. “Fluorescent microscopy can light up proteins within a cell, and you get a great picture, but there’s no real context of what’s around it. On the other hand, with traditional electron microscopy, you can get a great image of the whole cell, but there’s little differentiation.” For that reason, Betzig said he and other researchers have turned to light-sheet microscopy, which allows an image to be generated across the focal plane using a Bessel beam. The specific method he uses is called lattice light sheet microscopy, where successive planes of an image are captured. “We have shared this methodology with other groups, and I will see them walk away with smiles on their faces because they discovered something new and now have 10 terabytes of data,” he said. “Then, days later they will call me crying because they have 10 terabytes of data they don’t know what to do with. We will ultimately need advances in computational technology to figure out what to do with the vast amount of data that’s being produced.” The future of science, he said, will be the convergence of different microscopic techniques and adaptive optics into one piece of equipment. That prospect is challenging enough for developers, as is the requirement that it be produced in a cost-effective manner. “A big challenge we are facing is how to making existing microscope technology accessible and put it in the hands of people who will be able to make a difference,” Betzig said.