A new, advanced, light-based microscope invented at UT Austin offers a glimpse deep inside living cells

microscope illustrationPacked inside every cell is an exciting scene — there’s the nucleus, DNA, RNA, rocketing vesicles, walking vesicles, proteins, mitochondria and other biological structures bustling with activity. But because of their diminutive size and constant motion, it remains difficult even for the most advanced microscopes to deliver an image of these structures.

Enter Cockrell School professor Thomas Milner and College of Natural Sciences professor Martin Poenie who have developed a microscope to help scientists and engineers navigate this tiny, moving cellular landscape.

After years of development, they will soon be introducing a new light-based microscope that they believe offers an improved platform for viewing cells, viruses and other biological structures. A microscope with the ability to reveal more about how cells and viruses work can open up new avenues for scientific discoveries, disease diagnostics and drug discovery.

With an eye on commercializing the tool, which they call the SpectraPol microscope, Milner and Poenie have teamed up on a startup called Intelligent Light Sciences. This year, the startup received a $48,200 Innovation Grant from the Cockrell School’s Innovation Center. In the near future, the first SpectraPol microscope will be accessible through one of UT Austin’s microscope service centers where scientists and engineers from the university and around the world can use the tool.

The microscope is being fine-tuned, but the researchers have already been able to see viruses emerging from living cells—which has not been possible before. And they are attempting to image the cytoskeletal structures inside T-lymphocyte cells to gain a better understanding of how the immune system kills cancer cells. Other researchers have been able to image T-cells responding to tumor cells but have not yet been able to see inside a T-cell to glean more information about what is happening.

The UT Austin microscope can produce images that show structures as small as 25 nanometers (about 3,000 times smaller than the diameter of a human hair) for sustained periods of time, and what’s perhaps most groundbreaking is that the microscope can do this without the need for fluorescent dyes or other contrast agents.

A major shortcoming of other advanced microscopes is that they rely on fluorescent dyes for contrast, and these fluorescent molecules typically offer only seconds of continuous imaging at a high resolution. The UT Austin microscope, however, offers continuous imaging of a cell for hours without the need for contrast agents. In addition, the polarized light generates sharper images than those that use fluorescent dyes.

“With our new microscope, you can really see structures that you can’t normally see with current microscopes,” Poenie said. “For example, you can see individual microtubules that are 20 to 25 nanometers in diameter, and you are seeing these objects without stains or contrast agents going onto the specimen.”

Their new light-based microscope relies on spectroscopy, the use of different colors or wavelengths of light to extract information about an object and create an image. Specifically, the microscope takes advantage of polarized light, a type of light wave, to generate contrast with a biological sample.

Milner and Poenie are still working to collect data on their microscope’s capabilities, but they believe their microscope could be better than existing technologies at producing images of specific biological structures, such as viruses. To date, scientists have struggled to successfully use fluorescent dyes to tag a virus that can be consistently utilized in the diagnosis of an infection.

Ultimately, Milner and Poenie hope to develop algorithms to display their images in real time, which would allow scientists and engineers to leverage even greater information about an object than is now possible.

“It’s just amazing what you can see,” Milner said. “You can see vesicles light up, presumably because of the collagen inside them. You see all sorts of things in and around the nucleus where things have never been observed.”

Texas Engineer Monogram