Holonayk Lab professor receives patent for new form of biosensor microscopy

4/7/2020 3:09:58 PM Allie Arp, CSL

Seven years ago, when Holonyak Micro & Nanotechnology Lab Professor Brian Cunningham was researching how cell membranes react to different stimuli, he wanted to be able to observe the behavior of live cell membranes through a microscope. However, current technology didn’t allow it, so he wrote down exactly what he needed from a biosensor surface and got to work. 

Brian Cunningham
Brian Cunningham

“We wanted to see, in great detail, things that happen on the cell membrane and what sorts of interesting features allow it to interact with its environment,” said Cunningham, the Donald Biggar Willett Professor in Engineering. “To do this, we needed to be able to look at cells under a microscope while they’re alive. In order to see interactions, you usually have to kill cells with a stain or add fluorescent molecules that only remain visible for a short time.”

This research need led Cunningham and his team to develop a new form of microscopy called photonic resonator outcoupler microscopy, or PROM. In a PROM microscope, the glass microscope slide that is usually used as the surface for supporting cells is replaced with a nanostructured device called a “photonic crystal” which concentrates illumination into the cell membrane and makes an image of places in the cell membrane that scatter light the most.

Cunningham explained that existing methods are not effective when it comes to seeing how cells latch onto surfaces, grow to heal a wound, or respond to different drugs. While stains make the cells easier to see, they destroy the ability to see how live cells dynamically react and change. A drawback of fluorescent dyes is that they often fade after a few minutes, which does not allow observation of processes that take several days, such as cells growing and dividing or stem cells differentiating into other types of cells.

“We showed for the first time how you could take a very detailed and label-free image of the cell membrane to visualize cell membrane changes over long periods of time,” said Cunningham, an electrical and computer engineering professor. “Instead of an ordinary glass slide, we attach cells to a nanostructured biosensor surface that enables us to visualize locations on the cell membrane that scatter light slightly more than surrounding areas.  Any places where protein materials concentrate themselves, like focal adhesions, stand out very clearly when observed by PROM.”

This new method of viewing cells was so novel that in 2017 the group applied for patent. After a 3-year review process, they were recently awarded with Patent 10,605,735 Photonic resonator outcoupler microscopy (PROM).

“The patent serves to acknowledge that PROM is a novel form of microscopy that is enabled by nanostructured biosensor surfaces that allows us to look at live cell membranes, using their light-scattering properties to provide image contrast,” said Cunningham. “We hope that the patent will attract companies to consider licensing the approach and offer a new tool to the arsenal of microscopies available to biologists.”

Co-inventors on the patent include Brendan Harley, of professor of chemical and biomolecular engineering, Cunningham’s former doctoral student Yue Zhuo, Harley’s former postdoc Sunny Choi, and Thibeau Marin.