In 2016, the Nobel Prize in Chemistry was awarded to a team who developed a high-resolution technique to view the inside of cells. But their technique works best on cells in petri dishes, Scott Howard, professor of electrical engineering, said, and the challenge of looking inside the cells of a living organism remained.
Over the next few years, Howard and his team searched for a convenient – and cheap – method to get a high-resolution view of the chemical processes that happen inside of cells.
“All good science kind of starts with some need or challenge that you're thinking about,” Howard said. “And so we started with kind of the fundamental science and physics and derivations and theory and developed, this little missing picture about how it is supposed to work if we were to use these techniques.”
Howard started by looking at ways to create 3-D super resolution images using normal microscopes people have in their labs, he said. Then he started applying physics, he said.
“We kept looking at how you can use this simple approach, one that anyone can use with just a microscope,” Howard said. “And if you tweak it a little bit, you can actually extract out some really quantitative chemical information in addition to just the pictures.”
They ended up developing a technique called DeSOS, which is a combination of two techniques called blind deconvolution and stepwise optical saturation.
DeSOS can produce high-resolution images of cellular processes inside the cells of living organisms – not just cells in petri dishes. It can even be used to create videos of those processes, also called 4-D images.
“We found that there was a whole direction of experiments and things that people really haven't been exploring yet,” he said. “And the consequences of these ideas were that you can get really high-resolution images, without requiring a lot of expensive components other people were using – and it was compatible with a lot of existing microscopes.”
Before DeSOS, most people were using a technique called fluorescent lifetime imaging microscopy (FLIM), graduate student Xiaotong Yuan said.
But FLIM cannot effectively capture images of cells inside a living organism. DeSOS, on the other hand, can, so it has the potential to greatly impact biology research, Yuan said.
Since developing this technique, Howard has collaborated with the Harper Cancer Research Institute and the Indiana University Medical School to use DeSOS in various research projects, including biochemistry and kidney research.
“A nice technology isn’t as important or impactful if you don’t had collaborators,” she said.
Yuan said she was drawn to Howard’s research because of its potential to help disease research, which she is considering pursuing once she graduates.
“For example, I just read yesterday that zebrafish have an extremely unique heart regeneration ability. If we can capture 3-D and 4-D images of that, it could be a great way to figure out how to treat cardiovascular disease in humans,” she said.
People have never been able to make 4-D images quite like the ones DeSOS can produce, Howard said. He gave credit to his team, especially Yide Zhang, currently a postdoc fellow at California Institute of Technology.
“We’re combining all of this understanding of devices and light, what goes on in the nanoscale and the quantum world to these medically relevant questions,” Howard said. “We can do a lot of things people haven’t done.”
