Kidney (Image by Lisa Rutledge and Seth Ruffins)

Kidney (Image by Lisa Rutledge and Seth Ruffins)

Previously, when Andy McMahon, W.M. Keck Provost Professor of Stem Cell Biology and Regenerative Medicine and Biological Sciences at the Keck School of Medicine, wanted a three-dimensional image of a kidney, he would ship the organ to Australia. Now, he can send the organ down the hall to the university’s new specialized microscope — built by a team of five undergraduates from the USC Viterbi School of Engineering as part of the course ENGR 499 Microscope Design and Construction.

Called an optical projection tomography (OPT) microscope, the instrument produces three-dimensional images of pea-sized biological samples, such as organs and embryos. This provides a valuable tool that enables biologists, such as McMahon, to study how organs develop, maintain and repair themselves.

“To acquire an OPT image, light is either projected through the specimen, or the specimen is illuminated for fluorescent imaging. Then a camera captures images at 1,000 different angles all the way around the specimen,” said Seth Ruffins, who taught the course and directs the Microscopy Core Facility at the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC. “And through a mathematical process, called a ‘back plane projection,’ you can then construct those images from all these different angles into a three-dimensional shape.”

With funding secured by McMahon and input from USC Viterbi Professor Andrea Armani and Provost Professor Scott E. Fraser, the undergraduates built and assembled the microscope hardware in their ENGR 499 course during Fall 2014, and continued to troubleshoot the software as volunteers during Spring 2015. Chao-Yuan (Joe) Yeh, a graduate student in the lab of Cheng Ming-Chuong at the Keck School of Medicine of USC, further refined the instrument control software.

The microscope began capturing its first state-of-the-art images, including three-dimensional renderings of kidneys and lungs, in June 2015.

“This is probably only the fourth or fifth microscope of this design built in the United States,” said Ruffins. “This particular design comes from a group up in Toronto, Mark Henkelman’s group. And they built it as an open source project.”

Even with the Henkelman designs in hand, the process of building the OPT microscope presented many unexpected challenges.

“It wasn’t a step-by-step blueprint at all, so we had to fill in the gaps and a lot of blanks there,” said Stephanie Fong, a biomedical engineering major with a digital studies minor. “So in a sense, this was more representative of the real world than a classroom situation. It was really just jumping in and getting hands on right away with very little prior knowledge. I’d say that it was definitely a great learning experience.”

Biomedical engineering major Dinesh Seemakurty added: “It shows you that, even with a plan, it’s still very difficult to make something happen. There are bugs, or there’s something that goes wrong. And no one actually has documented how you solve that, so you end up having to figure that part out.”

The students did everything from machining the parts to building the microscope’s computer, from assembling the components to programming the software.

“I have to say it’s a very different course,” said Beibo Zhao, a biomedical engineering major with a statistics minor. “You have to get your hands dirty to do stuff, to learn to make a computer. So that’s something very valuable.”

The hands-on nature of the course taught the students a great deal in a short time. “I learned a lot of concepts about optical tomography in general,” said Ahmed Abdelhalim, a biomedical engineering major with a physics minor. “I learned a lot about machining parts, especially. I learned how programs interact with devices in interesting ways.”

In the process, they discovered how to work as a team to solve a real-world problem on a tight deadline.

“We’re all biomedical engineers, but we all have different strengths,” said Kathleen Roche, a biomedical engineering major with a French minor. “I mean, some people are more comfortable with mechanical parts, like machining. And then I know a couple of us are really comfortable with software and the computer aspects. I’m in between, so it’s been good to learn and pick up some stuff. In most of our classes, we don’t really get the chance to build a machine, especially something as complicated as this from the ground up, so it’s been a really cool experience. We learned how to be innovative.”

Teaching assistant Sahar Elyahoodayan, a biomedical engineering PhD student in the Armani Lab, was impressed by the undergraduates’ success in building such a complicated, specialized and useful microscope.

“Overall, I’ve learned that the students are very brilliant,” she said. “They come from different backgrounds, and they’ve done a great job.”

In the coming months, Ruffins looks forward to exploring and expanding the potential of what the students built.

“As an open source project, we have a wonderful opportunity to experiment with improving OPT performance and usability,” he said. “I believe that this is a project that will provide us with useful and compelling imagery as well as continue providing interesting engineering opportunities.”

McMahon will continue cultivate opportunities for collaboration and interdisciplinary thinking through the university-wide USC Stem Cell initiative, which connects nearly 100 researchers from all disciplines.

“I look forward to continuing to work with students and colleagues at USC Viterbi and across the university,” he said. “The fact that this undergraduate course has produced a working OPT microscope, which will be tremendously useful to stem cell researchers including myself, underscores the synergy that results when we reach across disciplines.”

by Cristy Lytal