MSOE students try to develop synthetic blood substitute in ambitious project

For the past four years, successive teams of seniors at the Milwaukee School of Engineering have worked on a research project not short on ambition: developing a synthetic blood substitute that can transport oxygen in the body. The project understandably may seem quixotic — or, at the least, maybe a little too ambitious. At least one multibillion-dollar corporation and several well-funded startups have failed in similar pursuits. And the MSOE students are, after all, undergraduates, not post-docs with PhDs working at a large research university. But each MSOE team — in some years, there have been more than one — working with Wujie Zhang, an assistant professor of biomolecular engineering, for their required senior project has overcome the next challenge of the ultimate quest. The students also have learned the value of patience and persistence in research.

“That is not to say it didn’t come without a fight,” said Kellen O’Connell, one of the five students on this year’s team. “I definitely had my doubts along the way.” The research project was the outgrowth of a serendipitous discovery by Zhang and Jung Lee, also an assistant professor at the school, while working on a way to encapsulate a drug for colon cancer in natural polymers derived from crab shells and orange peels.

They discovered that the substance took the biconcave shape — having a surface that curves inward on the top and bottom — of red blood cells.  Zhang was intrigued by the prospect that the substance could be used to create a carrier or capsule for hemoglobin, the protein in red blood cells that carries oxygen and carbon dioxide through the body. Developing a red blood substitute that could be used in war zones, remote areas and accident sites has long been a scientific goal. It theoretically could be freeze-dried and would not have to match a blood type. Researchers at Washington University in St. Louis also have developed a polymer to encase hemoglobin. And several small companies are working on similar approaches.

The research project at MSOE has received some small grants, including a $50,000 grant from the National Science Foundation Innovation Corps program. And the school has filed for a patent on the process for making the capsules. The project faces long odds. But Zhang and his students have cleared the first few hurdles. The first research projects focused on getting the right size for the capsules that would enclose the hemoglobin or another substance that could transport oxygen. The capsules must be seven to 10 microns. (A micron is one-millionth of a meter.) This year’s team was given the challenge of perfecting that process by sorting out capsules that were too big or too small. The work wasn’t without frustrations.

“We tried to remain optimistic,” said Sydney Stephens, a biomolecular engineering major who was the project manager. “It was a little challenging at first.” The capsules are made using what is known as an electrospray device in which a polymer solution is electrically charged and sprayed into a petri dish, where it interacts with another polymer. “At first, we were stumped on why we weren’t getting the results we wanted to see,” O’Connell said. The students did some research on electrospray devices to get a better understanding of how they could change the size of the capsules by varying voltage, flow rate, height and other parameters.

They also drew on Design-Expert, statistical software used in designing experiments, and sought out the advice of a statistics professor, who helped them interpret the data and suggested ways they could improve their experiments. “The whole process was a really good learning experience,” said O’Connell, who is from Ashwaubenon. They learned more about the design of experiments and became more comfortable with problem-solving in the lab. They also got to apply some of what they learned in classes such as statistics and chemistry.

In addition, they also learned that working as a team was essential, said Stephens, who is from the St. Louis area and who also played soccer at MSOE. The team worked six to 20 hours per week, including some Saturdays. They also felt an obligation of sorts to the previous teams. “This project would not have gotten as far were it not for other teams,” Stephens said. Next year’s team will work on improving the capsules’ stability and testing whether capsules can carry oxygen.

The short-term goal is to develop a working prototype. If Zhang and MSOE reached that point, they then would need to collaborate with a medical school. However, even if the MSOE research project isn’t successful, many of Zhang’s students have been co-authors of published research papers — an impressive credential for an undergraduate. So far, five papers have been published from the project, Zhang said. Several of his students also have gone on to attend medical school at universities such as California Institute of Technology; University of California, Davis; Emory University; and University of Wisconsin-Madison. Zhang has been realistic with his students about the chances of the project resulting in a successful product, O’Connell said

But the long odds, too, are part of research. “You have to try,” O’Connell said, “if you want to make progress.”

Read the original article from the Journal Sentinel.