The UNC/NC State Joint Department of Biomedical Engineering shows how cross-disciplinary collaboration makes an impact during the Covid-19 crisis.
Usually when Devin Hubbard walks into the biomedical engineering lab at the University of North Carolina at Chapel Hill, he might turn on the 3D printers and get to work. But this time was different. As the coronavirus pandemic ramped up, Hubbard wasn’t there to use the printers. He was there to take three of them home with him. The chair of the biomedical engineering department had sent a message to Hubbard and other faculty saying they should be prepared to work remotely at home, and they could request permission to take their computers home for remote work. Thinking ahead, Hubbard also requested and received permission to use the 3D printers remotely. His foresight paid off. Just a couple of weeks later when University labs were closed, he was using those same printers to create a physical prototype of a device that may protect doctors and nurses as they care for COVID-19 patients.
“I went up there and grabbed everything we would need, and I now actually have three 3-D printers at my house that I borrowed from the BME department,” said Hubbard, a teaching assistant professor in the UNC/NC State Joint Department of Biomedical Engineering, who has been working to create a novel face mask device that could help address hospital shortages of N95 masks.
Hubbard’s 3D-printed mask design is one of several initiatives that faculty and students in the BME department are working on as part of the University’s COVID-19 response efforts. Another recent example is the emergency ventilator design team led by Yueh Lee, an associate professor of radiology at the UNC School of Medicine and adjunct assistant professor biomedical engineering. And while each of the research projects is different, they’re all products of the culture and break-through-the-barriers mindset that that biomedical engineering department breeds.
“Biomedical engineering is very diverse, but we don’t normally think about making face masks,” said Paul Dayton, interim chair of the biomedical engineering department and William R. Kenan Jr. Distinguished Professor. “That’s not something that our department has specific expertise in, but what our faculty and students do have expertise in is how to think about and approach technology needs in health care.”
When Carol Lewis, vice president of UNC Health Enterprises, connected with Dayton to see how the biomedical engineering department’s problem-solving prowess might help the UNC Health system address shortages in personal protective equipment (PPE), Dayton knew that faculty and students were well positioned to help. Lewis is leading a task force comprised of teams from UNC-Chapel Hill and NC State University focused on rapidly ramping up in-house manufacturing of PPE – everything from face masks and face shields to ventilator designs and hand sanitizer.
Dayton sees the interdisciplinary foundation of the biomedical engineering department – which is co-located at UNC-Chapel Hill and NC State – as a key to why it’s been heavily involved in working as a part of Lewis’ taskforce to find solutions to a wide variety of pandemic-response issues.
“Let’s face it, all the easy problems in science have been solved. The things that remain take groups of people with different expertise,” he said. “Being able to pull people together from different disciplines and campuses helps us to solve complex and impactful problems.”
Hubbard jumped in to help tackle one of the most significant problems that Lewis’ UNC Health task force faced: creating face masks for frontline medical caregivers. He and Dayton pulled together a core team of biomedical engineering students and colleagues from FastTraCS (where Hubbard is the lead design engineer and host of the GuideWire podcast) at the North Carolina Translational and Clinical Sciences (NC TraCS) Institute to get started. The team has been working on an innovation that may help convert standard surgical masks – which offer limited protection – into masks that do a better job of keeping coronavirus particles at bay.
An early 3D-printed respirator prototype developed by Ethan Smith, one of his biomedical engineering students, sparked an idea for Hubbard. After testing Smith’s initial prototype, Hubbard wondered: Rather than trying to 3D print a full respirator, what if the team took Smith’s original respirator design and cut it into a hard, but flexible plastic frame that could be placed around the fabric of an existing mask?
Hubbard already had fabric on hand from Behnam Pourdeyhimi, faculty director of the Nonwovens Cooperative Research Center at the Wilson College of Textiles at North Carolina State University. And because a team in the North Carolina Governor’s Office worked with UNC Health and Hubbard to find a company that rents N95 fit testing equipment, he had the right tools available at his house to put his question into action.
“I went crazy one weekend and took a bunch of material from Benham, stuffed it through the frame and wore it on my face. It passed the N95 fit test with no problem,” explained Hubbard. “I said, ‘Let’s back up a step. If we use this frame and put it over the existing masks that we’d been working on at UNC, will that pass the test, too? So I grabbed a version of that mask, put it on my face and put a frame over the top, and it also passed the fit test.”
Hubbard’s idea is simple, but powerful: Could adding this frame to existing – and much more plentiful – standard tie-on surgical masks fill a huge PPE gap that is bedeviling hospital and government leaders across the country who are searching for N95 masks? Could the team create a highly protective alternative?
“Our idea is that you wear a mask that you already have and just put this frame over top of it,” he said.
Hubbard worked with the U.S. Environmental Protection Agency to obtain preliminary testing data and filed a provisional patent on the 3D-printed frame, which he estimates can be manufactured at mass scale by industry partners at a low cost.
Concerned about a scarcity of PPE on multiple fronts, Hubbard worked with Lewis’ UNC Health taskforce on another project. The specific challenge? Convert adult surgical ear-loop masks into pediatric masks.
“For children, we didn’t want to go through an entirely new design process, because we wanted to use something that was already cleared by the FDA,” Hubbard explained.
So he teamed with biomedical engineering senior Emily Joyce and Nicole Wiley, a prototype and design engineer with FastTraCS, to explore an option using approved materials. “We worked on folding patterns and figured out that if you make a few simple folds to an adult mask, it turns into almost the exact same size as the pediatric mask.”
After Hubbard and Joyce tested several unsuccessful methods – including using surgical glue – for adhering the mask folds, Hubbard had an ah-ha moment.
“The first thing that popped into my mind is that we should use a heat sealer. I have one at my house that we use for food, so I tested it,” Hubbard said. “I did a heat seal on the edge of on an adult mask, and it worked way better than I expected.”
The upshot, Hubbard explains, is that by using a standard packaging heat sealer that costs about $100, you can convert an adult face mask into a pediatric mask in less than a minute. So, he and Dayton recruited graduate and undergraduate students to help them do exactly that. The student volunteers – who work in teams of four in the lab according to CDC guidelines – can crank out 300 to 600 masks over the course of a day.
After delivering a first set of masks to UNC Hospitals, Hubbard said the reaction was, ‘These are awesome. We need and want more.’”
Dayton cites the project as an example of faculty and students working smart to make a big impact fast. “It required a little bit of thinking about the best way to do this, and it was only about a week from conceptualization to turning it around,” he said.
Weighing on the minds of many is the longer-term issue of finding an effective COVID-19 vaccine. Biomedical engineering professor David Zaharoff is putting his expertise in cancer immunotherapy to work on this critical problem in a way that other vaccine scientists aren’t.
“It just so happens that some of the principles that we apply to amp up and direct the immune response against cancer are ones we think would be good to generate a vaccine against coronavirus,” said Zaharoff, whose lab at NC State University develops strategies to train the immune system to recognize and eliminate cancer.
Developing vaccines against previous coronaviruses has been a challenge, Zaharoff notes, pointing out that scientists have yet to find safe and effective vaccine candidates for SARS-CoV and MERS-CoV.
“There was something that struck me: If this is the third coronavirus outbreak, why don’t we have a vaccine against this? So that caused me to look at the literature.”
What Zaharoff found during his literature review is concerning: a history of vaccine candidates developed against respiratory viruses that, rather than protecting people who received the vaccine, actually exacerbated their response to the viruses. It’s a pattern he observed in previous preclinical studies, including those for coronaviruses SARS-CoV and MERS-Cov, along with the attempt to administer a vaccine for respiratory syncytial virus (RSV) in the 1960’s.
“It’s just a thread that you continue to pull, and you go back and read the papers from the 1960’s and 1970’s with other vaccine programs that didn’t pan out,” Zaharoff said. “It turns out that there are certain lower track respiratory viruses that share the same behavior: you try to vaccinate against it, and you make the disease worse.”
Zaharoff is working with doctoral students Siena Mantooth, Maura Vrabel and postdoctoral fellow Khue Nguyen to use the principles of cancer immunotherapy to develop a vaccine that avoids the pitfalls of previous respiratory vaccine candidates.
Because the coronavirus is a more challenging virus to combat than the seasonal influenza virus, Zaharoff explains, he believes that a COVID-19 vaccine needs to engage the body’s helper T cells to induce a different type of immune response than other vaccines currently in development.
“Our strategy is to make a vaccine that is going to give very high-affinity antibodies – meaning binding strongly to the virus – that will stick. I think the previous coronavirus and RSV vaccines did not do that,” Zaharoff said. “You need the antibody to stick on really tightly to the virus, and you need to also shift the immune response in a certain way to get a certain type of response. That’s the way I see a vaccine working.”
Next steps for Zaharoff’s team involve moving the vaccine into initial animal testing. And even beyond the immediate work on his lab’s vaccine or others, he hopes the broader lessons of this pandemic endure.
“When COVID-19 is over, I really hope we don’t forget about this,” he said. “The reason we got here was because we weren’t prepared. So if we don’t forget that, maybe in the future we can put more resources and thought about how we develop the next vaccine against the next pandemic.”
An enduring lesson experienced by professor Bill Polacheck and his biomedical engineering students during the COVID-19 pandemic is that labs aren’t the only academic avenues to activate during times of crisis. Courses and curricula play a role, too.
“It’s surprising that one of the most productive areas hasn’t been in our own lab, but serving in a more advisory capacity to undergraduate design and research groups that have been pretty creative,” said Polacheck, an assistant professor of biomedical engineering whose lab is based at UNC-Chapel Hill.
“The undergraduate class that I teach each spring is focused on mass transfer and fluid mechanics for biomedical engineers,” he said. “We talk a lot about flow, and how mass gets from one point to another, how it crosses the vasculature in the body and drug delivery. So there are a lot of questions that are popping up about coronavirus related to content in that class.”
Rather than having his students take an exam, Polacheck gave his students the chance to write a design paper that uses concepts in the class to address issues related to the coronavirus.
Polacheck said his students rose to the challenge. One group worked on new ways to change resistance in ventilators so that a single machine could serve two patients with different lung capacities. Another team sketched out a design for how to make a lung on a chip to understand how the virus moves from the vasculature into the alveoli, the tiny air sacs of the lungs. And several student groups looked at how particles move through porous structures to quantitatively design better masks.
“A lot of the students emailed me to say ‘Now I understand why we covered this in class. Because I can use it to understand how air moves through a mask or how a virus moves through a blood vessel,’” Polacheck said. “They feel like they are addressing a real-world problem, and they are starting to really understand the material taught in the class.”
Polacheck, who has research expertise in microfluidics and developing new microfluidic devices, also worked with a group of students on a senior design project from Hubbard’s BME capstone design course that involved developing a microfluidic diagnostic for COVID-19.
“What they’re trying to do is to develop a closed-form microfluidic chip – something that is less than the size of a business card – that would allow health care providers to put in samples from a nasal swap and, all in one, process the sample and give a readout on whether or not there is coronavirus present in the patient,” he said. “You can think about it a little bit like a pregnancy test – it’s a self-contained system.”
The goal of the device is to make COVID-19 testing, which could be performed at the point of sample collection rather than at central processing location, faster and more accurate. One of the students has plans to continue development on the diagnostic through the summer, Polacheck said. But regardless of where this diagnostic project lands, he wants the students to keep a longer-range message in mind.
“I’ve been impressed with – not only the ideas that students have – but also their true belief that they can make these things happen and make a difference,” he said. “And I hope that’s a lesson they take with them even beyond the coronavirus – that their classroom work and time on campus can be used to make a difference. That would be a really strong positive to come out of a bad situation.”