Fighting for faster virus detection
An electronic nose developed by Notre Dame researchers is helping sniff out bird flu biomarkers for faster detection and fewer sick birds.
Notre Dame researchers have developed an “electronic nose” that can sniff out bird flu before it spreads—helping farmers protect their flocks and livelihoods.
Brothers Thomas and Jordan Hertzfeld are fourth-generation egg farmers. Their great-grandfather started a humble enterprise in 1938 in Grand Rapids, Ohio. Today, Hertzfeld Poultry Farms raises more than one million hens on its sprawling farm, and another 300,000 at satellite farms. The operation processes about 120,000 eggs each day. And it employs 75 people—family and neighbors alike—in rural Ohio. So when avian flu began infecting, and decimating, egg and turkey flocks, worry seized the Hertzfelds.
“On a day-to-day basis, we're facing things that I don't think we ever imagined that we would have to face with bird flu. The entire operation that we have has been flipped on its head as we determine how we can keep the birds safe, as well as how we can continue to produce for the consumers that are out there and continue to strive to have a livelihood for generations to come,” Thomas Hertzfeld said.
Stopping the spread of avian flu
Highly pathogenic avian influenza, commonly known as bird flu, is a virus spread among birds and livestock. The virus infects chickens, hens, ducks, geese, water birds, pigeons, sparrows, cows, and, on occasion, humans. It can be spread through direct contact with a sick animal; contact with animal byproducts like saliva, mucus, or feces; or, perhaps most nerve-racking, through airborne transmission.
Bird-to-person transmission is rare, and typically only results from close, unprotected exposure to an infected bird—but for egg producers like the Hertzfelds, that is a fear. What's more, given how contagious the disease is, if one bird is infected, the entire flock needs to be depopulated.
To protect the safety of their flock and employees, the Hertzfelds sprang to action with enhanced biosecurity measures. They built a large truck wash, scrubbing down each vehicle that comes onto the property.
They blacktopped the long driveway leading to their buildings to smooth out the surface and reduce the number of puddles, which could be contaminated by wild birds.
Their employee breakroom, once a detached building, got a skywalk addition to eliminate the need for people to go outside during the day and risk accidentally bringing the virus into a barn.
“The hardest part with these investments is you don't really know if they work,” Thomas Hertzfeld said. “The only way you know if they work is if you don't get bird flu.”
The Hertzfelds also needed to start regularly monitoring and testing their birds for infection.
Dr. Rebecca Wilkes, a veterinary microbiologist and director of the Veterinary Diagnostic Lab at the University of Kentucky, which runs tests for avian influenza, explained that testing birds can be easier said than done.
“Samples are collected based on the type of farm. For the most part, though, an oropharyngeal [middle part of the throat] swab has to be collected from these birds. So it takes a lot of effort and multiple birds per farm have to be tested,” she said.
“Once the samples get to the laboratory, we have to extract nucleic acid from the sample. So that takes time. Then we have to use a different machine that will detect the virus in the sample. So it's not a quick, within-a-few-minutes process,” she said. “All of this—the testing that happens, the sample collection that has to happen on the farm, then the sample has to be submitted to the laboratory, then the laboratory has to receive that sample in and do all of the testing—it delays detection.”
Should a test come back positive, Wilkes explained, not only is the immediate flock at risk, but so are flocks within a 10-kilometer (6.2-mile) radius. Surrounding farms must also start taking swabs.
“It can be a lot of samples because there are tons of farms within a small area. Not only that, each of those farms has multiple bird houses, and so birds from each of those houses also have to be tested. So you can see there's an exponential growth of samples that have to be collected and sent to the laboratory for testing,” Wilkes said, noting that labs can quickly get overinundated. “Any time we can move detection directly to the farm, it's going to speed up the detection.”
Sniffing out the virus
Nosang Myung, the Bernard Keating-Crawford Professor of Engineering and an expert in nanoengineering materials and sensor technology, has long dreamed of an electronic nose.
Five percent of the population has a very limited sense of smell, he notes, and he wanted a way to help them feel safer—to create a device that could help them smell gas leaks or small fires. Then, during the COVID pandemic, he realized the application could extend to disease.
“The technology that we have developed at Notre Dame is similar to a sniffing dog,” Myung said. “Humans can detect certain things in the air. Dogs have way more receptors to be able to only identify odor, and this technology can identify and quantify odors. We know dogs can sense drugs and ammo and illnesses, so that's what we're training this technology to do.”
Avian flu was not the initial goal for this technology. But when Myung began reading about the dangers this virus could possess for farmers and consumers alike, he began to steer the first application this way. It made for a compelling trial market.
Real-time disease detection
Myung, the faculty director of the Sensor Initiative, is the brains behind how to make the sniffing sensors work, but he recognized he needed complementary skills for other aspects of this product. He needed help with manufacturing, with industry partners, and with designing a device people could, and would, actually use. He created a team with experts from Colorado State University; Monell Chemical Senses Center; Purdue University; University of California, Riverside; and, from Notre Dame, James Rudolph, the Paul Down Assistant Professor of Industrial Design and a practicing designer known for his work in designing solutions for complex health care challenges. He has worked on everything from robotics to drug delivery devices to wearable monitors.
“Technologists develop the technology to be able to measure, look at things, to do things that humans can't do. As a designer, my role is to make that technology accessible, usable, safe, and a good experience for users,” Rudolph explained.
Together, they interviewed nearly 100 potential users to see what they would want and need in a sensor. They learned how time-consuming the standard swabs were. They learned about how feathers could clog a sensor. They learned the device would need changeable filters. And they learned that the interface needed to be simple and user-friendly for busy farmers so they don't need to bring in technicians. The result is two small, straightforward prototypes, Rudolph said. One is for larger farms and can be mounted in a barn, almost like a smoke detector, to provide continuous monitoring. The other is a handheld device for smaller farms or backyard enthusiasts. Neither format requires swabs; they instead continually sniff the air for scents of sickness.
“The initial idea that we had, it was not the same as where we ended up,” Myung acknowledged. “Having user interface and understanding the behavior and how important it is to have real-time monitoring was one of the most important things.”
Developed with support from the National Science Foundation, Myung's sensor will be adapted and updated for a number of diseases or applications.
He also joked that as an engineer he wanted to overcomplicate the design and add bells and whistles, but after listening to farmers, he learned that in this case, simple is better.
“We found out how people don't want more people to get into the farm because that can be a source of transmission from one flock to the other barn,” Myung said. “Understanding their desire and having that input from the user allowed us to reengineer.”
The end product, Myung attested, allows farmers to move from reactive mode after receiving bad news from the lab, to proactive mode, where they can test in real time and quickly isolate a sick bird before it has a chance to infect others.
“The beauty of this technology is that samples don't have to be collected from each individual bird. Also, the testing or the detection of the virus occurs on the farm. Samples don't have to be submitted to the laboratory, and the instrumentation, or the technology, is sensitive enough that it can detect the virus before we even have signs of illness in the birds. So all of this adds up to more rapid detection, which is key in an outbreak situation. The faster we detect this virus, the easier it can be controlled, and hopefully we can stop the spread,” Myung said.
The future of an electronic nose
The result has a whiff of the COVID-19 pandemic—how might testing and isolation have shifted with such a technology? Myung is hopeful that avian flu is only one application of a platform technology that can be versatile and used for any number of diseases, in any number of hosts, including humans.
“If and when new diseases crop up, a software update can add it to the sensor's detection capabilities,” he said confidently.
Myung has considered the far-reaching future of this application. He can see it detecting and tracing the movement of airborne viruses such as COVID. He can see it sniffing out insulin leaks for diabetics wearing insulin pumps. He can see it looping back to his initial hope of providing smell for those with limited capabilities.
“I like to do translational science. I want people to use it. I don't want this sitting in my lab,” he said, noting that Notre Dame is the perfect place for researchers like him who want to be impact-focused in their work. “Notre Dame is a mission-driven university. We want to be a force of good. It's not driven by the fact that I want to design new technology; it's that we want to be at the forefront of detecting a disease.”
Rudolph echoed his sentiment: “If you can't translate the research into something that's useful and impactful and could be used safely, like medical devices ... then you're not going to generate the impact, the positive change.”
Back on the farm, the Hertzfelds, both longtime Notre Dame fans, believe this technology will stem the tide of avian flu.
“When the University of Notre Dame steps in and helps with research of bird flu, it's important because of the resources that they have behind them and the minds that they have behind them, ” Thomas Hertzfeld said.
He hopes this work helps keep his flock healthy. He hopes it keeps his family's farm stable for the future. And he hopes that he can go back to focusing solely on providing a great product for his customers so his children will want to join him as the fifth generation at Hertzfeld Poultry Farms.