Even as COVID-19 vaccines are being rolled out across the country, the numerous challenges posed by the pandemic won’t all be solved immediately. Because herd immunity will take some time to reach and the vaccine has not yet been approved for some groups, such as children under 16 years of age, the coming months will see a continued need for tools to rapidly track the disease using real-time community monitoring.
A team of Penn researchers is working on a new “electronic nose” that could help track the spread of COVID-19. Led by physicist Charlie Johnson, the project, which was recently awarded a $2 million grant from the NIH, aims to develop rapid and scalable handheld devices that could spot people with COVID-19 based on the disease’s unique odor profile.
Long before “coronavirus” entered into the vernacular, Johnson was collaborating with Cynthia Otto, director of the Penn Vet Working Dog Center, and Monell Chemical Senses Center’s George Preti to diagnose diseases using odor. Diseases are known to alter a number of physical processes, including body odors, and the goal of the collaboration was to develop new ways to detect the volatile organic compounds (VOCs) that were unique to ovarian cancer.
Since 2012, the researchers have been developing new ways to diagnose early-stage ovarian cancer. Otto trained dogs to recognize blood plasma samples from patients with ovarian cancer using their acute sense of smell. Preti, who passed away last March, was looking for the specific VOCs that gave ovarian cancer a unique odor. Johnson developed a sensor array, an electronic version of the dog’s nose, made of carbon nanotubes interwoven with single-stranded DNA. This device binds to VOCs and can determine samples that came from patients with ovarian cancer.
Last spring, as the pandemic’s threat became increasingly apparent, Johnson and Otto shifted their efforts to see if they could train their disease-detecting devices and dogs to spot patients with COVID-19.
In the early days of the pandemic, Otto and colleagues at the Working Dog Center established a process for collecting samples from people who were being tested for COVID-19. After identifying people who have recently been tested, plain cotton T-shirts are sent out to study participants to wear overnight. After absorbing the person’s odor, T-shirts are shipped back to Penn, where Otto cuts them in half and places each half into glass Ball jars, with one going to Johnson’s lab and the other to the Working Dog Center.
Otto and her team at the Working Dog Center continue to move forward with their COVID-19 canine scent detection pilot training program. While the team has conducted some training with limited samples from hospitalized patients, with early results submitted for peer review, Otto is currently focused on collecting at least 1,000 T-shirt samples from nonhospitalized individuals (both positive and negative for SARS-CoV2) in order to have enough material to continue training without interruption.
“What we found early on in ovarian cancer is when we ran low and reused samples, the dogs actually started to home in on the individuals as opposed to the more generalized odor, and the same thing can happen for COVID,” Otto explains. “We know that dogs can identify patients with COVID-19 and that they can generalize, but if we train with limited samples, they start to respond only to the individual samples.”
If the research program is successful in validating the sensitivity and specificity of the dogs’ performance in the laboratory and in an operational setting, the dogs could help screen people in public spaces like airports, train stations, or other places where a sniffer device may not be as easy to deploy.
In the Johnson lab, pieces of the T-shirts are placed onto the sensor array and a gas line is used to “push” the aroma out. If a specific VOC signature linked to a disease state is detected, the sensor array generates a pattern of electrical currents that are analyzed by a computer using machine learning algorithms. Results come back in two to five minutes and the system doesn’t require any reagents.
“At this early stage, we actually are using the same identical array for ovarian cancer for this task, and it looks like this system can detect odor differences from disease,” Johnson explains. “We’ve measured 30 of those T-shirt samples and our ability to discriminate is 92% sensitive and 87% specific.” In other words, the device can consistently detect the unique VOC signature of a person with COVID-19 and can also determine if someone is negative for the virus.
“This is our version of Warp Speed,” Johnson says about the newly funded project. “The goal is to have a handheld instrument—not measuring T-shirts, but trying to measure people. It’s a big leap, but we think we can do it.”
To achieve the lofty goal of developing a fast, portable COVID-sniffing device, Johnson is collaborating with a group of researchers from Penn and other institutions. This includes Otto, who will be involved in additional sample collection, emergency care doctor Benjamin Abella who will coordinate patient outreach in the Penn Medicine ER and at community clinics in West Philadelphia, dermatologist Carrie Lynn Kovarik for gaining a better understanding how VOCs emanate from skin, and computer scientist Lyle Ungar for optimizing machine learning algorithms for data analysis. The Penn Libraries' Biomedical Library provided 3D printing services.
We’re hoping to scale this up rapidly, and we think the technology could be useful not just against COVID-19 but also against future pandemic illnesses. Penn Medicine emergency care doctor Benjamin Abella
Then, to help translate their lab-based system into a commercial portable device, the researchers will work with VOC Health on developing designs for a handheld instrument that could be produced at scale. “Richard Postrel and I founded VOC Health to adeptly join and commercialize our technologies,” says Johnson. “Richard’s innovative thinking allows us to skillfully harness and capitalize on the work done by Penn’s talented researchers.” The team will also be collaborating with Kenneth G. Furton from Florida International University, who will be conducting chemical analyses on T-shirt samples to determine what VOCs are responsible for COVID-19’s odor profile. With more insights as to what exactly these compounds are, the researchers can refine the device and make it more specific to COVID-19.
The goal is to develop a prototype device for testing on patients in the next year and be ready to apply for Food and Drug Administration clearance in two years. “We’re hoping to scale this up rapidly, and we think the technology could be useful not just against COVID-19 but also against future pandemic illnesses,” says Abella. And because their approach can be adopted for other disease states, this work could someday enable new approaches for tracking diseases caused by new pathogens or enabling more sensitive ways to screen for cancers.
Despite the challenges ahead, Johnson is excited and eager to get involved in ongoing efforts to combat COVID-19. “It’s really opening eyes to the idea that the system we have could be applied to large number of different disease states, and it’s a great opportunity to do something that’s also of tremendous importance and urgent need,” he says. “We’re feeling the pressure, but we’re having fun.”
Benjamin Abella is a professor in the Department of Emergency Medicine in the Perelman School of Medicine at the University of Pennsylvania.
Charlie Johnson is the Rebecca W. Bushnell Professor of Physics and Astronomy in the Department of Physics and Astronomy in Penn’s School of Arts & Sciences.
Carrie Lynn Kovarik is a professor in the Department of Dermatology in Penn’s Perelman School of Medicine.
Cynthia Otto is a professor of Working Dog Sciences & Sports Medicine in Penn’s School of Veterinary Medicine and Director of the Penn Vet Working Dog Center.
Lyle Ungar is a professor in the Department of Computer and Information Science in Penn’s School of Engineering and Applied Science. Ungar also holds an appointment in the Department of Psychology in Penn’s School of Arts & Sciences.
In April 2020, Johnson, Otto, and Preti’s collaboration was highlighted by Science Friday.
Homepage image: Charlie Johnson’s physics lab uses atomically-thin sheets of graphene on electronic chips (pictured) to detect different disease states. A team of Penn researchers led by Johnson is now developing this technology further to create rapid and scalable handheld devices that could spot people with COVID-19.