Wearable sensors may one day detect impending seizures and give a warning roughly 20 minutes before an attack happens. Researchers at Know Biological in Milton, Georgia, and Sandia National Laboratories have developed a sensor that can reproduce the seizure-sniffing abilities of trained dogs that they hope will one day be wearable like a wristwatch.
In the United States alone, there are nearly 4 million people with epilepsy—“roughly 1 in every 100 people,” says Gary Arnold, founder and CEO of Know Biological. The World Health Organization estimates that around 50 million people have the disease worldwide.
Advance warning can give people with epilepsy time to take medication that can halt more seizures, or at least get somewhere safe and private. “The uncertainty of uncontrolled seizures can take an enormous toll physically, mentally, and emotionally,” Arnold says.
Seizure-alert dogs can warn a person with epilepsy of an impending seizure an hour or more before it happens. However, “there are so many people in need and so few dogs,” Arnold says. This led Arnold and his team to try and replicate this canine ability with technology.
In 2016, researchers at Florida International University, in Miami, and Atlanta-based service-dog school Canine Assistants found that 11 patients with epilepsy released molecules known as volatile organic chemicals (VOCs) during seizures. VOCs are organic compounds that are abundant in the air at room temperature, and are responsible for odors like the smell of fresh-cut grass or drying nail polish. Arnold says that the changes in a person’s body odor are likely what seizure-alert dogs sniff out.
In a 2021 study published in Epilepsy & Behavior, researchers
focused on three VOCs that the 2017 research had detected from all the epilepsy patients immediately after seizures. After observing 60 patients in the epilepsy monitoring unit at Denver Health Medical Center, the researchers found dogs trained to recognize this trio of VOCs succeeded at predicting seizures 82.2 percent of the time, with an average alert time of more than 68 minutes. “These results gave us great confidence that we were indeed looking for the correct biomarkers,” Arnold says.
A researcher works on a miniaturized sensor system able to detect specific gases warning of an impending seizure.Craig Fritz
Arnold then reached out to Sandia National Laboratories after hearing about work developing a handheld chemical detector for the military. Sandia and Know Biological have now developed a prototype to detect these seizure-linked molecules. So far, they have received four joint patents based on this research and have two other patent applications under review.
The prototype detects the seizure-linked VOCs in a process that has several steps. First, a silicon-based device called a preconcentrator, slightly smaller than the inner loop of a mini–paper clip, acts like a sponge. The preconcentrator currently collects VOCs from gauze swiped on a patient’s skin, although the researchers want to eventually cut out the intermediate gauze step. The device can hold onto VOCs while letting much smaller atmospheric gases such as oxygen and nitrogen flow through freely. After collecting the VOCs, the preconcentrator then gets rapidly heated for less than a second, which releases the VOCs and conveys them to the next stage of the sensor.
When released, the VOCs enter tiny serpentine channels etched into a square of silicon 3 centimeters on a side. These channels separate the gases based on their chemical properties.
Finally, a miniature ion mobility spectrometer analyzes gases exiting the channels. The device is sensitive enough to detect even tiny amounts of gases such as those released by epilepsy patients during seizures.
In experiments, gauze swiped on the skin of patients at Denver Health Medical Center’s epilepsy monitoring unit were sent to Sandia for analysis using the new sensor. “Our monitor detected the target VOCs from a sample that was taken 22 minutes before a seizure occurred in a patient,” Arnold says.
These results “proved that a wearable chemical-based sensor for presymptomatic detection of seizures is possible,” says Philip Miller, a biomedical engineer at Sandia National Laboratories in Albuquerque. “People without hope for epilepsy management are really excited by the work. I’ve been surprised by the number of people who have reached out and want to help.”
The scientists are working on upgrading the preconcentrator to “sniff” directly from a person’s skin, instead of from a strip of gauze, which would allow them to one day create a version of the sensor that could be continuously worn on a person’s body. “We have an existing wearable prototype that we’ve shown can collect and transfer volatiles to the VOC sensor system,” Miller says. “The device looks and feels to the user like a watch.”
In preliminary experiments, the sensor takes 5 minutes to analyze a sample from start to finish. However, this research “focused solely on correct identification of the biomarkers, and prior work by our team has shown rapid analysis is feasible but added potential complexity at this initial clinical testing stage,” Miller says. “Analysis of the known volatile biomarkers can happen in less than 30 seconds, and that performance is nearly ready.”
Currently, the entire sensor is about the size of a hardcover novel, Miller says. “We’d like to get it to half that size, and believe that is possible in the next one to two years,” he notes. “Reaching that size would increase the deployment opportunities for wearable comfort to the end user.”
Arnold expects to enroll patients in beta testing of the device soon, with the hope of bringing the sensor to market by the end of 2024. Ultimately, the researchers would like to get the entire system “to a wrist-wearable size,” he says.
More research is needed beyond producing the device, Arnold cautions. “Determining exactly what to do when alerted to oncoming seizures will be the responsibility of users, their caregivers, and doctors,” he says. “We know the data collected by the device will help, but there will still be some trial and error involved in determining best practices for rescue protocols.”
Arnold notes they plan to continue their research to look for specific VOC fingerprints associated with other chronic health conditions. “Advanced knowledge is always a good thing for people who have chronic health concerns,” he says.
This story was updated on 7 July 2023 to correct the year in which Florida International University and Canine Assistants collaborated on VOC research.
