First-of-its-kind sensor enables real-time monitoring of protein fluctuations in the body. In an animal study, the device successfully tracked inflammation biomarkers and could also monitor protein indicators for other conditions, including heart failure.
Scientists at Northwestern University have developed an innovative implantable device capable of continuously monitoring protein levels in the body.
Drawing inspiration from the way fruit falls from trees, the device utilizes DNA strands that attach to proteins, release them, and then capture new ones. This inventive approach allows the device to track various proteins over time, helping to measure changes in inflammation markers.
In initial experiments, the sensors effectively measured protein biomarkers related to inflammation in diabetic rats. This research paves the way for real-time management and prevention of both acute and chronic health issues by monitoring important proteins, including cytokines associated with inflammation and protein markers linked to heart failure, among others.
The findings will be published on Friday (Dec. 6) in the journal Science.
“The design of this device is similar to a continuous glucose monitor that resides on your arm and tracks levels just beneath the skin,” explained Shana O. Kelley, the lead researcher at Northwestern. “You can observe real-time glucose level changes; if you take insulin, you can see the levels drop. It’s crucial to identify both positive and negative trends. The same goes for protein levels relating to inflammation. Monitoring these fluctuations provides a comprehensive understanding of bodily changes. This technology represents a groundbreaking capability to observe inflammation live. We are only beginning to explore its vast potential applications.”
Kelley holds titles as the Neena B. Schwartz Professor of Chemistry and Biomedical Engineering at Northwestern and is affiliated with the Weinberg College of Arts and Sciences, McCormick School of Engineering, and Feinberg School of Medicine. Additionally, she presides over the Chan Zuckerberg Biohub Chicago, part of a larger network of education and research institutions.
Inspired by nature
While many sensors are available for continuously monitoring small molecules, proteins present a tougher challenge due to their size and complexity. Traditionally, scientists use DNA receptors designed to bind with proteins and extract them from biological fluids.
However, these receptor mechanisms often hold onto proteins for extended periods—more than 20 hours—making real-time monitoring impractical. After attempting multiple methods to “reset” these sensors, Hossein Zargartalebi, the primary author of the study, found inspiration in nature.
“I reflected on how shaking an apple tree releases ripe fruit,” shared Zargartalebi, a postdoctoral fellow in Kelley’s lab. “This observation sparked a thought: what if we could effectively ‘shake’ our DNA receptors to release previously captured proteins? I applied an alternating electric field, which caused the DNA strands to oscillate, achieving the desired result. The proteins released, allowing the sensor to reset.”
The nanoscale sensors resemble a series of swinging pendulums made of double-stranded DNA. One end connects to an electrode, while the other links to a segment of DNA that attaches to a specific protein. By applying an alternating electric field, the sensors oscillate, effectively shedding proteins within just a minute and capturing new ones.
“Hossein demonstrated remarkable creativity with his unexpected solution,” Kelley praised. “Upon testing it in the lab, it worked seamlessly. It was both a simple and elegant fix.”
“I felt a surge of excitement knowing this natural inspiration led to a significant breakthrough,” Zargartalebi recounted. “Just as trees grow and release apples, our DNA sensors can continuously release proteins after each measurement cycle, allowing for real-time monitoring within the body. This experience reaffirmed that nature provides valuable insights for those willing to observe closely.”
Exploring inside the body
After successfully testing the device in the laboratory, the research team aimed to determine its effectiveness in live animals. They constructed an implantable microdevice housed within a slender microneedle, about the size of three human hairs. Similar to a continuous glucose monitor, the device is placed on the skin while the microneedle penetrates it to sample fluids.
The team engineered sensors designed to attach to two specific protein cytokines, which are essential markers for inflammation. They implanted the device into the skin of diabetic rats, given the close relationship between diabetes and inflammation—many complications stemming from diabetes arise due to inflammatory responses.
The sensors successfully tracked variations in the concentration of both proteins in the fluid. They recorded cytokine levels decreasing when the rats fasted or received insulin. Conversely, when the researchers introduced a substance to stimulate the immune system, cytokine levels spiked dramatically.
The sensors exhibited remarkable sensitivity; for instance, every time a rat was given insulin, the device detected a minor spike in inflammatory markers at the needle’s injection point. Additionally, readings from the sensors corresponded with high-level laboratory protein detection methods, confirming their effectiveness.
The ultimate preventative measure
Although the device is currently effective for monitoring inflammation, Kelley envisions its potential to track various other protein indicators. She specifically mentions heart failure, which involves the protein B-type natriuretic peptide (BNP). Clinicians routinely measure BNP to diagnose and manage heart failure, yet there are currently no methods for continuous real-time tracking of this marker.
“Patients with heart failure might only visit the doctor every three months,” Kelley noted. “However, symptoms can occur in the interim. It’s not always clear that a patient’s discomfort is connected to heart failure. With continuous monitoring, when a patient feels unwell, the doctor could access their BNP data immediately. Subsequently, treatment plans can be adjusted before the situation worsens. We aspire for this technology to one day benefit many, akin to the advancements made with continuous glucose monitoring—we hope it will become an essential preventative tool.”
The study, titled “Active-reset protein sensors enable continuous in vivo monitoring of inflammation,” received support from the National Institutes of Health, Canadian Institutes of Health Research, Ontario Genomics, National Institutes of Health Heart Failure, Chan Zuckerberg Biohub Chicago, and the Natural Sciences and Engineering Research Council of Canada.
