Northwestern University and Chan Zuckerberg Biohub Chicago have developed a novel implantable sensor capable of continuously monitoring inflammation in real-time. This innovative technology, published in Science, addresses the critical need for tools that can track inflammation at its earliest stages, potentially preventing the progression of various diseases.
Overcoming Limitations of Existing Sensors
Traditional methods of measuring inflammation often rely on analyzing interstitial fluid, which is difficult to extract and limited in volume. Existing wearable or implantable sensors have primarily focused on small molecules, while real-time, continuous in vivo protein monitoring has remained challenging due to the slow dissociation kinetics of affinity receptors like antibodies. Shana O. Kelley, PhD, Professor of Chemistry and Bioengineering at Northwestern University and President of the Chan Zuckerberg Biohub Chicago, explained that their team sought to create a sensor similar to continuous glucose monitors (CGMs) but engineered to detect protein markers of inflammation.
The "Active-Reset" Mechanism
The key innovation lies in the sensor's "active-reset" mechanism. The sensor uses electrochemical sensors to detect cytokines, specifically IL-6 and TNF-α, which are key indicators of inflammation. However, when cytokine protein levels rise, the electrochemical sensors bind the protein, detect it, and form a strong complex. This complex prevents the sensors from responding when the protein levels decrease. To overcome this, the researchers discovered that vibrating the sensors at high frequencies could dissociate the complex, thereby continuously priming the sensors for subsequent measurements.
"We learned to shake the sensors on the surface of the electrode, and if you shake them hard enough, the protein comes off, and then you reset the sensor to be ready for taking another measurement," said Kelley. This allows the sensor to track both increases and decreases in cytokine levels in real-time, a capability that was previously unattainable.
In Vivo Validation and Future Directions
The researchers validated the sensor's performance in vitro using simulated interstitial fluid and then created a microneedle-shaped housing for the wire-based electrodes. These microdevices were implanted into rodents, and the active-reset mechanism effectively tracked sharp changes in cytokine levels after the injection of lipopolysaccharide (LPS) to induce inflammation. The results showed strong agreement with ELISA results, demonstrating the sensor's accuracy.
The next step is to translate the rodent design to a platform suitable for clinical settings. Kelley envisions integrating the sensor into a device similar to existing CGMs like the Freestyle Libre 3 or Dexcom G7. While the technological aspects are largely ready, the primary challenges lie in navigating regulatory hurdles and product development, which Kelley believes would be best handled by a startup or partnership with a larger company.
Potential Impact on Disease Management
With the ability to monitor inflammation in real-time and at earlier stages, this technology has the potential to significantly impact how inflammation is treated. Kelley emphasized that the current approach often focuses on treating late-stage disease. By detecting inflammation early, interventions can be implemented to potentially prevent disease progression or mitigate its severity.
Furthermore, continuous inflammation monitoring could provide valuable insights into the etiology of inflammation, allowing for personalized treatment strategies. By understanding how factors like diet, environment, and stress levels affect an individual's inflammatory response, healthcare professionals can tailor interventions to optimize patient outcomes. The technology also holds promise for managing late-stage chronic diseases like heart failure, kidney failure, and diabetes, where protein biomarkers are needed to inform treatment decisions. The global CGM market was valued at approximately $6.32 billion in 2023, highlighting the potential market for a continuous inflammation monitor.
