Inflammation is a natural and essential bodily response to an injury, during which your body sends out signaling proteins, called cytokines, that tell your immune system to repair tissue or fight off germs.
Doctors need to track fluctuations in protein levels to get a full picture of what’s happening in the body. Now, Northwestern scientists have designed a new implantable device that can monitor fluctuating levels of cytokines within the body in real time, laying the groundwork for more immediate management and prevention of acute and chronic conditions.
Inspired by fruit being shaken from the branches of a tree, the device comprises strands of DNA that stick to proteins, shake them off and then grab more proteins. This enables the device to measure changes in inflammatory markers.
“The device’s design is analogous to a continuous glucose monitor that sits on your arm and measures levels right beneath your skin,” says study leader Shana O. Kelley, the Neena B. Schwartz Professor of Chemistry and Biomedical Engineering at Northwestern. “You need to be able to measure [those] trends. ... It’s the same with proteins in inflammation. We need to track fluctuations in order to get a full picture of what’s happening.
“This is a completely new capability — to be able to watch inflammation in real time. There are a huge number of [potential] applications.”
Continuous glucose monitors have existed for years. But sensors for proteins — which are larger, more complex molecules — are much more challenging to design. To detect proteins in biological fluids, scientists typically use DNA receptors that bind to proteins and pull them out of biofluids. These attachments are so strong, however, that they hold onto proteins for over 20 hours, making it impossible to measure real-time fluctuations.
Seeking a solution to “reset” the sensors, postdoctoral fellow Hossein Zargartalebi drew inspiration from nature.
“I thought about how shaking an apple tree ... makes ripe apples detach and fall,” says Zargartalebi, who works in Kelley’s lab. “This simple observation sparked an idea. What if we could ‘shake’ the DNA receptors on our sensors to release the captured proteins?”
The researchers used nanoscale sensors that resemble rows of bulbous pendulums, each comprising a double-stranded cord of DNA. One end of the DNA strand is attached to an electrode, and the other end is attached to another bit of DNA that binds to a specific protein. When the researchers apply an alternating electric field, the sensors swing back and forth, flinging off proteins and catching others.
“Our DNA sensors can ‘release’ their proteins after each measurement cycle, enabling continuous, real-time monitoring inside the body,” Zargartalebi says.
The researchers next built an implantable microdevice with the electrode and sensors inside a microneedle the width of just three human hairs. Like a continuous glucose monitor, the device sits on the skin while the microneedle pricks the skin to sample fluids.
The team designed sensors to bind to two protein cytokines. They then attached the device to diabetic rats. (Many complications associated with diabetes are caused by inflammation.)
The sensors successfully measured concentration changes of both proteins within the rats in real time. Measurements from the sensors also matched gold-standard laboratory methods to detect proteins in bodily fluids, validating the device’s success.
Kelley envisions using the device to track many other protein markers, including a protein that clinicians measure to diagnose and monitor heart failure. Currently, there is no way to continuously track this protein biomarker in real time.
“We hope one day this technology will benefit many people. ... It could be the ultimate preventive measure,” says Kelley.
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