New implantable sensor recognizes potential signals of osteoporosis

New implantable sensor recognizes potential signals of osteoporosis

Researchers have developed a flexible, implantable sensor that can continuously monitor nitric oxide in a rabbit’s knee. Gas may signal the onset of arthritis caused by damage. Credit: Shangbin Liu / Penn State / Tsinghua University

If smoke indicates a fire, nitric oxide indicates inflammation. The chemical mediator stimulates inflammation, but researchers believe it can do its job very well after an anterior cruciate ligament (ACL) rupture, related injuries and early onset of osteoarthritis. Typically, degenerative disease isn’t diagnosed until progressive symptoms appear, but it’s likely to be recognized much earlier by monitoring nitric oxide, according to Huanyu “Larry” Cheng and James E. Henderson, Memorial Professor of Engineering Sciences and Mechanics at Penn State. .

Cheng and his student Shangbin Liu, who holds a master’s degree in engineering sciences and mechanics from Penn State University this year, collaborated with researchers based in China to develop a flexible biosensor capable of continuous and wireless detection of nitric oxide in rabbits. They published their approach in Proceedings of the National Academy of Sciences.

“Real-time evaluation of biomarkers associated with inflammation, such as nitric oxide in the joint cavity, can indicate pathological progression in the initial development of osteoarthritis, providing key information for improving treatments after traumatic knee injury,” Cheng said.

The challenge, according to Cheng, is that the detection of nitric oxide requires highly sensitive, stable electrochemical sensors that are also flexible and biocompatible so that the geographical origins of nitric oxide can be accurately identified. Corresponding author Lan Yin, assistant professor in the School of Materials Science and Engineering at Tsinghua University in China, led the development of a flexible and sensitive electrochemical sensor for nitric oxide, but relied on an electrode configuration that limited its capabilities.

“The limited surface area made it difficult to achieve high sensitivity and high spatial resolution at the same time,” Yin said, meaning the device might be able to detect nitric oxide, but it might not be able to pinpoint exactly where it originated, so it wasn’t clear If the signal is related to the site of the injury or surrounding tissue. “Recalibration was also required on a regular basis to ensure the desired accuracy.”

New implantable sensor recognizes potential signals of osteoporosis

The researchers tuned the channel geometry in the sensing mechanism to improve how gas enters the sensing channel prior to detection. The inset image highlights the drainage (D), length (L), source (S), and width (W) of the channel. Credit: Shangbin Liu / Penn State / Tsinghua University

The researchers turned to the potential solution of flexible and biocompatible organic electrochemical transistors (OECTs), which can use voltage and currents to identify and amplify signals. Even small ion concentrations can be detected and amplified once they oxidize on the gate electrode and push electrolyte ions into the device channel; However, the channel is made of a polymer, known as PEDOT:PSS, which often operates at a different gate voltage than nitric oxide.

“We tuned the channel geometry and gate materials to align how electrochemical nitric oxide signals enter the channel and how the device detects them, improving the sensing capabilities,” Cheng said. “The reference-free sensor with a miniature active sensing area enables nitric oxide detection with improved spatial resolution compared to previously reported electrochemical nitric oxide sensors, which can allow mapping of electrochemical signals to provide comprehensive diagnostic information.”

The researchers combined the sensors with a custom circuit unit, resulting in a device that continuously and wirelessly monitored nitric oxide levels, which was transmitted via Bluetooth to a cell phone app. To test the design, the researchers implanted the devices into rabbits. Over the course of eight days, the researchers found that the devices successfully detected nitric oxide concentrations.

“The results suggest that early signs of high nitric oxide concentrations could be associated with inflammation and later-stage cartilage degeneration, which may provide key information for assessing arthritis progression after ACL injury and improving post-traumatic therapies,” Cheng said.

The researchers plan to further investigate the relationship between nitric oxide concentrations and osteoporosis and improve sensing technology, according to Cheng.

“Overall, the proposed material and device design choices can provide a critical engineering basis for deciphering health conditions at an early stage and maximizing therapeutic outcomes for degeneration and associated disorders,” Yin said.


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more information:
Yuping Deng et al, A flexible and highly sensitive organic electrochemical transistor-based biosensor for continuous and wireless detection of nitric oxide, Proceedings of the National Academy of Sciences (2022). DOI: 10.1073/pnas.2208060119

Provided by Penn State University


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