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Implantable Sensing Device for Continuous, Wireless Nitric Oxide Tracking

If smoke points to a fire, nitric oxide points to inflammation. Normally, the degenerative disease is only identified after progressive symptoms, but it possibly could be detected much earlier via nitric oxide tracking, according to Huanyu “Larry” Cheng, James E. Henderson Jr. Memorial Associate Professor of Engineering Science and Mechanics at Penn State.

Implantable Sensing Device for Continuous, Wireless Nitric Oxide Tracking
Researchers developed a flexible, implantable sensor that can continuously monitor nitric oxide in the knee of a rabbit. The gas may indicate the onset of damage-induced osteoarthritis. Image Credit: Shangbin Liu/Penn State/Tsinghua University.

Cheng and his student, Shangbin Liu, who obtained a master’s degree in engineering science and mechanics at Penn State this year, partnered with scientists based in China to create a flexible biosensor that can carry out continuous and wireless detection of nitric oxide in rabbits. The team reported their method in the Proceedings of the National Academy of Sciences.

Real-time assessment of biomarkers associated with inflammation, such as nitric oxide in the joint cavity, could indicate pathological evolution at the initial development of osteoarthritis, providing essential information to optimize therapies following traumatic knee injury.

Huanyu “Larry” Cheng, James E. Henderson Jr. Memorial Associate Professor, Engineering Science and Mechanics, Penn State University

According to Cheng, the challenge with nitric oxide detection is the requirement of very sensitive and stable electrochemical sensors that are also biocompatible and flexible so the geographic source of the nitric oxide can be charted accurately.

Corresponding author Lan Yin, associate professor in the School of Materials Science and Engineering at Tsinghua University in China, earlier guided the creation of a flexible, nitric oxide-sensitive electrochemical sensor, but it depended on an electrode configuration that limited its capabilities.

“The limited surface area made it challenging to simultaneously attain both high sensitivity and high spatial resolution,” Yin said, meaning the device could be able to identify nitric oxide, but not its exact origination, so it was not evident if the signal was associated with the injury area or adjacent tissue. “Recalibration was also required on a regular basis to ensure desirable accuracy.”

The scientists picked the probable solution of flexible and biocompatible organic electrochemical transistors (OECTs), which can utilize voltage and currents to detect and intensify signals.

Even tiny ion concentrations are noticeable and magnifiable when they oxidize on the gate electrode and push ions of the electrolyte into the device’s channel; however, the channel is composed of a polymer, called PEDOT:PSS, that frequently works at a diverse gate voltage than nitric oxide.

We tuned the channel geometry and gate materials to align how the nitric oxide electrochemical signals enter the channel and how the device detects them, optimizing the sensing capabilities.

Huanyu “Larry” Cheng, James E. Henderson Jr. Memorial Associate Professor, Engineering Science and Mechanics, Penn State University

“The reference-free sensor with a miniaturized active sensing region enables nitric oxide detection with improved spatial resolution compared with previously reported electrochemical nitric oxide sensors, which could allow the mapping of electrochemical signals to offer comprehensive diagnostic information,” Cheng added.

The scientists combined the sensors with a tailored circuit module, resulting in a device that uninterruptedly and wirelessly tracks nitric oxide levels, which are conveyed via Bluetooth to a cell phone app. To put the design test, the scientists embedded the devices in rabbits. Across eight days, the scientists learned that the devices positively sensed nitric oxide concentrations.

Cheng says, “The results indicate that early signs of high nitric oxide concentrations could be correlated with inflammation and cartilage degeneration at the later stage, which could potentially offer essential information to evaluate the progression to osteoarthritis after ACL injury and optimize posttraumatic treatments.”

According to Cheng, the team plans to carry on examining the connection between nitric oxide concentrations and osteoarthritis and optimizing the sensing technology.

Overall, the proposed materials options and device design could offer critical engineering basis for decoding health conditions at an early stage and maximizing therapeutic outcomes of associated degeneration and disorders.

Lan Yin, Corresponding author and Associate Professor, School of Materials Science and Engineering, Tsinghua University

Other study contributors include Yuping Deng, Zhenhu Guo, Kuntao Chen, and Lingyun Zhao, Tsinghua University; Hui Qi, Yongsheng Jie, Rui Zheng, and Jinzhu Jing, Beijing Institute of Traumatology and Orthopaedics; Yuan Ma, Milin Zhang, Kaiyuan Zhang, and Xing Sheng, Tsinghua University; Mingyou Zhao, Peking University; He Ding and Guoqing Lv, Beijing Institute of Technology; and Rongfeng Li, Beijing Institute of Collaborative Innovation. Guo is also affiliated with Central South University.

This research was supported by the National Natural Science Foundation of China, the Beijing Municipal Health Commission, the Tsinghua University-Peking Union Medical College Hospital Initiative Scientific Research Program, and the University of Tokyo-Tsinghua Collaborative Research Fund. 

Journal Reference:

Deng, Y., et al. (2022) A flexible and highly sensitive organic electrochemical transistor-based biosensor for continuous and wireless nitric oxide detection. Proceedings of the National Academy of Sciences.

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