Implantable sensor for wireless tracking of nitric oxide

Implantable sensor for wireless tracking of nitric oxide

If smoke indicates a fire, nitric oxide indicates inflammation. Usually, degenerative disease isn’t recognized until after progressive symptoms, but it can be detected much earlier by tracing nitric oxide, according to Huanyu “Larry” Cheng and James E. Henderson, an associate professor of Memorial Engineering and Mechanics at Pennsylvania state.

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. Image Credit: Shangbin Liu / Penn State / Tsinghua University.

Cheng and his student, Shangbin Liu, who received a master’s degree in engineering sciences and mechanics from Penn State this year, partnered with scientists based in China to create a flexible biosensor that can perform continuous, wireless detection of nitric oxide in rabbits. Inform the team about their method of Proceedings of the National Academy of Sciences.

Real-time assessment of inflammation-related biomarkers, 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.

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

According to Cheng, the challenge for nitric oxide discovery is the need for electrochemical sensors that are highly sensitive, stable, biocompatible and also flexible so that the geographical source of nitric oxide can be mapped accurately.

Corresponding author Lan Yin, associate professor in the College of Materials Science and Engineering at Tsinghua University in China, previously directed to create 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,” Which means the device could be able to identify nitric oxide, but not its exact source, Yin said, so it wasn’t clear if the signal was related to the area of ​​injury or nearby tissue. “Recalibration was also required on a regular basis to ensure the desired accuracy.”

The scientists chose a potential solution for flexible and biocompatible organic electrochemical transistors (OECTs), which can use voltage and currents to detect and intensify signals.

Even small ion concentrations are noticeable and amplify When oxidized on the gate electrode and pushes the electrolyte ions into the channel of the device; However, the channel is made of a polymer, called PEDOT:PSS, which operates frequently at a more varied gate voltage than nitric oxide.

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

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

“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,” Cheng added.

The scientists combined the sensors with a custom circuit unit, resulting in a device that wirelessly and uninterruptedly tracks nitric oxide levels, which are transmitted via Bluetooth to a cell phone app. To put the design to the test, the scientists inserted the devices into rabbits. During eight days, the scientists learned that the devices positively sense concentrations of nitric oxide.

Cheng says, “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.”

According to Cheng, the team plans to further examine the relationship between nitric oxide concentrations and osteoporosis and to improve the sensing technology.

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

Lan Yin, correspondent author and associate professor, College of Materials Science and Engineering, Tsinghua University

Other contributors to the study include Yuping Deng, Zhenhu Guo, Kuntao Chen, and Lingyun Zhao from Tsinghua University. Hui Qi, Yongsheng Jie, Rui Zheng, and Jinzhu Jing, Beijing Institute of Traumatology and Orthopedics; Yuan Ma, Meilin Zhang, Kaiyuan Zhang, and Xing Sheng, Tsinghua University; Mingyu Zhao, Peking University; He Ding and Guoqing Lv, Beijing Institute of Technology; and Rongfeng Li, Beijing Institute of Collaborative Innovation. Guo also belongs to Central South University.

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

Journal reference:

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


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