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A highly adsorptive electrochemical fiber sensor for real-time and accurate detection of intracranial nitric oxide

高吸附电化学纤维传感器用于实时、准确检测颅内 一氧化氮

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Abstract

Electrochemical nitric oxide (NO) sensors are capable of real-time monitoring of intracranial NO concentration, which is crucial for understanding the functions of NO in the brain. However, traditional rigid electrochemical sensors used in the brain face the dilemma of low sensitivity and abnormal NO concentrations caused by neuroin-flammatory responses. Here, we report a highly sensitive and accurate electrochemical NO sensor that combines both physical and chemical adsorption capabilities for NO. The physical and chemical adsorption capabilities can be attributed to the high specific surface area and abundant carboxyl functional groups of the electrode, respectively. Besides, it is soft and matches the mechanical property of brain tissue, enabling an adaptable interface. The resulting NO sensor exhibits the highest reported sensitivity of 3245 pA nmol−1 L, with a low detection limit of 0.1 nmol L−1. No significant inflammatory response or excess NO expression is observed after implantation, improving the detection accuracy. The sensor successfully captures NO fluctuations in the brain and enables simultaneous NO detection in multiple brain regions, facilitating research on NO physio-pathological actions in the brain.

摘要

电化学一氧化氮传感器能够实时监测颅内一氧化氮浓度, 对于 了解大脑中一氧化氮的功能至关重要. 然而, 在大脑中使用的传统刚性 传感电极面临着灵敏度低和植入后神经炎症引起一氧化氮浓度异常的 问题. 在这里, 我们报道了一种结合物理和化学吸附能力、具有高灵敏 度和准确性的电化学一氧化氮传感器. 其对一氧化氮的物理和化学吸 附能力分别来自于电极的高比表面积和丰富的羧基官能团. 此外, 柔软 的电极可以与脑组织的力学性能相匹配, 实现了一个高度适应的电极/组织界面. 由此设计的颅内一氧化氮传感器表现出迄今为止所报道文 献中最高的灵敏度, 为3245 pA nmol−1L, 检测限为0.1 nmol L−1. 电极 在植入后未观察到显著的炎症反应以及过量的一氧化氮表达, 提高了 检测的准确性. 该传感器成功捕捉了大脑中的一氧化氮波动, 并实现了 对多个脑区的同时检测, 促进了对大脑中一氧化氮生理病理作用的 研究.

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Acknowledgements

This work was financially supported by the National Natural Science Foundation of China (22175086, 22005137, 22205098, and 82201992), the Natural Science Foundation of Jiangsu Province (BK20200321 and BK20210681), the Postdoctoral Research Foundation of Jiangsu Province (2021K007A), China Postdoctoral Science Foundation (2021M700067), the National Postdoctoral Program for Innovative Talents (BX20200161), the Program for Innovative Talents and Entrepreneurs in Jiangsu (JSSCTD202138), the Fundamental Research Funds for the Central Universities (021314380234), and the Natural Science Foundation of Nanjing University of Chinese Medicine (XPT82201992).

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  1. These authors contributed equally to this work.

Authors and Affiliations

  1. National Laboratory of Solid State Microstructures, Jiangsu Key Laboratory of Artificial Functional Materials, Chemistry and Biomedicine Innovation Center, Collaborative Innovation Center of Advanced Microstructures, College of Engineering and Applied Sciences, Nanjing University, Nanjing, 210023, China

    Rui Gao  (高睿), Lie Wang  (王列), Jie Song  (宋杰), Qianming Li  (栗乾明), Jiang Lu  (卢江), Luhe Li  (李录河), Yiran Li  (李亦冉), Tingting Ye  (叶婷婷), Jiacheng Wang  (王嘉诚), Yiding Jiao  (焦一丁), Fangyan Li  (李方琰), Er He  (何儿), Junye Ren  (任俊烨) & Ye Zhang  (张晔)

  2. Department of Immunology, School of Medicine and Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China

    Dan Li  (李丹)

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  1. Rui Gao  (高睿)
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  2. Lie Wang  (王列)
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Contributions

Author contributions Zhang Y conceived the general idea. Gao R designed and conducted the experiments, wrote the paper with support from Wang L. Li D conducted the biological experiments. Song J, Li Q and Lu J assisted in the electrochemical tests. Li L, Li Y and Li F carried out the SEM tests. Ye T, Wang J, Jiao Y, He E and Ren J helped analyze the data. All authors discussed the results and commented on the manuscript.

Corresponding author

Correspondence to Ye Zhang  (张晔).

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Conflict of interest The authors declare that they have no conflict of interest.

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Supplementary information Supporting data are available in the online version of the paper.

Rui Gao received her BS degree in materials physics from Nanjing University in 2021. Currently, she is pursuing her MS degree in materials science and engineering at Nanjing University. Her current research interest focuses on implantable sensors.

Lie Wang received his BS degree from Zhejiang Sci-Tech University in 2015 and PhD degree in polymer chemistry from Fudan University in 2020. Afterwards, he worked as a postdoctoral fellow for three years at Nanjing University. His current research focuses on wearable sensors and implantable bioelectronic devices.

Dan Li received her PhD degree in polymer chemistry from the Medical School, Nanjing University in 2020. Now, she is an associate professor at the School of Medicine and Holistic Integrative Medicine, Nanjing University of Chinese Medicine. Her research interest focuses on the analyses of the pathogenesis of immune diseases based on the diversity of MDSCs cell phenotypes, monitoring and evaluation of drug treatment of immune diseases based on flexible fibers.

Ye Zhang is currently an associate professor at the College of Engineering and Applied Sciences, Nanjing University. She received her PhD degree in macromolecular chemistry and physics from Fudan University in 2018 and then joined Harvard Medical School as a postdoctoral research fellow. Her research focuses on the development of soft electronics including batteries, sensors, and bioelectronic devices.

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Gao, R., Wang, L., Li, D. et al. A highly adsorptive electrochemical fiber sensor for real-time and accurate detection of intracranial nitric oxide. Sci. China Mater. 67, 1320–1331 (2024). https://doi.org/10.1007/s40843-024-2808-2

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