微电极阵列上功能化传感界面构建及用于单细胞实时监测研究

Cells are the fundamental unit of life, and efficient, fast and accurate acquirement of the information of biomolecules at the single cell levels is of great significance to deep insight into the life process. Electrochemical methods based on the microelectrode array (MEA) have played important roles in real-time monitoring of single cells and showed excellent prospects in biomedical research. However, further application of MEA methods is hampered by their limited sensitivity in detection of very small number of molecules, easily contaminated electrode surface and poor cell compatibility in cell mobilization and culture. In this project, we will develop novel strategies for construction of functionalized sensing interface on microelectrode array for real-time monitoring of cells. Firstly, various nanomaterials interface will be constructed on the MEA in a controllable manner to improve the detection sensitivity. Secondly, nanocomposite photocatalysts with both high detection sensitivity and high photocatalytic capability will be developed and used to photocatalytically clean the pollution on the electrode for repeat usage of MEA. Furthermore, we will develop excellent cell compatibale interfaces between cell and electrode, so as to realize the cell mobilization, long-term culture and sensitive acquirement of the dynamic information from cells. The project would provide useful tools for high-throughput monitoring of single cell in real-time, and possibly facilitate the development of the interdisciplinary research area across analytical chemistry and biomedical science.

细胞是生命体结构和功能的基本单元，高效、快速、准确获取单细胞水平上生物分子动态信息对于深入理解生命过程至关重要。基于微电极阵列的检测方法已在单细胞信号分子实时动态监测方面显示了很好的前景，但目前仍存在电极检测灵敏度尚待提高、电极易污染难重复利用以及细胞相容性差等急需解决的问题。本项目拟在微电极阵列上构建高性能的功能化传感界面并用于细胞实时监测。通过可控构建高灵敏的纳米材料传感界面进一步提高检测灵敏度；开发并利用兼具高灵敏及高光降解能力的纳米复合光催化剂材料，实现微电极阵列的高效、方便、无损光催化自清洁；在此基础上开发基于细胞粘附小分子的细胞与电极之间的良好相容性界面，从而实现细胞在微电极阵列表面的长期培养以及实时动态信息的灵敏获取。本项目的实施将为单细胞高通量实时监测提供一种有效的方法，以期促进生物医学与分析化学相关交叉领域的发展。

在本项目中，我们成功发展了多种高性能电化学传感界面用于单细胞及亚细胞实时监测研究。我们构建了高灵敏、高选择、生物相容性好的电化学传感界面，首次实现了植物细胞生长素胞吐释放的实时监测；通过将纳米光催化材料与电化学传感材料复合，提出了电化学传感器光催化自清洁以及循环利用的新思路；发展了基于纳米管网络结构的弹性可拉伸电化学传感器，突破了现有刚性电极无法用于形变细胞监测的局限，为细胞的机械信号转导研究提供了新方法；建立了基于纳米电极的高时空分辨亚细胞实时探测方法，突破了纳米级突触间隙内神经递质胞吐释放动力学监测和神经信号传导过程实时跟踪难题。项目接收和发表SCI论文 22篇（其中Angew. Chem.7篇, ACS Nano1篇, Chem. Sci. 2篇，Anal. Chem. 6篇），研究成果在不同尺度上为单细胞甚至亚细胞实时电化学监测提供了极具潜力的分析方法，可望促进生物医学与分析化学相关交叉领域的发展。