Towards an Artificial Synapse: Synthesis and Characterization of a Carbon Nanotube-based, Switchable Nanofluidic Transport System for Neurotransmitters

在细胞生物学中，许多重要的过程是由化学物质在非常小的空间和时间尺度上的传递和释放所控制的。我们神经系统中的信息处理和传输就是最有趣的例子之一。尽管有许多宏观方法可以在确定的位置和时间点释放化学物质，但它们仍然缺乏与生物学相关尺度相匹配的空间和时间分辨率。碳纳米管是纳米流体应用的理想候选者，因为它们的尺寸与生物相关的孔和突触的尺寸相匹配。在这个项目中，碳纳米管将用于构建一个膜系统，用于空间和暂时控制神经递质的传递。在本研究的第一部分，将在基于库尔特计数的微流控装置中研究小神经递质通过不同碳纳米管的转运。在第二步中，放置在纳米管入口处的光开关基团将用于创建可逆的开/闭状态。因此，开放与封闭人工突触的复杂模式可以由光等简单刺激产生。最后，碳纳米管将被放入微流体装置内的膜中，在膜上培养成肌细胞，模拟神经肌肉连接处。神经递质向这些细胞的释放可以被光精确地控制，细胞在这种空间/暂时控制释放上的行为将被研究。综上所述，本项目将研究碳纳米管中分子的运输。此外，化学修饰的碳纳米管将集成到膜中，以构建可光切换的神经递质传递系统。这种设置为在生物学上相关的长度尺度上研究神经元细胞行为提供了很大的希望。因此，这个项目代表了为人工突触铺平道路的第一步。

In cell biology many important processes are governed by delivery and release of chemicals on a very small spatial and temporal scale. Information processing and transport in our nervous system is one of the most intriguing examples. Although there are many macroscopic methods to release chemicals at defined positions and time points, they are still lacking a spatial and temporal resolution that matches the biologically relevant scale. Carbon nanotubes are ideal candidates for nanofluidic applications because their dimensions match the dimensions of biologically relevant pores and synapses. In this project, carbon nanotubes will be used to build a membrane system for spatially and temporarily controlled delivery of neurotransmitters.In the first part of this work, transport of small neurotransmitters through different carbon nanotubes will be studied in a microfluidic setup based on coulter counting. In a second step, photoswitchable groups placed at the entrance of the nanotubes will be used to create reversible open/closed states. Thus, complex patterns of open versus closed artificial synapses can be generated by a simple stimulus such as light. Finally, carbon nanotubes will be incorporated into a membrane inside a microfluidic setup, with myoblasts cultivated on top of this membrane, mimicking the neuromuscular junction. The release of neurotransmitters to these cells can then be precisely controlled by light and cell behaviour upon this spatially/temporarily controlled release will be studied. In summary, in this project the transport of molecules in carbon nanotubes will be investigated. Additionally, chemically modified carbon nanotubes will be integrated into a membrane to build a photoswitchable delivery system for neurotransmitters. This setup holds great promises for the study of neuronal cell behaviour on biologically relevant length scales. Therefore, this project represents the first step to pave the way towards an artificial synapse.