Sensor for Probing Intercellular Communications

组织和器官中的细胞通过相互交流来协调它们的活动，这种交流由称为间隙连接的专门通道介导。通过差距连接通道，细胞同步其电和代谢活动，传递细胞间信号，从而调节细胞生长和分化，并维持代谢稳态。本研究旨在开发一种新型的微流控传感器，该传感器能够在单细胞水平上通过间隙连接通道探测细胞间的通讯。所提出的方法利用微流控芯片的多流层流特性来精确地将相邻细胞限制在不同的环境中，从而使得受控的手段能够通过荧光和/或阻抗方法来实时研究单对细胞之间的细胞间通信。该传感器将提供研究试剂的特异性和缝隙连接对细胞外刺激的响应的能力。本项目将完成多个研究目标，包括设计和控制微流通道中的多股流，在传感器的功能化区域中进行芯片上细胞培养，使用荧光和阻抗测量检测细胞间的通信途径及其对细胞外刺激的响应，并开发用于研究间隙连接通道的水渗透性的传感策略。

Cells in tissues and organs coordinate their activities by communicating with each other, and this communication is mediated by specialized channels, called gap junctions. Through the gap junction channels, cells synchronize their electrical and metabolic activities, transmit intercellular signals, resulting in regulation of cell growth and differentiation, and maintenance of metabolic homeostasis. This proposal aims to develop a novel microfluidic sensor that is capable of probing intercellular communications via gap junction channels at the single-cell level. The proposed approach utilizes the multi-stream laminar flow characteristics of a microfluidic chip to precisely confine adjacent cells to different environments, thereby enabling a controlled means to study intercellular communications between a single pair of cells in real-time by both fluorescence and/or impedance methods. The sensor would provide an ability to study the specificity of reagents and response of gap junctions to extracellular stimuli. Several research goals will be accomplished in this project, including design and control of the multi-stream flow in a microfluidic channel, on-chip cell culture in the functionalized regions of the sensor, detection of intercellular communication pathways using fluorescence and impedance measurements and their response to extracellular stimuli, and develop sensing strategies for studying water permeability of gap junction channels.