Micro fluidic system for characterization of endothelial permeability and transendothelial leucocyte migration

血管的渗透性增加和白细胞从血液中通过血管壁迁移到炎症组织中是炎症反应的标志。在该项目中，将首次开发具有集成穿孔膜的微流体室，其将用于生理环境中肺内皮细胞渗透性和白细胞跨内皮迁移的实时和空间分辨表征。将平面微电极阵列沉积在穿孔膜的两侧，以使用阻抗谱测量技术局部和定量地表征渗透性和迁移行为。电测量将与标准荧光技术进行比较。该微流控室将用于在蛋白酶底物CX 3CL 1、CXCL 16、JAM-A VE-钙粘蛋白和ERLR配体的水平上研究表面蛋白酶ADAM 10和ADAM 17在内皮通透性和白细胞迁移中的调节和功能。该系统将允许在生理条件下以定量和时间有效的方式表征针对这些分子的新型抑制剂。

The increased permeability of the blood vessel and the transmigration of leucocytes out of the blood through the vessel wall into the inflammed tissue are hallmarks of inflammatory response. In this project a microfluidic chamber with an integrated perforated membrane will be developed for the first time which will be used for real-time and space-resolved characterization of pulmonary endothelial cells permeability and transendothelial migration of leucocytes in a physiological environment. Planar microelectrode arrays will be deposited on both sides of the perforated membrane to characterize the permeability and transmigration behavior locally and quantitatively using impedance spectroscopy measurement techniques. The electrical measurements will be compared with standard fluorescence techniques. The microfluidic chamber will be used to investigate the regulation and function of the surface proteases ADAM 10 and ADAM 17 in endothelial permeability and leukocyte transmigration at the levele og the protease substrates CX3CL1, CXCL16, JAM-A VE-cadherin and ERLR ligands. The system will allow characterizing novel inhibitors against these molecules under physiological conditions in a quantitative and time-effective manner.