Microfluidic trapping of 3D spheres in microfluidic reaction systems for real time biosensing of flow chemistry derived compounds

微流体反应系统中 3D 球体的微流体捕获，用于流动化学衍生化合物的实时生物传感

• 批准号: 405360269
• 负责人: Dr. Heinz-Georg Jahnke, since 1/2020
• 金额: --
• 依托单位: Biotechnologisch-Biomedizinisches Zentrum (BBZ)
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/405360269?language=en
• 关键词: Microfluidic; trapping; 3D; spheres; microfluidic

The topic of the research project of the 2nd funding period will be the combination of a 3D organoid based multiparametric real time biological activity monitoring and the adaptation of the microfluidic lab-on-chip design (1st funding period). Coupling an inline real time bioanalysis under a high degree of environmental control for the bioelectronic monitoring of complex 3D cell aggregates under flow will be the challenge. During the 1st funding period we were successful in establishing a fast, sensitive real time analytical tool based on viable 2D cell monolayer for impedimetric monitoring of chemical synthesis educts/products with regard to biological activity. Now the on-chip microfluidic trapping of 3D organoids i.e. organotypic cardiac spheres that recapitulate the in vivo situation will be the main research topic. The drug discovery shall be realized on a microfluidic chip consisting of two levels (i) for the microsynthesis area, the µFFE field and the microchannels connecting the 3D microcavity-electrode as a multi-well format on the (ii) second level including positioning channels for the 3D cultures. The novel microcavity array structures (200 – 500 µm length, 130-330 µm depth) with at least four electrodes per microcavity will be produced in fused silica substrates using the innovative technology of selective laser etching. These integrated microcavity structures on the multilevel microfluidic chip will be contacted by a hybrid multiplexer electronic board, which is based on the impedance multiplexer board developed during the 1st funding period. For the synchronous multimodal measurement of the biological targets, the electronic board will be extended by an electronic module for the field potential recording. The extended multimodal system comprises, a switch between impedance spectroscopy, field potential recording, and photonic monitoring of 3D cardiac clusters under fluidic conditions, which allows to analyse physiological biomechanical and electrophysiological properties in real-time. Thus, the microfluidic chip for viable cell monolayer from the 1st funding period will be extended by a novel module for 3D organoid trapping and real time hybrid live-sensing of 3D spheres in microcavity arrays based on experiences demonstrated in the past.

第二期资助项目的研究课题为基于三维类器官的多参数实时生物活性监测与微流控芯片实验室的适配设计相结合（第一期资助）。在高度环境控制下对复杂的三维细胞聚集体进行生物电子监测的在线实时生物分析将是一个挑战。在第一个资助期内，我们成功地建立了一个快速，敏感的实时分析工具，基于活的二维细胞单层，用于化学合成产物/产物的生物活性障碍监测。目前，再现体内情况的三维类器官即器官型心脏球体的片上微流控捕获将是主要的研究课题。药物发现应在微流控芯片上实现，微流控芯片由两层组成(i)用于微合成区，µFFE场和连接3D微腔电极的微通道作为（ii）第二层的多孔格式，包括用于3D培养的定位通道。新型微腔阵列结构（长度200 - 500 μ m，深度130-330 μ m），每个微腔至少有四个电极，将使用选择性激光蚀刻的创新技术在熔融硅衬底上生产。这些集成在多级微流控芯片上的微腔结构将通过混合多路复用电子板进行连接，该电子板是在第一期资助期间开发的阻抗多路复用板的基础上开发的。对于生物靶的同步多模态测量，电子板将被一个用于场电位记录的电子模块扩展。扩展的多模态系统包括阻抗谱、场电位记录和流体条件下三维心脏簇的光子监测之间的切换，可以实时分析生理生物力学和电生理特性。因此，从第一个资助期开始，用于活细胞单层的微流控芯片将在过去的经验基础上扩展为用于三维类器官捕获和微腔阵列中三维球体实时混合实时传感的新型模块。