Simms Helen M, Bowman Christopher M, Anseth Kristi S
Department of Chemical and Biological Engineering, ECCH 111, CB424, University of Colorado, Boulder, CO 80309-0424, USA.
Biomaterials. 2008 May;29(14):2228-36. doi: 10.1016/j.biomaterials.2008.02.001. Epub 2008 Feb 21.
High throughput screening tools are expediting cell culture studies with applications in drug discovery and tissue engineering. This contribution demonstrates a method to incorporate 3D cell culture sites into microfluidic devices and enables the fabrication of high throughput screening tools with uniquely addressable culture environments. Contact lithographic photopolymerization (CLiPP) was used to fabricate microfluidic devices with two types of 3D culture sites: macroporous rigid polymer cell scaffolds and poly(ethylene glycol) (PEG) encapsulated cell matrices. Cells were cultured on-device with both types of culture sites, demonstrating material cytocompatibility. Multilayer microfluidic devices were fabricated with channels passing the top and bottom sides of a series of rigid porous polymer scaffolds. Cells were seeded and cultured on device, demonstrating the ability to deliver cells and culture cells on multiple scaffolds along the length of a single channel. Flow control through these rigid porous polymer scaffolds was demonstrated. Finally, devices were modified by grafting of PEG methacrylate from surfaces to prevent non-specific protein adsorption and ultimately cell adhesion to channel surfaces. The living radical component of this CLiPP device fabrication platform enables facile incorporation of 3D culture sites into microfluidic cell culture devices, which can be utilized for high throughput screening of cell-material interactions.
高通量筛选工具正在加速细胞培养研究，并应用于药物发现和组织工程领域。本文展示了一种将三维细胞培养位点整合到微流控设备中的方法，并能够制造出具有独特可寻址培养环境的高通量筛选工具。接触光刻光聚合（CLiPP）被用于制造具有两种三维培养位点的微流控设备：大孔刚性聚合物细胞支架和聚乙二醇（PEG）包裹的细胞基质。细胞在这两种培养位点上进行了原位培养，证明了材料的细胞相容性。制造了多层微流控设备，其通道穿过一系列刚性多孔聚合物支架的顶部和底部。细胞在设备上接种并培养，证明了在单个通道长度上的多个支架上输送细胞和培养细胞的能力。展示了通过这些刚性多孔聚合物支架的流量控制。最后，通过从表面接枝甲基丙烯酸PEG对设备进行改性，以防止非特异性蛋白质吸附并最终防止细胞粘附到通道表面。这个CLiPP设备制造平台的活性自由基成分能够将三维培养位点轻松整合到微流控细胞培养设备中，可用于高通量筛选细胞与材料的相互作用。
