Institute of Applied Synthetic Chemistry and Institute of Chemical Technologies and Analytics, Faculty of Technical Chemistry, Vienna University of Technology, Vienna, Getreidemarkt 9/163-164, 1060, Vienna, Austria.
Austrian Cluster for Tissue Regeneration, Vienna, Austria.
Sci Rep. 2019 Jun 26;9(1):9287. doi: 10.1038/s41598-019-45633-x.
In the advent of affordable photo- and soft-lithography using polydimethylsiloxane (PDMS), low cost multi-step microfabrication methods have become available to a broad scientific community today. Although these methods are frequently applied for microfluidic prototype production in academic and industrial settings, fast design iterations and rapid prototyping within a few minutes with a high degree of flexibility are nearly impossible. To reduce microfluidic concept-to-chip time and costs, a number of alternative rapid prototyping techniques have recently been introduced including CNC micromachining, 3D printing and plotting out of numeric CAD designs as well as micro-structuring of thin PDMS sheets and pressure sensitive adhesives. Although micro-structuring of pressure sensitive adhesives promises high design flexibility, rapid fabrication and simple biochip assembly, most adhesives are toxic for living biological systems. Since an appropriate bio-interface and proper biology-material interaction is key for any cell chip and organ-on-a-chip system, only a limited number of medical-grade materials are available for microfluidic prototyping. In this study, we have characterized four functional biomedical-grade pressure sensitive adhesives for rapid prototyping (e.g. less than 1 hour) applications including structuring precision, physical and optical properties as well as biocompatibilities. While similar biocompatibility was found for all four adhesives, significant differences in cutting behavior, bonding strength to glass and polymers as well as gas permeability was observed. Practical applications included stability testing of multilayered, membrane-integrated organ-on-a-chip devices under standard cell culture conditions (e.g. 2-3 weeks at 37 °C and 100% humidity) and a shear-impact up to 5 dynes/cm. Additionally, time- and shear-dependent uptake of non-toxic fluorescently labelled nanoparticles on human endothelial cells are demonstrated using micro-structured adhesive-bonded devices. Our results show that (a) both simple and complex microdevices can be designed, fabricated and tested in less than 1 hour, (b) these microdevices are stable for weeks even under physiological shear force conditions and (c) can be used to maintain cell monolayers as well as 3D cell culture systems.
在使用聚二甲基硅氧烷 (PDMS) 进行经济实惠的光和软光刻的时代，如今，低成本的多步微制造方法已广泛应用于科学界。尽管这些方法经常用于学术和工业环境中的微流控原型生产，但几乎不可能在几分钟内快速设计迭代和快速原型制作，并具有高度的灵活性。为了减少微流控概念到芯片的时间和成本，最近引入了许多替代快速原型制作技术，包括数控微加工、3D 打印和数值 CAD 设计的绘图以及 PDMS 薄片和压敏胶的微结构。尽管压敏胶的微结构具有高度的设计灵活性、快速制造和简单的生物芯片组装，但大多数粘合剂对活体生物系统都有毒。由于适当的生物界面和适当的生物材料相互作用是任何细胞芯片和器官芯片系统的关键，因此只有有限数量的医疗级材料可用于微流控原型制作。在这项研究中，我们对四种用于快速原型制作（例如少于 1 小时）的功能性生物医学级压敏胶进行了特性描述，包括结构精度、物理和光学性能以及生物相容性。虽然所有四种粘合剂的生物相容性相似，但在切割行为、与玻璃和聚合物的粘合强度以及透气性方面存在显著差异。实际应用包括在标准细胞培养条件（例如 37°C 和 100%湿度下 2-3 周）和高达 5 达因/厘米的剪切冲击下，对多层、膜集成器官芯片设备进行稳定性测试。此外，使用微结构化的粘合剂粘合设备，证明了非毒性荧光标记纳米颗粒的时间和剪切依赖性摄取。我们的结果表明：(a) 可以设计、制造和测试简单和复杂的微设备，时间少于 1 小时；(b) 即使在生理剪切力条件下，这些微设备也能稳定数周；(c) 可用于维持细胞单层和 3D 细胞培养系统。
