Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA.
Vanderbilt Institute for Integrative Biosystems Research and Education, Vanderbilt University, Nashville, TN, USA.
Lab Chip. 2021 Dec 7;21(24):4814-4822. doi: 10.1039/d1lc00744k.
Fabrication of microfluidic devices by photolithography generally requires specialized training and access to a cleanroom. As an alternative, 3D printing enables cost-effective fabrication of microdevices with complex features that would be suitable for many biomedical applications. However, commonly used resins are cytotoxic and unsuitable for devices involving cells. Furthermore, 3D prints are generally refractory to elastomer polymerization such that they cannot be used as master molds for fabricating devices from polymers ( polydimethylsiloxane, or PDMS). Different post-print treatment strategies, such as heat curing, ultraviolet light exposure, and coating with silanes, have been explored to overcome these obstacles, but none have proven universally effective. Here, we show that deposition of a thin layer of parylene, a polymer commonly used for medical device applications, renders 3D prints biocompatible and allows them to be used as master molds for elastomeric device fabrication. When placed in culture dishes containing human neurons, regardless of resin type, uncoated 3D prints leached toxic material to yield complete cell death within 48 hours, whereas cells exhibited uniform viability and healthy morphology out to 21 days if the prints were coated with parylene. Diverse PDMS devices of different shapes and sizes were easily cast from parylene-coated 3D printed molds without any visible defects. As a proof-of-concept, we rapid prototyped and tested different types of PDMS devices, including triple chamber perfusion chips, droplet generators, and microwells. Overall, we suggest that the simplicity and reproducibility of this technique will make it attractive for fabricating traditional microdevices and rapid prototyping new designs. In particular, by minimizing user intervention on the fabrication and post-print treatment steps, our strategy could help make microfluidics more accessible to the biomedical research community.
通过光刻技术制造微流控器件通常需要专门的培训和洁净室的使用。作为替代方法，3D 打印可以以具有成本效益的方式制造具有复杂特征的微器件，这些微器件适用于许多生物医学应用。然而，常用的树脂具有细胞毒性，不适合涉及细胞的器件。此外，3D 打印通常对弹性体聚合具有抗性，因此不能用作从聚合物（聚二甲基硅氧烷，或 PDMS）制造器件的母模。已经探索了不同的后打印处理策略，例如热固化、紫外线照射和硅烷涂层，以克服这些障碍，但没有一种被证明是普遍有效的。在这里，我们表明，沉积一层薄薄的聚对二甲苯，一种常用于医疗器械应用的聚合物，可使 3D 打印件具有生物相容性，并允许它们用作弹性体器件制造的母模。当将其放置在含有人类神经元的培养皿中时，无论树脂类型如何，未涂层的 3D 打印件都会浸出有毒物质，导致在 48 小时内完全细胞死亡，而如果打印件涂有聚对二甲苯，则细胞表现出均匀的活力和健康的形态，直至 21 天。不同形状和尺寸的各种 PDMS 器件可以很容易地从涂有聚对二甲苯的 3D 打印模具中浇铸出来，没有任何可见的缺陷。作为概念验证，我们快速原型制作并测试了不同类型的 PDMS 器件，包括三腔灌注芯片、液滴发生器和微井。总的来说，我们建议该技术的简单性和可重复性将使其成为制造传统微器件和快速原型新设计的有吸引力的方法。特别是，通过最大限度地减少用户在制造和后打印处理步骤中的干预，我们的策略可以帮助使微流控技术更容易为生物医学研究界所接受。
