i3S - Instituto de Investigação e Inovação em Saúde Universidade do Porto Rua Alfredo Allen, 208 Porto 4200-135 Portugal.
INEB - Instituto de Engenharia Biomédica Universidade do Porto Rua Alfredo Allen, 208 Porto 4200-135 Portugal.
Adv Sci (Weinh). 2021 Feb 8;8(8):2003273. doi: 10.1002/advs.202003273. eCollection 2021 Apr.
Organ-on-a-chip technology promises to revolutionize how pre-clinical human trials are conducted. Engineering an in vitro environment that mimics the functionality and architecture of human physiology is essential toward building better platforms for drug development and personalized medicine. However, the complex nature of these devices requires specialized, time consuming, and expensive fabrication methodologies. Alternatives that reduce design-to-prototype time are needed, in order to fulfill the potential of these devices. Here, a streamlined approach is proposed for the fabrication of organ-on-a-chip devices with incorporated microactuators, by using an adaptation of xurography. This method can generate multilayered, membrane-integrated biochips in a matter of hours, using low-cost benchtop equipment. These devices are capable of withstanding considerable pressure without delamination. Furthermore, this method is suitable for the integration of flexible membranes, required for organ-on-a-chip applications, such as mechanical actuation or the establishment of biological barrier function. The devices are compatible with cell culture applications and present no cytotoxic effects or observable alterations on cellular homeostasis. This fabrication method can rapidly generate organ-on-a-chip prototypes for a fraction of cost and time, in comparison to conventional soft lithography, constituting an interesting alternative to the current fabrication methods.
器官芯片技术有望彻底改变临床前人体试验的进行方式。构建能够模拟人体生理学功能和结构的体外环境对于开发药物和个性化医疗的更好平台至关重要。然而,这些设备的复杂性需要专门的、耗时且昂贵的制造方法。为了充分发挥这些设备的潜力,需要减少设计到原型的时间的替代方案。在这里,提出了一种简化的方法,用于使用 xurography 的改编来制造带有内置微执行器的器官芯片设备。该方法可以使用低成本的台式设备在数小时内生成多层、膜集成的生物芯片。这些设备能够承受相当大的压力而不会分层。此外,该方法适用于器官芯片应用所需的柔性膜的集成,例如机械致动或建立生物屏障功能。这些设备与细胞培养应用兼容,对细胞稳态没有细胞毒性作用或可观察到的改变。与传统的软光刻相比,这种制造方法可以快速生成器官芯片原型,成本和时间仅为其一小部分,是当前制造方法的有趣替代方案。