Thin cell culture membranes in organ-on-a-chip (OOC) devices are used to model a wide range of thin tissues. While early and most current platforms use microporous or fibrous elastomeric or thermoplastic membranes, there is an emerging class of devices using extra-cellular matrix (ECM) protein-based membranes to improve their biological relevance. These ECM-based membranes present physiologically relevant properties, but they are difficult to integrate into OOC devices due to their relative fragility. Additionally, the specialized fabrication methods developed to date make comparison between methods difficult. This work presents the development and characterization of a method to produce ultrathin matrix-derived membranes (UMM) in OOC devices that requires only a preassembled thermoplastic device and a micropipette, decoupling the device and UMM fabrication processes. Control over the thickness and permeability of the UMM is demonstrated, along with integration of the UMM in a device enabling high-resolution on-chip microscopy. The reliability of the UMM fabrication method is leveraged to develop a medium-throughput well-plate format device with 32 independent UMM-integrated samples. Finally, proof-of-concept cell culture experiments are demonstrated. Due to its simplicity and controllability, the presented method has the potential to overcome technical barriers preventing wider adoption of physiologically relevant ECM-based membranes in OOC devices.

中文翻译：

---

器官芯片装置中超薄细胞外基质衍生膜的可调节原位合成

芯片器官 (OOC) 装置中的薄细胞培养膜用于模拟各种薄组织。虽然早期和大多数当前平台使用微孔或纤维弹性体或热塑性膜，但有一类新兴的设备使用基于细胞外基质 (ECM) 蛋白质的膜来提高其生物相关性。这些基于 ECM 的膜具有生理相关特性，但由于其相对脆弱，很难集成到 OOC 设备中。此外，迄今为止开发的专门制造方法使得方法之间的比较变得困难。这项工作介绍了一种在 OOC 设备中生产超薄基质衍生膜 (UMM) 的方法的开发和表征，该方法仅需要预组装的热塑性设备和微量移液器，从而将设备和 UMM 制造过程解耦。演示了对 UMM 厚度和磁导率的控制，以及将 UMM 集成到支持高分辨率片上显微镜的设备中。利用 UMM 制造方法的可靠性来开发具有 32 个独立 UMM 集成样本的中等通量孔板格式装置。最后，演示了概念验证细胞培养实验。由于其简单性和可控性，所提出的方法有可能克服阻碍在 OOC 设备中更广泛采用生理相关 ECM 膜的技术障碍。