Division of Biotechnology, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.
University of Chinese Academy of Sciences, Beijing, China.
Biotechnol J. 2024 Jan;19(2):e2300390. doi: 10.1002/biot.202300390.
Organ-on-a-chip technology has shown great potential in disease modeling and drug evaluation. However, traditional organ-on-a-chip devices are mostly pump-dependent with low throughput, which makes it difficult to leverage their advantages. In this study, we have developed a generic, pump-free organ-on-a-chip platform consisting of a 32-unit chip and an adjustable rocker, facilitating high-throughput dynamic cell culture with straightforward operation. By utilizing the rocker to induce periodic fluid forces, we can achieve fluidic conditions similar to those obtained with traditional pump-based systems. Through constructing a gut-on-a-chip model, we observed remarkable enhancements in the expression of barrier-associated proteins and the spatial distribution of differentiated intestinal cells compared to static culture. Furthermore, RNA sequencing analysis unveiled enriched pathways associated with cell proliferation, lipid transport, and drug metabolism, indicating the ability of the platform to mimic critical physiological processes. Additionally, we tested seven drugs that represent a range of high, medium, and low in vivo permeability using this model and found a strong correlation between their P values and human Fa, demonstrating the capability of this model for drug absorption evaluation. Our findings highlight the potential of this pump-free organ-on-a-chip platform as a valuable tool for advancing drug development and enabling personalized medicine.
器官芯片技术在疾病建模和药物评估方面显示出巨大的潜力。然而，传统的器官芯片设备大多依赖于泵，通量较低，这使得难以发挥其优势。在本研究中，我们开发了一种通用的、无泵的器官芯片平台，由一个 32 单元的芯片和一个可调节的摇床组成，便于进行高通量的动态细胞培养，操作简单。通过利用摇床来诱导周期性的流体力，我们可以实现类似于传统泵基系统获得的流体条件。通过构建肠道芯片模型，我们观察到与静态培养相比，屏障相关蛋白的表达和分化肠细胞的空间分布有显著增强。此外，RNA 测序分析揭示了与细胞增殖、脂质转运和药物代谢相关的富集途径，表明该平台能够模拟关键的生理过程。此外，我们使用该模型测试了七种代表高、中、低体内渗透性的药物，发现它们的 P 值与 Fa 值之间存在很强的相关性，表明该模型在药物吸收评估方面具有良好的性能。我们的研究结果突出了这种无泵器官芯片平台作为推进药物开发和实现个体化医疗的有价值工具的潜力。
