Multicellular Cell Seeding on a Chip: New Design and Optimization towards Commercialization.
Multicellular Cell Seeding on a Chip: New Design and Optimization towards Commercialization.
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DOI：
10.3390/bios12080587
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发表时间：
2022-08-01
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本文展示了在微流体平台上的实验和深入的理论研究（包括模拟和分析解决方案），以优化其设计并用于3D多细胞共培养应用，例如，创建用于研究肺动脉高压（PAH）等疾病的组织芯片模型。组织微流控芯片通常具有两个以上的通道来接种细胞和供应培养基。这些通道通常由微柱制成的屏障隔开。这些微柱的结构和它们的间距的优化是以前没有考虑的，特别是对于快速和成本有效的制造方面，以扩大规模和商业化。我们的实验和理论（COMSOL模拟和分析解决方案）结果表明：（i）当两个柱上的压降显著大于通道宽度上的压降时，该平台成功地进行了细胞接种。圆形柱可用于六边形或其他形状的位置。(ii)在这项工作中，圆形的职位是制造和使用的第一次。它们提供优异的阻隔效果，即，防止液体和凝胶从一个通道迁移到另一个通道。(iii)至于快速和具有成本效益的生产，我们的计算机辅助制造（CAM）模拟证实，当利用微加工技术时，圆形柱的制造比六边形柱更容易和更快速，例如，用于形成母模的微铣削，即，用于聚合物注射成型的垫片。这一发现为使用微铣削代替昂贵的洁净室（软）光刻技术快速、经济、大规模制造组织芯片开辟了可能性，从而提高了通过热塑性聚合物注射成型生产生物芯片并实现商业化。
This paper shows both experimental and in-depth theoretical studies (including simulations and analytical solutions) on a microfluidic platform to optimize its design and use for 3D multicellular co-culture applications, e.g., creating a tissue-on-chip model for investigating diseases such as pulmonary arterial hypertension (PAH). A tissue microfluidic chip usually has more than two channels to seed cells and supply media. These channels are often separated by barriers made of micro-posts. The optimization for the structures of these micro-posts and their spacing distances is not considered previously, especially for the aspects of rapid and cost-efficient fabrication toward scaling up and commercialization. Our experimental and theoretical (COMSOL simulations and analytical solutions) results showed the followings: (i) The cell seeding was performed successfully for this platform when the pressure drops across the two posts were significantly larger than those across the channel width. The circular posts can be used in the position of hexagonal or other shapes. (ii) In this work, circular posts are fabricated and used for the first time. They offer an excellent barrier effect, i.e., prevent the liquid and gel from migrating from one channel to another. (iii) As for rapid and cost-efficient production, our computer-aided manufacturing (CAM) simulation confirms that circular-post fabrication is much easier and more rapid than hexagonal posts when utilizing micro-machining techniques, e.g., micro-milling for creating the master mold, i.e., the shim for polymer injection molding. The findings open up a possibility for rapid, cost-efficient, large-scale fabrication of the tissue chips using micro-milling instead of expensive clean-room (soft) lithography techniques, hence enhancing the production of biochips via thermoplastic polymer injection molding and realizing commercialization.
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影响因子：
1.2
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Xu, Sulei;Li, Xiang;He, Pingnian
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