Rapid Prototyping of Multilayer Microphysiological Systems.
Rapid Prototyping of Multilayer Microphysiological Systems.
复制标题
DOI：
10.1021/acsbiomaterials.0c00190
复制
发表时间：
2021-07-12
影响因子：
5.8
通讯作者：
Koppes AN
中科院分区：
文献类型：
--
作者：
Hosic S;Bindas AJ;Puzan ML;Lake W;Soucy JR;Zhou F;Koppes RA;Breault DT;Murthy SK;Koppes AN
与传统的二维静态细胞培养相比，微流控芯片上的器官旨在实现更多的生物悬浮体外实验。通常，这种器件是通过聚(二甲基硅氧烷)(PDMS)软光刻制造的，这提供了优点(例如，高特征分辨率)和缺点(例如，原型时间/成本)。在这里，我们报告了通过激光切割和双面粘合剂组装的多层、不含PDMS的热塑性芯片上器官的台式制造，克服了传统PDMS光刻的一些限制。切割和组装的芯片对原型来说是经济的(每个芯片2美元)，可以在几个小时内并行制造，并且与Luer兼容。与上皮系Caco-2细胞和原代人小肠有机质具生物相容性。与对照静态Transwell培养相比，培养在芯片上的Caco-2和有机物形成了融合的单层，表达了低渗透性的紧密连接。与对照组相比，芯片上的Caco-2细胞分化∼的速度快4倍，包括粘液增加。为了证明切割和组装的健壮性，我们制造了一种双膜三层芯片，集成了2D和3D隔室，具有可接近的尖端和基底侧流室。作为概念验证，我们在多层接触隔间内共培养了一个人类、分化的单层和完整的3D有机体。上皮细胞呈3D组织结构，细胞器类物质在邻近单层附近扩张，保留增殖干细胞10天以上。总而言之，切割和组装提供了快速和经济地制造微流控设备的能力，从而为开发各种几何结构的芯片上器官以研究多细胞组织提供了一种引人注目的制造技术。
Microfluidic organs-on-chips aim to realize more biorelevant in vitro experiments compared to traditional two-dimensional (2D) static cell culture. Often such devices are fabricated via poly(dimethylsiloxane) (PDMS) soft lithography, which offers benefits (e.g., high feature resolution) along with drawbacks (e.g., prototyping time/costs). Here, we report benchtop fabrication of multilayer, PDMS-free, thermoplastic organs-on-chips via laser cut and assembly with double-sided adhesives that overcome some limitations of traditional PDMS lithography. Cut and assembled chips are economical to prototype ($2 per chip), can be fabricated in parallel within hours, and are Luer compatible. Biocompatibility was demonstrated with epithelial line Caco-2 cells and primary human small intestinal organoids. Comparable to control static Transwell cultures, Caco-2 and organoids cultured on chips formed confluent monolayers expressing tight junctions with low permeability. Caco-2 cells-on-chip differentiated ∼4 times faster, including increased mucus, compared to controls. To demonstrate the robustness of cut and assemble, we fabricated a dual membrane, trilayer chip integrating 2D and 3D compartments with accessible apical and basolateral flow chambers. As proof of concept, we cocultured a human, differentiated monolayer and intact 3D organoids within multilayered contacting compartments. The epithelium exhibited 3D tissue structure and organoids expanded close to the adjacent monolayer, retaining proliferative stem cells over 10 days. Taken together, cut and assemble offers the capability to rapidly and economically manufacture microfluidic devices, thereby presenting a compelling fabrication technique for developing organs-on-chips of various geometries to study multicellular tissues.
登录
查看更多内容
在药物发现的边界，片上的器官。
DOI：
10.1038/nrd4539
发表时间：
2015-04
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
Esch EW;Bahinski A;Huh D
通讯作者：
Huh D
影响因子：
6.1
作者：
Aran K;Sasso LA;Kamdar N;Zahn JD
通讯作者：
Zahn JD
影响因子：
7.4
作者：
Heo, Yun Seok;Cabrera, Lourdes M.;Takayama, Shuichi
通讯作者：
Takayama, Shuichi
影响因子：
19
作者：
Huh, Dongeun;Hamilton, Geraldine A.;Ingber, Donald E.
通讯作者：
Ingber, Donald E.
影响因子：
1.6
作者：
Imura, Yuki;Asano, Yasuyuki;Yoshimura, Etsuro
通讯作者：
Yoshimura, Etsuro