Scaffold-integrated microchips for end-to-end in vitro tumor cell attachment and xenograft formation.
Scaffold-integrated microchips for end-to-end in vitro tumor cell attachment and xenograft formation.
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DOI：
10.1142/s2339547815500065
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发表时间：
2015-12
期刊：
影响因子：
--
通讯作者：
Parekkadan B
中科院分区：
文献类型：
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作者：
Lee J;Kohl N;Shanbhang S;Parekkadan B
微流控技术通过分离罕见循环肿瘤细胞（ctc）用于诊断和预后，极大地推进了癌症研究。由于难以恢复和生长高保真的分离细胞，分离的ctc的表征受到限制。在这里，我们提出了一种策略，将3D支架集成到微流体装置中，作为可转移的底物，可以在设备操作后很容易地分离出来，作为移植组织床在体内连续使用。水凝胶支架在结合之前被纳入PDMS流体室，并在流体接触后在室中再水化。水凝胶基质完全填充了液腔，显著提高了比表面积与体积比，在显微镜下可以直接观察到。计算模型定义了不同的流量和压力状态，以指导芯片的操作条件。作为使用模型细胞系的概念验证，我们证实了人类前列腺肿瘤细胞在微流控支架芯片上的附着，支架的整体检索，以及支架连续植入具有保存异种移植物发育的小鼠模型。随着捕获效率的进一步提高，这种方法可以为从生物液体到小鼠异种移植物的分离癌细胞的连续研究提供端到端平台。
Microfluidic technologies have substantially advanced cancer research by enabling the isolation of rare circulating tumor cells (CTCs) for diagnostic and prognostic purposes. The characterization of isolated CTCs has been limited due to the difficulty in recovering and growing isolated cells with high fidelity. Here, we present a strategy that uses a 3D scaffold, integrated into a microfludic device, as a transferable substrate that can be readily isolated after device operation for serial use in vivo as a transplanted tissue bed. Hydrogel scaffolds were incorporated into a PDMS fluidic chamber prior to bonding and were rehydrated in the chamber after fluid contact. The hydrogel matrix completely filled the fluid chamber, significantly increasing the surface area to volume ratio, and could be directly visualized under a microscope. Computational modeling defined different flow and pressure regimes that guided the conditions used to operate the chip. As a proof of concept using a model cell line, we confirmed human prostate tumor cell attachment in the microfluidic scaffold chip, retrieval of the scaffold en masse, and serial implantation of the scaffold to a mouse model with preserved xenograft development. With further improvement in capture efficiency, this approach can offer an end-to-end platform for the continuous study of isolated cancer cells from a biological fluid to a xenograft in mice.