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3D 打印贴壁微流控技术用于从整个器官中分离和分析生物标志物。

3D printed conformal microfluidics for isolation and profiling of biomarkers from whole organs.

机构信息

Department of Industrial and Systems Engineering, Virginia Tech, Blacksburg, VA 24061 USA.

出版信息

Lab Chip. 2017 Jul 25;17(15):2561-2571. doi: 10.1039/c7lc00468k.

DOI:10.1039/c7lc00468k
PMID:28632265
Abstract

The ability to interface microfluidic devices with native complex biological architectures, such as whole organs, has the potential to shift the paradigm for the study and analysis of biological tissue. Here, we show 3D printing can be used to fabricate bio-inspired conformal microfluidic devices that directly interface with the surface of whole organs. Structured-light scanning techniques enabled the 3D topographical matching of microfluidic device geometry to porcine kidney anatomy. Our studies show molecular species are spontaneously transferred from the organ cortex to the conformal microfluidic device in the presence of fluid flow through the organ-conforming microchannel. Large animal studies using porcine kidneys (n = 32 organs) revealed the profile of molecular species in the organ-conforming microfluidic stream was dependent on the organ preservation conditions. Enzyme-linked immunosorbent assay (ELISA) studies revealed conformal microfluidic devices isolate clinically relevant metabolic and pathophysiological biomarkers from whole organs, including heat shock protein 70 (HSP-70) and kidney injury molecule-1 (KIM-1), which were detected in the microfluidic device as high as 409 and 12 pg mL, respectively. Overall, these results show conformal microfluidic devices enable a novel minimally invasive 'microfluidic biopsy' technique for isolation and profiling of biomarkers from whole organs within a clinically relevant interval. This achievement could shift the paradigm for whole organ preservation and assessment, thereby helping to relieve the organ shortage crisis through increased availability and quality of donor organs. Ultimately, this work provides a major advance in microfluidics through the design and manufacturing of organ-conforming microfluidic devices and a novel technique for microfluidic-based analysis of whole organs.

摘要

将微流控设备与原生复杂生物结构(如整个器官)相连接的能力,有可能改变研究和分析生物组织的模式。在这里,我们展示了 3D 打印可用于制造与整个器官表面直接接口的仿生顺应性微流控器件。结构光扫描技术实现了微流控器件几何形状与猪肾解剖结构的 3D 地形匹配。我们的研究表明,在器官顺应性微通道中存在流体流动的情况下,分子物质会自发地从器官皮质转移到顺应性微流控器件。使用猪肾进行的大动物研究(n = 32 个器官)表明,器官顺应性微流中的分子物质特征取决于器官保存条件。酶联免疫吸附测定(ELISA)研究表明,顺应性微流控器件可从整个器官中分离出临床相关的代谢和病理生物标志物,包括热休克蛋白 70(HSP-70)和肾损伤分子 1(KIM-1),分别在微流控装置中检测到高达 409 和 12 pg mL。总的来说,这些结果表明,顺应性微流控器件能够实现一种新颖的微创“微流控活检”技术,用于从整个器官中分离和分析生物标志物,时间间隔在临床相关范围内。这一成就有可能改变整个器官保存和评估的模式,从而通过增加供体器官的可用性和质量来缓解器官短缺危机。最终,这项工作通过设计和制造器官顺应性微流控器件以及用于整个器官的基于微流控的分析的新方法,为微流控领域提供了重大进展。

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