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Robotic fluidic coupling and interrogation of multiple vascularized organ chips.
Nature Biomedical Engineering ( IF 28.1 ) Pub Date : 2020-01-27 , DOI: 10.1038/s41551-019-0497-x
Richard Novak 1 , Miles Ingram 1 , Susan Marquez 1 , Debarun Das 2 , Aaron Delahanty 1 , Anna Herland 1, 3 , Ben M Maoz 1, 4, 5 , Sauveur S F Jeanty 1, 6 , Mahadevabharath R Somayaji 2 , Morgan Burt 1 , Elizabeth Calamari 1 , Angeliki Chalkiadaki 1 , Alexander Cho 2 , Youngjae Choe 1 , David Benson Chou 1, 7 , Michael Cronce 1 , Stephanie Dauth 1, 4 , Toni Divic 1 , Jose Fernandez-Alcon 1, 6 , Thomas Ferrante 1 , John Ferrier 1, 4 , Edward A FitzGerald 1 , Rachel Fleming 1 , Sasan Jalili-Firoozinezhad 1, 8 , Thomas Grevesse 1, 4 , Josue A Goss 1, 4 , Tiama Hamkins-Indik 1 , Olivier Henry 1 , Chris Hinojosa 1, 6 , Tessa Huffstater 1 , Kyung-Jin Jang 1, 6 , Ville Kujala 1, 4, 6 , Lian Leng 1, 6 , Robert Mannix 1, 9 , Yuka Milton 1 , Janna Nawroth 1, 4, 6 , Bret A Nestor 1 , Carlos F Ng 1 , Blakely O'Connor 1, 4 , Tae-Eun Park 1 , Henry Sanchez 1 , Josiah Sliz 1, 6 , Alexandra Sontheimer-Phelps 1, 10 , Ben Swenor 1 , Guy Thompson 1, 6 , George J Touloumes 1, 4 , Zachary Tranchemontagne 1 , Norman Wen 1, 6 , Moran Yadid 1, 4 , Anthony Bahinski 1, 11 , Geraldine A Hamilton 1, 6 , Daniel Levner 1, 6 , Oren Levy 1 , Andrzej Przekwas 2 , Rachelle Prantil-Baun 1 , Kevin K Parker 1, 4 , Donald E Ingber 1, 9, 12
Affiliation  

Organ chips can recapitulate organ-level (patho)physiology, yet pharmacokinetic and pharmacodynamic analyses require multi-organ systems linked by vascular perfusion. Here, we describe an 'interrogator' that employs liquid-handling robotics, custom software and an integrated mobile microscope for the automated culture, perfusion, medium addition, fluidic linking, sample collection and in situ microscopy imaging of up to ten organ chips inside a standard tissue-culture incubator. The robotic interrogator maintained the viability and organ-specific functions of eight vascularized, two-channel organ chips (intestine, liver, kidney, heart, lung, skin, blood-brain barrier and brain) for 3 weeks in culture when intermittently fluidically coupled via a common blood substitute through their reservoirs of medium and endothelium-lined vascular channels. We used the robotic interrogator and a physiological multicompartmental reduced-order model of the experimental system to quantitatively predict the distribution of an inulin tracer perfused through the multi-organ human-body-on-chips. The automated culture system enables the imaging of cells in the organ chips and the repeated sampling of both the vascular and interstitial compartments without compromising fluidic coupling.

中文翻译:

多血管器官芯片的机器人流体耦合和询问。

器官芯片可以概括器官水平(病理)生理学,但药代动力学和药效学分析需要通过血管灌注连接的多器官系统。在这里,我们描述了一个“询问器”,它采用液体处理机器人、定制软件和集成的移动显微镜,用于自动培养、灌注、培养基添加、流体连接、样本收集和原位显微镜成像,最多可对一个内部的十个器官芯片进行成像。标准组织培养箱。机器人询问器保持了八种带血管的双通道器官芯片(肠、肝、肾、心脏、肺、皮肤、血脑屏障和脑)培养 3 周,当通过它们的介质储库和内皮衬里的血管通道通过普通血液替代品间歇地流体耦合时。我们使用机器人询问器和实验系统的生理多室降阶模型来定量预测通过多器官人体芯片灌注的菊粉示踪剂的分布。自动化培养系统能够对器官芯片中的细胞进行成像,并在不影响流体耦合的情况下对血管和间质隔室进行重复采样。我们使用机器人询问器和实验系统的生理多室降阶模型来定量预测通过多器官人体芯片灌注的菊粉示踪剂的分布。自动化培养系统能够对器官芯片中的细胞进行成像,并在不影响流体耦合的情况下对血管和间质隔室进行重复采样。我们使用机器人询问器和实验系统的生理多室降阶模型来定量预测通过多器官人体芯片灌注的菊粉示踪剂的分布。自动化培养系统能够对器官芯片中的细胞进行成像,并在不影响流体耦合的情况下对血管和间质隔室进行重复采样。
更新日期:2020-01-27
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