The drug development pipeline is severely limited by a lack of reliable tools for prediction of human clinical safety and efficacy profiles for compounds at the pre-clinical stage. Here we present the design and implementation of a platform technology comprising multiple human cell-based tissue models in a portable and reconfigurable format that supports individual organ function and crosstalk for periods of up to several weeks. Organ perfusion and crosstalk are enabled by a precision flow control technology based on electromagnetic actuators embedded in an arrayed format on a microfluidic platform. We demonstrate two parallel circuits of connected airway and liver modules on a platform containing 62 electromagnetic microactuators, with precise and controlled flow rates as well as functional biological metrics over a two week time course. Technical advancements enabled by this platform include the use of non-sorptive construction materials, enhanced scalability, portability, flow control, and usability relative to conventional flow control modes (such as capillary action, pressure heads, or pneumatic air lines), and a reconfigurable and modular organ model format with common fluidic port architecture. We demonstrate stable biological function for multiple pairs of airway-liver models for periods of 2 weeks in the platform, with precise control over fluid levels, temperature, flow rate and oxygenation in order to support relevant use cases involving drug toxicity, efficacy testing, and organ-organ interaction.
A portable and reconfigurable multi-organ platform for drug development with onboard microfluidic flow control.
一种便携式、可重构的多器官药物研发平台,带有板载微流体流量控制功能
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作者:Coppeta J R, Mescher M J, Isenberg B C, Spencer A J, Kim E S, Lever A R, Mulhern T J, Prantil-Baun R, Comolli J C, Borenstein J T
| 期刊: | Lab on a Chip | 影响因子: | 5.400 |
| 时间: | 2016 | 起止号: | 2016 Dec 20; 17(1):134-144 |
| doi: | 10.1039/c6lc01236a | 研究方向: | 其它 |
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