A portable and reconfigurable multi-organ platform for drug development with onboard microfluidic flow control

被引:76
作者
Coppeta, J. R. [1 ]
Mescher, M. J. [1 ]
Isenberg, B. C. [1 ]
Spencer, A. J. [1 ]
Kim, E. S. [1 ]
Lever, A. R. [1 ]
Mulhern, T. J. [1 ]
Prantil-Baun, R. [1 ]
Comolli, J. C. [1 ]
Borenstein, J. T. [1 ]
机构
[1] Draper, Mat & Microfabricat Directorate, Cambridge, MA 02139 USA
关键词
DEVELOPMENT SUCCESS RATES; SECRETORY PROTEIN CC16; HUMAN HEPATOCYTES; CELLS; LIVER; CHIP; FABRICATION; METABOLISM; DELIVERY; ALBUMIN;
D O I
10.1039/c6lc01236a
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:134 / 144
页数:11
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