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

Lab Chip. 2016 Dec 20;17(1):134-144. doi: 10.1039/c6lc01236a.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Bronchi / cytology
  • Cells, Cultured
  • Coculture Techniques
  • Cytochrome P-450 CYP3A / metabolism
  • Drug Discovery
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism
  • Hepatocytes / cytology
  • Hepatocytes / metabolism
  • Humans
  • Magnetic Fields
  • Microfluidics / instrumentation
  • Microfluidics / methods*
  • Microscopy, Fluorescence

Substances

  • Cytochrome P-450 CYP3A