Modular System for Integrated Culture of Multiple Microphysiological Systems with Microbiome

Applications

This technology is a microfluidic system for co-culturing multiple microphysiological organ systems with applications as a research tool and for testing drug efficacy, pharmacokinetics, and toxicity.

Problem Addressed

The vast majority of drug candidates fail in clinical trials of safety and efficacy, with only 10% of drugs entering clinical stage trials achieving FDA approval. This incredibly high fail-rate indicates that the current pre-clinical testing practice of using animal models is insufficient to predict how the human body will respond to a drug. Therefore, there is a dire need to develop humanized models to validate pre-clinical candidate drugs. Recent advances in tissue engineering technology has led to “organ on a chip” microfluidic devices that can serve as a model of human organ function, however, these technologies have thus far been limited by a short length of culture time and modular integration of multiple organ systems. These inventors have created a revolutionary human microphysiological system that integrates up to seven organ systems.

Technology

This technology is an open microfluidic device designed to co-culture multiple microphysiological organ systems. The device is composed of three layers. The first layer contains a mixing well and individual wells into which cells from different organs are plated. This layer has precisely engineered spillways that passively distribute culture medium from the mixing well into each microphysiological organ well in ratios that reflect systemic circulation. Next, a membrane separates the cell culture layer from a lower layer that has integrated on-board pneumatic pumps. The pumps in this lower layer circulate oxygen and nutrients in each individual well, and resupply the mixing well with media that has passed through each of the organ wells. Each pump can be independently programmed to meet the specific oxygen and culturing needs of the cells in each well. This microfluidic device has been used to co-culture up to seven microphysiological systems for up to 3 weeks. The system has been used to co-culture tissues including pancreas, gut, liver, endometrial tissue, lung, heart, brain, kidney, skin, and muscle. Additionally, this system can facilitate co-culture with microbiota to model the metabolic effects that these organisms have on physiology and drug responses. Finally, this microfluidic system is highly modular and the number of microphysiological systems and individual tissue types can be tailored to answer specific pharmacology, metabolism, or toxicology questions.

Advantages

  • Integrated microfluidic system for co-culture of multiple microphysiological organ systems
  • Highly tunable design
  • Composed of chemically inert materials to reduce adsorption of growth factors and drugs
  • On-board pneumatic pumping system reduces footprint of fluidic device
  • Precise control of fluid flow both between wells and within individual wells
  • Culture with or without microbiota