A High Throughput Microfluidic Chip With Precise Environmental Control for Cell and Organoid Culture

SUMMARY

• Microfluidic chips are useful in applications such as drug discovery assays because of their ability to replicate dynamic cellular environments in a high-throughput and automatable fashion. Despite this, currently available chips are limited by experimental variation, inability to track single cell behavior, and the requirement to custom design a unique chip for each set of experiments. 
• The inventors developed a novel microfluidic technology that uses passive diffusion for nutrient and ligand delivery to the cultured cells. This enables delivery of a wide range of dynamic signaling inputs to the cells without disrupting cell culture with sheer fluid flow.
• The product is a microfluidic chip that can culture 1500 independent conditions simultaneously. The device can accommodate adherent or non-adherent cells in monolayer or organoid format. Also included is a software package that can be used to program the on-chip pumps to prepare experimental dilutions.
• A series of experiments showed the capability of the microfluidic chip to culture sensitive cell lines for periods up to a week with no compromise in viability. Using the on-chip machinery for various effector molecule dilutions produced expected changes in cellular gene expression.

FIGURE

(A) Schematic design overview of the passive diffusion technology illustrating how fast fluid flow in one layer of the chip does not impact the culture area of the chip. (B) Fraction of active 3T3 fibroblast cells as a function of TNFa concentration introduced to the culture. TNFa dilutions were performed via pipette (blue circles) or on-chip microfluidics pumps (red circles). Results demonstrate the capability of the device to automatically model dynamic signaling environments.

ADVANTAGES

ADVANTAGES

• 150-fold increase in throughput 
• Adaptable to different experiments
• No sheering of cells
• On-chip dilution preparation

APPLICATIONS

• Drug discovery
• Research tools

September 15, 2019

Proof of concept

Patent Pending

Licensing

Savas Tay

• PCT/US18/32727