| Project Detail |
This project will develop high-throughput 3D cell culture devices with perfusion by interfacing microfluidics and droplet printing technologies and subsequently applying them to model neuro-development disorders. For decades, 2D cell culture followed by animal testing has been the standard for therapeutic drug discovery. 3D systems have the potential to recreate more faithful physiological conditions (cell interactions, gradients, perfusion, flow). Thus, they are expected to be more predictive for efficacy and toxicity than 2D systems and minimize the use of animals. However, there is currently no 3D model which enables high-throughput (HT) and perfusion at once: spheroids and organoids in plates can be HT but without perfusion, pressure-driven microfluidics has perfusion but is not HT, droplet microfluidics is HT but cannot handle large drug libraries and has no perfusion. Here, we will leverage the physics of wetting and capillarity to design chamber arrays with liquid-trapping geometries, which can be entirely operated by external droplet injection. We will set up designs and protocols for the embedding of cells in 3D hydrogel matrices and submit them to perfusion of medium and drug, including uniform or gradient conditions in each chamber. We will demonstrate the HT interfacing with droplet printers. Finally, we will apply the device to screen compounds and monitor the modulation of microglia (the immune cell of the brain) inflammation that affects the lives of >2 million preterm babies every year. |
