| Project Detail |
Novel microfluidic platform for 3D high-throughput drug screening
A combination of drugs can lead to the discovery of new therapies through synergy by boosting the effects of existing drug and accelerating drug discovery for poorly addressed diseases. However, predicting and establishing synergies requires high-throughput screening (HTS) in advanced cell models. A previously developed microfluidic platform for HTS of drug combinations in 3D culture enables high-density routine assays and results with a throughput increase of up to 100 times. The 3D culture models are better suited to predict later physiological responses, increasing the probability of successful drug development. The ERC-funded SYNEBIO project aims to demonstrate the applicability of the HTS microfluidic platform using existing screens for breast cancer cells.
Drug combinations can lead to the discovery of novel drugs by increasing efficacy or lowering toxicity through synergy. This can boost existing drugs, rescue drug candidates, and accelerate drug discovery for yet poorly addressed diseases. However, predicting synergy is difficult, and finding synergies requires high-throughput screening (HTS) in advanced cell models. Current solutions propose either HTS in 2D cell cultures or low throughput assays in 3D cell cultures, but not both.
On the basis of a technology developed in the ERC-funded AbioEvo project, we devised an innovative microfluidic platform for 3D culture and HTS of drug combinations. Miniaturization densifies routine 3D assays, resulting in a throughput increase of 10 to 100 times. Fluidic automation reduces liquid handling 500 times for a 100x100 drug library at a 10-point dose-response combinatorial screening. Furthermore, 3D culture models better predict later physiological responses, thus increasing the success probability of downstream drug development stages. We have shown dose-response measurements of 144 antibiotic combinations on bacteria on a single chip.
In this POC, we aim to demonstrate the applicability of our technology to human cells and benchmark it based on existing screens for breast cancer cells. We will adapt the cell culture conditions and data analysis, perform market analysis, and examine industrialization feasibility. This will put us in a position to create a spin-off to reach the preclinical drug screening market and identify the most promising therapeutic areas. Indeed, the technology has the potential to screen for synergistic drug combinations at an earlier stage of the drug discovery process (thanks to miniaturization and automation) while providing a more reliable cellular response for later stages (thanks to 3D culture). |
