On the development of a microfluidic instrument for preclinical cell analysis

Abstract

The evolution of a new drug is initiated by testing new compounds in a preclinical laboratory setting. The methods for discovering new drugs involve scrutiny of a drug’s efficacy on a cell model of a disease. Current methods of creating these cell culture models are highly dependent on consumables and manual time. New methods such as high-throughput screening of drugs has progressed the ability to test multiple drugs on cells. However, current high-throughput methods lack the ability to create live cultures that are biologically relevant and can be manipulated non-invasively. The research presented here furthers drug analysis technology by creating a microfluidic instrument for the generation of individual reactions under 1ul in volume. This is a continuous system that can create an unlimited amount of live cell cultures. Validation of this system is both the identification of antibiotic resistance and creating cancer models in microfluidic droplets and being able to monitor these cultures non-invasively in real time. For biologically relevant models a new method of forming 3D cell cultures within the microfluidic droplets is presented. These form structures that are equivalent to micro-tumours within a 600nl reaction. A novel aspect of this research is that breast cancer models are treated within the microfluidic droplets and show the same gene expression signature as found in literature from larger cultures. This demonstrates the integrity of the new method in reducing the amount of cells and reagents required to perform reactions. The treatment and monitoring of the cultures within a bench top instrument allows for thousands of reactions to be evaluated for preclinical analysis.