Grant: Collaborative Health Research Projects (NSERC partnered)

OBJECTIVE: This project will develop a microfluidic system to culture, characterize, image, and screen cells within a single automated, portable platform, with large potential impact to improve cell-based drug screening. BACKGROUND: The 2-D monolayer-based method of cell culture is well established in molecular and cell biology. Recently, there has been increased interest in 3-D cell culture, in which cells are embedded in a material that mimics the ECM. Interaction between cells and the ECM in vivo regulates differentiation, migration, and many other functions. As a cancer model, the tissue culture environment can have a dramatic influence on cell behaviour, such as modified morphology, gene expression, and proliferation. This phenomenon will have a crucial impact in the pharmacological response of a tumour cell to therapeutic agents. Thus, drugs developed using a 2-D screening system may not subsequently have the same activity against solid tumours, contributing to the high attrition rate in drug development. APPROACH: As a new paradigm for cell-based testing, this microscale platform will address a gap between in vitro and animal models by providing a simple, scalable tool to apply standardized protocols used in cellular response assays. This research will combine a hydrogel-based method 3-D of culturing cells with on-chip microfluidic flow control for precise fluid handling. Breast tumour cells will be seeded into an array of chambers where they can form tumour-like aggregates. We will use this system will to conduct controlled, repeated treatments and monitoring of the effects of therapeutic drugs and drug combinations on the cells. We will use the on-chip mixing and fluid handling capability to recreate more realistic pharmacokinetic profiles of compounds to examine the relationship between dose and concentration with response. The use of transparent materials allows the integration of these chips onto high-throughput imaging systems, with advantages in speed, cost, and efficiency. This platform will thus provide a means to assess the impact of treatment standards as well as new treatments designed to achieve more personalized therapy.