Development of an Integrated Microfluidics System for Multi-level High Content Screening of Anti-tumor Drugs

Drug development is a time consuming and expensive process, which generally requires 10-15 years and a total cost of USD1.5 billion to develop a new drug. Drug screening is the first step in the process where identification of lead compounds and elimination of false candidates from thousands to millions of compounds are critical to the subsequent steps. Thus, it is very important for pharmaceutical companies to develop and adopt efficient and cost-effective screening technologies. High-throughput screening (HTS) allows screening of millions of chemicals for their biological or pharmacological activities to identify active compounds, and serve as a starting point for further drug design and development. High-content screening (HCS) is a complementary technology to HTS, allows for the evaluation of biochemical and morphological parameters in intact cell-based biological systems. However, HTS is expensive and requires large consumption of reagents, and HCS suffers from low throughput, slow speed, and a lack of microenvironments to accurately reflect the effects of a compound on cellular behavior. Therefore, there is a great demand for new high-throughput and high-content platforms that would reduce reagent consumption and mimic the in vivo environment to which cells are exposed, for efficient screening of potential drug candidates. In this project, we propose to develop an integrated microfluidics system that combine HTS with HCS in an integrated platform that mimics the physiological and pathological microenvironments for cell-based assays. The technology will provide a microenvironment to simulate the in vivo conditions of cell growth, communication, and migration, for high-throughput and high-content screening of drugs targeting/affecting cell-cell interactions. We will use the microfluidic device to screen for drugs/drug combinations that may alter/interfere with the cell-cell interactions occurring during tumor metastasis. The technology and products, once developed, will offer a novel tool for efficient drug screening with reduced drug development time and cost, and be beneficial to pharmaceutical companies as well as patients and the society.