A microfluidic platform for personalized throughput drug screening using cancer spheroids

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Cancer remains the leading cause of death worldwide. For many patients, standard-of-care therapy involves surgical removal of the primary tumour, however the surgery is often followed by the growth of secondary microtumours at distant locations. Therapies are required that are either toxic toward micrometastases or that lock them in the dormant state, yet there is a challenge to assess the effectiveness of drugs for microtumors grown in different environments with varying protective properties. ** Currently, there is lack of tools that recreate micrometastasis for the evaluation of therapeutic agents. Animal models are expensive, labor- and time-consuming; generally, provide only endpoint analyses and arguably, are not relevant for humans. Two-dimensional cell culture yields microtumor models that differ considerably in their properties and phenotype from those grown in physiological 3D environments, and thus may not serve as an efficient model for drug screening. Multicellular cancer spheroids (MCS) bridge 2D cell culture and animal models, and have very promising applications in drug screening however presently used MCS models for drug screening suffer from a number of limitations. ** This proposal aims at the development of a microfluidic (MF) platform for screening of new drugs and optimization of existing drug formulations for therapeutic cancer treatment. The technology utilizes large arrays of uniformly-sized MCSs derived from patient-derived cells that are grown in a biomimetic hydrogel in a MF device, the delivery of drugs to these MCSs under close-to-physiological flow conditions, and throughput screening of drug efficacy for MCS treatment. The MF-MCS platform includes multiple parallel rows of microwells, with up to 100 MCSs in each row. The platform enables systematic variation of a particular factor between different rows, thus enabling screening of drug efficacy for MCSs grown from a particular cell type in a specific environment, and the effect of drug dosages and combinations, to name just a few, all in one series of experiments conducted in a single MF device. **************