Drug-Combination Platform

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Description: Drug Combinations have been an advantageous for the treatment of cancer as targeting two pathways can lead to an improvement in efficacy and has been shown to aid in overcoming resistance mechanisms. Clinical trials involving combinational therapies are very costly and time consuming, thus most pharmaceutical companies first assess drug combinations in-vitro. Current screening methods make the evaluating a large set of drug combinations very timely and expensive. Microfluidic techniques have attempted to increase the number of potential drug combinations. However, drug concentrations can only be diluted linearly, which prevents the full elucidation of IC50 values Multiplex Drug-Combination Screening Platform A multiplexed drug combination-screening chip enables effective drug combination in-vitro screening of both live cell and patient-derived-xenograft models. A ‘Bias Tree’ mixing structure enables log scale dilutions for obtaining accurate IC50 parameters of the combinations, and ‘Sudoku array’ inlets enable the optimal number of inlets for large-scale system integration. Proof-of-concept design was implement on an 8-drug combination chip utilizing MCF7, SUM159, and a pancreatic cancer PDX cell line. Combining 28 drug combinations, 5 mixing ratios, 2 sphere sizes, and 5 replicates, a total of 1,400 drug efficacy screening experiments was accomplished on a single chip. Applications ·         Platform for high-throughput, cell based, drug combination screening method ·         Platform for chemical synthesis condition optimization ·         Chemical mixing applications Advantages ·         High-throughput drug combination screening of multiple drugs ·         Thousands of spheres formed from a single cell loading step ·         “Biased tree” mixer enables log-scale concentration gradients ·         Large scale integration ·         Reliable and consistent spheroid formation and controllable size