(338c) Microfluidic Cell Isolation Technology for Drug Testing of Single Tumor Cells and Their Clusters
In this study, we present a pipette-based microfluidic cell isolation (MCI) technology that is capable of conducting single cell resolution drug assays with a small number of tumor cells or their clusters present in small sample volumes (e.g. 10 â?? 100 cells in 10 mL). A micropipette is used to deliver both the carrier fluid as well as the assay fluid through a microchannel network to nanoliter-sized fluidic traps. The method can digitize the assay fluid producing an array of stationary droplets laden with single cells or their clusters. To establish proof-of-principle of our pipette-based MCI method, we use breast cancer cells (MCF-7) and a chemotherapy drug, doxorubicin. We demonstrate that (i) our method can efficiently isolate single MCF-7 cells without appreciable loss during the pipetting and digitization steps (ii) our method can isolate clustered tumor cells with a distribution of 2-22 cells/cluster (iii) the droplet surrounded by an immiscible carried fluid does not adversely affect the viability of anchorage-dependent breast cancer cells (iv) although individual tumor cells display significant heterogeneity in the kinetics of uptake of doxorubicin, they all undergo apoptosis when a critical amount of drug is accumulated (v) the overall viability of clusters is improved simply due to a greater number of cells per cluster suggesting that a CTC cluster has a better chance of surviving chemotherapy drug treatment than a single CTC. Thus, our microfluidic cell isolation technology has significant potential as a simple yet efficient tool for time-resolved analysis of rare tumor cells and their clusters.