Highly efficient capture of circulating tumor cells by microarray in a microfluidic device

Abstract

We established a versatile microarray-based platform that is able to capture single target cell from large background populations. To show the efficacy of the device, we consider the challenging application of detecting circulating tumor cells (CTCs) - where the target cell appears in a concentration of about one cell in a billion. The cells were incubated with a biotinylated antibody cocktail, targeted cells are extracted on a streptavidin microarray in a herringbone design microfluidic chip. The accessibility to the captured target cell on our device facilitates subsequent recovery of the targets for further analysis. Our previous results (Brinkmann et al., 2015) have shown that analyzing blood samples from cancer patients with our platform reaches, and partly outreaches, gold standard performance, demonstrating feasibility for clinical application. Currently, we aim to optimize the design of our device to further increase the capturing rate. We tried 3 different herringbone designs of our microfluidic chips (which we will refer to as the HA, HB and HC chips), 3 different patterns of streptavidin depositions (dots with a pitch of 25 μm, 50 μm, and a homogenous coating). The combination of 50 μm pitch dots, the HC chip showed the highest capturing rate. In the viability test, 90% tumor cells were alive after capturing. Furthermore, we can easily open the PDMS cap to access the alive tumor cells, which allows us to do further downstream analysis. Our device allows clinical researchers to freely choose the desired antibody and detect different rare bio-targets. This facilitates virtually arbitrary capturing of target species and therefore a wide spread application in the biomedical sciences.