Capture of circulating melanoma cells using a microfluidic device

Abstract

Purpose: Circulating tumor cells (CTCs) are present in metastatic cancers and may potentially be used for disease profiling and prognostication. Herein we developed a microfluidic device to isolate circulating melanoma cells (CMCs).

Methods: Human uveal melanoma Mel 270 and Mel 290, and mouse melanoma B16F10, B16LS9 cell lines were cultured. Murine intraocular xenografts were performed via trans-scleral inoculation or mice were injected with melanoma cells via the tail vein. A microfluidic system, casted in polydimethylsiloxane (PDMS), was used to capture viable tumor cells from PBS, spiked blood and peripheral whole blood samples mediated by the interaction of target CMCs with antibodies-coated microchannels under precisely controlled flow conditions.

Results: The microfluidic-based system exhibited high capture rates for B16F10, B16LS9, Mel 270 and Mel 290 cell lines in PBS- or blood-spiked screening experiments. Increased cell capture rates were found with relatively slow flow rates and high cell concentrations. Using an experimental metastasis model established by tail vein injection in severe combined immunodeficient mice, we successfully isolated CMCs from peripheral blood samples. The system further allowed detection of CMCs in a mouse model of xenografts with metastatic melanoma.

Conclusions: The study shows antibody-based capture of circulating melanoma cells using a microfluidic device in tumor-bearing mice. This microfluidic-based system exhibits promise as a clinical tool for capturing circulating uveal melanoma cells.

Keywords: 744 tumors • 745 uvea