The Overall Release of Circulating Tumor Cells by Using Temperature Control and Matrix Metalloproteinase-9 Enzyme on Gelatin Film

Abstract

The efficient capture and high-activity release of circulating tumor cells (CTCs) remain a challenge for the microfluidic chip. We have fabricated a dual-mode gelatin-polydimethylsiloxane (PDMS) microfluidic chip with a sawtooth columnar microstructure of channels that can capture the efficiency of this substrate up to 95%. Increasing the gelatin temperature to physiologic temperature (37 °C) with a baking table facilitates the overall release of CTCs. With melting of the gelatin substrate, the cells will enter into the PDMS corresponding channel; however, the released cells will be wrapped by a layer of gelatin, which may affect further proliferation of the cells. Another way to release CTCs is to use a matrix metalloproteinase-9 (MMP-9) enzyme to dissolve the gelatin and release the tumor cells with high cellular viability. This dual-mode microfluidic chip has been applied successfully to capturing and releasing CTCs, thus serving as a powerful clinical tool that facilitates the subsequent bioanalysis of CTCs for clinical and biological research.