Research Impact Of Hypoxic Microenvironment On Tumor Cytotoxicity And Metabolize On Microfluidic Chip

Hypoxia is the most common tumor microenvironment and represents an independent prognostic factor for different cancer types. Although many chemotherapeutic agents have good pharmacological activity during screening research in vitro, poor efficiency or severe rejection reactions are observed in clinical trials due to the reduced oxygen contents in tumor tissues. Thus, it is important to take the effects of oxygen tensions into consideration in further studies of anticancer drug screening and clinical chemotherapy.In this paper, we firstly constructed a microfluidic device with an oxygen gradient to study the hypoxia dependent cytotoxicity of anticancer drug under the microenvironment of hypoxia. Oxygen concentration gradually changed and the resulting oxygen concentration gradient range was from 2% to 11%, which accurately simulates the microenvironment of the tumor cells in the body. During the drug test, the results showed that the oxygen content has an influence on the effectiveness of anticancer drugs.This paper constructed a kind of three layers of oxygen gradient with eight channels array microfluidic chip combining with mass spectrometry by solid-phase extraction chip for studying the metabolism of cells under different oxygen environment. This paper studied the metabolite behavior under oxygen gradient. This device can not only observe the cells physiological behavior under different oxygen environment at the same time and at a one-time control experiment, but also come true parallel stimulation and regional test. Lactic acid could separate and enrich on solid-phase extraction chip, meanwhile by mass spectrum real-time detection, the cells metabolize different lactic acid under various oxygen concentration. With the reduction of oxygen content, the lactic acid metabolized trend to increase. So the union of microfluidic chip and mass spectrometry can more intuitive and more accurately detect cell metabolites, which provides theoretical basis for the study of tumor cell under hypoxia.