Development Of Microfluidic Chip For High-Throughput Drug Screening Technology

The development and screening of new drugs has always been a large-scale,long-term project,often subject to factors such as low efficiency,high cost,difficulty,and large sample consumption,leading to slow development of new drugs,especially in the screening of anticancer drugs.With the rapid development and application of microfluidic technology,microfluidic chips have received more and more attention in the field of anticancer drug screening because of its unique advantages,such as analysis of miniaturization and rapidization,integration,high throughput and good bioaffinity.This paper focused on the requirements of high-throughput drug screening in anticancer drugs.According to micro-nano flow and transmission theory and micro-nano fabrication technologies,the integrated microfluidic chips for high-throughput anticancer drug screening was designed and developed.This designed chip consists of two functional regions including the drug-generating area and the single-cell capture area,which can implement efficiently capture and location of single cells,single drug screening and combination drug screening of anticancer drug.It meets the requirements of rapid,high-throughput,improving drug screening efficiency.Considering the functional requirements of the chip and its unique properties of fluid at the micro-scale,the whole chip was designed as a two-layer structure.The drug-generating area and the single-cell capture area were arranged from left to right.In the structural design and geometrical dimensions of the overall chip,combined with Hagen-Poiseu’s law in fluid mechanics and computational fluid dynamics(CFD),the core structure size of the chip(microtrap positioning radius R,micro-trap internal gap b,micro-trap spacing m,aspect ratio core mixing region h/w)was numerically simulated,and the optimal geometric parameters suitable for the research chip are obtained.On the geometrical parameters of the determined chip model,the inlet speed was simulated,providing a reference for the experiments.According to the simulation,drug testing and functional testing were carried out on the chip,to explore different inlet velocity,the initial concentration of cells on different trapping effect and the time required to reach steady state and other factors,to determine the optimum initial velocity and the inlet concentration of cells.In the cell based on the well-positioned,drug screening was studied on the chip,to explore the effect of a single drug with a drug combination,the effect on cell viability chip.It provided the foundation for study of integrated design and function of the application of subsequent chip.The research indicated that when R=6μm,b=5μm,m=25μm,h/w=1/4,the inlet drive speed V=100μm/s,the chip could achieve good results.In the experimental study,the functional testing and drug research in the chip were separately performed.In the functional testing,using different driving speeds(0.2 μl/s-0.8 μl/s)and initial cell concentration(1×105/ml-1.5×106/ml),to explore the impact on the position and state of single cell,the optimal experimental conditions were determined(V=0.6μl/s-0.8μl/s,Ccell=1×106/ml).On the basis of cell experiments,single drug screening and combination drug screening were studied.In single drug screening,the optimal drug concentration suitable for the chip was determined:cisplatin,lobaplatin and gemcitabine hydrochloride was 50μg/ml,paclitaxel was 20μg/ml.Paclitaxel has the strongest effect.In combination drug screening,four kinds of effects of different drug combination were studied,which showed synergistic.In a word,the chip designed in this paper can be applied to the screening function of anticancer drugs.Through the establishment of microfluidic experimental platform,the screening process of anticancer drugs was realized in microfluidic cell chip,which provided strong support for the research of new drug development and pharmacological effects.