Development And Application Research On Inertial Microfludic Cell Enrichment Chips And Devices

Inertial microfluidic cell enrichment chips and separation devices are of great significance for pre-cancer prevention and treatment.However,their high processing costs and professional operation of precision supporting devices limit their promotion.Therefore,the development of low-cost devices without environmental use restrictions is of great significance for early cancer treatment.Based on inertial microfluidic chip,a low-cost microfluidic device is developed with no environmental restrictions and easy operation,which mainly includes the following three parts:(1)High-throughput multilayer thin film chips are designed by means of horizontal array stacking,and the enrichment experiments of algae species and cancer cells are realized by using them.This chapter designs a stacked with complex three-dimensional flow control path film chips.This chip consists of seven functional layers,including a parallel channel layer,three glue layers,two converging channel layer and a export layer.The core layer is parallel channel layer.This layer is composed of 12 radial arrangement of serpentine channel.This chip uses the method of array configuration to improve flux while maintaining one inlet and two outlet.This chip which stacked seven function layers still has the good transparency and the very small thickness.Then the device was used to concentrate the particles,which included algae filament and breast cancer cells.After concentration,it was found that the device could achieve better recovery rate and higher concentration multiple for these particles.Continuous repeated use can achieve better results.After the multi-step serial concentration of tumor cells with very low concentration,the concentration multiple is about 14 and the recovery rate can reach~80%,while the sample size has been successfully reduced from 15ml to less than 1 ml.(2)A kind of power free cancer cell separation device was designed by using passive regulating valve,double inlet screw chip and double hole booster.In this chapter,aiming at the real-time field detection requirements of low-cost microfluidic devices,a handheld microfluidic device that can completely rely on the mechanical structure to achieve the separation of cancer cells is designed.The integrated device consists of two parts:composite chip and double hole booster.Firstly compound chip design mainly contains double entry spiral structure and two passive flow regulating valve.The flow channel structure need be reused to explore new chip processing technology as well as the sealing way.Machining chips encapsulation film be used to make the chip encapsulation process.The results of particle experiments has good separation effect.At the same time,this part improve the simple passive flow control valve structure and processing technology to provide a stable driving velocity.The study of several factors influencing the passive control valve include PDMS film through hole diameter,chamber size,chamber height.The control of various parameters found that the passive valve has a good flow stability effect between pressure of 100~200 kPa.The device can meet the requirements of chip injection,including two boosters(10 ml and 60 ml),two syringes and two 15 ml test tubes.Each booster is mainly divided into three parts,namely booster chamber,baffle and pressure spring.Meanwhile,the influence of pressure spring parameters on the injection pressure is studied.Finally,the separation effect of the device for7?m and 20?m particles was tested.After separation,the recovery efficiency of large particles at the inner outlet was as high as 95.81%.The purity of large particles was as high as80.72%.Then,the device was used to separate the blood samples of breast cancer cells with a relatively high concentration of doping in the blood(10~5 counts/ml).After separation,the collection rate of cancer cells in the collection solution was 88.75%.The purity was 16.48%.At the same time,the blood samples(500 counts/ml)doped with cancer cells at a lower concentration were separated.After the separation by the device,the recovery rate reached 78.67%,and the blood cell removal rate exceeded 96%.(3)Completed the design of a small multifunctional cancer cell processing instrument and verified its separation and enrichment performance for cancer cells(MCF-7,PC,Hela cells)in three blood samples.Firstly,the instrument consists of cell separation,enrichment and cleaning functions.This system use a diaphragm pump to drive and the different sizes of constant flow resistance chips for liquid injection velocity.The way is lower cost and stable flow.The machining include double entry spiral chip separation and enrichment of functional unit.To reduce the equipment volume and convenient use,The system use plug type kits as instrument liquid filling device and each function has a corresponding kit.The instrument structure is mainly divided into three layers,which include the circuit layer,the component layer and the kit layer.Lithium battery is used as the power supply.The air circuit and liquid circuit are controlled by touch screen solenoid valve to achieve various functions.After the assembly,the appearance size is about 190*160*140 cubic millimeter and the weight of the whole machine is only 2 kg.It need debug the software and hardware of the prototype and determine the timing parameters of each functional module.Then it need debug the flow resistance chip parameter selection and flow stability performance of the instrument injection system.Finally the prototype is used to separate and enrichment three kind of mixed samples from cancer cells(MCF-7,PC,Hela).After the instrument sorting samples respectively,red blood cells of removal rate of three kinds of cancer cells has reached more than 94.5%.The purity of three kinds of cancer cells were more than 13%.The capture rate of three kinds of cancer cells to is more than 87%.It can be seen that has good separation effect.The enrichment function was continued to concentrate the collected solution after separation.The recovery rate of all three types of cancer cells was more than 89%.The concentration ratio of the collected solution after enrichment and the initial solution was more than 2.6 times.