Research On The Integrated Microfluidic System For Particle Sorting,Trapping And Fluid Mixing And Transportation

Biological particles(such as cells)separation and single cell trapping have shown great potential in a variety of applications,such as,medical and biological research fields as well as environment detection.Particles sorting technology is the first step in the clinical diagnosis and treatment process.For example,it will be helpful for early diagnosis of cancer by detecting the several tumor cells in millions of blood cells.Single cell trapping and analysis can allow the observation of single cell behavior and show great potential in genetic metabolism,genetic engineering and drug detection.To achieve cell sorting and trapping,lots of technologies exist currently,such as,based on the interaction between antibody and antigen and fluorescence activated cell sorting(FACS)which requires multiple complicated sampling routines,labels,cumbersome and expensive,limiting widespread use.Microfluidic technology owns lots of advantages,such as,small volume of sample,low cost,short analysis time and small size.It will be desirable to develop an integrated chip by incorporating particle sorting,trapping,fluid mixing and transporting functions.Thus,the first step is to address how to sort,trap single particle and mix nutrients or drugs for long-term observation and further analysis of cells in the integrated microfluidic chip.At bipolar electrode arrays,we first investigated the mechanism of single cell or particle trapping under a rotating electric field by considering the rotating field induced charged electroosmosis(ICEO),dielectrophoresis(DEP),and electrorotation theories.Based on ICEO and DEP,a new method for large-scale single particle trapping is proposed.Via combining theoretical analysis and simulation results,influence of many key parameters,such as,particle size,conductivity,sample concentration,electrode size,voltage,and frequency,on single cell trapping performance is analyzed experimentally.Single yeast cell or PS particle can be trapped efficiently at an array of bipolar electrodes by negative DEP force or ICEO through adjusting applied frequency and conductivity.Simulated and experimental results demonstrate this method owns unique advantages in single particle trapping.For effective mixing of solutions with different conductivities,we further researched on the mixing process in aqueous solutions with different conductivities.Based on an enhanced model for AC electrothermal in aqueous solutions with high conductivity,we built a 3D simulation model by introducing three dimensional electrodes embedded on the channel sides and investigated the key geometrical and electric parameters.For mixing the aqueous solution with a lower conductivity,we analyzed the mechanism of the fixed potential induced charged electroosmosis.The influence of AC signal applied to the gate electrode on zeta potential and slip velocity was investigated in detail,showing the asymmetric ICEO vortexes on the electrode surface can be used for improving micromixing.We also studied the effect of phase difference and signal waveform on mixing performance.The micromixers are designed and fabricated accordingly.A series of experiments are carried out to investigate the influence of key parameters and the theory of the fixed potential induced charged electroosmosis was modified.A critical analysis of our micromixers in comparison with different micromixer designs is performed by a comparative mixing index,demonstrating the great mixing performance of current micromixers.At last,based on single particle trapping and micromixing components,we exploited an integrated microfluidic chip for achieving multiple functions,such as,cell separation,single cell manipulation and trapping.In the separation area,the label-free separation of cells and microbeads can be achieved first by defective DEP barriers using actuation electrodes.We built a simulation model and analyzed the influence of several key factors,such as,structure size,applied frequency,solution conductivity,and inlet velocity,on the process of sorting yeast cells and PS beads,achieving good separation efficiency.In the particle trapping and manipulation area,the structure of bipolar electrode array is further optimized and investigated.Under a rotating electric field,the simulation model is built in terms of travelling wave DEP force,traditional DEP force,electric rotational torque and ICEO flow.We studied the movements of yeast cells and PS beads at the bipolar electrodes and proposed a new method for trapping,propelling,and steering the yeast cells bidirectionally at the bipolar electrode edges.In terms of the theoretical and simulated results,the key parameters that affected the cell's behavior were investigated experimentally.Single cell-cell pairing can be realized through changing cell concentration and electrode size,showing great potential in cell-cell fusion and intercellular interactions.Furthermore,after cell separation,single cell manipulating and micromixing parts are integrated together,we experimentally conducted the mixing and transporting glucose solutions with different concentrations.Single yeast cell can be trapped stably for long term observation and analysis after sorting at a constant flow rate when the glucose solutions were supplied using micromixing components.Above all,this integrated microfluidic chip system owns multiple functions,such as particles sorting,single cell trapping,propelling,fluid mixing and transporting,and is easy to fabricate,low cost,and simple operation,holding particular promise for various biomedical applications and academic research.