The Study Of A Microfluidic Chip For Single Microsphere Capture Array And Single Cell Mechanical Analysis

Microfluidic technology is a technique for manipulation of fluid(generally laminar flow)on the submicron to micrometer scale.It can be combined with microelectromechanical systems(MEMS)process technology to create micro/nano devices with coupled electro-acousto-optic effects.It can realize a variety of manipulation methods on the same chip to efficiently complete complex biochemical reactions,so it is called Lab-on-a-chip.With proper designs,microfluidic chips can achieve high throughput,processing tens to hundreds of cells in parallel.The size of the microchannels is comparable to that of cells(typically a few to a few tens of microns),making microfluidic technology highly versatile at both single cell and even single molecule levels.Thus,the microfluidic chip is a platform that is particularly suitable for single cell analysis.Its advantages are mainly reflected in:(1)high-throughput parallelization operations that can process multiple cells at the same time;(2)integration of multi-step operations such as cell capture,separation and lysis,in-situ detection and save the cost of experiment;(3)a small amount of reagents is needed to accurately control the ion concentration,temperature,carbon dioxide concentration and other factors outside the cell environment,model the extracellular environment in the body,improve detect data confidence.In this study,we designed and fabricated a high-flux single-cell/particle capture microarray based on fluid mechanics combined with microfluidic cell capture technology and cell mechanical property stress measurement technology.It provides a basis for high-precision cell biomechanical performance detection.Two functions of single particle capture and cellular mechanical performance characterization on the same microfluidic chip are achieved.The main contents of this work are as follows:Firstly,the force applied on particles in micro-scale fluids is analyzed based on the theory of fluid dynamics,and a microstructure array capable of high-throughput single microsphere/single cell capture is designed,and the split ratio formula is derived.After that,the flow field distribution of each microchannel is analyzed by multi-physics simulation software(COMSOL),and the theoretical formula is verified.Secondly,the fabrication of the microfluidic chips was achieved by soft photolithography techniques.The negative photoresist is selected for UV lithography micromachining on a 4-inch silicon wafer,and the transparent polymer material polydimethylsiloxane(PDMS)is used for replica of the mold to obtain the microfluidic chip.Finally,microfluidic platform was built and tested.The array chip was first used to capture polystyrene microspheres one by one.The results showed that the capture efficiency could reach 100%.Then Hela cells with similar size of the microspheres were taken into the chip for capture.Flow rate on both sides of the cells was adjusted to increase the pressure drop.The amount of deformation of the cell could be measured to characterize the biomechanical parameters of the cell.