Ultra-low Aspect Ratio Inertial Microfluidic Chip Construction And Cell Manipulation Research

Cell manipulation techniques facilitate the isolation and purification of target cells,beneficial to biomedical research applications,clinical diagnosis,drug discovery,and so on.Circulating tumor cells are free cells shed from primary tumors into peripheral blood and can be used for early cancer detection and treatment monitoring.The traditional methods of cell counting,sorting and detection use flow cytometry,density gradient centrifugation,fluorescence or magnetically activated cell separation.Although these methods are mature and reliable,the systems used are complex,labor-intensive and cumbersome to operate.Target cells may be lost.Inertial microfluidics technology can precisely manipulate particles or cells in microchannels,and can achieve the functions of cell enrichment and sorting.And it has the advantages of high throughput,simple operation,low price,low sample consumption,easy integration with sensors,etc.,which can meet the use of POCT.However,the current inertial microfluidic technology still has challenges such as complex design,contradictory flux and efficiency,etc.For this reason,this study designed an inertial microfluidic chip with ultra-low aspect ratio.Micro-pillars array accelerate the inertial migration of particles and improve cell focusing and sorting performance.The main test results are as follows:1.Utilizing the unique integration of ordered micro-pillars array and curved channels,a single-layer micro-channel platform with ultra-low AR ratio(1;9)was developed.Using ESI-CFD software analysis,it was demonstrated that the introduction of micro-pillars array in curved microchannels can change and regulate the spiral vortices and Dean vortices by introducing flow rates.2.Using the developed curved inertial microchannel with ultra-low AR ratio(1:9),the production and generation of multivortices were systematically explored by varying the number of micro-pillars in the microchannel,the operating flow rate,the length of the micropillars,and the channel height.It is demonstrated that the purposeful modulation of micropillars in curved microchannel can induce Dean and spiral vortices of different sizes.3.Using the combination of micro-pillars and curved channels distributed in iso-sequence,a sheath flow-assisted ultra-low AR ratio(1:18)curved inertial microfluidic chip was drawn using Auto CAD software.The focusing performance of the chip is characterized by particles of different sizes,which can be collected at different outlets through size differences,providing a theoretical basis for the sorting of cancer cells in blood.4.Using the ultra-low aspect ratio curved microfluidic chip assisted by different diluted blood and two types of cancer cell perfusion sheath flow,when a separate experiment is performed,it can be collected from different outlets under the same co-flow rate conditions,which proves the design of the chip structure has the ability to sort circulating tumor cells from diluted whole blood.5.Using the combination of micro-pillars and spiral channels distributed in equal sequence,the spiral inertial microfluidic chip with ultra-low AR ratio(1:18)without sheath flow assistance was drawn using Auto CAD software.The changes of vortex flow in the microchannel were explored using computational fluid dynamics simulations,and it was proved that the micropillar array can complete the secondary flow enhancement.6.Using the spiral inertial microfluidic chip accelerated by secondary flow,three sizes of microspheres and three types of cancer cells were successfully focused.The enhanced secondary flow achieves insensitivity to flow rate and particle size while achieving cell focusing,which is suitable for the development of microflow cytometers.This experiment explored the secondary flow acceleration effect of micro-pillars in curved and spiral channels,and designed microfluidic devices for particle manipulation and cell manipulation.The developed device has the characteristics of ultra-low AR ratio,which makes the chip device easier to manufacture and can be used to simulate cancer cell sorting and cancer cell focusing,which provides a platform for sample preparation for further diagnosis and research.