Construction And Applications Of Multifunctional Inertial Microfluidic Chip With Microstructures

With the rapid progress of promising microfluidic technologies,much attention in the field of inertia effect has been directed to microfluidic devices.Compared with other existing systems,inertial microfluidic techniques have various significant advantages,such as continuous efficient processing,non-invasive operation without special labels and excellent performance in manipulating particles or fluids without external fields.However,inertial microfluidic techniques still need to be explored to satisfy the growing need of biomedical technology,industrial production,analytical chemistry,and material science.It is because grand challenges stemming from some drawbacks of these techniques(e.g.,high consumption of sheath fluid reagent,laborious multi-pump operational procedures,challenging production of high-aspect-ratio microchannel,complicated fabrication process of multilayered structures,and high standard fluid viscoelasticity)have not been entirely overcome.In the present study,we presented three types of straightforward and efficient platforms using the unique combinations of different microstructures and inertial microfluidic chips(contraction and expansion channels with microstructures,semicircle channels with microstructures,spiral microchannels with microstructures).Using these different types of platforms,we successfully achieved various applications including rare cell separation,sample mixing,blood plasma extraction,and particle/cell manipulation.Our study showed practical potential for improving the commercialization process of inertial microfluidic technologies in biomedicine,clinical diagnostics,and industrial production applications.The results obtained in the present work are as follows:1.In this study,a passive multistage microfluidic device was developed using a unique combination of inertial microfluidics(contraction and expansion channels)with microstructures in turn.The serial complementary combination of the two different mechanism sorting methods achieved high-throughput and highly sensitive cell separation.Firstly,the microfluidic device was designed using AutoCAD software,and the chrome plated glass substrate was used as photomask,then the mold was produced by photolithographic process,and finally the microfluidic device with distinct structures was generated using soft lithography.The device comprised four functional regions:(i)filter region,(ii)inertial focusing region,(iii)inertial separation region,and(iv)steric hindrance region.The filter region could effectively block foreign debris to avoid downstream clogging in microchannels.Under the influence of inertial lift forces and unique secondary flow in the inertial focusing region,relatively larger rare cells and a few blood cells passed through the center channel of the inertial separation region and enter the steric hindrance region.Subsequently,based on cell size and deformability,the steric hindrance region could further remove the unseparated blood components and enrich rare cells.2.The separation mechanisms and performance of designed device were first investigated using theoretical calculations and experimental studies of fluorescence-labeled microspheres.Simultaneously,the optimal conditions for cell separation were also explored.Afterward,as an actual application of this microfluidic system,tumor cells(MCF-7 and He La cells)and leukemic(K562)cells spiked into 1% Hct blood were successfully separated with throughput of 2.24 × 107 cells/min,cell recovery of > 90%,and an impressive cell enrichment of > 2.02 × 105-fold.Compared with existing rare cell isolation technologies,the current microfluidic device possesses high throughput,cell recovery,and cell enrichment.It provides a new microfluidic technology for establishing micro-diagnosis platform for cancer patients3.In this study,a passive microfluidic strategy was developed by combining two types of chaotic convection micromixer technology.Based on this renewed understanding,we propose a novel micromixer consisting of inertial microfluidics(low-aspect-ratio semicircle channels)interspersed with a series of sequenced microstructures,which can produce synergistic combination of two kinds of vortices(Dean vortices and helical vortices)to promote the fluid mixing.Firstly,the microfluidic device was designed using AutoCAD software,and the mold was produced by photolithographic process,then the microfluidic device with distinct structures was generated using soft lithography with PDMS.Additionally,in order to further prove the advantages of micromixer,the same low-aspect-ratio semicircle channel without microstructures was designed and fabricated.4.The fluid motion mechanism and distribution of designed devices were first investigated using numerical simulation.Afterward,to explore the advantage of the design strategy and the function of microstructures on fluid motion in low-aspect-ratio semicircle channels,fluid mixing was simulated using Volume-Of-Fluid module,and the experimental studies by pumping fluorescein solution were also processed.The results demonstrated that Dean vortices induced semicircle channels and helical vortices induced microstructures could increase the interfacial area in the vertical and horizontal plane of microchannels for diffusive mixing.Compared with existing mixer technologies,the advantages of the passive micromixer employed here include:(i)the relatively simple design and fabrication in a single lithography step,(ii)high efficient mixing over a wide range of flow rate,(iii)easy operation and no external stimulus required,(iv)considerable flexibility in mixing path and interface surface,and(v)convenient topology optimization for enhancing mixing performance and integrating with other microfluidic systems.The novel inertial microfluidics approach provides a new direction for developing a variety of microfluidic mixers.5.In this study,a novel inertial microfluidic system was developed using a unique combination of inertial spiral channel interspersed with a series of sequenced microstructures.Firstly,the microfluidic device was designed using AutoCAD software,and the mold was produced by photolithographic process,then the microfluidic device with distinct structures was generated using soft lithography with PDMS.In the section of “particle motion characterization”,eight low-aspect-ratio spiral microchannels(device 1~8)were designed,which consisted of four-loop channels with one inlet and one outlet.Device 1,as blank control,has not sequenced microcantilevers in microchannels.Other devices were designed by sequentially arranging different size and spacing microcantilevers in microchannels.In the sections of “particle application” and “biologic application”,the device 3(one outlet)was changed into device 3A(three outlets)with other conditions unchanged.The three outlets(outlet 1,outlet 2,and outlet 3)of device 3A are used for demonstrate the advantage of isolation efficiency in our inertial platform.6.The dynamic characterization of fluorescent particles was first performed in these designed devices,which were helpful to explore inertial platform design for further particle and cell application.Afterward,the studies of particle applications(particle focusing and sorting)and cell applications(cell focusing,separation,liquid-medium recovery,and blood plasma extraction)were conducted to demonstrate the versatility and practicability of the proposed systems.Compared with other techniques,this approach has huge competitive advantages benefiting from simplified fabrication(single-layer and large-dimension channel design),reproducible and high stability(long-term operation with consistent quality),easy-to-use manner(without the assistance of sheath fluid),and high processing throughput(~m L min-1)without the need for parallelization design,which can support volume-produce and high-efficient operation.The study provides a novel microfluidic technology for developing micro-diagnosis instrument in biomedical applications.