Studies On Dynamic Behaviors Of Magnetic Beads And Its Mechanisms Of Enhanced Mixing And Separation In Magnetophoretic Microfluidic Chips

Microfluidics is one of the interdisciplinary frontiers in science and technology. The microfluidicchip can integrate many chemical and biological processes including sample-getting, mixing, reaction,separation, detection as well as cell cultivation, sorting and lysis within an area of only several squarecentimeters so that it can replace the conventional laboratory. The chip has the advantages of very lowreagent consumption, extremely fast detection and plentiful analyzed information. The greatadvantages of microfluidic analysis system make its potential applications very extensive in biology,medicine, energy saving, environmental motoring and protection.The development of microfluidics not only depends on interdisciplinary researches in the fields ofbiological, chemical, material and electronics, etc., but also depends on the mastering of heat and masstransfer mechanisms at micro scale. Electric and magnetic fields dominate the means to control masstransfer process in microfluidic chips. As compared with electric field, magnetic field has thefollowing unique advantages. The magnetic force is not affected by sample parameters such asconcentration and pH value. And also, magnetic microspheres (beads) are of good controllabilityunder magnetic field. Moreover, there are various functionalizations on the surface of magnetic beads.Therefore combination of magnetic field (magnetic beads) and microfluidics is an important focalpoint of research in recent years. However, most of the researches are focused on proof-of-conceptdemonstrations of mass transfer process in microfluidic chip. It is still lack of quantitative studies onthe mass transfer mechanisms under magnetic actuation. Especially, there is no efficient way toovercome the difficulty on the magnetophoretic separation of small magnetic beads at high fluidvelocities. And also, no simple and effective mean was found to solve the contradiction betweenenhancing separation efficiency and reducing the joule heating effect in magnetophoretic chipintegrated with electromagnetic coils. Moreover, the mixing efficiency of functional magnetic beadand biological sample is still needed to be improved. Therefore in this thesis, theoretical, numericaland experimental studies were carried out on heat and mass transfer mechanisms in magnetophoreticmicrofluidic chips. A series of important achievements and conclusions were obtained.(1) A dynamic model was established to describe magnetic bead moving in microchannels undermagnetic field and flow field. The combined use of finite element method and Runge-Kutta methodwere adopted to study the dynamic behaviour and characteristics of magnetic beads. The applicabilityof one-way coupling and two-way coupling models was analyzed. The magnetic force distribution,magnetic bead trajectory and velocity as well as capture time and capture efficiency were obtained.Three modes of micro magnet configurations influencing the dynamic behaviors of magnetic beadswere discussed including single-side configuration, double-side symmetrical configuration anddouble-side staggered configuration. It was found that the magnetic bead trajectory in microchannelreveals oscillatory under the actuation of soft magnetic array integrated on the side of microchannel. As compared with single-side configuration, this oscillation will be weakened in double-sidesymmetrical configuration and amplified in double-side staggered configuration. The symmetrical andstaggered magnet configurations have great effect on magnetic bead trajectory whereas little effect oncapture efficiency. The double-side configurations have larger capture efficiency than the single-sideconfiguration, but the corresponding capture time is also longer. The capture efficiency in double-sideconfigurations is obviously smaller than the two times of capture efficiency in single-sideconfiguration, which indicates that the magnetic force on each side of the microchannel has greatoverlapping and weakens each other.(2) An experimental study on magnetophoretic separation characteristics was carried out byusing superparamagnetic beads at high fluid velocities. The capture and release processes of themagnetic beads in the microchannel were observed and recorded with the help of high speed CCDcamera. The relations between the number of captured beads and time, fluid velocity and magneticfield intensity were obtained by imaging analysis. It was found that the trend for the number ofcaptured beads with time is linear at high fluid velocities or low magnetic field intensities whereas it isnonlinear (increase initially quickly and then slowly) at low fluid velocities or high magnetic fieldintensities. There exists a critical fluid velocity above which the capture efficiency decreasesdrastically from100%to a very small value and then decrease slowly with the increase of fluidvelocity. The captured magnetic beads increase more and more quickly with the increase of magneticfield intensity.(3) A novel method to improve the separation efficiency in microchannels was proposed andproved for the first time by utilizing synergy principle of magnetic field and flow field. From the basicequation describing the movement of magnetic bead, it was theoretically analyzed and proved that themagnetic bead is always in the state of quasi-equilibrium during the motion process in microchannels.Based on this deduction, a novel and important impact factor on separation efficiency can be derived.The factor is the synergy angle, i.e., the angle between the vectors of magnetic force and fluid velocity,which means the synergy (coordination) of magnetic force field and flow field (good coordinationmeans small synergy angle). It was confirmed that the separation efficiency of magnetophoresis inmicrochannels can be improved by reducing the synergy angle between magnetic force field and fluidflow field, so a new approach was found to optimize the magnetophoretic chip design in terms ofseparation efficiency enhancement.(4) A novel magnetophoretic chip (i.e., L/T-shaped configuration) integrated with micro softmagnets was designed and fabricated based on the proposed synergy principle of magnetic field andflow field. Numerical simulation was conducted in terms of separation efficiency in the designed chipsby varying influential parameters including fluid velocity, magnetic field intensity, magnetic beaddiameter and fluid temperature. The result shows that the separation efficiency of the L/T-shapedmagnetophoretic chips can be improved greatly as compared with the conventionalstraight-microchannel magnetophoretic chip. For example, the separation efficiency instraight-microchannel chip is only43.7%at fluid velocity of0.01m/s for the magnetic bead withdiameter of0.5μm whereas it can be enhanced to63.4%and100%in L-shaped and T-shaped chipsrespectively at the same conditions. Based on the above studies, an experiment on magnetophoresis of fluorescent magnetic bead was conducted in straight and L/T-shaped microchannels to validate theproposed synergy principle between magnetic force field and flow field.(5) Based on the principles of improving separation efficiency, reducing joule heating effect andguaranteeing the chip transparency, a novel magnetophoretic chip integrated with electromagneticcoils was designed and fabricated with the sandwich structure of glass/silicon/glass. An experimentalinvestigation on magnetophoretic separation was carried out in the proposed chip by using fluorescentmagnetic beads. Since joule heating was generated during the process of magnetophoresis, thetemperature of the chip was measured by an infrared thermography. Further, through finite elementmethod the thermal performances of the designed chip were compared with the chips based on PDMSwhich were widely used in open literatures. The result shows that the distribution of fluorescentintensity is related with magnetic flux density of the integrated microcoil. It was also found that thetemperature increase in the designed chip with the sandwich structure is less than10℃when thecapture efficiency of magnetic beads is as high as87.4%. This temperature increase is much smaller ascompared with the chip based on the structures of PDMS/PDMS and PDMS/glass (62.4℃and30.7℃,respectively) at the same conditions so that the proposed chip allows larger input electric current (thusthe magnetic force is increased) to increase the capture efficiency, which indicates that the proposedchip is a new structural option for overcoming the contradiction between enhancing capture efficiencyand decreasing joule heating effect in transparent magnetophoretic chip integrated withelectromagnetic coils.(6) The mixing process by functional magnetic bead in microchannels was numerically studied byutilizing low-frequency intermittent magnetic field. A multi physical model coupling with magneticfield, flow field and concentration field was established to study mixing characteristics. The magneticbead concentration, fluid velocity and pressure distribution as well as mixing efficiency were studied.The influential parameters on mixing efficiency were analyzed including Reynolds number, Strouhalnumber (relevant to the magnetic field frequency), magnetic force, microchannel dimension and fluidtemperature. It was found that the mixing efficiency can be improved significantly by the disturbancewith low-frequency intermittent magnetic field. There exists a minimum magnetic force to make themixing enhanced siginificantly and an optimal frequency to maximum the mixing efficiency underspecific conditions.Through the above studies, the dynamic behaviours of magnetic beads in microchannels weresystematically and thoroughly revealed. At the same time, a series of novel theory and technologicalmethods were proposed in terms of joule heating dissipation enhancement, separation and mixingefficiency improvement in magnetophoretic chips. It is anticipated that the presented results are usefulfor improvement of heat and mass transfer efficiency and helpful for the structural design andoptimization of magnetophoretic microfluidic chips. Moreover, the synergy principle proposed in thisthesis could provide a theoretical instruction for improvement of transfer performance in otherprocesses involving with multi physical problems in micro systems.