Study Of Surface Acoustic Wave Lab On Chip Based Microfluidics

Microfluidics is an emerging technology with widespread applications in chemical and biological analysis,medicine research,diagnosis of illness and diseases etc.Microfluidics is able to handle liquid biosamples and reagents in microliter,nanoliter scales or smaller for sample transportation,pumping,mixing,cell handling,bioreaction,biodetection etc.,with new functions emerging continuously.Lab-on-chips is an extension of microfluidics with more functions,such as biosensing,integrated on a single small chip.Microfluidics and lab-on-chips have many advantages compared with traditional analysis methods,small dimension device thus allowing analysis on small quantity of samples and use of small quantity of reagents,multifunctions integrated on a closed chip,thus avoid potential cross contamination and operational errors by human,very fast with typical outcome results in minutes not hours or days as for traditional analysis,low cost,and they could be one-time use and disposable etc.Owing to their unique features and great application potential,the technologies have been explored intensively.Recently,surface acoustic waves(SAW)generated on piezoelectric substrates have been utilized as the actuation force for the development of microfluidics.As SAW can be utilized to develop multiple functions for lab-on-chips,including transportation,pump,mixing,nebulization,droplet generation,biosensing,particle(cells)concentration,sorting and separation etc.microfluidics and lab-on-chips with a single SAW actuation mechanism can be developed,making them even simpler in structures and fabrication with better function at lower cost,particularly useful and important for the forthcoming aging society for healthcare and medical applications.The objectives of my PhD research are to explore novel and innovative applications of SA W-based microfluidics or lab-on-chips,particularly for healthcare and medical applications.The main researches include three types of innovative SAW-based microfluidics:1.SAW based tensiometry to measure interfacial or surface tension between fluids;2.lensless CMOS imaging system with integrated SAW microfluidics for cell imaging and counting;3.SAW microfluidic system for on-chip cryopreservation agent(CPA)loading to and removal from cells for stem cell cryopreservation.Surface acoustic waves are generated on a piezoelectric substrate,travel on the substrate surface along the wave path.When SAW meets a droplet on the wave path,it interacts with liquid,and acoustic energy is coupled into the droplet,or inserting an acoustic pressure on the droplet,inducing acoustic streaming,or pumping droplet along the wave path etc.This has been utilized for developing micromixer and micropump to move and mix small volumes of liquids in two dimensional and three dimensional channel geometries for both biological and medical applications.For instance,the SAW-based technique enables us to analyze the complex interplay of the biochemical and physical properties of cells,proteins and chemicals in blood flow conditions.For the proposed tensiometry system,SAW has been utilized to deform droplets embedded in traveling mineral oil in a microchannel,by varying the radio frequency(RF)power on the interdigitated transducers(IDTs),a series of IDTs can generate SAWs with different acoustic pressures applied to droplets,using fast imaging technique,the deformed droplets can be imaged and analyzed.We have also developed corresponding mathematical model,so that the interfacial tension of the droplets can be extracted.This is the first kind of SAW-based microfluidic system for surface tension measurement,very useful for chemical,biological sample analysis,and it possibly could be extended to cell-based analysis through cell deformation by SAW for diagnosis and medical research.Cell imaging and counting are very useful for diagnosis of illness and diseases,especially for cancer diagnosis as tumor cells are very different from normal cells in mechanics.Lensless CMOS based imaging chips have been intensively studied and explored for cell imaging and counting as they are small,low cost,automated analysis etc.,however the current lensless CMOS imaging chips require separated fluidic pump system for transporting biosamples/reagent,mixing etc,it is bulky,requires large quantity of biosamples and special operation,and is only suitable for laboratory or hospitals use.We have proposed and developed a novel lensless CMOS based imaging chip with an integrated SAW micropump for transporting biosamples in small quantity,and investigated its performance.An efficient temporal-differencing based motion detection algorithm has also been proposed for continuous flowing cell detection and counting.Human bone marrow stromal cells were used for experiments,and demonstrated that the SAW microfluidics integrated imaging system can automatically detect and count cells with a low statistical error rate of-6.53%.This is the first lensless microfluidic imaging system integrated with SAW based micropump for flowing cell detection and counting towards portable POC biomedical diagnosis.In third case,SAW was utilized as a micromixer for on-chip CPA loading/unloading application.Cryopreservation requires CPA to suppress intracellular ice formation during freezing,but it must be removed prior to clinical use due to its toxicity.Conventional multistep CPA loading and unloading approaches are hand-based operation,thus it is time-consuming,often creates osmotic shocks and causes mechanical injuries for biological samples.We designed a novel SAW based lab-on-chip system which can load CPA to cells for cryopreservation and remove CPA from cells after preservation efficiently.The CAP loading and unloading processes takes only 10 sec,and the whole multiple CPA loading or unloading(to minimize osmotic shocks)is completed in about one minute,with drastically reduced operation time.Cell viability tests showed that the technique possesses the least harm on umbilical cord matrix mesenchymal stem cells as compared with conventional methods,and an average of 24%higher cell recovery rate is achieved while preserving the integrity and morphology of the cells.This is the first kind of lab-on-chip system for cryopreservation application.This would make a good contribution to cell-based therapies using stem cells.