Research On Particle Manipulation Mechanism And Functional Applications Based On Acoustic Microfluidics

Efficient manipulation of biological particles(such as cells,extracellular vesicles,etc.)has a wide range of applications in the field of disease detection and diagnosis.Acoustic microfluidic technology,also known as acoustofluidics,utilizes a specific type of sound field established in microfluidics to realize particle manipulation functions.Acoustofluidics has many advantages such as non-contact,label-free,high precision,low cost,and short-time consumption.It is considered as an ideal candidate technology for miniaturized microfluidic analytical instruments.It is of great significance to study the mechanism of acoustofluidic particle manipulation and develop a new type of acoustofluidic device to speed up the in vitro detection process and improve the detection accuracy.Taking demand as the traction,this thesis firstly conducts systematic research on the design,particle deflection mechanism and chip preparation involved in the particle sorting process of the tilted-angle standing surface acoustic wave(SSAW)microfluidic devices.Secondly,based on the principle of acoustic wave-driven droplet vibration,two acoustofluidic chip for realizing particle enrichment at micron and submicron scales was developed.Finally,a new method for trapping stable adhering bubbles within microfluidic channels was proposed,and acoustically activated vibrating bubbles were applied to the manipulation of particles in continuous flow.Our major results are detailed as follows.1)Particle separation mechanism in tilted-angle SSAW microfluidics:Aiming at the physical principles involved in the particle separation process,a multi-physics coupled numerical model for studying the acoustic field and particle motion was established.Based on the model,the influence of parameters such as flow and sound field on particle trajectory was revealed,and the model was used to simulate the acoustofluidic separation of exosomes in whole blood.An analytical model for predicting particle migration distance and deflection angle under acoustic and flow field was established,and the migration laws of0.1-0.7μm and 1-7μm particles were studied.Based on the modeling results,chip parameters for acoustofluidic sorting of blood cells and plasma exosomes was optimized.The results show that the numerical modeling method has unique advantages in acoustofluidic research and can effectively shorten the development cycle of prototype devices.Using micro-nano processing technology,a tilted SSAW microfluidic sorting chip was prepared,and a particle motion characterization platform was built based on an inverted fluorescence microscope.Microscopic observation and image processing methods were used to achieve quantitative analysis of particle migration characteristics.2)Particle enrichment in acoustofluidic droplets: Based on the principle of flexural wave droplet manipulation,a chip was developed to realize the enrichment of micron particles in the droplet.The mechanism of acoustic field formation and particle enrichment in droplets was revealed by numerical calculation,and the enrichment process of various micro-particles can be realized within 300 s.Based on the existing surface acoustic wave droplet manipulation technology,an acoustofludiic chip was proposed to drive droplet spin and achieve rapid enrichment of 0.1-1μm particles within 30 s.Based on numerical modeling,the acoustic streaming and particle motion were predicted,and the particle enrichment mechanism in spining droplet was revealed.3)Acoustofluidic manipulation based on vibrating bubbles:This research breaks through the bubbles trapping method in fluidic channel based on cavities.Based on the principle of minimum surface energy in the microfluidic system,a chip design method for capturing stable adhering bubbles was proposed.The process and principle of bubble trapping were analyzed through experiments and theoretical formulas.The trapped bubbles can maintain good stability within high flow rates.By introducing flexural waves to excite bubble vibration in the flow channel,a variety of particle manipulation functions were realized,such as particle focusing,enrichment,and sorting.Combined with analytical formulas,the mechanism of particle motion under vibrating bubbles was analyzed.4)The functional application of the acoustofluidic device: Based on the particle sorting and enrichment chips explored above,research on the expansion of functions of the device was carried out to verify the applicability of the device in the manipulation of biological particles.First,the exosome separation from body fluids was realized based on the tilted SSAW microfluidic sorting chip.The removal efficiency of large vesicle particles could reach 80%,and exosomes with higher purity were collected at the outlet.Secondly,based on the principle of flexural wave driven droplet enrichment,the application of enriching liver cancer cells in multiple droplets was realized.Finally,based on the principle of surface acoustic wave-driven droplet centrifugation,the application of enriching whole blood cells within 1s and enriching extracellular vesicles within 60 s was realized.Compared with the gold standard high-speed centrifugation technology,the acoustofluidic technology has a unique advantage in the overall performance of processing biological samples.The relevant research plays an important role in promoting the efficient acoustofluidic separation and enrichment of biological samples and the development of bubble-based acoustofluidic device.