Regulating Protein Interactions Using Gigahertz Acoustic Streaming

Interactions between protein molecules are the basis of all life activities,and the regulation of protein interactions at the molecular level is of great significance in scientific research and practical applications.In this thesis,we utilize the standard MEMS fabrication technology to fabricate the gigahertz(GHz)bulk acoustic resonator,and the stimulated GHz acoustic streaming is used to realize the accurate control of micro-scale fluid,and further realize the precise regulation of protein interactions on the sensing surface,nanoparticle interfaces as well as cell surface.We investigate the regulation mechanism and corresponding regulation effect of micro-scale acoustic streaming on protein interactions on different interfaces at the molecular level,which is highly important in promoting the applications of acousticofluidic technology in biomedical fields such as immune biosensing and cellular drug delivery.The main topics of this thesis are listed as follows:1.The finite element model and particle image velocimetry system are utilized to analyse the induced special acoustic streaming on solid-liquid interface,and further investigate the effect of acoustic streaming at the jet and shear mode on regulating protein molecules interactions.2.At jet mode of GHz acoustic streaming,due to the efficient jetting and mixing effects of the acoustofluidics,the directional transfer of molecules is accelerated,the diffusion limitation at the solid-liquid interface in biomolecular binding process is broken,and eventually the adsorption rate of molecules onto the sensor surface is improved.Since this hydrodynamic approach has excellent biocompatibility,the binding enhancement could be precisely controlled,and such hydrodynamic approach could be widely used in surface-based biosensing platforms.3.At shear mode of GHz acoustic streaming,the acoustic flow can generate drag force on the solid-liquid interface,which is utilized to remove the nonspecific bindings(NSB).In addition,since the resonator can be used as a gravimetric sensor,a multifunctional detection platform for NSB removal/biosensing is developed on the same GHz acoustic resonator.4.The precise regulation of the interactions between biomolecules and gold nanoparticle interface is investigated based on the ultrafast mixing effect of GHz acoustic streaming.By controlling the power applied to the GHz resonator,different level of fluorescence quenching can be achieved,that is,the binding density of fluorescent protein molecules onto gold nanoparticles is tuned.Upon competitive reaction,GHz acoustic streaming can enhance the fluorescence recovery effect.The GHz acoustic streaming is then applied to the detection of protein molecules based on the fluorescence quenching effect,and the array detection method verifies the versatility of the method and its potential as a biochip.5.The effect of GHz acoustic streaming on the interaction between protein molecules and the flexible cell membrane is investigated,and the direct delivery of protein molecules into cells and nucleus is accomplished.Delivery of bioactive proteins related to apoptosis or genetic recombination is realized by using the GHz acousticsmediated delivery approach.The generalizability of this developed method is evaluated in different cell lines.