Bio-interfacial Effect Of Gigahertz Acoustic Streaming And Its Applications In Drug Delivery System

The development of drug delivery system is of great value in the fields of life science and clinical medicine.The main purpose of a drug delivery system is to ensure that an appropriate amount of medicine can reach the target location of the organism at a specific time,thereby improving the drug utilization efficiency and reducing its toxic side effects.Controlled release of target drug molecules and the improvement of drug penetration through various biological barriers have always been the research focus in drug delivery.In this thesis,we developed a novel drug delivery platform which is based on the micro-scaled acoustic streaming effect generated by a gigahertz(GHz)bulk acoustic resonator.The platform utilizes the interfacial interaction between the GHz acoustic streaming and the biological materials such as drug molecules or biological barriers,and drug delivery functions including controllable drug molecules release,intracellular drug delivery and transdermal drug absorption are finally realized.Detailed contents and main achievements of the thesis are as follows:1)A gigahertz bulk acoustic resonator based on micro-electromechanical system(MEMS)technology is fabricated and its electrical properties are tested.The gigahertz acoustic streaming phenomenon generated by this resonator is studied through theoretical calculation and finite element simulation,and the distribution of the fluid field under different environmental conditions is analyzed.The fluid velocity and fluid force are further experimentally characterized using a self-established high-speed particle tracing system,an atomic force microscope and a commercialized force sensor.2)The shear stress and the molecular peeling effect of the GHz acoustic streaming at the interface are studied,and a controllable drug release system based on Layer-byLayer(Lb L)self-assembled films embedded with DNA molecules is constructed.Drug release rate and release amount under different power and resonator distance are calculated.Furthermore,the behavior of the acoustic streaming at the interface of porous materials is studied.Different shear forces generated on the outer and inner interfaces of the films are analyzed,and are used to achieve the co-release of two drugs with different release rates.3)The cell squeezing effect generated by the GHz acoustic streaming on the surface of adherent cells is studied,and flexible control of cell morphology is achieved by adjusting the intensity,treating time and switching frequency of the acoustic field.Cell membrane reorganization and its permeability change during cell deformation process are discovered,and controllable intracellular drug delivery using different deformation extent and deformation patterns is realized.Moreover,a novel phenomenon is revealed by our system that fast and periodic cell deformation under hydrodynamic stimulation will facilitate the production of larger cracks on membrane for intracellular transportation,providing a reliable way for drugs uptake.4)The high-pressure liquid needle effect and skin deformation effect on the liquidskin interface generated by the GHz acoustic streaming are studied,which are used to realize power-regulated transdermal drug delivery.The utilization of a device array platform for the improvement of delivery efficiency is also proved to be feasible.