Experimental Investigation On Fabrication Of Multi-functional Complex Microcarriers By Flow Focusing

As a type of advanced materials with special structures or multiple functions,the multifunctional complex microcarriers have a wide range of applications in many fields such as agriculture,food,chemical engineering,optical imaging,biomedicine and material science.Flow focusing is a new type of microfluidic technology for the production of microcarriers.When a group of fluids flow through the small orifice,a liquid jet forms and breaks up into monodisperse microdroplets due to perturbation propagation along the jet surface.The flow focusing technology has advantages in fabricating multifunctional complex microcarriers because of it's simple setup,easy scale-up,high encapsulation efficiency,good stability and controllability.In this thesis,we use multiplex coaxial flow focusing method to fabricate some types of multifunctional complex microcarriers,and solve the technical difficulties in the production of them.In addition,we demonstrate the applications of multifunctional complex microcarriers in cell encapsulation,optical imaging,drug delivery and cancer therapy.The main contents are given as follows:1.We propose a simple but efficient multiplex coaxial flow focusing(MCFF)process for single-step fabrication of multicompartment Janus microcapsules(MJMs),which combine the advantageous features of Janus microparticles and multicompartment microcapsules.The magnetic nanoparticles are loaded into one of the shell compartments and photopolymerized under ultraviolet light for controlled alignment and rotation of the microcapsules in a magnetic field.For the in vitro experiment,four different types of cells are encapsulated in the desired compartments of sodium alginate MJMs and co-cultured for seven days.By increasing the number of coaxial needles,we are also able to produce MJMs with three or more compartments.Our studies have shown that the proposed MCFF process is able to produce MJMs with desired material compositions and narrow size distribution.This process is inexpensive and scalable for mass production of various MJMs in its potential applications in biomedical imaging,micro-sensor,photonic crystals,drug delivery,and regenerative medicine.2.We fabricate complex microcarriers with irregular shapes in the microscale by the multiplex coaxial flow focusing process.A multiphase cone-jet structure is steadily formed,and the compound liquid jet eventually break up into Janus microdroplets due to the perturbations propagating along the jet interfaces.The microdroplet shapes can be exclusively controlled by interfacial tensions of adjacent phases.Crescent-moon-shaped microparticles and microcapsules with designated structural characteristics are further produced under ultraviolet light of photopolymerization after removing FC-77 phases of the Janus microdroplets and Janus double emulsions.These complex microcarriers have potential applications in bioscience,food,functional materials,and controlled drug delivery.3.We fabricate oxygen and Indocyanine Green(ICG)loaded microparticles(OI-MPs)by flow focusing method for dual-mode imaging and sonodynamic therapy(SDT).The produced OI-MPs agent shows stable optical properties,superior imaging depth in near infrared fluorescence imaging,and enhances acoustic contrast after ultrasound mediation.Encapsulating ICG and oxygen in microparticles will enhance reactive oxygen species production in sonodynamic therapy,which is validated in a cell-free environment.In vitro experiment indicate that ultrasound mediated fragmentation of the OI-MPs would induce cytotoxicity and apoptosis of cancer cells.Our research demonstrate that OI-MPs can be potentially used for ultrasound imaging,near infrared fluorescence imaging,and cancer therapy with SDT.