Design And Fabrication Of Functional Microfluidic Channels:Applications For Biodetection And Hierarchical Biomaterials

Microfluidics or lab-on-a-chip is a technology featured by micro-or nano-scale fluid control.Experiment operation in microscale can be easily achieved by microfluidic system,which is suitable for biomedical research such as cell culture,bacterial detection and DNA analysis.A lot of technologies like high-throughput assays,organ-on-a-chip,DNA amplification,single-cell culture and analysis benefit from the development of microfluidic technology.Besides analytical applications,microfluidic systems are shown to be suitable for the preparation of natural polymer fiber materials,such as silk,cellulose and alginate.Regenerated fiber materials with special structure can be synthesized by designing suitable microfluidic chips and are widely used in the field of biomedical research.The main work of this thesis is aimed to expand the application of microfluidic technology in biomedical research.Firstly,a PDMS microfluidic chip with switchable and renewable bio functionality was prepared based on host-guest interaction.Different biofunctions(biotin binding and bacterial adhesion)were incorporated on microchannel surface via the host-guest interaction between p-cyclodextrin derivatives modified with multiple bioactive ligands and its guest molecule-adamantane(Ada).The surface bio functions can be switched and recycled though dynamic binding of host-guest interaction.Then,a microfluidic chip was designed to construct hierarchical silk fiber biomaterials by accurately controlling fluid in chips.In this work,shearing force was introduced in the microchannel to induce self-assembly,orientation and hierarchical structure formation of silk nanofibers.The detailed research content is as follows:(1)Construction of modified PDMS microchannels with renewable and switchable bio functions by the combination of visible light-induced grafting and host-guest interactionIn this work,we fabricated a PDMS microfluidic chip with switchable and renewable biofunctions via host-guest interaction.First,oligo(ethylene glycol)methacrylate(OEGMA)and adamantane-containing OEGMA(OEGMA-Ada)were graft copolymerized on PDMS substrate(PDMS-POA).Then two different p-cyclodextrin derivatives,CD-biotin and CD-mannose,were incorporated on the PDMS-POA surface by host-guest interaction between p-cyclodextrin and adamantine.The resulted channels exhibited high binding capacity with avidin and E.coli,respectively.The data show that the modified microchannel surface can resist the non-specific adsorption of proteins and bacteria and selectively recognize target proteins and bacteria.The binding ability of the modified microchannels was also observed in complex physiological solution.In addition,the p-CDs with binding targets could be released by treatment with sodium dodecyl sulfate(SDS)solution to break the host-guest interaction between β-CDs and Ada.The bio functions of the PDMS microchannels could be switched and recycled simply by treatment with SDS and different p-CDs.(2)Construction of hierarchical structured silk fibers by fluid control in a biomimetic microfluidic chip.In this work,a micro fluidic chip was designed to mimick the geometries of the natural spinning ducts.And a new silk fiber material with hierarchical oriented structure was fabricated by combining biomimetic chips and silk nanofiber solutions.Firstly,a spinning solution based on silk nanofibers was prepared by adjusting the self-assembly of aqueous silk solution.Then,by mimicking natural spinning apparatus,a microfluidic chip with shearing and elongational sections was designed to induce the self-assembly and hierarchical structure formation.Finally,silk fibers were produced in the ethanol coagulation bath.The data show that the silk fiber material is composed of oriented nanofibers with high β-sheet structure.The cell behaviors(cell proliferation,growth,orientation and differentiation)of smooth muscle cells,schwann cells and PC 12 were investigated.The results show that the silk fiber with hierarchical structure could simulate the cell microenvironment of the above cells and promote cell proliferation and oriented growth.For PC 12 cells,the materials could effectively promote its differentiation.In summary,functional microfluidic chips have been designed for biodetection and fabrication of hierarchical biomaterials.The strategies adopted in this thesis may further broaden the biomedical applications of micro fluidic systems.