Research On Customization Of Individualized Microfluidic Chips Via Additive Manufacturing

Microfluidics is a novel and multidisciplinary technology,which covers many fields,including chemistry,biology,medicine and mechanics.Due to its small sample volumes,high sensitivity and resolution,and short time for analysis,microfluidics has been widely deployed in the past 30 years.Though the traditional fabrication methods of microfluidic chips that are represented by soft lithography and hot embossing could achieve batch production,traditional fabrication methods are still limited in the realization of complex channel structures and the materials for chip fabrication.3D printing,which is also called additive manufacturing,is a novel rapid prototyping technology for 3D objects fabrication and it could satisfy the demands for the fabrication of both 2D and 3D microfluidic chips.Moreover,3D printing has the advantages that it could implement small batch production for customized design with a relatively low cost while the fabrication process is automated.At present,there're still many challenges for 3D printing of microfluidic chips,and these can be listed as follows.(1)Materials for 3D printing of chips are limited.For example,PDMS(Polydimethylsiloxane),which is commonly used in chip fabrication,cannot be printed via existing methods.(2)3D-printed chips' resolution and quality are inferior to those of traditional chips,and the unavoidable stair-stepping effect in 3D printing could increase the channels'surface roughness.(3)Chips' manufacturing efficiency needs to be improved,because printing single chip usually costs several hours.And in comparison with other methods,like hot embossing,injection molding and soft lithography,which use molds to realize batch production of chips,each 3D-printed chip needs to be post-processed individually,making it hard to realize batch fabrication of printed chips.(4)General standard design of microchips' connectors is missing,and this leads to the impossible integration of different chips fabricated by different methods,so 3D printing's merits for rapid customization are hard to be utilized,limiting the rapid design and fabrication of 3D-printed chips.So,it's meaningful for researchers to adopt different 3D printing techniques to fabricate microfluidic chips and apply the 3D-printed microfluidic chips in chemical and biological researches,while they have to avoid the printing resolution limitations via proper printing process.In this thesis,based on different typical 3D printing techniques that included photopolymerization and material extrusion,and focusing on different application conditions,several methods for 3D printing of microfluidic chips were proposed and the 3D-printed microfluidic chips were used for further biomedical researches.The main contribution of this thesis is summarized as follows:(1)As precise control of fluid flow in the microchannel is the basis of microfluidic chips,the demands for microchannel fabrication are to ensure smooth channel surface,accurate fabrication resolution for channel size and good sealing of microchips.But 3D printing's unavoidable stair-stepping effect makes 3D-printed chips' channel surface very rough.To satisfy the demands for smooth channel,a method utilizing embedded sacrificial elements was proposed for 3D printing of PDMS chips,and it could realize the printing of PDMS chips with smooth channels.The principle of this method was to use dissolvable sacrificial materials(maltitol was a good choice)and make the most of the merit that the surface tension led to the auto-smooth surface in the filaments when melted material was printed.The printing process for this method included:First,dissolvable maltitol was chosen as sacrificial material and sacrificial microchannel structures could be printed with maltitol.Microchannels were then achieved through removing the sacrificial elements after PDMS was poured and cured.And further sealing was not needed after the one-step fabrication of microfluidic chips.Moreover,based on this method,a printing system with two printheads was built.And after detailed analysis of printing process,it was conformed that microchannel sizes could be precisely controlled by the adjustment of different printing parameters.Meanwhile,liquid PDMS was directly printed as supporting material in each layer,which could help realize the fabrication of complex microfluidic chips assisted by supporting structures.(2)Now,microfluidic chips show several trends,including miniaturization,low cost and POCT(Point-of-care testing),and rapid customization of microchips becomes the key part,which demands the rapid response of chip fabrication from design to fabrication.To satisfy the current trends,the printing time cost for 3D printing of microfluidic chips has to be solved,which means fabricating chips within one hour to improve the chip fabrication efficiency.However,compared to other 3D printing techniques,DLP(Digital Light Processing)technique enabled products across projection and this could increase the chips' printing speed,thus leading to printing microfluidic chips within several minutes and ensuring a high printing resolution.To solve the problem concerning the low chip printing efficiency,the printing process for rapid fabrication of monolithic micro fluidic chips with resin materials was studied based on DLP technique.With the help of DLP technique,monolithic integrated microfluidic chips could be printed directly.At the same time,to solve the blocking problem caused by residual resin in the 3D-printed microchannels,another method that used adhesive tape to seal printed open microchannels was taken to fabricate microfluidic chips with intricate microstructures.Then the influence of different printing parameters on the printing resolution of 3D-printed chips and the printed microchannels' quality was studied,and characterization of chips' printing materials was also presented in terms of material's hydrophility/hydrophobicity and biocompatibility.(3)As PDMS is transparent,gas-permeable and biocompatible,it's suitable for microfluidic chip fabrication,but batch production of PDMS chips via 3D printing is still hard to be carried out.It's convenient for researchers to fabricate PDMS chips with chip molds through traditional methods,so applying 3D-printed molds in the customized batch production of microfluidic chips,could not only solve the time cost problem for individual 3D-printed chips,but also decrease the manufacturing time of chip molds.So,with 3D printing techniques,a method utilizing 3D-printedchip molds for microfluidic chip fabrication was studied to satisfy the needs for rapid customization of microfluidic chips.And combined with rapid packaging method for microfluidic chips,high fabrication efficiency was achieved.First,with a number of experiments,we evaluated the capacities of different 3D printing techniques in molds' and chips' fabrication,and detailed evaluation criteria with printing parameters was presented for the appropriate adoption of 3D printing techniques.Meanwhile,the stable sealing of PDMS chips with the adhesive-free packaging method was verified by different analysis results which ranged from simulation to experiment fields.This chip fabrication method made the most of chip molds' rapid customization and PDMS chips' batch production,and satisfied the demands for stable and simple sealing under normal experiment circumstances.(4)3D printing of monolithic integrated chips has to face repeated optimization and settle the high manufacturing difficulty in the fabrication,for example,different functional components are difficult to be integrated into one microchip.And modular design could solve the above problems,but lack of design standards for chip connectors leads to a high cost for modular chips,which restricts the application of modular chips.So this thesis made use of 3D printing's capacity for rapid customization and aimed to solve the cost problem in the customization of modular chips.Based on 3D printing techniques and modular design,a novel method for fabrication of modular microfluidic chips with 3D printing was proposed and could meet the needs of rapid customization of chip functions.The modular parts of microfluidic chips were first generalized according to each part's function,and after this step,different chip modules was 3D printed with resin and PDMS.Then according to the chip design,resin modules could be assembled into a complete Microfluidic chip with fit-to-flow interconnects.But PDMS modules were assembled into final chip with adhesive-free packaging method.In addition,as 3D bioprinting could directly print cell or tissue structures on the microfluidic chips,we combined this idea and proposed a new way for fabrication of micro-bioreactor based on the 3D-printed modular chips.