Nghiên cứu chế tạo giọt chất lỏng kích thước micro mét sử dụng công nghệ vi lưu

Nghiên cứu chế tạo giọt chất lỏng kích thước micro mét sử dụng công nghệ vi lưu Nghiên cứu chế tạo giọt chất lỏng kích thước micro mét sử dụng công nghệ vi lưu Nghiên cứu chế tạo giọt chất lỏng kích thước micro mét sử dụng công nghệ vi lưu luận văn tốt nghiệp,luận văn thạc sĩ, luận văn cao học, luận văn đại học, luận án tiến sĩ, đồ án tốt nghiệp luận văn tốt nghiệp,luận văn thạc sĩ, luận văn cao học, luận văn đại học, luận án tiến sĩ, đồ án tốt nghiệp

MINISTRY OF EDUCATION AND TRAINING HANOI UNIVERSITY OF TECHNOLOGY AND SCIENCE INTERNATIONAL TRAINING INSTITUTE FOR MATERIALS SCIENCE - NGUYEN THI THAI FABRICATION OF DROPLETS USING T-JUNCTION MICROFLUIDIC SYSTEM MASTER THESIS OF MATERIALS SCIENCE Batch ITIMS-2015 SUPERVISOR Dr CHU THI XUAN Hanoi – 2017 ACKNOWLEDGMENTS First, I would like to express my sincere gratitude to my supervisor, Dr Chu Thi Xuan, International Training Institute for Materials Science (ITIMS), for her great guidance, advice, and supports during my dissertation performance It gives me great pleasure in acknowledging the supports and the useful instructions of Assoc Prof Mai Anh Tuan, and Dr Pham Duc Thanh, ITIMS I would like to convey my profound thanks to all members of Biosensor group in ITIMS for their enthusiastic help during practicing period Finally, thanks should also be given to my family and my friends, who always supported me in life Hanoi, October 2017 i DECLARATION I hereby declare that all the result in this document has been obtained and presented in accordance with academic rules and ethical conduct I also declare that, as required by these rules and conduct, I have fully cited and referenced all material and results that are not original to this work Author Nguyen Thi Thai ii CONTENTS ACKNOWLEDGMENTS .i DECLARATION .ii LIST OF FIGURE vi LIST OF TABLE viii INTRDUCTION Chapter 1: THEORY & FUNDAMENTALS 1.1 Microdroplets and applications 1.2 Droplet fabrication with traditional methods 10 1.3 1.2.1 Syringe 10 1.2.2 Stirring 10 1.2.3 Static mixing 13 Droplet fabrication with microfluidic methods 14 1.3.1 Co-flowing 14 1.3.2 Flow-focusing 16 1.3.3 T-junction 19 Chapter 2: FABRICATION OF MICRODROPLETS USING PDMS BASED T-JUNCTION MICROFLUIDIC SYSTEM 22 2.1 Procedure of mixing SU-8 for mold thickness 23 2.2 T-junction microfluidic system design 24 2.3 PDMS-based T-junction microfluidic system fabrication 25 2.3.1 Chemicals 25 iii 2.4 2.3.2 Fabrication of SU-8 mold 26 2.3.3 Fabrication of PDMS channel 27 Microdroplet fabrication procedure 28 2.4.1 Fluids Selection 28 2.4.2 Experimental setups 29 Chapter 3: SIMULATION OF DROPLET FORMATION IN T-JUNCTION 30 3.1 3.2 3.3 Basic theory for the simulation of the droplet formation 30 3.1.1 Laminar Flow vs Turbulent Flow 30 3.1.2 Level set method 32 3.1.3 Dominant equations 34 Model of the T-junction channel 37 3.2.1 Structure of T-junction 37 3.2.2 Finite Element Modeling 38 Calculation of droplet velocity 39 Chapter 4: RESULTS AND DISCUSSIONS 40 4.1 Thickness controlled by the mixture of SU-8 3050 and cyclopentanone 40 4.1.1 Influence of heating 40 4.1.2 Dependence of SU-8 layer thickness on volume of the Cyclopentanone in mixture solution 42 4.2 Fabrication of T-junction microfluidic devices 45 4.3 Droplet Formation 46 iv 4.4 Dependence of droplet size on the flow rate of channel and system geometry 49 4.5 Velocity of droplets 51 CONCLUSIONS 52 REFERENCES 54 v LIST OF FIGURE Fig 1.1: Illustration of the three microfluidic devices that form the droplet-based microfluidic photosensitizer screening platform [11] Fig 1.2: Applications of microfluidic technologies in clinical [93] Point-of-care ELISA microchip: a) picture of the chip; b) microscopy image; c) optical image of microchannels; d) passive flow delivery of multiple reagents requires no moving parts on- chip; e) immunoassay steps in detection zones Fig 1.3: A schematic of the microfluidic device which consists of parts: (1) compartmentalization of the sample with the probe and selective growth media; (2) incubation for the probe to be converted to fluorescent or colored product; (3) detection of fluorescent or colored droplets [58] Fig 1.4: Time-averaged fluorescence arising from rapid mixing inside plugs of solutions of Fluo-4 (54 mm) and CaCl2 (70 mm) in aqueous sodium morphine propane-sulfonate buffer (20 mm, pH 7.2) [67] Fig 1.5: Stirring method for droplets formation [44] 11 Fig 1.6: Size distribution of microbead using 1.8% Aldrich alginate, 2% Span 80, and calcium citrate containing 50 mM Ca 2+ in a round-bottomed reactor without baffles stirred with a marine impeller at 400 rpm: h, peak height; h/2, half peak height; d, diameter of beads: σ, diameter standard deviation; S, B, A, peaks of bead sizes [56] 12 Fig 1.7: A schematic of static mixer [34] 13 Fig 1.8: Example of droplet formation in a co-flowing device [62] 15 Fig 1.9: The different regimes for droplet formation in a co-flowing geometry (a) device geometry, (b) dripping regime, (c) jetting regime with narrowing jet and (d) jetting regime with widening jet [84] 16 Fig 1.10: Illustrations of flow-focusing geometry used for droplet formation [3] 18 vi Fig 1.11: Droplet formation images in a flow-focusing geometry Droplet breakup occurs within the orifice, (A) uniform drops are generated; Qc is 𝜇L/min and φ = 1/4, (B) small satellite droplets are generated with each large drop; Qc is 25 𝜇L/min and φ = 1/40 [1] 18 Fig 1.12: Schematic of T-junction microfluidic system [36] 19 Fig 1.13: Numerical simulations illustrate the dependency of capillary number and flow rate ratio (with fixed viscosity ratio) for the three regimes: squeezing, dripping and jetting Ca is (A) 0.006, (B) 0.032 and (C) 0.056; flow rate ratio φ is (i) 1/8, (ii) 1/4 and (iii) 1/2 [36] 21 Fig 2.1: Mixing process of SU-8 3050 and Cyclopentanone 23 Fig 2.2: A schematic illustration (A) three-dimensional and (B) two-dimensional of the microfluidic T-junction 25 Fig 2.3: Mask design for SU-8 mold fabrication 26 Fig 2.4: The SU-8 mold fabrication 27 Fig 2.5: Process scheme of fabrication of PDMS-base T-junction microfluidic devices 28 Fig 2.6: Experimental setups for studying droplets 29 Fig 3.1: A schematic of laminar flow (A) and turbulent flow (B) 31 Fig 3.2: Representation of level-set function [38] 33 Fig 3.3: The contact angle, θ, and the slip length, β 36 Fig 3.4: The modeling domain of the T-junction 37 Fig 3.5: Shape and distribution of meshing elements in T-junction channel 38 Fig 3.6: Calculation of droplet velocity 39 Fig 4.1: Images of silicon wafer after being spin-coated with the mixed solution, (A) no heating mix solution (mixing procedure 1); (B) heating mix solution (mixing procedure 2) 41 Fig 4.2: Image of the mixture of SU-8 and Cyclopentanone 41 vii Fig 4.3: SEM image of mixture at volume ratio 1:1 42 Fig 4.4: Profilometer images of micro-device at volume ratio 1:1 43 Fig 4.5: Profilometer images of micro-device at different volume ratios 43 Fig 4.6: Dependence of layer thickness on SU-8: Cyclopentanone volume ratio 44 Fig 4.7: SEM image of PDMS T-junction channel 45 Fig 4.8: Test the bonding between PDMS channel and glass substrate 46 Fig 4.9: Snapshots of simulations (left) and experiments (right) of droplet formation at a T-junction The channel size: wd = 100𝜇m; wc = 100 𝜇m and h = 70 𝜇m 47 Fig 4.10: The three-dimensional process of droplet generation 48 Fig 4.11: (A) (C) experiment results; (B) (D) simulation results Effect of flow rate on length of droplet (A) (B) fixed Qc = µL/min; (C) (D) fixed Qd = µL/min Dependence of droplet length on T-junction size, there are three T-junction geometries with different the width of the lateral channel wd from 25 to 100 𝜇m 50 Fig 4.12: Droplet velocity in T-junction (Qc = µL/min, Qd = µL/min) 51 LIST OF TABLE Table 2.1: Dimensions of the T-junction microfluidic 25 Table 2.2: Physical properties of used liquids [13] 28 viii INTRODUCTION Droplet microfluidic with faster reaction rate, less cross-infection and reducing sample volume, has been growing strongly for two decades [91] Recently, microdroplets have been successfully applied in a broad range of research areas from bio-chemical analysis to electronic microsystems [86] Several microfluidic geometries have been developed to synthesize uniform droplet, including T-junction geometries [78], flow-focusing geometries [1], co-flowing geometries [14] T-junction has been commonly microfluidic devices used to generate microdroplets This geometry was first demonstrated in 2001 by Thorsen et al [78], who produced water droplets with pressure controlled laminar flow in microchannels Since then, many studies were performed using T-junction geometries by both experimental [24] and numerical approaches [26], to achieve a better understanding of the formation mechanism of droplet and the role of several physical parameters therein The droplet size depends on the flow rate of two liquids [78], the relative viscosity between the two phases [79], and the size of the channels [24] In this work, we focus on investigating the dependence of microdroplet size on the flow rates of the two immiscible fluids and the influence of the width of the lateral channels on the droplet formation In experimental part, PDMS-base T-junction microfluidic systems were made by photolithography COMSOL Multiphysics is used for simulation In this simulation, a T-junction model can be built using Laminar TwoPhase Flow and Level Set interface The model uses the predefined wetted wall boundary condition at the solid walls, with a contact angle of 135° This thesis consists of four chapters: In chapter 1, fundamental of droplet-base microfluidics such as droplet applications, and droplet fabrication methods will be introduced Fig 4.10: The three-dimensional process of droplet generation 48 4.4 Dependence of droplet size on the flow rate of channel and system geometry Length of droplet was analyzed using CCD camera and ImageJ software Fixing flow rate of one channel, we calculated the dependence of droplet size on flow rate of continuous phase (Fig 4.11 A, B) and dispersed phase (Fig 4.11 C, D) In Fig 4.11 A and B, we fixed Qc = µL/min and Qd varied from 0.1 to µL/min, droplet size increases linearly with the flow rate of dispersed phase (Qd) Fig 4.11 C, D represents the dependence of the droplet length on the oil flow rate for fixed Qd = µL/min It can be seen that the size of droplet is inversely proportional to the flow rate of oil according to exponential function Similarly, we fixed the flow rate of each channel in T-junction and varied channel size The dependence of droplets’ lengths on channel size as well as the flow rate of channels is depicted in Fig 4.11 From the observation results, we can see that droplet size was closely proportional to the width of lateral channel When continuousphase flow rate was fixed, the relation between droplet size and disperse-phase’s flow rate exhibited to be linear However, that of fixed dispersed-phase case was logarithmic We also see that when the width of the lateral channels increases, the size of the droplet fabricated increases These results are very important in system design to fabricate desired micro-droplets From Fig 4.11, we can see that simulation results have the same rules as the experimental results However, as the width of the disperse channel decreases, the difference between experiment and simulation grows larger This can be explained that smaller the size, harder for fabrication to achieve high accuracy Simulation can only be implemented in a small area of the channel due to limitations of device storage and simulation time 49 Fig 4.11: Effect of flow rate on length of droplet (A) (B) fixed Qc = µL/min; (C) (D) fixed Qd = µL/min (A) (C) experiment results; (B) (D) simulation results 50 4.5 Velocity of droplets Fig 4.12: Droplet velocity in T-junction (Qc = µL/min, Qd = µL/min); (A) wd = 100 𝜇m; (B) wd = 50 𝜇m; wd = 25 𝜇m As we can see in Fig 4.12, the velocity of droplet was around 14 (mm/s) In experimental results, the droplets velocity is separated into two values causes may be due to the pulse of syringe pumps 51 CONCLUSIONS The mixing process for SU-8 3050 and Cyclopentanone was improved The heating was proved to play an important role in reducing bubbles and favoring the unity of the mixture After the process, the mixed solution can be used as photoresist to fabricate the microstructures Some different volume ratios of SU-8: Cyclopentanone was described The smallest thickness was 540 nm when the mixing ratio of SU-8: Cyclopentanone were 1:4 The thickness of thin layer formulated by SU8 3000 series following this process is similar to that of SU-8 2000, which allows to extend the applications of SU-8 3000 series We have successfully fabricated PDMS-base T-junction microfluidic systems for microdroplet generation The droplet size can be controlled by changing the flow rate of two immiscible fluids and change T-junction size The minimum and the maximum length of the droplet was about 100 µm and 1400 µm respectively as the flow rate of the continuous phase was changed from 0.1 to 20 µL/min The droplet size increases linearly with the flow rate of dispersed phase (Qd) and decreases according to the exponential function with the continuous phase rate (Qc) Similarly, when the width of the lateral channel increases, size of the droplet fabricated increases The experiment results match very well with the simulation results This is the basis for using the COMSOL software for subsequent calculations which will help reduce the time as well as the cost of the experiment In this case, the velocity of droplet was from 14 to 15 mm/s That velocity is quite fast but it is suitable for drug delivery applications In experimental results, the droplets velocity is separated into two values causes may be due to the pulse of syringe pumps The results obtained in this thesis are just the initial research In the future, we will try to develop and optimize the microfluidic system in both application and 52 fabrication Improved this microfluidic system for use microcapsule manufacturing which is used in drug delivery applications Besides, the results of this thesis are the basic for the use of COMSOL software for further studies 53 REFERENCES [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] Anna, S L., N Bontoux, and H A Stone, (2003), “Formation of dispersions using ‘flow focusing’ in microchannels,” 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photosensitizer screening platform [11] Application of microdroplet in molecular detection Droplet-base microfluidics... 1.1: Illustration of the three microfluidic devices that form the droplet-based microfluidic photosensitizer screening platform [11] Fig 1.2: Applications of microfluidic technologies in