CO2 Laser Fabrication of PMMA Microfluidic Double T-Junction Device with Modified Inlet-Angle for Cost-Effective PCR Application
Abstract
:1. Introduction
2. Materials and Methods
2.1. Device Description and Design Modification
2.2. Governing Equations
2.3. Simulation Model Verification
2.4. Channel Fabrication and Dimension Repeatability
2.5. Chip Bonding and Its Final Dimension
2.6. Experimental Setup
3. Results and Discussion
3.1. Simulation Results
3.2. Experimental Results
4. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- Cao, L.; Cui, X.; Hu, J.; Li, Z.; Choi, J.R.; Yang, Q.; Lin, M.; Li, Y.H.; Xu, F. Advances in digital polymerase chain reaction (dPCR) and its emerging biomedical applications. Biosens. Bioelectron. 2017, 90, 459–474. [Google Scholar] [CrossRef] [PubMed]
- Laird, P.W. Principles and challenges of genome-wide DNA methylation analysis. Nat. Rev. Genet. 2010, 11, 191–203. [Google Scholar] [CrossRef] [PubMed]
- Fan, S.; Chi, W. Methods for genome-wide DNA methylation analysis in human cancer. Brief. Funct. Genomics 2016, 15, 432–442. [Google Scholar] [CrossRef] [PubMed]
- Whale, A.S.; Huggett, J.F.; Cowen, S.; Speirs, V.; Shaw, J.; Ellison, S.; Foy, C.A.; Scott, D.J. Comparison of microfluidic digital PCR and conventional quantitative PCR for measuring copy number variation. Nucleic Acids Res. 2012, 40, e82. [Google Scholar] [CrossRef] [PubMed]
- Bu, M.; Perch-Nielsen, I.R.; Sørensen, K.S.; Skov, J.; Sun, Y.; Bang, D.D.; Pedersen, M.E.; Hansen, M.F.; Wolff, A. A temperature control method for shortening thermal cycling time to achieve rapid polymerase chain reaction (PCR) in a disposable polymer microfluidic device. J. Micromech. Microeng. 2013, 23, 74002. [Google Scholar] [CrossRef]
- Angeli, P.; Gavriilidis, A. Hydrodynamics of Taylor flow in small channels: A Review. Proc. Inst. Mech. Eng. Part C J. Mech. Eng. Sci. 2008, 222, 737–751. [Google Scholar] [CrossRef]
- Raj, R.; Mathur, N.; Buwa, V.V. Numerical Simulations of Liquid−Liquid Flows in Microchannels. Ind. Eng. Chem. Res. 2010, 49, 10606–10614. [Google Scholar] [CrossRef]
- Zhang, C.; Xing, D. Miniaturized PCR chips for nucleic acid amplification and analysis: Latest advances and future trends. Nucleic Acids Res. 2007, 35, 4223–4237. [Google Scholar] [CrossRef]
- Bandara, T.; Chandrashekar, M.; Rosengarten, G. Cfd Modelling of Liquid-Liquid Slug Flowheat Transfer in Microchannels. 28th Int. Symp. Transp. Phenom. 2017, 22–24. [Google Scholar]
- Zhang, Y.; Ozdemir, P. Microfluidic DNA amplification—A review. Anal. Chim. Acta 2009, 638, 115–125. [Google Scholar] [CrossRef]
- Daw, R.; Finkelstein, J. Lab on a chip. Nature 2006, 442, 367. [Google Scholar] [CrossRef]
- Teh, S.-Y.; Lin, R.; Hung, L.-H.; Lee, A.P. Droplet microfluidics. Lab Chip 2008, 8, 198. [Google Scholar] [CrossRef] [PubMed]
- Trantidou, T.; Friddin, M.S.; Salehi-Reyhani, A.; Ces, O.; Elani, Y. Droplet microfluidics for the construction of compartmentalised model membranes. Lab Chip 2018, 18, 2488–2509. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Christopher, G.F.; Anna, S.L. Microfluidic methods for generating continuous droplet streams. J. Phys. D Appl. Phys. 2007, 40, R319. [Google Scholar] [CrossRef]
- Chakraborty, I.; Ricouvier, J.; Yazhgur, P.; Tabeling, P.; Leshansky, A.M. Droplet generation at Hele-Shaw microfluidic T-junction. Phys. Fluids 2019, 31, 22010. [Google Scholar] [CrossRef]
- Muijlwijk, K.; Berton-Carabin, C.; Schroën, K. Cross-flow microfluidic emulsification from a food perspective. Trends Food Sci. Technol. 2016, 49, 51–63. [Google Scholar] [CrossRef]
- Faustino, V.; Catarino, S.O.; Lima, R.; Minas, G. Biomedical microfluidic devices by using low-cost fabrication techniques: A review. J. Biomech. 2016, 49, 2280–2292. [Google Scholar] [CrossRef] [Green Version]
- Zhang, Y.; Jiang, H.R. A review on continuous-flow microfluidic PCR in droplets: Advances, challenges and future. Anal. Chim. Acta 2016, 914, 7–16. [Google Scholar] [CrossRef] [Green Version]
- Islam, M.M.; Loewen, A.; Allen, P.B. Simple, low-cost fabrication of acrylic based droplet microfluidics and its use to generate DNA-coated particles. Sci. Rep. 2018, 8, 8763. [Google Scholar] [CrossRef] [Green Version]
- Muck, A.; Wang, J.; Jacobs, M.; Chen, G.; Chatrathi, M.P.; Jurka, V.; Výborný, Z.; Spillman, S.D.; Sridharan, G.; Schöning, M.J. Fabrication of poly(methyl methacrylate) microfluidic chips by atmospheric molding. Anal. Chem. 2004, 76, 2290–2297. [Google Scholar] [CrossRef]
- Kim, J.A.; Lee, J.Y.; Seong, S.; Cha, S.H.; Lee, S.H.; Kim, J.J.; Park, T.H. Fabrication and characterization of a PDMS-glass hybrid continuous-flow PCR chip. Biochem. Eng. J. 2006, 29, 91–97. [Google Scholar] [CrossRef]
- Greener, J.; Li, W.; Rem, J.; Voicu, D.; Pakharenko, V.; Tang, T.; Kumacheva, E. Rapid, cost-efficient fabrication of microfluidic reactors in thermoplastic polymers by combining photolithography and hot embossing. Lab Chip 2010, 10, 522–524. [Google Scholar] [CrossRef] [PubMed]
- Chiarello, E.; Gupta, A.; Mistura, G.; Sbragaglia, M.; Pierno, M. Droplet breakup driven by shear thinning solutions in a microfluidic T-junction. Phys. Rev. Fluids 2017, 2, 123602. [Google Scholar] [CrossRef] [Green Version]
- Nisisako, T.; Torii, T.; Higuchi, T. Droplet formation in a microchannel network. Lab Chip 2002, 2, 24–26. [Google Scholar] [CrossRef] [PubMed]
- Liu, Z.; Xu, W.; Hou, Z.; Wu, Z. A Rapid Prototyping Technique for Microfluidics with High Robustness and Flexibility. Micromachines 2016, 7, 201. [Google Scholar] [CrossRef] [PubMed]
- Au, A.K.; Lee, W.; Folch, A. Mail-order microfluidics: Evaluation of stereolithography for the production of microfluidic devices. Lab Chip 2014, 14, 1294–1301. [Google Scholar] [CrossRef] [PubMed]
- He, Y.; Wu, Y.; Fu, J.; Gao, Q.; Qiu, J. Developments of 3D Printing Microfluidics and Applications in Chemistry and Biology: A Review. Electroanalysis 2016, 28, 1658–1678. [Google Scholar] [CrossRef]
- Torabi, K.; Farjood, E.; Hamedani, S. Rapid Prototyping Technologies and their Applications in Prosthodontics, a Review of Literature. J. Dent. (Shiraz, Iran) 2015, 16, 1–9. [Google Scholar]
- Ogilvie, I.R.G.; Sieben, V.G.; Floquet, C.F.A.; Zmijan, R.; Mowlem, M.C.; Morgan, H. Reduction of surface roughness for optical quality microfluidic devices in PMMA and COC. J. Micromech. Microeng. 2010, 20, 65016. [Google Scholar] [CrossRef]
- Prakash, S.; Kumar, S. Fabrication of microchannels on transparent PMMA using CO2 Laser (10.6 μm) for microfluidic applications: An experimental investigation. Int. J. Precis. Eng. Manuf. 2015, 16, 361–366. [Google Scholar] [CrossRef]
- Pal, P.; Sato, K. Various shapes of silicon freestanding microfluidic channels and microstructures in one-step lithography. J. Micromech. Microeng. 2009, 19, 55003. [Google Scholar] [CrossRef]
- Cheng, Y.; Sugioka, K.; Midorikawa, K.; Masuda, M.; Toyoda, K.; Kawachi, M.; Shihoyama, K. Control of the cross-sectional shape of a hollow microchannel embedded in photostructurable glass by use of a femtosecond laser. Opt. Lett. 2003, 28, 55. [Google Scholar] [CrossRef]
- Osellame, R.; Maselli, V.; Vazquez, R.M.; Ramponi, R.; Cerullo, G. Integration of optical waveguides and microfluidic channels both fabricated by femtosecond laser irradiation. Appl. Phys. Lett. 2007, 90, 231118. [Google Scholar] [CrossRef]
- Nieto, D.; Couceiro, R.; Aymerich, M.; Lopez-Lopez, R.; Abal, M.; Flores-Arias, M.T. A laser-based technology for fabricating a soda-lime glass based microfluidic device for circulating tumour cell capture. Colloids Surf. B 2015, 134, 363–369. [Google Scholar] [CrossRef] [PubMed]
- Lim, D.; Kamotani, Y.; Cho, B.; Mazumder, J.; Takayama, S. Fabrication of microfluidic mixers and artificial vasculatures using a high-brightness diode-pumped Nd:YAG laser direct write method. Lab Chip 2003, 3, 318–323. [Google Scholar] [CrossRef] [PubMed]
- Liu, H.-B.; Gong, H.-Q. Templateless prototyping of polydimethylsiloxane microfluidic structures using a pulsed CO2 laser. J. Micromech. Microeng. 2009, 19, 3702. [Google Scholar] [CrossRef]
- Day, D.; Gu, M. Microchannel fabrication in PMMA based on localized heating by nanojoule high repetition rate femtosecond pulses. Opt. Express 2005, 13, 5939. [Google Scholar] [CrossRef] [PubMed]
- Wang, S.-C.; Lee, C.-Y.; Chen, H.-P. Thermoplastic microchannel fabrication using carbon dioxide laser ablation. J. Chromatogr. A 2006, 1111, 252–257. [Google Scholar] [CrossRef] [PubMed]
- Yu, H.; Chong, Z.Z.; Tor, S.B.; Liu, R.; Loh, N.H. Low temperature and deformation-free bonding of PMMA microfluidic devices with stable hydrophilicity via oxygen plasma treatment and PVA coating. RSC Adv. 2015, 5, 8377–8388. [Google Scholar] [CrossRef]
- Chen, X.; Li, T.; Shen, J. CO2 Laser Ablation of Microchannel on PMMA Substrate for Effective Fabrication of Microfluidic Chips. Int. Polym. Process. 2016, 31, 233–238. [Google Scholar] [CrossRef]
- Maselli, V.; Osellame, R.; Cerullo, G.; Ramponi, R.; Laporta, P. Fabrication of long microchannels with circular cross section using astigmatically shaped femtosecond laser pulses and chemical etching. Appl. Phys. Lett. 2006, 88, 191107. [Google Scholar] [CrossRef]
- Hnatovsky, C.; Taylor, R.S.; Simova, E.; Rajeev, P.P.; Rayner, D.M.; Bhardwaj, V.R.; Corkum, P.B. Fabrication of microchannels in glass using focused femtosecond laser radiation and selective chemical etching. Appl. Phys. A 2006, 84, 47–61. [Google Scholar] [CrossRef]
- Prakash, S.; Kumar, S. Fabrication of rectangular cross-sectional microchannels on PMMA with a CO2 laser and underwater fabricated copper mask. Opt. Laser Technol. 2017, 94, 180–192. [Google Scholar] [CrossRef]
- Helmy, M.O.; Fath El-Bab, A.M.; El-Hofy, H.A. Elimination of Clogging in PMMA Microchannels Using Water Assisted CO2 Laser Micromachining. Appl. Mech. Mater. 2015, 799–800, 407–412. [Google Scholar] [CrossRef]
- Helmy, M.O.; Fath El-Bab, A.R.; El-Hofy, H.A. Fabrication and characterization of polymethyl methacrylate microchannel using dry and underwater CO2 laser. Proc. Inst. Mech. Eng. Part N J. Nanomater. Nanoeng. Nanosyst. 2018, 232, 23–30. [Google Scholar] [CrossRef]
- Imran, M.; Rahman, R.A.; Ahmad, M.; Akhtar, M.N.; Usman, A.; Sattar, A. Fabrication of microchannels on PMMA using a low power CO2 laser. Laser Phys. 2016, 26, 96101. [Google Scholar] [CrossRef]
- Bhuyan, M.K.; Courvoisier, F.; Lacourt, P.-A.; Jacquot, M.; Furfaro, L.; Withford, M.J.; Dudley, J.M. High aspect ratio taper-free microchannel fabrication using femtosecond Bessel beams. Opt. Express 2010, 18, 566. [Google Scholar] [CrossRef]
- Brown, L.; Koerner, T.; Horton, J.H.; Oleschuk, R.D. Fabrication and characterization of poly(methylmethacrylate) microfluidic devices bonded using surface modifications and solvents. Lab Chip 2006, 6, 66–73. [Google Scholar] [CrossRef]
- Tsao, C.-W.; DeVoe, D.L. Bonding of thermoplastic polymer microfluidics. Microfluid. Nanofluid. 2009, 6, 1–16. [Google Scholar] [CrossRef]
- Kelly, R.T.; Woolley, A.T. Thermal bonding of polymeric capillary electrophoresis microdevices in water. Anal. Chem. 2003, 75, 1941–1945. [Google Scholar] [CrossRef]
- DU, L.; Chang, H.; Song, M.; Liu, C. The effect of injection molding PMMA microfluidic chips thickness uniformity on the thermal bonding ratio of chips. Microsyst. Technol. 2012, 18, 815–822. [Google Scholar] [CrossRef]
- Abdel Nasser, G.; Fath El-Bab, A.M.R.; Mohamed, H.; Abouelsoud, A. Low Cost Micro-Droplet Formation Chip with a Hand-Operated Suction Syringe. In Proceedings of the 2018 IEEE 18th International Conference on Bioinformatics and Bioengineering (BIBE), Taichung, Taiwan, 29–31 October 2018; pp. 73–78. [Google Scholar]
- Gu, Z.; Liow, J.L. Micro-droplet formation with non-Newtonian solutions in microfluidic T-junctions with different inlet angles. In Proceedings of the 2012 7th IEEE International Conference on Nano/Micro Engineered and Molecular Systems (NEMS), Kyoto, Japan, 5–8 March 2012; pp. 423–428. [Google Scholar]
- Thorsen, T.; Roberts, R.W.; Arnold, F.H.; Quake, S.R. Dynamic Pattern Formation in a Vesicle-Generating Microfluidic Device. Phys. Rev. Lett. 2001, 86, 4163–4166. [Google Scholar] [CrossRef] [Green Version]
- Ngo, I.-L.; Woo Joo, S.; Byon, C. Effects of Junction Angle and Viscosity Ratio on Droplet Formation in Microfluidic Cross-Junction. J. Fluids Eng. 2016, 138, 51202. [Google Scholar] [CrossRef]
- Yu, W.; Liu, X.; Zhao, Y.; Chen, Y. Droplet generation hydrodynamics in the microfluidic cross-junction with different junction angles. Chem. Eng. Sci. 2019, 203, 259–284. [Google Scholar] [CrossRef]
- Jin, B.-J.; Yoo, J.Y. Visualization of droplet merging in microchannels using micro-PIV. Exp. Fluids 2012, 52, 235–245. [Google Scholar] [CrossRef]
- Diehl, F.; Li, M.; He, Y.; Kinzler, K.W.; Vogelstein, B.; Dressman, D. BEAMing: Single-molecule PCR on microparticles in water-in-oil emulsions. Nat. Methods 2006, 3, 551–559. [Google Scholar] [CrossRef]
- Rosenfeld, L.; Lin, T.; Derda, R.; Tang, S.K.Y. Review and analysis of performance metrics of droplet microfluidics systems. Microfluid. Nanofluid. 2014, 16, 921–939. [Google Scholar] [CrossRef]
- Nekouei, M.; Vanapalli, S.A. Volume-of-fluid simulations in microfluidic T-junction devices: Influence of viscosity ratio on droplet size. Phys. Fluids 2017, 29, 32007. [Google Scholar] [CrossRef] [Green Version]
- Osher, S.; Sethian, J.A. Fronts propagating with curvature-dependent speed: Algorithms based on Hamilton-Jacobi formulations. J. Comput. Phys. 1988, 79, 12–49. [Google Scholar] [CrossRef] [Green Version]
- Brackbill, J.; Kothe, D.; Zemach, C. A continuum method for modeling surface tension. J. Comput. Phys. 1992, 100, 335–354. [Google Scholar] [CrossRef]
- Hirt, C.; Nichols, B. Volume of fluid (VOF) method for the dynamics of free boundaries. J. Comput. Phys. 1981, 39, 201–225. [Google Scholar] [CrossRef]
- Garstecki, P.; Fuerstman, M.J.; Stone, H.A.; Whitesides, G.M. Formation of droplets and bubbles in a microfluidic T-junction—scaling and mechanism of break-up. Lab Chip 2006, 6, 437. [Google Scholar] [CrossRef]
- Chinaud, M.; Roumpea, E.-P.; Angeli, P. Studies of plug formation in microchannel liquid–liquid flows using advanced particle image velocimetry techniques. Exp. Therm. Fluid Sci. 2015, 69, 99–110. [Google Scholar] [CrossRef]
- Lin, C.H.; Chao, C.H.; Lan, C.W. Low azeotropic solvent for bonding of PMMA microfluidic devices. Sens. Actuators B 2007, 121, 698–705. [Google Scholar] [CrossRef]
- Lankveld, J.M.; Lyklema, J. Adsorption of polyvinyl alcohol on the paraffin—water interface. I. Interfacial tension as a function of time and concentration. J. Colloid Interface Sci. 1972, 41, 454–465. [Google Scholar] [CrossRef]
Parameters | Simulation | Experimental | ||
---|---|---|---|---|
MDTJ | DTJ | MDTJ | DTJ | |
Diameter (μm) | 94 | 102 | 80 ± 2.5 | 93 ± 4 |
Frequency (d/s) | 138 | 111.1 | 121 | 101 |
Distance (μm) | 1608 | 2081 | 745 ± 40 | 875 ± 60 |
Reference | [39] | [30] | [15] | [19] | Our work | |
Geometry | DTJ | - | T-junction | DTJ | DTJ | MDTJ |
Material | PMMA | PMMA | PDMS | PMMA | PMMA | PMMA |
Fabrication tech. | Lithography, micromold | CO2 Laser | Soft lithography | CO2 Laser | CO2 Laser | CO2 Laser |
Ch. Width | ||||||
Cross Section | Square | Gaussian | Rectangle | Gaussian | Gaussian | Gaussian |
Oil flow rate | - | |||||
Water flow rate | - | |||||
Droplet Dia. | - | |||||
Cost/chip | >>1$ | - | >1$ | 1$ | <30 cents | <30 cents |
Fabric. time | >1 day | - | >1 hr | 10–20 min. | 20 min. | 20 min. |
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Nasser, G.A.; Fath El-Bab, A.M.R.; Abdel-Mawgood, A.L.; Mohamed, H.; Saleh, A.M. CO2 Laser Fabrication of PMMA Microfluidic Double T-Junction Device with Modified Inlet-Angle for Cost-Effective PCR Application. Micromachines 2019, 10, 678. https://0-doi-org.brum.beds.ac.uk/10.3390/mi10100678
Nasser GA, Fath El-Bab AMR, Abdel-Mawgood AL, Mohamed H, Saleh AM. CO2 Laser Fabrication of PMMA Microfluidic Double T-Junction Device with Modified Inlet-Angle for Cost-Effective PCR Application. Micromachines. 2019; 10(10):678. https://0-doi-org.brum.beds.ac.uk/10.3390/mi10100678
Chicago/Turabian StyleNasser, Gamal A., Ahmed M.R. Fath El-Bab, Ahmed L. Abdel-Mawgood, Hisham Mohamed, and Abdelatty M. Saleh. 2019. "CO2 Laser Fabrication of PMMA Microfluidic Double T-Junction Device with Modified Inlet-Angle for Cost-Effective PCR Application" Micromachines 10, no. 10: 678. https://0-doi-org.brum.beds.ac.uk/10.3390/mi10100678