Abstract
Most of the existing microfluidic chip fabrication techniques are very complex, time-consuming, costly, and are not amenable to mass manufacturing. Impending commercialization of lab-on-a-chip devices demand development of new microfabrication methods that involve least procedural complexities using cost-effective materials. This paper proposes an inexpensive and time-efficient procedure for constructing microfluidic devices on a flexographic sheet which is available as commercial-off-the-shelf material, using a mould-free soft-lithography approach. Microchannel design is transferred to a negative-resist photopolymer sheet (PPS) using collimated ultraviolet (UV) rays and etching is performed to remove unexposed material. The microchannel network is sealed on the top by a photopolymer sheet of the same material and pressure-assisted bonding is performed in the presence of UV. The cross-linking between photopolymers in the mating surfaces ensures relatively high bond strength and perfect sealing. Simple and complex microchannel network with 100–500 \(\upmu\)m width is created using this method and various characterization tests are performed. A functional leakage test ensured that the fabricated chip could withstand 200 kPa pressure at a maximum flow rate of 12 mL/min. Cell culture, biomolecule visualization, and droplet mixing dynamics are studied in the microchip to demonstrate its practical utility. Moreover, a large-area chip with 260 \(\times\) 190 mm\(^2\) is created using PPS with this three-step method. Most importantly, this method could mass produce 24 microchips with multiple designs within a span of 2 h. In other words, the average time incurred for the fabrication of a single microchip (50 \(\times\) 30 mm\(^2\)) is less than 5 min. Results suggest that it is a promising method flexible enough to create large-sized chips and to bulk-fabricate microchips having versatile channel designs with high fidelity. Since flexographic infrastructure and materials are very cheap and common in resource-limited settings, the proposed method assumes more importance in the context of rapid commercialization of lab-on-a-chip devices.
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References
Alhareb AO, Akil HM, Ahmad ZA (2017) Impact strength, fracture toughness and hardness improvement of PMMA denture base through addition of nitrile rubber/ceramic fillers. Saudi J Dent Res 8(1–2):26–34
Andrzejewska E (2001) Photopolymerization kinetics of multifunctional monomers. Prog Polym Sci 26(4):605–665
Annabestani M, Esmaeili-Dokht P, Fardmanesh M (2020) A novel, low cost, and accessible method for rapid fabrication of the modifiable microfluidic devices. Sci Rep 10(1):1–10
Areid N, Peltola A, Kangasniemi I, Ballo A, Närhi TO (2018) Effect of ultraviolet light treatment on surface hydrophilicity and human gingival fibroblast response on nanostructured titanium surfaces. Clin Exp Dent Res 4(3):78–85
Arjun A, Ajith R, Kumar Ranjith S (2020) Mixing characterization of binary-coalesced droplets in microchannels using deep neural network. Biomicrofluidics 14(3):034111
Aziz AA, Azmi MAM, Zulkifli MN, Nordin AN, Bahrain AK, Makmon FZ, Badruzzaman NA, Sabdin S (2019) Rapid fabrication and characterization of PDMS microfluidics device using printed conductive silver ink. Mater Today Proc 16:1661–1667
Azizipour N, Avazpour R, Rosenzweig DH, Sawan M, Ajji A (2020) Evolution of biochip technology: a review from lab-on-a-chip to organ-on-a-chip. Micromachines 11(6):599
Borók A, Laboda K, Bonyár A (2021) PDMS bonding technologies for microfluidic applications: a review. Biosensors 11(8):292
Bourguignon N, Olmos CM, Sierra-Rodero M, Penaherrera A, Rosero G, Pineda P, Vizuete K, Arroyo CR, Cumbal L, Lasorsa C et al (2018) Accessible and cost-effective method of PDMS microdevices fabrication using a reusable photopolymer mold. J Polym Sci Part B Polym Phys 56(21):1433–1442
Bourguignon N, Karp P, Attallah C, Chamorro DA, Oggero M, Booth R, Ferrero S, Bhansali S, Pérez MS, Lerner B et al (2022) Large area microfluidic bioreactor for production of recombinant protein. Biosensors 12(7):526
Chen Y, Zhang L, Chen G (2008) Fabrication, modification, and application of poly (methyl methacrylate) microfluidic chips. Electrophoresis 29(9):1801–1814
Choi NW, Cabodi M, Held B, Gleghorn JP, Bonassar LJ, Stroock AD (2007) Microfluidic scaffolds for tissue engineering. Nat Mater 6(11):908–915
Chou J, Du N, Ou T, Floriano PN, Christodoulides N, McDevitt JT (2013) Hot embossed polyethylene through-hole chips for bead-based microfluidic devices. Biosens Bioelectron 42:653–660
Convery N, Gadegaard N (2019) 30 years of microfluidics. Micro Nano Eng 2:76–91
Duffy DC, McDonald JC, Schueller OJ, Whitesides GM (1998) Rapid prototyping of microfluidic systems in poly (dimethylsiloxane). Anal Chem 70(23):4974–4984
Fiorini GS, Lorenz RM, Kuo JS, Chiu DT (2004) Rapid prototyping of thermoset polyester microfluidic devices. Anal Chem 76(16):4697–4704
Fujii T (2002) PDMS-based microfluidic devices for biomedical applications. Microelectron Eng 61:907–914
Ghaemmaghami AM, Hancock MJ, Harrington H, Kaji H, Khademhosseini A (2012) Biomimetic tissues on a chip for drug discovery. Drug Discov Today 17(3–4):173–181
Giel DK, Berłowska J (2009) Evaluation of yeast cell vitality using different fluorescent dyes
Golhin AP, Tonello R, Frisvad JR, Grammatikos S, Strandlie A (2023) Surface roughness of as-printed polymers: a comprehensive review. Int J Adv Manuf Technol 1–57
Guan T, Yuket S, Cong H, Carton DW, Zhang N (2022) Permanent hydrophobic surface treatment combined with solvent vapor-assisted thermal bonding for mass production of cyclic olefin copolymer microfluidic chips. ACS Omega 7(23):20104–17
Han X, Zhang Y, Tian J, Wu T, Li Z, Xing F, Fu S (2022) Polymer-based microfluidic devices: a comprehensive review on preparation and applications. Polym Eng Sci 62(1):3–24
Hashmi A, Xu J (2014) On the quantification of mixing in microfluidics. J Lab Autom 19(5):488–491
Ito T, Kawaguchi T, Miyoshi H, Maruyama K, Honda A, Kaneko S, Ohya S, Niwa O, Terasaka K, Suzuki K (2006) Fabrication of high performance polymeric microfluidic device by a simple imprinting method using a photosensitive sheet. Jpn J Appl Phys 45(1L):64
Jaimon C, Ranjith SK (2017) Numerical investigations on mixing in microchannels with transverse hydrophobic strips. Microsyst Technol 23(7):2881–2890
Kim P, Kwon KW, Park MC, Lee SH, Kim SM, Suh KY (2008) Soft lithography for microfluidics: a review. Biochip J 2(1):1
Kim S, Sojoudi H, Zhao H, Mariappan D, McKinley GH, Gleason KK, Hart AJ (2016) Ultrathin high-resolution flexographic printing using nanoporous stamps. Sci Adv 2(12):1601660
Koerner T, Brown L, Xie R, Oleschuk RD (2005) Epoxy resins as stamps for hot embossing of microstructures and microfluidic channels. Sens Actuators B Chem 107(2):632–639
Kojic SP, Stojanovic GM, Radonic V (2019) Novel cost-effective microfluidic chip based on hybrid fabrication and its comprehensive characterization. Sensors 19(7):1719
Liang F, Qiao Y, Duan M, Ju A, Lu N, Li J, Tu J, Lu Z (2018) Fabrication of a microfluidic chip based on the pure polypropylene material. RSC Adv 8(16):8732–8738
Liga A, Morton JA, Kersaudy-Kerhoas M (2016) Safe and cost-effective rapid-prototyping of multilayer pmma microfluidic devices. Microfluid Nanofluid 20(12):1–12
Lin L, Chung C-K (2021) PDMS microfabrication and design for microfluidics and sustainable energy application. Micromachines 12(11):1350
Mair DA, Rolandi M, Snauko M, Noroski R, Svec F, Fréchet JM (2007) Room-temperature bonding for plastic high-pressure microfluidic chips. Anal Chem 79(13):5097–5102
Mathur A, Roy S, Tweedie M, Mukhopadhyay S, Mitra S, McLaughlin J (2009) Characterisation of PMMA microfluidic channels and devices fabricated by hot embossing and sealed by direct bonding. Curr Appl Phys 9(6):1199–1202
McDonald JC, Whitesides GM (2002) Poly (dimethylsiloxane) as a material for fabricating microfluidic devices. Acc Chem Res 35(7):491–499
Metz S, Holzer R, Renaud P (2001) Polyimide-based microfluidic devices. Lab Chip 1(1):29–34
Miranda I, Souza A, Sousa P, Ribeiro J, Castanheira EM, Lima R, Minas G (2021) Properties and applications of PDMS for biomedical engineering: a review. J Funct Biomater 13(1):2
Niculescu A-G, Chircov C, Bîrcă AC, Grumezescu AM (2021) Fabrication and applications of microfluidic devices: a review. Int J Mol Sci 22(4):2011
Novaković D, Dedijer S, Gojo M, Poljaček SM (2010) Analsys of surface roughness factors of solid printing areas on flexo printing plates
Ogończyk D, Węgrzyn J, Jankowski P, Dąbrowski B, Garstecki P (2010) Bonding of microfluidic devices fabricated in polycarbonate. Lab Chip 10(10):1324–1327
Olmos CM, Vaca A, Rosero G, Peñaherrera A, Perez C, de Sá Carneiro I, Vizuete K, Arroyo CR, Debut A, Pérez MS et al (2019) Epoxy resin mold and PDMS microfluidic devices through photopolymer flexographic printing plate. Sens Actuators B Chem 288:742–748
Olmos CM, Peñaherrera A, Rosero G, Vizuete K, Ruarte D, Follo M, Vaca A, Arroyo CR, Debut A, Cumbal L et al (2020) Cost-effective fabrication of photopolymer molds with multi-level microstructures for PDMS microfluidic device manufacture. RSC Adv 10(7):4071–4079
Pandey R (2014) Photopolymers in 3D printing applications
Poliaiek SM, Tomaiegovi MG (2012) Influence of UV exposure on the surface and mechanical properties of flexographic printing plate. In: Proceedings of the GRID 2012 symposium, Novi Sad, Serbia, pp 15–16
Rahmanian O, DeVoe DL (2013) Pen microfluidics: rapid desktop manufacturing of sealed thermoplastic microchannels. Lab Chip 13(6):1102–1108
Raj MK, Chakraborty S (2020) PDMS microfluidics: a mini review. J Appl Polym Sci 137(27):48958
Ren K, Zhao Y, Su J, Ryan D, Wu H (2010) Convenient method for modifying poly (dimethylsiloxane) to be airtight and resistive against absorption of small molecules. Anal Chem 82(14):5965–5971
Renaud P, Lintel Hv, Heuschkel M, Guérin L (1998) Photo-polymer microchannel technologies and applications. In: Micro total analysis systems’ 98. Springer, pp 17–22
Rusu MC, Block C, Van Assche G, Van Mele B (2012) Influence of temperature and UV intensity on photo-polymerization reaction studied by photo-dsc. J Therm Anal Calorim 110(1):287–294
Sackmann EK, Fulton AL, Beebe DJ (2014) The present and future role of microfluidics in biomedical research. Nature 507(7491):181–189
Sales FC, Ariati RM, Noronha VT, Ribeiro JE (2022) Mechanical characterization of PDMS with different mixing ratios. Proc Struct Integr 37:383–388
Shakeri A, Khan S, Didar TF (2021) Conventional and emerging strategies for the fabrication and functionalization of PDMS-based microfluidic devices. Lab Chip 21(16):3053–3075
Shakeri A, Jarad NA, Khan S, Didar FT (2022) Bio-functionalization of microfluidic platforms made of thermoplastic materials: a review. Analyt Chim Acta 1209:339283
Suryawanshi PL, Gumfekar SP, Bhanvase BA, Sonawane SH, Pimplapure MS (2018) A review on microreactors: reactor fabrication, design, and cutting-edge applications. Chem Eng Sci 189:431–448
Thai DA, Lee NY et al (2022) Bonding strategies for thermoplastics applicable for bioanalysis and diagnostics. Micromachines 13(9):1503
Tomašegović T (2016) Functional model of photopolymer printing plate production process. PhD thesis, University of Zagreb
Tomašegović T, Mahović Poljaček S, Strižić Jakovljević M, Urbas R (2020) Effect of the common solvents on UV-modified photopolymer and EPDM flexographic printing plates and printed ink films. Coatings 10(2):136
Tran HH, Wu W, Lee NY (2013) Ethanol and UV-assisted instantaneous bonding of PMMA assemblies and tuning in bonding reversibility. Sens Actuators B Chem 181:955–962
Trinh KTL, Thai DA, Chae WR, Lee NY (2020) Rapid fabrication of poly (methyl methacrylate) devices for lab-on-a-chip applications using acetic acid and UV treatment. ACS Omega 5(28):17396–17404
Tsao C-W (2016) Polymer microfluidics: simple, low-cost fabrication process bridging academic lab research to commercialized production. Micromachines 7(12):225
Waddell EA, Locascio LE, Kramer GW (2002) UV laser micromachining of polymers for microfluidic applications. JALA J Assoc Lab Autom 7(1):78–82
Walsh DI III, Kong DS, Murthy SK, Carr PA (2017) Enabling microfluidics: from clean rooms to makerspaces. Trends Biotechnol 35(5):383–392
Wang Y, He Q, Dong Y, Chen H (2010) In-channel modification of biosensor electrodes integrated on a polycarbonate microfluidic chip for micro flow-injection amperometric determination of glucose. Sens Actuators B Chem 145(1):553–560
Wang Y, Balowski J, Phillips C, Phillips R, Sims CE, Allbritton NL (2011) Benchtop micromolding of polystyrene by soft lithography. Lab Chip 11(18):3089–3097
Wolf MP, Salieb-Beugelaar GB, Hunziker P (2018) PDMS with designer functionalities-properties, modifications strategies, and applications. Prog Polym Sci 83:97–134
Xie S, Wu J, Tang B, Zhou G, Jin M, Shui L (2017) Large-area and high-throughput PDMS microfluidic chip fabrication assisted by vacuum airbag laminator. Micromachines 8(7):218
Yao Y, Li L, Jiang J, Zhang Y, Chen G, Fan Y (2022) Reversible bonding for microfluidic devices with UV release tape. Microfluid Nanofluid 26(3):1–10
Young EW, Berthier E, Guckenberger DJ, Sackmann E, Lamers C, Meyvantsson I, Huttenlocher A, Beebe DJ (2011) Rapid prototyping of arrayed microfluidic systems in polystyrene for cell-based assays. Anal Chem 83(4):1408–1417
Zhang Y, Han J-H, Zhu L, Shannon MA, Yeom J (2014) Soft lithographic printing and transfer of photosensitive polymers: facile fabrication of free-standing structures and patterning fragile and unconventional substrates. J Micromech Microeng 24(11):115019
Zhou P, He H, Ma H, Wang S, Hu S (2022) A review of optical imaging technologies for microfluidics. Micromachines 13(2):274
Acknowledgements
All India Council for Technical Education (AICTE) of the Government of India is gratefully acknowledged by the authors for providing funding for this study under the RPS [No. 8-64/FDC/RPS/Policy-1/2021-22] and MODROB scheme [No. 9-11/RIFD/MODROB/Policy-1/2017-19] . The authors would also like to thank A. S Saranya of Microbiology lab, Department of Civil Engineering, College of Engineering Trivandrum for biological assistance and Central Laboratory for Instrumentation and Facilitation (CLIF), University of Kerala for the instrumentation support.
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RR conducted the experiments and wrote the main manuscript text, NP helped with methodology, ARR helped with the fabrication, SP designed the experiments, MRS conceptualized, arranged funding, supervised research, and and RSK conceptualized, analyzed results, supervised research. All authors reviewed the manuscript.
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Rahul, R., Prasad, N., Ajith, R.R. et al. A mould-free soft-lithography approach for rapid, low-cost and bulk fabrication of microfluidic chips using photopolymer sheets. Microfluid Nanofluid 27, 78 (2023). https://doi.org/10.1007/s10404-023-02688-7
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DOI: https://doi.org/10.1007/s10404-023-02688-7