Advertisement

Characterization and evaluation of 3D printed microfluidic chip for cell processing

  • Jia Min Lee
  • Meng Zhang
  • Wai Yee Yeong
Research Paper

Abstract

Microfluidics has found ubiquitous presence in biological applications such as tissue spheroid fabrication and pharmacology investigation. The increasing prevalence and complexity demand a highly adaptable fabrication method for the rapid and convenient production of these microfluidic systems. 3D printing, as an emerging fabrication technique, was investigated in this paper. Microfluidic features were fabricated using two most widely used 3D printing technologies namely the inkjet printing and filament deposition techniques. The printing resolution, accuracy, repeatability, surface roughness, wetting ability, and biocompatibility of the printed microfluidic chips were characterized. The capability of 3D printing was demonstrated by printing a number of microfluidic devices such as rotational flow device and gradient generator. Results showed that 3D printing techniques were successful in making intricate microscale architectures and have the potential of greatly simplifying the manufacturing process.

Keywords

3D printing Additive manufacturing Rapid prototyping Microfluidics Material characterization Cells Tissue engineering 

Notes

Compliance with ethical standards

Conflict of interest

The authors do not have conflict of interest to declare.

References

  1. Anderson JR, Chiu DT, Jackman RJ, Cherniavskaya O, McDonald JC, Wu H, Whitesides GM (2000a) Fabrication of topologically complex three-dimensional microfluidic systems in PDMS by rapid prototyping. Anal Chem 72(14):3158–3164CrossRefGoogle Scholar
  2. Anderson JR, Chiu DT, Wu H, Schueller OJ, Whitesides GM (2000b) Fabrication of microfluidic systems in poly (dimethylsiloxane). Electrophoresis 21:27–40CrossRefGoogle Scholar
  3. Au AK, Bhattacharjee N, Horowitz LF, Chang TC, Folch A (2015) 3D-printed microfluidic automation. Lab Chip 15(8):1934–1941. doi: 10.1039/C5LC00126A CrossRefGoogle Scholar
  4. Benavente-Babace A, Gallego-Perez D, Hansford DJ, Arana S, Perez-Lorenzo E, Mujika M (2014) Single-cell trapping and selective treatment via co-flow within a microfluidic platform. Biosens Bioelectron 61:298–305. doi: 10.1016/j.bios.2014.05.036 CrossRefGoogle Scholar
  5. Bhagat AAS, Kuntaegowdanahalli SS, Papautsky I (2008) Continuous particle separation in spiral microchannels using dean flows and differential migration. Lab Chip 8(11):1906–1914. doi: 10.1039/b807107a CrossRefGoogle Scholar
  6. Capel AJ, Edmondson S, Christie SD, Goodridge RD, Bibb RJ, Thurstans M (2013) Design and additive manufacture for flow chemistry. Lab Chip 13(23):4583–4590CrossRefGoogle Scholar
  7. Chan HF, Zhang Y, Ho Y-P, Chiu Y-L, Jung Y, Leong KW (2013) Rapid formation of multicellular spheroids in double-emulsion droplets with controllable microenvironment. Sci Rep. doi: 10.1038/srep03462 Google Scholar
  8. Choi J-W, Wicker RB, Cho S-H, Ha C-S, Lee S-H (2009) Cure depth control for complex 3D microstructure fabrication in dynamic mask projection microstereolithography. Rapid Prototyp J 15(1):59–70CrossRefGoogle Scholar
  9. Chu D, Nemoto A, Ito H (2014) Effects of geometric parameters for superhydrophobicity of polymer surfaces fabricated by precision tooling machines. Microsyst Technol 20(2):193–200. doi: 10.1007/s00542-013-1758-3 CrossRefGoogle Scholar
  10. Chua C-K, Yeong W-Y, Leong K-F (2005) Rapid prototyping in tissue engineering: a state-of-the-art report. In: Virtual modelling and rapid manufacturing—advanced research in virtual and rapid prototyping, pp 19–27Google Scholar
  11. Cui X, Dean D, Ruggeri ZM, Boland T (2010) Cell damage evaluation of thermal inkjet printed Chinese hamster ovary cells. Biotechnol Bioeng 106(6):963–969CrossRefGoogle Scholar
  12. Feng Z, Skommer J, Macdonald NP, Friedrich T, Kaslin J, Wlodkowic D (2015) Three-dimensional printed millifluidic devices for zebrafish embryo tests. Biomicrofluidics 9(4):1–10. doi: 10.1063/1.4927379 Google Scholar
  13. Fiorini GS, Chiu DT (2005) Disposable microfluidic devices: fabrication, function, and application. Biotechniques 38(3):429–446CrossRefGoogle Scholar
  14. Good RJ, Koo M (1979) The effect of drop size on contact angle. J Colloid Interface Sci 71(2):283–292CrossRefGoogle Scholar
  15. Gurrala PK, Regalla SP (2014) Part strength evolution with bonding between filaments in fused deposition modelling. Virtual Phys Prototyp 9(3):141–149. doi: 10.1080/17452759.2014.913400 CrossRefGoogle Scholar
  16. Ho C-M, Tai Y-C (1998) Micro-electro-mechanical-systems (MEMS) and fluid flows. Annu Rev Fluid Mech 30(1):579–612CrossRefGoogle Scholar
  17. Holmes D, Whyte G, Bailey J, Vergara-Irigaray N, Ekpenyong A, Guck J, Duke T (2014) Separation of blood cells with differing deformability using deterministic lateral displacement. Interface Focus 4(6):20140011CrossRefGoogle Scholar
  18. Hsiao AY, Torisawa Y-S, Tung Y-C, Sud S, Taichman RS, Pienta KJ, Takayama S (2009) Microfluidic system for formation of PC-3 prostate cancer co-culture spheroids. Biomaterials 30(16):3020–3027. doi: 10.1016/j.biomaterials.2009.02.047 CrossRefGoogle Scholar
  19. Huang LR, Cox EC, Austin RH, Sturm JC (2004) Continuous particle separation through deterministic lateral displacement. Science 304(5673):987–990. doi: 10.1126/science.1094567 CrossRefGoogle Scholar
  20. Huang Y, Liu S, Yang W, Yu C (2010) Surface roughness analysis and improvement of PMMA-based microfluidic chip chambers by CO2 laser cutting. Appl Surf Sci 256(6):1675–1678CrossRefGoogle Scholar
  21. Ismagilov RF, Rosmarin D, Kenis PJA, Chiu DT, Zhang W, Stone HA, Whitesides GM (2001) Pressure-driven laminar flow in tangential microchannels: an elastomeric microfluidic switch. Anal Chem 73(19):4682–4687. doi: 10.1021/ac010374q CrossRefGoogle Scholar
  22. Kang E, Jeong GS, Choi YY, Lee KH, Khademhosseini A, Lee S-H (2011) Digitally tunable physicochemical coding of material composition and topography in continuous microfibres. Nat Mater 10(11):877–883CrossRefGoogle Scholar
  23. Khoo ZX, Teoh JEM, Liu, Y, Chua CK, Yang S, An J, Leong, KF, Yeong WY (2015) 3D printing of smart materials: a review on recent progresses in 4D printing. Virtual Phys Prototyp 10(3):103–122. doi: 10.1080/17452759.2015.1097054 CrossRefGoogle Scholar
  24. Kuo C-T, Chiang C-L, Chang C-H, Liu H-K, Huang G-S, Huang RY-J, Wo AM (2014) Modeling of cancer metastasis and drug resistance via biomimetic nano-cilia and microfluidics. Biomaterials 35(5):1562–1571. doi: 10.1016/j.biomaterials.2013.11.008 CrossRefGoogle Scholar
  25. Lee JM, Yeong WY (2015) A preliminary model of time-pressure dispensing system for bioprinting based on printing and material parameters. Virtual Phys Prototyp 10(1):3–8. doi: 10.1080/17452759.2014.979557 CrossRefGoogle Scholar
  26. Liao Y, Song J, Li E, Luo Y, Shen Y, Chen D, Midorikawa K (2012) Rapid prototyping of three-dimensional microfluidic mixers in glass by femtosecond laser direct writing. Lab Chip 12(4):746–749CrossRefGoogle Scholar
  27. Takai H, Kojima M, Ohara K, Horade M, Tanikawa T, Mae Y, IEEE (2013) Microfluidic device for automated generation of toroidal-like spheroids. In: 2013 10th international conference on ubiquitous robots and ambient intelligence, pp 140–143Google Scholar
  28. Malda J, Visser J, Melchels FP, Jüngst T, Hennink WE, Dhert WJ, Hutmacher DW (2013) 25th anniversary article: engineering hydrogels for biofabrication. Adv Mater 25(36):5011–5028CrossRefGoogle Scholar
  29. Marmur A (1996) Equilibrium contact angles: theory and measurement. Colloids Surf A 116(1–2):55–61. doi: 10.1016/0927-7757(96)03585-6 CrossRefGoogle Scholar
  30. McDonald JC, Chabinyc ML, Metallo SJ, Anderson JR, Stroock AD, Whitesides GM (2002) Prototyping of microfluidic devices in poly(dimethylsiloxane) using solid-object printing. Anal Chem 74(7):1537–1545. doi: 10.1021/ac010938q CrossRefGoogle Scholar
  31. Mironi-Harpaz I, Wang DY, Venkatraman S, Seliktar D (2012) Photopolymerization of cell-encapsulating hydrogels: crosslinking efficiency versus cytotoxicity. Acta Biomater 8(5):1838–1848. doi: 10.1016/j.actbio.2011.12.034 CrossRefGoogle Scholar
  32. Moltzahn F, Olshen AB, Baehner L, Peek A, Fong L, Stöppler H, Blelloch R (2011) Microfluidic-based multiplex qRT-PCR identifies diagnostic and prognostic microRNA signatures in the sera of prostate cancer patients. Cancer Res 71(2):550–560. doi: 10.1158/0008-5472.can-10-1229 CrossRefGoogle Scholar
  33. Moore J, McCuiston A, Mittendorf I, Ottway R, Johnson RD (2011) Behavior of capillary valves in centrifugal microfluidic devices prepared by three-dimensional printing. Microfluid Nanofluid 10(4):877–888. doi: 10.1007/s10404-010-0721-1 CrossRefGoogle Scholar
  34. Nagrath S, Sequist LV, Maheswaran S, Bell DW, Irimia D, Ulkus L, Toner M (2007) Isolation of rare circulating tumour cells in cancer patients by microchip technology. Nature 450(7173):U1235–U1240. doi: 10.1038/nature06385 CrossRefGoogle Scholar
  35. Novik E, Maguire TJ, Chao P, Cheng KC, Yarmush ML (2010) A microfluidic hepatic coculture platform for cell-based drug metabolism studies. Biochem Pharmacol 79(7):1036–1044. doi: 10.1016/j.bcp.2009.11.010 CrossRefGoogle Scholar
  36. Okushima S, Nisisako T, Torii T, Higuchi T (2004) Controlled production of monodisperse double emulsions by two-step droplet breakup in microfluidic devices. Langmuir 20(23):9905–9908. doi: 10.1021/la0480336 CrossRefGoogle Scholar
  37. Onoe H, Okitsu T, Itou A, Kato-Negishi M, Gojo R, Kiriya D, Kuribayashi-Shigetomi K (2013) Metre-long cell-laden microfibres exhibit tissue morphologies and functions. Nat Mater 12(6):584–590CrossRefGoogle Scholar
  38. Ota H, Kodama T, Miki N (2010a) Microfluidic experimental array using micro-rotation flow for producing size-controlled three-dimensional spheroids. Paper presented at the 2010 International Symposium on Micro-NanoMechatronics and Human Science (MHS), 7–10 Nov 2010Google Scholar
  39. Ota H, Yamamoto R, Deguchi K, Tanaka Y, Kazoe Y, Sato Y, Miki N (2010b) Three-dimensional spheroid-forming lab-on-a-chip using micro-rotational flow. Sens Actuators B 147(1):359–365. doi: 10.1016/j.snb.2009.11.061 CrossRefGoogle Scholar
  40. Ota H, Kodama T, Miki N (2011) Rapid formation of size-controlled three dimensional hetero-cell aggregates using micro-rotation flow for spheroid study. Biomicrofluidics. doi: 10.1063/1.3609969 Google Scholar
  41. Paydar OH, Paredes CN, Hwang Y, Paz J, Shah NB, Candler RN (2014) Characterization of 3D-printed microfluidic chip interconnects with integrated O-rings. Sens Actuators A 205:199–203. doi: 10.1016/j.sna.2013.11.005 CrossRefGoogle Scholar
  42. Polzin C, Spath S, Seitz H (2013) Characterization and evaluation of a PMMA-based 3D printing process. Rapid Prototyp J 19(1):37–43CrossRefGoogle Scholar
  43. Rival A, Jary D, Delattre C, Fouillet Y, Castellan G, Bellemin-Comte A, Gidrol X (2014) An EWOD-based microfluidic chip for single-cell isolation, mRNA purification and subsequent multiplex qPCR. Lab Chip 14(19):3739–3749. doi: 10.1039/C4LC00592A CrossRefGoogle Scholar
  44. Rogers CI, Qaderi K, Woolley AT, Nordin GP (2015) 3D printed microfluidic devices with integrated valves. Biomicrofluidics 9(1):016501. doi: 10.1063/1.4905840 CrossRefGoogle Scholar
  45. Sakai S, Ito S, Inagaki H, Hirose K, Matsuyama T, Taya M, Kawakami K (2011) Cell-enclosing gelatin-based microcapsule production for tissue engineering using a microfluidic flow-focusing system. Biomicrofluidics. doi: 10.1063/1.3516657 Google Scholar
  46. Schrott W, Slouka Z, Červenka P, Ston J, Nebyla M, Přibyl M, Šnita D (2009) Study on surface properties of PDMS microfluidic chips treated with albumin. Biomicrofluidics 3(4):044101CrossRefGoogle Scholar
  47. Shallan AI, Smejkal P, Corban M, Guijt RM, Breadmore MC (2014) Cost-effective three-dimensional printing of visibly transparent microchips within minutes. Anal Chem 86(6):3124–3130. doi: 10.1021/ac4041857 CrossRefGoogle Scholar
  48. Shen F, Li X, Li PCH (2014) Study of flow behaviors on single-cell manipulation and shear stress reduction in microfluidic chips using computational fluid dynamics simulations. Biomicrofluidics 8(1):014109. doi: 10.1063/1.4866358 CrossRefGoogle Scholar
  49. Shih SCC, Barbulovic-Nad I, Yang X, Fobel R, Wheeler AR (2013) Digital microfluidics with impedance sensing for integrated cell culture andanalysis. Biosens Bioelectron 42:314–320. doi: 10.1016/j.bios.2012.10.035 CrossRefGoogle Scholar
  50. Sing SL, An J, Yeong WY, Wiria FE (2015) Laser and electron-beam powder-bed additive manufacturing of metallic implants: a review on processes, materials and designs. J Orthop Res. doi: 10.1002/jor.23075 Google Scholar
  51. Singh R (2011) Process capability study of polyjet printing for plastic components. J Mech Sci Technol 25(4):1011–1015. doi: 10.1007/s12206-011-0203-8 CrossRefGoogle Scholar
  52. Sun J, He Y, Tao W, Yin X, Wang H (2012) Roughness effect on flow and thermal boundaries in microchannel/nanochannel flow using molecular dynamics-continuum hybrid simulation. Int J Numer Methods Eng 89(1):2–19. doi: 10.1002/nme.3229 CrossRefzbMATHGoogle Scholar
  53. Takai H, Kojima M, Ohara K, Horade M, Tanikawa T, Mae Y, Arai T (2013) Microfluidic device for automated generation of toroidal-like spheroids. Paper presented at the 2013 10th International Conference on Ubiquitous Robots and Ambient Intelligence (URAI), 30 Oct 2013–2 Nov 2013Google Scholar
  54. Vaezi M, Yang S (2015) A novel bioactive PEEK/HA composite with controlled 3D interconnected HA network. Int J Bioprinting 1(1):66–76. doi: 10.18063/IJB.2015.01.004 Google Scholar
  55. Wang C-C, Yang K-C, Lin K-H, Liu H-C, Lin F-H (2011) A highly organized three-dimensional alginate scaffold for cartilage tissue engineering prepared by microfluidic technology. Biomaterials 32(29):7118–7126CrossRefGoogle Scholar
  56. Wang S, Lee JM, Yeong WY (2015) Smart hydrogels for 3D bioprinting. Int J Bioprinting 1:3–14. doi: 10.18063/IJB.2015.01.005 Google Scholar
  57. Wu LY, Di Carlo D, Lee LP (2008) Microfluidic self-assembly of tumor spheroids for anticancer drug discovery. Biomed Microdevices 10(2):197–202. doi: 10.1007/s10544-007-9125-8 CrossRefGoogle Scholar
  58. Xu JH, Li SW, Tan J, Wang YJ, Luo GS (2006) Controllable preparation of monodisperse O/W and W/O emulsions in the same microfluidic device. Langmuir 22(19):7943–7946. doi: 10.1021/la0605743 CrossRefGoogle Scholar
  59. Yamada M, Nakashima M, Seki M (2004) Pinched flow fractionation: continuous size separation of particles utilizing a laminar flow profile in a pinched microchannel. Anal Chem 76(18):5465–5471. doi: 10.1021/ac049863r CrossRefGoogle Scholar
  60. Yan J, Pedrosa VA, Enomoto J, Simonian AL, Revzin A (2011) Electrochemical biosensors for on-chip detection of oxidative stress from immune cells. Biomicrofluidics. doi: 10.1063/1.3624739 Google Scholar
  61. Yap YL, Yeong WY (2015) Shape recovery effect of 3D printed polymeric honeycomb. Virtual Physic Prototyp 10(2):91–99. doi: 10.1080/17452759.2015.1060350 CrossRefGoogle Scholar
  62. Yeong WY, Chua CK, Leong KF, Chandrasekaran M (2004) Rapid prototyping in tissue engineering: challenges and potential. Trends Biotechnol 22(12):643–652. doi: 10.1016/j.tibtech.2004.10.004 CrossRefGoogle Scholar
  63. Yeong W-Y, Chua C-K, Leong K-F, Chandrasekaran M, Lee M-W (2005) Development of scaffolds for tissue engineering using a 3D inkjet model maker. In: Virtual modelling and rapid manufacturing-advanced research in virtual and rapid prototyping, pp 115–118Google Scholar
  64. Yeong WY, Yap CY, Mapar M, Chua CK (2014) State-of-the-art review on selective laser melting of ceramics. In: High value manufacturing: advanced research in virtual and rapid prototyping, pp 65–70. doi: 10.1201/b15961-14
  65. Young EWK, Beebe DJ (2010) Fundamentals of microfluidic cell culture in controlled microenvironments. Chem Soc Rev 39(3):1036–1048. doi: 10.1039/B909900J CrossRefGoogle Scholar
  66. Yu L, Chen MCW, Cheung KC (2010) Droplet-based microfluidic system for multicellular tumor spheroid formation and anticancer drug testing. Lab Chip 10(18):2424–2432. doi: 10.1039/c004590j CrossRefGoogle Scholar
  67. Zhang J, Yan S, Sluyter R, Li W, Alici G, Nguyen N-T (2014) Inertial particle separation by differential equilibrium positions in a symmetrical serpentine micro-channel. Sci Rep. doi: 10.1038/srep04527
  68. Zhao S, Cong H, Pan T (2009) Direct projection on dry-film photoresist (DP 2): do-it-yourself three-dimensional polymer microfluidics. Lab Chip 9(8):1128–1132CrossRefGoogle Scholar
  69. Zhu F, Macdonald NP, Cooper JM, Wlodkowic D (2013) Additive manufacturing of lab-on-a-chip devices: promises and challenges. In: Proceedings of SPIE-the international society for optical engineering, art. no. 892344. doi:  10.1117/12.2033400

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  1. 1.Centre for 3D Printing, School of Mechanical and Aerospace EngineeringNanyang Technological UniversitySingaporeSingapore

Personalised recommendations