Advertisement

Springer Nature is making Coronavirus research free. View research | View latest news | Sign up for updates

Reliable magnetic reversible assembly of complex microfluidic devices: fabrication, characterization, and biological validation

Abstract

Current standard procedures for fabrication of microfluidic devices combine polydimethylsiloxane (PDMS) replica molding with subsequent plasma treatment to obtain an irreversible sealing onto a glass/silicon substrate. However, irreversible sealing introduces several limitations to applications and internal accessibility of such devices as well as to the choice of materials for fabrication. In the present work, we describe and characterize a reliable, flexible and cost effective approach to fabricate devices that reversibly adhere to a substrate by taking advantage of magnetic forces. This is shown by implementing a PDMS/iron micropowder layer aligned onto a microfluidic layer and coupled with a histology glass slide, in union with either temporary or continuous use of a permanent magnet. To better represent the complexity of microfluidic devices, a Y-shaped configuration including lower scale parallel channels on each branch has been employed as reference geometry. To correctly evaluate our system, current sealing methods have been reproduced on the reference geometry. Sealing experiments (pressure control, flow control and hydraulic characterization) have been carried out, showing consistent increases in terms of maximum achievable flow rates and pressures, as compared to devices obtained with other available reversible techniques. Moreover, no differences were detected between cells cultured on our magnetic devices as compared to cells cultured on permanently sealed devices. Disassembly of our devices for analyses allowed to stain cells by hematoxylin and eosin and for F-actin, following traditional histological processes and protocols. In conclusion, we present a method allowing reversible sealing of microfluidic devices characterized by compatibility with: (i) complex fluidic layer configurations, (ii) micrometer sized channels, and (iii) optical transparency in the channel regions for flow visualization and inspection.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

References

  1. Abgrall P, Lattes C, Conédéra V, Dollat X, Colin S, Gué AM (2006) A novel fabrication method of flexible and monolithic 3d microfluidic structures using lamination of. J Micromech Microeng 16(1):113–121

  2. Arroyo MT, Fernàndez LJ, Agirregabiria M, Ibañez N, Aurrekoetxea J, Blanco FJ (2007) Novel all-polymer microfluidic devices monolithically integrated within metallic electrodes for sds-cge of proteins. J Micromech Microeng 17(7):1289–1298

  3. Becker H, Gartner C (2000) Polymer microfabrication methods for microfluidic analytical applications. Electrophoresis 21(1):12–26. doi:10.1002/(SICI)1522-2683(20000101)21:1<12:AID-ELPS12>3.0.CO;2-7

  4. Brown L, Koerner T, Horton JH, Oleschuk RD (2006) Fabrication and characterization of poly(methylmethacrylate) microfluidic devices bonded using surface modifications and solvents. Lab Chip 6(1):66–73. doi:10.1039/b512179e

  5. Brydson J (1999) Plastics materials, 7th edn. Elsevier, Amsterdam

  6. Buch JS, Kimball C, Rosenberger F, Highsmith WE Jr, DeVoe DL, Lee CS (2004) DNA mutation detection in a polymer microfluidic network using temperature gradient gel electrophoresis. Anal Chem 76(4):874–881. doi:10.1021/ac034913y

  7. Dang F, Shinohara S, Tabata O, Yamaoka Y, Kurokawa M, Shinohara Y, Ishikawa M, Baba Y (2005) Replica multichannel polymer chips with a network of sacrificial channels sealed by adhesive printing method. Lab Chip 5(4):472–478. doi:10.1039/b417398h

  8. Démarteau O, Wendt D, Braccini A, Jakob M, Schafer D, Heberer M, Martin I (2003) Dynamic compression of cartilage constructs engineered from expanded human articular chondrocytes. Biochem Biophys Res Commun 310(2):580–588. doi:S0006291X03018655

  9. Fischer AH, Jacobson KA, Rose J, Zeller R (2008) Media for mounting fixed cells on microscope slides. Cold Spring Harb Protoc 4. doi:10.1101/pdb.ip52

  10. Griebel A, Rund S, Schonfeld F, Dorner W, Konrad R, Hardt S (2004) Integrated polymer chip for two-dimensional capillary gel electrophoresis. Lab Chip 4(1):18–23. doi:10.1039/b311032j

  11. Herold KE, Rasooly A (2009) Lab-on-a-chip technology, vol 1: fabrication and microfluidics. Caister Academic Press, Norfolk

  12. Hromada LP, Nablo BJ, Kasianowicz JJ, Gaitan MA, DeVoe DL (2008) Single molecule measurements within individual membrane-bound ion channels using a polymer-based bilayer lipid membrane chip. Lab Chip 8(4):602–608. doi:10.1039/b716388f

  13. Huang FC, Chen YF, Lee GB (2007) Ce chips fabricated by injection molding and polyethylene/thermoplastic elastomer film packaging methods. Electrophoresis 28(7):1130–1137. doi:10.1002/elps.200600351

  14. Jakob M, Demarteau O, Schafer D, Hintermann B, Dick W, Heberer M, Martin I (2001) Specific growth factors during the expansion and redifferentiation of adult human articular chondrocytes enhance chondrogenesis and cartilaginous tissue formation in vitro. J Cell Biochem 81(2):368–377. doi:10.1002/1097-4644(20010501)81:2<368:AID-JCB1051>3.0.CO;2-J

  15. Jang K, Sato K, Igawa K, Chung U-i, Kitamori T (2008) Development of an osteoblast-based 3d continuous-perfusion microfluidic system for drug screening. Anal Bioanal Chem 390(3):825–832. doi:10.1007/s00216-007-1752-7

  16. Johansson BL, Larsson A, Ocklind A, Öhrlund Å (2002) Characterization of air plasma-treated polymer surfaces by ESCA and contact angle measurements for optimization of surface stability and cell growth. J Appl Polym Sci 86(10):2618–2625. doi:10.1002/app.11209

  17. Khademhosseini A, Yeh J, Eng G, Karp J, Kaji H, Borenstein J, Farokhzad OC, Langer R (2005) Cell docking inside microwells within reversibly sealed microfluidic channels for fabricating multiphenotype cell arrays. Lab Chip 5(12):1380–1386. doi:10.1039/b508096g

  18. Le Berre M, Crozatier C, Velve Casquillas G, Chen Y (2006) Reversible assembling of microfluidic devices by aspiration. Microelectron Eng 83(4–9):1284–1287. doi:10.1016/j.mee.2006.01.257

  19. Li L, Ismagilov RF (2010) Protein crystallization using microfluidic technologies based on valves, droplets, and slipchip. Annu Rev Biophys 39(1):139–158. doi:10.1146/annurev.biophys.050708.133630

  20. McDonald JC, Duffy DC, Anderson JR, Chiu DT, Wu H, Schueller OJ, Whitesides GM (2000) Fabrication of microfluidic systems in poly(dimethylsiloxane). Electrophoresis 21(1):27–40. doi:10.1002/(SICI)1522-2683(20000101)21:1<27:AID-ELPS27>3.0.CO;2-C

  21. Ong SM, Zhang C, Toh YC, Kim SH, Foo HL, Tan CH, van Noort D, Park S, Yu H (2008) A gel-free 3d microfluidic cell culture system. Biomaterials 29(22):3237–3244. doi:10.1016/j.biomaterials.2008.04.022

  22. Pocius A (2002) Adhesion and adhesives technology: an introduction, 2nd edn. Hanser/Gardner Publications, Cincinnati

  23. Rafat M, Raad DR, Rowat AC, Auguste DT (2009) Fabrication of reversibly adhesive fluidic devices using magnetism. Lab Chip 9(20):3016–3019. doi:10.1039/b907957b

  24. Rodriguez-Villarreal AI, Arundell M, Carmona M, Samitier J (2010) High flow rate microfluidic device for blood plasma separation using a range of temperatures. Lab Chip 10(2):211–219. doi:10.1039/b904531g

  25. Rötting O, Röpke W, Becker H, Gärtner C (2002) Polymer microfabrication technologies. Microsyst Technol 8(1):32–36. doi:10.1007/s00542-002-0106-9

  26. Shenton MJ et al (2001) Adhesion enhancement of polymer surfaces by atmospheric plasma treatment. J Phys D 34(18):2754–2760

  27. Sui G, Lee CC, Kamei K, Li HJ, Wang JY, Wang J, Herschman HR, Tseng HR (2007) A microfluidic platform for sequential ligand labeling and cell binding analysis. Biomed Microdev 9(3):301–305

  28. Sun Y, Kwok YC, Nguyen N-T (2006) Low-pressure, high-temperature thermal bonding of polymeric microfluidic devices and their applications for electrophoretic separation. J Micromech Microeng 16(8):1681–1688

  29. Taberham A, Kraft M, Mowlem M, Morgan H (2008) The fabrication of lab-on-chip devices from fluoropolymers. J Micromech Microeng 18(6):064011

  30. Unger MA, Chou HP, Thorsen T, Scherer A, Quake SR (2000) Monolithic microfabricated valves and pumps by multilayer soft lithography. Science 288(5463):113–116. doi:10.1126/science.288.5463.113

  31. Wallow TI, Morales AM, Simmons BA, Hunter MC, Krafcik KL, Domeier LA, Sickafoose SM, Patel KD, Gardea A (2007) Low-distortion, high-strength bonding of thermoplastic microfluidic devices employing case-ii diffusion-mediated permeant activation. Lab Chip 7(12):1825–1831. doi:10.1039/b710175a

  32. Xia Y, Whitesides GM (1998) Soft lithography. Annu Rev Mat Sci 28:153–184. doi:10.1146/annurev.matsci.28.1.153

Download references

Acknowledgments

The authors appreciate helpful conversations with Dr Giancarlo Franceschetti, who made important contributions to the formative stages of this research. The authors also thank Mara Licini, Clara Nozza, Alice Sormani and Lia Volpatti for their valuable help during hydraulic measurements. This work was partially supported by Cariplo Foundation grant # 2008-2531 and Progetto Roberto Rocca.

Author information

Correspondence to Marco Rasponi.

Additional information

Francesco Piraino and Nasser Sadr have contributed equally.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Rasponi, M., Piraino, F., Sadr, N. et al. Reliable magnetic reversible assembly of complex microfluidic devices: fabrication, characterization, and biological validation. Microfluid Nanofluid 10, 1097–1107 (2011). https://doi.org/10.1007/s10404-010-0738-5

Download citation

Keywords

  • Microfluidics
  • Reversible bonding
  • Magnetism
  • Micropowder
  • Chondrocyte