Capillary Pinning Assisted Patterning of Cell-Laden Hydrogel Microarrays in Microchips

Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1771)

Abstract

We present a capillary pinning technique that gives complete control on the local patterning of hydrogel structures in closed microchips. The technique relies on selective trapping of liquids at predefined locations in a microchip using capillary barriers. In selective patterning, the abrupt expansion in the cross-sectional geometry of a microchannel at capillary barriers results in a confined advancement of the liquid–air meniscus. This protocol describes a detailed procedure to design and fabricate microarrays of different hydrogel types, fabricated with photopolymerization or thermogelation. The process can be subdivided into two parts. First, a PDMS microchip containing microfeatures with customized patterns is fabricated. Second, the microchip is filled with a hydrogel precursor to be cross-linked by either photopolymerization or thermogelation. The production of the microchip takes approximately 2 days, depending on the substrate selection. Preparation of the hydrogel solutions takes 1–2 h, whereas the patterning and reaction to cross-link the hydrogels is completed in a few minutes.

Key words

Hydrogel microarrays Polyacrylamide Polyethylene glycol diacrylate Collagen Microfluidic chip UV induced polymerization Thermogelation Fabrication Cell-laden hydrogel arrays 

Notes

Acknowledgments

This work was supported by the Dutch network for Nanotechnology NanoNext NL, in the subprogram of “Nanofluidics for Lab-on-a-chip.” The authors thank Johan G. Bomer for his help during the development of SU-8 master fabrication procedure.

References

  1. 1.
    Verhulsel M, Vignes M, Descroix S, Malaquin L, Vignjevic DM, Viovy JL (2014) A review of microfabrication and hydrogel engineering for micro-organs on chips. Biomaterials 35:1816–1832CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Qi H, Du Y, Wang L, Kaji H, Bae H, Khademhosseini A (2010) Patterned differentiation of individual embryoid bodies in spatially organized 3D hybrid microgels. Adv Mater 22:5276–5281CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Liu VA, Bhatia SN (2002) Three-dimensional photopatterning of hydrogels containing living cells. Biomed Microdevices 4:257–266CrossRefGoogle Scholar
  4. 4.
    Sung JH, Yu J, Luo D, Shuler ML, March JC (2011) Microscale 3-D hydrogel scaffold for biomimetic gastrointestinal (GI) tract model. Lab Chip 11:389–392CrossRefGoogle Scholar
  5. 5.
    Gumuscu B, Bomer JG, van den Berg A, Eijkel JCT (2015) Photopatterning of hydrogel microarrays in closed microchips. Biomacromolecules 16:3802–3810CrossRefGoogle Scholar
  6. 6.
    Papavasiliou G, Songprawat P, Pérez-Luna V, Hammes E, Morris M, Chiu YC, Brey E (2008) Three-dimensional patterning of poly (ethylene glycol) hydrogels through surface-initiated photopolymerization. Tissue Eng Part C Methods 14:29–140CrossRefGoogle Scholar
  7. 7.
    Khademhosseini A, Langer R (2007) Microengineered hydrogels for tissue engineering. Biomaterials 28:5087–5092CrossRefPubMedGoogle Scholar
  8. 8.
    Mironov V, Boland T, Trusk T, Forgacs G, Markwald RR (2003) Organ printing: computer-aided jet-based 3D tissue engineering. Trends Biotechnol 21:157–161CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Mironov V, Visconti RP, Kasyanov V, Forgacs G, Drake CJ, Markwald RR (2009) Organ printing: tissue spheroids as building blocks. Biomaterials 30:2164–2174CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Jang M, Neuzil P, Volk T, Manz A, Kleber A (2015) On-chip three-dimensional cell culture in phaseguides improves hepatocyte functions in vitro. Biomicrofluidics 9:034113CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Moreno EL, Hachi S, Hemmer K, Trietsch SJ, Baumuratov AS, Hankemeier T, Vulto P, Fleming RM (2015) Differentiation of neuroepithelial stem cells into functional dopaminergic neurons in 3D microfluidic cell culture. Lab Chip 15:2419–2428CrossRefPubMedGoogle Scholar
  12. 12.
    Trietsch SJ, Israëls GD, Joore J, Hankemeier T, Vulto P (2013) Microfluidic titer plate for stratified 3D cell culture. Lab Chip 13:3548–3554CrossRefPubMedGoogle Scholar
  13. 13.
    Kim DH, Lipke EA, Kim P, Cheong R, Thompson S, Delannoy M, Suh KY, Tung L, Levchenko A (2010) Nanoscale cues regulate the structure and function of macroscopic cardiac tissue constructs. Proc Natl Acad Sci U S A 107:565–570CrossRefPubMedGoogle Scholar
  14. 14.
    Sekiya S, Muraoka M, Sasagawa T, Shimizu T, Yamato M, Okano T (2010) Three-dimensional cell-dense constructs containing endothelial cell-networks are an effective tool for in vivo and in vitro vascular biology research. Microvasc Res 80:549–551CrossRefPubMedGoogle Scholar
  15. 15.
    Moraes C, Chen JH, Sun Y, Simmons CA (2010) Microfabricated arrays for high-throughput screening of cellular response to cyclic substrate deformation. Lab Chip 10:227–234CrossRefPubMedGoogle Scholar
  16. 16.
    Gumuscu B, Bomer JG, van den Berg A, Eijkel JCT (2015) Large scale patterning of hydrogel microarrays using capillary pinning. Lab Chip 15:664–667CrossRefPubMedGoogle Scholar
  17. 17.
    Gumuscu B, Haase AS, Benneker AM, Hempenius MA, van den Berg A, Lammertink RGH, Eijkel JCT (2016) Desalination by electrodialysis using a stack of patterned ion-selective hydrogels on a microfluidic device. Adv Funct Mater.  https://doi.org/10.1002/adfm.201603242
  18. 18.
    Chibbaro S, Costa E, Dimitrov DI, Diotallevi F, Milchev A (2009) Capillary filling in microchannels with wall corrugations: a comparative study of the Concus-Finn criterion by continuum, kinetic, and atomistic approaches. Langmuir 25:12653–12660CrossRefPubMedGoogle Scholar
  19. 19.
    Man PF, Mastrangelo CH, Burns MA, Burke DT (1998) Microfabricated capillarity-driven stop valve and sample injector. In: MEMS’98 Proc., p 45Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.BIOS Lab-on-a-Chip Group, MESA+ Institute for Nanotechnology, MIRA Institute for Biomedical Technology and Technical MedicineUniversity of TwenteEnschedeThe Netherlands
  2. 2.California Institute for Quantitative BiosciencesUniversity of California, BerkeleyBerkeleyUSA

Personalised recommendations