Cell-Based Microarrays Using Superhydrophobic Platforms Patterned with Wettable Regions

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

Abstract

The use of patterned platforms to print cellular arrays enables the high-throughput study of cell behavior under a multitude of different conditions. This rapid, cost-saving and systematic way of acquiring biologically relevant information has found application in diverse scientific and industrial fields. In an initial stage of development, platforms targeting high-throughput cellular studies were restricted to standard two-dimensional (2D) setups. The design of novel platforms compatible with three-dimensional (3D) cell culture arose after the elucidation of the extreme importance of culturing cells in matrices resembling the native extracellular matrix–cells and cell–cell interactions. This need for biomimetic environments has been established in fields like drug discovery and testing, disease model development, and regenerative medicine. Here, we provide a description of the processing of flat platforms based on wettability contrast, compatible with the high-throughput generation and study of cell response in 3D biomaterials, including cell-laden hydrogels and porous 3D scaffolds. The application of the aforementioned platforms to produce 3D microtissues, which may find application as tissue models for drug screening or as biomimetic building blocks for tissue engineering, is also addressed. In this chapter, a description of the steps for (1) high-throughput platform processing, (2) deposition of cell and biomaterial arrays, and (3) image-based results screening is provided.

Key words

Bioinspired Superhydrophobic Patterned platforms High-throughput Three-dimensional Cell microarrays 

Notes

Acknowledgments

M.B.O. acknowledges the Portuguese Fundação para a Ciência e a Tecnologia (FCT) (SFRH/BPD/111354/2015) for the postdoctoral grant.

References

  1. 1.
    Macarron R, Banks MN, Bojanic D, Burns DJ, Cirovic DA, Garyantes T et al (2011) Impact of high-throughput screening in biomedical research. Nat Rev Drug Discov 10:188–195CrossRefPubMedGoogle Scholar
  2. 2.
    Oliveira MB, Mano JF (2014) High-throughput screening for integrative biomaterials design: exploring advances and new trends. Trends Biotechnol 32:627–636CrossRefPubMedGoogle Scholar
  3. 3.
    Bleicher KH, Bohm H-J, Muller K, Alanine AI (2003) Hit and lead generation: beyond high-throughput screening. Nat Rev Drug Discov 2:369–378CrossRefPubMedGoogle Scholar
  4. 4.
    Pereira DA, Williams JA (2007) Origin and evolution of high throughput screening. Br J Pharmacol 152:53–61CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Mayr LM, Fuerst P (2008) The future of high-throughput screening. J Biomol Screen 13:443–448CrossRefPubMedGoogle Scholar
  6. 6.
    Cox B, Denyer JC, Binnie A, Donnelly MC, Evans B, Green DV et al (2000) Application of high-throughput screening techniques to drug discovery. Prog Med Chem 37:83–133CrossRefPubMedGoogle Scholar
  7. 7.
    Hubbell JA (2004) Biomaterials science and high-throughput screening. Nat Biotech 22:828–829CrossRefGoogle Scholar
  8. 8.
    Flaim CJ, Chien S, Bhatia SN (2005) An extracellular matrix microarray for probing cellular differentiation. Nat Meth 2:119–125CrossRefGoogle Scholar
  9. 9.
    Amin YYI, Runager K, Simoes F, Celiz A, Taresco V, Rossi R et al (2016) Combinatorial biomolecular nanopatterning for high-throughput screening of stem-cell behavior. Adv Mater 28:1472–1476CrossRefPubMedGoogle Scholar
  10. 10.
    Patel AK, Tibbitt MW, Celiz AD, Davies MC, Langer R, Denning C et al (2016) High throughput screening for discovery of materials that control stem cell fate. Curr Opinion Solid State Mater Sci 20:202–211CrossRefGoogle Scholar
  11. 11.
    Hook AL, Anderson DG, Langer R, Williams P, Davies MC, Alexander MR (2010) High throughput methods applied in biomaterial development and discovery. Biomaterials 31:187–198CrossRefPubMedGoogle Scholar
  12. 12.
    Hynes RO (2009) The extracellular matrix: not just pretty fibrils. Science 326:1216–1219CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Murphy WL, McDevitt TC, Engler AJ (2014) Materials as stem cell regulators. Nat Mater 13:547–557CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Anderson DG, Levenberg S, Langer R (2004) Nanoliter-scale synthesis of arrayed biomaterials and application to human embryonic stem cells. Nat Biotech 22:863–866CrossRefGoogle Scholar
  15. 15.
    Gobaa S, Hoehnel S, Roccio M, Negro A, Kobel S, Lutolf MP (2011) Artificial niche microarrays for probing single stem cell fate in high throughput. Nat Meth 8:949–955CrossRefGoogle Scholar
  16. 16.
    Salgado CL, Oliveira MB, Mano JF (2012) Combinatorial cell-3D biomaterials cytocompatibility screening for tissue engineering using bioinspired superhydrophobic substrates. Integr Biol 4:318–327CrossRefGoogle Scholar
  17. 17.
    Oliveira MB, Salgado CL, Song W, Mano JF (2013) Combinatorial on-chip study of miniaturized 3d porous scaffolds using a patterned superhydrophobic platform. Small 9:768–778CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Yoshii Y, Furukawa T, Waki A, Okuyama H, Inoue M, Itoh M et al (2015) High-throughput screening with nanoimprinting 3D culture for efficient drug development by mimicking the tumor environment. Biomaterials 51:278–289CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Dolatshahi-Pirouz A, Nikkhah M, Gaharwar AK, Hashmi B, Guermani E, Aliabadi H et al (2014) A combinatorial cell-laden gel microarray for inducing osteogenic differentiation of human mesenchymal stem cells. Sci Rep 4(3896)Google Scholar
  20. 20.
    Mabry KM, Schroeder ME, Payne SZ, Anseth KS (2016) Three-dimensional high-throughput cell encapsulation platform to study changes in cell-matrix interactions. ACS Appl Mater Interfaces 8:21914–21922CrossRefPubMedGoogle Scholar
  21. 21.
    Nuno NO, Ana IN, Wenlong S, Mano JF (2010) Two-dimensional open microfluidic devices by tuning the wettability on patterned superhydrophobic polymeric surface. Appl Phys Express 3:085205CrossRefGoogle Scholar
  22. 22.
    Neto AI, Custodio CA, Song W, Mano JF (2011) High-throughput evaluation of interactions between biomaterials, proteins and cells using patterned superhydrophobic substrates. Soft Matter 7:4147–4151CrossRefGoogle Scholar
  23. 23.
    Oliveira MB, Ribeiro MP, Miguel SP, Neto AI, Coutinho P, Correia IJ et al (2014) In vivo high-content evaluation of three-dimensional scaffolds biocompatibility. Tissue Eng Part C Methods 20:851–864CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Neto AI, Vasconcelos NL, Oliveira SM, Ruiz-Molina D, Mano JF (2016) High-throughput topographic, mechanical, and biological screening of multilayer films containing mussel-inspired biopolymers. Adv Funct Mater 26:2745–2755CrossRefGoogle Scholar
  25. 25.
    Ma K, Rivera J, Hirasaki GJ, Biswal SL (2011) Wettability control and patterning of PDMS using UV/ozone and water immersion. J Colloid Interface Sci 363:371–378CrossRefPubMedGoogle Scholar
  26. 26.
    Oliveira MB, Neto AI, Correia CR, Rial-Hermida MI, Alvarez-Lorenzo C, Mano JF (2014) Superhydrophobic chips for cell spheroids high-throughput generation and drug screening. ACS Appl Mater Interfaces 6:9488–9495CrossRefPubMedGoogle Scholar
  27. 27.
    Hancock MJ, He J, Mano JF, Khademhosseini A (2011) Surface-tension-driven gradient generation in a fluid stripe for bench-top and microwell applications. Small 7:892–901CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

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

Authors and Affiliations

  1. 1.Department of ChemistryCICECO – Aveiro Institute of MaterialsAveiroPortugal

Personalised recommendations