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A versatile approach to high-throughput microarrays using thiol-ene chemistry

Nature Chemistry volume 2, pages 138–145 (2010)Cite this article

An Addendum to this article was published on 23 April 2012

This article has been updated

Abstract

Microarray technology has become extremely useful in expediting the investigation of large libraries of materials in a variety of biomedical applications, such as in DNA chips, protein and cellular microarrays. In the development of cellular microarrays, traditional high-throughput printing strategies on stiff, glass substrates and non-covalent attachment methods are limiting. We have developed a facile strategy to fabricate multifunctional high-throughput microarrays embedded at the surface of a hydrogel substrate using thiol-ene chemistry. This user-friendly method provides a platform for the immobilization of a combination of bioactive and diagnostic molecules, such as peptides and dyes, at the surface of poly(ethylene glycol)-based hydrogels. The robust and orthogonal nature of thiol-ene chemistry allows for a range of covalent attachment strategies in a fast and reliable manner, and two complementary strategies for the attachment of active molecules are demonstrated.

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Figure 1: General procedure for the fabrication of hydrogel microarrays using thiol-ene chemistry.
Figure 2: Thiol- and alkene-functional hydrogel microarrays.
Figure 3: Direct coupling of cell-adhesive peptides to microarrays.
Figure 4: Synthesis of orthogonal heterobifunctional crosslinkers and their postfunctionalization in printed microarrays.
Figure 5: Orthogonal ligation reaction on a single microarray using thiol-ene, hydrazone and NHS-active ester chemistries.
Figure 6: Combination of direct printing of peptides with orthogonal postfunctionalization on individual microarray spots.

Change history

  • 13 March 2012

    The authors wish to add the following to the Acknowledgements section of this Article: "We gratefully acknowledge the use of the UCSB Laboratory for Stem Cell Biology and Engineering and funding from the California Institute for Regenerative Medicine." The online versions of the Article have been amended accordingly.

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Acknowledgements

This work made use of Materials Research Laboratory's Central Facilities supported by the Materials Research Science & Engineering Centers Program of the National Science Foundation (No. DMR05-20415). N.G. thanks the National Science Foundation for a Graduate Research Fellowship. L.M.C. thanks the University of California for a Presidential Fellowship. We gratefully acknowledge the use of the UCSB Laboratory for Stem Cell Biology and Engineering and funding from the California Institute for Regenerative Medicine.

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Authors and Affiliations

  1. Materials Research Laboratory, University of California, Santa Barbara, 93105, California, USA

    Nalini Gupta, Brian F. Lin, Luis M. Campos, Michael D. Dimitriou, Neil D. Treat, Matthew V. Tirrell, Edward J. Kramer & Craig J. Hawker

  2. Materials Department, University of California, Santa Barbara, 93105, California, USA

    Nalini Gupta, Michael D. Dimitriou, Neil D. Treat, Matthew V. Tirrell, Edward J. Kramer & Craig J. Hawker

  3. Department of Chemistry and Biochemistry, University of California, Santa Barbara, 93105, California, USA

    Brian F. Lin & Craig J. Hawker

  4. Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, 93105, California, USA

    Sherry T. Hikita & Dennis O. Clegg

  5. Center for Stem Cell Biology and Engineering, University of California, Santa Barbara, 93106, California, USA

    Sherry T. Hikita, Matthew V. Tirrell, Dennis O. Clegg & Craig J. Hawker

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Contributions

C.J.H, L.M.C. and N.G. contributed to the conception and experimental design. N.G. performed the experiments. B.F.L. contributed to the cell studies. M.D. contributed to the X-ray photoelectron spectroscopy experiments. N.D.T. contributed to the profilometry experiments. M.V.T., E.J.K., D.O.C. and S.T.H. contributed to experimental analysis. All authors contributed to discussion of the results and commented on the manuscript.

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Correspondence to Craig J. Hawker.

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Gupta, N., Lin, B., Campos, L. et al. A versatile approach to high-throughput microarrays using thiol-ene chemistry. Nature Chem 2, 138–145 (2010). https://doi.org/10.1038/nchem.478

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