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Ordered, Random, Monotonic and Non-Monotonic Digital Nanodot Gradients

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  • Grant Ongo
  • Sébastien G Ricoult
  • Timothy E Kennedy
  • David Juncker

Abstract

Cell navigation is directed by inhomogeneous distributions of extracellular cues. It is well known that noise plays a key role in biology and is present in naturally occurring gradients at the micro- and nanoscale, yet it has not been studied with gradients in vitro. Here, we introduce novel algorithms to produce ordered and random gradients of discrete nanodots – called digital nanodot gradients (DNGs) – according to monotonic and non-monotonic density functions. The algorithms generate continuous DNGs, with dot spacing changing in two dimensions along the gradient direction according to arbitrary mathematical functions, with densities ranging from 0.02% to 44.44%. The random gradient algorithm compensates for random nanodot overlap, and the randomness and spatial homogeneity of the DNGs were confirmed with Ripley's K function. An array of 100 DNGs, each 400×400 µm2, comprising a total of 57 million 200×200 nm2 dots was designed and patterned into silicon using electron-beam lithography, then patterned as fluorescently labeled IgGs on glass using lift-off nanocontact printing. DNGs will facilitate the study of the effects of noise and randomness at the micro- and nanoscales on cell migration and growth.

Suggested Citation

  • Grant Ongo & Sébastien G Ricoult & Timothy E Kennedy & David Juncker, 2014. "Ordered, Random, Monotonic and Non-Monotonic Digital Nanodot Gradients," PLOS ONE, Public Library of Science, vol. 9(9), pages 1-11, September.
    • Handle: RePEc:plo:pone00:0106541
    DOI: 10.1371/journal.pone.0106541
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    References listed on IDEAS

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    1. J. B. Gurdon & P.-Y. Bourillot, 2001. "Morphogen gradient interpretation," Nature, Nature, vol. 413(6858), pages 797-803, October.
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