TY - JOUR T1 - Ordered, Random, Monotonic, and Non-monotonic Digital Nanodot Gradients JF - bioRxiv DO - 10.1101/001305 SP - 001305 AU - Grant Ongo AU - Sébastien G. Ricoult AU - Timothy E. Kennedy AU - David Juncker Y1 - 2013/01/01 UR - http://biorxiv.org/content/early/2013/12/13/001305.abstract N2 - 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. ER -