AbstractWe present a dry lift‐off method using a chemically resistant spin‐on plastic, polyimide, to pattern surfaces with high accuracy and resolution. Using well‐known lithographic and reactive ion etching techniques, the spin‐on polymer is patterned over a silicon dioxide surface. The plastic efficiently adheres to the silicon dioxide surface during the chemical modification and is readily lifted‐off following the derivatization process, permitting highly reliable surface derivatization. The verticality of the reactive ion etch enables sub‐micrometer features to be patterned, down to 0.8 µm. The technique is used to pattern neurons on silicon dioxide surfaces: efficient neuron placement over a 4 mm area is shown for patterns larger than 50 µm while process guidance is shown for 10 µm patterns. Biotechnol. Bioeng. 2013; 110: 2236–2241. © 2013 Wiley Periodicals, Inc.