A Combined Photolithographic and Molecular‐Assembly Approach to Produce Functional Micropatterns for Applications in the Biosciences

Abstract Chemical patterns have attracted substantial interest for applications in the field of biosensors, fundamental cell–surface interaction studies, tissue engineering, and biomaterials. A novel micropatterning technique is proposed here that combines a top–down approach based on photolithography and a bottom–up strategy through self‐organization of multifunctional molecules. The development of the molecular‐assembly patterning by lift‐off (MAPL) has been driven by the need to economically produce patches incorporating a controlled surface density of bioligands while inhibiting non‐specific adsorption. In the MAPL process, a photoresist pattern is transferred into the desired biochemical pattern by means of spontaneous adsorption of biologically relevant species and photoresist lift‐off. The surface between the interactive patches is subsequently rendered non‐fouling through immobilization of a polycationic poly(ethylene glycol) (PEG)‐graft polymer. We demonstrate that surface density of biotin molecules inside adhesive islands can be tailored quantitatively and that cells grow selectively on cell‐adhesive peptide patterns. MAPL is considered to be a valuable addition to the toolbox of soft‐lithography techniques for life‐science applications combining simplicity (no clean‐room equipment needed), cost‐effectiveness, reproducibility on the scale of whole wafer surfaces, and flexibility in terms of pattern geometry, chemistry, and substrate choice.