A combined photolithographic and molecular-assembly approach to produce functional micropatterns for applications in the biosciences

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 pepticle 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.