Organic and Macromolecular Films and Assemblies as (Bio)reactive Platforms: From Model Studies on Structure-Reactivity Relationships to Submicrometer Patterning

In this contribution we review our recent progress in studies that aim at the understanding of the relationship between structure and surface reactivity of organic thin films on the one hand, and at the micro- and nanofabrication of bioreactive or biocompatible platforms on the other hand. Self-assembled monolayers (SAMs) of n,n′-dithiobis(N-hydroxysuccinimidyl-n-alkanoate) exposing NHS reactive ester groups were studied as model systems for immobilization reactions of DNA, proteins, and receptors. Reaction kinetics and activation energies were determined quantitatively at length scales ranging from millimeters down to nanometers using, for example, surface infrared spectroscopy and in situ inverted chemical force microscopy (iCFM), respectively. The increase in conformational order with increasing alkane segment length was found to result in reduced reactivity due to steric crowding. This drawback of highly organized monolayer architectures and the inherently limited loading can be circumvented by utilizing well-defined macromolecular thin films. Using amine-terminated polyamidoamine (PAMAM) dendrimers immobilized via soft lithography, as well as scanning probe lithography (SPL) approaches (dip-pen nanolithography, DPN) on NHS ester surfaces, robust micrometer and submicrometer patterned (bio)reactive surfaces, which allow one to achieve high molecular loading in coupling reactions for chip-based assays and sensor surfaces, were fabricated. Covalent coupling afforded the required robustness of the patterned assemblies. Finally, we address micro- and nanopatterned bilayer-based systems. SPL was applied in order to fabricate nanoscale biocompatible supramolecular architectures on solid supports. The adsorption of vesicles onto lipid bilayers was spatially controlled and directed in situ with nanometer-scale precision using SPL. This methodology, which provides a platform for research on proteins incorporated in the lipid bilayers comprising the vesicles, does not require that the vesicles are chemically labeled in order to guide their deposition.