For many applications in the biomedical sector (especially for cell screening assays, guidance and migration experiments), gradient patterns comprising bioactive compounds over comparably (in regard to a cell size) large areas are key. Polymer pen lithography (PPL), as an inherent highly parallel and large area technique has a great potential to serve in the fabrication of such patterns. We present strategies for the printing of functional phospholipid patterns via PPL that provide tunable feature size and feature density gradients over surface areas of several square millimeters. By controlling of the printing parameters, two transfer modes can be achieved, each providing different feature morphologies. By increasing the force applied to the elastomeric pens, which increases the tip-surface contact area and boosts the ink delivery rate, a switch between a dip-pen nanolithography (DPN) to a microcontact printing (µCP) transfer mode can be induced, which was observed for the first time. A careful inking procedure ensuring a homogeneous and not too high ink-load on the PPL stamp ensures a membrane-spreading dominated transfer mode, which, used in combination with highly hydrophilic substrates, generates features with constant height, independently of the applied force of the pens. Ultimately, this allows us to obtain a gradient of feature sizes over a mm2 substrate, all having the same height on the order of that of a biological cellular membrane. These strategies allow the construction of membrane structures by direct transfer of the lipid mixture to the substrate, without requiring previous substrate functionalization, in contrast to other molecular inks, where structure is directly determined by the printing process itself. The patterns are demonstrated to be viable for subsequent protein binding, therefore adding to a flexible feature library when gradients of protein presentation are desired.
Polymer Pen Lithography with Lipids for Large-Area Gradient Patterns
R. Kumar, A. Urtizberea, S. Ghosh, U. Bog, Q. Rainer, S. Lenhert, H. Fuchs, M. Hirtz
Langmuir 33 (2017) 8739-8748