Project Description (2-PE-SONS-029-NANO-SMAP)
The proposed project "NANO-SMAP" addresses the spontaneous molecular assembly of multifunctional molecules to produce geometrically defined surface patterns of biologically functional and specific (recognition) chemistry with dimensions of <100 nm, ultimately <10 nm. The underlying invention, Selective Molecular Assembly Patterning (SMAP), relies on the observation that long-chain alkane phosphonates and phosphates form self-assembled monolayers on transition metal oxide surfaces such as titanium oxide, but not on silicon oxide. Starting with a pre-patterned TiO2/SiO2 surface, the alkane phosphate self-assembly results in hydrophobic, strongly interactive TiO2 areas, whereas in a second step, a polycationic PEG-grafted polymer is selectively applied to the negatively charged SiO2 areas rendering them highly non-interactive, e.g. protein-resistant.
The basic feasibility of SMAP has been successfully demonstrated on TiO2/SiO2 micropatterned surfaces produced by photolithography. Since the resolution of the SMAP technique should be limited by the size of the used molecular systems only, the production of surface patterns with dimensions in the low nanometer range seems feasible. A second approach exploits the selective formation of supported phospholipid lipid bilayers (SPB) from vesicles on SiO2, but not on TiO2 allowing for the production of biologically inspired patterns. This can actually be combined with the SMAP technique, since SPBs form spontaneously from small vesicles on SiO2, while the same vesicles form intact vesicles on TiO2.
Furthermore both vesicles and SPBs can be made protein and cell resistant, or alternatively provided with special functional groups to make them cell and protein specific. The combination of SMAP and SPBs therefore has the potential of producing unique patterned surfaces for biological functions in vivo and in vitro.
There has been substantial progress lately in the production of small colloids of low polydispersity and of organized patterns of such colloids at surfaces. Novel and suitable techniques to organize the colloids at surfaces include spontaneous arrangement due to electrostatic interactions (which are influenced by solution pH and ion concentration), the use of colloidal particles enclosed in micelles and the controlled placement by optical tweezer techniques. Surface-immobilized colloids can serve as lithographic masks to produce, via dry etching techniques of TiO2 thin film coated glass, inorganic TiO2/SiO2 patterns of dimension <100 nm, serving as pre-patterns for the selective molecular assembly steps.
The project aims at bringing together the multidisciplinary and complementary expertise of the proposing partners in the areas of chemical synthesis of multifunctional organophosph(on)ates and PEG-based polyionic copolymers, supported phospholipid bilayers (SPBs), colloid production/assembly, lithography, molecular self-assembly techniques and surface physics. The aim is to develop a novel platform for the fabrication of nanopatterns of dimensions 100 - <10 nm, with highly controlled chemical and biological properties within the adhesive/non-adhesive areas. In comparison to the state-of-the-art of SMAP, much smaller features, corresponding ultimately to single molecule arrays, improved regularity of the pattern geometry, and generation of assembled layers of higher hierarchy and improved macromolecular functionality will be aimed at. Potential applications in the biotech field of this simple, cost-effective, parallel patterning technology range from high-density biosensor nanoarrays, model surfaces for cell-biological and single-molecule-interaction studies, to nanoarrays for molecular motors and engines. Since it is a bottom-up approach, further potential applications in science and technology are likely to emerge in the course of this 3-year project.
Figure 1: A schematic illustration of the SMAP methodology. (a) Sample exhibiting a material contrast, produced using common lithographic techniques. TiO2 squares within the SiO2 matrix are shown. (b) An atomic force microscope image of the surface shown in (a). TiO2 squares are located 35 nm below the SiO2 matrix. (c) Schematic view of the surface after the surface modification procedures: DDP on TiO2, protein on DDP, and PLL-g-PEG on SiO2, with the poly(lysine) backbone lying flat on the surface and PEG chains extending away from it. (d) Fluorescence microscopy: 5x5µm adhesive patterns (OG-labelled streptavidin, red) on protein-resistant PLL-g-PEG background (fluorescein-labeled polymer, green). (e) SMAP of 80 nm diameter TiO2 patches decorated with streptavidin and 100 nm diameter biotinylated liposomes (AFM image), produced according to sketch in (f).
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Figure 2 (left): SEM picture of core-shell ZnS-silica (core 333 nm, total radius 350 nm) particles deformed into an oblate ellipsoidal shape by ion irradiation. Ion beam in plane (top-bottom) with respect to the image plane.
Figure 3 (right): Image of a pattern of 153 1.4 µm-diameter silica particles arranged on a hcp(1100)-lattice, taken with DIC microscopy in suspension. The arrows indicate two smaller particles that have been incorporated as defects in the pattern.