The past 20 years have witnessed simultaneous multidisciplinary explosions in experimental techniques for synthesizing new materials, measuring and manipulating nanoscale structures, understanding biological processes at the nanoscale, and carrying out large-scale computations of many-atom and complex macromolecular systems. These advances have led to the new disciplines of nanoscience and nanoengineering. For reasons that are discussed here, most nanoparticles do not 'self-assemble' into their thermodynamically lowest energy state, and require an input of energy or external forces to 'direct' them into particular structures or assemblies. We discuss why and how a combination of self- and directed-assembly processes, involving interparticle and externally applied forces, can be applied to produce desired nanostructured materials.

The surface forces apparatus (SFA) has been used for many years to measure the physical forces between surfaces, such as van der Waals (including Casimir) and electrostatic forces in vapors and liquids, adhesion and capillary forces, forces due to surface and liquid structure (e.g. solvation and hydration forces), polymer, steric and hydrophobic interactions, bio-specific interactions as well as friction and lubrication forces. Here we describe recent developments in the SFA technique, specifically the SFA 2000, its simplicity of operation and its extension into new areas of measurement of both static and dynamic forces as well as both normal and lateral (shear and friction) forces. The main reason for the greater simplicity of the SFA 2000 is that it operates on one central simple-cantilever spring to generate both coarse and fine motions over a total range of seven orders of magnitude (from millimeters to ångstroms). In addition, the SFA 2000 is more spacious and modulated so that new attachments and extra parts can easily be fitted for performing more extended types of experiments (e.g. extended strain friction experiments and higher rate dynamic experiments) as well as traditionally non-SFA type experiments (e.g. scanning probe microscopy and atomic force microscopy) and for studying different types of systems.

We have investigated the formation of phospholipid bilayers of the neutral (zwitterionic) lipid dimyristoyl-phosphatidylcholine (DMPC) on various glass surfaces from vesicles in various aqueous solutions and temperatures using a number of complementary techniques: the surface forces apparatus (SFA), quartz crystal microbalance (QCM), fluorescence recovery after photobleaching (FRAP), fluorescence microscopy, and streaming potential (SP) measurements. The process involves five stages: vesicle adhesion to the substrate surfaces via electrostatic and van der Waals forces, steric interactions with neighboring vesicles, rupture, spreading via hydrophobic fusion of bilayer edges, and ejection of excess lipid, trapped water, and ions into the solution. The forces between DMPC bilayers and silica were measured in the SFA in phosphate buffered saline (PBS), and the adhesion energy was found to be 0.5-1 mJ/m(2) depending on the method of bilayer preparation. This value is stronger than the expected adhesion predicted by van der Waals interactions. Theoretical analysis of the bilayer-silica interaction shows that the strong attraction is likely due to an attractive electrostatic interaction between the uncharged bilayer and negatively charged silica owing to the surfaces interacting at "constant potential." However, the bilayer-silica interaction in distilled water was found to be repulsive at all distances, which is attributed to the surfaces interacting at "constant charge." These results are consistent with QCM measurements that show vesicles readily forming bilayers on silica in high salt but only weakly adhering in low salt conditions. We conclude that the electrostatic interaction is the most important interaction in determining the adhesion between neutral bilayers and charged hydrophilic surfaces. SP and FRAP experiments gave insights into the bilayer formation process as well as information on the surface coverage, lateral diffusion of the lipid molecules, and surface potential of the bilayers during the spreading process.

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DNA vaccines have many potential benefits but have failed to generate robust immune responses in humans. Recently, methods such as in vivo electroporation have demonstrated improved performance, but an optimal strategy for safe, reproducible, and pain-free DNA vaccination remains elusive. Here we report an approach for rapid implantation of vaccine-loaded polymer films carrying DNA, immune-stimulatory RNA, and biodegradable polycations into the immune-cell-rich epidermis, using microneedles coated with releasable polyelectrolyte multilayers. Films transferred into the skin following brief microneedle application promoted local transfection and controlled the persistence of DNA and adjuvants in the skin from days to weeks, with kinetics determined by the film composition. These “multilayer tattoo” DNA vaccines induced immune responses against a model HIV antigen comparable to electroporation in mice, enhanced memory T-cell generation, and elicited 140-fold higher gene expression in non-human primate skin than intradermal DNA injection, indicating the potential of this strategy for enhancing DNA vaccination.