Molecular movement in confined spaces is of broad scientific and technological importance in areas ranging from molecular sieving and membrane separation to active transport along intracellular networks. Whereas measurements of ensemble diffusion provide information about the overall behavior of the guests in a nanoporous host, tracking of individual molecules provides insight into both the heterogeneity and the mechanistic details of the molecular diffusion, as well as into the structure of the host.

We first show how single dye molecules can be used as nanoscale probes to map the structure of nanoporous silica channel systems. These channel systems are prepared as thin films via cooperative self-assembly of surfactant molecules with polymerizable silicate species. In order to correlate the porous structure of the host with the diffusion dynamics of single molecules, we present a unique combination of transmission electron microscopic (TEM) mapping and optical single-molecule tracking experiments (SMT). With this approach, we can uncover how a single luminescent dye molecule travels through various defect structures in a thin film of nanoporous silica, how it varies its mobility in the channel structure, and how it bounces off a domain boundary having a different channel orientation. Additional polarization-dependent studies reveal simultaneous orientational and translational movements. In single-molecule measurements with very high positioning accuracy, we show how lateral motions between leaky channels allow a molecule to cross through defect structures into the neighboring channels and how the adsorption of single molecules at the walls of the nanoporous host can be observed as trapping events. Furthermore, a mechanism to switch on and off the diffusion of the guest molecules was discovered. These experiments reveal unprecedented details of the guesthost interactions and of the hosts structure, its domains, defects, and the accessibility as well as the connectivity of the nanostructured channel systems. The knowledge of these details and the use of mesoporous nanoparticles with functionalized pore walls will finally lead to novel drug delivery systems. Another type of drug delivery systems is synthetic viruses. Live cell experiments have been performed and the targeting and uptake of DNA-polyplexes as synthetic viruses were investigated. Single-molecule techniques can be used to improve the efficiencies of such synthetic viruses in novel gene therapy applications.

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