Single-Molecule Imaging
Total internal reflection fluorescence microscopy (TIRFM) 
allows us to image millions of individual molecules dynamically at聽solid/liquid and liquid/liquid interfaces.聽聽As with all聽single-molecule experimental methods, these experiments go beyond understanding the average behavior of adsorbates and聽enable us to probe variability in surface chemistry, molecular conformations, and adsorbate dynamics.聽聽Making such聽measurements, we often find that the behavior is much richer and more interesting than previously suspected. 聽 聽 聽 聽 聽 聽 聽 聽
Molecular Transport at Interfaces
The dynamic behavior of molecules and nanoparticles at 
interfaces leads to complex phenomena, where heterogeneity may arise from spatial variation of the interface itself, from molecular structures, or through inhomogeneous dynamic behavior. To obtain relevant information about these complex dynamics, we have developed highly multiplexed single-molecule/single-particle tracking methods that acquire large numbers of trajectories permitting rigorous analysis using statistical modeling and machine learning. A specific discovery that was enabled by these methods involves the ubiquitous intermittent motion (i.e. 鈥渉opping diffusion鈥�) of molecules at interfaces, which was explicitly confirmed using 3D double-helix point spread function imaging. Ongoing research studies the impacts of interfacial dynamics on various technological applications, membrane biophysics, and separations processes.
Mapping Using A肠肠耻尘耻濒补迟别诲听Probe
Trajectories (MAPT)
In MAPT, a time series of images is obtained using聽single-molecule TIFRM, and imaging processing is used to聽determine the locations of all the individual molecules. By tracking these locations through a time series, physical properties of probe/surface interactions (such as adsorption聽rates, local diffusion, desorption probability and surface coverage) are determined.聽聽By distributing these events to聽appropriate locations on the surface, one can determine聽characteristic values as a function of position. The use of聽single-molecule localization makes the MAPT analysis聽intrinsically super-resolution and we have demonstrated resolution of ~100 nm in our un-optimized initial results.聽聽In contrast with all previous super-resolution methods, MAPT can be used on any surface and provides absolute quantitative values of physical interaction properties. Homogenous surfaces can then be characterized and used as 鈥渃alibration鈥� points to connect small scale heterogeneities to specific surface chemistries.聽聽Using such maps, we found the first experimental evidence for desorption-mediated diffusion at the solid-liquid interface.聽
MAPT images of a photopatterned surface using multiple modes of contrast. (a) adsorption rate (1013 碌m-2s-1M-1) (b) average diffusion coefficient (碌m2/s) (c) desorption probability per 400 ms and (d) surface coverage/occupancy (1013 碌m-2s-1M-1).
Amyloidogenic Protein Refolding in
Lipidic and Polymeric Environments
Amyloid fibrils are highly stable protein species that are correlated to numerous diseases, including Alzheimer's and Parkinson's. In the Schwartz Lab, we utilize functional biomaterials to stabilize amyloidogenic proteins, inhibit their fibrillization, and in some cases, even completely reverse that fibrillization. These functional materials, namely lipid vesicles and polymer brush functionalized nanoparticles, can be tuned to be optimally stabilizing for specific proteins. Numerous techniques including fluorescence spectroscopy, circular dichroism spectroscopy, and single molecule methods give insight into how these materials work.
Dynamics in Confined Environments
Understanding molecular behavior under confinement is critical to various applications including biosensing, material synthesis, intracellular and extracellular transport, and a number of industrial separation processes. 聽In order to understand these environments, we have investigated systems ranging from surface crowding at the solid-liquid interface to structurally-induced confinement within synthesized materials. 聽Based on single molecule trajectories, we have characterized dynamics using a variety of empirical and model dependent analyses. 聽For example, it was discovered that poly(ethylene glycol) chains exhibited behavior consistent with the generalized continuous-time random walk model over a large range of surface coverage, from the dilute to well above the surface overlap concentration. 聽 Additionally, the polymer molecules had three distinct regimes of dynamics as a function of surface crowding, as shown by measurements of short-time diffusion coefficients, mean squared displacement, and surface waiting times. 聽In other experiments, nanoparticle trajectories in porous polymer membranes were analyzed in order to measure the tortuosity of the membrane, which was found to be a function of the operating conditions and not merely a constant value. 聽Moreover, distributions of the tortuosity indicated a large degree of spatiotemporal heterogeneity within the membranes, where anomalous, highly confined regions appeared to exist. 聽Further experiments investigating dynamics in inverse opal structures are currently underway, where individual particle trajectories are being investigated in the context of the narrow escape problem in order to provide a better understanding of confined diffusion in periodic nanostructures.聽
Molecular Modification of Heterogeneous
Catalysts
Performing selective conversions of reagents with multiple functional groups is a challenging objective since each group can potentially adsorb and react on a catalytic surface. One approach involves the modification of supported metal catalysts with organic ligands such as alkanethiols.聽Alkanethiols can be deposited on metal surfaces to form聽organized self-assembled monolayers (SAMs) that can greatly alter surface chemistry and potentially be used to significantly enhance selectivity of traditional catalytic systems. We have recently shown that such a strategy can be applied to technical supported catalysts such as Pd/Al2O3. This attachment strategy was found to dramatically enhance the selectivity to the desired products during furfural聽聽hydrogenation from < 5% on uncoated catalysts to > 90% on SAM coated catalysts by selectively blocking sites associated with the undesirable reaction pathway. By understanding how these ligands interact both with the surface as well as the reactants, we aim to tune their molecular structure to promote specific interactions for enhancing product selectivity.