Poly(amidoamine) (PAMAM) dendrimers are increasingly studied as model nanoparticles for a variety of biomedical applications, notably in systemic administrations. However, with respect to blood contacting applications, amine-terminated dendrimers have recently been shown to activate platelets and cause a fatal, disseminated intravascular coagulation (DIC)-like condition in mice and rats. We here demonstrate that, upon addition to blood, cationic G7 PAMAM dendrimers induce fibrinogen aggregation, which may contribute to the in vivo DIC-like phenomenon. We demonstrate that amine-terminated dendrimers act directly on fibrinogen in a thrombin-independent manner to generate dense, high-molecular-weight fibrinogen aggregates with minimal fibrin fibril formation. In addition, we hypothesize this clot-like behavior is likely mediated through electrostatic interactions between the densely charged cationic dendrimer surface and negatively charged fibrinogen domains. Interestingly, cationic dendrimers also induced aggregation of albumin, suggesting that many negatively charged blood proteins may be affected by cationic dendrimers. To investigate this further, zebrafish embryos (ZFE) were employed to more specifically determine the speed of this phenomenon and the pathway- and dose-dependency of the resulting vascular occlusion phenotype. These novel findings show that G7 PAMAM dendrimers significantly and adversely impact many blood components to produce rapid coagulation and strongly suggest that these effects are independent of classic coagulation mechanisms. These results also strongly suggest the need to fully characterize amine-terminated PAMAM dendrimers in regards to their adverse effects on both coagulation and platelets, which may contribute to blood toxicity.

Diffusion coefficients of the Suwannee River fulvic acid (SRFA) obtained using fluorescence correlation spectroscopy (FCS), pulsed-field gradient nuclear magnetic resonance spectroscopy (PFG-NMR), and flow field-flow fractionation (FlFFF) were compared as a function of pH (4.0−8.5) and ionic strength (5−500 mM). Diffusion coefficients of the SRFA ranged between 1.9 and 3.5 × 10-10 m2 s-1. These values were fairly constant as a function of both pH and ionic strength and comparable to the limited literature values available. Polydispersity data are shown indicating that there is some degree of size and chemical heterogeneity for this humic sample including a small fraction of SRFA components with a diffusion coefficient smaller than 1 × 10-10 m2 s-1. The results imply that the majority of SRFA components have hydrodynamic diameters between 1.5 and 2.5 nm.

Surface roughness has been reported to both increase as well as decrease colloid retention. In order to better understand the boundaries within which roughness operates, attachment of a range of colloid sizes to glass with three levels of roughness was examined under both favorable (energy barrier absent) and unfavorable (energy barrier present) conditions in an impinging jet system. Smooth glass was found to provide the upper and lower bounds for attachment under favorable and unfavorable conditions, respectively. Surface roughness decreased, or even eliminated, the gap between favorable and unfavorable attachment and did so by two mechanisms: (1) under favorable conditions attachment decreased via increased hydrodynamic slip length and reduced attraction and (2) under unfavorable conditions attachment increased via reduced colloid-collector repulsion (reduced radius of curvature) and increased attraction (multiple points of contact, and possibly increased surface charge heterogeneity). Absence of a gap where these forces most strongly operate for smaller (<200 nm) and larger (>2 μm) colloids was observed and discussed. These observations elucidate the role of roughness in colloid attachment under both favorable and unfavorable conditions.

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High performance size exclusion chromatography (HPSEC) was used to obtain the molecular weight distributions of natural organic matter (NOM) from two South Australian drinking water sources. The NOM was separated into five nominal molecular weight fractions (<500, 500-3K, 3K-10K, 10K-30K, and >30K) using ultrafiltration membranes prior to HPSEC analysis. The use of HPSEC as a tool for NOM characterization was compared with an independent method, flow field-flow fractionation (FlFFF), which separates molecules via a different mechanism. Unlike HPSEC, which uses a porous gel with a controlled pore size distribution to separate molecules, FlFFF uses hydrodynamic and molecular diffusion principles to separate molecules on the basis of molecular size, in the absence of a porous gel. The comparison was made using the following parameters: weight-average molecular weight (M w ), numberaverage molecular weight (M n ), peak molecular weight (M p ), polydispersivity (M w /M n ), and molecular weight range (80% confidence limits). Within the technical limitations of each method, good agreement was obtained between HPSEC and FlFFF for the different fractions. Although solutegel interactions were identified with the HPSEC system, the validation of the technique with FlFFF indicates that HPSEC can provide useful and reliable molecular weight distributions of NOM in drinking water supplies.