The interactions between globular proteins in the presence of poly (ethylene glycol) (PEG) are probed through the measurement of the protein solution second virial coefficient (B2). The solution properties of PEG are characterized for four molecular weights (400, 1000, 6000, and 12 000), providing an opportunity for quantitative comparison of measurements and theoretical predictions of B2. PEG displays a buffer and molecular weight-dependent lower critical solution temperature. As the polymer solution approaches phase separation, the consequences of depletion attractions increase significantly. For lysozyme and bovine serum albumin in sulfate buffers with PEG, B2 is not well described by standard depletion models. This failure is accentuated in acetate buffers where B2 is a nonmonotonic function of polymer concentration. The attractive minima in B2 are closely associated with the proximity of the heating-induced phase separation of aqueous PEG solutions. The experimental data for both proteins in the presence of PEG are well captured by the thermal polymer reference interaction site model for depletion interactions where the polymer density fluctuation correlation length is treated as a function of temperature, polymer concentration, and molecular weight.

A robust correlation between experimentally determinable parameter, B2/B2HS, and protein solubility is explored. Here B2 is the protein solution second virial coefficient and B2HS=2πσ3/3 is the hard sphere second virial coefficient of the protein whose core is described as a sphere with diameter σ. The origin of this correlation, which extends over three decades in solubility, is discussed in terms of the phase behavior of simple fluids composed of particles experiencing short range attractions. For a given solubility B2/B2HS values cluster in a narrow range for a variety of protein solution conditions. However, the value of B2/B2HS at the metastable fluid/fluid transition remains as sensitive solution conditions. We discuss this sensitivity in terms of phase behavior predicted for particles interacting with the three parameter, square well and Yukawa potentials where metastable critical points are sensitive to the range of attraction. The position of this critical point relative to the solubility boundary and the ease of crystal nucleation are found to depend on solution conditions.

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The equilibrium and nonequilibrium phase behavior of a protein suspension is investigated as a function of strength of interparticle attraction and protein concentration. The equilibrium phase behavior suggests that the range of the particle attractions is a small fraction of their diameter. At volume fractions and strengths of attractions smaller than those characterizing the spinodal of a metastable fluid-fluid transition, the suspensions gel before they crystallize. At higher volume fractions and lower strengths of attraction, gels are formed first from which crystals nucleate over a period of time. However, at higher strength of attraction, crystals form first at lower volume fractions while gels are observed at higher volume fractions. We hypothesize that this behavior results from the competition between the rates of gelation and crystal nucleation. The location of the gel line is well predicted by mode coupling theories adapted for low volume fractions and square well fluids. At low strength of attraction, the gel line occurs at small supersaturations suggesting gels will be seen before nucleation. However, at higher strengths of attraction the gel line occurs at greatly increased supersaturations such that crystal nucleation can occur before the gel line is crossed. That mode coupling theories should predict gelation when crystallization does not intervene is tested by investigating the gel dynamics.

Water-soluble ≤6 nm tantalum oxide nanoparticles have been synthesized and characterized in solution using HPLC-ICP, DLS, and multinuclear NMR. Nanoparticle formulation permitted intravenous injection, in vivo imaging, and subsequent renal clearance. A clinical CT scanner provided excellent resolution following agent injection, and distribution to the arterial system was visualized. In vitro CT imaging studies indicated that at equal molar concentration of tantalum and iodine, tantalum produced greater image contrast than iodine across the diagnostic X-ray spectrum with contrast benefit increasing with peak X-ray energy.