Nigel K. H. Slater

A micro-capillary film has been developed that offers the potential for an at-line analytical tool for rapid aggregate analysis during biopharmaceutical antibody production. A non-porous walled micro-capillary film (NMCF) with cation exchange functionality was demonstrated to act as a chromatography medium that could be operated with high linear fluid velocities and was highly resistant to blockage by entrained particulates, including cells. The NMCF containing 19 parallel microcapillaries was prepared using a melt extrusion process from poly(ethylene-vinyl alcohol) copolymer (EVOH). The NMCF-EVOH was modified to have cation-exchange functionality (NMCF-EVOH-SP) and shown to differentially bind monomer and aggregated species of IgG antibody directly from a bioreactor. The use of NMCF-EVOH-SP to quantify aggregate concentrations in monoclonal antibody preparations in less than 20 minutes was demonstrated.

Highly aqueously dispersible (soluble) TiO2 nanoparticles are usually synthesized by a solution-based sol–gel (solvolysis/condensation) process, and no direct precipitation of titania has been reported. This paper proposes a new approach to synthesize stable TiO2 nanoparticles by a non-solvolytic method - direct liquid phase precipitation at room temperature. Ligand-capped TiO2 nanoparticles are more readily solubilized compared to uncapped TiO2 nanoparticles, and these capped materials show distinct optical absorbance/emission behaviors. The influence of ligands, way of reactant feeding, and post-treatment on the shape, size, crystalline structure, and surface chemistry of the TiO2 nanoparticles has been thoroughly investigated by the combined use of X-ray diffraction, transmission electron microscopy, UV-visible (UV–vis) spectroscopy, and photoluminescence (PL). It is found that all above variables have significant effects on the size, shape, and dispersivity of the final TiO2 nanoparticles. For the first time, real-time UV–vis spectroscopy and PL are used to dynamically detect the formation and growth of TiO2 nanoparticles in solution. These real-time measurements show that the precipitation process begins to nucleate after an initial inhibition period of about 1 h, thereafter a particle growth occurs and reaches the maximum point after 2 h. The synthesis reaction is essentially completed after 4 h.

One of the most significant challenges to stabilization of blood in the dry state is mitigation of hemoglobin oxidation. Here, oxidation of free hemoglobin vacuum desiccated in phosphate-buffered saline alone reached 65%±5%. Arabinose, glucose, sucrose, trehalose, and raffinose at 100 mM were shown to reduce oxidation to 24%±2%, 23%±2%, 3%±1%, 8%±3%, and 7%±2%, respectively. For comparison, 100 mM glutathione allowed 5%±2% hemoglobin oxidation. Oxidation protection provided by glucose, sucrose, and trehalose was shown to increase with concentration between 5 and 100 mM, plateauing thereafter. Oxidation of hemoglobin dried in the presence of 100 mM trehalose was shown to increase with decreasing initial pH.