Fouling Behavior during Sterile Filtration of Different Glycoconjugate Serotypes Used in Conjugate Vaccines.

PURPOSE: Sterile filtration can be a particular challenge when processing very large glycoconjugate vaccines. The objective of this study was to examine the sterile filtration performance of a series of glycoconjugate vaccines produced by coupling different polysaccharide serotypes to an immunogenic protein. METHODS: Sterile filtration was performed at constant filtrate flux using 0.22 µm pore size Durapore® polyvinylidene fluoride membranes. Glycoconjugates were characterized by dynamic light scattering, rheological measurements, and nanoparticle tracking analysis (NTA). Confocal microscopy was used to examine glycoconjugate capture profiles within the membrane. Transmembrane pressure data were analyzed using a recently developed fouling model. RESULTS: All glycoconjugates deposited in a narrow band near the entrance of the Durapore® membranes. The rate of fouling varied significantly for the different serotypes, with the fouling parameter correlated with the fraction of glycoconjugates larger than 200 nm in size. CONCLUSIONS: The fouling behavior and sterile filter capacity of the different glycoconjugate serotypes are determined primarily by the presence of large species (>200 nm in size) as determined by nanoparticle tracking analysis. The modified intermediate pore blockage model provides a framework for predicting the sterile filtration performance for these glycoconjugate vaccines.

Impact of protein fouling on nanoparticle capture within the Viresolve® Pro and Viresolve® NFP virus removal membranes.

Virus filtration is a robust size-based technique that can provide the high level of viral clearance required for the production of mammalian-derived biotherapeutics such as monoclonal antibodies. Several studies have shown that the retention characteristics of some, but not all, virus filters can be significantly affected by membrane fouling, but there have been no direct measurements of how protein fouling might alter the location of virus capture within these membranes. The objective of this study was to directly examine the effect of protein fouling by human immunoglobulin G (IgG) on virus capture within the Viresolve® Pro and Viresolve® NFP membranes by scanning electron microscopy using different size gold nanoparticles. IgG fouling shifted the capture location of 20 nm gold nanoparticles further upstream within the Viresolve® Pro filter due to the constriction and/or blockage of the pores in the virus retentive region of the filter. In contrast, IgG fouling had no measurable effect on the capture of 20 nm nanoparticles in the Viresolve® NFP membrane, and IgG fouling had no effect on the capture of larger 40 and 100 nm nanoparticles in either membrane. These results provide important insights into how protein fouling alters the virus retention characteristics of different virus filters.

Conducting polymer microcontainers for biomedical applications.

Advancement in the development of metallic-based implantable micro-scale bioelectronics has been limited by low signal to noise ratios and low charge injection at electrode-tissue interfaces. Further, implantable electrodes lose their long-term functionality because of unfavorable reactive tissue responses. Thus, substantial incentive exists to produce bioelectronics capable of delivering therapeutic compounds while improving electrical performance. Here, we have produced hollow poly(pyrrole) microcontainers (MCs) using poly(lactic-co-glycolic) acid (PLGA) as degradable templates. We demonstrate that the effective surface area of the electrode increases significantly as deposition charge density is increased, resulting in a 91% decrease in impedance and an 85% increase in charge storage capacity versus uncoated gold electrodes. We also developed an equivalent circuit model to quantify the effect of conducting polymer film growth on impedance. These MC-modified electrodes offer the potential to improve the electrical properties of implantable bioelectronics, as well as provide potential controlled release avenues for drug delivery applications.

Conducting Polymer Microcups for Organic Bioelectronics and Drug Delivery Applications.

An ideal neural device enables long-term, sensitive, and selective communication with the nervous system. To accomplish this task, the material interface should mimic the biophysical and the biochemical properties of neural tissue. By contrast, microfabricated neural probes utilize hard metallic conductors, which hinder their long-term performance because these materials are not intrinsically similar to soft neural tissue. This study reports a method for the fabrication of monodisperse conducting polymer microcups. It is demonstrated that the physical surface properties of conducting polymer microcups can be precisely modulated to control electrical properties and drug-loading/release characteristics.