Protein fouling during constant-flux virus filtration: Mechanisms and modeling

As biomanufacturers consider the transition from batch to continuous processing, it will be necessary to re-examine the design and operating conditions for many downstream processes. For example, the integration of virus removal filtration in continuous biomanufacturing will likely require operation at low and constant filtrate flux instead of the high (constant) transmembrane pressures (TMPs) currently employed in traditional batch processing. The objective of this study was to examine the effect of low operating filtrate flux (5–100 L/m²/h) on protein fouling during normal flow filtration of human serum Immunoglobulin G (hIgG) through the Viresolve® Pro membrane, including a direct comparison of the fouling behavior during constant-flux and constant-pressure operation. The filter capacity, defined as the volumetric throughput of hIgG solution at which the TMP increased to 30 psi, showed a distinct minimum at intermediate filtrate flux (around 20–30 L/m²/h). The fouling data were well-described using a previously-developed mechanistic model based on sequential pore blockage and cake filtration, suitably modified for operation at constant flux. Simple analytical expressions for the pressure profiles were developed in the limits of very low and high filtrate flux, enabling rapid estimation of the filter performance and capacity. The model calculations highlight the importance of both the pressure-dependent rate of pore blockage and the compressibility of the protein cake to the fouling behavior. These results provide important insights into the overall impact of constant-flux operation on the protein fouling behavior and filter capacity during virus removal filtration using the Viresolve® Pro membrane.     

Effect of protein fouling on filtrate flux and virus breakthrough behaviors during virus filtration process

Virus filtration process is used to ensure viral safety in the biopharmaceutical downstream processes with high virus removal capacity (i.e., >4 log₁₀). However, it is still constrained by protein fouling, which results in reduced filtration capacity and possible virus breakthrough. This study investigated the effects of protein fouling on filtrate flux and virus breakthrough using commercial membranes that had different symmetricity, nominal pore size, and pore size gradients. Flux decay tendency due to protein fouling was influenced by hydrodynamic drag force and protein concentration. As the results of prediction with the classical fouling model, standard blocking was suitable for most virus filters. Undesired virus breakthrough was observed in the membranes having relatively a large pore diameter of the retentive region. The study found that elevated levels of protein solution reduced virus removal performance. However, the impact of prefouled membranes was minimal. These findings shed light on the factors that influence protein fouling during the virus filtration process of biopharmaceutical production.     

Tolerance of the invasive tunicate Styela clava to air exposure

Styela clava is a subtidal invasive marine species in Northern Europe, Atlantic Canada, Australia and New Zealand. It grows attached to solid substrata, including boat hulls, ropes, moorings, piers and aquaculture equipment, all of which can aid its spread to new locations. It interferes with feeding of mussels and oysters, and increases their harvesting costs. Being subtidal, it could be assumed that tunicates would rapidly die in air and thus exposure to air would be a practical method to prevent their spread on boats and equipment. This study tested their survival when exposed to air for up to (1) 120?h at a constant temperature of 10?°C, (2) shade ambient 15–27?°C, and (3) full sun ambient 15–29?°C. Humidity was consistently high (78–100%). The results indicated that survival was longer when the air temperature was cooler. Larger individuals of S. clava generally survived for longer out of seawater than smaller individuals. The results predict that two weeks of exposure to air for two weeks could be an effective management method to eradicate S. clava from marine equipment when the air temperature is 10?°C. However, drying time would be less under conditions of low humidity and under direct sunlight.     

Links between estuarine condition and spatial distributions of marine invaders

Aim Non‐indigenous species pose a significant threat to the environment and to global economies. Predictive and preventative measures are widely considered more effective in curtailing invasions than are eradication or control measures. Of key importance in the prediction of regional invasion risk are the environmental conditions that enable successful establishment. Location We surveyed native and non‐indigenous sessile invertebrate diversity in each of two commercial (600–1500 vessels per year) and two recreational estuaries (seven to nine marinas) in New South Wales, Australia. Methods A nested hierarchical design was employed to investigate variation in sessile invertebrate diversity at the scales of site (1–3 km apart) and estuary (40–180 km apart). Settlement plates (15 × 15 cm) were used to sample invertebrates and background heavy metal loads were assessed using bioaccumulation in experimentally deployed oysters. Other physico‐chemical variables were monitored monthly. Manipulative experiments were used to test the direct effects of exposure to copper and tributyltin (TBT) antifouling paints on sessile invertebrates. Results Native and non‐indigenous species richness differed at various spatial scales, but showed no consistent difference between commercial and recreational estuaries. Instead, individual species distributions were strongly related to metal contamination, temperature, turbidity and pH. In experimental studies, several species (mostly invaders) were more abundant on plates exposed to copper and/or TBT antifouling paints. We found higher levels of copper (and in some instances TBT) in recreational marinas than in commercial harbours. Main conclusions Our results demonstrate the importance of metal pollution and physico‐chemical variables in the establishment of invaders in new regions. We have identified several native Australian species that have been exported overseas and suggested mechanisms contributing to their transport and establishment. Combining physico‐chemical information about donor and recipient regions with species tolerances could go some way to predicting where future invasions may occur.     

Susceptibility of California gastropods to an introduced South African sabellid polychaete, Terebrasabella heterouncinata

Abstract. The outer surfaces of the shells of living marine gastropods are often colonized by other organisms. However, only one species, the sabellid worm Terebrasabella heterouncinata , is able to settle in the aperture of living gastropods. Native to South Africa, and introduced to California, this worm is a pest of abalone aquaculture and has been a threat to native gastropods in California. We investigated the intrinsic susceptibility of 15 marine gastropods from California to this apertural fouling organism. Intrinsic susceptibility was significantly different among gastropod species. Overall, caenogastropods tended to be more resistant than were the vetigastropods and patellogastropods. This suggests that variability in susceptibility could be due to characteristics associated with closely related gastropod hosts. However, this only partially explained the variation in susceptibility to individuals of T. heterouncinata . Intrinsic susceptibility was not associated with potential host species from similar habitats. We discuss host susceptibility to T. heterouncinata , including implications for potential control of this pest species, and for understanding factors enabling this polychaete to inhabit the apertural region, an area typically free of all other epibionts.     

Global distribution patterns provide evidence of niche shift by the introduced African dung beetle Digitonthophagus gazella

The establishment of cattle ranches throughout the world has prompted the release of dung beetles as biological control agents that reduce pasture fouling and control dung-breeding flies. One of these beetles, Digitonthophagus gazella (Fabricius) (Coleoptera: Scarabaeidae), that is native to southeast Africa, has been introduced into the Americas, Australia, and New Zealand. Distribution records for this species have been used to develop climate models of potential future establishment. Recent studies, however, identify D. gazella as a complex of seven species. Taking into account this revision, and the clear identification of the records belonging to the actual D. gazella, we developed environmental models to identify factors that have contributed to the establishment of this species across regions and habitats. We compared the environmental conditions of D. gazella in its native range against those in the regions where the species has or has not established. Our results indicate that D. gazella is still absent in certain parts of Central and South America and parts of Africa where it could potentially establish. We speculate that its distribution in Africa is limited by competitive exclusion. The introduction of D. gazella in America is relatively recent, such that the full extent of its distribution has probably yet to be realized. In Australia and North America, D. gazella is present in regions not predicted according to its native environmental conditions. This discrepancy may reflect a lack of competitive exclusion, phenotypic plasticity, and/or genetic adaptation. Our analyses suggest that the species has the ability to adapt to a wide range of environmental conditions that are extremely different from those in their native region. The species represents a useful case study to indicate that an introduced species may expand its realized niche beyond what is expected based on apparent environmental limits in the species native range.     

Succession of Fouling Communities on an Artificial Substrate of a Mussel Culture in the White Sea

The pattern of development of a fouling community, based on research data on their formation in the mussel culture in the White Sea is presented. The succession may come to an end either by the mussel community or by the community of Styela rustica, which is analogous to the natural epitbenthic biocenosis of Laminaria saccharina. It also might develop with the deletion of some stages. The presence of the mussel phase is not necessary in the development of fouling. The final stage of the fouling development is determined, apparently, by hydrological conditions.