Liquid Hanford nuclear wastes are highly concentrated caustic aqueous electrolyte solutions. They contain elevated dissolved aluminum concentrations compared to simple NaOH(aq) solutions in ...equilibrium with gibbsite γ-Al(OH)3. The reason for this elevated solubility has been debated for years, with slow gibbsite precipitation kinetics or various unverified thermodynamic factors being historically offered as explanations. The present study determines whether there is a kinetic or thermodynamic explanation. Here, dissolved aluminum in real tank waste was equilibrated with excess gibbsite, approached from both above and below saturation at 40 °C. In both cases, the samples equilibrated to an aluminum concentration up to four times higher than in pure NaOH(aq) solutions of the same hydroxide concentration. However, in one case, when all of the gibbsite dissolved during heating, no measurable precipitation was observed from the supersaturation direction when gibbsite seed was unavailable for nucleation. These results indicate that there is a real (and, as of yet, unknown) thermodynamic effect that accounts for the elevated solubility of aluminum exhibited by the waste. There is also a kinetic effect superimposed under some conditions.
Abstract Compared to batch operation, continuous bioprocessing can offer numerous advantages, including increased productivity, improved process control, reduced footprint, and increased flexibility. ...However, integration of traditional batch operations into a connected process can be challenging. In contrast to batch operations run at constant pressure or high flux, virus filtration in continuous processes may be operated at very low flux. This change in operating conditions may reduce the viral retention performance of the filter which has inhibited adoption of truly continuous virus filtration. To overcome this limitation, a novel approach is described that utilizes serial virus filtration, with a high area ratio between first to second stage filters, to achieve virus retention targets. In this study, virus filters were operated continuously (except for planned process interruptions) for 200 h in a serial configuration at a first to second stage filter area ratio of 13:1 and at a first stage flux of 5 L/m 2 /h. While the minute virus of mice (MVM) retention performance of the first stage filter was about 4 log reduction value (LRV), there was no virus detected in the second stage filtrate, translating to an MVM LRV across the filtration train of ≥6.7. The second stage filter was the dominant flow resistance at the start of the run but, as it was protected from foulants by the first stage filter, it suffered minimal fouling and the life of the filter train was controlled by the first stage. A theoretical case study projected that continuous virus filtration using serial configuration at high area ratio would have about 30% longer filter changeout time, 14% higher productivity, and virus retention nearly six LRV greater than single stage operation. The findings of this research are expected to provide valuable insights into optimizing virus filtration in continuous bioprocessing.
Adoptive T‐cell therapies (ATCTs) are increasingly important for the treatment of cancer, where patient immune cells are engineered to target and eradicate diseased cells. The biomanufacturing of ...ATCTs involves a series of time‐intensive, lab‐scale steps, including isolation, activation, genetic modification, and expansion of a patient's T‐cells prior to achieving a final product. Innovative modular technologies are needed to produce cell therapies at improved scale and enhanced efficacy. In this work, well‐defined, bioinspired soft materials are integrated within flow‐based membrane devices for improving the activation and transduction of T‐cells. Hydrogel coated membranes (HCM) functionalized with cell‐activating antibodies are produced as a tunable biomaterial for the activation of primary human T‐cells. T‐cell activation utilizing HCMs lead to highly proliferative T‐cells that express a memory phenotype. Further, transduction efficiency is improved by several folds over static conditions by using a tangential flow filtration (TFF) flow‐cell, commonly used in the production of protein therapeutics, to transduce T‐cells under flow. The combination of HCMs and TFF technology leads to increased cell activation, proliferation, and transduction compared to current industrial biomanufacturing processes. The combined power of biomaterials with scalable flow‐through transduction techniques provides future opportunities for improving the biomanufacturing of ATCTs.
Well‐defined, bioinspired soft materials are integrated within scalable, flow‐based membrane devices for improving the activation and transduction of T‐cells, which are essential steps in the production of adoptive T‐cell therapies. These innovative technologies provide opportunities for improving the manufacturing of cell therapies.
Thesis (M.S. in environmental engineering)--Washington State University, August 2009.
Title from PDF title page (viewed on Aug. 7, 2009). "Department of Civil and Environmental Engineering." Includes ...bibliographical references (p. 73-76).
