Scott Michael Husson

Traditional filtration methods for separating host cell proteins and DNA from adeno-associated viral capsids often result in substantial yield losses. Here, we introduce a new high-yield purification strategy termed Ionic Regulation of Permeation (IROP) for removing major impurities within a single unit operation. Rather than relying on static size exclusion or binding interactions, IROP dynamically modulates AAV transport within a nanoporous membrane. At low ionic strength, AAV permeation was negligible, while high ionic strength markedly increased the sieving coefficient, revealing an electrostatic gating mechanism. AAVs retained under low-salt conditions could not be efficiently recovered by a static high-salt wash, indicating steric-electrostatic trapping within membrane pores. In contrast, high-salt filtration enabled high recovery. Leveraging this mechanism, a two-step IROP process, involving low-salt impurity clearance followed by high-salt AAV recovery, achieved greater than 90% AAV recovery with a greater than 95% reduction in HCPs and host cell DNA.

Extracting radionuclides from natural and anthropogenic sources addresses two challenges: remediating contaminated environments and enabling the separation of technologically important isotopes. Understanding how actinides interact and form complexes with polymer-based ligands allows the development of efficient extractants for selective remediation, supporting sustainable environmental protection and resource recovery strategies. Here, we report on the structure and actinide sorption properties of eco-friendly hybrid nanocomposite systems based on the natural mineral halloysite and multifunctional conjugated polymers. Three polyaniline (PANI)-based polymers and their nanocomposites with halloysite nanotubes (HNT) were synthesized and evaluated as sorbents for removing uranium and plutonium from aqueous solutions. The study included two PANI variants synthesized at high (60 °C) and low (1-2 °C) temperatures using different acid-dopants, H₂SO₄ and p-toluenesulfonic acid, and a PANI copolymer incorporating aminoterephthalic acid (PANIATA), which introduces carboxylic functional groups. X-ray photoelectron spectroscopy and electron microscopy revealed the formation of core-shell nanocomposites with HNT as the core and a polymer shell several nanometers thick. The HNT/PANI nanocomposites exhibited a synergistic enhancement in actinide retention capacity, exceeding the additive performance of the individual components. Sorption experiments with artificial groundwater and seawater confirmed the nanocomposites' selectivity for uranium. Analysis of the FTIR spectra of the polymer composites before and after uranium sorption provided detailed insight into uranyl cation-polymer complexation mechanisms responsible for high selectivity and sorption performance.

Technologies for large‐scale manufacturing of viral vectors for gene therapies, such as tangential flow filtration and membrane chromatography, are under development. In these early stages of process development, techno‐economic analyses are useful for identifying membrane properties yielding the greatest impact on process performance. In this study, we adapted a techno‐economic framework used for monoclonal antibody capture for adeno‐associated viral vector purification. We added mechanistic models to simulate flux decline during harvesting and separating full and empty capsids during polishing. Graphical user interfaces were added to help users explore the design search space. We selected a base process and manipulated selected variables to see their impact on large‐scale manufacturing performance. These sensitivity analyses revealed that, under the selected process conditions, increasing module capacity reduces cost of goods more effectively than increasing operational flux in tangential flow membrane filtration modules for virus harvesting. Membrane chromatography columns with relatively low dynamic binding capacity (DBC) and short residence time (RT) offered similar or better economic performance than those with high DBC and long RT. Additionally, the difference in equilibrium solid‐phase concentration between full and empty capsids as a function of salt concentration significantly affects purity.

Continuous manufacturing platforms and membrane chromatography are process technologies with the potential to reduce production costs and minimize process variability in monoclonal antibody production. This study presents a simulation and optimization framework to perform techno‐economic analyses of these strategies. Multi‐objective optimization was used to compare batch and continuous multicolumn operating modes and membrane and resin process alternatives, revealing performance differences in productivity and cost of goods attributed to variations in dynamic binding capacity, media geometry, and process residence time. From the set of optimal process configurations, we selected one membrane and one resin platform alternative yielding the highest net present values to undergo sensitivity analyses involving variations in batch cadence and product selling price. For the scenarios considered in this work, membrane continuous platforms showed benefits in the cost of goods and process mass intensity. Their shorter residence time compared to resins positions them as a viable alternative for single‐use capture chromatography. Moreover, this low residence time makes membrane platforms more flexible to changes in throughput, an essential feature for integrating capture into fully continuous processes.