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Protein fouling can significantly reduce the filtrate flux, capacity, and virus retention during processing of plasma- or mammalian cell-derived biopharmaceuticals through virus removal filters. We use focused ion beam (FIB) milling and scanning electron microscopy (SEM) to directly evaluate changes in 3D pore structure in a Viresolve® Pro membrane due to fouling by human serum immunoglobulin G. Protein fouling causes a significant reduction in the membrane porosity, which decreases by approximately 40% in the size-selective region near the exit of the highly asymmetric Viresolve® Pro membrane after the filter is fouled to 90% flux decline. There is a corresponding reduction in the number of small pores by more than a factor of two. Model simulations of flow and particle transport in the protein-fouled membrane are in good agreement with independent experimental measurements of the permeability and location of particle capture. Simulations show an upstream shift in the location of nanoparticle capture (away from the filter exit) by about 0.4 µm for the membrane fouled to 90% flux decline. This is due to pore constriction from protein deposition, highlighting how fouling redistributes flow paths within the membrane. These results demonstrate the capability of using FIB-SEM to directly evaluate the effects of protein fouling on the 3D pore structure in virus removal filters, providing important insights into how protein fouling alters the performance of these highly selective membranes. 

Gratev2 enables near-real time HRTEM analysis: a graph-based pipeline extracts d-spacing, orientation, and shape metrics; Bayesian optimization auto-tunes parameters; a Wasserstein-distance signals when data collection is sufficient. 

Recent advances in the water–energy landscape hinge upon our improved understanding of the complex morphology of materials involved in water treatment and energy production. Due to their versatility and tunability for applications ranging from drug delivery to fuel cells, polymeric systems will play a crucial role in shaping the future of water–energy nexus applications. Electron tomography (ET) stands as a transformative approach for elucidating the intricate structures inherent to polymers, offering unparalleled insights into their nanoscale architectures and functional properties in three dimensions. In particular, the various morphological and chemical characteristics of polymer membranes provide opportunities for perturbations to standard ET for the study of these systems. We discuss the applications of transmission electron microscopy in establishing structure–function relationships in polymeric membranes with an emphasis on traditional ET and cryogenic ET (cryo-ET). The synergy between ET and cryo-ET to unravel structural complexities and dynamic behaviors of polymer membranes holds immense potential in driving progress and innovation across frontiers related to water–energy nexus applications. Expected final online publication date for the Annual Review of Chemical and Biomolecular Engineering , Volume 15 is June 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates. 

Abstract Thermogels that exhibit a sol‐gel transition at body temperature represent a promising class of injectable biomaterials for biomedical applications. Thermogels reported thus far are generally composed of amphiphilic block copolymer micelles with an isotropic thermosensitive surface that induces intermicellar aggregation upon heating. Despite the promise, these hydrogels exhibit low mechanical strengths due to their uncontrollable aggregation resulting in void formation. To gain better control over intermicellar assembly, herein a novel thermogel design concept is presented based on patchy polymeric micelles bearing multiple thermosensitive surface domains. These domains serve as “patches” to bridge the micelles to form a percolated network structure. Patchy micelles are prepared from a binary mixture of amphiphilic block copolymers: Poly(N‐acryloylmorpholine)‐b‐poly(N‐benzylacrylamide) (PAM‐PBzAM) and poly (N‐isopropyl acrylamide)‐b‐poly(N‐benzylacrylamide) (PNIPAM‐PBzAM), where PBzAM, PAM and PNIPAM are the hydrophobic, hydrophilic and thermosensitive blocks, respectively. At 25 °C, the polymers self‐assembled into mixed shell micelles having a phase‐separated shell with PAM‐ and PNIPAM‐rich domains. At 37 °C, the PNIPAM domains undergo a hydrophilic‐to‐hydrophobic transition to induce intermicellar assembly into entangled worm‐like structures resulting in hydrogel formation. Patchy micelles form a homogeneous network structure without voids. The micelle design significantly affects the inter‐micellar assembly, the thermogelling behavior, and the mechanical properties of the hydrogels. 

Abstract Mesenchymal–epithelial transition (MET) is essential for tissue and organ development and is thought to contribute to cancer by enabling the establishment of metastatic lesions. Despite its importance in both health and disease, there is a lack of in vitro platforms to study MET and little is known about the regulation of MET by mechanical cues. Here, hyaluronic acid‐based hydrogels with dynamic and tunable stiffnesses mimicking that of normal and tumorigenic mammary tissue are synthesized. The platform is then utilized to examine the response of mammary epithelial cells and breast cancer cells to dynamic modulation of matrix stiffness. Gradual softening of the hydrogels reduces proliferation and increases apoptosis of breast cancer cells. Moreover, breast cancer cells exhibit temporal changes in cell morphology, cytoskeletal organization, and gene expression that are consistent with mesenchymal–epithelial plasticity as the stiffness of the matrix is reduced. A reduction in matrix stiffness attenuates the expression of integrin‐linked kinase, and inhibition of integrin‐linked kinase impacts proliferation, apoptosis, and gene expression in cells cultured on stiff and dynamic hydrogels. Overall, these findings reveal intermediate epithelial/mesenchymal states as cells move along a matrix stiffness‐mediated MET trajectory and suggest an important role for matrix mechanics in regulating mesenchymal–epithelial plasticity. 

Abstract All‐solid‐state batteries have the potential for enhanced safety and capacity over conventional lithium ion batteries, and are anticipated to dominate the energy storage industry. As such, strategies to enable recycling of the individual components are crucial to minimize waste and prevent health and environmental harm. Here, we use cold sintering to reprocess solid‐state composite electrolytes, specifically Mg and Sr doped Li₇La₃Zr₂O₁₂with polypropylene carbonate (PPC) and lithium perchlorate (LLZO−PPC−LiClO₄). The low sintering temperature allows co‐sintering of ceramics, polymers and lithium salts, leading to re‐densification of the composite structures with reprocessing. Reprocessed LLZO−PPC−LiClO₄exhibits densified microstructures with ionic conductivities exceeding 10⁻⁴ S/cm at room temperature after 5 recycling cycles. All‐solid‐state lithium batteries fabricated with reprocessed electrolytes exhibit a high discharge capacity of 168 mA h g⁻¹at 0.1 C, and retention of performance at 0.2 C for over 100 cycles. Life cycle assessment (LCA) suggests that recycled electrolytes outperforms the pristine electrolyte process in all environmental impact categories, highlighting cold sintering as a promising technology for recycling electrolytes.