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            In the biopharmaceutical industry, virus filters are crucial for ensuring the removal of endogenous and adventitious viruses as part of the viral clearance strategy. Although traditionally described as a size-exclusion mechanism, virus retention has a pro-cess-dependent nature where challenging conditions, such as process disruptions, may compromise membrane retention and significantly increase virus filtrate concentrations. The detailed mechanisms underlying this loss of retention are challenging to determine using traditional breakthrough experiments. In this work, single particle tracking and kinetic simulations were employed to connect individual particle behavior to the observed macroscopic losses in virus retention. Our experiments, using fluorescently labeled ΦX174 bacteriophage as a model parvovirus, replicated conditions representative of process disruptions within the Pegasus SV4, a homogeneous polymeric virus filtration membrane. During flow, phage particles retained were trapped within relatively large cavity spaces that had downstream constrictions aligned with the flow direction; the trapped particles were dynamic and exhibited significant intra-cavity motion. Upon flow stoppage, particles escaped from these retention locations rapidly, with approximately 90% of previously trapped particles being remobilized for process dis-ruption time ranging from 2 to 10 minutes, suggesting that local cavity escape had reached saturation at these timescales. Diffusion experiments within the membrane revealed isotropic and Fickian motion, hindered by more than an order of mag-nitude compared to diffusion in unconfined liquid. Despite the reduced mobility within the membrane, the substantial diffusion coefficient of 4.19 ± 0.06 µm²/s indicated that virus particles could travel tortuous but non-retentive pathways through the membrane on length scales equal to or greater than the membrane thickness during a disruption event. A 1D kinetic Monte-Carlo simulation successfully connected single-particle behavior to macroscopically observed virus release, indicating that significant diffusive release into the filtrate can occur even without the resumption of flow. This work provides crucial insights into the retention behavior of homogeneous membranes during periods of disruption, enabling the design of more robust mitigation strategies and filter designs.more » « lessFree, publicly-accessible full text available January 1, 2026
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            Control over the surface chemistry of elastomers such as polydimethylsiloxane (PDMS) is important for many applications. However, achieving nanostructured chemical control on amorphous material interfaces below the length scale of substrate heterogeneity is not straightforward, and can be particularly difficult to decouple from changes in network structure that are required for certain applications (e.g., variation of elastic modulus for cell culture). We have recently reported a new method for precisely structured surface functionalization of PDMS and other soft materials, which displays high densities of ligands directly on the material surface, maximizing steric accessibility. Here, we systematically examine structural factors in the PDMS components (e.g., base and cross-linker structures) that impact efficiency of the interfacial reaction that leads to surface functionalization. Applying this understanding, we demonstrate routes for generating equivalent nanometer-scale functional patterns on PDMS with elastic moduli from 0.013 to 1.4 MPa, establishing a foundation for use in applications such as cell culture.more » « less
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            Hydrogels are broadly used in applications where polymer materials must interface with biology. The hydrogel network is amorphous, with substantial heterogeneity on length scales up to hundreds of nanometers, in some cases raising challenges for applications that would benefit from highly structured interactions with biomolecules. Here, we show that it is possible to generate ordered patterns of functional groups on polyacrylamide hydrogel surfaces. We demonstrate that when linear patterns of amines are transferred to polyacrylamide, they pattern interactions with DNA at the interface, a capability of potential importance for preconcentration in chromatographic applications, as well as for the development of nanostructured hybrid materials and supports for cell culture.more » « less
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            Abstract Lamellar phases of alkyldiacetylenes in which the alkyl chains lie parallel to the substrate represent a straightforward means for scalable 1‐nm‐resolution interfacial patterning. This capability has the potential for substantial impacts in nanoscale electronics, energy conversion, and biomaterials design. Polymerization is required to set the 1‐nm functional patterns embedded in the monolayer, making it important to understand structure–function relationships for these on‐surface reactions. Polymerization can be observed for certain monomers at the single‐polymer scale using scanning probe microscopy. However, substantial restrictions on the systems that can be effectively characterized have limited utility. Here, using a new multi‐scale approach, we identify a large, previously unreported difference in polymerization efficiency between the two most widely used commercial diynoic acids. We further identify a core design principle for maximizing polymerization efficiency in these on‐surface reactions, generating a new monomer that also exhibits enhanced polymerization efficiency.more » « less
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