Optimizing virus filtration for continuous processing using serial filtration at high area ratio.

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.

Defect Detection Sensitivity of Bubble-Point-Type Tests for Sterilizing-Grade Membrane Cartridge Filters.

Bubble point tests are widely used for assessing the integrity of sterilizing-grade membrane cartridge filters. While many authors have considered the limitations of bubble point tests as applied to cartridge filters, the level of bacterial retention assurance provided by this test as conducted with automated integrity testers (AITs) has not, until now, been quantified. Contrary to the notion that filter leaks result in a depressed bubble point, it was shown that the bubble point as reported by AITs was insensitive to defect size up until the point where the AIT either determined a gross leak failure or was not able to return a valid result.

A Solid-State Hard Microfluidic-Nanopore Biosensor with Multilayer Fluidics and On-Chip Bioassay/Purification Chamber.

Solid-state nanopores are an emerging biosensor for nucleic acid and protein characterization. For use in a clinical setting, solid-state nanopore sensing requires sample preparation and purification, fluid handling, a heating element, electrical noise insulators, and an electrical readout detector, all of which hamper its translation to a point-of-care diagnostic device. A stand-alone microfluidic-based nanopore device is described that combines a bioassay reaction/purification chamber with a solid-state nanopore sensor.

Stimuli responsive charge-switchable lipids: Capture and release of nucleic acids.

Stimuli responsive lipids, which enable control over the formation, transformation, and disruption of supramolecular assemblies, are of interest for biosensing, diagnostics, drug delivery, and basic transmembrane protein studies. In particular, spatiotemporal control over a supramolecular structure can be achieved using light activated compounds to induce significant supramolecular rearrangements. As such, a family of cationic lipids are described which undergo a permanent switch in charge upon exposure to 365 nm ultraviolet (UV) light to enable the capture of negatively charged nucleic acids within the self-assembled supramolecular structure of the lipids and subsequent release of these macromolecules upon exposure to UV light and disruption of the assemblies.

Functionalized Nanofiber Meshes Enhance Immunosorbent Assays.

Three-dimensional substrates with high surface-to-volume ratios and subsequently large protein binding capacities are of interest for advanced immunosorbent assays utilizing integrated microfluidics and nanosensing elements. A library of bioactive and antifouling electrospun nanofiber substrates, which are composed of high-molecular-weight poly(oxanorbornene) derivatives, is described. Specifically, a set of copolymers are synthesized from three 7-oxanorbornene monomers to create a set of water insoluble copolymers with both biotin (bioactive) and triethylene glycol (TEG) (antifouling) functionality.

A nanopore-nanofiber mesh biosensor to control DNA translocation.

Solid-state nanopores show promise as single-molecule sensors for biomedical applications, but to increase their resolution and efficiency, analyte molecules must remain longer in the nanopore sensing volume. Here we demonstrate a novel, facile, and customizable nanopore sensor modification that reduces the double-stranded DNA translocation velocity by 2 orders of magnitude or more via interactions outside the nanopore. This is achieved by electrospinning a copolymer nanofiber mesh (NFM) directly onto a solid-state nanopore (NP) chip.