Observation of small cluster formation in concentrated monoclonal antibody solutions and its implications to solution viscosity.

Monoclonal antibodies (mAbs) are a major class of biopharmaceuticals. It is hypothesized that some concentrated mAb solutions exhibit formation of a solution phase consisting of reversibly self-associated aggregates (or reversible clusters), which is speculated to be responsible for their distinct solution properties. Here, we report direct observation of reversible clusters in concentrated solutions of mAbs using neutron spin echo. Specifically, a stable mAb solution is studied across a transition from dispersed monomers in dilute solution to clustered states at more concentrated conditions, where clusters of a preferred size are observed. Once mAb clusters have formed, their size, in contrast to that observed in typical globular protein solutions, is observed to remain nearly constant over a wide range of concentrations. Our results not only conclusively establish a clear relationship between the undesirable high viscosity of some mAb solutions and the formation of reversible clusters with extended open structures, but also directly observe self-assembled mAb protein clusters of preferred small finite size similar to that in micelle formation that dominate the properties of concentrated mAb solutions.

Sharp Hydrophilicity Switching and Conformality on Nanostructured Surfaces Prepared via Initiated Chemical Vapor Deposition (iCVD) of a Novel Thermally Responsive Copolymer.

A novel thermally responsive copolymer p(NIPAAm-co-DEGDVE) is synthesized using the substrate independent method of iCVD and exhibits a sharp lower critical solution temperature (LCST) transition centered at ≈28.5 ± 0.3 °C determined via quartz crystal microbalance measurements with dissipation monitoring (QCM-D). Swelling with water below the LCST produces a reversible change of ≈3× in film thickness. The layer is conformal on nanostructured surfaces including MWCNT forests and electrospun nanofiber mats. Modified planar substrates exhibit ≈30°change in static contact angle over the LCST, while through conformal coating on nanostructured substrates changes in static contact angle up to 135° are achieved. Additionally, coated surfaces exhibit temperature sensitive BSA adsorption measured by QCM-D and is reversible as shown through fluorescence imaging of a coated electrospun nanofiber mat.