During production of concentrated monoclonal antibody formulations by tangential flow ultrafiltration (TFF), high viscosities and aggregation often cause extensive membrane fouling, flux decay and low product yields. To address these challenges, the co-solutes histidine or imidazole were added at high concentrations from 250 to 320 mM to reduce the viscosity by up to ten-fold relative to conventional low co-solute formulations, to as low as 40 cP at 250 mg/mL. At high mAb concentrations of up to 280 mg/mL, the transmembrane flux was increased threefold by adding high concentrations of co-solutes that also lowered the viscosity. Furthermore, the co-solutes also increased the mAb gel point concentration cg by up to 100 mg/mL mAb and thus enhanced concentration polarization-driven back-diffusion of the mAb at the membrane wall, which led to increased fluxes. The low viscosity and hollow fiber filter modules with straight flow paths enabled more uniform TMP and wall shear stress τw profiles, which mitigated the reversible flux decay that results from an axial decline in the local TMP. The concentrated mAb was stable by SEC before and after extended storage at 4 °C and 37 °C.
Subwavelength grating waveguide-based micro-ring resonators (SWGMRs) are a promising platform for research in light–matter interaction. However, it is extremely difficult to achieve small radius SWGMR devices (e.g., 5 μm) with satisfying quality factors (e.g., ∼10,000). One major issue is the large bend loss of small radius SWGMRs. In this work, we report the use of trapezoidal silicon pillars instead of conventional rectangular silicon pillars as building blocks of SWGMRs. We found that an asymmetric effective refractive index profile created by trapezoidal silicon pillars can significantly reduce the bend loss and therefore increase the quality factors of SWGMRs. For the first time to the best of our knowledge, we have experimentally demonstrated a 5 μm radius SWGMR made of trapezoidal silicon pillars (T-SWGMR) with an applicable quality factor as high as 11,500, 4.6 times of that (∼2800) offered by a conventional SWGMR made of rectangular silicon pillars, which indicates an 81.4% reduction of the propagation loss. This approach can also be readily employed to enhance SWGMRs with larger radii. We have also experimentally demonstrated a 10 μm radius T-SWGMR with a quality factor as high as 45,000, which indicates a propagation loss as low as 6.07 dB/cm.
The design of surfactants for stabilizing CO2-in-water (brine) (C/W) foams at high temperature is challenging given the low density (solvent strength) of CO2, limited surfactant solubility in brine, and a lack of knowledge of the interfacial and rheological properties. Herein, the tail length of trimethylammonium cationic surfactants was optimized to provide the desired phase behavior and interfacial properties for formation and stabilization of the C/W foams. The headgroup was properly balanced with a C12–14 hydrocarbon tail to achieve aqueous solubility in 22% total dissolved solids (TDS) brine up to 393 K (120 °C) along with high surfactant adsorption (area/surfactant molecule of 154 Å2) at the CO2–water (C–W) interface which reduced the interfacial tension from ∼40 mN/m to ∼6 mN/m. For C12–14N(CH3)3Cl, these properties enabled stabilization of a C/W foam with an apparent viscosity of 14 mPa·s at 393 K in both a crushed calcium carbonate packed bed (75 μm2 or 76 Darcy) and a capillary tube downstream of the bed. In addition, the partition coefficient of the surfactant between oil and 22% TDS (255 kg/m3) brine was less than 0.15, which would be beneficial for minimizing the loss of the surfactant to an oil phase in applications including enhanced oil recovery and hydraulic fracturing.
Diffusion of transmembrane and peripheral membrane-bound proteins within the crowded cellular membrane environment is essential to diverse biological processes including cellular signaling, endocytosis, and motility. Nonetheless we presently lack a detailed understanding of the influence of physiological levels of crowding on membrane protein diffusion. Utilizing quantitative in vitro measurements, here we demonstrate that the diffusivities of membrane bound proteins follow a single linearly decreasing trend with increasing membrane coverage by proteins. This trend holds for homogenous protein populations across a range of protein sizes and for heterogeneous mixtures of proteins of different sizes, such that protein diffusivity is controlled by the total coverage of the surrounding membrane. These results demonstrate that steric exclusion within the crowded membrane environment can fundamentally limit the diffusive rate of proteins, regardless of their size. In cells this "speed limit" could be modulated by changes in local membrane coverage, providing a mechanism for tuning the rate of molecular interaction and assembly.
Engineered nanoparticles have been proposed for use as contrast agents to enhance geophysical characterization of oil and gas reservoirs. Under saline conditions and in the presence of fine materials, nanoparticle mobility in porous media can be severely limited. To address this issue, a series of column experiments was performed to evaluate the ability of selected polymers and surfactants to enhance the transport of magnetite nanoparticles (nMag) coated with cross-linked polymers in the presence of American Petroleum Institute (API) brine (8 wt % NaCl + 2 wt % CaCl2). Aqueous suspensions containing nMag and API brine were injected at pore-water velocities of 2 ± 0.04 m/day or 10 ± 0.40 m/day through columns packed with either 40–50 mesh Ottawa sand or 60–170 mesh crushed Berea sandstone. When nMag (2500 mg/L) was introduced into Ottawa sand, 97% of the injected mass was recovered in the column effluent, indicating high mobility under saline conditions. However, the injection of nMag (2500 mg/L) into crushed Berea sandstone resulted in >60% nMag retention within the column. In order to improve delivery, nMag (2500 mg/L) was co-injected with 1000 mg/L hydroxyethyl cellulose (HEC-10), which increased nMag mobility 2-fold (78% effluent recovery). Co-injection of nMag with 1000 mg/L Gum Arabic or Calfax 16L-35, an anionic surfactant, resulted in slightly lower effluent recoveries of 72% and 69%, respectively. A preflood with 1000 mg/L HEC-10, followed by the injection of nMag alone (2500 mg/L), yielded an additional 20% improvement in nMag mobility (93% effluent recovery), suggesting that HEC-10 screened nMag attachment sites. A multisite nanoparticle transport model that accounts for heterogeneous mineralogy with variable attachment kinetics was able to accurately reproduce the effluent concentration data. Coupled with the observed 7-fold reduction in maximum retention capacity, the model parameter fits provide further evidence to support a site-blocking mechanism. These findings demonstrate the potential for relatively small additions (0.1%) of commercially available polymers and surfactants to greatly improve nMag mobility in porous media