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Results for “antibody viscosity”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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All sources NASA NTRS DOE OSTI

DOE OSTI2026

High-throughput small-angle X-ray scattering reveals effective structure factor transitions linked to high-concentration antibody viscosity

High-concentration monoclonal antibody (mAb) formulations are often constrained by elevated viscosity, largely driven by protein–protein interactions, which complicates manufacturing and limits subcutaneous delivery. Early viscosity risk assessment is essential during discovery, yet traditional measurements require large sample volumes, and lack high-throughput capability. Here, we develop a high-throughput small-angle X-ray scattering (SAXS) protocol to detect mAb self-association at dilute concentrations, enabling early predictive insights into high-concentration viscosity. Synchrotron SAXS measurements were conducted for 21 mAbs formulated in a histidine buffer at pH 6.0. An initial subset of 10 mAbs analyzed across 1–150 mg/mL revealed that effective structure factor transitions in the low-q region, indicative of interparticle interactions, consistently emerged below 25 mg/mL. Subsequently, 11 additional mAbs were analyzed at 1–25 mg/mL using automated liquid handling and flow cells to enable high-throughput screening. High-viscosity mAbs exhibited detectable low-q upturns at concentrations ≤10 mg/mL, whereas low-viscosity mAbs showed downturns. A classification criterion based on effective structure factor transitions accurately classified all high- and low-viscosity mAbs at 150 mg/mL, offering a scalable, sample-efficient alternative to conventional methods. These results extend recent findings on the concentration-dependent sensitivity of SAXS to short-range attractions, demonstrating that they can emerge at lower concentrations than previously reported. This study presents the most comprehensive and diverse SAXS dataset for mAbs reported to date within a single formulation, providing a valuable resource for developing and validating coarse-grained models that can more accurately capture intermolecular interactions governing high-concentration solution behavior, thereby enabling rational antibody engineering and improved developability.

36 MATERIALS SCIENCE↗

DOE OSTI2024

Variable domain mutational analysis to probe the molecular mechanisms of high viscosity of an IgG 1 antibody

Subcutaneous injection is the preferred route of administration for many antibody therapeutics for reasons that include its speed and convenience. However, the small volume limit (typically ≤2 mL) for subcutaneous delivery often necessitates antibody formulations at high concentrations (commonly ≥100 mg/mL), which may lead to physicochemical problems. For example, antibodies with large hydrophobic or charged patches can be prone to self-interaction giving rise to high viscosity. Here, we combined X-ray crystallography with computational modeling to predict regions of an anti-glucagon receptor (GCGR) IgG 1 antibody prone to self-interaction. An extensive mutational analysis was undertaken of the complementarity-determining region residues residing in hydrophobic surface patches predicted by spatial aggregation propensity, in conjunction with residue-level solvent accessibility, averaged over conformational ensembles from molecular dynamics simulations. Dynamic light scattering (DLS) was used as a medium throughput screen for self-interaction of ~200 anti-GCGR IgG 1 variants. A negative correlation was found between the viscosity determined at high concentration (180 mg/mL) and the DLS interaction parameter measured at low concentration (2–10 mg/mL). Additionally, anti-GCGR variants were readily identified with reduced viscosity and antigen-binding affinity within a few fold of the parent antibody, with no identified impact on overall developability. The methods described here may be useful in the optimization of other antibodies to facilitate their therapeutic administration at high concentration.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2025

High‐Concentration Antibody Formulation via Solvent‐Based Dehydration

Abstract Although subcutaneous (SC) delivery is the preferred administration route for immunotherapies and other biologics for improved patient compliance and lower healthcare costs, it necessitates high‐concentration antibody formulations. However, high‐concentration antibody solutions face significant instabilities and prohibitively high viscosities. Other approaches for high‐concentration formulations have been developed, including non‐aqueous solutions, which can be irritating or painful, and antibody‐laden hydrogel microparticles, which require centrifugation and are limited to concentrations <300 mg mL −1 . This work presents a new formulation process wherein the antibody is concentrated and encapsulated into hydrogel microparticles via solvent‐based dehydration. The final dosage form is an aqueous particle suspension with a formulation concentration of 360 mg mL −1 . In this process, microparticles are synthesized continuously, and antibody precipitation is realized simultaneously to dehydration, which allows for higher antibody concentrations. Antibody phase behavior and precipitation–dehydration kinetics are analyzed. The antibody is structurally and functionally stable in the microparticle post‐processing and after 4 months. Injectability of the suspension meets clinical standards with glide force <20 N. For the first time, an aqueous antibody formulation at high concentrations comparable to non‐aqueous formulations is presented, ideal for subcutaneous administration. The process is envisioned to be generalizable as a platform for SC delivery in multiple clinical applications.

Zheng, Talia [Department of Chemical Engineering M↗

NASA NTRS2008

Piezoelectric cantilever sensors

A piezoelectric cantilever with a non-piezoelectric, or piezoelectric tip useful as mass and viscosity sensors. The change in the cantilever mass can be accurately quantified by monitoring a resonance frequency shift of the cantilever. For bio-detection, antibodies or other specific receptors of target antigens may be immobilized on the cantilever surface, preferably on the non-piezoelectric tip. For chemical detection, high surface-area selective absorbent materials are coated on the cantilever tip. Binding of the target antigens or analytes to the cantilever surface increases the cantilever mass. Detection of target antigens or analytes is achieved by monitoring the cantilever's resonance frequency and determining the resonance frequency shift that is due to the mass of the adsorbed target antigens on the cantilever surface. The use of a piezoelectric unimorph cantilever allows both electrical actuation and electrical sensing. Incorporating a non-piezoelectric tip (14) enhances the sensitivity of the sensor. In addition, the piezoelectric cantilever can withstand damping in highly viscous liquids and can be used as a viscosity sensor in wide viscosity range.

Shih, Wan Y.↗

DOE OSTI2020

Microbiological, Physicochemical, and Immunological Analysis of a Commercial Cashew Nut-Based Yogurt

Nut-based milks and yogurts are gaining popularity, but may not offer the same benefits as dairy yogurts to consumers. Cashew nuts often cause severe allergic reactions, and cashew nut allergens are stable to several types of processing. To compare its characteristics to dairy yogurt and characterize the effects of fermentation on the Ana o 1–3 cashew nut allergens, a commercial yogurt made from cashew nuts (Cashewgurt) was evaluated for microbiological, physiochemical, and immunological properties. Average counts for lactobacilli and Streptococcus thermophilus were greater than 10 million colony forming units per milliliter, indicating the capacity to provide a health benefit. Cashewgurt pH and viscosity values were comparable to cow milk yogurts, and it was off white in color. SDS-PAGE analysis indicated a clear reduction in Ana o 1 and 2, and immuno-assay with polyclonal anti-cashew IgG antibody and cashew-allergic IgE indicated an overall reduction in allergen content. In contrast, SDS-PAGE, mass spectrometry, immunoblot, and ELISA all revealed that Ana o 3 was relatively unaffected by the fermentation process. In conclusion, Ana o 1 and Ana o 2 are sensitive to degradation, while Ana o 3 survives lactic acid bacterial fermentation during yogurt production. The analysis presented here indicates that cashew nut yogurt is not suitable for those with cashew nut allergy.

59 BASIC BIOLOGICAL SCIENCES↗