Microfluidic Stress Device to Decouple the Synergistic Effect of Shear and Interfaces on Antibody Aggregation
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Le résumé fourni par la source
Protein denaturation and aggregation resulting from the effects of interfacial stress, often enhanced by flow and shear stress, pose significant challenges in the production of therapeutic proteins and monoclonal antibodies. The influence of flow on protein stability is closely intertwined with interfacial effects. In this study, we have developed a microfluidic device capable of exposing low volume (< 320 µL) protein solutions to highly uniform shear. To disentangle the synergistic impact of flow and interfaces on protein aggregation, we fabricated two devices composed of different materials, namely poly(methyl methacrylate) (PMMA) and stainless steel. Upon application of shear, we observed formation of protein particles in the micron-size range. Notably, The number of particles generated in the steel devices was ∼ 3.5 fold lower than in the PMMA device, hinting at an interface-mediated effect. With increasing the protein concentration from 1 to 50 mg/mL we observed a saturation in the amount of aggregates, further confirming the key role of solid-liquid interfaces in inducing particle formation. Introduction of non-ionic surfactants prevented protein aggregation, even at the highest tested protein concentration and low surfactant concentrations of 0.05 mg/mL. Overall, our findings corroborate the synergistic impact of shear and interface effects on protein aggregation. The device developed in this study offers a small-scale platform for assessing the stability of antibody formulations throughout various stages of the development and manufacturing process.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Microfluidic Stress Device to Decouple the Synergistic Effect of Shear and Interfaces on Antibody Aggregation
- Date Crossref
- 01/08/2024
- Éditeur
- Elsevier BV
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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ETH Zurich pays non établi dans la noticeUniversité ou école supérieure
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Institute for Chemical and Bioengineering Department of Chemistry and Applied Biosciences pays non établi dans la noticeStructure de recherche
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Janssen (Switzerland) pays non établi dans la noticeEntreprise
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Cilag (Switzerland) pays non établi dans la noticeEntreprise
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Biochemical Engineering Laboratory pays non établi dans la noticeStructure de recherche
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Janssen Cilag AG pays non établi dans la noticeInstitution
ETH Zurich, Department of Chemistry and Applied Biosciences — Institute for Chemical and Bioengineering et Janssen (Switzerland), avec 3 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.