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Platelet Adhesion and Aggregation Under Flow using Microfluidic Flow Cells
Published on: October 27, 2009
18.7K
Using extensional flow to reveal diverse aggregation landscapes for three IgG1 molecules
Leon F Willis1,2, Amit Kumar1,2, John Dobson3
1Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, West Yorkshire, UK.
Biotechnology and Bioengineering
|January 10, 2018
Summary
Monoclonal antibodies (mAbs) are prone to aggregation under hydrodynamic forces. This study shows that extensional flow uniquely triggers mAb aggregation, enabling earlier optimization of drug candidates and formulations.
Area of Science:
- Biopharmaceutical development
- Protein aggregation
- Hydrodynamic forces
Background:
- Monoclonal antibodies (mAbs) are potent biotherapeutics but susceptible to aggregation, posing challenges in development and storage.
- Hydrodynamic forces, including shear and extensional flow, are implicated in protein aggregation, but their specific effects remain unclear.
Purpose of the Study:
- To quantify the impact of flow fields and protein concentration on the aggregation of three mAbs.
- To assess the utility of a controlled extensional flow device for biopharmaceutical development.
- To investigate the potential of this device as a formulation tool.
Main Methods:
- Utilized a previously developed device to control extensional flow.
- Quantified aggregation of three mAbs and bovine serum albumin (BSA) under varying flow conditions and concentrations.
- Evaluated the effect of different buffers on mitigating flow-induced aggregation.
Main Results:
- Monoclonal antibodies (mAbs) exhibit distinct aggregation responses to hydrodynamic flow compared to bovine serum albumin (BSA).
- Similar mAb sequences demonstrated varied sensitivity to hydrodynamic forces, highlighting individual protein characteristics.
- Different buffer formulations effectively ameliorated flow-induced aggregation for each mAb tested.
Conclusions:
- Extensional flow is a significant factor in mAb aggregation, with sensitivity varying between different antibodies.
- The controlled extensional flow device can identify aggregation-prone mAb candidates and optimize bio-process parameters and formulations early in drug discovery.
- This approach allows for optimization using small quantities of material, enhancing efficiency in biopharmaceutical development.
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