We are trying to help take colloidal rheology understanding beyond uniformly charged spheres to particles with more complex interactions, through new measurement and data analysis methods (for rheology of protein and model solutions).
A primary interest here is protein solution rheology and stability, involving bulk and interfacial properties and complemented by model solution measurements. Therapeutic protein solutions are highly concentrated during manufacturing and in finished dosage. At such concentrations, the fluid rheology is complex, creating the need for a convenient accurate method to measure viscosity. Here we develop rheology tools to help evaluate protein stability across a range of solution conditions and protein concentrations that are relevant to manufacturing and product formulation. One tool is a capillary viscometer that requires only a few micro-liters of solution to probe the range of flow rates and temperatures of interest. Another method probes concentrated protein films adsorbed to interfaces where aggregation may take place, and properties are suspected to correlate with solution stability. Teaming with collaborators, we test industrially relevant materials, evaluate structure and aggregation kinetics, and contribute to the development of an antibody SRM.
To develop measurement and data analysis methods to help take colloidal rheology understanding beyond uniformly charged spheres. More complex particles may be anything from synthetic "patchy" particles to proteins.
Proteins are of particular interest for their remarkable self-assembly and function.
The self assembly of proteins is well known, motivating synthesis of patchy particles that can assemble likewise. Model solutions help simplify interpretation and help to identify the measures that are most effective in characterizing effects.
In focusing on the rheology of protein solutions, we cover all bases: proteins of pharmaceutical interest and model solutions, and of both bulk and interfacial behavior.
Our approach in each of these areas is described below.
This method (when combined with scattering and other biophysical techniques) is now exploring correlations between viscosity, solution stability and cluster dynamics. Measuring the effects of pH, temperature, and salts is central to improving product yield during concentration of monoclonal antibodies (mAbs) in purification processes. Complex behavior is observed, and in some cases, flow can induce aggregation. The effects of pH and concentration are being measured over a much broader range than previously reported by others. The results demonstrate the failure of existing colloidal rheology models.
Model solution rheology
Protein interfacial rheology
Model interfacial measurements
Start Date:October 1, 2012
Lead Organizational Unit:mml
Source of Extramural Funding:
MedImmune, support of postdoctoral fellow.
Pharmaceutical companies are crucial contributors, with a deep knowledge and inventory of stable and unstable protein solutions. Rheology, scattering and particle analysis involves other collaborators at NIST.
Related Programs and Projects: