Rheology of concentrated protein solutions and attractive colloidal dispersions
Name
1103917231-MIT.pdf
Size
34.69 MB
Format
Adobe PDF
Checksum (MD5)
34d2f1910cf6a57f2c3e7cd42aa7aa36
Author(s)
Wang, Gang,Ph. D.Massachusetts Institute of Technology.
Advisor(s)
James W. Swan.
Date Issued
2018
Publisher
Massachusetts Institute of Technology
Abstract
Therapeutic protein products with high solution concentration often possess extremely high viscosity and have difficulties in processing and delivery. It is desirable to predict and control the viscosity of protein solutions based on their interactions at the molecular level. Fundamental understanding on their rheology will greatly facilitate the development and engineering of biopharmaceuticals. In general, viscosity of attractive colloidal dispersions increases with their concentration and attraction strength, and diverges at the gel point. In this thesis, we investigate the mechanism of enhanced viscosity of concentrated protein solutions and colloidal dispersions due to inter-particle attractions. Coarse-grained models of protein solutions and colloidal dispersions are developed.
We improve a previously developed 12-bead model by considering the hydro-dynamic interactions and using the correct forms of screened electrostatic potential and dispersion forces to simulate monoclonal antibody solutions. The model captures anisotropic effects and correctly recovers the solution micro-structures. A random patchy sphere model with controllable surface patchiness is also developed to describe more general colloidal particles with anisotropic interactions. We observe signicant deviations in micro-structure and thermodynamics from isotropic particles at modest particle concentrations. Dynamics and rheology are sensitive to near-field non-central interactions and the resulting rigid constraints. Considering these constraints improves the viscosity prediction of concentrated antibody solutions and explains the diverging viscosity during gelation of attractive colloidal dispersions.
It is also noticed that the rigid constraints in physical gels play a similar role in rheology as the cross-links in chemical gels. We have demonstrated that the rigid constraints, which are seldom accounted for in previous works, are indispensable when computing the stress of a sheared suspension.
Description
This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Thesis: Ph. D., Massachusetts Institute of Technology, Department of Chemical Engineering, 2018
Cataloged from student-submitted PDF version of thesis.
Includes bibliographical references.
Subjects
Chemical Engineering.
MIT Department
Massachusetts Institute of Technology. Department of Chemical Engineering
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