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High compositional resolution characterization of multi-component macromolecular systems

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thesis
posted on 17.11.2022, 22:23 authored by Deyu YangDeyu Yang

Biopharmaceutical proteins have attracted increasing interest and been developed for treatment of various diseases due to their low toxicity, high affinity, and high efficacy. Subcutaneous injection, the most common delivery route for therapeutic proteins, requires high protein concentration formulations due to limited injection volume, resulting in challenges in manufacture, delivery, and stability of the drug products. Limited availability hinders the effective characterization of the physical properties of therapeutic proteins, especially during the early stage of development, where a large number of candidate formulations across a huge compositional space need to be screened. In this thesis, a droplet-based microfluidic device is innovated by incorporating a variety of sensing methods to quantify different physical properties of the concentrated protein solutions accurately and efficiently over a wide range of process-relevant parameters. Multiple particle tracking microrheology, birefringence, and turbidity are applied as the sensing methods to investigate viscosity, crystalline phase transitions, and phase separation of the protein solutions, respectively. The microfluidic technique provides data with high compositional resolution, and only requires a small sample volume. This work has demonstrated the potential of the developed novel technique to rapidly screen candidate formulations and provide guidance to facilitate the design of protein formulations to achieve desired properties. This technique can also be potentially applied as a complementary approach for computational methods to predict behaviors of high concentration formulations and facilitate understanding of the underlying mechanisms.

History

Date

22/04/2022

Degree Type

Dissertation

Department

Chemical Engineering

Degree Name

  • Doctor of Philosophy (PhD)

Advisor(s)

Lynn Walker

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