A microliter capillary rheometer for characterization of protein solutions

Area of Science:

• Biophysical Chemistry
• Materials Science
• Pharmaceutical Engineering

Background:

• Rheometry is crucial for evaluating therapeutic protein solutions, assessing properties like syringeability, stability, and thermodynamic interactions.
• Current rheological methods often require large sample volumes and lack the dynamic range needed for comprehensive biopharmaceutical characterization.
• There is a significant industry demand for advanced rheometers that are miniaturized, offer a broad shear rate range, and eliminate air-sample interfaces.

Purpose of the Study:

• To develop and validate a miniaturized capillary rheometer tailored to the specific needs of the biopharmaceutical industry.
• To enable precise rheological measurements on therapeutic protein solutions using only microliter sample volumes.
• To achieve a wide dynamic range of shear rates and eliminate the air-sample interface in rheometric measurements.

Main Methods:

• Development of a novel miniaturized capillary rheometer system.
• Characterization of monoclonal antibody solutions across varying concentrations and temperatures.
• Validation of instrument performance against existing rheological techniques.
• Demonstration of measurement uncertainty within a few percent.

Main Results:

• The developed rheometer successfully measures rheological properties using only a few microliters of sample.
• The instrument exhibits a dynamic range of approximately three decades in shear rate.
• It accurately captures diverse solution behaviors, including Newtonian, shear thinning, and yielding.
• Performance was validated on monoclonal antibody solutions, showing good agreement with established methods.

Conclusions:

• The miniaturized capillary rheometer effectively meets the biopharmaceutical industry's demand for small-volume, high-dynamic-range rheological analysis.
• This technology offers a scalable solution, potentially adaptable to multiwell formats for high-throughput screening.
• The instrument provides a valuable tool for understanding therapeutic protein solution behavior, stability, and processing characteristics.