Automated viscometry measurement with Junior

Significance of the topic

Monoclonal antibody formulations often require high protein concentration to be effective which increases viscosity and complicates delivery and manufacturing. Accurate viscosity profiling is key to screening formulation developability and ensuring process feasibility.

Objectives and study overview

This work compares an automated microcapillary viscosity station integrated on a Junior platform with a conventional rotational rheometer. Six antibody formulations with concentrations from 20 to 200 mg per mL were analyzed to assess result agreement, throughput, hands-on time and sample consumption.

Methodology and instrumentation

Calibration used water and standard solutions covering 1 to 51 cP. Each sample of 100 microliter was aspirated with a positive displacement tip and injected into a temperature controlled capillary at 20 °C. Automated washing and drying cycles preceded each run. Viscosity was derived from measured shear rate and pressure response. Measurement time per sample was approximately 6 minutes.

A Malvern Kinexus rheometer performed rotational measurements with 180 microliter sample volume according to vendor guidelines. Each rheometer run required around 30 minutes including manual loading and cleaning.

Main results and discussion

Viscosity increased with protein concentration and trends matched closely between both instruments. Slight differences at intermediate concentrations reflect method specific flow and shear conditions. The automated station achieved consistent replicates with relative standard deviations below 10 percent across all shear rates.

Throughput analysis for 40 samples showed the viscosity station produced results in under four hours with five minutes hands-on time. In contrast the rheometer needed over twenty hours and returned to the instrument after each run. Volume requirements were reduced by over fifty percent with the automated system.

Benefits and practical applications

• High throughput screening enabling analysis of over 200 samples per day by a single operator
• Reduced sample consumption (100 microliter)
• Fully unattended operation minimizes manual intervention
• Integration with pH, turbidity and particle analysis on automated platforms accelerates formulation workflows

Future trends and potential applications

Expansion of automated viscosity profiling into larger integrated platforms can further streamline biologics development. Real time monitoring and machine learning driven data analysis may enhance predictive developability assessments. Miniaturization and coupling with orthogonal measurements will enable comprehensive high content screening of candidate formulations.

Conclusion

The Junior viscosity station delivers equivalent viscosity data to conventional rotational rheometry while achieving five times faster analysis and a forty fold reduction in hands-on time. Its low sample consumption and automation make it a valuable tool for high throughput antibody formulation screening.

References

1. Lorenz T et al Developability Assessment of Biologics by Integrated Profiling American Pharmaceutical Review August 2014
2. Yang X et al Developability Studies Before Process Development mAbs 2013 5(5) 787–794