Let it flow: automated low volume viscosity measurements with Junior

Significance of the Topic

Measuring the viscosity of high-concentration biologic formulations, especially monoclonal antibodies (mAbs), is critical for evaluating manufacturability, stability and deliverability. Traditional viscometry often consumes large sample volumes and extensive hands-on time, limiting throughput in early-stage development. Automated low-volume methods enable rapid profiling of multiple candidates under controlled conditions, accelerating formulation optimization.

Objectives and Study Overview

This study assessed the performance of an automated micro-capillary viscometer (Junior with a viscosity station) for:

• Accuracy and reproducibility against published glycerol viscosity standards
• Comparison to a manual microVISC™ benchtop viscometer
• Viscosity profiling of a mAb concentration series (1–150 mg/mL)

Methodology and Instrumentation

Samples were analyzed at 20 °C using the Junior viscosity station (100 µL per measurement, 15 µL/s flow rate) and, for comparison, a microVISC™ at room temperature. Calibration employed triplicate measurements of glycerol standards (0–70% w/w) to determine the capillary’s apparent inner radius. A mAb stock was prepared in histidine buffer (10 mM, pH 6.0, 0.1% PS80) and diluted to various concentrations. Data acquisition, experiment design and analysis were managed through LEA software modules (Library Studio, Automation Studio, Excel Analysis Add-in).

Used Instrumentation

• Junior (Unchained Labs) with viscosity station and cooled storage bay
• Big Kahuna (Unchained Labs) as equivalent automated platform
• microVISC™ (Rheosense) manual viscometer

Main Results and Discussion

Glycerol standard viscosities measured on the viscosity station matched published values with excellent linearity (slope 0.997, R² 0.9999) and low variability (<3% RSD). The microVISC™ showed strong correlation (R² 0.9998) but underestimated viscosity (slope 0.85) due to ambient temperature variation. In the mAb series, viscosity rose exponentially with concentration, reaching ~9.5 cP at 150 mg/mL. Triplicate measurements on Junior exhibited high precision (≤6% RSD).

Benefits and Practical Applications of the Method

• Low sample volume (100 µL) conserves material for orthogonal assays
• Automated cleaning eliminates cross-contamination and reduces hands-on time
• User-defined temperature and flow control expand experimental flexibility up to 100 cP
• High throughput supports early formulation screening and developability assessment

Future Trends and Applications

Advances in automated micro-viscometry will integrate viscosity measurements with complementary biophysical assays (e.g., DLS, SEC). Miniaturization and AI-driven experimental design could further enhance throughput and predictive modeling of formulation behavior. Real-time viscosity feedback during bioprocessing and high-throughput stability studies represent emerging applications.

Conclusion

The Junior viscosity station delivers accurate, reproducible low-volume viscosity measurements comparable to published standards and outperforming manual methods in temperature control. Its automation, minimal sample requirements and flexible parameters make it a valuable tool for high-concentration biologic formulation development.

References

1. Segur J.B., Oberstar H.E. Viscosity of Glycerol and Its Aqueous Solutions. Industrial and Engineering Chemistry, 1951.