Streamline particle counting, turbidity, and color measurement into one automated platform with Big Kahuna VIS

Significance of the topic

Rapid and reproducible assessment of visible particles, color, and turbidity is critical in biologic drug formulation to ensure product quality and accelerate development timelines. Integrating these measurements into an automated platform reduces manual effort, enhances data consistency, and supports regulatory compliance.

Study Objectives and Overview

This application note describes the integration of a Visual Inspection Station (VIS) into the Unchained Labs Big Kahuna platform. The study demonstrates automated workflows for non-destructive measurement of visible particle counts, color matching, and turbidity in small-volume vials commonly used in biologics formulation.

Instrumentation

• Big Kahuna automated liquid handling system configured for biologics.
• Visual Inspection Station (VIS) with spinning vial mechanism, controlled illumination, and high-resolution imaging.
• Lab Execution and Analysis (LEA) software for motion control, image acquisition, data processing, and archiving.
• 3 mL and 20 mL glass vials with NIST-certified particle standards and turbidity standards (1–100 NTU).

Methodology

Particle Counting:

1. Prepare vials with ~8–9 polystyrene beads in water and ~50–60 glass beads in 65% glycerol (∼15 cP).
2. Automatically load vials into VIS; spin to resuspend particles, then stop and capture up to 8 fps images.
3. Perform image differencing to remove static features, convert to binary, and count particles within a central region of interest.

Color Assessment:

1. Image unknown samples and compare to a library of color standards using LEA software.
2. Calculate match scores to identify closest standard.

Turbidity Measurement:

1. Acquire blank image (no vial), then sample image in VIS.
2. Compute normalized luminance (ΔL/L) and correlate to NTU via calibration curves generated for each vial size.
3. Repeat measurements to assess reproducibility.

Key Results and Discussion

• Particle Counting: VIS counts (8–9 beads in water; 50–60 beads in glycerol) matched manual expectations with run-to-run variability attributed to particle overlap and ROI limits.
• Color Matching: Thirty replicates of a BY4 standard yielded match scores of 99.99–100%, demonstrating high precision.
• Turbidity: Calibration curves for 3 mL and 20 mL vials displayed linear responses from 1–100 NTU. Repeated measurements over two days remained within ±5% of nominal values.

Benefits and Practical Applications

Automating particle counting, color assessment, and turbidity measurement on a single platform significantly reduces hands-on time and sample consumption. The VIS provides quantitative, archivable data and supports high‐throughput formulation screening in biologics development.

Future Trends and Potential Applications

Extensions may include detection of sub-visible particles below 50 µm, multispectral color analysis for advanced formulation characterization, real-time inline monitoring during bioprocessing, and integration with machine-learning models for predictive stability assessments.

Conclusion

The Big Kahuna VIS system delivers accurate, reproducible, and fully automated analysis of visible particles, color, and turbidity in biologic formulations, enhancing productivity and data integrity in drug development workflows.

References

1. Rathore et al. ‘Challenges and Strategies for Implementing Automated Visual Inspection for Biopharmaceuticals.’ Pharmaceutical Technology, 2009.