Big Tuna

Significance of the Topic

Automated buffer exchange and sample concentration are critical preparatory steps in biochemical and biopharmaceutical workflows. Traditional manual methods are labor-intensive, time-consuming, and prone to variability. A high-throughput, hands-off solution can accelerate research, improve reproducibility, and free scientists for more value-added tasks.

Objectives and Overview

This document presents Big Tuna, a fully automated platform designed for rapid buffer exchange, formulation, concentration, and cleanup of proteins, viral vectors (AAVs, VLPs), lipid nanoparticles (LNPs), and nucleic acids. The system aims to minimize setup time (<15 min), process up to 96 samples in parallel, and seamlessly integrate with existing lab automation and data systems.

Methodology and Instrumentation

Big Tuna leverages a pressure-based ultrafiltration/diafiltration (UF/DF) process coupled with gentle orbital mixing to achieve uniform exchange across all wells. Key features include:

• Two plate formats: Unfilter 96 (100–450 µL per well) and Unfilter 24 (0.45–8 mL per well).
• Multiple MWCO membrane options (3, 10, 30, 100 kDa regenerated cellulose).
• Ultrasonic sensors for real-time volume measurement in each well.
• Programmable exchange pressures (15, 30, 60 psi) and orbital mixing speeds (700–875 rpm).
• Automated liquid handling with disposable tips (reusable up to 12 times per run).
• Software wizard for intuitive sample and buffer mapping, run customization, and API (SILA-2) support for LIMS and third-party integration.

Key Results and Discussion

Performance benchmarks demonstrate:

• High recovery (≥96%) and concentration accuracy (±10%).
• Efficient buffer exchange: Unfilter 96 completes 96% exchange of 10 mg/mL IgG in ~3 h; Unfilter 24 in ~4.5 h.
• Concentration capability: up to 24 samples concentrated from 48 mL to 8 mL.
• Automated volume monitoring ensures consistent exchange across all wells without manual supervision.

Benefits and Practical Applications

Big Tuna offers laboratory and industrial users:

• Scalable throughput (24 or 96 samples) for formulation screening and process development.
• Substantial reduction in hands-on time and bench monitoring.
• Versatility for proteins, viral vectors, LNPs, and nucleic acids.
• Reliable, reproducible sample preparation with minimal cross-contamination risk.
• Smooth integration into automated pipelines and data management systems.

Future Trends and Applications

Advancements in gene therapy and biologics production will drive the need for even more integrated, high-throughput sample prep platforms. Potential developments include AI-driven process optimization, continuous flow buffer exchange, expanded membrane chemistries, and tighter coupling with downstream analytics (e.g., mass spectrometry, biophysical characterization).

Conclusion

Big Tuna streamlines critical sample preparation tasks, delivering reproducible, high-throughput buffer exchange and concentration with minimal hands-on effort. Its flexibility, speed, and integration capabilities position it as a valuable tool for accelerating research and development in biopharmaceutical and analytical laboratories.