📋 Case Study

Bioreactor Scale-Up Twin for Cell Therapy Manufacturing

Loss of viability (>30%) and inconsistent glycosylation profiles during scale-up

🏗️ Project Overview

Closed-system bioreactor digital twin supporting clinical-to-commercial scale-up (5 L → 200 L → 2,000 L)

🎯 Challenge

Loss of viability (>30%) and inconsistent glycosylation profiles during scale-up

🔧 Design Approach

CFD-coupled metabolic twin using Monod kinetics + oxygen mass transfer correlations; validated with tracer studies and off-gas analysis

📐 Design Diagram

Bioreactor Scale-Up Twin for Cell Therapy Manufacturing Challenge: Viability loss >30% & inconsistent glycosylation Lab Scale V = 2 L Production Scale V = 200 L CFD-Metabolic Twin Monod + kLa Corr. Tracer Studies Off-Gas Analysis Scaling Metrics kLa ∝ (P/V)⁰·⁴·N⁰·⁵ = 0.78 τₘₐₓ = 10·ρ·N²·D² = 1.4 Pa

AI-generated project design illustration

📐 Key Calculations

kLa Scaling Factor

kLa ∝ (P/V)^0.4 · N^0.5
Result: 0.78
Ensures consistent oxygen transfer across scales

Shear Stress Threshold

τ_max = 10·ρ·N²·D²
Result: 1.4 Pa
Cell viability drops sharply above 1.2 Pa

📊 Results

Viability maintained ≥94% across scales, glycosylation profile CV reduced from 18% to 5.3%, accelerated tech transfer by 11 weeks

💡 Lessons Learned

  • Geometric similarity alone is insufficient—must match dimensionless numbers (Re, Fr, Da)
  • Twin requires real-time dissolved O₂ and pH microprobes for closed-loop control

Key Takeaways

  • 1Geometric similarity alone is insufficient—must match dimensionless numbers (Re, Fr, Da)
  • 2Twin requires real-time dissolved O₂ and pH microprobes for closed-loop control