Comparing Turbulent Mixing and Microfluidics for LNP Manufacturing in 2026
- Michael Nguyen
- 15 hours ago
- 3 min read
In recent conversations with clients, there's been a surge of interest around a rather intriguing subject in the biotech world: lipid nanoparticles (LNPs) and, specifically, the state-of-the-art mixing techniques used in their production. Clients do not know the difference between the turbulent mixing approach and that of microfluidics - they often come to us to enlighten them and explain which one is better!
Over the years, our team has witnessed the evolution of numerous mixing technologies and geometries. Given the complexity and the transformative potential of this topic, I think it’s time to dive deep and share some insights based on our extensive experience in this field.
Feature | Microfluidics (Laminar Flow) | Turbulent Mixing (Impingement Jet Mixers/T mixers) |
Mixing Mechanism | Diffusion dominated mixing under low Reynolds numbers. Relies on precise channel geometry and flow control. | High energy jet and vortex driven mixing at elevated Reynolds numbers. Rapid homogenization through controlled turbulence. |
Typical Scale | Primarily suited for early stage screening and low throughput research. Scaling requires parallelization. | Designed for seamless transition from development to clinical and commercial production. Linear scale up without redesign. |
Particle Size | Strong control under tightly defined conditions, but sensitive to minor parameter changes. | Consistent particle formation across a broader operating window, enabling robust and reproducible production. |
Encapsulation Efficiency | High encapsulation | High encapsulation |
Cost Profile | Higher recurring costs due to single-use consumable chips. | Lower global costs; mixers are often reusable after simple cleaning. |
Operational Robustness | Microchannels prone to clogging and fouling with complex formulations. | Open flow architecture minimizes clogging risk and handles higher concentrations with ease. |
Understanding Turbulent Mixing in LNP Production
Turbulent mixing technology, which involves the high-velocity collision of fluids to create nanoparticles, has been a game-changer in the production of LNPs. This technique allows for precise control over particle size and uniformity, crucial for the stability and effectiveness of RNA therapies.
Key Features of Turbulent Mixing
High throughput: Turbulent mixers can process large volumes quickly, making them suitable for industrial-scale production.
Simple equipment: The setup often involves standard pumps and mixers, reducing initial investment.
Scalability: Scaling up involves increasing flow rates or parallelizing mixers without major redesign.
Recent Improvements
In 2026, advances in mixer design have improved control over particle size distribution and encapsulation efficiency. For example, new static mixers with optimized geometries create more uniform turbulence, reducing batch variability. Integration with real-time monitoring tools allows operators to adjust parameters dynamically, ensuring consistent product quality.
Understanding Microfluidic Mixing in LNP Production
Microfluidics uses microscale channels to control fluid flow and mixing with high precision. Lipids and nucleic acids combine in these tiny channels, allowing fine-tuned control over nanoparticle formation.
Advantages of Microfluidics
Precise control: Microfluidic devices enable tight regulation of flow rates and mixing times, producing highly uniform LNPs.
Low reagent consumption: Working with small volumes can reduce waste and cost, though offset with consummable chip costs.
Some flexibility: Channel design or flow conditions can be adjusted for different formulations, but changes may require optimization.
Turbulent Mixer and Microfluidics Recent Comparisons
Process Robustness and Encapsulation: A 2025 systematic study using a Quality-by-Design (QbD) approach found that coaxial turbulent jet mixers generally produced smaller LNPs with a narrower particle size distribution and higher encapsulation efficiency for antisense oligonucleotides (ASO) compared to staggered herringbone microfluidic mixers.
For Biomimetic Nanoparticle Liposomes: Turbulent jet mixing as implemented in systems like the Nova IJM can produce biomimetic nanoparticles with robust protein incorporation and functional targeting capabilities on par with microfluidic methods, while offering higher adaptibility to many types of proteins/lipids due to broad solvent compatibility.
Translation Consistency: Research published in late 2025 suggests that when parameters are properly optimized, both chaotic advection (microfluidics) and turbulent flow (IJM) can formulate similar mRNA LNP vaccines during the development stage, with comparable immune responses in vivo.
Future Directions in LNP Manufacturing
Looking ahead, both methods will benefit from integration with digital tools and automation. Artificial intelligence will play a larger role in optimizing process parameters, reducing trial and error. Advances in materials science may also lead to new mixer designs and microfluidic chips that further improve efficiency and product quality. Collaboration between equipment manufacturers, pharmaceutical companies, and researchers will accelerate these developments, ensuring LNP manufacturing keeps pace with the growing demand for advanced therapies.
