Sunscreen

Significance of the topic

Efficient formulation of lipid nanoparticles (LNPs) is critical for the development of nucleic acid therapeutics, including mRNA vaccines and gene therapies. High-throughput screening accelerates discovery of optimal lipid compositions, payload ratios and mixing conditions, reducing material waste and development timelines.

Objectives and study overview

This study introduces Sunscreen, an automated microfluidic platform designed to generate 96 unique LNP formulations in under six hours. The aim is to demonstrate rapid parallel screening, reproducible particle characteristics and seamless scale-up to larger production modules.

Methodology and instrumentation used

Sunscreen integrates a 96-well plate handler with interchangeable microfluidic mixing devices named Sunny T (T-mixing), Sunny X (cross-junction) and Sunny Trident (reverse-angle mixing with in-line dilution). A dedicated Sunny Suite software orchestrates sample loading, flow-rate programming (0.1–30 mL/min), lipid-to-payload ratios (1:1 to 5:1) and automated wash cycles. Key instrumentation features include:

• Pumps delivering consistent flow rates across wells
• Automated plate handling and fluid routing
• Reusable glass microfluidic chip mixers of varying channel geometries
• Integrated in-line dilution for broad concentration control

Main results and discussion

Sunscreen achieved 96 distinct LNP formulations in less than six hours, using 200 µL–2 mL volumes per experiment. Generated particles ranged from 40–200 nm with polydispersity indices below 0.2 and encapsulation efficiencies above 90%. Reproducibility across the full plate was confirmed by negligible variation in size and PDI for lipid mixtures such as DOTAP and ionizable lipids. Flow-rate studies showed tunable particle sizes by adjusting rates between 5 and 12 mL/min. The system eliminated cross-contamination through automated washes, ensuring consistent quality.

Benefits and practical applications of the method

• High throughput screening reduces formulation development time from weeks to hours
• Minimal consumption of costly payloads such as mRNA or plasmid DNA
• Scalable results transferable to larger continuous flow (Sunshine) and GMP (Sunbather) modules
• Automated software checks enhance reliability and minimize user error

Future trends and potential applications

Emerging directions include integration of real-time particle characterization, machine-learning algorithms for formulation optimization and on-chip analytical modules. This platform could be adopted in personalized medicine production, rapid vaccine development during pandemics and high-throughput screening of novel lipid chemistries.

Conclusion

Sunscreen offers a versatile, automated approach to accelerate LNP formulation screening with high reproducibility and minimal material use. Its compatibility with downstream scale-up modules ensures a streamlined workflow from discovery to GMP production.

Instrumentation

Key components:

• Sunscreen automated 96-well plate system with integrated pumps
• Sunny T, Sunny X and Sunny Trident glass microfluidic mixers
• Sunny Suite control software on dedicated computer (Windows 11)
• Fluidic connections: ¼”-28, 10–32 and Luer fittings
• Wetted materials: PTFE, PCTFE, FEP, ETFE, PEEK, FFKM, Hastelloy C276, SS316 and glass