Accelerate your LNP formulation screening with Sunscreen’s automated microfluidic technology

Significance of the Topic

LNPs are critical carriers for nucleic acid therapeutics, enabling rapid translation from design to clinic. Efficient formulation screening accelerates development while controlling critical parameters that influence particle size, stability and biological performance. Microfluidic automation addresses challenges in throughput, reproducibility and resource use in LNP discovery.

Objectives and Study Overview

This study demonstrates the application of the Sunscreen automated microfluidic platform to perform 96 independent LNP formulation experiments in under six hours without manual intervention. Three key evaluations were conducted: reproducibility assessment, combinatorial formulation screening, and flow rate impact analysis.

Instrumental Setup

The main components included:

• Sunscreen automated microfluidic system with Sunny 490 Trident T and Sunny 50 Micromixer chips
• Precision syringe pumps and robotic liquid-handling for reagent loading and integrated cleaning
• DLS measurements and PDI analysis via a 96-well plate particle sizer (e.g. Stunner)
• Encapsulation efficiency determined by Ribogreen assay and FLUOstar Omega plate reader

Main Results and Discussion

Reproducibility tests of a standard cLNP formulation (DOTAP:DSPC:Chol:DMG-PEG2000 40:10:37.5:2.5) over 96 runs yielded a mean size of 94.6 nm ±0.7 nm (RSD 0.8%) and PDI 0.14 ±0.01, with no cross-contamination after high-aggregation samples. In a 32-formulation screen, increasing PEG-lipid content reduced particle size, with DSPE-PEG2000 showing a stronger size modulation than DMG-PEG2000. DOPE-based structures exhibited higher PDI compared to DSPC, and DDAB/DSPE-PEG2000 combinations showed lower encapsulation efficiency. Varying total flow rate from 5 to 12 mL/min produced tunable particle sizes from ~138 nm to ~69 nm with consistent PDI, confirming precise hydrodynamic focusing control.

Benefits and Practical Applications

• High-throughput screening of complex LNP libraries in a single unattended run
• Reproducible and scalable microfluidic mixing with reusable glass chips
• Minimal sample waste and reduced consumable costs via integrated cleaning
• Customizable parameters for lipid ratios, flow conditions, and target properties

Future Trends and Potential Applications

Integration of Sunscreen with scale-up platforms, advanced lipid chemistries and active targeting ligands will expand formulation diversity. Coupling with machine-learning-driven design and in-line analytics promises rapid optimization cycles. The technology may be extended to continuous manufacturing and clinical-scale production of next-generation nanomedicines.

Conclusion

The Sunscreen automated microfluidic platform enables fast, reproducible LNP formulation screening, delivering precise control over particle attributes and supporting high-throughput workflows. Its automation and reusability offer significant advantages for research and development in nucleic acid delivery.

References

None reported in the source document.