Sunscreen：高通量 LNP 配方篩選的極致平台

Sunscreen: High-Throughput Automated LNP Formulation Screening Platform

The Sunscreen system represents a breakthrough in lipid nanoparticle (LNP) formulation development, combining the precision of microfluidic technology with walk-away automation to enable high-throughput screening of up to 96 unique formulations in a single day. As the leading delivery methodology for nucleic acid therapeutics, LNPs have demonstrated unprecedented translation speed from concept to clinic, exemplified by COVID-19 mRNA vaccines reaching clinical testing within 41 days of sequence publication. Sunscreen accelerates this development process further by transforming formulation screening from a time-consuming bottleneck into a streamlined workflow.

Automated Microfluidic Excellence

Sunscreen is the first commercial platform to combine automated, high-throughput testing with the essential precision, scalability, and reproducibility of microfluidics. The system processes samples from standard 96-well plates, with robotic arms automatically aspirating reagents requiring as little as 105 µL per input. Each experiment runs in 3-4 minutes, with the system completing full 96-sample plates in under 6 hours without operator intervention. The platform achieves remarkable reproducibility with coefficient of variation (CV) below 1%, ensuring that differences in particle properties reflect formulation variations rather than process inconsistencies.

Reusable Glass Microfluidic Technology

At the heart of Sunscreen's performance are the Sunny microfluidic chips, composed of ultra-smooth, inert glass with channel roughness of only ±5 nm. Unlike disposable plastic chips common in other systems, Sunnies are infinitely reusable thanks to automated washing integrated into each experimental cycle. The system offers multiple Sunny geometries including the Sunny 490 Trident T utilizing hydrodynamic flow focusing (HFF) for highly controlled laminar flow, and the Sunny 50 Micromixer intentionally inducing chaotic flow for smaller particle sizes at lower flow rates. All Sunnies are compatible with both Sunscreen and Sunshine systems, enabling seamless transition between development stages.

Comprehensive Parameter Control

The platform provides extensive control over critical LNP formation parameters. Total flow rates (TFR) range from 100 µL/min to 30 mL/min, while flow rate ratios (FRR) between aqueous and organic phases can be adjusted from 1:1 to 5:1. Collected sample volumes span 200 µL to 2 mL, with fully customizable head and tail cuts ensuring collection of the highest-quality sample core. Anti-dispersion technology (ADT) protects sample packets from driving fluids, maintaining high reagent concentrations and recovery rates. This flexibility enables optimization of particle size (typically 40-200 nm), polydispersity index (PDI < 0.2), and encapsulation efficiency (EE% > 90%) across diverse formulation spaces.

Validated Performance Across Applications

Extensive validation demonstrates Sunscreen's capabilities across multiple dimensions. Reproducibility testing with 90 replicates of a single DOTAP formulation achieved Z-average of 94.59 ± 0.71 nm with RSD of 0.76%. Large-scale formulation screening of 32 cationic LNP variants (in triplicate, 96 total experiments) completed in 5.5 hours revealed clear structure-property relationships, including the differential responsiveness of particle size to DSPE-PEG2000 versus DMG-PEG2000, and the influence of structural lipids (DSPC vs DOPE) on PDI. Flow rate screening demonstrated precise control over particle size, with statistically significant differences between each tested TFR from 5 to 12 mL/min.

Integrated Workflow Solutions

Sunscreen seamlessly integrates with complementary platforms to create complete LNP development workflows. When paired with Stunner AF for automated particle size and encapsulation efficiency analysis, users can synthesize and characterize a full 96-formulation plate within a single working day. Post-synthesis, samples can proceed directly to Big Tuna or Unagi systems for automated buffer exchange and purification. The Sunny Suite Software provides intuitive experiment design with plate mapping, real-time run monitoring, built-in validation checks, and complete audit trails for regulatory compliance.

Scalable Path to Production

As part of the Sunny Suite family, Sunscreen enables direct translation from screening to GMP manufacturing. All three systems—Sunscreen for screening, Sunshine for process optimization, and Sunbather for GMP production—share identical pump technology and Sunny chip geometries. Optimal mixing parameters identified during Sunscreen screening transfer directly to larger-scale production without process redevelopment, eliminating a traditional bottleneck in LNP commercialization. This seamless scalability accelerates the path from formulation discovery to clinical supply.

Applications Across Nucleic Acid Therapeutics

Sunscreen supports the full spectrum of LNP-based delivery applications including mRNA vaccines, siRNA therapeutics, gene editing vectors (CRISPR/Cas9), DNA vaccines, and other nucleic acid drugs. The system accommodates diverse lipid components including ionizable lipids (SM-102, DLin-MC3-DMA), cationic lipids (DOTAP, DDAB), structural lipids (DSPC, DOPE), cholesterol derivatives, and various PEGylated lipids (DSPE-PEG2000, DMG-PEG2000). This versatility enables exploration of passive and active targeting strategies for organ- and cell-type-specific delivery, advancing personalized medicine approaches.

Technical Specifications

The Sunscreen system measures 60 H x 90 W x 40 D cm with a weight of 57 kg, operating on 100-240V AC (50-60 Hz). Sample loops hold 2.5 mL, with four 1000 mL fluid storage bottles. Wetted materials include PTFE, PCTFE, FEP, ETFE, PEEK, polypropylene, FFKM, Hastelloy C276, stainless steel T316, and glass, ensuring chemical compatibility with diverse formulation components. The system requires a separate computer with Windows 11, monitor, keyboard, and mouse for operation. Nine different Sunny chip types are available, each optimized for specific mixing regimes and particle size ranges.

Advancing LNP Development

Sunscreen addresses the fundamental challenge in LNP development: the vast design space created by multiple lipid components, mixing parameters, and cargo types. Traditional manual approaches or low-throughput systems cannot efficiently explore this space, limiting innovation. By enabling rapid screening of 96 unique conditions per day with minimal material consumption and exceptional reproducibility, Sunscreen empowers researchers to discover optimal formulations faster, test more payload variants, and accelerate translation of nucleic acid therapeutics from concept to patient impact. The platform's combination of automation, microfluidic precision, and scalable technology positions it as an essential tool for any laboratory engaged in LNP development.