Sunshine — LNP 製程開發/優化平台

Sunshine LNP Process Development and Optimization Platform by Unchained Labs

Sunshine is a comprehensive nanoparticle process development and optimization platform from Unchained Labs, designed specifically for lipid nanoparticles (LNPs), liposomes, and polymer nanoparticles used in therapeutic drug delivery applications. As a core member of the Sunny Suite product line, Sunshine bridges the gap between high-throughput formulation screening with Sunscreen and GMP-compliant clinical manufacturing with Sunbather.

The Sunshine platform leverages advanced microfluidic technology based on hydrodynamic flow focusing to achieve precise, reproducible nanoparticle synthesis. By combining reagents in a controlled laminar flow environment within Sunnies microfluidic chips, researchers can produce highly uniform nanoparticles with narrow size distributions (PDI less than 0.2) and excellent encapsulation efficiencies exceeding 90 percent.

Three Flexible Configurations

Sunshine is available in three modular configurations to meet different research and development needs. Sunshine Single is designed for rapid, single-experiment payload encapsulation with sample volumes as low as 400 microliters, completing each run in under 5 minutes. This configuration is ideal for early-stage payload development where precious nucleic acid constructs require quick encapsulation for performance testing.

Sunshine Lite adds automated experiment sequencing through Protocol Mode, enabling researchers to automatically execute multiple experiments with varying flow rate ratios (FRR), total flow rates (TFR), and dilution parameters. The system can complete 10 different experiments in just 15 minutes from a single reagent loading step. Sunshine Lite also supports continuous production mode for generating larger volumes of nanoparticles.

The full-featured Sunshine configuration includes all capabilities of Sunshine Lite plus in-line dilution functionality. This critical feature allows real-time pH adjustment and solvent concentration reduction during particle formation, essential for maintaining nanoparticle stability and preparing for downstream processing.

Protocol Mode for Automated Parameter Optimization

Protocol Mode enables systematic exploration of process parameters with minimal hands-on time. Researchers can define experiment tables specifying different FRR, TFR, and dilution conditions, and the system automatically executes each experiment, performs flowpath cleaning, and collects samples to designated locations. This automated approach significantly accelerates process optimization while ensuring reproducibility.

Key parameters that can be optimized include flow rate ratio (controlling aqueous to organic phase proportions), total flow rate (affecting mixing time and particle size), dilution ratio (for pH and solvent adjustment), and N/P ratio (optimizing cationic lipid to nucleic acid charge ratio). Application data demonstrates that mRNA-LNP particle size can be precisely controlled from 58 to 94 nanometers by varying TFR from 2.5 to 10 milliliters per minute, with PDI values consistently below 0.15.

Continuous Mode for Scale-Up Production

Once optimal process conditions are identified, Sunshine seamlessly transitions to Continuous Mode using identical flow parameters. This capability allows production of tens of liters of nanoparticle suspension per day, sufficient for pre-clinical trials and extensive downstream characterization. Particle quality remains consistent between Protocol Mode experiments and Continuous Mode production, with size differences typically less than 7 nanometers.

Reusable Sunnies Microfluidic Chips

Sunshine utilizes Sunnies microfluidic mixing chips manufactured from high-precision glass with ultra-smooth channel surfaces. These chips support automated cleaning and can be reused indefinitely, dramatically reducing consumable costs and plastic waste. Nine different chip geometries are available including Sunny Trident (reverse-angle mixing with in-line dilution), Sunny X (cross-type mixing), and Sunny T (T-mixing), with multiple channel sizes to suit various applications.

Broad Application Range

Sunshine has been validated for producing diverse nanoparticle types including mRNA-LNPs using ionizable lipids such as SM-102 and cationic lipids like DOTAP, PEGylated liposomes based on DMPC and cholesterol formulations, phospholipid-based liposomes using Phospholipon 90G, and biodegradable polymer nanoparticles including PLGA and PLGA-PEG. The chemically resistant flowpath ensures compatibility with various organic solvents and reagent types.

Seamless GMP Transfer

As part of the Sunny Suite ecosystem, process parameters developed on Sunshine transfer directly to the GMP-compliant Sunbather system. Both platforms utilize identical pumping technology and Sunnies microfluidic chips, minimizing scale-up validation requirements and accelerating the path from development to clinical manufacturing.

Sunshine represents the ideal solution for nanomedicine researchers seeking to optimize lipid nanoparticle formulations for mRNA vaccines, gene therapies, CRISPR delivery systems, and other nucleic acid therapeutics, combining automated process development with scalable production capabilities in a single integrated platform.