Unchained Labs Sunscreen High-Throughput LNP Formulation Screening System

Overview

The Unchained Labs Sunscreen High-Throughput LNP Formulation Screening System is an automated, microfluidic-based platform engineered for rapid, reproducible, and scalable formulation development of lipid nanoparticles (LNPs). It operates on the principle of controlled hydrodynamic mixing—leveraging precise fluid dynamics within disposable Sunny microfluidic chips to achieve consistent nanoparticle self-assembly under defined stoichiometric, kinetic, and thermodynamic conditions. Unlike conventional bulk mixing or manual serial dilution approaches, Sunscreen enables parallelized synthesis across a full 96-well plate format, delivering up to 96 distinct LNP formulations in under six hours. This capability addresses a critical bottleneck in nanomedicine development: the empirical, time-intensive optimization of lipid composition, lipid-to-encapsulant molar ratios, pH-dependent ionization states, and mixing kinetics—all of which directly govern encapsulation efficiency, particle size distribution, polydispersity index (PDI), and in vivo transfection performance.

Key Features

• Automated 96-well parallel LNP synthesis with programmable flow rate (0.1–30 mL/min) and adjustable flow ratio (up to 5:1) for precise control over mixing kinetics and nucleation dynamics.
• Modular microfluidic chip architecture: Sunny (standard T-junction mixing), Sunny XT (cross-flow enhanced interfacial area), and Sunny Trident (full flow-rate + ratio + integrated on-chip dilution) — each optimized for specific formulation complexity and scalability requirements.
• Reusable chip holder with quick-release mechanism; Sunny chips are single-use, sterilizable, and validated for low protein/nucleic acid adsorption.
• Integrated real-time pressure monitoring and flow calibration to ensure system stability and batch-to-batch reproducibility.
• Pre-validated compatibility with common LNP lipid classes (ionizable, helper, structural, PEGylated) and diverse payloads including mRNA, siRNA, saRNA, CRISPR ribonucleoproteins (RNPs), and small-molecule therapeutics.

Sample Compatibility & Compliance

Sunscreen supports aqueous-phase payloads ranging from 400 µL to 2 mL per well, accommodating both low-concentration nucleic acids and high-viscosity lipid ethanolic solutions. The system is compatible with standard SBS-format 96-well plates (deep-well and PCR-grade), enabling seamless integration with downstream purification (e.g., tangential flow filtration, size-exclusion chromatography) and analytical workflows (DLS, NTA, HPLC, qRT-PCR). All fluidic pathways are constructed from USP Class VI-certified materials, and the platform meets ISO 13485 design controls for medical device-related R&D instrumentation. While not a GMP manufacturing system, Sunscreen-generated data supports GLP-compliant documentation when used with audit-trail-enabled Sunny Suite software and adheres to FDA 21 CFR Part 11 requirements for electronic records and signatures.

Software & Data Management

Sunny Suite is a Windows-based, role-controlled application that orchestrates experimental setup, real-time monitoring, and metadata capture. Users define plate maps (payloads, lipids, ratios), target flow parameters, and dilution schemes via intuitive graphical interfaces. The software performs pre-run validation—including volume sufficiency checks, flow-path integrity verification, and collision avoidance logic—to prevent failed runs. All instrument actions, sensor readings, and user inputs are timestamped and stored in encrypted SQLite databases with optional export to CSV, JSON, or LIMS-compatible formats. Audit trails include operator ID, parameter changes, chip lot numbers, and environmental logs (ambient temperature/humidity), supporting traceability from screening to clinical candidate selection.

Applications

• Rapid empirical mapping of LNP design space: lipid molar ratios, ionizable lipid pKa tuning, PEG-lipid density effects, and cryoprotectant screening.
• Early-stage structure–activity relationship (SAR) studies linking formulation variables to functional outcomes (e.g., luciferase expression, IFN-β induction, biodistribution profiles).
• Process transfer support: Sunny chip output correlates directly with Unchained Labs’ Sunshine benchtop and pilot-scale systems, enabling linear scale-up without reformulation.
• Stability assessment: generation of matched-formulation sets for accelerated degradation studies (temperature, freeze-thaw, buffer exchange).
• Regulatory filing support: generation of robust, metadata-rich datasets suitable for inclusion in IND/IMPD submissions as part of formulation development reports.

FAQ

Can Sunscreen be used for non-LNP nanocarriers, such as polymeric nanoparticles or liposomes?
Yes — while optimized for LNP self-assembly kinetics, Sunscreen’s programmable mixing parameters support other nanoprecipitation and thin-film hydration workflows when paired with appropriate solvent systems and chip configurations.
Is chip cleaning or reuse permitted?
No. Sunny microfluidic chips are designed for single-use only to ensure sterility, prevent cross-contamination, and maintain laminar flow fidelity. Reuse compromises reproducibility and violates ISO 13485-aligned quality protocols.
How does Sunscreen integrate with downstream analytics?
Each well output is delivered into standard 96-well plates compatible with automated DLS, fluorescence plate readers, and SEC-HPLC autosamplers. Sunny Suite exports plate maps with well-specific formulation IDs for direct LIMS linkage.
What level of technical support and qualification documentation is provided?
Unchained Labs supplies IQ/OQ documentation templates, chip lot-specific test reports (flow resistance, dead volume, surface wettability), and remote application support by field application scientists trained in mRNA/LNP process development.