KNAUER IJM SingleCore NanoProducer Impingement Jet Mixer

Overview

The KNAUER IJM SingleCore NanoProducer is a precision-engineered microfluidic impingement jet mixing system designed for the reproducible, scalable synthesis of lipid nanoparticles (LNPs), particularly for nucleic acid delivery applications including mRNA vaccine development. It operates on the principle of controlled hydrodynamic impingement: two precisely metered fluid streams—typically an ethanolic lipid solution and an aqueous phase containing active pharmaceutical ingredient (API), such as mRNA or siRNA—are accelerated to high velocities and directed toward each other within a geometrically defined mixing chamber. The resulting turbulent collision induces rapid solvent displacement, supersaturation, and spontaneous self-assembly of lipids into uniform, sub-100 nm particles. Unlike passive diffusion-based methods, this process delivers exceptional batch-to-batch consistency, narrow polydispersity index (PDI < 0.1), and tunable particle size via real-time adjustment of flow rate ratio, total flow, and temperature—parameters directly linked to nucleation kinetics and lipid phase transition behavior.

Key Features

• Single-core impingement jet architecture optimized for high-fidelity LNP formation under GMP-aligned conditions
• Four high-accuracy KNAUER 80P high-pressure metering pumps with integrated pressure monitoring and pulsation dampening
• Four Coriolis-type mass flowmeters (KNAUER) enabling true mass-based flow control independent of fluid density or viscosity changes
• Stainless steel 1.4301 (AISI 304) structural frame and wetted path components, electropolished to Ra ≤ 0.4 µm for bioburden control and cleanability
• Integrated quench module with programmable post-mixing temperature stabilization (4–60 °C) to halt particle growth and lock morphology
• Full system validation support: Factory Acceptance Testing (FAT) performed at KNAUER’s Berlin facility; Site Acceptance Testing (SAT) protocol included

Sample Compatibility & Compliance

The IJM SingleCore NanoProducer accommodates a broad range of formulation chemistries, including ionizable cationic lipids (e.g., DLin-MC3-DMA, SM-102), phospholipids (DSPC), cholesterol, and PEGylated lipids dissolved in ethanol or isopropanol, paired with nucleic acid payloads in Tris, citrate, or acetate buffers. All fluid paths are compatible with common LNP solvents and aqueous media. The system conforms to ISO 13485:2016 design controls for medical device manufacturing infrastructure and supports compliance with FDA 21 CFR Part 11 (electronic records/signatures), EU Annex 11, and ICH Q5A(R2) guidelines for characterization of biotechnological products. Full audit trail, user role management, and electronic signature workflows are embedded in the CDS software platform.

Software & Data Management

Control and data acquisition are managed through KNAUER’s validated CDS (Control & Data System) software, built on a deterministic real-time operating environment. The interface provides synchronized logging of all critical process parameters—including individual pump flow rates, pressure transients, temperature setpoints, valve actuation events, and flowmeter diagnostics—at ≥10 Hz resolution. Data export is compliant with ASTM E2500-13 (good practice for specification of pharmaceutical equipment) and supports CSV, PDF, and XML formats for integration into LIMS or MES systems. Electronic signatures, change control logs, and automated backup to network-attached storage ensure ALCOA+ (Attributable, Legible, Contemporaneous, Original, Accurate, Complete, Consistent, Enduring, Available) data integrity throughout the product lifecycle.

Applications

• Preclinical and clinical-scale LNP formulation development for mRNA, saRNA, and CRISPR-Cas ribonucleoprotein delivery
• Process parameter mapping (DoE) studies to establish design space per ICH Q5B and Q8(R2)
• Comparability assessments across manufacturing scales (lab to pilot to commercial)
• Stability-indicating process optimization for encapsulation efficiency (>90%), particle size (50–120 nm), and PDI (<0.12)
• Support for regulatory filings requiring detailed process understanding, including CMC sections of IND/IMPD submissions

FAQ

What is the minimum and maximum recommended flow rate per channel?
The system supports individual channel flow rates from 0.05 to 250 mL/min, with optimal LNP formation typically observed between 0.2 and 0.8 mL/min per stream at total flow rates up to 1 L/min.
Can the mixer core be replaced or sterilized in place?
Yes—the impingement chamber is a modular, autoclavable component (121 °C, 20 min) made from 1.4301 stainless steel; replacement kits and torque-spec tooling are supplied with full traceability documentation.
Does the system support integration with downstream tangential flow filtration (TFF)?
Standardized 1/2″ TC outlet ports and pressure-rated tubing connections enable direct coupling to commercial TFF skids; KNAUER provides interface schematics and flow compatibility guidance.
Is remote operation and monitoring supported?
CDS software includes secure OPC UA server functionality for integration into centralized SCADA environments; remote desktop access is permitted only via customer-controlled, firewall-protected VLANs per cybersecurity policy.
What validation documentation is provided with the system?
Delivery includes IQ/OQ protocols, FAT/SAT reports, material certifications (EN 10204 3.1), pump calibration certificates (traceable to DKD), and software validation summary per GAMP5 Category 4.