Self-regulating microfluidic system for lipid nanoparticle production

Journal of Controlled Release, vol. 388, pp. 114370

Abstract

Lipid nanoparticles have emerged as valuable gene delivery systems paving the way for next-generation vaccine and cancer therapeutics. Inevitably, this evolution is carried by dissecting and rationalizing the vehicles’ complex formulation process. Given the vast design space, in silico methods resemble an elegant and cost-effective optimization approach. Here, we provide a proof-of-concept study on how data-driven automatization leverages rapid formulation parameterization, using readily obtainable, low-cost microfluidic hardware. Insights gained from both computational fluid dynamics simulations and microfluidic screenings are harnessed to derive and complement machine learning algorithms that predict critical quality attributes, such as size and encapsulation efficiency. Subsequently, these models are used to deploy a self-regulating microfluidic device, thereby bridging the gap between our computational and experimental work and enabling fully automated lipid nanoparticle formulation optimization on the fly, with minimal human intervention required. We envision our approach to accelerate the discovery of optimized nanoparticles in future designs. • Simulated fluid flow dynamics of lipid nanoparticle formulations. • Experimentally formulated particles using an automated microfluidic system. • Built machine learning algorithms to complement simulation-based interpretations. • Implemented a self-regulating optimization mechanism without human intervention.

Authors 11

1. Elena Reus

   University of Würzburg

   Affiliation as printed

   Institute for Pharmacy and Food Chemistry, University of Würzburg, Am Hubland, 97074 Würzburg, Germany

2. Johann Savinsky Aachen Chair of Chemical Process Engineering

   RWTH Aachen University

   Affiliation as printed

   Chair of Chemical Process Engineering, RWTH Aachen University, Forckenbeckstr. 51, 52074 Aachen, Germany

3. Simon Wennemaring Aachen Chair of Chemical Process Engineering

   RWTH Aachen University

   Affiliation as printed

   Chair of Chemical Process Engineering, RWTH Aachen University, Forckenbeckstr. 51, 52074 Aachen, Germany

4. Jonas Käsbach Aachen Chair of Bioprocess Engineering

   RWTH Aachen University

   Affiliation as printed

   Chair of Bioprocess Engineering, RWTH Aachen University, Forckenbeckstr. 51, 52074 Aachen, Germany

5. Felix Kerkhoffs Aachen Chair of Chemical Process Engineering

   RWTH Aachen University

   Affiliation as printed

   Chair of Chemical Process Engineering, RWTH Aachen University, Forckenbeckstr. 51, 52074 Aachen, Germany

6. Josef Kehrein

   University of Würzburg

   Affiliation as printed

   Institute for Pharmacy and Food Chemistry, University of Würzburg, Am Hubland, 97074 Würzburg, Germany

7. Tessa C. Lühmann

   University of Würzburg

   Affiliation as printed

   Institute for Pharmacy and Food Chemistry, University of Würzburg, Am Hubland, 97074 Würzburg, Germany

8. Anna Christina Adams Aachen Chair of Bioprocess Engineering

   RWTH Aachen University

   Affiliation as printed

   Chair of Bioprocess Engineering, RWTH Aachen University, Forckenbeckstr. 51, 52074 Aachen, Germany

9. Matthias Weßling Aachen DWI - Leibniz Institute for Interactive Materials Chair of Chemical Process Engineering

   RWTH Aachen University · DWI – Leibniz Institute for Interactive Materials

   Affiliation as printed

   Chair of Chemical Process Engineering, RWTH Aachen University, Forckenbeckstr. 51, 52074 Aachen, Germany; DWI - Leibniz Institute for Interactive Materials, RWTH Aachen University, Forckenbeckstr. 50, 52074 Aachen, Germany

10. Jørgen Barsett Magnus corresponding Aachen Chair of Bioprocess Engineering

    RWTH Aachen University

    Affiliation as printed

    Chair of Bioprocess Engineering, RWTH Aachen University, Forckenbeckstr. 51, 52074 Aachen, Germany. Electronic address: jorgen.magnus@avt.rwth-aachen.de

11. Lorenz Meinel corresponding

    University of Würzburg · Helmholtz Institute for RNA-based Infection Research

    Affiliation as printed

    Institute for Pharmacy and Food Chemistry, University of Würzburg, Am Hubland, 97074 Würzburg, Germany; Helmholtz Institute for RNA-based Infection Research (HIRI), Josef-Schneider-Strasse 2, 97080 Würzburg, Germany. Electronic address: lorenz.meinel@uni-wuerzburg.de