title: High-Throughput Fabrication of Nanocomplexes Using 3D-Printed Micromixers.
abstract: 3D printing allows a rapid and inexpensive manufacturing of custom made and prototype devices. Micromixers are used for rapid and controlled production of nanoparticles intended for therapeutic delivery. In this study, we demonstrate the fabrication of micromixers using computational design and 3D printing, which enable a continuous and industrial scale production of nanocomplexes formed by electrostatic complexation, using the polymers poly(diallyldimethylammonium chloride) and poly(sodium 4-styrenesulfonate). Several parameters including polymer concentration, flow rate, and flow ratio were systematically varied and their effect on the properties of nanocomplexes was studied and compared with nanocomplexes prepared by bulk mixing. Particles fabricated using this cost effective device were equally small and homogenous but more consistent and controllable in size compared with those prepared manually via bulk mixing. Moreover, each micromixer could process more than 2 liters per hour with unaffected performance and the setup could easily be scaled-up by aligning several micromixers in parallel. This demonstrates that 3D printing can be used to prepare disposable high-throughput micromixers for production of therapeutic nanoparticles.
authors.affiliation: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address: adam.bohr@sund.ku.dk.
authors.forename: Adam
authors.initials: A
authors.lastname: Bohr
authors.affiliation: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Johan
authors.initials: J
authors.lastname: Boetker
authors.affiliation: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Yingya
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Henrik
authors.initials: H
authors.lastname: Jensen
authors.affiliation: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jukka
authors.initials: J
authors.lastname: Rantanen
authors.affiliation: Institut Galien, Faculté de Pharmacie, Université Paris-Sud, Chatenay-Malabry, France.
authors.forename: Moritz
authors.initials: M
authors.lastname: Beck-Broichsitter
mesh_terms: D057166:High-Throughput Screening Assays / Q000295:instrumentation / Q000379:methods*; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation / Q000379:methods; D044085:Microfluidics / Q000295:instrumentation / Q000379:methods*; D049329:Nanostructures / Q000737:chemistry*; D066330:Printing, Three-Dimensional / Q000295:instrumentation / Q000706:statistics & numerical data*
keywords: 3D printing; continuous manufacturing; high throughput; microfluidics; micromixer; nanocomplex; nanoparticles