title: A Microfluidic Platform for the Rapid Determination of Distribution Coefficients by Gravity-Assisted Droplet-Based Liquid-Liquid Extraction.
abstract: The determination of pharmacokinetic properties of drugs, such as the distribution coefficient (D) is a crucial measurement in pharmaceutical research. Surprisingly, the conventional (gold standard) technique used for D measurements, the shake-flask method, is antiquated and unsuitable for the testing of valuable and scarce drug candidates. Herein, we present a simple microfluidic platform for the determination of distribution coefficients using droplet-based liquid-liquid extraction. For simplicity, this platform makes use of gravity to enable phase separation for analysis and is 48 times faster and uses 99% less reagents than performing an equivalent measurement using the shake-flask method. Furthermore, the D measurements achieved in our platform are in good agreement with literature values measured using traditional shake-flask techniques. Since D is affected by volume ratios, we use the apparent acid dissociation constant, pK', as a proxy for intersystem comparison. Our platform determines a pK' value of 7.24 ± 0.15, compared to 7.25 ± 0.58 for the shake-flask method in our hands and 7.21 for the shake-flask method in the literature. Devices are fabricated using injection molding, the batchwise fabrication time is <2 min per device (at a cost of $1 U.S. per device), and the interdevice reproducibility is high.
authors.affiliation: †Department of Micro- and Nanotechnology, Technical University of Denmark, Kgs. Lyngby, Denmark.
authors.forename: Carl Esben
authors.initials: CE
authors.lastname: Poulsen
authors.affiliation: ‡Institute of Chemical and Bioengineering, Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland.
authors.forename: Robert C R
authors.initials: RC
authors.lastname: Wootton
authors.affiliation: †Department of Micro- and Nanotechnology, Technical University of Denmark, Kgs. Lyngby, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Wolff
authors.affiliation: ‡Institute of Chemical and Bioengineering, Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: deMello
authors.affiliation: ‡Institute of Chemical and Bioengineering, Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland.
authors.forename: Katherine S
authors.initials: KS
authors.lastname: Elvira
mesh_terms: D059625:Liquid-Liquid Extraction; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation; D010316:Particle Size; D011803:Quinine / Q000032:analysis*; D013499:Surface Properties
chemical_list: D011803:Quinine