Droplet microfluidics with magnetic beads: a new tool to investigate drug-protein interactions.
In this study, we give the proof of concept for a method to determine binding constants of compounds in solution. By implementing a technique based on magnetic beads with a microfluidic device for segmented flow generation, we demonstrate, for individual droplets, fast, robust and complete separation of the magnetic beads. The beads are used as a carrier for one binding partner and hence, any bound molecule is separated likewise, while the segmentation into small microdroplets ensures fast mixing, and opens future prospects for droplet-wise analysis of drug candidate libraries. We employ the method for characterization of drug-protein binding, here warfarin to human serum albumin. The approach lays the basis for a microfluidic droplet-based screening device aimed at investigating the interactions of drugs with specific targets including enzymes and cells. Furthermore, the continuous method could be employed for various applications, such as binding assays, kinetic studies, and single cell analysis, in which rapid removal of a reactive component is required.
Department of Chemistry and Applied Biosciences, ETH Zurich, Wolfgang-Pauli-Str. 10, 8093 Zurich, Switzerland.
Dario
D
Lombardi
Petra S
PS
Dittrich
D000925:Anticoagulants / Q000737:chemistry; D006801:Humans; D007700:Kinetics; D008280:Magnetics; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation / Q000379:methods*; D011485:Protein Binding; D012709:Serum Albumin / Q000737:chemistry*; D014859:Warfarin / Q000737:chemistry*
D000925:Anticoagulants; D012709:Serum Albumin; D014859:Warfarin