title: Flow induced dispersion analysis rapidly quantifies proteins in human plasma samples.
abstract: Rapid and sensitive quantification of protein based biomarkers and drugs is a substantial challenge in diagnostics and biopharmaceutical drug development. Current technologies, such as ELISA, are characterized by being slow (hours), requiring relatively large amounts of sample and being subject to cumbersome and expensive assay development. In this work a new approach for quantification based on changes in diffusivity is presented. The apparent diffusivity of an indicator molecule interacting with the protein of interest is determined by Taylor Dispersion Analysis (TDA) in a hydrodynamic flow system. In the presence of the analyte the apparent diffusivity of the indicator changes due to complexation. This change in diffusivity is used to quantify the analyte. This approach, termed Flow Induced Dispersion Analysis (FIDA), is characterized by being fast (minutes), selective (quantification is possible in a blood plasma matrix), fully automated, and being subject to a simple assay development. FIDA is demonstrated for quantification of the protein Human Serum Albumin (HSA) in human plasma as well as for quantification of an antibody against HSA. The sensitivity of the FIDA assay depends on the indicator-analyte dissociation constant which in favourable cases is in the sub-nanomolar to picomolar range for antibody-antigen interactions.
authors.affiliation: Department of Pharmacy, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark. henrik.jensen@sund.ku.dk.
authors.forename: Nicklas N
authors.initials: NN
authors.lastname: Poulsen
authors.forename: Nina Z
authors.initials: NZ
authors.lastname: Andersen
authors.forename: Jesper
authors.initials: J
authors.lastname: Østergaard
authors.forename: Guisheng
authors.initials: G
authors.lastname: Zhuang
authors.forename: Nickolaj J
authors.initials: NJ
authors.lastname: Petersen
authors.forename: Henrik
authors.initials: H
authors.lastname: Jensen
mesh_terms: D001798:Blood Proteins / Q000032:analysis*; D017022:Flow Injection Analysis / Q000379:methods*; D006801:Humans; D010949:Plasma / Q000737:chemistry*; D013997:Time Factors
chemical_list: D001798:Blood Proteins