Aqueous Two-Phase System Rehydration of Antibody-Polymer Microarrays Enables Convenient Compartmentalized Multiplex Immunoassays

Anal Chem. 2016 Dec 6;88(23):11328-11334. doi: 10.1021/acs.analchem.6b02960. Epub 2016 Nov 17.

Abstract

Multiplex immunoassays are rapidly increasing in popularity due to the offered advantages of increased throughput and decreased sample volume requirements. However, a major weakness inherent to multiplex enzyme-linked immunosorbent assays (ELISA) is generation of false signals through reagent-driven cross-talk. Typically, multiplex platforms necessitate bath application of antibody cocktails, increasing probability of nonspecific antibody binding, especially when multiplexing large numbers of analytes. Aqueous two-phase systems (ATPS) exploiting the phase-separating polymers poly(ethylene) glycol (PEG) and dextran (DEX) have been used to compartmentalize antibodies and prevent cross-talk in multliplex, plate-based ELISA. However, the resulting protocol is tedious and lengthy, and requires too many user steps to be practical for widespread use. Here, we report an improved, user-friendly, cross-talk-free multiplex ELISA method in which dehydrated arrays of colocalized capture and detection antibodies in DEX are prepared on multiwell plates. Addition of a PEG-based sample buffer rehydrates antibody/DEX droplets for analysis. In this report, we demonstrate rehydrated ATPS components for multiplex ELISA retain the ability to compartmentalize antibodies and prevent cross-talk, while analytes in sample buffer partition into rehydrated DEX droplets for analysis. Utility of this method was demonstrated through successful quantitative analysis of five inflammatory cytokines in lipopolysaccharide-stimulated ThP-1 cell culture supernatant.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antibodies / analysis*
  • Cells, Cultured
  • Cytokines / analysis
  • Cytokines / biosynthesis
  • Dextrans / chemistry*
  • Enzyme-Linked Immunosorbent Assay*
  • Fluid Therapy
  • Humans
  • Lipopolysaccharides / pharmacology
  • Polyethylene Glycols / chemistry*
  • Water / chemistry

Substances

  • Antibodies
  • Cytokines
  • Dextrans
  • Lipopolysaccharides
  • Water
  • Polyethylene Glycols