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Review
. 2011 Jul;400(9):2847-64.
doi: 10.1007/s00216-011-5047-7. Epub 2011 May 11.

Lanthanide-based time-resolved luminescence immunoassays

Affiliations
Review

Lanthanide-based time-resolved luminescence immunoassays

A K Hagan et al. Anal Bioanal Chem. 2011 Jul.

Abstract

The sensitive and specific detection of analytes such as proteins in biological samples is critical for a variety of applications, for example disease diagnosis. In immunoassays a signal in response to the concentration of analyte present is generated by use of antibodies labeled with radioisotopes, luminophores, or enzymes. All immunoassays suffer to some extent from the problem of the background signal observed in the absence of analyte, which limits the sensitivity and dynamic range that can be achieved. This is especially the case for homogeneous immunoassays and surface measurements on tissue sections and membranes, which typically have a high background because of sample autofluorescence. One way of minimizing background in immunoassays involves the use of lanthanide chelate labels. Luminescent lanthanide complexes have exceedingly long-lived luminescence in comparison with conventional fluorophores, enabling the short-lived background interferences to be removed via time-gated acquisition and delivering greater assay sensitivity and a broader dynamic range. This review highlights the potential of using lanthanide luminescence to design sensitive and specific immunoassays. Techniques for labeling biomolecules with lanthanide chelate tags are discussed, with aspects of chelate design. Microtitre plate-based heterogeneous and homogeneous assays are reviewed and compared in terms of sensitivity, dynamic range, and convenience. The great potential of surface-based time-resolved imaging techniques for biomolecules on gels, membranes, and tissue sections using lanthanide tracers in proteomics applications is also emphasized.

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Figures

Fig. 1
Fig. 1
Two representative immunoassay formats—a heterogeneous sandwich immunoassay (left) and a homogeneous immunoassay based on LRET between two luminescent labels (indicated by purple arrow; right). Antibodies labeled with tags (teardrop) are used for detection of antigens (circles)
Fig. 2
Fig. 2
Luminescence emission processes of a general europium chelate. An antenna ligand absorbs the excitation energy and transfers it to the T1 level via intersystem crossing, from which it is transferred to the chelated Eu3+ and emitted via several transitions
Fig. 3
Fig. 3
General principle of time-resolved luminescence measurements
Fig. 4
Fig. 4
Selected chelating, antenna, and protein-reactive groups for labeling of biomolecules with lanthanides
Fig. 5
Fig. 5
Non-luminescent lanthanide chelators for use in DELFIA assays
Fig. 6
Fig. 6
Luminescent PAC-based lanthanide chelators
Fig. 7
Fig. 7
β-diketonate-based lanthanide chelating agents. Abbreviations: BTBCT, 4,4′-bis(1″,1″,1″-trifluoro-2″,4″-butanedion-4″-yl)-chlorosulfo-o-terphenyl; BPPCT, 4,4′-bis(1″,1″,1″,2″,2″-pentafluoro-3″,5″-pentanedion-5″-yl)-chlorosulfo-o-terphenyl; BHHCT, 4,4′-bis(1″,1″,1″,2″,2″,3″,3″-heptafluoro-4″,6″-hexanedion-6″-yl)-chlorosulfo-o-terphenyl; BHHST, 4,4′-bis(1″,1″,1″,2″,2″,3″,3″-heptafluoro-4″,6″-hexanedion-6″-yl)-sulfonylaminopropyl ester-N-succinimide ester-o-terphenyl; BCDOT, 1,10-bis(4″-chlorosulfo-1,1″-diphenyl-4′-yl)-4,4,5,5,6,6,7,7,-octafluorodecane-1,3,8,10-tetraone; BCOT, 1,10-bis(8′-chlorosulfodibenzothiophene-2′-yl)-4,4,5,5,6,6,7,7,-octafluorodecane-1,3,8,10-tetraone; BCTOT, 1,10-bis(5′-chlorosulfothiophene-2′-yl)-4,4,5,5,6,6,7,7,-octafluorodecane-1,3,8,10-tetraone
Fig. 8
Fig. 8
Structures of BCDPA and the Cis-Bio bipyridine cryptate
Fig. 9
Fig. 9
Enzyme-amplified lanthanide luminescence. Top: enzyme-mediated conversion of a substrate into a product that forms luminescent chelates with lanthanides. Bottom: conversion of salicylic acid phosphate derivatives by ALP affords the corresponding salicylic acid which forms luminescent chelates with Tb-EDTA

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