Time-resolved fluorescence resonance energy transfer assay for point-of-care testing of urinary albumin

Clin Chem. 2003 Jul;49(7):1105-13. doi: 10.1373/49.7.1105.

Abstract

Background: Microalbuminuria is an established early marker of diabetic nephropathy and an important cardiovascular risk factor in diabetes and hypertension. We aimed to develop a rapid point-of-care assay for the measurement of urine albumin.

Methods: The competitive homogeneous assay used an albumin-specific monoclonal antibody labeled with a stable fluorescent europium chelate as donor and an albumin labeled with cyanine 5 (Cy5) as acceptor. The assay was performed at room temperature in single microtitration wells that contained all the required dry-form reagents. The close proximity between the two labels in the immune complex allowed fluorescence resonance energy to be transferred from the pulse-excited europium chelate to the acceptor Cy5. The emission of long-lived energy transfer signal from the sensitized Cy5 was measured at 665 nm with time-resolved fluorometry that eliminated short-lived background.

Results: The assay procedure required 12 min for a 10- micro L urine sample. The working range was from 10 to approximately 320 mg/L, and the lower limit of detection was 5.5 mg/L. The within- and between-run CVs were 6.9-10% and 7.5-13%, respectively. Recovery was 103-122%. The assay correlated well (r(2) = 0.98; n = 37) with a laboratory-based immunoassay, although mean (SD) results were 7 (29)% lower.

Conclusions: The speed and ease of performance of this assay recommend it for near-patient use. The assay is the first to combine a fluorescence resonance energy transfer-type rapid competitive assay with an all-in-one dry reagent.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albumins / analysis*
  • Albumins / chemistry
  • Albuminuria / diagnosis*
  • Albuminuria / urine
  • Antibodies, Monoclonal / chemistry
  • Biomarkers / urine
  • Carbocyanines / chemistry
  • Chelating Agents / chemistry
  • Energy Transfer
  • Europium / chemistry
  • Fluorescent Dyes / chemistry
  • Fluoroimmunoassay
  • Humans
  • Kinetics
  • Nephelometry and Turbidimetry
  • Point-of-Care Systems*

Substances

  • Albumins
  • Antibodies, Monoclonal
  • Biomarkers
  • Carbocyanines
  • Chelating Agents
  • Fluorescent Dyes
  • cyanine dye 5
  • Europium