Whole blood immunoassay based on centrifugal bead sedimentation

Clin Chem. 2011 May;57(5):753-61. doi: 10.1373/clinchem.2011.162206. Epub 2011 Mar 17.

Abstract

Background: Centrifugal "lab on a disk" microfluidics is a promising avenue for developing portable, low-cost, automated immunoassays. However, the necessity of incorporating multiple wash steps results in complicated designs that increase the time and sample/reagent volumes needed to run assays and raises the probability of errors. We present proof of principle for a disk-based microfluidic immunoassay technique that processes blood samples without conventional wash steps.

Methods: Microfluidic disks were fabricated from layers of patterned, double-sided tape and polymer sheets. Sample was mixed on-disk with assay capture beads and labeling antibodies. Following incubation, the assay beads were physically separated from the blood cells, plasma, and unbound label by centrifugation through a density medium. A signal-laden pellet formed at the periphery of the disk was analyzed to quantify concentration of the target analyte.

Results: To demonstrate this technique, the inflammation biomarkers C-reactive protein and interleukin-6 were measured from spiked mouse plasma and human whole blood samples. On-disk processing (mixing, labeling, and separation) facilitated direct assays on 1-μL samples with a 15-min sample-to-answer time, <100 pmol/L limit of detection, and 10% CV. We also used a unique single-channel multiplexing technique based on the sedimentation rate of different size or density bead populations.

Conclusions: This portable microfluidic system is a promising method for rapid, inexpensive, and automated detection of multiple analytes directly from a drop of blood in a point-of-care setting.

Publication types

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

MeSH terms

  • Animals
  • C-Reactive Protein / analysis
  • Centrifugation, Zonal
  • Humans
  • Immunoassay / instrumentation
  • Immunoassay / methods*
  • Interleukin-6 / blood
  • Mice
  • Microfluidic Analytical Techniques
  • Microspheres*
  • Particle Size

Substances

  • Interleukin-6
  • C-Reactive Protein