Analytical and Bioanalytical Chemistry

, Volume 402, Issue 7, pp 2407–2415 | Cite as

Particle size measurement of lipoprotein fractions using diffusion-ordered NMR spectroscopy

  • Roger Mallol
  • Miguel A. Rodríguez
  • Mercedes Heras
  • Maria Vinaixa
  • Núria Plana
  • Lluís Masana
  • Gareth A. Morris
  • Xavier Correig
Original Paper


The sizes of certain types of lipoprotein particles have been associated with an increased risk of cardiovascular disease. However, there is currently no gold standard technique for the determination of this parameter. Here, we propose an analytical procedure to measure lipoprotein particles sizes using diffusion-ordered nuclear magnetic resonance spectroscopy (DOSY). The method was tested on six lipoprotein fractions, VLDL, IDL, LDL1, LDL2, HDL2, and HDL3, which were obtained by sequential ultracentrifugation from four patients. We performed a pulsed-field gradient experiment on each fraction to obtain a mean diffusion coefficient, and then determined the apparent hydrodynamic radius using the Stokes–Einstein equation. To validate the hydrodynamic radii obtained, the particle size distribution of these lipoprotein fractions was also measured using transmission electron microscopy (TEM). The standard errors of duplicate measurements of diffusion coefficient ranged from 0.5% to 1.3%, confirming the repeatability of the technique. The coefficient of determination between the hydrodynamic radii and the TEM-derived mean particle size was r2 = 0.96, and the agreement between the two techniques was 85%. Thus, DOSY experiments have proved to be accurate and reliable for estimating lipoprotein particle sizes.


Lipoprotein NMR DOSY TEM 



Cardiovascular disease


Diffusion-ordered NMR spectroscopy


Double-stimulated echo


Gradient gel electrophoresis


High-density lipoprotein


Intermediate density lipoprotein


Low-density lipoprotein


Longitudinal eddy current delay


Light scattering


Nuclear magnetic resonance


Pulsed-field gradient


Root mean squared percentage error


Small, dense LDL


Standard error


Signal-to-noise ratio


Transmission electron microscopy




Very low-density lipoprotein

Supplementary material

216_2011_5705_MOESM1_ESM.pdf (878 kb)
ESM 1(PDF 878 kb)


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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Roger Mallol
    • 1
    • 2
    • 3
  • Miguel A. Rodríguez
    • 2
    • 3
  • Mercedes Heras
    • 3
    • 4
  • Maria Vinaixa
    • 1
    • 2
    • 3
  • Núria Plana
    • 3
    • 4
  • Lluís Masana
    • 3
    • 4
  • Gareth A. Morris
    • 5
  • Xavier Correig
    • 1
    • 2
    • 3
  1. 1.Department of Electronic EngineeringUniversitat Rovira i VirgiliTarragonaSpain
  2. 2.Metabolomics Platform, IISPVUniversitat Rovira i VirgiliTarragonaSpain
  3. 3.CIBERDEMBarcelonaSpain
  4. 4.Lipids and Atherosclerosis Research Unit, Sant Joan University Hospital, IISPVUniversitat Rovira i VirgiliReusSpain
  5. 5.School of ChemistryUniversity of ManchesterManchesterUK

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