Multimodal Dispersion of Nanoparticles: A Comprehensive Evaluation of Size Distribution with 9 Size Measurement Methods



Evaluation of particle size distribution (PSD) of multimodal dispersion of nanoparticles is a difficult task due to inherent limitations of size measurement methods. The present work reports the evaluation of PSD of a dispersion of poly(isobutylcyanoacrylate) nanoparticles decorated with dextran known as multimodal and developed as nanomedecine.


The nine methods used were classified as batch particle i.e. Static Light Scattering (SLS) and Dynamic Light Scattering (DLS), single particle i.e. Electron Microscopy (EM), Atomic Force Microscopy (AFM), Tunable Resistive Pulse Sensing (TRPS) and Nanoparticle Tracking Analysis (NTA) and separative particle i.e. Asymmetrical Flow Field-Flow Fractionation coupled with DLS (AsFlFFF) size measurement methods.


The multimodal dispersion was identified using AFM, TRPS and NTA and results were consistent with those provided with the method based on a separation step prior to on-line size measurements. None of the light scattering batch methods could reveal the complexity of the PSD of the dispersion.


Difference between PSD obtained from all size measurement methods tested suggested that study of the PSD of multimodal dispersion required to analyze samples by at least one of the single size particle measurement method or a method that uses a separation step prior PSD measurement.

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Atomic force microscopy


Asymmetrical flow field-flow fractionation


Differential centrifugal sedimentation


Dynamic light scattering


Electron microscopy




Nanoparticle tracking analysis


Photon cross-correlation spectroscopy




Particle size distribution


Particle tracking analysis


Quasi elastic light scattering


Sedimentation field-flow fractionation


Scanning electron microscopy


Static light scattering


Transmission electron microscopy


Tunable resistive pulse sensing


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This work was supported by BpI France (Project NICE). The authors acknowledge the Région Ile-de-France (“Equipement mi-lourd 2012” program, DIM Malinf) and the JPK Company for their active support. The authors acknowledge all persons who performed measurement with different instruments: Camille Roesch (Izon Science Europe Ltd, Magdalen Centre, The Oxford Science Park, Oxford, UK), Pierre Peotta (Malvern, Parc club de l’Université, Orsay, France), Philippe Violle (Sympatec, Orsay, France), Serge Réteaud (Beckman Coulter, Villepinte, France), Caroline Ferré and Alain Jalocha (Cilas, Orléans, France). The present work has benefited from the facilities and expertise of the Electron Micoscopy facilities of Imagerie-Gif ( This core facility is member of the Infrastructures en Biologie Santé et Agronomie (IBiSA), and is supported by the French national Research Agency under Investments for the Future programs “France-BioImaging”, and the Labex “Saclay Plant Science” (ANR-10-INSB-04-01 and ANR-11-IDEX-0003-02, respectively).

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Correspondence to Christine Vauthier.

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Varenne, F., Makky, A., Gaucher-Delmas, M. et al. Multimodal Dispersion of Nanoparticles: A Comprehensive Evaluation of Size Distribution with 9 Size Measurement Methods. Pharm Res 33, 1220–1234 (2016).

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  • light scattering
  • microscopy
  • nanoparticle tracking analysis
  • particle size distribution
  • tunable resistive pulse sensing