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Method for determining the size distribution of a mixture of particles of (macro)molecules using taylor dispersion and associated system

Reference

00957-03

Patents status

Priority patent application n° 12 56050 filed on June 26th, 2012 and entitled “Method for determining the size distribution of a mixture of particles using Taylor dispersion, and associated system”

WO2014001409

Inventors

Hervé COTTET
Luca CIPELLETTI
Michel MARTIN
Jean-Philippe BIRON

commercial status

Exclusive or non-exclusive licence

Laboratory

Institut des Biomolécules Max Mousseron (UMR CNRS 5247) in Montpellier, France.
http://www.ibmm.univ-montp1.fr/

Laboratoire Charles Coulomb (UMR CNRS 5221) in Montpellier, France
http://www.coulomb.univ-montp2.fr/

Physique et Mécanique des Milieux Hétérogènes (UMR CNRS 7636) in Paris, France.
https://www.pmmh.espci.fr

Description

CONTEXT

Taylor Dispersion Analysis is a simple analytical technique leading to the size characterization of a sample mixture via the analysis of the dispersion of a sample band in an open capillary tube. The term "deconvolution" of a Taylor signal consisted in finding the hydrodynamic radius of each component of the mixture species and determining the concentration of each of these species.
The international application published under number WO 2010 009907 A1 discloses a method of the aforementioned type which the analysis step implements various deconvolution algorithms an experimental Taylor dispersion signal. However, these algorithms can be used only in the particular case of a binary mixture, that is to say a mixture of two species. Consequently, these known algorithms do not allow to analyze any sample, but only samples that are previously known to result from the mixing of two kinds.
In practice, it is currently considered impossible to solve the general problem of deconvolution Taylor experimental signal of a sample of any mixture of species. The invention therefore aims to overcome this problem, in particular by offering a real-time method for analyzing experimental Taylor signal from a sample of any mixture.

TECHNICAL DESCRIPTION

This invention concerns methods for determining the size distribution of a mixture of particles or (macro)molecules by implementing the Taylor dispersion and associated system, including the following steps:
§  injecting a sample of the mixture to be analyzed inside an open tubular capillary in which an eluent is flowing;
§  transporting the sample injected along the capillary from an injection section to a detection section thereof, in experimental conditions suitable to generate a Taylor dispersion phenomenon that is measurable at the level of the detection section;
–  generating, by means of a suitable sensor included in the detection section, a
–  signal characteristic of the Taylor dispersion of the transported sample;
–  acquiring the detection signal in order to obtain an experimental Taylor signal; and
–  analyzing the experimental Taylor signal.

DEVELOPMENT STAGE

The product has been already successfully tested and a software prototype is available for demonstration.  Deconvolution of the Taylor signal has been successfully applied to the size characterization of many samples such as (bio)polymers, nanoparticles, polyplexes, proteins…  

BENEFITS

The method allows the size distribution of a mixture of species, as well as the concentrations of these species in the mixture, to be obtained automatically and in real time, no matter what the polydispersity of the sample analyzed is, i.e., the number of species included in this sample and the respective concentrations thereof.
The advantages of the characterization of a sample by means of the Taylor dispersion phenomenon are: low volume of the sample to be injected into the capillary, no need to calibrate the experimental device, no dust sensitivity, use of a simple experimental device, technique that is particularly well adapted to size measurements of polydisperse nano-objects, full mass concentration distribution is obtained without bias toward larger solutes, etc.

INDUSTRIAL APPLICATIONS

The fields of application of the device and method described above include the size characterization of (bio)polymers, colloids, latexes, nanomaterials, emulsions, liposomes, vesicles, proteins and molecules or biomolecules, in general. One important field of application is the study of the stability/degradation/aggregation of proteins for the pharmaceuticals industry. In fact, the fields of application are the same as those targeted by the dynamic light scattering (DLS), and in the case of small molecules and oligomers that are difficult to access by DsL.
Other possible applications are the monitoring of polymerization reactions, the study of polymer degradation, control of the stability and aging of the micro-emulsions, rapid control in production / quality. In all cases, the information concerns the size and size distribution of the constituents of the mixture

For further information, please contact us (Ref 00957-03)

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