WO2018065547A1 - Dispositif de surveillance de la densité d'un échantillon et procédé associé - Google Patents

Dispositif de surveillance de la densité d'un échantillon et procédé associé Download PDF

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Publication number
WO2018065547A1
WO2018065547A1 PCT/EP2017/075410 EP2017075410W WO2018065547A1 WO 2018065547 A1 WO2018065547 A1 WO 2018065547A1 EP 2017075410 W EP2017075410 W EP 2017075410W WO 2018065547 A1 WO2018065547 A1 WO 2018065547A1
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sample
nanometers
light beam
component
wavelength
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PCT/EP2017/075410
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English (en)
Inventor
Laurent KIGER
Michael Marden
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Institut National De La Sante Et De La Recherche Medicale (Inserm)
Université Paris Est Créteil Val De Marne
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Publication of WO2018065547A1 publication Critical patent/WO2018065547A1/fr

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
    • G01N21/35—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light
    • G01N21/3577—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light for analysing liquids, e.g. polluted water
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0075—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by spectroscopy, i.e. measuring spectra, e.g. Raman spectroscopy, infrared absorption spectroscopy
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
    • G01N21/33—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using ultraviolet light
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
    • G01N21/314—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry with comparison of measurements at specific and non-specific wavelengths
    • G01N2021/3155—Measuring in two spectral ranges, e.g. UV and visible
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
    • G01N21/35—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light
    • G01N21/359—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light using near infrared light
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2201/00—Features of devices classified in G01N21/00
    • G01N2201/02—Mechanical
    • G01N2201/022—Casings
    • G01N2201/0221—Portable; cableless; compact; hand-held
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2201/00—Features of devices classified in G01N21/00
    • G01N2201/06—Illumination; Optics
    • G01N2201/062—LED's
    • G01N2201/0627—Use of several LED's for spectral resolution
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/483—Physical analysis of biological material
    • G01N33/487—Physical analysis of biological material of liquid biological material
    • G01N33/49—Blood

Definitions

  • the present invention concerns a device for monitoring at least one data relative to the density of a sample comprising a first component, notably protein, and a second component, notably water.
  • the invention also relates to a method for monitoring at least one data relative to the density of such sample.
  • Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. In 2012 about 14.1 million new cases of cancer occurred globally (not including skin cancer other than melanoma). It caused about 8.2 million deaths or 14.6% of human deaths.
  • the most common types of cancer in males are lung cancer, prostate cancer, colorectal cancer and stomach cancer. In females, the most common types are breast cancer, colorectal cancer, lung cancer and cervical cancer.
  • CTCs circulating tumor cells
  • HD-CTCs were more massive than leukocytes: 33.6- 3.2 pg (HD-CTC) compared to 18.7- 0.6 pg (leukocytes), p O.001 ; had greater volumes: 518.3- 24.5 fl_ (HD-CTC) compared to 230.9- 78.5 fl_ (leukocyte), p ⁇ 0.001 ; and possessed a decreased dry mass density with respect to leukocytes: 0.065- 0.006 pg/fL (HD-CTC) compared to 0.085- 0.004 pg/fL (leukocyte), p ⁇ 0.006.
  • the invention aims at providing a device for monitoring the density of a sample which is easier to implement.
  • the specification describes a device for monitoring at least one data relative to the density of a sample comprising a first component and a second component.
  • the device comprises a first light source adapted to emit a first light beam towards the sample, the first light beam comprising at least one first wavelength comprised between 200 nanometers and 300 nanometers and a second light source adapted to emit a second light beam towards the sample, the second beam comprising at least one second wavelength comprised between 700 nanometers and 3500 nanometers, the second light source being distinct from the first light source.
  • the device also comprises a first detector adapted to measure the absorption of the first light beam at each first wavelength, to obtain at least one first measured absorption, a second detector adapted to measure the absorption of the second light beam at each second wavelength to obtain at least one second measured absorption, the second detector being distinct from the first detector, and a calculator adapted to obtain the relative amount of the first component and the second component in the sample by using each first measured absorption and each second measured absorption, the data relative to the density being the relative of amount of the first component and the second component in the sample.
  • the invention provides a device for monitoring the density of a sample which is easier to implement.
  • the device may be used in other context, such as for monitoring the water content.
  • the device might incorporate one or several of the following features, taken in any technically admissible combination:
  • the device comprises a sample holder adapted to hold the sample.
  • the first component is a protein
  • the first component is lipid
  • the second component is water.
  • the device is adapted for monitoring at least one data relative to the density of a biological sample.
  • the biological sample is blood and the first component is an heme protein.
  • the biological sample is a tissue
  • the first light beam fulfills at least one of the following properties the first light beam comprises one first wavelength comprised between 200 nanometers and 220 nanometers, and the first light beam comprises one first wavelength comprised between 270 nanometers and 290 nanometers.
  • the second light beam fulfills at least one of the following properties the second light beam comprises one second wavelength comprised between 1 175 nanometers and 1225 nanometers, the second light beam comprises one second wavelength comprised between 1425 nanometers and 1475 nanometers, the second light beam comprises one second wavelength comprised between 1910 nanometers and 1990 nanometers, and the second light beam comprises one second wavelength comprised between 2900 nanometers and 3100 nanometers.
  • the device further comprises a housing defining an internal volume inferior to 5000 cm 3 , the light sources, the detectors and the calculator being in the internal volume.
  • the device further comprises a third light source adapted to emit a third light beam towards the sample, the third beam comprising at least one third wavelength comprised between 400 nanometers and 950 nanometers, a third detector adapted to measure the absorption of the third light beam at the third wavelength to obtain a third measured absorption, the calculator being adapted to obtain the relative of amount of first component and second component in the sample by also using the third measured absorption.
  • the third beam comprises at least one third wavelength comprised between 500 nanometers and 950 nanometers to detect hemoglobin.
  • the light sources and the detectors are adapted to obtain measured absorption for several respective wavelengths so as to form an absorbance spectra
  • the calculator being further adapted to calculate the second derivative of each absorbance spectra with relation to the wavelength.
  • the light sources are electroluminescent diodes.
  • the device further comprises an optical filter adapted to shift an absorption band.
  • At least one light source comprises an optical filter with a bandwidth inferior to 50 nanometers.
  • the specification also describes a method for monitoring at least one data relative to the density of a sample comprising a first component and a second component.
  • the method comprising at least the step of holding the biological sample in a sample holder, the step of emitting with a first light source a first light beam towards the sample, the first light beam comprising at least one first wavelength comprised between 200 nanometers and 300 nanometers, the step of emitting with a second light source a second light beam towards the sample, the second beam comprising at least one second wavelength comprised between 700 nanometers and 3500 nanometers, the second light source being distinct from the first light source, the step of measuring with a first detector the absorption of the first light beam at each first wavelength, to obtain at least one first measured absorption, the step of measuring with a second detector the absorption of the second light beam at each second wavelength to obtain at least one second measured absorption, the second detector being distinct from the first detector, and the step of obtaining with a calculator the relative amount of the first component and the second component in the sample by using
  • FIG. 1 shows schematically a subject from which a sample is extracted and an example of device for monitoring the density of the sample
  • figure 2 shows another view of the device of figure 1 ,
  • FIG. 3 is a flowchart of an example of carrying out a method for monitoring the density of the sample
  • Figure 1 shows a sample 10 extracted from a part of a subject 1 1 and a device 12.
  • the sample 10 comprises a first component C1 and a second component C2.
  • the first component C1 is a protein
  • the second component C2 is water.
  • the sample 10 is a biological sample 10.
  • sample 10 comes from a subject 1 1 .
  • the subject 1 1 is a human being according to the example of figure 1 , the part being a finger of the subject 1 1 .
  • the part is an ear lobe of the subject 1 1 .
  • the biological sample 10 is blood (a drop flowing from the finger and in the device 12 are represented on figure 1 ).
  • the first component C1 is an heme protein.
  • the first component C1 is lipid.
  • the sample 10 is a tissue.
  • the sample 10 is excised.
  • the sample 10 is an in vivo sample.
  • the device 12 is a device 12 for monitoring at least one data relative to the density of the sample 10.
  • monitoring it is meant in this context a temporal control of the data.
  • the data relative to the density is a data relative to the mass of the sample 10 or a data relative to the volume of the sample 10.
  • the data relative to the density is the relative amount of the first component C1 and the second component C2 in the sample 10.
  • such value is expressed in form of a percentage corresponding to the ration of the mass of the second component C2 to the sum of the mass of both components C1 and C2.
  • the fraction of water in a solution that is the fraction of the second component C2 is a data relative to the density.
  • the device 12 comprises a sample holder 14, a collecting organ 15, a first light source 16, a second light source 18, a first detector 20, a second detector 22, a calculator 24 and a display unit 26.
  • the sample holder 14 is adapted to hold the sample 10.
  • the collecting organ 15 is a retractable needle 27 which is actionable with a button 29.
  • a drop of blood, plasma or a tissue sample already extracted may be directly provided to the device 12.
  • the first light source 16 is adapted to emit a first light beam towards the sample 10.
  • the first light beam comprises at least one first wavelength ⁇ 1 comprised between 200 nanometers (nm) and 300 nm.
  • the first light beam comprises one first wavelength ⁇ 1 comprised between 200 nm and 220 nm.
  • the first light beam comprises one first wavelength ⁇ 1 comprised between 270 nm and 290 nm.
  • the first light beam comprises two first wavelengths ⁇ 1 which are equal to 205 nm and 280 nm.
  • the first light source 16 is an electroluminescent diode.
  • the first light source 16 may be construed as a light source devoted to excite the first component C1 of the sample 10.
  • the second light source 18 is distinct from the first light source 16.
  • the second light source 18 is comprised between 200 nm and 300 nm.
  • the second beam comprises at least one second wavelength ⁇ 2 comprised between 700 nm and 3000 nm.
  • the second beam comprises at least one second wavelength ⁇ 2 comprised between 900 nm and 3500 nm.
  • the second light beam comprises one second wavelength ⁇ 2 comprised between 1 175 nm and 1225 nm. According to a specific embodiment, the second light beam comprises one second wavelength ⁇ 2 comprised between 1425 nm and 1475 nm.
  • the second light beam comprises one second wavelength ⁇ 2 comprised between 1910 nm and 1990 nm.
  • the second light beam comprises one second wavelength ⁇ 2 comprised between 2900 nm and 3100 nm.
  • the second light beam comprises any one of the precited second wavelengths ⁇ 2.
  • the second light beam comprises five second wavelengths ⁇ 2 which are 975 nm, 1200 nm, 1445 nm, 1950 nm and 2940 nm.
  • the second light beam comprises two second wavelengths ⁇ 2 which are 1200 nm and 1445 nm.
  • the second light source 18 is an electroluminescent diode.
  • the first detector 20 is adapted to measure the absorption of the first light beam at each first wavelength ⁇ 1 , to obtain at least one first measured absorption A1 .
  • the first detector 20 is a photodiode.
  • the first measured absorption A1 is measured by obtaining the transmission of the first light beam through the sample 10 and subtracting this value to 1 .
  • the first measured absorption A1 is obtained by averaging several transmission values.
  • the second detector 22 is distinct from the first detector 20.
  • the second detector 22 is adapted to measure the absorption of the second light beam at each second wavelength ⁇ 2 to obtain at least one second measured absorption A2.
  • the second detector 22 is a photodiode.
  • the calculation of the second measured absorption A2 is similar to the calculation of the first measured absorption A1 .
  • the calculator 24 is adapted to obtain the relative amount of the first component C1 and the second component C2 in the sample 10.
  • the calculator 24 is adapted to obtain the relative amount of the first component C1 and the second component C2 in the sample 10 by using each first measured absorption A1 and each second measured absorption A2.
  • the display unit 26 is adapted to display the value of the relative amount of the first component C1 and the second component C2 in the sample 10.
  • the display unit 26 comprises a digital screen 28 on which the figures of the value of the relative amount of the first component C1 and the second component C2 in the sample 10 is displayed.
  • the device 12 further comprises a housing 30 defining an internal volume inferior to 5000 cm 3 , the light sources, the detectors and the calculator 24 being in the internal volume.
  • the internal volume is inferior to 1500 cm 3 .
  • the method comprises a step of sample holding, a first step of emitting S40, a second step of emitting S42, a first step of measuring S44, a second step of measuring S46 and a step of obtaining a calculated result S48.
  • the sample 10 is held by the sample holder 14.
  • the first light beam is emitted by the first light source 16. Such first light beam is emitted towards the sample 10 so that the first light beam passes through the sample 10.
  • the second light beam is emitted by the second light source 18. Such second light beam is emitted towards the sample 10 so that the second light beam passes through the sample 10.
  • the intensity of the first light beam which is incident to the first detector 20 is measured. This corresponds to the intensity transmitted by the sample 10.
  • the first measured absorption A1 is deduced from this transmitted intensity.
  • the path followed by the first light beam is indicated by an arrow on figure 2.
  • the intensity of the second light beam which is incident to the second detector 22 is measured. This corresponds to the intensity transmitted by the sample 10.
  • the second measured absorption A2 is deduced from this transmitted intensity.
  • the path followed by the second light beam is indicated by an arrow on figure 2.
  • both measuring steps S44 and S46 are carried out simultaneously.
  • the calculator 24 uses each first measured absorption A1 and each second measured absorption A2 to obtain the relative amount of the first component C1 and the second component C2 in the sample 10.
  • a coupler 50 is inserted between the light sources 16 and 18 and the housing 30.
  • the coupler 50 is a set of mirrors or a bifurcated fiber optic to combine the light beams in order to cross the sample together.
  • Such embodiment corresponds to a concrete implementation according to which, rather than bringing the sample 10 to the sample holder, the light can be brought to the sample 10.
  • the housing 30 comprises the light sources 16 and 18 and the detectors 20 and 22 while the collecting organ 15 is removable.
  • the collecting organ 15 is a clamp.
  • the light beams are taken outside towards an external sample and returned to the detectors, using for example fiber optics.
  • Such case resembles a modified pulse oximeter.
  • the device 12 further comprises a third light source 52 and a third detector 54.
  • the third light source 52 is adapted to emit a third light beam towards the sample 10.
  • the third light source 52 is adapted to detect the heme protein.
  • the third light source 52 is an electroluminescent diode and the third detector 54 is a photodiode.
  • the third beam comprises at least one third wavelength ⁇ 3 comprised between 400 nm and 950 nm.
  • the third light beam comprises one third wavelength ⁇ 3 comprised between 400 nm and 440 nm.
  • the third light beam comprises one third wavelength ⁇ 3 comprised between 530 nm and 590 nm.
  • the third light beam comprises one third wavelength ⁇ 3 comprised between 755 nm to 765 nm.
  • the third light beam comprises one third wavelength ⁇ 3 which corresponds to a reference line. 710 nm is an example of reference line.
  • the third detector 54 is adapted to measure the absorption of the third light beam at the third wavelength ⁇ 3 to obtain a third measured absorption A3.
  • the calculator 24 is adapted to obtain the relative of amount of first component C1 and second component C2 in the sample 10 by also using the third measured absorption A3.
  • Operation of the device 12 of figure 6 is similar to the operation of device 12 according to the embodiment of figure 1 .
  • the third light beam is emitted by the third light source 52.
  • Such third light beam is emitted towards the sample 10 so that the third light beam passes through the sample 10.
  • the intensity of the third light beam which is incident to the third detector 54 is measured. This corresponds to the intensity transmitted by the sample 10.
  • the third measured absorption A3 is deduced from this transmitted intensity.
  • the third measured absorption A3 is taken into account.
  • Figure 7 corresponds to the spectra in the ultraviolet region where protein absorption dominates in blood.
  • the mains bands are at 280 nm and 220 nm (off scale here).
  • the insert shows the structure for the second derivative, providing additional information on the aromatic amino acids.
  • Figure 8 shows the hemoglobin absorption bands in the visible region, for in the oxy (see curve C1 ) and deoxy (see curve C2) state.
  • Figure 9 shows the near infrared absorption of water (curve C3) and a compacted red blood cell solution (curve C4).
  • the protein has a higher absorption below 1000 nm, but the water peaks dominate at 1450 and 1950 nm.
  • the insert shows a second derivate of the spectrum to better characterize specific bands.
  • a simple spectroscopic method is proposed to determine the relative amounts of protein and water in a sample 10.
  • the method is based on absorption spectra of the spectra for proteins (figures 7 and 8) and pure water (figure 9). By combining such measurements on the same sample 10, the water content is determined. As these bands have different intensities, a combination is found to allow for a direct comparison on the same scale.
  • Such device 12 enables to monitor the density of a sample which is easier to implement. Notably, there is no need of drying the sample 10 before carrying out the method.
  • the method can be easily applied on biological samples. Spectra have been made on samples of various thicknesses, or on individual cells. Single cell spectroscopy in is more difficult, but could provide a more "local" measurements for specific cases.
  • the device 12 may be a hand-held device.
  • Such method may be used for diagnosis purpose.
  • Applications would include pathological cases of dense cells and amyloids usually due to undesired protein aggregates.
  • dense subpopulations can lead to exaggerated effects on the cell function.
  • a range of densities can also be expected for cancer cells.
  • Other proteins aggregates form amyloids such as for transthyretin, or proteins in Alzheimer's disease.
  • the device 12 is also able to monitor dehydration of the sample 10. Other embodiments may be considered.
  • the light sources and the detectors are adapted to obtain measured absorption for several respective wavelengths so as to form an absorbance spectrum
  • the calculator 24 being further adapted to calculate the second derivative of each absorbance spectra with relation to the wavelength.
  • the light detectors are a diode array. If full spectra a measured, then the second derivative method can be employed to improve the precision.
  • the device 12 further comprises a filter adapted to select part of the absorption band where the bulk water has a higher absorbance. This is notably interesting for cancer cells having a higher percentage of water which would lead those cells to absorb more after such shifting.
  • At least one light source comprises an optical filter with a bandwidth inferior to 50 nm and superior to 2 nm.
  • the light sources could be broad (white light) and provided with a filter.
  • the light sources are modular for rapid change of application.
  • one compact solution is modular electroluminescent diodes. Since each electroluminescent diode occupies about 1 cm 3 , the device 12 comprises three or four electroluminescent diode slots and each electroluminescent diode corresponds to a cube shape that can be swapped for a different wavelength. Such embodiment is both compact and economical.
  • the second wavelengths belong either to a first range comprised between 1 150 nm and 1250 nm or to a second range comprised between 1650 nm to 1800 nm.
  • the device 12 is a watch which can be worn on a wrist.
  • Such a watch comprises a strap and a dial.
  • the dial is, in such embodiment, the housing 30 defining the internal volume in which the light sources, the detectors and the calculator 24 are situated.
  • the dial has a parallelepiped shape defined by a base with rectangular shape and a height.
  • the rectangular shape is defined by a length and a width, the length being comprised between 5 cm and 10 cm and the width being comprised between 3 cm and 8 cm. It results from this that the area of the rectangular shape is comprised between 15 cm 2 and 80 cm 2 .
  • the height is comprised between 1 cm and 5 cm. This means that the internal volume is comprised between 15 cm 3 and 400 cm 3 .
  • the device 12 comprises a clip that can be fixed to a finger.
  • the clip comprises two pieces, one piece being mounted rotative on the other piece such that, in operating, the finger be pinched between the two pieces.
  • Such device 12 can notably be obtained by modifying an existing pulse oximeter with the addition of the first light source 16 and the first detector 20.
  • the clamp is adapted to be fixed on a hand, on an ear or on a wrist.
  • the clip is the housing 30 defining the internal volume in which the light sources, the detectors and the calculator 24 are situated.
  • both pieces have a similar rectangular shape defined by a length and a width, the length being comprised between 4 cm and 8 cm and the width being comprised between 3 cm and 6 cm. It results from this that the area of the rectangular shape is comprised between 12 cm 2 and 48 cm 2 .
  • the height is comprised between 1 cm and 3 cm. This means that the internal volume is comprised between 12 cm 3 and 144 cm 3 .
  • the internal volume is comprised between 24 cm 3 and 288 cm 3 .
  • the device 12 comprises a module, the clip and an optical link between the module and the clip.
  • the module comprises the different light sources and the batteries.
  • the module is devoted to be worn in a pocket.
  • the optical link is made by optical fibers.
  • the clip only comprises the detectors and the calculator 24.
  • the internal volume is defined by the sum of three volumes: the volume of the module, the volume of the optical link and the volume of the clip.
  • the module has a parallelepiped shape whose volume is comprised between 400 cm 3 and 600 cm 3 so as to be easily put in a pocket.
  • the optical link may be assimilated to a cylinder whose base is a disk.
  • the volume of the optical link is comprised between 20 cm 3 and 40 cm 3 .
  • the internal volume is comprised between 432 cm 3 and 728 cm 3 .
  • the device 12 is a box containing each element.
  • the box is of a cubic form whose side is comprised between 10 cm and 17 cm. This results in an internal volume comprised between 1728 cm 3 and 4913 cm 3 .
  • the internal volume is inferior to 5000 cm 3 . This means that such value enables to obtain hand-held device.
  • the internal volume is also inferior to 1500 cm 2 which gives the possibility to the user to wear the device 12.
  • the device 12 is adapted to be used in a variety of applications without modifying the device 12.
  • the device 12 may be used as a sensor adapted to measure the content of oxyhemoglobin in a sample, as a sensor adapted to measure the hydration of a sample and as a sensor adapted to measure the content of protein in a sample.
  • the device 12 is thus a convenient device because of its portability and its high versatility, that is its ability to be used in different contexts without any modification. In other words, the device 12 is a multi-skill apparatus with small dimensions.

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  • Investigating Or Analysing Materials By Optical Means (AREA)

Abstract

La présente demande concerne le domaine de la mesure de la densité d'un échantillon (10), notamment pour évaluer la quantité relative d'un premier composant et d'un second composant dans l'échantillon. Pour ce faire, on sait réaliser la mesure optique de l'indice mais ce type de mesure implique le séchage de l'échantillon. Il existe par conséquent un besoin en termes de dispositif capable d'être utilisé in vivo et de réaliser une pluralité de mesures différentes. Cette polyvalence est fournie par un dispositif (12) comprenant : un premier détecteur (20) conçu pour mesurer l'absorption par l'échantillon (10) d'un premier faisceau lumineux (F1) ayant une première longueur d'onde comprise entre 200 et 300 nanomètres, un second détecteur (22) conçu pour mesurer l'absorption par l'échantillon (10) d'un second faisceau lumineux (F2) ayant une seconde longueur d'onde comprise entre 700 et 3500 nanomètres, et un calculateur (24) conçu pour obtenir les quantités relatives du premier composant et du second composant dans l'échantillon (10) à l'aide des première et seconde absorptions mesurées.
PCT/EP2017/075410 2016-10-06 2017-10-05 Dispositif de surveillance de la densité d'un échantillon et procédé associé WO2018065547A1 (fr)

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EP16306317.5 2016-10-06

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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6841778B1 (en) * 2001-11-09 2005-01-11 Environmental Systems Products Holdings Inc. Method and apparatus for measuring particulates in vehicle emissions
WO2009150325A1 (fr) * 2008-05-20 2009-12-17 Callebaut De Blicquy Mesureur d'absorption, tel que notamment colorimètre, dans la gamme spectrale visible, infrarouge ou encore ultraviolet, pour l'analyse d'un fluide en transmission
EP2156787A1 (fr) * 2008-08-21 2010-02-24 Palo Alto Research Center Incorporated Procédé de détection d'analyse
US20100134794A1 (en) * 2004-02-05 2010-06-03 Medpro Holdings, Llc Analyzer for determining the concentration, potency and purity of pharmaceutical compounds
JP2011064533A (ja) * 2009-09-16 2011-03-31 Nippon Soken Inc 燃料判別装置
WO2011073789A2 (fr) * 2009-12-18 2011-06-23 Schlumberger Technology B.V. Sonde à immersion utilisant un rayonnement ultraviolet et infrarouge pour une analyse d'écoulement polyphasique

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6841778B1 (en) * 2001-11-09 2005-01-11 Environmental Systems Products Holdings Inc. Method and apparatus for measuring particulates in vehicle emissions
US20100134794A1 (en) * 2004-02-05 2010-06-03 Medpro Holdings, Llc Analyzer for determining the concentration, potency and purity of pharmaceutical compounds
WO2009150325A1 (fr) * 2008-05-20 2009-12-17 Callebaut De Blicquy Mesureur d'absorption, tel que notamment colorimètre, dans la gamme spectrale visible, infrarouge ou encore ultraviolet, pour l'analyse d'un fluide en transmission
EP2156787A1 (fr) * 2008-08-21 2010-02-24 Palo Alto Research Center Incorporated Procédé de détection d'analyse
JP2011064533A (ja) * 2009-09-16 2011-03-31 Nippon Soken Inc 燃料判別装置
WO2011073789A2 (fr) * 2009-12-18 2011-06-23 Schlumberger Technology B.V. Sonde à immersion utilisant un rayonnement ultraviolet et infrarouge pour une analyse d'écoulement polyphasique

Non-Patent Citations (3)

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Title
J. LIANG ET AL., DETERMINATION OF REFRACTIVE INDEX FOR SINGLE LIVING CELL USING INTEGRATED BIOCHIP, July 2005 (2005-07-01)
K.G. PHILLIPS ET AL.: "the review frontiers in oncology", OPTICAL QUANTIFICATION OF CELLULAR MASS, VOLUME, AND DENSITY OF CIRCULATING TUMOR CELLS IDENTIFIED IN AN OVARIAN CANCER PATIENT, 2012
KEVIN G. PHILLIPS ET AL: "Optical Quantification of Cellular Mass, Volume, and Density of Circulating Tumor Cells Identified in an Ovarian Cancer Patient", FRONTIERS IN ONCOLOGY, vol. 2, 18 July 2012 (2012-07-18), XP055352112, DOI: 10.3389/fonc.2012.00072 *

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