• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    The present invention relates to a device and a method for measuring the concentration of a compound present in the blood.
    公开号:FR3046048A1
    申请号:FR1563262
    申请日:2015-12-23
    公开日:2017-06-30
    发明作者:Nadia Arfaoui；Sylvain Zorman；Pierre-Yves Frouin
    申请人:Bioserenity SAS；
    IPC主号:
    专利说明:

    DEVICE AND METHOD FOR MEASURING THE CONCENTRATION OF A COMPOUND PRESENT IN BLOOD
    FIELD OF THE INVENTION
    The present invention relates to a device and a method for measuring the concentration of a compound present in the blood by near infrared spectroscopy.
    STATE OF THE ART
    As part of the daily monitoring of diabetes in a patient, measurement of blood glucose level is a common act and is performed by the patient directly using a medical device. Most commercial medical devices dedicated to diabetes are invasive, that is to say that they require the piercing of the epidermis to obtain the measurement of the glucose level. Non-invasive devices have been developed more recently.
    Thus, the article by Masab Ahmad, Awais Kamboh, Ahmed Khan, EDN Network, October 16, 2013, discloses a non-invasive device for measuring glucose levels by using near-infrared spectroscopy, said device being placed at the level of the lobe of the ear.
    This device comprises five LEDs: two emit light beams at a wavelength of 1550 nm, one emits light beams whose wavelength is in the red, one emits light beams whose wavelength is located in the infrared, a light source emits light beams whose wavelength is qualitatively in green, that is to say that it is in the wavelength range of 490 nm at 580 nm and a photodiode having a strong response at 1550 nm.
    To determine the level of glucose in the blood, the device uses LEDs emitting light beams whose wavelength is located in the red or the infrared to measure the glucose and oxygenation rate. Indeed, it is necessary to normalize the measured glucose level to the blood volume at the time of measurement to account for fluctuations in blood volume due to cardiac activity. The light source emitting in the green makes it possible to measure the thickness of the lobe of the ear, or more generally, the thickness of the zone considered in order to know the distance traveled by the light beam because it determines the absorption of the light beam by the lobe according to an exponential law depending on the distance. Therefore, to be able to determine the glucose level, it is necessary to consider and determine the rate of oxygenation of the blood. The determination of the glucose or oxygenation level is carried out in transmittance. This method requires the use of a second light source, in this case a diode emitting light beams at a wavelength in the range of 490 nm to 580 nm.
    Thus, glucose measurement can not be done without intermediate measures. It is indeed necessary to measure the rate of oxygenation and the distance of material traversed by the light beam. The immediate consequence of these intermediate measurements is a loss of precision due to errors from one side of the thickness measurement and the other from the errors from the determination of oxygenation.
    There is therefore a need for medical devices having reliability, reproducibility and accuracy in their measurements.
    In addition, this type of device described in the prior art does not measure the amount of other compounds present in the blood.
    Thus, the invention proposes a device and a method which allow the precise determination of the concentration of at least one compound present in the blood without resorting to intermediate measures such as the determination of a distance traversed and the rate of oxygenation. . SUMMARY The invention relates to a device for measuring the concentration of a compound present in the blood comprising an adjustable support able to coat a part of the human body, said adjustable support comprising: at least one light source, said at least one source light emitting light beams of at least one wavelength, said wavelength being in the range of 700 nm to 3000 nm, said light beams being backscattered by the human body portion constituting a source of backscattering; at least one photodiode receiver, said device not comprising a diode emitting light beams at a wavelength in a range from 490 nm to 580 nm.
    According to one embodiment, the at least one light source is an LED or a laser diode.
    According to one embodiment, the device comprises a spectral decomposition means of the backscattered light.
    According to one embodiment, the measuring device comprises from 2 to 50 light sources.
    According to one embodiment, the measuring device comprises from 2 to 50 photodiode receivers.
    According to one embodiment, the at least one wavelength of the light beam emitted by the at least one light source is included in at least one of the wavelength ranges centered on the wavelengths adapted to measure the following compounds: total hemoglobin (HbT), de-oxyhemoglobin, oxyhemoglobin, glucose, albumin, lactic acid, triglycerides, and urea.
    According to one embodiment, the device is able to be arranged around the lobe of the ear, finger, forehead, chin, wrist, foot, hand or neck.
    According to one embodiment, the device can communicate via a wireless system. The invention also relates to a method for measuring the concentration of a compound present in the blood comprising the following steps: • emitting at least one light beam at least one wavelength ranging from 700 nm to 3000 nm from at least one light source, • measure the intensity of the backscattered light as a function of time, • determine the intensity of the backscattered light at the maximum of the pulsatile component and the backscattered light at the minimum of the pulsatile component • calculate the concentration of said compound present from the measured intensity of the at least one backscattered light beam at the minimum and maximum of the pulsatile component. The invention also relates to the use of the device for simultaneously determining the concentration of different compounds present in the blood, these compounds include but are not limited to: total hemoglobin (HbT), de-oxyhemoglobin, oxyhemoglobin, hematocrit, platelets, cholesterol, urea, ammonia, ammonia, creatinine, calcium, sodium, potassium, chloride, bicarbonate.
    DEFINITIONS "Pulsatile component": periodic oscillations over time of light absorption or, conversely, of the intensity of backscattered light of a part of the human body related to the variation of arterial blood volume due to the activity heart. The minimum of the pulsatile component corresponds to the continuous component. Its maximum is noted AC and its minimum is noted DC. "Continuous component": stationary value of the light absorption or, conversely, the intensity of the backscattered light of a part of the human body. It consists of tissue, bone, venous blood and the non-pulsatile component of arterial blood. Its value is noted DC. "LED": Light-Emitting Diode (LED), is an opto-electronic device capable of emitting non-coherent monochromatic or polychromatic radiation from the conversion of electrical energy when a current flows through it. . "Laser diode" means an optoelectronic device based on semiconductor materials emitting coherent monochromatic light. "Microcontroller": an integrated circuit that combines the essential elements of a computer such as the processor, memories, peripheral devices and input-output interfaces.
    DETAILED DESCRIPTION The invention relates to a device for measuring the concentration of a compound present or dissolved in the blood comprising an adjustable support able to coat a part of the human body, said adjustable support comprising: at least one light source, said at least one minus a light source emitting light beams of at least one wavelength, said wavelength being in a range from 700 nm to 3000 nm, said light beams being backscattered by the part of the human body constituting a source of light. backscattering, - at least one photodiode receiver, said device not comprising a diode emitting light beams at a wavelength in a range from 490 nm to 580 nm.
    According to one embodiment, the device comprises at least two light sources, each emitting light beams at a wavelength distinct from each other.
    According to one embodiment, the device comprises at least one light source emitting light beams having at least two wavelengths.
    According to one embodiment, the at least one light source is an LED or a laser diode.
    According to one embodiment, the light source is a white source.
    According to one embodiment, the measuring device comprises at least 2 light sources.
    According to one embodiment, the measuring device comprises from 2 to 50 light sources.
    According to one embodiment, the measuring device comprises 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49 to 50 light sources.
    According to one embodiment, the device may further comprise a spectral decomposition means of the backscattered light.
    According to another embodiment, the device may further comprise a spectral decomposition means of the backscattered light disposed before the at least one photodiode receiver.
    According to one embodiment, the spectral decomposition means of the backscattered light is a diffraction grating.
    According to another embodiment, the spectral decomposition means of the backscattered light is a prism.
    According to another embodiment, the spectral decomposition means of the backscattered light is composed of at least two filters adapted to the wavelengths emitted.
    According to one embodiment, the at least one wavelength of the light beam emitted by the at least one light source is included in at least one of the wavelength ranges centered on the wavelengths adapted to measure the following compounds, but not limited to: total hemoglobin (HbT), de-oxyhemoglobin, oxyhemoglobin, glucose, albumin, lactic acid, triglycerides, water, globulin, urea, hematocrit, platelets, cholesterol, ammonia, ammonia, creatinine, calcium, sodium, potassium, chloride or bicarbonate.
    According to one embodiment, the at least one wavelength of the light beam emitted by the at least one light source is included in at least one of the wavelength ranges centered on the wavelengths adapted to measure the following compounds but not limited to: total hemoglobin (HbT), de-oxyhemoglobin, oxyhemoglobin, glucose, albumin, lactic acid, triglycerides, water, cholesterol, globulin .
    According to one embodiment, the at least one wavelength of the light beam emitted by the at least one light source is included in at least one of the wavelength ranges centered on the wavelengths adapted to measure the following but not limited to: total hemoglobin (HbT), de-oxyhemoglobin, oxyhemoglobin, glucose, albumin, lactic acid, triglycerides, and urea.
    For hemoglobin, the suitable wavelength range is 730 nm to 980 nm.
    For de-oxyhemoglobin, the suitable wavelength range is 730 nm to 805 nm.
    For oxyhemoglobin, the suitable wavelength range is 805 nm to 980 nm.
    For glucose, albumin, lactic acid, triglycerides, cholesterol, globulin or urea, the suitable wavelength range is 1000 nm to 3000 nm, more precisely 2000 nm to 3000 nm. nm and even more precisely, from 2100 nm to 2300 nm.
    For water, the suitable wavelength range is from 1 μm to 11 μm; and more precisely from 6 pm to 10 pm and even more precisely from 8 pm to 10 pm.
    According to one embodiment, the at least one wavelength of the light beam emitted by the at least one light source corresponds to at least one of the wavelengths suitable for measuring the following compounds, but without being limited thereto: hemoglobin total (HbT), de-oxyhemoglobin, oxyhemoglobin, glucose, albumin, lactic acid, triglycerides, water, cholesterol, globulin, urea, hematocrit, platelets, cholesterol, ammonia, ammonia, creatinine, calcium, sodium, potassium, chloride or bicarbonate.
    According to one embodiment, the at least one wavelength of the light beam emitted by the at least one light source corresponds to at least one of the wavelengths suitable for measuring the following compounds, but without being limited thereto: total hemoglobin (HbT), de-oxyhemoglobin, oxyhemoglobin, glucose, albumin, lactic acid, triglycerides, water, cholesterol, globulin.
    According to one embodiment, the at least one wavelength of the light beam emitted by the at least one light source corresponds to at least one of the wavelengths suitable for measuring the following compounds, but without being limited thereto: hemoglobin total (HbT), de-oxyhemoglobin, toxyhemoglobin, glucose, albumin, lactic acid, triglycerides, and urea.
    The wavelength suitable for measuring total hemoglobin (HbT) is 805 nm.
    According to one embodiment, the measuring device comprises at least 2 photodiode receivers.
    According to one embodiment, the measuring device comprises from 2 to 50 photodiode receivers.
    According to one embodiment, the measuring device comprises 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49 to 50 photodiode receivers.
    According to one embodiment, the device is characterized by the absence of a diode emitting light beams at a wavelength ranging from 490 nm to 580 nm. In the prior art, the diode makes it possible to measure the distance traveled by the beam emitted by the light source, this distance being necessary for the application of the Beer-Lambert law in transmittance.
    The device of the invention eliminates this distance measurement because it uses a reflectance measurement based on a ratio between the different intensities measured for at least two compounds such as glucose and hemoglobin.
    According to one embodiment, the adjustable support is in the form of a coating or an accessory, such as a t-shirt, a headband, a watchband.
    According to one embodiment, the support has elastic or adjustable properties making it possible to apply a mechanical stress at the emitters and receivers improving the mechanical contact between the emission, the reception and the cutaneous measuring zone, that is to say say the part of the human body.
    According to one embodiment, the device is able to be arranged around the lobe of the ear, finger, forehead, chin, wrist, foot, hand or neck.
    In the following article, Tur et al. Basal Perfusion of the Cutaneous Microcirculation: Measurements as a Function of Anatomy Position, The Journal of Investigate Dermatology, Vol. 84, No. 5, pp. 442-446, is described the set of anatomical positions on which spectroscopic measurements can be conducted.
    According to one embodiment, the device further comprises a system for determining the concentration of said compound present capable of determining said concentration from the backscattered light beams.
    This determination system is an electronic device known to those skilled in the art such as a microcontroller. H receives information from the at least one photodiode receiver in order to process them and to extract the DC component and the pulsatile component maximum (AC) for each of the compounds under consideration.
    This microcontroller allows the implementation of a specific method for measuring the concentration of a compound present in the blood, this specific method being described below.
    According to one embodiment, the device can communicate via a wireless system. The invention also relates to a method for measuring the concentration of a compound present in the blood comprising the following steps: • emitting at least one light beam at least one wavelength ranging from 700 nm to 3000 nm from at least one light source, • measure the intensity of the backscattered light as a function of time, • determine the intensity of the backscattered light at the maximum of the pulsatile component and the backscattered light at the minimum of the pulsatile component • calculate the concentration of said compound present from the measured intensity of the at least one backscattered light beam at the minimum and maximum of the pulsatile component. The invention also relates to a method for measuring the concentration of a compound present in the blood comprising the following steps: • emitting at least one light beam at least one wavelength ranging from 700 nm to 3000 nm from at least one light source, • measure the intensity of the backscattered light as a function of time, • determine the intensity of the backscattered light at the minimum of the pulsatile component, • determine the intensity of the backscattered light at maximum of the pulsatile component, • calculate the concentration of said compound present from the measured intensity of the at least one backscattered light beam at the minimum and maximum of the pulsatile component. The invention also relates to a method for measuring the concentration of a compound present in the blood comprising the following steps: • emitting at least one light beam at least one wavelength ranging from 700 nm to 3000 nm from at least one light source, • measure the intensity of the backscattered light as a function of time, • determine the intensity of the backscattered light at the maximum of the pulsatile component, • determine the intensity of the backscattered light at minimum of the pulsatile component; • calculate the concentration of said compound present from the measured intensity of the at least one backscattered light beam at the minimum and maximum of the pulsatile component.
    According to one embodiment, the method is implemented by the use of at least two light sources, each of which emits light beams at at least one wavelength distinct from each other.
    According to one embodiment, the method is implemented by the use of at least three light sources, each of which emits light beams at two wavelengths, said wavelengths being distinct from one another and included in at least one of the wavelength-centered wavelength ranges adapted to measure the following, but not limited to, total hemoglobin (HbT), de-oxyhemoglobin, oxyhemoglobin, glucose, albumin, lactic acid, triglycerides, and urea.
    According to one embodiment, the method is implemented by the use of at least six light sources, each of which emits light beams at a wavelength, said wavelengths being distinct from one another and are included in at least one of the wavelength-centered wavelength ranges adapted to measure the following, but not limited to, total hemoglobin (HbT), de-oxyhemoglobin, oxyhemoglobin, glucose, albumin, lactic acid, triglycerides, and urea.
    According to one embodiment, the method is implemented by the use of at least three light sources, each of which emits light beams at two wavelengths, said wavelengths being distinct from one another and are included in FIG. least one of the wavelength-centered wavelength ranges adapted to measure the following, but not limited to, total hemoglobin (HbT), glucose, albumin, acid lactic acid, triglycerides, and urea.
    According to one embodiment, the method is implemented by the use of at least six light sources, each of which emits light beams at a wavelength, said wavelengths being distinct from one another and are included in at least one of the wavelength centered wavelength ranges adapted to measure the following compounds, but not limited to, total hemoglobin (HbT), glucose, albumin, lactic acid, triglycerides, and urea.
    According to one embodiment, the method is implemented by the use of at least three light sources, each of which emits light beams at two wavelengths, said wavelengths being distinct from one another and corresponding to the lengths total hemoglobin (HbT) wave, de-oxyhemoglobin, oxyhemoglobin, glucose, albumin, lactic acid, triglycerides, and urea.
    According to one embodiment, the method is implemented by the use of at least six light sources, each of which emits light beams at a wavelength, said wavelengths being distinct from one another and corresponding to the wavelengths of total hemoglobin (HbT), de-oxyhemoglobin, oxyhemoglobin, glucose, albumin, lactic acid, triglycerides, and urea.
    According to one embodiment, the method is implemented by the use of at least three light sources, each of which emits light beams at two wavelengths, said wavelengths being distinct from one another and corresponding to the wavelengths of total hemoglobin (HbT), glucose, albumin, lactic acid, triglycerides, and urea.
    According to one embodiment, the method is implemented by the use of at least six light sources, each of which emits light beams at a wavelength, said wavelengths being distinct from one another and corresponding to the wavelengths of total hemoglobin (HbT), glucose, albumin, lactic acid, triglycerides, and urea.
    In one embodiment, the device and the method described above make it possible simultaneously to determine the concentration of different compounds present in the blood. These compounds include but are not limited to: total hemoglobin (HbT), de-oxyhemoglobin, oxyhemoglobin, hematocrit, platelets, cholesterol, urea, ammonia, ammonia, creatinine , calcium, sodium, potassium, chloride, bicarbonate.
    BRIEF DESCRIPTION OF THE FIGURES
    Figure 1 shows schematically the temporal evolution of the received intensity. EXAMPLES
    The present invention will be better understood on reading the following examples which illustrate the invention in a nonlimiting manner.
    Example 1: Determination of the level of glucose in the blood
    For a given subject and in everyday circumstances, the blood volume is proportional to the total hemoglobin (HbT) concentration. Total hemoglobin (HbT) consists of de-oxyhemoglobin and oxyhemoglobin. The evolution of the glucose concentration in the blood has a pulsatile component.
    In this example, the device comprises at least six light sources each emitting beams at a wavelength distinct from each other. These six (6) wavelengths allow the detection of molecules in the blood which are the following: 1) λπι-, τ for the detection of total hemoglobin (HbT), 2) Xciucose for the detection of glucose, 3 ) λΑΐίχιιηίηο for the detection of albumin, 4) Xal for the detection of lactic acid (AL), 5) λχι ^ ίγοέπίΐε for the detection of triglycerides, 6) λυ ^ ε for the detection of urea.
    Since the evolution of the glucose concentration in the blood has a pulsatile component, the curves obtained have the following form presented in FIG.
    Thus, according to the modified Beer-Lambert law, it is necessary to solve the system with six (6) equations and six (6) unknowns according to:
    With: aÇkt): intensity measured at the maximum of the pulsatile component at the wavelength i (AC).
    Ib (Aj): intensity measured at the minimum of the pulsatile component at the wavelength i (DC). L (Àj): length of the light path from the light source to the detector. Bi: molar absorption coefficient of component i.
    Ci: blood concentration of the component i.
    The resolution of the system of preceding equations makes it possible to find the variations of the concentrations, that is to say the maximum of the pulsatile component, denoted AC, of all the chemical substances considered.
    The device described above makes it possible to calculate the ratio which makes it possible to determine the concentration of glucose in the blood.
    权利要求:
    Claims (10)
    [1" id="c-fr-0001]
    1. Device for measuring the concentration of a compound present in the blood comprising an adjustable support capable of coating a part of the human body, said adjustable support comprising: at least one light source, said at least one light source emitting light beams at least one wavelength, said wavelength being in a range from 700 nm to 3000 nm, said light beams being backscattered by the portion of the human body constituting a backscattering source, at least one photodiode receiver, said device not comprising a diode emitting light beams at a wavelength in the range of 490 nm to 580 nm.
    [2" id="c-fr-0002]
    2. Device according to claim 1 characterized in that the at least one light source is an LED or a laser diode.
    [3" id="c-fr-0003]
    3. Device according to claims 1 or 2 characterized in that it comprises a spectral decomposition means of the backscattered light.
    [4" id="c-fr-0004]
    4. Device according to one of the preceding claims characterized in that said measuring device comprises from 2 to 50 light sources.
    [5" id="c-fr-0005]
    5. Device according to one of the preceding claims characterized in that said measuring device comprises from 2 to 50 photodiode receivers.
    [6" id="c-fr-0006]
    6. Device according to one of the preceding claims characterized in that the at least one wavelength of the light beam emitted by the at least one light source is included in at least one of the wavelength ranges centered on wavelengths suitable for measuring the following compounds: total hemoglobin (HbT), de-oxyhemoglobin, oxyhemoglobin, glucose, albumin, lactic acid, triglycerides, and urea.
    [7" id="c-fr-0007]
    7. Device according to one of the preceding claims characterized in that it is able to be arranged around the lobe of the ear, finger, forehead, chin, wrist, foot, hand or neck .
    [8" id="c-fr-0008]
    8. Device according to one of the preceding claims characterized in that it can communicate via a wireless system.
    [9" id="c-fr-0009]
    9. A method for measuring the concentration of a compound present in the blood comprising the following steps: • emitting at least one light beam at least one wavelength ranging from 700 nm to 3000 nm at least one light source, • measure the intensity of the backscattered light as a function of time, • determine the intensity of the backscattered light at the maximum of the pulsatile component and the backscattered light at the minimum of the pulsatile component, • calculate the concentration of said compound present from the measured intensity of the at least one backscattered light beam at the minimum and maximum of the pulsatile component.
    [10" id="c-fr-0010]
    10. Use of the device according to one of the preceding claims for simultaneously determining the concentration of various compounds present in the blood, these compounds include but are not limited to: total hemoglobin (HbT), de-oxyhemoglobin, oxyhemoglobin , hematocrit, platelets, cholesterol, urea, ammonia, ammonia, creatinine, calcium, sodium, potassium, chloride, bicarbonate.
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    法律状态:
    2016-12-22| PLFP| Fee payment|Year of fee payment: 2 |
    2017-06-30| PLSC| Publication of the preliminary search report|Effective date: 20170630 |
    2017-12-21| PLFP| Fee payment|Year of fee payment: 3 |
    2019-12-19| PLFP| Fee payment|Year of fee payment: 5 |
    2020-12-23| PLFP| Fee payment|Year of fee payment: 6 |
    2021-12-24| PLFP| Fee payment|Year of fee payment: 7 |
    优先权:
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    FR1563262A|FR3046048B1|2015-12-23|2015-12-23|DEVICE AND METHOD FOR MEASURING THE CONCENTRATION OF A BLOOD COMPOUND|
    FR1563262|2015-12-23|FR1563262A| FR3046048B1|2015-12-23|2015-12-23|DEVICE AND METHOD FOR MEASURING THE CONCENTRATION OF A BLOOD COMPOUND|
    PCT/FR2016/053668| WO2017109440A1|2015-12-23|2016-12-23|Device and method for measuring the concentration of a chemical compound in blood|
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    JP2018532636A| JP2019505275A|2015-12-23|2016-12-23|Apparatus and method for measuring the concentration of a compound present in blood|
    US16/065,158| US20180317825A1|2015-12-23|2016-12-23|Device and method for measuring the concentration of a chemical compound in blood|
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