• 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 method of the invention makes it possible to identify a pathology on a patient by studying its NO emission curve measured by a sensor sensitive element on its skin during a predefined sequence of activity.
    公开号:FR3081559A1
    申请号:FR1854495
    申请日:2018-05-28
    公开日:2019-11-29
    发明作者:Philippe Riviere；Luc Vialard；Yoann Perez；Frederic Daumas；Jean-Christophe Aubagnac；Marc Labrunee；Gilles Favre
    申请人:Noptrack；
    IPC主号:
    专利说明:

    The invention relates to a method for detecting, on a living human or animal subject, a pathology by using information relating to the production of NO by the subject studied. The invention also relates to an autonomous device making it possible to measure NO for the purpose of diagnosing and / or preventing the appearance of pathologies linked to this molecule.
    We know that nitric oxide NO is a gas which constitutes a cellular messenger. NO plays an important role in protecting against the onset and progression of certain cardiovascular diseases. Associated cardiovascular pathologies include hyper-cholesterolemia, hypertension and diabetes. The underlying disease for most cardiovascular disease is arteriosclerosis, which is, in turn, associated with dysfunctional endothelial. The cardio-protective role of NO includes regulation of blood pressure and vascular tone, inhibition of platelet accumulation, leukocyte adhesion and proliferation of smooth muscle fiber cells. NO is also involved in bronchial inflammation; in particular, it has been measured that the concentration of NO is greater in asthmatic subjects than in non-asthmatic subjects. It has also been found that NO is involved, depending on its concentration, in the appearance or regression of tumors. All of the diseases affected by NO fall under long-term conditions, the annual cost of which increases each year and makes it necessary to prevent and predict the appearance of these diseases.
    In the case of a cardiovascular disease, the currently existing devices and the prevention and prediction tools are either limited to an indirect measurement of the NO of the patient at rest, or limited to a direct measurement delayed by several hours compared to an observation of a pathological problem. In all cases, the measurements can only be carried out in a medical environment.
    According to the present invention, an apparatus is proposed allowing a direct, continuous and immediate measurement of NO in sweat, at the cutaneous level, on a patient, in his everyday life, possibly over several days and under all environmental conditions, in particular in terms of pressure, humidity and temperature; such a device makes it possible to detect and deduce the evolution of a risk of occurrence of pathologies.
    The subject of the present invention is a method for detecting, on a living human or animal subject, at least one parameter associated with a pathology, in which the quantity of NO produced by said subject is identified during a sequence of a state of predefined activity, characterized in that an area of investigation of the skin of said subject is chosen, there is identified, directly and continuously, the production of NO in sweat by means of a device formed by a first part, carried by said investigation area and held thereon in a sealed manner, this first part being secured to a sensitive element, which ensures the detection of NO by means of a sensor, and which is sent by said sensor, thanks to an energy generator associated with said sensitive element, a signal, the reading of which allows the desired detection.
    In a first variant of the method, at least one unit is used, which supplies a signal as a result of an electrochemical measurement made using the sweat produced by the subject in the area of investigation, as an electrolyte between two working electrodes carried by an insulating planar support.
    In another variant of the method according to the invention, the signal is the result of a detection of molecular de-excitation carried out on the sweat obtained on the area of investigation of the skin of the subject or of an implementation of a technique NO electrophilic polymers.
    It can be provided that, in the method according to the first variant of the invention, there is associated with the two working electrodes, a reference electrode. It is also possible to provide that the sensor comprises a plurality of similar units, the signals of which are combined to improve the output signal. Provision may be made for the plotting of the electrodes relative to their support to follow a Hilbert curve, in order to improve the power of the output signal per unit area of the support.
    For an implementation of the method according to the invention, it is possible to provide that the two parts of the device providing the signal, are arranged one above the other, the first part comprising the sensor and the second containing electronics. to collect the raw sensor measurements, translate them into NO concentration and ensure the signal transmission with, possibly, other parameters linked to the environment.
    Provision can be made for measurements to be made at the orifices provided in the planar support, which is located at the level of the conductive traces of the electrodes. In an interesting embodiment, the electrodes consist of metal deposits, in particular Ag, Au, Pt, or of graphene deposits doped with Ag or Au nanoparticles functionalized with NO binders, in particular guanylyl-cyclase or porphyrins.
    It can be foreseen that, in the method according to the invention, the device used performs and transmits measurements at a frequency which depends on the state of activity of the subject, this state being identified by means of a gyroscopic and / or accelerometric module. of the second part of the device.
    The invention also relates to an apparatus for detecting, on a living human or animal subject, at least one parameter associated with a pathology, in which the quantity of NO produced by said subject is identified during a sequence of a predefined activity state. This device allows the implementation of the method as defined above, and it is characterized in that, on an area of investigation of the skin of said subject, the production of NO is directly and continuously identified in sweat by means of a device formed by a first part carried by said investigation zone and held thereon in a sealed manner, this first part being secured to a sensitive element which ensures the detection of NO by means of a sensor, and that is sent by said sensor, thanks to an energy generator associated with said sensitive element, a signal, the reading of which allows the desired detection.
    It is possible to provide that the apparatus according to the invention comprises at least one unit, which supplies the signal as a result of an electrochemical measurement made using the sweat produced by the subject in the investigation area, as an electrolyte between two electrodes of work carried by an insulating planar support.
    In another variant, the signal supplied by the sensor is the result of a photo-acoustic detection carried out on the sweat obtained on the area of investigation of the subject's skin or of an implementation of a technique of NO-sensitive electro-spun polymer.
    In the first variant mentioned above, provision may be made for a reference electrode to be associated with the two working electrodes.
    Provision may be made for the sensor of a device according to the invention to comprise a plurality of similar units, the signals of which are combined to improve the output signal.
    It can be provided that in the apparatus according to the invention, the plot of the electrodes with respect to their support follows a Hilbert curve to improve the strength of the output signal per unit area of the support.
    It can be provided that, in the apparatus according to the invention, the two parts of the device providing the signal are arranged one above the other, the first part comprising the sensor and the second containing electronics for collecting the raw measurements of the sensor, to translate them into NO concentration and ensure the transmission of the signal with possibly other parameters related to the environment. In such an apparatus, the measurements are carried out at the right of orifices provided in the planar support, which is located at the line of the conductive traces of the electrodes.
    It can be provided that, in the apparatus according to the invention, the device performs and transmits measurements at a frequency depending on the state of activity of the subject, this state being identified by means of a gyroscopic and / or accelerometric module. of the second part of the device.
    It is possible to provide that, in the apparatus according to the invention, the electrodes consist of metallic deposits, in particular Ag, Au, Pt, or of graphene deposits doped with nanoparticles of Ag or Au functionalized by binders of the NO, in particular guanylyl-cyclase or porphyrins.
    To better understand the object of the invention, we will describe below, by way of purely illustrative and not limiting, an embodiment re presented in the accompanying drawing. On this drawing :
    FIG. 1 represents in perspective, a general external view of a detection device according to the invention;
    FIG. 2 represents an overall view of a patient on which an apparatus according to the invention has been put in place;
    FIG 3 shows an exploded view of the device of Figure 1;
    FIG. 4 represents a block diagram corresponding to the operation of the apparatus of FIG. 3;
    FIG. 5 represents a plan view of a planar support carrying two electrodes put in place according to Hilbert curves;
    FIG. 6 represents a curve obtained on a healthy subject equipped with an apparatus according to the invention, as indicated in FIG. 2.
    Referring to the drawing, it can be seen that the apparatus according to the invention is designated by 1 as a whole; it is intended to make a NO measurement on a healthy human patient; in the example described, the subject is subjected to physical activity by the use of a bicycle corresponding to an activity of 160 W. As shown in FIG. 6, the detection of NO is carried out at the start of the test ( point 11) until the end of the test (point 12), i.e. for a time sequence of approximately 500 seconds. The device 1 is generally in the form of a self-adhesive patch-dressing, which can be positioned directly on the patient's skin.
    The apparatus according to the invention comprises a fixing base 3 made of a flexible biocompatible and sticky material; this base ensures maintenance on the skin of the complete device; the central part 4a of the base 3 is a circular recess where the first part of the device is positioned, which makes it possible to identify the production of NO in the area of investigation of the skin 2 of the subject.
    The circular recess 4a therefore allows the positioning of the first part 4 of the measuring device directly on the skin 2 of the patient.
    This first part 4 is secured to a sensitive element 5, which overcomes it to form the base of a stack. The sensitive element 5 ensures the detection of NO by means of a sensor, which will be defined below. The sensor sends its information to a converter 5a, which itself powers a processor 5b, powered by an energy generator 5d associated with said sensitive element 5. The processor 5b powers a radio-communication system 5c, which sends the information on an instrumentation capable of translating it into a curve such as that shown in FIG. 6.
    In this FIG. 6, the part constituting the measurement of the NO produced by the patient, is that which is between the points 11 and 12 of the curve. All the elements ensuring the various functions shown diagrammatically in FIG. 4, are brought together in on-board electronics, designated by 6 as a whole. The components 4, 5 and 6 form a stack, which is maintained on the skin of the subject by means of a flexible and waterproof envelope of the silicone type, designated by 7 as a whole.
    The on-board electronics of the element 6 provides the control functions of the organs of the sensitive element 5; it also includes a gyroscopic and accelerometric unit and a temperature sensor.
    The sensitive element of the example described is electrochemical; that shown in FIG. 5 constitutes a sensor supported by an insulating planar support 10, on which two electrodes 8 and 9 have been put in place between which is the sweat produced by the patient in line with the stack 4, 5, 6 In the element represented, it can be seen that there are four identical units each making it possible to obtain a measurement of NO, the installation of several sensitive units advantageously making it possible to obtain a cutaneous map of production of NO within the covered area.
    The current intensities which are obtained with the apparatus according to the invention are between the pico and the milliampere.
    权利要求:
    Claims (20)
    [1" id="c-fr-0001]
    1. Method for detecting, on a living human or animal subject, at least one parameter associated with a pathology, in which the quantity of NO produced by said subject is identified during a sequence of a predefined activity state, characterized in that an area of investigation of the skin (2) of said subject is chosen, there is identified, directly and continuously, the production of NO in sweat by means of a device formed from a first part (4), carried by said investigation area and held thereon in a sealed manner, this first part (4) being secured to a sensitive element (5), which ensures the detection of NO by means of a sensor (8 , 9,10), and that is sent by said sensor, thanks to an energy generator associated with said sensitive element (5), a signal, the reading of which allows the desired detection.
    [2" id="c-fr-0002]
    2. Method according to claim 1, characterized in that at least one unit is used, which supplies the signal as a result of an electrochemical measurement made using the sweat produced by the subject in the investigation area, as an electrolyte between two working electrodes (8,9) carried by an insulating planar support (10).
    [3" id="c-fr-0003]
    3. Method according to claim 1, characterized in that the signal is the result of a detection of molecular de-excitation carried out on the sweat obtained on the area of investigation of the skin of the subject or of an implementation of a NO-sensitive electro-spun polymer technique.
    [4" id="c-fr-0004]
    4. Method according to claim 2, characterized in that associated with the two working electrodes (8,9) a reference electrode.
    [5" id="c-fr-0005]
    5. Method according to one of claims 1 or 2, characterized in that the sensor comprises a plurality of similar units, whose signals are associated to improve the output signal.
    [6" id="c-fr-0006]
    6. Method according to claim 2, characterized in that the plot of the electrodes (8,9) relative to their support follows a Hilbert curve to improve the power of the output signal per unit area of the support (10).
    [7" id="c-fr-0007]
    7. Method according to one of claims 1 to 6, characterized in that the two parts (4,5) of the device providing the signal are arranged one above the other, the first part (4) comprising the sensor and the second (5) containing electronics to collect the raw sensor measurements, translate them into NO concentration and ensure the signal transmission with possibly other parameters related to the environment.
    [8" id="c-fr-0008]
    8. Method according to claim 7, characterized in that the measurements are made at the orifices (11) provided in the planar support, which is located at the right of the conductive traces of the electrodes (8, 9).
    [9" id="c-fr-0009]
    9. Method according to claim 8, characterized in that the electrodes consist of metallic deposits, in particular Ag, Au, Pt, or of graphene deposits doped with nanoparticles of Ag or Au functionalized by binders of NO, in particular guanylyl-cyclase or porphyrins.
    [10" id="c-fr-0010]
    10. Method according to claim 7, characterized in that the device performs and transmits measurements at a frequency depending on the activity state of the subject, this state being identified by means of a gyroscopic and / or accelerometric module of the second part (5) of the device.
    [11" id="c-fr-0011]
    11. Apparatus (1) for detecting, on a living human or animal subject, at least one parameter associated with a pathology, in which the quantity of NO produced by said subject is identified during a sequence of a state of predefined activity, this apparatus allowing the implementation of the method according to claim 1, characterized in that, on an area of investigation of the skin (2) of said subject, the production is directly and continuously identified NO in sweat by means of a device formed by a first part (4) carried by said investigation area and held thereon in a sealed manner, this first part being secured to a sensitive element (5), which ensures detection of NO by means of a sensor, and which is sent by said sensor, thanks to an energy generator (5d) associated with said sensitive element (5), a signal, the reading of which allows the desired detection .
    [12" id="c-fr-0012]
    12. Apparatus according to claim 11, characterized in that it comprises at least one unit, which supplies the signal as a result of an electrochemical measurement made using the sweat, produced by the subject in the area of investigation, as electrolyte between two working electrodes (8,9) carried by an insulating planar support (10).
    [13" id="c-fr-0013]
    13. Apparatus according to claim 1, characterized in that the signal provided by the sensor is the result of a photo-acoustic detection carried out on the sweat obtained on the area of investigation of the skin of the subject or a setting work of an electro-spun polymer technique sensitive to NO.
    [14" id="c-fr-0014]
    14. Apparatus according to claim 12, characterized in that a reference electrode is associated with the two working electrodes.
    [15" id="c-fr-0015]
    15. Apparatus according to one of claims 11 or 12, characterized in that the sensor comprises a plurality of similar units, whose signals are associated to improve the output signal.
    [16" id="c-fr-0016]
    16. Apparatus according to claim 12, characterized in that the trace of the electrodes (8,9) relative to their support (10) follows a Hilbert curve to improve the strength of the output signal per unit area of the support.
    [17" id="c-fr-0017]
    17. Apparatus according to one of claims 11 to 16, characterized in that the two parts of the device providing the signal are arranged one above the other, the first part (4) comprising the sensor and the second (5) containing electronics for collecting the raw measurements from the sensor, for translating them into NO concentration and ensuring the transmission of the signal with possibly other parameters linked to the environment.
    [18" id="c-fr-0018]
    18. Apparatus according to claim 17, characterized in that the measurements are made in line with orifices (11) provided in the planar support (10), which is located in line with the conductive traces of the electrodes (8, 9).
    [19" id="c-fr-0019]
    19. Apparatus according to one of claims 11 to 18, characterized in that the device performs and transmits measurements at a frequency depending on the state of activity of the subject, this state being identified by means of a gyroscopic module and / or accelerometric of the second part (5) of the device.
    [20" id="c-fr-0020]
    20. Apparatus according to claim 12, characterized in that the electrodes (8, 9) consist of metallic deposits, in particular Ag, Au, Pt, or graphene deposits doped with nanoparticles of Ag or Au functionalized by NO binders, in particular guanylyl-cyclase or porphyrins.
    类似技术:
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    同族专利:
    公开号 | 公开日
    CA3100055A1|2019-12-05|
    FR3081559B1|2020-05-08|
    KR20210020941A|2021-02-24|
    CN112165896A|2021-01-01|
    EP3801213A1|2021-04-14|
    JP2021526443A|2021-10-07|
    US20210137421A1|2021-05-13|
    WO2019229380A1|2019-12-05|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    WO1998008480A2|1996-08-30|1998-03-05|The Research Foundation Of State University Of New York|Method of using tetracycline compounds for inhibition of nitric oxide production|
    WO2016061362A2|2014-10-15|2016-04-21|Eccrine Systems, Inc.|Sweat sensing device communication security and compliance|
    FR3103901A1|2019-11-28|2021-06-04|Noptrack|DETECTION OF A CHEMICAL SPECIES IN THE SWEAT OF A SUBJECT|
    CN111685755B|2020-05-29|2021-09-21|华南理工大学|AgNWs-PDMS composite flexible conductive optical fiber micro-lens and preparation method thereof|
    法律状态:
    2019-05-31| PLFP| Fee payment|Year of fee payment: 2 |
    2019-11-29| PLSC| Search report ready|Effective date: 20191129 |
    2020-05-30| PLFP| Fee payment|Year of fee payment: 3 |
    2021-05-31| PLFP| Fee payment|Year of fee payment: 4 |
    优先权:
    申请号 | 申请日 | 专利标题
    FR1854495A|FR3081559B1|2018-05-28|2018-05-28|METHOD FOR DETECTING A PATHOLOGY BY LOCATING A QUANTITY OF NO PRODUCED BY THE SUBJECT STUDIED AND APPARATUS FOR IMPLEMENTING SAID METHOD|
    FR1854495|2018-05-28|FR1854495A| FR3081559B1|2018-05-28|2018-05-28|METHOD FOR DETECTING A PATHOLOGY BY LOCATING A QUANTITY OF NO PRODUCED BY THE SUBJECT STUDIED AND APPARATUS FOR IMPLEMENTING SAID METHOD|
    EP19739677.3A| EP3801213A1|2018-05-28|2019-05-28|Method for detecting a quantity of no produced by the subject under test, and apparatus for carrying out said method|
    CA3100055A| CA3100055A1|2018-05-28|2019-05-28|Method for detecting a quantity of no produced by the subject under test, and apparatus for carrying out said method|
    US17/058,588| US20210137421A1|2018-05-28|2019-05-28|Method for detecting a quantity of no produced by the subject under test, and apparatus for carrying out said method|
    JP2021517535A| JP2021526443A|2018-05-28|2019-05-28|A method for detecting the amount of NO produced by a subject, and a device for carrying out the method.|
    PCT/FR2019/051261| WO2019229380A1|2018-05-28|2019-05-28|Method for detecting a quantity of no produced by the subject under test, and apparatus for carrying out said method|
    KR1020207037605A| KR20210020941A|2018-05-28|2019-05-28|Method for detecting the amount of NO produced by a subject and apparatus for performing the method|
    CN201980035627.1A| CN112165896A|2018-05-28|2019-05-28|Method for detecting the amount of NOproduced by a test object and device for carrying out said method|
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