WO2016142610A1 - Device for identifying a woman's infertile period - Google Patents

Device for identifying a woman's infertile period Download PDF

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Publication number
WO2016142610A1
WO2016142610A1 PCT/FR2016/050506 FR2016050506W WO2016142610A1 WO 2016142610 A1 WO2016142610 A1 WO 2016142610A1 FR 2016050506 W FR2016050506 W FR 2016050506W WO 2016142610 A1 WO2016142610 A1 WO 2016142610A1
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WO
WIPO (PCT)
Prior art keywords
pdg
zone
woman
urine
antibody
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PCT/FR2016/050506
Other languages
French (fr)
Inventor
Stephanus Alexander Paulus Van Der Geest
André Ulmann
Original Assignee
Laboratoire Hra-Pharma
Cemag
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Publication date
Application filed by Laboratoire Hra-Pharma, Cemag filed Critical Laboratoire Hra-Pharma
Publication of WO2016142610A1 publication Critical patent/WO2016142610A1/en

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Classifications

    • 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
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/74—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving hormones or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors
    • G01N33/743—Steroid hormones
    • 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
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54366—Apparatus specially adapted for solid-phase testing
    • G01N33/54386—Analytical elements
    • G01N33/54387—Immunochromatographic test strips
    • G01N33/54388—Immunochromatographic test strips based on lateral flow
    • 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
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/558—Immunoassay; Biospecific binding assay; Materials therefor using diffusion or migration of antigen or antibody

Definitions

  • the invention relates to a device enabling a woman to determine reliably and simply whether or not she is in an infertile period.
  • the invention finds applications when a woman wishes to check punctually whether or not she is in a fertile period of her menstrual cycle.
  • the ovarian cycle refers to all the physiological phenomena that occur most often periodically, which prepare the body of a woman for possible fertilization.
  • ovulation consists of the release of at least one egg from one of the ovaries. This egg is prepared in a follicle for several weeks before release, under the influence of FSH ("Follicle Sittmdanting Hormone") secreted by the hypothalamus and pituitary gland.
  • FSH Follicle Sittmdanting Hormone
  • the follicle produces estrogen, which in turn ensures a change in the uterus and the preparation of the endometrium to the potential implantation of an embryo.
  • the pituitary gland releases a high dose of luteinizing hormone LH (Luteinizing Hormone), which triggers ovulation.
  • LH Luinizing Hormone
  • the cells that previously formed the follicle then form the corpus luteum. This releases progesterone, ensuring the maintenance of the uterine lining for a possible pregnancy.
  • the life of an egg in the female genital tract is relatively short, of the order of 24 hours. Beyond that, the egg can no longer be fertilized.
  • the possibility of fertilization is limited in time due to the short life of the egg.
  • the survival of sperm in the female genital tract is about 5 days, the window of fertilization includes the period of about 4 days before ovulation and the day of ovulation itself.
  • the timing of ovulation during a cycle is unpredictable, even in women with a regular cycle. Also, it is difficult for a woman to know at any time if she is in a period of risk of pregnancy or in an infertile period. Contraceptive means must therefore most often be taken throughout a cycle, when a woman wishes to avoid pregnancy during sexual intercourse. This is particularly the case of the contraceptive pill.
  • condoms in women who do not use the pill should be used for most of the cycle to prevent the risk of unwanted pregnancy.
  • some women use natural methods of family planning. Among these methods are the observation of clinical signs specific to different periods of the cycle, such as menstruation, body temperature or the appearance of cervical mucus. These methods, however, require strict knowledge and monitoring of their cycles and remain unreliable. In fact, ovulation can occur at any point in the cycle, especially in the event of external disturbances, such as stress, illness, jet lag, etc., so that it is difficult to identify 5-day period during which fertilization is possible in case of unprotected sexual intercourse, that is to say in the absence of a contraceptive method, or when it fails.
  • Ovulation tests have been developed to tell a woman whether or not she will ovulate in the coming hours. These tests, usually in the form of small impregnated strips, work on the principle of detection of luteinizing hormone (LH) in the urine, a peak of LH being generally followed within 24 to 48 hours of ovulation. Nevertheless, these tests are unable to predict whether ovulation will occur within 4 or 5 days, and therefore do not allow the woman to reliably assess whether she is in an infertile period or on the contrary in a period at risk of pregnancy in the event of unprotected intercourse. Other methods have been considered to allow a woman to identify the period during which she is not fertile. This can be particularly useful for women who do not use contraception regularly and / or systematically.
  • LH luteinizing hormone
  • PDG preganediol-3cc-glucuronide
  • application EP0367615 discloses a method for evaluating the infertile period in a woman, taking into account, in particular, the level of PDG in the urine.
  • the proposed method is difficult to implement and requires the study of at least one menstrual cycle. Subsequently, no less than four successive steps are necessary to obtain a result, the respect of this succession of steps conditioning the reliability of the test.
  • the constraints related to the storage conditions of the various reagents involved in this test make it practically impossible for it to be used by a layman.
  • the object of the invention is to solve the problem stated above, by proposing a device revealing the absence or the presence of PDGs in the urine such that it enables a woman to determine at a glance. whether or not she is in an infertile period. More specifically, the device according to the present invention is based on a competitive immunological binding principle for detecting a predetermined PDG threshold in the urine.
  • the device according to the invention therefore allows a woman to reliably determine, at any time during her cycle, whether she is in an infertile period or not.
  • the device according to the invention intended to receive a urine sample, contains not only a labeled anti-PDG antibody capable of being driven by a flow of urine, but also exogenous PDG attached downstream of the anti , Chairman and CEO.
  • the labeled antibody is present in a concentration sufficient to allow differentiation between a urine sample containing a PDG concentration below the predetermined threshold and a urine sample containing a PDG concentration above the predetermined threshold.
  • all the reagents necessary for the evaluation of the PDG level in a urine sample are integrated in the device, so that apart from the depositing of the urine sample in the dedicated part of the device, no further manipulation is required to read the test result.
  • the invention therefore relates to a device for identifying the infertile period of a woman, comprising successively
  • a receiving zone made of dry porous material, intended to receive a urine sample
  • a dry porous material reaction zone comprising at least one detectably labeled anti-pregnanediol-3cc-glucuronide (PDG) antibody, said anti-PDG antibody being freely mobile in the porous materials when wet; , and
  • the "infertile period" of an ovarian cycle corresponds to the period between at least 24 hours after ovulation and the end of the cycle considered. During this infertile period, a woman wishing to avoid pregnancy knows that she can have unprotected sex, knowing that the chances of pregnancy are almost nil. Conversely, a woman wishing to become pregnant knows that during this period sexual intercourse is very unlikely to lead to pregnancy.
  • the concept of "unprotected intercourse” means when no means of contraception is used or when the means of contraception is not properly used (in particular, non-compliance with dosage in case of oral contraception, rupture or withdrawal of the condom or diaphragm, error in the evaluation of the period of abstinence, etc.), but in no case vis-à-vis the risks of transmission of disease (s) sexual (s).
  • dry porous material a porous material which has not yet been brought into contact with a liquid sample and in particular a urine sample. More generally, the term “dry state” of a porous material, a state in which no non-immobilized reagent is able to migrate into said material.
  • the device according to the invention preferably comprises at least one solid support on which are formed the successive zones of dry porous material.
  • the solid supports may be of dry porous material. It is also possible to provide all or part of the zones of porous material are laid or fixed on the (s) said (s) support (s) solid, or attached thereto.
  • upstream and downstream refer to a flow of urine that would be deposited at the receiving zone.
  • the different zones of the device are arranged successively, in the order of enumeration of said zones, so that a flow of urine deposited at the level of the reception zone can pass by capillarity through each of said areas. More specifically, the receiving zone, or upstream end, is adjacent to the reaction zone, itself adjacent to the revelation zone. By “adjacent” is meant arranged “next to”, without necessarily being contiguous. The arrangement of the different zones must, however, allow their successive humidification by a urine sample which would be deposited on the reception zone.
  • the anti-PDG antibodies can be transported from the reaction zone to the revelation zone by the flow of 'urine.
  • the anti-PDG antibodies are then likely to fix the immobilized PDG at the level of the revelation zone.
  • the immobilization of the PDG can be carried out by any appropriate technique, such as adsorption or covalent bonds.
  • PDG can be immobilized on the porous material of the developing zone by binding to a carrier protein, such as bovine serum albumin.
  • a carrier protein such as bovine serum albumin.
  • the PDG is uniformly immobilized over the entire surface of the revelation zone.
  • the PDG is immobilized in a particular pattern, such as a transverse band, on said area.
  • the device further comprises a control zone made of dry porous material, preferably disposed downstream of the revelation zone, at the level of which an antibody specific for a control reagent is immobilized.
  • the control reagent is an immunoglobulin G (IgG), preferentially non-human.
  • the reaction zone then comprises detectably labeled, freely movable control reagent in the successive porous materials when in the wet state.
  • the labeled control reagent is driven by the urine flow to the control zone, where it can bind to the specific antibodies.
  • the detection of the control reagents in said control zone makes it possible to confirm that there has been sufficient humidification of the successive zones by the urine sample.
  • the labeled control reagent is mouse IgG.
  • the specific antibody of the control reagent can then be a goat anti-mouse IgG antibody. It may also be useful to provide an additional zone, or absorption end, downstream of the control zone, intended to absorb excess urine.
  • the urine sample is deposited on the receiving zone, the urine is absorbed by the successive porous materials until the downstream end of the device.
  • the urine stream entrains the detectably labeled compounds from the reaction zone to the revelation and / or control zone and / or the downstream end.
  • the principle of revelation of the PDG according to the invention is based on a principle of competition between the PDG likely to be present in the urine sample and the PDG immobilized on the device. If the level of PDG in the urine sample is below a predetermined threshold, the labeled anti-PDG antibodies can bind at least partially to the PDG of the revealing zone, where they can be detected.
  • the labeled compounds may be by any known means for their visualization, preferably with the naked eye.
  • the compounds may be labeled with a dye, an isotope, or a fluorochrome, the developing means being adapted to the selected marking.
  • the anti-PDG antibody and / or the control reagent are labeled by coupling to p articular markers, such as colloidal gold beads.
  • the device comprises a nitrocellulose membrane, forming all or part of the successive zones.
  • the device comprises an absorbent paper receiving zone secured to a reaction zone also made of absorbent paper, said reaction zone being integral with a nitrocellulose membrane on which are formed the revealing zone and the control zone.
  • the absorption end may, in turn, consist of an absorbent paper attached to the downstream end of the nitrocellulose membrane.
  • the device has a general strip form, whose dimensions allow easy handling.
  • the strip may have a length of between 5 and 10 cm and a width of between 0.5 and 1 cm.
  • length we mean the most large dimension of the device, extending from the receiving zone to the downstream end.
  • width is meant the smallest dimension, extending perpendicular to the length, in the same plane.
  • all or part of the strip or successive zones of porous material is housed in a protective housing.
  • the housing may for example include an access to the reception area for the urine sample and reading windows to at least partially visualize the revealing area and / or control from the outside of the housing .
  • the labeled anti-PDG antibodies of the device when the amount of PDG contained in the urine sample is above a certain threshold previously fixed, the labeled anti-PDG antibodies of the device all bind to the urinary PDG and are carried beyond the zone. revealing, so that they are not detectable. Conversely, when the amount of PDG in the urine sample is below said threshold, the labeled anti-PDG antibodies bind at least partially to the PDG of the reaction zone, at which point they can then be detected.
  • the device according to the invention makes it possible to reveal labeled anti-PDG antibodies when the amount of PDG in a urine sample is below a threshold concentration, preferably between 5 and 15 ⁇ g of PDG per ml of urine, and in particular less than or equal to 10 ⁇ g / ml, +/- 2 ⁇ g / ml.
  • the threshold of 10 .mu.g / ml is particularly advantageous because it offers enhanced security to the users of the device, avoiding any risk of false positives.
  • the invention also provides a method for determining whether a woman is in an infertile period, said method comprising contacting a urine sample of the woman with a device according to the invention, detecting the immobilized PDG in the revealing zone indicative of a potentially fertile period. More specifically, the detection of labeled anti-PDG antibodies in the revealing zone indicates that ovulation has not yet occurred or occurred less than 24 hours ago. In contrast, the absence of labeled anti-PDG antibodies in the revealing zone is indicative of an infertile period. According to the invention, the presence of the labeled anti-PDG antibodies can be visualized by a colored pattern appearing in the revealing zone, the anti-PDG antibodies being then labeled with a colored marker such as a particulate marker. In a particular example, the colored marker is gold colloidal. Thus, the band appearing in the revelation zone in potentially fertile period is red in color and can be visualized quickly and reliably.
  • the device according to the invention may be particularly useful for a woman not taking contraceptives and who wishes however to avoid any risk of pregnancy in case of unprotected sex. Indeed, if the test indicates that she is in an infertile period, she can have unprotected sex without fear of pregnancy, until the beginning of the next cycle. Conversely, as long as the test results indicate that she is in a potentially risky period of pregnancy, the woman will take care to avoid unprotected intercourse. It should be noted that the test according to the invention can be practiced at any moment of the cycle and renewed if necessary until the identification of the infertile period.
  • the device according to the invention can be used by a woman wishing to avoid any risk of pregnancy and who has had unprotected sex. By practicing the test less than six hours after unprotected sex, she can check that she is not in a period of risk of pregnancy. In the opposite case, she may then consider using emergency contraception.
  • the device according to the invention may be useful for a woman wanting a child.
  • a couple in desire of child generally increases the number of their sexual intercourse, to increase the chances of fertilization.
  • these reports will not lead to a pregnancy.
  • the woman can easily determine the infertile period of her cycle, and thus know that from that moment all sexual intercourse will be infertile, and that until the beginning of the next cycle. It is then possible for her, if she wishes, to interrupt her sexual activities.
  • Figure 1 A schematic representation of a first embodiment of the device according to the invention
  • Figure 2 A schematic representation in section of a device according to the invention and reagents it contains;
  • Figure 3 A representation of an exemplary embodiment of the device of the invention provided with a housing.
  • FIG. 1 shows an exemplary embodiment of a device 10 for identifying the fertile period of a woman, according to the invention, of generally elongated strip form.
  • the device 10 comprises a support 11, preferably rigid, on which a nitrocellulose membrane 12 rests. A revealing zone 13 and a control zone 14 follow one another along said membrane 12.
  • the device 10 further comprises a reception zone 15 of porous material and an adjacent reaction zone 16, also of porous material. For example, these two zones 15 and 16 each consist of an absorbent paper secured to the support 11, by gluing or otherwise.
  • the receiving zone 15 partially overlaps the reaction zone 16, so that a urine sample deposited at the receiving zone 15 will also be able to humidify the reaction zone 16 downstream.
  • the nitrocellulose membrane 12 disposed downstream of the reaction zone 16 is in contact with said reaction zone 16, which allows a urine sample moistening the reaction zone 16 to also humidify the membrane 12 .
  • a downstream end 17, or absorption zone is disposed downstream of the nitrocellulose membrane 12, which it overlaps partially.
  • the absorption zone 17 is thus able to absorb any excess urine by capillarity.
  • the device 10 has a generally elongate shape, the areas of porous material 15, 16, 13, 14 and 17 extending successively in a larger dimension, or length, of said device 10.
  • Figure 2 are shown schematically the different areas of a device 20 according to the invention in strip form, and the reagents they contain.
  • a reaction zone 22, disposed downstream of a receiving zone 21, contains a detectably labeled control reagent 26, as well as anti-PDG antibodies 27, also detectably labeled.
  • the control reagent 26 as the anti-PDG antibodies 27 are for example deposited on the surface of the porous material forming the reaction zone 22. They may otherwise be contained in the porous material.
  • the control reagent 26 and the anti-PDG antibodies 27 are not integral with the reaction zone 22 and can move in and / or on the porous material when it is wet, as well as only in and / or on wet porous materials downstream.
  • a revelation zone 23 and a control zone 24 follow each other along the strip, which terminates in an end swallowed to absorb excess urine.
  • PDG 28 is immobilized for example by means of bovine serum albumin (not shown) on the revelation zone 23.
  • Control anti-reagent antibodies 29 are themselves immobilized on the control zone 24, for example by means of serum bovine albumin (not shown).
  • the urine flow of a urine sample, when deposited on the receiving zone 21, is represented by an arrow extending from said receiving zone 21 to the downstream end 25.
  • the urine moistens the receiving zone 22 to then reach the zones 23, 24, 25 disposed downstream, it carries with it the control reagent 26 and the anti-PDG antibodies 27.
  • the concentration of PDG in the Urine sample endogenous PDG
  • a greater or lesser amount of anti-PDG antibody will be able to be attached to the PDG 28 of the revelation zone 23.
  • the labeled anti-PDG antibodies already bound to endogenous PDG will not be retained at the revelation zone 23 and will be evacuated together with the excess urine in the absorption zone 25.
  • the anti-PDG antibodies may be detected by the user at said zone 23 at the end of the test.
  • the control reagent 26 will be driven to the control zone 24 where it will bind to the control anti-reagent antibodies 29.
  • the detection of the labeled control reagents 26 at the control zone 24 confirms that the test has been conducted properly and that the result obtained at the revelation zone 23 is reliable.
  • the anti-PDG antibodies 27 and the control reagents 26 are detectably labeled, so that the detection of their presence at the level of the revelation zone 23 and of the control zone 24 respectively, is done directly, without the addition of an additional developer compound and / or the use of a specific device is required.
  • the labeling is done by means of a dye or colored particles, such as colloidal gold particles. The user can thus directly visualize a colored marking on the areas of interest 23, 24.
  • FIG. 3 also shows an exemplary embodiment of a device 30 according to the invention, according to which a strip comprising successive zones made of porous materials is housed in a housing provided with a cap 31. More specifically, the cap 31 covers the the upstream end of the strip, and once removed to release access to the receiving area 32 of the device 30. A user can then deposit a urine sample on the receiving area 32.
  • the urine sample can be deposited either a directing the receiving area 32 directly under a stream of urine, or by soaking said receiving area 32 in a container containing a urine sample.
  • the porous material used to form the receiving end of the device according to the invention is advantageously such that it is in a wet state sufficient for the good practice of the test after 5 to 15 seconds under a jet of water. urine, or after 5 to 15 seconds immersed in a urine sample.
  • the housing also comprises a main body 33 in which are housed the reaction zone, the detection zone and the control zone.
  • the reaction zone is entirely covered by the main body 33 and is not visible in the housing.
  • two windows 34 and 35 are provided on the main body 33 which respectively make it possible to visualize at least partially the detection zone and the control zone, from the outside of the main body 33.
  • a downstream end 36 of the housing covers the absorption zone intended to recover an excess potential of urine.

Abstract

The invention relates to a device (10) for identifying a woman's infertile period, said device successively comprising a receiving area (15) consisting of a dry porous material and used to receive a urine sample, a reaction area (16) consisting of a dry porous material and comprising at least one anti-pregnanediol-3a-glucuronide (PDG) antibody marked in a detectable manner, said anti-PDG antibody being able to move freely through the porous materials when they are in a moist state, and a results area (13) consisting of a dry porous material and comprising immobilised PDG, said immobilised PDG being able to compete with PDG present in a urine sample once same has been deposited in the receiving area.

Description

Dispositif pour l'identification de la période infertile d'une femme  Device for identifying the infertile period of a woman
L'invention a trait à un dispositif permettant à une femme de déterminer de manière fiable et simple si elle est ou non dans une période infertile. L'invention trouve des applications dès lors qu'une femme souhaite vérifier ponctuellement si elle est ou non dans une période fécondable de son cycle menstruel. The invention relates to a device enabling a woman to determine reliably and simply whether or not she is in an infertile period. The invention finds applications when a woman wishes to check punctually whether or not she is in a fertile period of her menstrual cycle.
Le cycle ovarien, ou cycle menstruel, désigne l'ensemble des phénomènes physiologiques survenant le plus souvent de manière périodique, qui préparent l'organisme d'une femme à une éventuelle fécondation. Parmi ces événements, l'ovulation consiste en la libération d'au moins un ovule par un des ovaires. Cet ovule est préparé dans un follicule pendant plusieurs semaines avant sa libération, sous l'influence de la FSH (« Follicle Sîitmdaîing Hormone ») sécrétée par l'hypothalamus et l'hypophyse. Le follicule produit quant à lui des œstrogènes, ce qui assure en parallèle une modification de l'utérus et la préparation de l'endomètre à la potentielle nidation d'un embryon. Lorsque le follicule est à un stade de développement avancé, l'hypophyse décharge une forte dose d'hormone lutéinisante LH (« Luteinizing Hormone »), ce qui déclenche l'ovulation. Les cellules qui formaient auparavant le follicule forment alors le corps jaune. Celui-ci libère de la progestérone, assurant le maintien de la muqueuse utérine en vue d'une éventuelle grossesse. Une fois libéré, la durée de vie d'un ovule dans le tractus génital féminin est relativement courte, de l'ordre de 24 heures. Au-delà, l'ovule ne peut plus être fécondé. The ovarian cycle, or menstrual cycle, refers to all the physiological phenomena that occur most often periodically, which prepare the body of a woman for possible fertilization. Among these events, ovulation consists of the release of at least one egg from one of the ovaries. This egg is prepared in a follicle for several weeks before release, under the influence of FSH ("Follicle Sittmdanting Hormone") secreted by the hypothalamus and pituitary gland. The follicle produces estrogen, which in turn ensures a change in the uterus and the preparation of the endometrium to the potential implantation of an embryo. When the follicle is in an advanced stage of development, the pituitary gland releases a high dose of luteinizing hormone LH (Luteinizing Hormone), which triggers ovulation. The cells that previously formed the follicle then form the corpus luteum. This releases progesterone, ensuring the maintenance of the uterine lining for a possible pregnancy. Once released, the life of an egg in the female genital tract is relatively short, of the order of 24 hours. Beyond that, the egg can no longer be fertilized.
Au cours du cycle, la possibilité de fécondation est limitée dans le temps du fait de la courte durée de vie de l'ovule. La survie des spermatozoïdes dans le tractus génital féminin étant quant à elle de 5 jours environ, la fenêtre de fécondation comprend la période d'environ 4 jours précédant l'ovulation et le jour de l'ovulation lui-même. Le moment de l'ovulation au cours un cycle est imprévisible, même chez les femmes ayant un cycle régulier. Aussi, il est difficile pour une femme de savoir à tout moment si elle est dans une période à risque de grossesse ou dans une période infertile. Des moyens de contraception doivent donc le plus souvent être pris tout au long d'un cycle, lorsqu'une femme souhaite éviter une grossesse lors d'un rapport sexuel. C'est le cas notamment de la pilule contraceptive. De même, le préservatif, chez les femmes n'utilisant pas la pilule, doit être utilisé pendant la quasi- totalité du cycle pour prévenir tout risque de grossesse non désirée. De manière alternative, certaines femmes ont recours à des méthodes naturelles de planification familiale. On peut citer parmi ces méthodes l'observation de signes cliniques propres aux différentes périodes du cycle, tels que les menstruations, la température corporelle ou l'aspect de la glaire cervicale. Ces méthodes requièrent cependant une connaissance et un suivi strict de leurs cycles et restent peu fiables. En effet, l'ovulation peut intervenir à n'importe quel moment du cycle, notamment en cas de perturbations extérieures, telles que le stress, les maladies, le décalage horaire, etc., de sorte qu'il est difficile d'identifier la période de 5 jours au cours de laquelle la fécondation est possible en cas de rapport sexuel non protégé, c'est-à-dire en l'absence de méthode contraceptive, ou lorsque celle-ci est défaillante. During the cycle, the possibility of fertilization is limited in time due to the short life of the egg. The survival of sperm in the female genital tract is about 5 days, the window of fertilization includes the period of about 4 days before ovulation and the day of ovulation itself. The timing of ovulation during a cycle is unpredictable, even in women with a regular cycle. Also, it is difficult for a woman to know at any time if she is in a period of risk of pregnancy or in an infertile period. Contraceptive means must therefore most often be taken throughout a cycle, when a woman wishes to avoid pregnancy during sexual intercourse. This is particularly the case of the contraceptive pill. Of even condoms in women who do not use the pill should be used for most of the cycle to prevent the risk of unwanted pregnancy. Alternatively, some women use natural methods of family planning. Among these methods are the observation of clinical signs specific to different periods of the cycle, such as menstruation, body temperature or the appearance of cervical mucus. These methods, however, require strict knowledge and monitoring of their cycles and remain unreliable. In fact, ovulation can occur at any point in the cycle, especially in the event of external disturbances, such as stress, illness, jet lag, etc., so that it is difficult to identify 5-day period during which fertilization is possible in case of unprotected sexual intercourse, that is to say in the absence of a contraceptive method, or when it fails.
Des tests d'ovulation ont été développés, pour indiquer à une femme si elle va ou non ovuler dans les heures qui viennent. Ces tests, généralement présentés sous forme de petites bandelettes imprégnées, fonctionnent sur le principe de la détection d'hormone lutéinisante (LH) dans les urines, un pic de LH étant généralement suivi dans les 24 à 48h d'une ovulation. Néanmoins ces tests sont incapables de prédire si l'ovulation va intervenir dans les 4 ou 5 jours qui suivent, et de ce fait ne permettent pas à la femme d'évaluer de manière fiable si elle est dans une période infertile ou au contraire dans une période à risque de grossesse en cas de rapport sexuel non protégé. D'autres méthodes ont été envisagées pour permettre à une femme d'identifier la période pendant laquelle elle n'est pas fertile. Cela peut notamment être particulièrement utile pour les femmes qui n'utilisent pas de moyens de contraception de manière régulière et/ou systématique. Par exemple, des méthodes basées sur l'évaluation du niveau de preganediol-3cc-glucuronide (PDG), un métabolite de la progestérone, dans l'urine d'une femme ont été envisagées. En effet, la progestérone qui est l'une des hormones sexuelles impliquées dans la préparation de l'organisme à la grossesse est métabolisée et excrétée dans l'urine sous forme de PDG lorsque l'ovulation a eu lieu et donc lorsque la femme n'est plus fertile. Ovulation tests have been developed to tell a woman whether or not she will ovulate in the coming hours. These tests, usually in the form of small impregnated strips, work on the principle of detection of luteinizing hormone (LH) in the urine, a peak of LH being generally followed within 24 to 48 hours of ovulation. Nevertheless, these tests are unable to predict whether ovulation will occur within 4 or 5 days, and therefore do not allow the woman to reliably assess whether she is in an infertile period or on the contrary in a period at risk of pregnancy in the event of unprotected intercourse. Other methods have been considered to allow a woman to identify the period during which she is not fertile. This can be particularly useful for women who do not use contraception regularly and / or systematically. For example, methods based on the assessment of the level of preganediol-3cc-glucuronide (PDG), a metabolite of progesterone, in a woman's urine have been considered. Indeed, progesterone, which is one of the sex hormones involved in the body's preparation for pregnancy, is metabolized and excreted in the urine as PDG when ovulation has occurred and so when the woman does not is more fertile.
Cependant, jusqu'à présent, les tests basés sur la détection de PDG sont d'utilisation complexe. Par exemple, on connaît de la demande EP0367615 une méthode pour évaluer la période infertile chez une femme, tenant compte notamment du niveau de PDG dans l'urine. La méthode proposée est cependant difficile à mettre en œuvre et demande l'étude préalable d'au moins un cycle menstruel. Par la suite, pas moins de quatre étapes successives sont nécessaires pour obtenir un résultat, le respect de cette succession d'étapes conditionnant la fiabilité du test. En outre, les contraintes liées aux conditions de conservation des différents réactifs intervenant dans ce test rendent pratiquement impossible son utilisation par une profane. However, until now, tests based on PDG detection are complex in use. For example, application EP0367615 discloses a method for evaluating the infertile period in a woman, taking into account, in particular, the level of PDG in the urine. The However, the proposed method is difficult to implement and requires the study of at least one menstrual cycle. Subsequently, no less than four successive steps are necessary to obtain a result, the respect of this succession of steps conditioning the reliability of the test. In addition, the constraints related to the storage conditions of the various reagents involved in this test make it practically impossible for it to be used by a layman.
Il existe donc un réel besoin pour les femmes de pouvoir disposer d'un test fiable et simple à mettre en œuvre leur permettant d'évaluer rapidement et par elles-mêmes si elles sont dans une période infertile ou au contraire dans une période de leur cycle à risque potentiel de grossesse en cas de rapport sexuel non protégé. L'invention a pour objectif de résoudre le problème énoncé ci-dessus, en proposant un dispositif révélant l'absence ou la présence de PDG dans l'urine tel qu'il permet à une femme de déterminer d'un simple coup d'œil si elle est ou non dans une période infertile. Plus précisément, le dispositif selon la présente invention est basé sur un principe de liaison immunologique compétitive permettant de détecter un seuil de PDG prédéterminé dans l'urine. Si le seuil prédéterminé est dépassé, l'ovulation a eu lieu au moins 24 heures avant, et la femme n'est plus dans une période fertile, et cela jusqu'au début du cycle suivant, date à laquelle le niveau de PDG dans l'urine s'effondre. A l'inverse, si le seuil prédéterminé n'est pas dépassé, la femme est dans une période de son cycle potentiellement fertile. Le dispositif selon l'invention permet donc à une femme de déterminer de manière fiable et à n'importe quel moment de son cycle, si elle est dans une période infertile ou non. Pour cela, le dispositif selon l'invention, destiné à recevoir un échantillon d'urine, contient non seulement un anticorps anti- PDG marqué apte à être entraîné par un flux d'urine, mais également du PDG exogène fixé en aval des anticorps anti-PDG. L'anticorps marqué est présent dans une concentration suffisante pour permettre une différenciation entre un échantillon d'urine contenant une concentration en PDG inférieure au seuil prédéterminé et un échantillon d'urine contenant une concentration en PDG supérieure au seuil prédéterminé. Selon l'invention, l'ensemble des réactifs nécessaires à l'évaluation du taux de PDG dans un échantillon d'urine est intégré dans le dispositif, de sorte qu'à part le dépôt de l'échantillon d'urine dans la partie dédiée du dispositif, aucune manipulation supplémentaire n'est requise pour pouvoir lire le résultat du test. L'invention a donc pour objet un dispositif pour l'identification de la période infertile d'une femme, comprenant successivement There is therefore a real need for women to have a reliable and simple test to implement allowing them to assess quickly and by themselves if they are in an infertile period or on the contrary in a period of their cycle at risk of pregnancy in case of unprotected intercourse. The object of the invention is to solve the problem stated above, by proposing a device revealing the absence or the presence of PDGs in the urine such that it enables a woman to determine at a glance. whether or not she is in an infertile period. More specifically, the device according to the present invention is based on a competitive immunological binding principle for detecting a predetermined PDG threshold in the urine. If the predetermined threshold is exceeded, ovulation has occurred at least 24 hours before, and the woman is no longer in a fertile period, and this until the beginning of the next cycle, the date at which the level of CEO in the urine collapses. Conversely, if the predetermined threshold is not exceeded, the woman is in a period of its potentially fertile cycle. The device according to the invention therefore allows a woman to reliably determine, at any time during her cycle, whether she is in an infertile period or not. For this, the device according to the invention, intended to receive a urine sample, contains not only a labeled anti-PDG antibody capable of being driven by a flow of urine, but also exogenous PDG attached downstream of the anti , Chairman and CEO. The labeled antibody is present in a concentration sufficient to allow differentiation between a urine sample containing a PDG concentration below the predetermined threshold and a urine sample containing a PDG concentration above the predetermined threshold. According to the invention, all the reagents necessary for the evaluation of the PDG level in a urine sample are integrated in the device, so that apart from the depositing of the urine sample in the dedicated part of the device, no further manipulation is required to read the test result. The invention therefore relates to a device for identifying the infertile period of a woman, comprising successively
- une zone de réception en matériau poreux sec, destinée à recevoir un échantillon d'urine, a receiving zone made of dry porous material, intended to receive a urine sample,
- une zone de réaction en matériau poreux sec comprenant au moins un anticorps anti- pregnanediol-3cc-glucuronide (PDG) marqué de manière détectable, ledit anticorps anti-PDG étant librement mobile dans les matériaux poreux lorsqu'ils sont à l'état humide, et a dry porous material reaction zone comprising at least one detectably labeled anti-pregnanediol-3cc-glucuronide (PDG) antibody, said anti-PDG antibody being freely mobile in the porous materials when wet; , and
- une zone de révélation en matériau poreux sec comprenant du PDG immobilisé, ledit PDG immobilisé étant apte à entrer en compétition avec du PDG contenu dans un échantillon d'urine une fois celui-ci déposé dans la zone de réception. Dans le contexte de l'invention, la « période infertile » d'un cycle ovarien correspond à la période comprise entre au moins 24 heures après l'ovulation et la fin du cycle considéré. Pendant cette période infertile, une femme souhaitant éviter une grossesse sait qu'elle peut avoir des rapports sexuels non protégés, en sachant que les risques de grossesse sont quasiment nuls. A l'inverse, une femme souhaitant tomber enceinte sait que durant cette période un rapport sexuel a très peu de chance d'aboutir à une grossesse. - A revelation zone of dry porous material comprising immobilized PDG, said immobilized PDG being able to compete with PDG contained in a urine sample once it deposited in the receiving zone. In the context of the invention, the "infertile period" of an ovarian cycle corresponds to the period between at least 24 hours after ovulation and the end of the cycle considered. During this infertile period, a woman wishing to avoid pregnancy knows that she can have unprotected sex, knowing that the chances of pregnancy are almost nil. Conversely, a woman wishing to become pregnant knows that during this period sexual intercourse is very unlikely to lead to pregnancy.
Dans le contexte de l'invention, la notion de « rapport sexuel non protégé » s'entend lorsqu' aucun moyen de contraception n'est utilisé ou lorsque le moyen de contraception n'est pas correctement utilisé (notamment, non-respect de la posologie en cas de contraception orale, rupture ou retrait du préservatif ou du diaphragme, erreur dans l'évaluation de la période d'abstinence, etc.), mais en aucun cas vis-à-vis des risques de transmission de maladie(s) sexuelle(s). In the context of the invention, the concept of "unprotected intercourse" means when no means of contraception is used or when the means of contraception is not properly used (in particular, non-compliance with dosage in case of oral contraception, rupture or withdrawal of the condom or diaphragm, error in the evaluation of the period of abstinence, etc.), but in no case vis-à-vis the risks of transmission of disease (s) sexual (s).
Dans le contexte de l'invention, on entend par « matériau poreux sec », un matériau poreux qui n'a pas encore été mis en contact avec un échantillon de liquide et notamment un échantillon d'urine. Plus généralement, on entend par « état sec » d'un matériau poreux, un état dans lequel aucun réactif non immobilisé n'est en mesure de migrer dans ledit matériau. In the context of the invention, the term "dry porous material", a porous material which has not yet been brought into contact with a liquid sample and in particular a urine sample. More generally, the term "dry state" of a porous material, a state in which no non-immobilized reagent is able to migrate into said material.
Le dispositif selon l'invention comporte préférentiellement au moins un support solide sur lequel sont ménagées les zones successives en matériau poreux sec. Notamment, le ou les supports solides peut(peuvent) être en matériau poreux sec. Il est également possible de prévoir que tout ou partie des zones en matériau poreux soient posées ou fixées sur le(s)dit(s) support(s) solide, ou fixées à celui-ci. The device according to the invention preferably comprises at least one solid support on which are formed the successive zones of dry porous material. In particular, the solid supports may be of dry porous material. It is also possible to provide all or part of the zones of porous material are laid or fixed on the (s) said (s) support (s) solid, or attached thereto.
Dans le contexte de l'invention, les terminologies « amont » et « aval » s'entendent par rapport à un flux d'urine qui serait déposé au niveau de la zone de réception. In the context of the invention, the terms "upstream" and "downstream" refer to a flow of urine that would be deposited at the receiving zone.
Selon l'invention, les différentes zones du dispositif sont disposées successivement, dans l'ordre d'énumération desdites zones, de manière à ce qu'un flux d'urine déposé au niveau de la zone de réception puisse transiter par capillarité par chacune desdites zones. Plus précisément, la zone de réception, ou extrémité amont, est adjacente à la zone de réaction, elle- même adjacente à la zone de révélation. Par "adjacente", on entend disposée "à côté de", sans être nécessairement accolée. La disposition des différentes zones doit cependant permettre leur humidification successive par un échantillon d'urine qui serait déposé sur la zone de réception. Ainsi, lorsqu'un flux d'urine déposé sur la zone de réception est absorbé par capillarité par les zones successives en matériau poreux, les anticorps anti-PDG peuvent être transportés depuis la zone de réaction jusque dans la zone de révélation par le flux d'urine. Les anticorps anti- PDG sont alors susceptibles de fixer le PDG immobilisé au niveau de la zone de révélation. According to the invention, the different zones of the device are arranged successively, in the order of enumeration of said zones, so that a flow of urine deposited at the level of the reception zone can pass by capillarity through each of said areas. More specifically, the receiving zone, or upstream end, is adjacent to the reaction zone, itself adjacent to the revelation zone. By "adjacent" is meant arranged "next to", without necessarily being contiguous. The arrangement of the different zones must, however, allow their successive humidification by a urine sample which would be deposited on the reception zone. Thus, when a flow of urine deposited on the receiving zone is absorbed by capillarity by the successive zones of porous material, the anti-PDG antibodies can be transported from the reaction zone to the revelation zone by the flow of 'urine. The anti-PDG antibodies are then likely to fix the immobilized PDG at the level of the revelation zone.
Selon l'invention, l'immobilisation du PDG peut être réalisée par toute technique appropriée, telle que adsorption ou des liaisons covalentes. Par exemple, le PDG peut être immobilisé sur le matériau poreux de la zone de révélation par liaison à une protéine support, telle que la sérumalbumine bovine. Dans un mode de réalisation, le PDG est uniformément immobilisé sur toute la surface de la zone de révélation. Dans un autre mode de réalisation, préféré, le PDG est immobilisé selon un motif particulier, tel qu'une bande transversale, sur ladite zone. According to the invention, the immobilization of the PDG can be carried out by any appropriate technique, such as adsorption or covalent bonds. For example, PDG can be immobilized on the porous material of the developing zone by binding to a carrier protein, such as bovine serum albumin. In one embodiment, the PDG is uniformly immobilized over the entire surface of the revelation zone. In another preferred embodiment, the PDG is immobilized in a particular pattern, such as a transverse band, on said area.
Dans un mode de réalisation de l'invention, le dispositif comprend en outre une zone de contrôle en matériau poreux sec, disposée préférentiellement en aval de la zone de révélation, au niveau de laquelle est immobilisé un anticorps spécifique d'un réactif de contrôle. Par exemple, le réactif de contrôle est une immunoglobuline G (IgG), préférentiellement non humaine. La zone de réaction comprend alors du réactif de contrôle marqué de manière détectable, librement mobile dans les matériaux poreux successifs lorsqu'ils sont à l'état humide. Lorsqu'un échantillon d'urine est déposé sur la zone de réception, le réactif de contrôle marqué est entraîné par le flux d'urine jusqu'à la zone de contrôle, où il peut se fixer sur les anticorps spécifiques. La détection des réactifs de contrôle dans ladite zone de contrôle permet de confirmer qu'il y a eu une humidification suffisante des zones successives par l'échantillon d'urine. Dans un mode de réalisation particulier, le réactif de contrôle marqué est une IgG de souris. L'anticorps spécifique du réactif de contrôle peut alors être un anticorps IgG de chèvre anti-souris. II peut par ailleurs être utile de prévoir une zone supplémentaire, ou extrémité d'absorption, en aval de la zone de contrôle, destinée à absorber l'excédent d'urine. In one embodiment of the invention, the device further comprises a control zone made of dry porous material, preferably disposed downstream of the revelation zone, at the level of which an antibody specific for a control reagent is immobilized. For example, the control reagent is an immunoglobulin G (IgG), preferentially non-human. The reaction zone then comprises detectably labeled, freely movable control reagent in the successive porous materials when in the wet state. When a urine sample is deposited on the receiving zone, the labeled control reagent is driven by the urine flow to the control zone, where it can bind to the specific antibodies. The detection of the control reagents in said control zone makes it possible to confirm that there has been sufficient humidification of the successive zones by the urine sample. In a particular embodiment, the labeled control reagent is mouse IgG. The specific antibody of the control reagent can then be a goat anti-mouse IgG antibody. It may also be useful to provide an additional zone, or absorption end, downstream of the control zone, intended to absorb excess urine.
Une fois l'échantillon d'urine déposé sur la zone de réception, l'urine est absorbée par les matériaux poreux successifs jusqu'à l'extrémité avale du dispositif. Le flux d'urine entraîne les composés marqués de manière détectable depuis la zone de réaction jusqu'à la zone de révélation et/ou de contrôle et/ou l'extrémité avale. Le principe de révélation du PDG selon l'invention repose sur un principe de compétition entre le PDG susceptible d'être présent dans l'échantillon d'urine et le PDG immobilisé sur le dispositif. Si le taux de PDG dans l'échantillon d'urine est inférieur à un seuil prédéterminé, les anticorps anti-PDG marqués peuvent se fixer au moins partiellement sur le PDG de la zone de révélation, où ils pourront être détectés. Selon l'invention, les composés marqués (anticorps anti-PDG et/ou réactif de contrôle contenus dans le dispositif) peuvent l'être par tout moyen connu permettant leur visualisation, préférentiellement à l'œil nu. Par exemple, les composés peuvent être marqués par un colorant, un isotope, ou un fluorochrome, les moyens de révélation étant adaptés au marquage choisi. Dans un mode de réalisation particulier, l'anticorps anti-PDG et/ou le réactif de contrôle sont marqués par couplage à des marqueurs p articulaire s, tels que des billes d'or colloïdal. Once the urine sample is deposited on the receiving zone, the urine is absorbed by the successive porous materials until the downstream end of the device. The urine stream entrains the detectably labeled compounds from the reaction zone to the revelation and / or control zone and / or the downstream end. The principle of revelation of the PDG according to the invention is based on a principle of competition between the PDG likely to be present in the urine sample and the PDG immobilized on the device. If the level of PDG in the urine sample is below a predetermined threshold, the labeled anti-PDG antibodies can bind at least partially to the PDG of the revealing zone, where they can be detected. According to the invention, the labeled compounds (anti-PDG antibody and / or control reagent contained in the device) may be by any known means for their visualization, preferably with the naked eye. For example, the compounds may be labeled with a dye, an isotope, or a fluorochrome, the developing means being adapted to the selected marking. In a particular embodiment, the anti-PDG antibody and / or the control reagent are labeled by coupling to p articular markers, such as colloidal gold beads.
Avantageusement, le dispositif comporte une membrane en nitrocellulose, formant tout ou partie des zones successives. Par exemple, le dispositif comporte une zone de réception en papier absorbant solidaire d'une zone de réaction également en papier absorbant, ladite zone de réaction étant solidaire d'une membrane en nitrocellulose sur laquelle sont ménagées la zone de révélation et la zone de contrôle. L'extrémité d'absorption peut, quant à elle, être constituée d'un papier absorbant rapporté sur l'extrémité avale de la membrane de nitrocellulose. Advantageously, the device comprises a nitrocellulose membrane, forming all or part of the successive zones. For example, the device comprises an absorbent paper receiving zone secured to a reaction zone also made of absorbent paper, said reaction zone being integral with a nitrocellulose membrane on which are formed the revealing zone and the control zone. . The absorption end may, in turn, consist of an absorbent paper attached to the downstream end of the nitrocellulose membrane.
Avantageusement, le dispositif a une forme générale en bandelette, dont les dimensions permettent une manipulation aisée. Notamment, la bandelette peut avoir une longueur comprise entre 5 et 10 cm et une largeur comprise entre 0,5 et 1 cm. Par longueur, on entend la plus grande dimension du dispositif, s'étendant depuis la zone de réception jusqu'à l'extrémité avale. Par largeur, on entend la plus petite dimension, s'étendant perpendiculairement à la longueur, dans un même plan. Advantageously, the device has a general strip form, whose dimensions allow easy handling. In particular, the strip may have a length of between 5 and 10 cm and a width of between 0.5 and 1 cm. By length, we mean the most large dimension of the device, extending from the receiving zone to the downstream end. By width is meant the smallest dimension, extending perpendicular to the length, in the same plane.
Dans un mode de réalisation particulier, tout ou partie de la bandelette ou des zones successives en matériau poreux est logé dans un boîtier de protection. Dans ce cas, le boîtier peut par exemple comporter un accès à la zone de réception pour l'échantillon d'urine et des fenêtres de lecture permettant de visualiser au moins partiellement les zone de révélation et/ou de contrôle depuis l'extérieur du boîtier. In a particular embodiment, all or part of the strip or successive zones of porous material is housed in a protective housing. In this case, the housing may for example include an access to the reception area for the urine sample and reading windows to at least partially visualize the revealing area and / or control from the outside of the housing .
Selon l'invention, lorsque la quantité de PDG contenue dans l'échantillon d'urine est supérieure à un certain seuil préalablement fixé, les anticorps anti-PDG marqués du dispositif se fixent tous au PDG urinaire et sont entraînés au-delà de la zone de révélation, de sorte qu'ils ne sont pas détectables. A l'inverse, lorsque la quantité de PDG dans l'échantillon d'urine est inférieure au dit seuil, les anticorps anti-PDG marqués se fixent au moins partiellement au PDG de la zone de réaction, au niveau de laquelle ils peuvent alors être détectés. Dans un exemple de réalisation particulier, le dispositif selon l'invention permet une révélation des anticorps anti-PDG marqués lorsque la quantité de PDG dans un échantillon d'urine est inférieure à une concentration seuil, préférentiellement comprise entre 5 et 15 μg de PDG par ml d'urine, et notamment inférieure ou égale à 10 μg/ml, +/- 2 μg/ml. Le seuil de 10μg/ml est particulièrement avantageux, car il offre une sécurité renforcée aux utilisatrices du dispositif, en évitant tout risque de faux positif. According to the invention, when the amount of PDG contained in the urine sample is above a certain threshold previously fixed, the labeled anti-PDG antibodies of the device all bind to the urinary PDG and are carried beyond the zone. revealing, so that they are not detectable. Conversely, when the amount of PDG in the urine sample is below said threshold, the labeled anti-PDG antibodies bind at least partially to the PDG of the reaction zone, at which point they can then be detected. In one particular embodiment, the device according to the invention makes it possible to reveal labeled anti-PDG antibodies when the amount of PDG in a urine sample is below a threshold concentration, preferably between 5 and 15 μg of PDG per ml of urine, and in particular less than or equal to 10 μg / ml, +/- 2 μg / ml. The threshold of 10 .mu.g / ml is particularly advantageous because it offers enhanced security to the users of the device, avoiding any risk of false positives.
L'invention propose également une méthode pour déterminer si une femme est dans une période infertile, ladite méthode comprenant la mise en contact d'un échantillon d'urine de la femme avec un dispositif selon l'invention, la détection du PDG immobilisé dans la zone de révélation étant indicatrice d'une période potentiellement fertile. Plus précisément, la détection d' anticorps anti-PDG marqués dans la zone de révélation indique que ovulation n' a pas encore eu lieu ou a eu lieu il y a moins de 24 heures. A l'inverse, l'absence d'anticorps anti-PDG marqués dans la zone de révélation est indicatrice d'une période infertile. Selon l'invention, la présence des anticorps anti-PDG marqués peut être visualisée par un motif coloré apparaissant dans la zone de révélation, les anticorps anti-PDG étant alors marqués par un marqueur coloré tel qu'un marqueur particulaire. Dans un exemple particulier, le marqueur coloré est de l'or colloïdal. Ainsi, la bande apparaissant dans la zone de révélation en période potentiellement fertile est de couleur rouge et peut être visualisée rapidement et de manière fiable. The invention also provides a method for determining whether a woman is in an infertile period, said method comprising contacting a urine sample of the woman with a device according to the invention, detecting the immobilized PDG in the revealing zone indicative of a potentially fertile period. More specifically, the detection of labeled anti-PDG antibodies in the revealing zone indicates that ovulation has not yet occurred or occurred less than 24 hours ago. In contrast, the absence of labeled anti-PDG antibodies in the revealing zone is indicative of an infertile period. According to the invention, the presence of the labeled anti-PDG antibodies can be visualized by a colored pattern appearing in the revealing zone, the anti-PDG antibodies being then labeled with a colored marker such as a particulate marker. In a particular example, the colored marker is gold colloidal. Thus, the band appearing in the revelation zone in potentially fertile period is red in color and can be visualized quickly and reliably.
Le dispositif selon l'invention peut s'avérer particulièrement utile pour une femme ne prenant pas de moyens de contraception et qui souhaite cependant éviter tout risque de grossesse en cas de rapports sexuels non protégés. En effet, si le test lui indique qu'elle est dans une période infertile, elle pourra avoir des rapports sexuels non protégés sans crainte de grossesse, et cela jusqu'au début du cycle suivant. A l'inverse, tant que les résultats du test lui indiquent qu'elle est dans une période potentiellement à risque de grossesse, la femme prendra soin d'éviter tout rapport sexuel non protégé. Il est à noter que le test selon l'invention peut être pratiqué à tout moment du cycle et renouvelé si besoin jusqu'à l'identification de la période infertile. The device according to the invention may be particularly useful for a woman not taking contraceptives and who wishes however to avoid any risk of pregnancy in case of unprotected sex. Indeed, if the test indicates that she is in an infertile period, she can have unprotected sex without fear of pregnancy, until the beginning of the next cycle. Conversely, as long as the test results indicate that she is in a potentially risky period of pregnancy, the woman will take care to avoid unprotected intercourse. It should be noted that the test according to the invention can be practiced at any moment of the cycle and renewed if necessary until the identification of the infertile period.
Par ailleurs, le dispositif selon l'invention peut être utilisé par une femme souhaitant éviter tout risque de grossesse et qui a eu un rapport sexuel non protégé. En pratiquant le test moins de six heures après le rapport sexuel non protégé, elle peut vérifier qu'elle n'était pas dans une période à risque de grossesse. Dans le cas inverse, elle peut alors envisager de recourir à une contraception d'urgence. Moreover, the device according to the invention can be used by a woman wishing to avoid any risk of pregnancy and who has had unprotected sex. By practicing the test less than six hours after unprotected sex, she can check that she is not in a period of risk of pregnancy. In the opposite case, she may then consider using emergency contraception.
De manière alternative, le dispositif selon l'invention peut s'avérer utile pour une femme désirant un enfant. En effet, un couple en désir d'enfant accroît généralement le nombre de ses rapports sexuels, pour augmenter les chances de fécondation. Cependant, durant toute la période infertile du cycle ces rapports ne permettront pas d'aboutir à une grossesse. En utilisant le dispositif selon l'invention, la femme peut aisément déterminer la période infertile de son cycle, et ainsi savoir qu'à partir de ce moment-là tout rapport sexuel sera infertile, et cela jusqu'au début du cycle suivant. Il lui est alors possible, si elle le souhaite, d'interrompre ses activités sexuelles. Alternatively, the device according to the invention may be useful for a woman wanting a child. In fact, a couple in desire of child generally increases the number of their sexual intercourse, to increase the chances of fertilization. However, during the entire infertile period of the cycle these reports will not lead to a pregnancy. By using the device according to the invention, the woman can easily determine the infertile period of her cycle, and thus know that from that moment all sexual intercourse will be infertile, and that until the beginning of the next cycle. It is then possible for her, if she wishes, to interrupt her sexual activities.
L'invention sera mieux comprise à la lecture de la description qui suit et à l'examen des figures qui l'accompagnent. Celles-ci sont présentées à titre indicatif et nullement limitatif de l'invention. Les figures représentent : The invention will be better understood on reading the description which follows and on examining the figures which accompany it. These are presented as an indication and in no way limitative of the invention. The figures represent:
Figure 1 : Une représentation schématique d'un premier exemple de réalisation du dispositif selon l'invention ; Figure 2 : Une représentation schématique en coupe d'un dispositif selon l'invention et des réactifs qu'il contient ; Figure 1: A schematic representation of a first embodiment of the device according to the invention; Figure 2: A schematic representation in section of a device according to the invention and reagents it contains;
Figure 3 : Une représentation d'un exemple de réalisation du dispositif de l'invention muni d'un boîtier. Figure 3: A representation of an exemplary embodiment of the device of the invention provided with a housing.
La figure 1 montre un exemple de réalisation d'un dispositif 10 pour l'identification de la période fertile d'une femme, selon l'invention, de forme générale en bandelette allongée. Le dispositif 10 comprend un support 11, préférentiellement rigide, sur lequel repose une membrane en nitrocellulose 12. Une zone de révélation 13 et une zone de contrôle 14 se succèdent le long de ladite membrane 12. Le dispositif 10 comprend en outre une zone de réception 15 en matériau poreux et une zone de réaction 16, adjacente, également en matériau poreux. Par exemple, ces deux zones 15 et 16 sont chacune constituées d'un papier absorbant solidarisé au support 11, par collage ou autre. FIG. 1 shows an exemplary embodiment of a device 10 for identifying the fertile period of a woman, according to the invention, of generally elongated strip form. The device 10 comprises a support 11, preferably rigid, on which a nitrocellulose membrane 12 rests. A revealing zone 13 and a control zone 14 follow one another along said membrane 12. The device 10 further comprises a reception zone 15 of porous material and an adjacent reaction zone 16, also of porous material. For example, these two zones 15 and 16 each consist of an absorbent paper secured to the support 11, by gluing or otherwise.
Comme cela est visible sur la figure 1, la zone de réception 15 chevauche partiellement la zone de réaction 16, de sorte qu'un échantillon d'urine déposé au niveau de la zone de réception 15 va pouvoir humidifier également la zone de réaction 16 aval. De même, la membrane en nitrocellulose 12, disposée en aval de la zone de réaction 16 est au contact de ladite zone de réaction 16, ce qui permet qu'un échantillon d'urine humidifiant la zone de réaction 16 puisse également humidifier la membrane 12. As can be seen in FIG. 1, the receiving zone 15 partially overlaps the reaction zone 16, so that a urine sample deposited at the receiving zone 15 will also be able to humidify the reaction zone 16 downstream. . Similarly, the nitrocellulose membrane 12 disposed downstream of the reaction zone 16 is in contact with said reaction zone 16, which allows a urine sample moistening the reaction zone 16 to also humidify the membrane 12 .
Enfin, une extrémité avale 17, ou zone d'absorption, est disposée en aval de la membrane de nitrocellulose 12, qu'elle recouvre partiellement. La zone d'absorption 17 est ainsi en mesure d'absorber un éventuel excédent d'urine par capillarité. Finally, a downstream end 17, or absorption zone, is disposed downstream of the nitrocellulose membrane 12, which it overlaps partially. The absorption zone 17 is thus able to absorb any excess urine by capillarity.
Le dispositif 10 a une forme générale allongée, les zones en matériau poreux 15, 16, 13, 14 et 17 s'étendant successivement dans une plus grande dimension, ou longueur, dudit dispositif 10. The device 10 has a generally elongate shape, the areas of porous material 15, 16, 13, 14 and 17 extending successively in a larger dimension, or length, of said device 10.
Sur la figure 2 sont représentées, de manière schématique, les différentes zones d'un dispositif 20 selon l'invention sous forme de bandelette, ainsi que les réactifs qu'elles contiennent. In Figure 2 are shown schematically the different areas of a device 20 according to the invention in strip form, and the reagents they contain.
Ainsi, une zone de réaction 22, disposée en aval d'une zone de réception 21, contient un réactif de contrôle 26 marqué de manière détectable, ainsi que des anticorps anti-PDG 27, également marqués de manière détectable. Le réactif de contrôle 26 comme les anticorps anti-PDG 27 sont par exemple déposés à la surface du matériau poreux formant la zone de réaction 22. Ils peuvent autrement être contenus dans le matériau poreux. Dans tous les cas, le réactif de contrôle 26 et les anticorps anti-PDG 27 ne sont pas solidaires de la zone de réaction 22 et peuvent se déplacer dans et/ou sur le matériau poreux lorsqu'il est à l'état humide, ainsi que dans et/ou sur des matériaux poreux humides situés en aval. Thus, a reaction zone 22, disposed downstream of a receiving zone 21, contains a detectably labeled control reagent 26, as well as anti-PDG antibodies 27, also detectably labeled. The control reagent 26 as the anti-PDG antibodies 27 are for example deposited on the surface of the porous material forming the reaction zone 22. They may otherwise be contained in the porous material. In any case, the control reagent 26 and the anti-PDG antibodies 27 are not integral with the reaction zone 22 and can move in and / or on the porous material when it is wet, as well as only in and / or on wet porous materials downstream.
Une zone de révélation 23 et une zone de contrôle 24 se succèdent le long de la bandelette, qui se termine par une extrémité avale 25 pour absorber l'excédent d'urine. Du PDG 28 est immobilisé par exemple au moyen de sérum albumine bovine (non représenté) sur la zone de révélation 23. Des anticorps anti-réactif de contrôle 29 sont quant à eux immobilisés sur la zone de contrôle 24, par exemple au moyen de sérum albumine bovine (non représenté). A revelation zone 23 and a control zone 24 follow each other along the strip, which terminates in an end swallowed to absorb excess urine. PDG 28 is immobilized for example by means of bovine serum albumin (not shown) on the revelation zone 23. Control anti-reagent antibodies 29 are themselves immobilized on the control zone 24, for example by means of serum bovine albumin (not shown).
Le flux d'urine d'un échantillon d'urine, lorsqu'il est déposé sur la zone de réception 21, est représenté par une flèche s'étendant depuis ladite zone de réception 21 jusqu'à l'extrémité avale 25. The urine flow of a urine sample, when deposited on the receiving zone 21, is represented by an arrow extending from said receiving zone 21 to the downstream end 25.
Lorsque l'urine humidifie la zone de réception 22 pour gagner ensuite les zones 23, 24, 25 disposées en aval, elle entraîne avec elle le réactif de contrôle 26 et les anticorps anti-PDG 27. En fonction de la concentration en PDG dans l'échantillon d'urine (PDG endogène) et donc en fonction de la période du cycle de la femme, une quantité plus ou moins importante voire nulle d'anticorps anti-PDG va pouvoir se fixer au PDG 28 de la zone de révélation 23. Les anticorps anti-PDG marqués déjà liés à du PDG endogène ne seront pas retenus au niveau de la zone de révélation 23 et seront évacués en même temps que l'excédent d'urine dans la zone d'absorption 25. Les anticorps anti-PDG marqués qui se seront liés au PDG fixé sur la zone de révélation 23, par contre, pourront être détectés par l'utilisatrice au niveau de ladite zone 23 à la fin du test. De manière similaire, le réactif de contrôle 26 va être entraîné jusqu'à la zone de contrôle 24 où il va se fixer aux anticorps anti-réactif de contrôle 29. La détection des réactifs de contrôle 26 marqués au niveau de la zone de contrôle 24 permet de confirmer que le test s'est déroulé convenablement et que le résultat obtenu au niveau de la zone de révélation 23 est fiable. When the urine moistens the receiving zone 22 to then reach the zones 23, 24, 25 disposed downstream, it carries with it the control reagent 26 and the anti-PDG antibodies 27. Depending on the concentration of PDG in the Urine sample (endogenous PDG) and therefore depending on the period of the woman's cycle, a greater or lesser amount of anti-PDG antibody will be able to be attached to the PDG 28 of the revelation zone 23. The labeled anti-PDG antibodies already bound to endogenous PDG will not be retained at the revelation zone 23 and will be evacuated together with the excess urine in the absorption zone 25. The anti-PDG antibodies However, those marked which are bound to the CEO fixed on the revealing zone 23, on the other hand, may be detected by the user at said zone 23 at the end of the test. Similarly, the control reagent 26 will be driven to the control zone 24 where it will bind to the control anti-reagent antibodies 29. The detection of the labeled control reagents 26 at the control zone 24 confirms that the test has been conducted properly and that the result obtained at the revelation zone 23 is reliable.
Avantageusement, les anticorps anti-PDG 27 et les réactifs de contrôle 26 sont marqués de manière détectable, de sorte que la détection de leur présence au niveau de la zone de révélation 23 et de la zone de contrôle 24 respectivement, se fait directement, sans que l'ajout d'un composé révélateur additionnel et/ou l'utilisation d'un dispositif spécifique ne soit requis. Par exemple, le marquage se fait au moyen d'un colorant ou de particules colorées, telles que des particules d'or colloïdal. L'utilisatrice peut ainsi visualiser directement un marquage coloré sur les zones d'intérêt 23, 24. Advantageously, the anti-PDG antibodies 27 and the control reagents 26 are detectably labeled, so that the detection of their presence at the level of the revelation zone 23 and of the control zone 24 respectively, is done directly, without the addition of an additional developer compound and / or the use of a specific device is required. By for example, the labeling is done by means of a dye or colored particles, such as colloidal gold particles. The user can thus directly visualize a colored marking on the areas of interest 23, 24.
La figure 3 montre également un exemple de réalisation d'un dispositif 30 selon l'invention, selon lequel une bandelette comprenant les zones successives en matériaux poreux est logée dans un boîtier muni d'un capuchon 31. Plus précisément, le capuchon 31 recouvre l'extrémité amont de la bandelette, et permet une fois retiré de libérer un accès à la zone de réception 32 du dispositif 30. Une utilisatrice peut alors déposer un échantillon d'urine sur la zone de réception 32. L'échantillon d'urine peut être déposé soit un orientant la zone de réception 32 directement sous un jet d'urine, soit en trempant ladite zone de réception 32 dans un récipient contenant un échantillon d'urine. FIG. 3 also shows an exemplary embodiment of a device 30 according to the invention, according to which a strip comprising successive zones made of porous materials is housed in a housing provided with a cap 31. More specifically, the cap 31 covers the the upstream end of the strip, and once removed to release access to the receiving area 32 of the device 30. A user can then deposit a urine sample on the receiving area 32. The urine sample can be deposited either a directing the receiving area 32 directly under a stream of urine, or by soaking said receiving area 32 in a container containing a urine sample.
D'une manière générale, le matériau poreux utilisé pour former l'extrémité de réception du dispositif selon l'invention est avantageusement tel qu'il est dans un état humide suffisant à la bonne pratique du test après 5 à 15 secondes sous un jet d'urine, ou après 5 à 15 secondes immergé dans un échantillon d'urine. In general, the porous material used to form the receiving end of the device according to the invention is advantageously such that it is in a wet state sufficient for the good practice of the test after 5 to 15 seconds under a jet of water. urine, or after 5 to 15 seconds immersed in a urine sample.
Le boîtier comprend également un corps principal 33 dans lequel sont logées la zone de réaction, la zone de détection et la zone de contrôle. La zone de réaction est entièrement recouverte par le corps principal 33 et n'est pas visible dans le boîtier. Par contre, deux fenêtres 34 et 35 sont ménagées sur le corps principal 33 qui permettent respectivement de visualiser au moins partiellement la zone de détection et la zone contrôle, depuis l'extérieur du corps principal 33. Enfin, une extrémité avale 36 du boîtier recouvre la zone d'absorption destinée à récupérer un potentiel excédant d'urine. The housing also comprises a main body 33 in which are housed the reaction zone, the detection zone and the control zone. The reaction zone is entirely covered by the main body 33 and is not visible in the housing. On the other hand, two windows 34 and 35 are provided on the main body 33 which respectively make it possible to visualize at least partially the detection zone and the control zone, from the outside of the main body 33. Finally, a downstream end 36 of the housing covers the absorption zone intended to recover an excess potential of urine.

Claims

REVENDICATIONS
1- Dispositif (10, 20, 30) pour l'identification de la période infertile d'une femme, comprenant successivement - une zone de réception (15, 21, 32) en matériau poreux sec, destinée à recevoir un échantillon d'urine, 1- Device (10, 20, 30) for the identification of the infertile period of a woman, comprising successively - a reception zone (15, 21, 32) made of dry porous material, intended to receive a urine sample ,
- une zone de réaction (16, 22) en matériau poreux sec comprenant au moins un anticorps anti- pregnanediol-3cc-glucuronide (PDG) marqué de manière détectable (27), ledit anticorps anti- PDG étant librement mobile dans les matériaux poreux lorsqu'ils sont à l'état humide, et - une zone de révélation (13, 23, 34) en matériau poreux sec comprenant du PDG immobilisé (28), ledit PDG immobilisé étant apte à entrer en compétition avec du PDG présent dans un échantillon d'urine une fois celui-ci déposé dans la zone de réception. a reaction zone (16, 22) of dry porous material comprising at least one detectably-labeled anti-pregnanediol-3cc-glucuronide (PDG) antibody (27), said anti-PDG antibody being freely mobile in the porous materials when they are in the wet state, and - a revelation zone (13, 23, 34) of dry porous material comprising immobilized PDG (28), said immobilized PDG being able to compete with PDG present in a sample urine once it has been deposited in the receiving area.
2- Dispositif selon la revendication 1, dans lequel la zone de réaction comprend également au moins un réactif de contrôle (26) marqué de manière détectable, librement mobile dans les matériaux poreux successifs lorsqu'ils sont à l'état humide, et comprenant en outre une zone de contrôle (14, 24, 35) en matériau poreux sec, adjacente à la zone de révélation, sur lequel un anticorps spécifique du réactif de contrôle (29) est immobilisé. 2- Device according to claim 1, wherein the reaction zone also comprises at least one control reagent (26) detectably labeled, freely movable in the successive porous materials when they are in the wet state, and comprising in particular in addition to a control zone (14, 24, 35) made of dry porous material, adjacent to the revelation zone, on which an antibody specific for the control reagent (29) is immobilized.
3- Dispositif selon la revendication 2, dans lequel le réactif de contrôle est une immunoglobuline G (IgG) d'un mammifère non-humain, préférentiellement une IgG de souris, et l'anticorps est un anticorps IgG, préférentiellement un anticorps IgG de chèvre anti-souris. 3. The device as claimed in claim 2, in which the control reagent is an immunoglobulin G (IgG) of a non-human mammal, preferentially a mouse IgG, and the antibody is an IgG antibody, preferably a goat IgG antibody. anti-mouse.
4- Dispositif selon l'une quelconque des revendications précédentes, dans lequel l'anticorps anti-PDG et/ou le réactif de contrôle sont marqués de manière détectable par couplage à des marqueurs particulaires, tels que des billes d'or colloïdal. The device according to any one of the preceding claims, wherein the anti-PDG antibody and / or the control reagent are detectably labeled by coupling to particulate markers, such as colloidal gold beads.
5- Dispositif selon l'une quelconque des revendications précédentes, comprenant une membrane de nitrocellulose (12) sur laquelle sont ménagées la zone de révélation et/ou la zone de contrôle. 5. Device according to any one of the preceding claims, comprising a nitrocellulose membrane (12) on which are formed the revealing zone and / or the control zone.
6- Dispositif selon l'une quelconque des revendications précédentes, dans lequel le PDG immobilisé dans la zone de révélation est lié à une protéine support, telle que la sérumalbumine bovine. 6. Device according to any one of the preceding claims, wherein the PDG immobilized in the revelation zone is bound to a carrier protein, such as bovine serum albumin.
7- Dispositif selon l'une quelconque des revendications précédentes, comprenant en outre une extrémité d'absorption (17, 25) en matériau poreux, disposée à une extrémité opposée à la zone de réception de l'urine, destinée à absorber un excédent d'urine, une fois l'échantillon d'urine déposé dans la zone de réception et au moins partiellement absorbé par les matériaux poreux successifs amont. 7- Device according to any one of the preceding claims, further comprising an absorption end (17, 25) of porous material, disposed at an end opposite the urine receiving zone, for absorbing a surplus of urine, once the urine sample is deposited in the receiving zone and at least partially absorbed by the successive porous materials upstream.
8- Dispositif selon l'une quelconque des revendications précédentes, dans lequel la quantité d'anticorps anti-PDG contenue dans la zone de réaction permet une détection du PDG marqué lorsque la concentration en PDG dans l'échantillon d'urine est inférieure ou égale à une valeur seuil prédéterminée, comprise entre 5 et 15 μg/ml, préférentiellement inférieure ou égale à 10 μg/ml +/- 2 μg/ml. The device according to any one of the preceding claims, wherein the amount of anti-PDG antibody contained in the reaction zone allows detection of labeled PDG when the PDG concentration in the urine sample is less than or equal to at a predetermined threshold value of between 5 and 15 μg / ml, preferably less than or equal to 10 μg / ml +/- 2 μg / ml.
9- Dispositif selon l'une quelconque des revendications précédentes, comprenant en outre un boîtier de protection (31, 33, 36) dans lequel sont logées les zones successives en matériaux poreux. 9- Device according to any one of the preceding claims, further comprising a protective housing (31, 33, 36) in which are housed the successive areas of porous materials.
10- Méthode pour déterminer si une femme est dans une période infertile, ladite méthode comprenant la mise en contact d'un échantillon d'urine de la femme avec un dispositif selon l'une des revendications précédentes, l'absence d'apparition d'un signal coloré dans la zone de révélation étant indicatrice d'une période infertile. 10- Method for determining whether a woman is in an infertile period, said method comprising contacting a urine sample of the woman with a device according to one of the preceding claims, the absence of occurrence of a colored signal in the revelation zone being indicative of an infertile period.
11- Méthode selon la revendication 10, dans laquelle aucun signal coloré n'apparaît tant que la concentration en PDG dans l'urine de la femme est supérieure ou égale à une valeur seuil prédéterminée, comprise entre 5 et 15 μg/ml, préférentiellement supérieure ou égale à 10 μg/ml +/- 2 μg/ml. 11- Method according to claim 10, in which no colored signal appears as long as the concentration of PDG in the woman's urine is greater than or equal to a predetermined threshold value of between 5 and 15 μg / ml, preferably greater than or equal to 10 μg / ml +/- 2 μg / ml.
12. Utilisation d'un dispositif selon l'une quelconque des revendications 1 à 9, pour déterminer si une femme ne désirant pas de grossesse peut avoir des rapports sexuels non protégés. 12. Use of a device according to any one of claims 1 to 9, to determine whether a woman not desiring pregnancy can have unprotected sex.
13. Utilisation d'un dispositif selon l'une quelconque des revendications 1 à 9, pour déterminer si une femme en désir de grossesse peut réduire ses activités sexuelles. 13. Use of a device according to any one of claims 1 to 9, to determine whether a woman in desire of pregnancy can reduce her sexual activities.
PCT/FR2016/050506 2015-03-06 2016-03-04 Device for identifying a woman's infertile period WO2016142610A1 (en)

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FR1551919A FR3033410B1 (en) 2015-03-06 2015-03-06 DEVICE FOR IDENTIFYING THE INFERTILE PERIOD OF A WOMAN

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3335638A1 (en) 2016-12-13 2018-06-20 Colorimetrix GmbH Method and device for estimation of ovulation date
EP3731751A4 (en) * 2017-12-28 2021-10-13 MFB Fertility, Inc. Systems and methods for tracking progesterone
US11573225B2 (en) 2017-02-17 2023-02-07 MFB Fertility, Inc. System for evaluating urine for the presence or absence of pregnanediol glucuronide and other hormones and analytes

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0367615A2 (en) 1988-11-04 1990-05-09 Quidel Corporation Method and kit for determining periodic infertility in females
WO1998039657A1 (en) * 1997-03-06 1998-09-11 Quidel Corporation Quantitative lateral flow assays and devices
US6352862B1 (en) * 1989-02-17 2002-03-05 Unilever Patent Holdings B.V. Analytical test device for imuno assays and methods of using same
WO2007049157A2 (en) * 2005-10-24 2007-05-03 Manawatu Biotech Investments Ltd. (Mbil) Ovulation cycle monitoring and management
WO2013132338A2 (en) * 2012-03-06 2013-09-12 Calpro As Competitive immunoassay for calprotectin

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0367615A2 (en) 1988-11-04 1990-05-09 Quidel Corporation Method and kit for determining periodic infertility in females
US6352862B1 (en) * 1989-02-17 2002-03-05 Unilever Patent Holdings B.V. Analytical test device for imuno assays and methods of using same
WO1998039657A1 (en) * 1997-03-06 1998-09-11 Quidel Corporation Quantitative lateral flow assays and devices
WO2007049157A2 (en) * 2005-10-24 2007-05-03 Manawatu Biotech Investments Ltd. (Mbil) Ovulation cycle monitoring and management
WO2013132338A2 (en) * 2012-03-06 2013-09-12 Calpro As Competitive immunoassay for calprotectin

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
R. ECOCHARD ET AL: "Use of urinary pregnanediol 3-glucuronide to confirm ovulation", STEROIDS, vol. 78, no. 10, 1 October 2013 (2013-10-01), pages 1035 - 1040, XP055196704, ISSN: 0039-128X, DOI: 10.1016/j.steroids.2013.06.006 *

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3335638A1 (en) 2016-12-13 2018-06-20 Colorimetrix GmbH Method and device for estimation of ovulation date
WO2018109025A1 (en) 2016-12-13 2018-06-21 Colorimetrix Gmbh Method and device for estimation of ovulation date
US11730456B2 (en) 2016-12-13 2023-08-22 Colorimetrix Gmbh Method and device for estimation of ovulation date
US11573225B2 (en) 2017-02-17 2023-02-07 MFB Fertility, Inc. System for evaluating urine for the presence or absence of pregnanediol glucuronide and other hormones and analytes
EP3731751A4 (en) * 2017-12-28 2021-10-13 MFB Fertility, Inc. Systems and methods for tracking progesterone

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