WO2012153048A1 - Device for analyzing a liquid sample - Google Patents
Device for analyzing a liquid sample Download PDFInfo
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- WO2012153048A1 WO2012153048A1 PCT/FR2012/050996 FR2012050996W WO2012153048A1 WO 2012153048 A1 WO2012153048 A1 WO 2012153048A1 FR 2012050996 W FR2012050996 W FR 2012050996W WO 2012153048 A1 WO2012153048 A1 WO 2012153048A1
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- sensor
- liquid sample
- measuring
- connection means
- sensors
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/483—Physical analysis of biological material
- G01N33/487—Physical analysis of biological material of liquid biological material
- G01N33/49—Blood
- G01N33/492—Determining multiple analytes
Definitions
- the present invention relates to the field of biomedical analysis, and particularly relates to a system comprising a device of the consumable type for the analysis of a liquid sample, in particular water or a biological solution such as a drop of blood.
- This analysis consists of measuring the pH, the oxidation-reduction potential and the electrical resistivity of the fluid.
- This analysis is then interpreted to determine the health status of the biological fluid donor.
- This device is advantageous in that it reduces the size of the system by miniaturizing the sensors used in the device of US2886771.
- the present invention aims to solve all or part of the disadvantages mentioned above.
- the subject of the present invention is an analysis system characterized in that it comprises a device for analyzing a liquid sample, in particular water or a biological solution such as a drop of blood, of the consumable type and comprising a substrate on which is deposited a set of sensors comprising at least a first sensor for measuring the pH of the liquid sample, a second sensor for measuring the oxidation-reduction potential of the liquid sample, a third sensor for measuring the resistivity or the conductivity electrical liquid sample, a set of connection means of all the sensors, and a reading interface of the device comprising a set of complementary connection means arranged to be connected to the set of connection means of the device, means for processing the measurement values of the set of sensors, representation means in at least three dimensions of the analysis of the liquid sample as a function of the processing of the values of the meters means for processing, means for interpreting the means of representation, said interpreting means of representation, said interpreting means being arranged to provide an analysis result, based on a comparison the position of a representative point of the measurements made and reference regions defined in
- This arrangement makes it possible to provide a system with a device of the consumable type that does not require a large quantity of liquid sample, which is simple to manufacture and at a lower cost, which makes it compatible with mass production in series.
- reference regions can be achieved through the use of reference point clouds, reference surfaces or reference volumes.
- the sensor assembly includes a fourth sensor for measuring the temperature of the liquid sample
- the set of connection means comprises first connection means of the first sensor, second connection means of the second sensor, and third connection means of the third sensor,
- the set of connection means comprises fourth connection means of the fourth sensor.
- the device comprises a surface layer maintained on the substrate by connecting means, said layer surface comprising at least one means for receiving the liquid sample, a microfluidic channel arranged to connect said at least one receiving means to at least one sensor of the set of sensors.
- This arrangement makes it possible to preserve the fluidity of the liquid sample by isolating it as much as possible from the air and also makes it possible to reduce to a minimum the quantity of fluid required by guiding it directly towards the sensors.
- the substrate is made of a silicon-based material.
- the surface layer is made of a material based on polymers.
- connection means of the surface layer on the substrate comprise glue.
- the first sensor comprises a reference electrode disposed inside a reservoir in communication with the microfluidic channel.
- the first sensor is of the ISFET type, thin potentiometric film or comprises an optical probe.
- the second sensor comprises a measuring electrode intended to be immersed in the liquid sample.
- the third sensor comprises two measuring electrodes intended to come into direct contact with the sample.
- the processing means consider that the value of the measurements of the first three sensors is a function of the measurement value of the fourth temperature sensor.
- Figure 1 shows a top view of the device included in the system according to the invention.
- Figure 2 shows a perspective view of the device included in the system according to the invention.
- Figure 3 shows a view of a system according to the invention.
- a device 1 of a system 100 for the analysis of a liquid sample comprises a substrate 2 on which a set of sensors 10 is deposited.
- This device 1 is of the consumable type and is therefore intended to be used once and to be discarded after use.
- This set of sensors 1 0 comprises a first sensor 1 1 for measuring the pH of the liquid sample, a second sensor 12 for measuring the oxidation-reduction potential of the liquid sample, a third sensor 13 for measuring the resistivity or the electrical conductivity of the liquid sample, and a fourth sensor 14 for measuring the temperature of the sample.
- Substrate 2 is made of a silicon-based material such as glass.
- the substrate 2 has a parallelepipedal shape with an upper face 3 having so-called lower edges 3a, left 3b, upper 3c and right 3d, these qualifiers being only arbitrary and being used here only for ease of identification on the different FIGS.
- the various sensors 1 1, 12, 13, 14 are formed by one or two electrodes which extend to the lower edge 3a of the upper face 3 of the substrate 2 to form a set of connection means 20 of the different sensors 1 1, 12, 13, 14 with a set of complementary connection means 20 'disposed on an analysis reader 50.
- this set of sensors 20 comprises first connection means 21 of the first sensor 1 1, second connection means 22 of the second sensor 1 2, third connection means 23 of the third sensor 13 and fourth connection means 24 of the fourth sensor 14.
- the first connection means 21 of the first sensor 1 1 are formed by the termini 1 1 a 'of a measuring electrode 11a and the end 1 1 b' of a reference electrode 11b.
- the termination 1 1 1 'of the measuring electrode 1 1a is disposed near the middle of the lower edge 3a of the upper face 3 of the substrate 2 while the termination 1 1 b' of the reference electrode 1 1b is eccentrically disposed at the lower edge 3a of the upper face 3 of the substrate 2 near the right edge 3d.
- the second connection means 22 of the second sensor 12 are formed by the termination 12a 'of a single measuring electrode 12a.
- the termination 1 2a 'of the measuring electrode 1 2a is disposed to the left of the termination 1 1 a' of the measuring electrode 1 1a of the first sensor January 1.
- the third connection means 23 of the third sensor 13 are formed by the termination 13a 'of a first measuring electrode 13a and the termination 13b' of a second measuring electrode 13b.
- the termination 1 3a 'of the first measuring electrode 1 3a is disposed to the left of the termination 1 2a' of the measuring electrode 1 2a of the second sensor 12 and the second termination 13b 'of the second measuring electrode 1 3b is arranged to the left of the termination 1 3a 'of the first measuring electrode 13a of the third sensor 13.
- the fourth connection means 24 of the fourth sensor 14 are formed by the termination 14a 'of a first measuring electrode 14a and by the termination 14b' of a second electrode 14b.
- the termination 14a 'of the first measuring electrode 14a is located to the right of the termination 1 1a' of the measuring electrode 11a of the first sensor 11 and the second termination 14b 'of the second measuring electrode 14b is located to the right of the termination 14a 'of the first measuring electrode 14a of the fourth sensor 14.
- Electrochemical precipitates are formed essentially platinum-based but may include an iridium oxide or a silver compound such as silver chloride for the reference electrode 11b of the first sensor 11 .
- the first sensor 1 1 intended for measuring the pH comprises a first measurement electrode 11a made from a field effect transistor of the ISFET type (Ion Sensitive Field Effect Transistor) itself made of semiconductor material. like silicon.
- ISFET type Ion Sensitive Field Effect Transistor
- the solution is in direct contact on the one hand with the insulating layer of the gate which controls the current flux of the transistor, and on the other hand with a reference electrode 11b realrise in silver / silver chloride (Ag / AgCl) which replaces the metallic layer of the grid.
- this ISFET sensor may be replaced by a potentiometric thin film sensor or may include an optical probe.
- the second sensor 1 2 is intended for measuring the oxidation-reduction or redox potential. This measurement is based on the difference in potential between a measuring electrode and a reference electrode. Since the reference electrode 11b of the first sensor can serve as a reference electrode for the second sensor 12, the second sensor 12 does not need any additional reference electrode and therefore only comprises a single electrode 12a. made of platinum.
- the third sensor 13 is intended for measuring the conductivity or the electrical resistivity, one size being the opposite of the other.
- One of these magnitudes can be determined by measuring the current flowing through two electrodes, made of platinum, when an alternating current is applied to these two measuring electrodes 13a, 13b.
- These two electrodes 3a, 13b are arranged to be in contact with the liquid sample and the voltage across these two electrodes 13a, 13b is of the order of a few hundred millivolts.
- the fourth sensor 14 is intended for measuring the temperature of the liquid sample. This sensor 14 is necessary to compensate for the output values of the other three sensors whose magnitudes depend on the temperature.
- This fourth sensor 14 is of the platinum resistance temperature sensor (PRTD) type thus comprising two platinum electrodes 14a, 14b. In contact with the liquid sample, the temperature thereof varies the resistance between the two electrodes 14a, 14b of the fourth sensor 14.
- PRTD platinum resistance temperature sensor
- the substrate 2 is partly covered by a surface layer 4 maintained on the substrate 2 by bonding means such as glue.
- This surface layer 4 is made of a material based on polymers, such as plastic.
- the surface layer 4 comprises three receiving means 5, 6, 7 of the liquid sample.
- These receiving means 5, 6, 7 have a cup shape open on their bottom to pass through the surface layer 4 and allow the liquid sample to reach the substrate 2.
- the first two receiving means 5, 6 are arranged on either side of an alignment of the set of sensors 1 0 and are in communication with each other via a microfluidic channel. 8 formed on the surface of the surface layer disposed facing the substrate 2.
- a liquid sample poured into one of the first two receiving means 5, 6 flows by capillary action inside the microfluidic channel 8 and comes into contact with the measuring electrodes of all the sensors 10.
- the third reception means 7 is in turn disposed away from the alignment of all the sensors 10, substantially above the second reception means 6.
- this third reception means 7 is in communication with a reservoir 9 itself in communication with the microfluidic channel 8 at the level of the measuring electrode 11a of the first sensor 11.
- the reference electrode 11b of the first sensor 11 is immersed in the reservoir 9.
- the measurement of pH, redox potential and conductivity biomarkers is electrochemical.
- Such a device 1 is able to provide values ranging from 7 to 9 to ⁇ 0.1 for the pH, from -600 to +800 mV to ⁇ 0.5 mV for the redox potential, from 1 to 700 ohm . cm to ⁇ 1 ohm. cm for electrical resistivity, and 10 to 50 ° C to within ⁇ 0.1 ° for temperature.
- this system 100 comprises a read interface 50 of the device 1 comprising means 51 for processing the measurement values of the set of sensors 10 as well as representation means 52 in at least three dimensions of the analysis of the sensor. sample as a function of the treatment of the values of the measurements by the processing means 51.
- the representation means 52 comprise software that organizes the positioning of a point, representative of the biological sample or water, in a three-dimensional space whose three axes are representative of the three biomarkers pH, redox potential and conductivity. .
- the coordinates of this representative point are determined by the processing means 51 taking into account the temperature value returned by the fourth temperature sensor 14.
- the blood of patients carrying the same disease is thus organized in a cloud of points of restricted volume or cluster between these 3 parameters and / or axes.
- the reading interface 50 comprises interpretation means 53 of the representation means 52, said interpretation means 53 being arranged to provide an analysis result, based on a comparison of the position of a representative point of the real measurements. and reference regions defined in the same space relating to the type of sample analyzed.
- Reproducibility of the measurement of a blood sample is also valid for a urine or saliva sample.
- a urine or saliva sample it is interesting to work with the 3D positioning of the 3 biological samples (blood, saliva, urine) in order to work with a total of 9 measurements and to obtain more detailed information that can be processed by algorithms.
- This metrological method is also valid for the measurement of water and any aqueous solution.
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Abstract
Description
Dispositif pour l'analyse d'un échantillon liquide Device for the analysis of a liquid sample
La présente invention concerne le domaine de l'analyse biomédicale, et a en particulier pour objet un système comprenant un dispositif du type consommable pour l'analyse d'un échantillon liquide, en particulier de l'eau ou une solution biologique telle une goutte de sang. The present invention relates to the field of biomedical analysis, and particularly relates to a system comprising a device of the consumable type for the analysis of a liquid sample, in particular water or a biological solution such as a drop of blood.
Il est connu du document US2886771 de disposer d'un système comprenant un dispositif pour analyser des fluides biologiques, notamment du sang, de l'urine ou du fluide cérébrospinal. It is known from US2886771 to have a system comprising a device for analyzing biological fluids, in particular blood, urine or cerebrospinal fluid.
Cette analyse consiste à mesurer l e pH , l e potentiel d'oxydo- réduction et la résistivité électrique du fluide. This analysis consists of measuring the pH, the oxidation-reduction potential and the electrical resistivity of the fluid.
Ces mesures sont réalisées à la température constante de 37°C correspondant à la température normale du corps humain. These measurements are made at a constant temperature of 37 ° C corresponding to the normal temperature of the human body.
Cette analyse est ensuite interprétée pour déterminer l'état de santé du donneur de fluide biologique. This analysis is then interpreted to determine the health status of the biological fluid donor.
Cependant, ce système est encom bra nt et nécessite une stérilisation du dispositif, en particulier de la chambre de réception de l'échantillon à chaque utilisation pour éviter une contamination de mesures ultérieures. However, this system is encumbered and requires sterilization of the device, particularly the sample receiving chamber at each use to avoid contamination of subsequent measurements.
II est également connu du document US723091 B1 de disposer d'un dispositif pour analyser des fluides biologiques, comprenant un capteur de pH, un capteur de potentiel d'oxydo-réduction et un capteur de conductivité regroupés sur un même circuit intégré. It is also known from US723091 B1 to have a device for analyzing biological fluids, comprising a pH sensor, a redox potential sensor and a conductivity sensor grouped on the same integrated circuit.
Ce dispositif est avantageux en ce qu'il réduit l'encombrement du système en miniaturisant les capteurs utilisés dans le dispositif du document US2886771 . This device is advantageous in that it reduces the size of the system by miniaturizing the sensors used in the device of US2886771.
Cependant, ce système nécessite d'une part une grande quantité de fluide biologique pour pouvoir fonctionner et d'autre part nécessite l'utilisation d'un contenant pour pouvoir stocker le fluide biologique et utiliser le système. However, this system requires on the one hand a large amount of biological fluid to be able to operate and on the other hand requires the use of a container to be able to store the biological fluid and use the system.
La présente invention a pour but de résoudre tout ou partie des inconvénients mentionnés ci-dessus. The present invention aims to solve all or part of the disadvantages mentioned above.
A cet effet, la présente invention a pour objet un système d'analyse caractérisé en ce qu'il comprend un dispositif pour l'analyse d'un échantillon liquide, en particulier de l'eau ou une solution biologique telle une goutte de sang, du type consommable et comprenant un substrat sur lequel est déposé un ensemble de capteurs comprenant au moins un premier capteur de mesure du pH de l'échantillon liquide, un deuxième capteur de mesure du potentiel d'oxydo-réduction de l'échantillon liquide, un troisième capteur de mesure de la résistivité ou de la conductivité électrique de l'échantillon liquide, un ensemble de moyens de connexions de l'ensemble des capteurs, et une interface de lecture du dispositif comprenant un ensemble de moyens de connexions complémentaires agencé pour être connecté à l'ensemble de moyens de connexions du dispositif, des moyens de traitement des valeurs de mesure de l'ensemble des capteurs, des moyens de représentation en au moins trois dimensions de l'analyse de l'échantillon liquide en fonction du traitement des va l e u rs d es m es u res pa r l es moye n s d e tra ite m e nt , d es m oyen s d'interprétation des moyens de représentation, lesdits moyens d'interprétation étant agencés pour fournir un résultat d'analyse, basé sur une comparaison de la position d'un point représentatif des mesures réalisées et de régions de référence définies dans le même espace relatifs au type d'échantillon analysé. For this purpose, the subject of the present invention is an analysis system characterized in that it comprises a device for analyzing a liquid sample, in particular water or a biological solution such as a drop of blood, of the consumable type and comprising a substrate on which is deposited a set of sensors comprising at least a first sensor for measuring the pH of the liquid sample, a second sensor for measuring the oxidation-reduction potential of the liquid sample, a third sensor for measuring the resistivity or the conductivity electrical liquid sample, a set of connection means of all the sensors, and a reading interface of the device comprising a set of complementary connection means arranged to be connected to the set of connection means of the device, means for processing the measurement values of the set of sensors, representation means in at least three dimensions of the analysis of the liquid sample as a function of the processing of the values of the meters means for processing, means for interpreting the means of representation, said interpreting means being arranged to provide an analysis result, based on a comparison the position of a representative point of the measurements made and reference regions defined in the same space relating to the type of sample analyzed.
Cette disposition permet de fournir un système avec dispositif du type consommable ne nécessitant pas une grande quantité d'échantillon liquide, simple de fabrication et à moindre coût, ce qui le rend compatible avec une production de masse en série. This arrangement makes it possible to provide a system with a device of the consumable type that does not require a large quantity of liquid sample, which is simple to manufacture and at a lower cost, which makes it compatible with mass production in series.
De plus, l'utilisation d'un tel système associé au dispositif permet d'obtenir un résultat fiable et rapide avec une manipulation minimale de l'échantillon liquide. In addition, the use of such a system associated with the device makes it possible to obtain a reliable and rapid result with minimal manipulation of the liquid sample.
La définition des rég ions de référence peut être réalisée par l'utilisation de nuages de points de références, de surfaces ou de volumes de référence. The definition of reference regions can be achieved through the use of reference point clouds, reference surfaces or reference volumes.
Selon un aspect de l'invention, l'ensemble de capteur comporte un quatrième capteur de mesure de la température de l'échantillon liquide According to one aspect of the invention, the sensor assembly includes a fourth sensor for measuring the temperature of the liquid sample
Selon un aspect de l'invention, l'ensemble des moyens de connexion comprend des premiers moyens de connexion du premier capteur, des deuxièmes moyens de connexion du deuxième capteur, et des troisièmes moyens de connexion du troisième capteur, According to one aspect of the invention, the set of connection means comprises first connection means of the first sensor, second connection means of the second sensor, and third connection means of the third sensor,
Selon un aspect de l'invention, l'ensemble des moyens de connexion comprend des quatrièmes moyens de connexion du quatrième capteur. According to one aspect of the invention, the set of connection means comprises fourth connection means of the fourth sensor.
Selon un aspect de l'invention, le dispositif comporte une couche superficielle maintenue sur le substrat par des moyens de liaison, ladite couche superficielle comportant au moins un moyen de réception de l'échantillon liquide, un canal microfluidique agencé pour relier ledit au moins un moyen de réception à au moins un capteur de l'ensemble de capteurs. According to one aspect of the invention, the device comprises a surface layer maintained on the substrate by connecting means, said layer surface comprising at least one means for receiving the liquid sample, a microfluidic channel arranged to connect said at least one receiving means to at least one sensor of the set of sensors.
Cette disposition permet de conserver la fluidité de l'échantillon liquide en l'isolant au maximum de l'air et permet également de réduire au minimum la quantité de fluide nécessaire en guidant celui-ci directement vers les capteurs. This arrangement makes it possible to preserve the fluidity of the liquid sample by isolating it as much as possible from the air and also makes it possible to reduce to a minimum the quantity of fluid required by guiding it directly towards the sensors.
Selon un aspect de l'invention, le substrat est réalisé en un matériau à base de silicium. According to one aspect of the invention, the substrate is made of a silicon-based material.
Selon un aspect de l'invention, la couche superficielle est réalisée en un matériau à base de polymères. According to one aspect of the invention, the surface layer is made of a material based on polymers.
Selon un aspect de l'invention, les moyens de liaisons de la couche superficielle sur le substrat comprennent de la colle. According to one aspect of the invention, the connection means of the surface layer on the substrate comprise glue.
Selon un aspect de l'invention, le premier capteur comprend une électrode de référence disposée à l'intérieur d'un réservoir en communication avec le canal microfluidique. According to one aspect of the invention, the first sensor comprises a reference electrode disposed inside a reservoir in communication with the microfluidic channel.
Selon un aspect de l'invention, le premier capteur est du type ISFET, à film fin potentiométrique ou comprend une sonde optique. According to one aspect of the invention, the first sensor is of the ISFET type, thin potentiometric film or comprises an optical probe.
Selon un aspect de l'invention, le deuxième capteur comprend une électrode de mesure destinée à être immergée dans l'échantillon liquide According to one aspect of the invention, the second sensor comprises a measuring electrode intended to be immersed in the liquid sample.
Selon un aspect de l'invention, le troisième capteur comprend deux électrodes de mesure destinée à entrer en contact direct avec l'échantillon. According to one aspect of the invention, the third sensor comprises two measuring electrodes intended to come into direct contact with the sample.
Selon u n aspect de l ' invention , les moyens de traitement considèrent que la valeur des mesures des trois premiers capteurs est fonction de la valeur de mesure du quatrième capteur de température. According to one aspect of the invention, the processing means consider that the value of the measurements of the first three sensors is a function of the measurement value of the fourth temperature sensor.
De toute façon, l'invention sera bien comprise à l'aide de la description qui suit, en référence au dessin schématique annexé représentant, à titre d'exemple non limitatif, une partie ou tout le système selon l'invention. In any case, the invention will be better understood with the aid of the description which follows, with reference to the appended schematic drawing showing, by way of nonlimiting example, a part or the whole system according to the invention.
La figure 1 montre une vue de dessus du dispositif compris dans le système selon l'invention. Figure 1 shows a top view of the device included in the system according to the invention.
La figure 2 montre une vue en perspective du dispositif compris dans le système selon l'invention. Figure 2 shows a perspective view of the device included in the system according to the invention.
La figure 3 montre une vue d'un système selon l'invention. Figure 3 shows a view of a system according to the invention.
Comme illustré aux figures 1 et 2, un dispositif 1 d'un système 100 pour l'analyse d'un échantillon liquide comprend un substrat 2 sur lequel est déposé un ensemble de capteurs 10. Ce dispositif 1 est du type consommable et est donc destiné à être utilisé une seule fois et à être jeté après utilisation. As illustrated in FIGS. 1 and 2, a device 1 of a system 100 for the analysis of a liquid sample comprises a substrate 2 on which a set of sensors 10 is deposited. This device 1 is of the consumable type and is therefore intended to be used once and to be discarded after use.
Cet ensemble de capteurs 1 0 comprend un premier capteur 1 1 de mesure du pH de l'échantillon liquide, un deuxième capteur 12 de mesure du potentiel d'oxydo-réduction de l'échantillon liquide, un troisième capteur 13 de mesure de la résistivité ou de la conductivité électrique de l'échantillon liquide, et un quatrième capteur 14 de mesure de la température de l'échantillon. This set of sensors 1 0 comprises a first sensor 1 1 for measuring the pH of the liquid sample, a second sensor 12 for measuring the oxidation-reduction potential of the liquid sample, a third sensor 13 for measuring the resistivity or the electrical conductivity of the liquid sample, and a fourth sensor 14 for measuring the temperature of the sample.
Le su bstrat 2 est réal isé dans u n matériau à base de silicium comme du verre. Substrate 2 is made of a silicon-based material such as glass.
Le substrat 2 présente une forme parallélépipédique avec une face supérieure 3 présentant des bords dits inférieur 3a, gauche 3b, supérieur 3c et droit 3d, ces qualificatifs n'étant qu'arbitraires et n'étant utilisés ici que pour facilité le repérage sur les différentes figures. The substrate 2 has a parallelepipedal shape with an upper face 3 having so-called lower edges 3a, left 3b, upper 3c and right 3d, these qualifiers being only arbitrary and being used here only for ease of identification on the different FIGS.
Les différents capteurs 1 1 , 12, 13, 14 sont formés par une ou deux électrodes qui se prolongent jusqu'au bord inférieur 3a de la face supérieure 3 du substrat 2 pour former un ensemble de moyens de connexions 20 des différents capteurs 1 1 , 12, 13, 14 avec un ensemble de moyens de connexion complémentaires 20' disposés sur un lecteur d'analyse 50. The various sensors 1 1, 12, 13, 14 are formed by one or two electrodes which extend to the lower edge 3a of the upper face 3 of the substrate 2 to form a set of connection means 20 of the different sensors 1 1, 12, 13, 14 with a set of complementary connection means 20 'disposed on an analysis reader 50.
Ainsi cet ensemble de capteurs 20 comprend des premiers moyens de connexion 21 du premier capteur 1 1 , des deuxièmes moyens de connexion 22 du deuxième capteur 1 2, des troisièmes moyens de connexion 23 du troisième capteur 13 et des quatrièmes moyens de connexion 24 du quatrième capteur 14. Thus this set of sensors 20 comprises first connection means 21 of the first sensor 1 1, second connection means 22 of the second sensor 1 2, third connection means 23 of the third sensor 13 and fourth connection means 24 of the fourth sensor 14.
Les premiers moyens de connexion 21 du premier capteur 1 1 sont formés par la term inaison 1 1 a' d'une électrode de mesure 1 1 a et par la terminaison 1 1 b' d'une électrode de référence 1 1 b. The first connection means 21 of the first sensor 1 1 are formed by the termini 1 1 a 'of a measuring electrode 11a and the end 1 1 b' of a reference electrode 11b.
La terminaison 1 1 a' de l'électrode de mesure 1 1 a est disposée à proximité du milieu du bord inférieur 3a de la face supérieure 3 du substrat 2 tandis que la terminaison 1 1 b' de l'électrode de référence 1 1 b est disposée de manière excentrée au bord inférieur 3a de la face supérieure 3 du substrat 2 à proximité du bord droit 3d. The termination 1 1 'of the measuring electrode 1 1a is disposed near the middle of the lower edge 3a of the upper face 3 of the substrate 2 while the termination 1 1 b' of the reference electrode 1 1b is eccentrically disposed at the lower edge 3a of the upper face 3 of the substrate 2 near the right edge 3d.
Les deuxièmes moyens de connexion 22 du deuxième capteur 12 sont formés par la terminaison 12a' d'une unique électrode de mesure 12a. The second connection means 22 of the second sensor 12 are formed by the termination 12a 'of a single measuring electrode 12a.
La terminaison 1 2a' de l'électrode de mesure 1 2a est disposée à gauche de la terminaison 1 1 a' de l'électrode de mesure 1 1 a du premier capteur 1 1 . Les troisièmes moyens de connexions 23 du troisième capteur 13 sont formés par la terminaison 13a' d'une première électrode de mesure 13a et par la terminaison 13b' d'une deuxième électrode de mesure 13b. The termination 1 2a 'of the measuring electrode 1 2a is disposed to the left of the termination 1 1 a' of the measuring electrode 1 1a of the first sensor January 1. The third connection means 23 of the third sensor 13 are formed by the termination 13a 'of a first measuring electrode 13a and the termination 13b' of a second measuring electrode 13b.
La terminaison 1 3a' de la première électrode de mesure 1 3a est disposée à gauche de la terminaison 1 2a' de l'électrode de mesure 1 2a du deuxième capteur 12 et la deuxième terminaison 13b' de la deuxième électrode de mesure 1 3b est disposée à gauche de la terminaison 1 3a' de la première électrode de mesure 13a du troisième capteur 13. The termination 1 3a 'of the first measuring electrode 1 3a is disposed to the left of the termination 1 2a' of the measuring electrode 1 2a of the second sensor 12 and the second termination 13b 'of the second measuring electrode 1 3b is arranged to the left of the termination 1 3a 'of the first measuring electrode 13a of the third sensor 13.
Les quatrièmes moyens de connexion 24 du quatrième capteur 14 sont formés par la terminaison 14a' d'une première électrode de mesure 14a et par la terminaison 14b' d'une deuxième électrode 14b. The fourth connection means 24 of the fourth sensor 14 are formed by the termination 14a 'of a first measuring electrode 14a and by the termination 14b' of a second electrode 14b.
La terminaison 14a' de la première électrode de mesure 14a est d isposée à droite de la terminaison 1 1 a' de l'électrode de mesure 1 1 a du premier capteur 1 1 et la deuxième terminaison 14b' de la deuxième électrode de mesure 14b est d isposée à droite de la terminaison 14a' de la première électrode de mesure 14a du quatrième capteur 14. The termination 14a 'of the first measuring electrode 14a is located to the right of the termination 1 1a' of the measuring electrode 11a of the first sensor 11 and the second termination 14b 'of the second measuring electrode 14b is located to the right of the termination 14a 'of the first measuring electrode 14a of the fourth sensor 14.
Certaines d e c e s d iffé re ntes é l ectrod es so nt form ées essentiellement à base de platine mais peuvent comprendre un oxyde d'iridium ou u n composé argenté comme le chlorure d'argent pour l'électrode de référence 1 1 b du premier capteur 1 1 . Some of the electrochemical precipitates are formed essentially platinum-based but may include an iridium oxide or a silver compound such as silver chloride for the reference electrode 11b of the first sensor 11 .
Le premier capteur 1 1 destiné à la mesure du pH comprend une première électrode de mesure 1 1 a réalisée à partir d'un transistor à effet de champ du type ISFET (Ion Sensitive Field Effect Transistor) lui-même réalisé en matériau semi-conducteur comme le silicium. The first sensor 1 1 intended for measuring the pH comprises a first measurement electrode 11a made from a field effect transistor of the ISFET type (Ion Sensitive Field Effect Transistor) itself made of semiconductor material. like silicon.
Dans ce type de capteur, la solution est en contact direct d'une part avec la couche isolante de la grille q u i contrôle le cou rant de d ra in du transistor, et d'autre part avec une électrode de référence 1 1 b réal isée en argent/chlorure d'argent (Ag/AgCI) qui remplace la couche métall ique de la grille. In this type of sensor, the solution is in direct contact on the one hand with the insulating layer of the gate which controls the current flux of the transistor, and on the other hand with a reference electrode 11b realisée in silver / silver chloride (Ag / AgCl) which replaces the metallic layer of the grid.
L'utilisation d'un ISFET rend ce capteur robuste et peu coûteux, ce qui est compatible avec une production de masse en série. The use of an ISFET makes this sensor robust and inexpensive, which is compatible with mass production in series.
Néan moins, ce capteu r ISFET pou rrait être remplacé par un capteur à film fin potentiométrique ou bien comprendre une sonde optique. However, this ISFET sensor may be replaced by a potentiometric thin film sensor or may include an optical probe.
Le deuxième capteur 1 2 est destiné à la mesure du potentiel d'oxydo-réduction ou rédox. Cette mesure est basée su r la d ifférence de potentiel entre une électrode de mesure et une électrode de référence. L'électrode de référence 1 1 b du prem ier capteur pouvant servir d'électrode de référence pour le deuxième capteur 12, le deuxième capteur 12 n'a pas besoin d'électrode de référence supplémentaire et ne comprend donc qu'une unique électrode 12a réalisée en platine. The second sensor 1 2 is intended for measuring the oxidation-reduction or redox potential. This measurement is based on the difference in potential between a measuring electrode and a reference electrode. Since the reference electrode 11b of the first sensor can serve as a reference electrode for the second sensor 12, the second sensor 12 does not need any additional reference electrode and therefore only comprises a single electrode 12a. made of platinum.
Le troisième capteur 13 est destiné à la mesure de la conductivité ou de la résistivité électrique, une grandeur étant l'inverse de l'autre. L'une de ces grandeurs peut être déterminée en mesurant le courant traversant deux électrodes, réalisées en platine, lorsqu'un courant alternatif est appliqué à ces deux électrodes de mesure 13a, 13b. The third sensor 13 is intended for measuring the conductivity or the electrical resistivity, one size being the opposite of the other. One of these magnitudes can be determined by measuring the current flowing through two electrodes, made of platinum, when an alternating current is applied to these two measuring electrodes 13a, 13b.
Ces deux électrodesl 3a, 13b sont agencés pour être au contact de l'échantillon liquide et la tension aux bornes de ces deux électrodes 1 3a, 1 3b est de l'ordre de quelques centaines de millivolts. These two electrodes 3a, 13b are arranged to be in contact with the liquid sample and the voltage across these two electrodes 13a, 13b is of the order of a few hundred millivolts.
Le quatrième capteur 14 est destiné à la mesure de la température de l'échantillon liquide. Ce capteu r 1 4 est nécessaire pour compenser les valeurs de sortie des trois autres capteurs dont les grandeurs dépendent de la température. The fourth sensor 14 is intended for measuring the temperature of the liquid sample. This sensor 14 is necessary to compensate for the output values of the other three sensors whose magnitudes depend on the temperature.
Ce quatrième capteur 14 est du type capteur de température à résistance de platine (PRTD) comprenant donc deux électrodes 14a, 14b en platine. Au contact de l'échantillon liquide, la température de celui-ci fait varier la résistance entre les deux électrodes 14a, 14b du quatrième capteur 14. This fourth sensor 14 is of the platinum resistance temperature sensor (PRTD) type thus comprising two platinum electrodes 14a, 14b. In contact with the liquid sample, the temperature thereof varies the resistance between the two electrodes 14a, 14b of the fourth sensor 14.
Afin de confiner l'échantillon l iqu ide, le substrat 2 est en partie recouvert par une couche superficielle 4 maintenue sur le substrat 2 par des moyens de liaison comme de la colle. In order to confine the sample liquid, the substrate 2 is partly covered by a surface layer 4 maintained on the substrate 2 by bonding means such as glue.
Seule la partie du substrat 2 comportant l'ensemble de moyens de connexion 20 n'est pas recouverte par la couche superficielle 4. Only the portion of the substrate 2 comprising the set of connection means 20 is not covered by the surface layer 4.
Cette couche superficielle 4 est réalisée en un matériau à base de polymères, comme du plastique. This surface layer 4 is made of a material based on polymers, such as plastic.
Dans le mode de réalisation illustré aux figures 1 et 2, la couche superficielle 4 comporte trois moyens de réception 5 , 6 , 7 de l'échantillon liquide. In the embodiment illustrated in Figures 1 and 2, the surface layer 4 comprises three receiving means 5, 6, 7 of the liquid sample.
Ces moyens de réception 5, 6, 7 présentent une forme de cuvette ouverte sur leur fond afin de traverser la couche superficielle 4 et permettre à l'échantillon liquide d'atteindre le substrat 2. These receiving means 5, 6, 7 have a cup shape open on their bottom to pass through the surface layer 4 and allow the liquid sample to reach the substrate 2.
Les deux premiers moyens de réception 5, 6 sont disposées de part et d'autre d'un al ignement de l'ensemble des capteurs 1 0 et sont en communication l'un avec l'autre par l'intermédiaire d'un canal microfluidique 8 ménagé sur la surface de la couche superficielle disposée en regard du substrat 2. The first two receiving means 5, 6 are arranged on either side of an alignment of the set of sensors 1 0 and are in communication with each other via a microfluidic channel. 8 formed on the surface of the surface layer disposed facing the substrate 2.
Ainsi, un échantillon liquide versé dans l'un des deux premiers moyens de réception 5, 6 s'écoule par capillarité à l'intérieur du canal microfluidique 8 et vient au contact des électrodes de mesure de l'ensemble des capteurs 10. Thus, a liquid sample poured into one of the first two receiving means 5, 6 flows by capillary action inside the microfluidic channel 8 and comes into contact with the measuring electrodes of all the sensors 10.
Le troisième moyen de réception 7 est quant à lui disposé à l'écart de l'alignement de l'ensemble des capteurs 10, sensiblement au dessus du deuxième moyen de réception 6. The third reception means 7 is in turn disposed away from the alignment of all the sensors 10, substantially above the second reception means 6.
Cependant, ce troisième moyen de réception 7 est en communication avec un réservoir 9 lui-même en communication avec le canal microfluidique 8 au niveau de l'électrode de mesure 11a du premier capteur 11. However, this third reception means 7 is in communication with a reservoir 9 itself in communication with the microfluidic channel 8 at the level of the measuring electrode 11a of the first sensor 11.
L'électrode de référence 11b du premier capteur 11 est quant à elle immergée dans le réservoir 9. The reference electrode 11b of the first sensor 11 is immersed in the reservoir 9.
La mesure des biomarqueurs pH, potentiel rédox et conductivité sont d'ordre électro-chimique. The measurement of pH, redox potential and conductivity biomarkers is electrochemical.
Un tel dispositif 1 est en mesure de fournir des valeurs allant de 7 à 9 à ± 0,1 près pour le pH, de -600 à +800 mV à ± 0,5 mV près pour le potentiel rédox, de 1 à 700 ohm. cm à ± 1 ohm. cm près pour la résistivité électrique, et de 10 à 50°C à ± 0,1 ° près pour la température. Such a device 1 is able to provide values ranging from 7 to 9 to ± 0.1 for the pH, from -600 to +800 mV to ± 0.5 mV for the redox potential, from 1 to 700 ohm . cm to ± 1 ohm. cm for electrical resistivity, and 10 to 50 ° C to within ± 0.1 ° for temperature.
En outre, ce système 100 comprend une interface de lecture 50 du dispositif 1 comprenant des moyens de traitement 51 des valeurs de mesure de l'ensemble des capteurs 10 ainsi que des moyens de représentation 52 en au moins trois dimensions de l'analyse de l'échantillon en fonction du traitement des valeurs des mesures par les moyens de traitement 51. In addition, this system 100 comprises a read interface 50 of the device 1 comprising means 51 for processing the measurement values of the set of sensors 10 as well as representation means 52 in at least three dimensions of the analysis of the sensor. sample as a function of the treatment of the values of the measurements by the processing means 51.
Les moyens de représentation 52 comprennent un logiciel qui organise le positionnement d'un point, représentatif de l'échantillon biologique ou de l'eau, dans un espace à trois dimensions dont les trois axes sont représentatifs des trois biomarqueurs pH, potentiel rédox et conductivité. The representation means 52 comprise software that organizes the positioning of a point, representative of the biological sample or water, in a three-dimensional space whose three axes are representative of the three biomarkers pH, redox potential and conductivity. .
Les coordonnées de ce point représentatif sont déterminées par les moyens de traitement 51 en tenant compte de la valeur de température renvoyée par le quatrième capteur 14 de température. The coordinates of this representative point are determined by the processing means 51 taking into account the temperature value returned by the fourth temperature sensor 14.
Pour un échantillon de sang, des « clusters » spécifiques ou régions de références spécifiques et reproductibles correspondant à une pathologie ou à une autre caractéristique connue sont également positionnés dans cet espace à trois dimensions. La définition des régions de référence dans l'espace considéré peut être réalisée par l'utilisation de nuages de points de références, de surfaces ou de volumes de référence. For a blood sample, specific "clusters" or specific and reproducible reference regions corresponding to a pathology or other known characteristic are also positioned in this three-dimensional space. The definition of the reference regions in the space under consideration can be achieved by the use of reference point clouds, surfaces or reference volumes.
Le sang de patients porteurs d'une même maladie s'organise ainsi en un nuage de points de volume restreint ou cluster entre ces 3 paramètres et/ou axes. The blood of patients carrying the same disease is thus organized in a cloud of points of restricted volume or cluster between these 3 parameters and / or axes.
La plupart des différents clusters étant généralement compacts, ces derniers s'interpénétrent peu et leur organisation spatiale est éclatée dans cet espace à trois dimensions. Since most clusters are generally compact, they are not very interpenetrating and their spatial organization is fragmented in this three-dimensional space.
L'interface de lecture 50 comporte des moyens d'interprétation 53 des moyens de représentation 52, lesdits moyens d'interprétation 53 étant agencés pour fournir un résultat d'analyse, basé sur une comparaison de la position d'un point représentatif des mesures réal isées et de régions de référence définies dans le même espace relatifs au type d'échantillon analysé. The reading interface 50 comprises interpretation means 53 of the representation means 52, said interpretation means 53 being arranged to provide an analysis result, based on a comparison of the position of a representative point of the real measurements. and reference regions defined in the same space relating to the type of sample analyzed.
La reproductibil ité de la mesure d'un échantillon de sang est également valable pour un échantillon d'urine ou de salive. Pour certaines maladies, il est intéressant de travailler avec le positionnement 3D des 3 échantillons biologiques (sang, salive, urine) afin de travailler avec un total de 9 mesures et d'obten ir une information plus fine pouvant être traitée par algorithmes. Reproducibility of the measurement of a blood sample is also valid for a urine or saliva sample. For certain diseases, it is interesting to work with the 3D positioning of the 3 biological samples (blood, saliva, urine) in order to work with a total of 9 measurements and to obtain more detailed information that can be processed by algorithms.
Cette méthode métrologique est également valable pour la mesure de l'eau et de toute solution aqueuse. This metrological method is also valid for the measurement of water and any aqueous solution.
Bien que l'invention ait été décrite en liaison avec des exemples particuliers de réalisation, il est bien évident qu'elle n'y est nullement limitée et qu'elle comprend tous les équivalents techniques des moyens décrits ainsi que leurs combinaisons. Although the invention has been described in connection with particular embodiments, it is obvious that it is not limited thereto and that it includes all the technical equivalents of the means described and their combinations.
Claims
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR1153992A FR2975183B1 (en) | 2011-05-10 | 2011-05-10 | DEVICE FOR ANALYZING A LIQUID SAMPLE |
| FR11/53992 | 2011-05-10 |
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| Publication Number | Publication Date |
|---|---|
| WO2012153048A1 true WO2012153048A1 (en) | 2012-11-15 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/FR2012/050996 Ceased WO2012153048A1 (en) | 2011-05-10 | 2012-05-04 | Device for analyzing a liquid sample |
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| Country | Link |
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| FR (1) | FR2975183B1 (en) |
| WO (1) | WO2012153048A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015025102A1 (en) | 2013-08-20 | 2015-02-26 | Ichtyo Developpement Et Environnement I.D.E.E. Sarl | Method for characterising the physiological quality of a medium for culturing living organisms |
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| GB2283572A (en) * | 1993-11-02 | 1995-05-10 | Siemens Plessey Controls Ltd | Water quality sensor apparatus |
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| FR1381201A (en) * | 1953-10-23 | 1964-12-14 | Combined device intended for the simultaneous measurement in the absence of air and at self-stabilized temperature of the ph, rh and electronic resistivity of any liquid, semi-liquid solution, or gel, and in particular of blood, of liquid cephalo-rachidia | |
| US2886771A (en) | 1955-06-14 | 1959-05-12 | George A Rubissow | Fluid-testing device |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2015025102A1 (en) | 2013-08-20 | 2015-02-26 | Ichtyo Developpement Et Environnement I.D.E.E. Sarl | Method for characterising the physiological quality of a medium for culturing living organisms |
Also Published As
| Publication number | Publication date |
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| FR2975183A1 (en) | 2012-11-16 |
| FR2975183B1 (en) | 2013-05-24 |
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