ELECTRONIC DEVICE FOR ANALYZING AN ANALYTE PRESENT IN A FLUID AND CONSUMABLE AND INTERCHANGEABLE SENSOR, METHOD OF MANUFACTURING SAID DEVICE AND SAID CONSUMABLE AND INTERCHANGEABLE SENSOR
20230243754 · 2023-08-03
Inventors
Cpc classification
B81C1/00293
PERFORMING OPERATIONS; TRANSPORTING
G01N33/0009
PHYSICS
G01N2021/458
PHYSICS
B81B2201/0214
PERFORMING OPERATIONS; TRANSPORTING
B81B7/0061
PERFORMING OPERATIONS; TRANSPORTING
International classification
Abstract
The invention relates to an electronic device for analyzing an analyte (2) present in a fluid, comprising: a consumable and interchangeable sensor (10) comprising temporary receptors (14) capable of an interaction with the analyte present in the fluid, causing a change in local property; a sensor holder (50) in which the sensor is intended to be reversibly placed; and a transducer for the change in local property (130, 131; 230, 231), positioned on the sensor and/or on the sensor holder and able to convert the change in local property into an electronic signal expressing the change in local property. The sensor comprises a protection (17) for the temporary receptors. The invention also relates to the method of manufacturing this device, as well as to the consumable and interchangeable sensor and to its method of manufacturing.
Claims
1. Electronic device for analyzing (1) an analyte (2) present in a fluid, characterized in that it comprises: A. a consumable and interchangeable sensor (10) comprising an electronic chip (12) and a cover (15) secured to the electronic chip, the electronic chip comprising a measurement chamber (11) comprising temporary receptors (14) capable of an interaction with the analyte present in the fluid, the interaction causing a change in local property, and the cover comprising an opening (16a, 16b) suitable for admitting the fluid into the measurement chamber and for discharging the fluid from the measurement chamber; B. a sensor holder (50) comprising a housing (51) in which the sensor is intended to be reversibly placed; C. a transducer for the change in local property (130, 131; 230, 231) caused by the interaction between the temporary receptors and the analyte; this transducer being: able to convert the change in local property into an electronic signal expressing the change in local property; and, positioned on the sensor and/or on the sensor holder, in that the sensor comprises a protection (17) for the temporary receptors which is configured to be active prior to placement of the sensor in the housing of the sensor holder and configured to cooperate with the sensor holder so as to be deactivated by placement of the sensor in the housing of the sensor holder.
2. Device according to claim 1, wherein the temporary receptors of the measurement chamber are selected among molecules, peptides, polymers, biomarkers, nanoparticles or carbon nanotubes.
3. Device according to claim 1, wherein the analyte is a combination of target compounds, for example volatile organic compounds, contained in the fluid; preferably the analyte is a mixture of volatile organic compounds that is characteristic of an odor contained in the fluid.
4. Device according to claim 1, wherein the protection for the temporary receptors comprises a protective wrapper (18) configured for: closing off the opening of the cover prior to placement of the sensor in the housing of the sensor holder, and cooperating with the sensor holder so as to get perforated face to the opening of the cover when the sensor is placed in the housing of the sensor holder.
5. Device according to claim 4, wherein the protective wrapper is a polymer film, for example a polyolefin, optionally a substituted one such as polytetrafluoroethylene (PTFE) or a silicone such as polydimethylsiloxane (PDMS); and/or a film having a thickness comprised between 50 μm and 150 μm.
6. Device according to claim 4, wherein the opening of the cover has an inlet opening (16a) configured to admit fluid into the measurement chamber and an outlet opening (16b) configured to discharge fluid from the measurement chamber, and wherein, preferably, the protective wrapper comprises a first cap (180a) configured to close off the inlet opening prior to placement of the sensor in the housing of the sensor holder and a second cap (180b) configured to close off the outlet opening prior to placement of the sensor in the housing of the sensor holder.
7. Device according to claim 1, wherein the change in local property is a change of optical index in the sensor or a change of mass of a membrane (23) in the sensor.
8. Device according to claim 1, wherein the electronic chip is a photonic chip comprising at least one light guide (13) in which the temporary receptors are arranged, the light guide comprising a light input (135) and a light output (136), and wherein the transducer (130, 131) comprises: a coherent light source (130) aligned with the light input of the light guide and capable of emitting a beam of coherent light into the light guide of the electronic chip; an optical detector (131) aligned with the light output of the light guide and able to measure an optical parameter of the beam of coherent light exiting the light guide.
9. Device according to claim 1, wherein the electronic chip is an electromechanical chip comprising a membrane (23) on which the temporary receptors are arranged, and wherein the transducer (230, 231) comprises an actuator (230) capable of causing the membrane to vibrate, and a vibration frequency detector (231) for detecting the vibration frequency of the membrane.
10. Device according to claim 1, wherein the sensor holder comprises: a positioning guide (52) for the sensor, configured to guide the sensor as it is placed in the housing of the sensor holder; a retaining member (53) for holding the sensor in the housing, configured to hold the sensor in the housing when the sensor is placed in the housing of the sensor holder; a connection socket (56a, 56b) configured to cooperate with the opening of the cover when the sensor is placed in the housing.
11. Device according to claim 10, wherein the opening of the cover and the connection socket are configured to allow the protective wrapper to get perforated face to the opening of the cover, and further wherein the protection for the temporary receptors comprises a protective wrapper (18) configured for: closing off the opening of the cover prior to placement of the sensor in the housing of the sensor holder, and cooperating with the sensor holder so as to pet perforated face to the opening of the cover when the sensor is placed in the housing of the sensor holder.
12. Consumable and interchangeable sensor (10) comprising an electronic chip (12) and a cover (15) integrally secured to the electronic chip, the electronic chip comprising a measurement chamber (11) comprising temporary receptors (14) capable of an interaction with an analyte (2) present in a fluid to be analyzed, the interaction causing a change in local property, and the cover comprising an opening (16a, 16b) suitable for admitting the fluid into the measurement chamber and for discharging the fluid from the measurement chamber, the sensor being intended to be reversibly placed in a housing (51) of a sensor holder (50), and optionally comprising all or part of a transducer for the change in local property (130, 131; 230, 231) caused by the interaction between the temporary receptors and the analyte, the transducer being able to convert the change in local property into an electronic signal expressing the change in local property, and the sensor comprises a protection (17) for the temporary receptors which is configured to be active prior to placement of the sensor in the housing of the sensor holder and configured to cooperate with the sensor holder so as to be deactivated by placement of the sensor in the housing of the sensor holder.
13. Sensor according to claim 12, wherein it comprises a protective wrapper (18) configured for: closing off the opening of the cover prior to placement of the sensor in the housing of the sensor holder, and cooperating with the sensor holder so as to get perforated face to the opening of the cover when the sensor is placed in the housing of the sensor holder.
14. Method of manufacturing a consumable and interchangeable sensor (10) according to claim 12, characterized in that it consists essentially of i) preparing a silicon wafer; ii) functionalizing the silicon wafer to form a plurality of electronic chips (12); iii) introducing temporary receptors (14) onto a surface of the silicon wafer, on each electronic chip, to form measurement chambers (11); iv) covering, with a protective layer, the surface of the silicon wafer onto which the temporary receptors have been introduced, the protective layer forming a cover (15) for each measurement chamber; v) providing an opening (16a, 16b) on each cover to allow admitting a fluid into the measurement chamber associated with the cover and discharging the fluid from the measurement chamber associated with the cover; vi) cutting the silicon wafer to separate each assembly formed by a measurement chamber and a cover; vii) providing a protection (17) on the opening of each cover so as to form the sensors; viii) collecting the sensors.
15. Method of manufacturing an electronic analysis device according to claim 1, characterized in that it essentially consists of i) mass-producing consumable sensors (10); ii) preferably, storing the mass-produced consumable sensors; iii) separately producing sensor holders (50); iv) assembling a consumable sensor with a sensor holder, preferably on a to-order basis.
16. Method according to claim 15, wherein the temporary receptors of the measurement chamber of the electronic analysis device are selected among molecules, peptides, polymers, biomarkers, nanoparticles or carbon nanotubes and further wherein the assembly step (iv) comprises: iv.1) taking a consumable sensor; iv.2) preparing a sensor holder, wherein the sensor holder comprises: a positioning guide (52) for the sensor, configured to guide the sensor as it is placed in the housing of the sensor holder; a retaining member (53) for holding the sensor in the housing, configured to hold the sensor in the housing when the sensor is placed in the housing of the sensor holder; a connection socket (56a, 56b) configured to cooperate with the opening of the cover when the sensor is placed in the housing; iv.3) positioning the consumable sensor relative to the sensor holder so that the opening of the cover is aligned with the connection socket (56a, 56b) of the sensor holder; iv.4) reversibly placing the sensor in the housing (51) of the sensor holder; iv.5) and, simultaneously or not simultaneously with step (iv.4), piercing the protective wrapper (18) facing the opening of the cover.
Description
BRIEF DESCRIPTION OF DRAWINGS
[0051] Other features, details and advantages will become apparent from reading the detailed description below, and from analyzing the accompanying drawings, in which:
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DESCRIPTION OF EMBODIMENTS
[0063] In the figures, the same references designate identical or similar elements.
[0064] In
[0065] This sensor 10 comprises an electronic chip 12. The electronic chip 12 comprises a measurement chamber 11. This measurement chamber 11 comprises temporary receptors 14. These temporary receptors 14 can interact with the analyte 2 contained in the fluid to be analyze. The interaction between temporary receptors 14 and analyte 2 causes a change in local property. Thus, when the temporary receptors 14 are in the presence of the analyte 2, at least one local property characteristic of the environment in which the temporary receptors 14 are positioned is modified. The local property may be the optical index of the medium or a change in mass of a membrane 23 on which the temporary receptors 14 are located.
[0066] The temporary receptors 14 may be selected among molecules, peptides, polymers, biomarkers, carbon nanotubes or nanoparticles.
[0067] The sensor 10 also comprises a cover 15 integrally secured to the electronic chip 12. The cover 15 comprises an inlet opening 16a allowing the fluid to be analyzed to be admitted into the measurement chamber 11 and an outlet opening 16b allowing the fluid to be discharged from the measurement chamber 11. The fluid can thus circulate from the inlet opening 16a to the outlet opening 16b. The inlet opening 16a and the outlet opening 16b are each formed by a pipe projecting from the cover 15.
[0068] The inlet opening 16a is positioned near a first end of the measurement chamber 11 and the outlet opening 16b is positioned near a second end of the measurement chamber 11, thus making it possible to ensure the passage of the fluid at the temporary receptors 14. In a variant not shown, the cover 15 could comprise a single opening which allows both admitting the fluid to be analyzed into the measurement chamber 11 and discharging the fluid from the measurement chamber 11.
[0069] The sensor 10 also comprises a protection 17 for the temporary receptors 14. This protection 17 makes it possible to protect the temporary receptors 14 from fluid, and in particular from the air surrounding the sensor 10, by isolating the temporary receptors 14 from the outside.
[0070] In the variant shown in
[0071] The protective wrapper 18 may be formed by a polymeric material, for example a polyolefin, optionally a substituted one such as polytetrafluoroethylene (PTFE) or a silicone such as polydimethylsiloxane (PDMS). In particular, the material is deformable, can be made into a film, is stretchable, is waterproof, and must not release volatile organic compounds (VOCs). For example, the amount of volatile organic compounds released is less than 0.1 μg/g.
[0072] The protective wrapper 18 has a thickness comprised between 50 μm and 150 μm. The first cap 180a and the second cap 180b have a thickness comprised between 50 μm and 100 μm.
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[0074] The electronic analysis device 1 also includes a sensor holder 50. The sensor holder 50 comprises a housing 51 into which the sensor 10 is reversibly placed. The sensor 10 can thus be removed from the sensor holder 50 without damaging the electronic analysis device 1 and the sensor holder 50.
[0075] The sensor holder 50 comprises an upper face 58 comprising a recess forming the housing 51. The upper face 58 is flat and the recess is defined by inclined side walls 59 of the housing 51. For example, the side walls 59 form an angle strictly greater than 85° and strictly less than 90°, preferably an angle of 89°, with the flat upper surface 58.
[0076] As can be seen in
[0077] The protective wrapper 18 therefore is only pierced when the sensor 10 is placed in the sensor holder 50. The sensor 10 can therefore only be used once it has been installed in the electronic analysis device 1, which guarantees the quality of the temporary receptors 14 of the installed sensor 10.
[0078] In order to properly place the sensor 10 in the housing 51, the sensor holder 50 comprises a positioning guide 52 for the sensor 10 in order to guide the sensor as it is placed in the housing 51 of the sensor holder 50. The positioning guide 52 is formed by the side walls 59 of the housing 51. The side walls 59 come into contact with the side walls of the sensor 10 and thus guide the sensor 10.
[0079] The sensor holder 50 also comprises a retaining member 53 for holding the sensor 10 in the housing 51 in order to hold the sensor 10 in the housing 51 when the sensor 10 is placed in the housing 51 of the sensor holder 50. The retaining member 53 comprises a bimetallic spring. The bimetallic spring is movable so as to allow the sensor 10 to pass through when it is placed in the housing 51, and so as to be positioned against the sensor 10 once the sensor is in place in the housing 51, thus preventing the sensor 10 from leaving the housing 51. When one wishes to remove the sensor 10 from the housing 51, the retaining member 53 can once again be moved to allow the sensor 10 to come out. The retaining member 53 thus forms a reversible retention of the sensor 10.
[0080] The sensor holder 50 also has an inlet connection socket 56a and an outlet connection socket 56b. The inlet connection socket 56a and the outlet connection socket 56b of the sensor holder 50 are each a cavity having a bottom. When the sensor 10 is placed in the housing 51, the inlet opening 16a is inserted into the inlet connection socket 56a. The inlet connection socket 56a then allows the protective wrapper 18 and the first cap 180a to get perforated face to the intake opening 16a. Similarly, when the sensor 10 is placed in the housing 51, the outlet opening 16b is inserted into the outlet connection socket 56b. The outlet connection socket 56b then allows the protective wrapper 18 and the second cap 180b to get perforated face to the outlet opening 16b.
[0081] The sensor holder 50 also comprises an inlet duct 57a for fluid and an outlet duct 57b for fluid. The inlet connection socket 56a of the sensor holder 50 communicates with the inlet duct 57a of the sensor holder 50 and the outlet connection socket 56b of the sensor holder 50 communicates with the outlet duct 57b of the sensor holder 50. The inlet duct 57a and outlet duct 57b each extend axially from one end, starting respectively from the bottom of the cavity forming connection socket 56a and from the bottom of the cavity forming outlet socket 56b.
[0082] Each projecting pipe forming the inlet opening 16a and outlet opening 16b has a shape and dimensions complementary to those of the end of the inlet duct 57a or outlet duct 57b, so as to allow the each pipe to fit onto the end of the corresponding inlet duct 57a or outlet duct 57b.
[0083] The electronic analysis device 1 also comprises a transducer for the change in local property caused by the interaction between the temporary receptors 14 and the analyte 2. This transducer makes it possible to convert the change in local property into an electronic signal expressing the change in local property.
[0084] In a first example, the transducer comprises a coherent light source 130 and an optical detector 131. The light source 130 may for example be a laser diode. The light source 130 and the optical detector 131 may be positioned on the sensor 10, as shown in
[0085] In this first example, the electronic chip 12 is a photonic chip comprising at least one light guide 13. The light guide has a light input 135 and a light output 136. The coherent light source 130 is aligned with the light input 135 so that the light source 130 can emit a beam of coherent light into the light guide 13. The optical detector 131 is aligned with the light output 136 so that the optical detector 131 can detect an optical parameter of the beam of coherent light exiting the light guide 130.
[0086] The light guide 13 is divided into a plurality of branches, and in each branch, the light guide 130 is again divided into two arms. A branch thus divided into two arms is shown in
[0087] Each branch of the light guide 130 forms an interferometer for detecting the presence of an analyte 2 in a fluid. In fact, when the fluid enters the measurement chamber 11, the temporary receptors 14 present in each measurement arm 133 of the branches of the light guide 13 will interact with the analyte 2. As can be seen in
[0088] In particular, for each branch of the optical guide 13, the optical detector 131 receives a specific light intensity distribution. The optical detector 131 then transforms each of these specific light intensity distributions received into an electronic signal, expressing the change in optical index in the measurement arm 133 of the corresponding measurement branch, and therefore the interaction between the analyte 2 and the temporary receptors 14 in the corresponding branch. The set of electronic signals generated then forms a multidimensional electronic signal 31.
[0089] Thus, by means of the light source 130, the optical guide 13, and the detector 131, it is possible to detect the change in optical index generated by the interaction between the analyte 2 and the temporary receptors 14, and therefore to detect the presence of the analyte 2 in the analyzed fluid.
[0090] In a second example, shown in
[0091] The transducer comprises an actuator 230 which makes it possible to vibrate the membrane 23, and a vibration frequency detector 231. The actuator 230 and the vibration frequency detector 231 may be positioned on the sensor 10, as shown in
[0092] The temporary receptors 14 are arranged on the membrane 23. When fluid enters the measurement chamber 11, the temporary receptors 14 arranged on the membrane 23 will interact with the analyte 2. The analyte will for example attach to the temporary receptors 14. The interaction between the temporary receptors 14 and the analyte 2 will then change the mass of the membrane 23. This change in the mass of the membrane 23 will cause a change in its vibration frequency. This change in vibration frequency is specific to the change in mass of the diaphragm 23. When the diaphragm 23 is vibrated by the actuator 230, the vibration frequency detector 231 can thus detect this change in vibration frequency.
[0093] The vibration frequency detector 231 then transforms the change in vibration frequency into an electronic signal expressing the change in mass of the membrane 23, and therefore the interaction between the analyte 2 and the temporary receptors 14.
[0094] In particular, the electromechanical chip comprises a plurality of membranes 23 which can be vibrated by one or more actuators 230. And the vibration frequency detector 231 generates, for each membrane 23, an electronic signal expressing the change in mass of the corresponding membrane 23. The set of electronic signals generated then forms a multidimensional electronic signal 31.
[0095] Thus, by means of the actuator 230 and the vibration frequency detector 231, it is possible to detect the change in vibration frequency of the membrane 23, and therefore to detect the presence of the analyte 2 in the analyzed fluid.
[0096] According to one example, not shown, the electronic chip 12 comprises a reflecting film on which the temporary receptors 14 are arranged, and the transducer comprises a source of polarized light and an optical detector. The interaction between the analyte 2 and the temporary receptors 14 is responsible for a change of optical index in the measurement chamber 11. When polarized light is emitted from the light source, the proportion of light reflected by the reflective film varies depending on the optical index in the measurement chamber 11. The optical detector allows detecting the proportion of reflected light. The optical detector then transforms the proportion of reflected light into an electronic signal expressing the proportion of light reflected by the reflecting film, and therefore of the interaction between the analyte 2 and the temporary receptors 14. It is thus possible to detect the presence of the analyte 2 in the analyzed fluid.
[0097] In particular, the electronic chip 12 comprises a plurality of reflective films, on each of which are arranged the temporary receptors 14. And, for each reflective film, the optical detector generates an electronic signal expressing the proportion of light reflected by the corresponding reflective film. The set of electronic signals generated then forms a multidimensional electronic signal 31.
[0098] An example of a multidimensional electronic signal 31 generated by the optical detector 131 or the vibration frequency detector 231 is shown in
[0099] During time period Tb, no fluid is introduced into the measurement chamber 11. The multidimensional electronic signal 31 has a baseline value. During time period Ti, the fluid to be analyzed is introduced into the measurement chamber 11. A change in the multidimensional electrical signal is then observed. This change is characteristic of the interaction between the analyte 2 and the temporary receptors 14. During period Tp, no fluid is introduced into the measurement chamber. The multidimensional electronic signal 31 returns to its baseline value. This time period Tp makes it possible to purge the measurement chamber 11 and also allows the analyte 2 that interacted with the temporary receptors 14 to exit the measurement chamber 11. At the end of period Tp, the measurement chamber 11 is then ready to receive a new fluid to be analyzed and the temporary receptors 14 are then ready to receive the analyte 2 of the new fluid to be analyzed.
[0100] However, it could be that a portion of the analyte 2 of the analyzed fluid remains on the temporary receptors 14. The multidimensional electronic signal does not return to its exact baseline value, but to a value close to this baseline value. If this value is too far from the baseline value, then the temporary receptors 14 must be changed. The sensor 10 must be replaced.
[0101] For example, the temporary receptors 14 can be tested before use, in ambient air. An initial baseline value for the multidimensional electronic signal 31 is then obtained. If during period Tp, the value of the multidimensional electronic signal 31 takes a value that differs by less than 10% from the initial baseline value, then the temporary receptors 14 can be retained, and the sensor 10 can be kept.
[0102] Conversely, if during time period Tp, the value of the multidimensional electronic signal 31 takes a value that differs by more than 10% from the initial baseline value, then the temporary receptors 14 must be changed, and the sensor 10 must be replaced.
[0103] The method of manufacturing the consumable and interchangeable sensor is shown in
[0104] In a first step E1, a silicon wafer is prepared. In a second step E2, the silicon wafer is functionalized to form a plurality of electronic chips 12. The temporary receptors 14 are then introduced onto a surface of the silicon wafer, on each electronic chip 12, during a third step E3, to form measurement chambers 11. In a fourth step E4, the surface of the silicon wafer onto which the temporary receptors 14 were introduced is covered by a protective layer. The protective layer forms the cover 15 for each measurement chamber 11. An opening is then provided on each cover 15 in a fifth step E5, to allow admitting fluid into the measurement chamber 11 associated with the cover 15 and discharging fluid from the measurement chamber 11 associated with the cover 15. Then, in a sixth step E6, the silicon wafer is cut to separate each assembly formed by a measurement chamber 11 and cover 15. A protection is then provided on the opening of each cover 15 during a seventh step E7, so as to form the sensors 10. The sensors 10 are then collected during an eighth step E8.
[0105] The method of manufacturing the electronic analysis device 1 is illustrated in
[0106] In a first step S1, the consumable and interchangeable sensors are mass produced. In particular, they may be produced according to the method of manufacturing as described above. The sensors 10 are then preferably stored during a second step S2. In a third step S3, the sensor holders 50 are produced separately. Then, a consumable and interchangeable sensor is assembled with a sensor holder 50, preferably on a to-order basis, during a fourth step S4.
[0107] The fourth step S4 may in particular consist of taking a consumable and interchangeable sensor in a step S4.1, preparing a sensor holder 50 in a step S4.2, positioning the consumable sensor relative to the sensor holder so that the opening of the cover is aligned with the connection socket of the sensor holder during a step S4.3, reversibly placing the sensor in the housing of the sensor holder during a step S4.4, and, simultaneously or not simultaneously with step S4.4, piercing the protective wrapper facing the opening of the cover during a step S4.5.