BODY ELECTROPHORESIS MONITORING SYSTEM

Abstract

The invention relates to a body monitoring device (3), comprising at least one needle (25) for contacting the interstitial fluid, the needle being configured to collect or measure a physical quantity of the interstitial fluid, characterized in that the device (3) comprises electrophoresis electrodes (41, 42) configured to be in contact with the skin and cause electrophoresis under the skin without the interstitial fluid passing through the skin, and in that at least one needle (25) is positioned in the vicinity of at least one of the electrodes (42), so that the electrophoresis causes an accumulation of interstitial fluid at the level of the needles (25).

Description

The pump can be made in different shapes. In Figure 1, the pump comprises a foam 21A, 21B, or 21C, or several foams 21A, 21B, and 21C in series, which draw in the fluid thanks to their hydrophilicity and capillary action. For example, foam 21A initially draws in the fluid, which is then drawn from foam 21A by foam 21B, which is then drawn from foam 21B by foam 21C. Foam 21C is in contact with the sensor 24, so that the latter can perform measurements on the interstitial fluid stored in foam 21B. Foam 21C, called the drain foam, functions to empty foam 21B and facilitate the evaporation of the liquid it stores. This evaporation can occur naturally, with the ambient air, or with the help of a radiator 46 which heats the foam 21b. The radiator 46 is then controlled by the data processing means 11. The circulation is then bidirectional, that is to say, an equilibrium is established between the foams and the interstitial fluid of the skin. The 21C foam is described in more detail in the French patent application filed concurrently with the present application by the same applicant, entitled "Body monitoring system with double foam". The numerical references are identical. The measuring foam 21B can be made mobile by means of a passive mechanism 50 in the capsule 3, attached to the foam 21B, and an active mechanism 60 in the housing 2, connected to each other by an interface 70, as described in the French patent application filed in the name of the same applicant concurrently with the present application, entitled "Body monitoring system with mobile foam". The numerical references are identical. System 1 may also include a conductivity meter 44, which determines whether the foams 21A or 21B are saturated with liquid. Specifically, the conductivity of the movable foam 21B (not shown) is measured. A system with multiple foams is described in detail in the French patent application filed concurrently with the present application by the same applicant, entitled "Body Monitoring System with Double Foam." The numerical references are identical. Alternatively, the pump 21 can be a piezoelectric micro-pump enabling aspiration via a membrane vibration system. When operating (controlled by the data processing means 11), it will cause the transcutaneous extraction (through the epidermis) of interstitial fluid from the body (the dermis beneath the epidermis), its circulation through the circuit 20 to the sensor 24 which will analyze it, and then its arrival at the level of the absorbent foam (not shown), thus allowing it to be stored and evacuated by evaporation (the foam is advantageously in exchange with the atmosphere, particularly through a gas-porous fabric, so as to allow this evaporation, but advantageously impermeable to liquids (by (Example: polytetrafluoroethylene-based) to prevent the penetration of liquids such as sweat from the outside. The flow is then unidirectional, meaning that the sampling device 25 is the only fluid input, and the foam is the only output. There is no cycle. Electrophoresis electrode assembly The electrode assembly 40 comprises at least two electrodes 41, 42 (of the type a positive electrode 41 and a negative electrode 42) which allow an electric field to be applied by means of a voltage difference. Under the influence of the electric field, the Na+ ions present in the interstitial fluid move towards the negative electrode, carrying glucose molecules with them, which causes an accumulation under the skin (via a mini-inflammation). Thanks to this concentration, sampling by transcutaneous sampling methods 25 is simplified. In addition, since electrophoresis is not used to allow interstitial fluid to pass through the skin, electrophoresis can be applied at lower values ​​(intensity from 10pA to 300pA), thus avoiding the prohibitive pain associated with this type of technique. An example of an electrophoresis signal includes a voltage of 23V, ±2V, with a frequency of 200Hz. The set of 40 electrodes can consist of needles or a flat surface such as a plate. The needle penetrates the skin while the plate remains on the skin. The negative electrode 42 is positioned near the sampling means 25 to increase the presence of interstitial fluid and facilitate its sampling. "Near" means that the sampling means 25 are positioned where the concentration of interstitial fluid increases due to the electrodes, preferably where the concentration is at its maximum. In one embodiment, the two electrodes 41 and 42 are located on either side of the sampling means 25. In a particularly advantageous embodiment described below, the sampling means 25 comprise a plurality of hollow microneedles. A microneedle simply means a small needle (of the dimensions mentioned above). In a preferred embodiment, the negative electrode 42 is a needle, positioned with the plurality of needles of the sampling means 25. In particular, this electrode can be a needle of the sampling means 25. This allows for a more compact device 3, which has fewer elements to be inserted into the skin, and which is particularly effective since the sampling takes place exactly at the level of the negative electrode. To this end, Figure 4 illustrates such a needle-electrode 25, 42. To function as an electrode, the needle (which is a hollow tube) has metal on its outer surface. To function as a sampling device 25, the needle-electrode 25, 42 has an internal coating 42b adapted for a microcannula. The presence of metal on the outer surface is achieved either by means of a metal electrode, in which case the interior may include the 42b coating, or by means of a polymer electrode with, for example, a 42a metal coating. In one variant, several 25 needles, or even all of the 25 needles, act as electrodes. Indeed, as illustrated in figures 2a to 2c, 3b and 4, all the needles 25 (more precisely their outer coating) are connected to the same electrode 42 typically by a metal plate, which ensures electrical continuity. Electrode assembly for conductivity System 1 may also include a conductivity meter with electrodes to measure skin conductivity (which changes depending on skin moisture – sweat, outside weather, for example). The conductivity meter also includes another electrical signal generator 15, configured to power the conductivity electrodes. In practice, this generator 15 is the same as the electrical signal generator 14. The electrical signal generator 15 is controlled by the data processing means 11. In a preferred embodiment illustrated in the figures, the conductivity electrodes are the same as the electrophoresis electrodes 41, 42. This allows for increased compactness and simplicity, but also provides an extremely relevant conductivity measurement for electrophoresis. The conductivity measurement is managed by the data processing means 11. From this measurement, the electrophoresis value is adapted to avoid using a voltage / current that is too low (therefore no concentration) or too high (therefore pain). Conductivity control is performed before or concurrently with the use of electrophoresis to collect interstitial fluid for sampling or measurement. By obtaining conductivity, we can characterize the human body and better adapt the values ​​used to measure glucose levels. A hygrometer, a heart rate sensor, and / or an accelerometer, particularly in combination with skin conductivity measurements, can be used to assess the level of perspiration on the skin. Knowing the perspiration level allows for better correction of measurements, especially for blood glucose or lactate, since sweat contains glucose and lactate. Measuring skin pH is a relevant parameter for characterizing sweat. This measurement can be performed using electrodes within the device, particularly electrophoresis electrodes, notably by applying a A special coating is applied to a specific area of ​​the electrode. The data processing system is then programmed to determine the sweat level from the pH measurement. By using both techniques (conductivity on the one hand, pH on the other), we can obtain a more precise data relating to sweat. Another conductivity measurement can be taken to determine whether the needles are properly inserted into the skin. For this purpose, the set of 25 needles includes at least one shorter needle (i.e., one whose tip does not reach the same level). This shorter needle is connected to one electrode, and a needle of normal length is connected to another electrode. By measuring the conductivity between these two electrodes, it is possible to determine whether the needles are correctly inserted for collecting interstitial fluid. A conductivity meter is defined in the same way as comprising the aforementioned shorter needle and another needle, as well as an electrical signal generator, which is generally generator 14. Measurement of the transverse conductivity of needles To verify that the needles 25 are indeed collecting interstitial fluid, one needle from among the plurality of needles 25 can be connected to a conductivity meter comprising electrodes, as illustrated in Figure 4 (this principle is applicable to all the needles). In particular, two electrodes 27, 28 are arranged on either side of the needle 25, in a cross-sectional plane orthogonal to the main extension axis of the needle. The electrodes can be formed by specific elements, for example at one end of the needle 25 (end opposite to the end that collects the interstitial fluid), as shown in Figure 4. By connecting the electrodes to a conductivity meter, the conductivity value of the needle can be determined. This conductivity depends on the presence or absence of of interstitial fluid in needle 25. In the presence of the latter, the conductivity meter will indicate a higher value. The conductivity meter further includes an electrical signal generator, typically generator 15. The electrical signal generator is driven by the data processing means 11. For obvious practical reasons, this is the electrical signal generator 14. The conductimetry data is then processed by the data processing means 11. Measurement of the overall conductivity of the needles In order to know the overall level of filling of the needles considered as a whole, it is possible to measure the overall conductivity, for example by placing an electrode on one side of the group of needles and an electrode on the other side of the group of needles. Capsule Unlike known systems, System 1 is integral. This means that there is no primary module, such as a mobile terminal wirelessly connected to a bulky and expensive secondary module (due to the need to equip it with a battery, wireless communication means, etc.) in the form of a patch attached to the skin. System 1 is therefore autonomous. To be used, it is either pressed against the skin by the user for a few seconds if necessary (in which case it has no means of attachment to the body), or worn directly on the body, particularly on a limb, and preferably on the wrist. Device 3 then takes the form, for example, of a watch, with one face (F) against the skin of the arm, and the opposite face accommodating, for example, a screen. As such, it advantageously includes reusable means of attachment to the body, typically consisting of a strap or bracelet configured to encircle the limb (and not an adhesive element), in particular a bracelet- watch. "Reusable" here is understood as the opposite of "single-use," as was the case with patches, which cannot be reused after being removed from the skin and must be discarded. A bracelet can be opened and closed many times. System 1 is configured so that when placed on the skin (i.e. when the attachment means fix it to the body) the transcutaneous harvesting means 25 are held against the skin (or at least in the immediate vicinity) to permit harvesting. In all cases, system 1 contains two subsets: - a case 2 in which are arranged at least the data processing means 11 (as well as the main components such as the battery, the memory, the possible user interface, etc.); - a capsule 3 in which are arranged the sensor 24, the electrode assembly 40, the pump 21 (when it is a foam, for example), the foam 21 A, B or C (as explained, preferably in exchange with the atmosphere to promote evaporation of the fluid and thus limit its stagnation, if necessary via a window 26 through the capsule 3 - see figures 3b and 3c) and the transcutaneous sampling means 25, the capsule 3 being configured to engage with the housing 2 in a removable manner. The capsule 3 preferably engages in a cavity C of the housing 2 located on its face F intended to be in contact with the skin. In this description, the term device 3 refers to the capsule. The capsule therefore includes a face designed to be placed on a substantially flat surface, such as the wrist of a hand. Electrodes 41, 42 and needles 25 are located on this face. Put another way, and as can be seen in Figure 1 and Figures 2a-2c which represent a preferred embodiment, system 1 remains composed of two modules 2, 3 but these are not physically separated as could be the case in the prior art and are even in direct, mechanical connection. The housing 2 and the capsule 3 include transmission means for transmitting electrical signals, such as contactless wireless links (transmitter / receiver) or electrical connectors 12a, 12b (contacts, see Figures 2a, 3a) and, in the case of a pump in the housing, fluid connectors (not shown). The electrical connectors 12a, 12b are configured so that, when the capsule 3 is engaged with the housing 2, said electrical connectors 12a, 12b provide a connection between, on the one hand, the data processing means 11, the electrical signal generator(s) 14, 15 and, on the other hand, the sensor 24 (for transmitting measurement data) and the electrophoresis electrode assembly 40 (and other components that require instructions and / or sending signals), and the conductivity electrodes 27, 28.When required, the aforementioned fluidic connections 22a, 22b, 22c, 22d ensure that the fluidic circuit 10 extends in a sealed manner both in the housing 2 and the capsule 3 (so that the suction power of the pump 21 is not altered). Capsule 3 thus constitutes an interchangeable subset of system 1, which can be selected according to the type of monitoring required. Indeed, since the capsule contains the sensor(s) 24, changing the capsule allows for the replacement of the sensors 24 if they reach the end of their lifespan or if a change in the physical quantity being measured is desired. This is achieved through a simple, quick, and safe operation, without having to discard other parts (in particular, the housing 2). It should be noted that capsule 3 very effectively preserves the sensors 24 and needs to be changed less frequently than a patch (the same capsule can be used for a month). And since capsule 3 contains neither a pump nor advanced electronic equipment such as a battery or wireless communication means, it is significantly cheaper than a patch. The present system 1 is therefore much more practical than the systems known from the prior art, but above all much cheaper to use, without the slightest hygienic risk, and without pain due to the insertion of a needle or strong electricity. In an advantageous embodiment (where the pump is inside the capsule), capsule 3 is the only part of system 1 that can come into contact with interstitial fluid, since it contains the absorbent foam 21 A, B, or C (beyond which the sampled fluid cannot rise). Thus, the removable capsule prevents contamination of the housing 2 and allows capsule 3 to be replaced at the end of the sensors' 24 service life, or for the type of capsule 3 to be changed, in a simple, quick, and safe operation, without having to discard any other parts. Capsule change Capsule 3 engages with housing 2 through two successive translational movements T1 and T2 (Figures 2a to 2c). The reverse movement disengages capsule 3. The first movement T1 brings capsule 3 towards housing 2 to attach the electrical connectors 12a / b, and the second movement T2 slides capsule 3 along housing 2 to engage the mechanical link 70. The electrical connectors 12a / b are flexible (with a spring, for example). Thanks to stops 3a (figure 3a), once the translation T2 has been completed, the capsule 2 is blocked in the direction of the translation T1. These stops 3a are wedged between the bottom of the cavity C and a rail 2b (figure 2a). Other general architectures In another embodiment, the device is similar to that described above, except that it does not include a sensor and is used simply to collect the fluid. The fluid is then recovered (for example, from the foams) for analysis elsewhere. In another embodiment, the device comprises at least one needle (preferably a plurality), which act as means of skin penetration. On the needle(s) are positioned one or more sensors, typically in the form of a coating (chemical sensor) at the tip of the needle which is inserted into the body. In this embodiment, there is therefore no transcutaneous fluid sampling. The measurement obtained by the sensor is then retrieved and processed. Figure 5 illustrates such sensor needles. The document by Yoon et al. (“Fabrication of a Microneedle / CNT Hierarchical Micro / Nano Surface Electrochemical Sensor and Its In-Vitro Glucose Sensing Characterization”, in Sensors 2013, 13(12), 16672-16681; doi:10.3390 / s131216672) describes a type of needle sensor. It is possible to foresee that some needles are used for measurement (and include a sensor) and that some needles are used only for electrophoresis (particularly for material and coating reasons). The needles are then usually solid, but they can also be hollow. Apart from the fluidic circuit and the elements that form it which are no longer present, the rest of the measurement system 1 is applicable to this embodiment (processing means, connectivity, etc.). Thus, the principles described previously for electrophoresis are identical, except that the needle allows direct measurement, without sampling. Process The system described above allows for the implementation of an interstitial fluid extraction process in an efficient, minimally invasive and virtually painless manner. Such a process includes: - a step of applying an electric field using electrodes (two electrodes, negative and positive), to accumulate interstitial fluid near the negative electrode by electrophoresis, and, - a step of sampling or measuring the accumulated interstitial fluid using transcutaneous sampling or measurement methods (typically needles) at the electrodes. The electrophoresis step is not calibrated to allow interstitial fluid to pass through the skin. Therefore, this procedure allows the use of an amperage between 10 and 300 pA, which is lower than the amperages required for electrophoresis to allow the molecules of interest to pass through the skin. More generally, this process is applicable to any membrane separating a liquid containing ions or charged elements located behind a membrane from another environment and from which it is desired to extract this liquid through the membrane. Use The system and method described above more generally involves the use of subcutaneous electrophoresis with two electrodes to concentrate the interstitial fluid and collect it with a needle. More generally, this use is applicable to any membrane separating a liquid containing ions or charged elements located behind a membrane from another environment and from which it is desired to extract this liquid through the membrane. Thanks to the system or process or use presented, it is possible to collect more than 4pl of interstitial fluid without causing prohibitive pain to the user.

Claims

DEMANDS 1. Body monitoring device (3), comprising at least one needle (25) configured to come into contact with interstitial fluid, the needle being configured to collect or measure a physical quantity of interstitial fluid, characterized in that The device (3) includes electrophoresis electrodes (41, 42) configured to be in contact with the skin and to cause electrophoresis under the skin without the interstitial fluid passing through the skin, and in this that at least one needle (25) is positioned in the vicinity of at least one of the electrodes (42), so that electrophoresis causes an accumulation of interstitial fluid at the needle (25).

2. Device (3) according to claim 1, wherein at least one needle (25) acts as an electrophoresis electrode (42), preferably all of the needles (25).

3. Device (3) according to claim 2, wherein the other electrophoresis electrode (41) is a flat surface, such as a plate.

4. Device (3) according to any one of the preceding claims, further comprising at least one sensor (24) of a physical quantity of interstitial fluid, the sensor being configured to be in contact with the interstitial fluid in order to measure a physical quantity of the interstitial fluid.

5. Device (3) according to any one of claims 1 to 4, wherein at least one needle forms means for transcutaneous sampling (25) for example in the form of one or a plurality of hollow needles.

6. Device (3) according to claim 4, wherein at least one sensor (24) is located at the end of the needle configured to be inserted into the body, the sensor (24) being formed by coating, and the sensor needle is preferably solid.

7. Device according to claim 6, further comprising at least one needle, separate from the sensor needle, acting as an electrophoresis electrode (42).

8. Device (3) according to any one of claims 1 to 7 in combination with claim 2, wherein said needle-electrode comprises metal (42a), entirely or on its outer surface only.

9. Device (3) according to any one of claims 1 to 8, wherein one of the needles (25) is shorter than the others, said needle forming an electrode for measuring conductivity to determine whether the needles are correctly inserted.

10. Device (3) according to any one of claims 1 to 9, in which a needle (25) comprises two electrodes (27, 28), configured to measure conductivity along a plane transverse to a direction of extension of the needle in order to know whether the needle is in contact with or filled with liquid.

11. Device (3) according to any one of claims 1 to 10, configured to measure skin pH, for example using at least one of the electrophoresis electrodes (27, 28) to measure the level of sweat.

12. Capsule (3) comprising a device according to any one of claims 1 to 11.

13. System (1) comprising: - a device (2) according to any one of claims 1 to 11 or a capsule according to claim 12, - data processing means (11) configured to process data from the sensor (24), and - a generator (14) of electrical signals configured to power the electrophoresis electrode assembly.

14. System (1) according to claim 13, wherein the electrical signal generator (14) is configured to generate signals less than or equal to 300pA in order to avoid or limit any pain.

15. System (1) according to any one of claims 13 to 14, comprising a conductivity meter configured to measure skin conductivity using electrodes, preferably electrophoresis electrodes.

16. System (1) according to claim 15, wherein the electrical signal generated by the electrical signal generator (14) takes into account the measurement of skin conductivity.

17. System (1) according to any one of claims 13 to 16 in combination with claim 4, and preferably with claim 11, further comprising a hygrometry sensor, a heart rate sensor and / or an accelerometer, for measuring skin perspiration and / or correcting the measurements of sensor (24).

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