System for characterizing the tissue structure of a living being

Abstract

The invention relates to a system for characterizing the tissue structure of a living organism, comprising: A tissue perforation device (1) comprising at least a first needle (10) and a second needle (11), the first and second needles being intended to be inserted through said tissues, the first needle (10) and the second needle (11) each being instrumented with a first electrode (100) and a second electrode (110) respectively; Measuring means to which the first electrode (100) and the second electrode (110) are connected; A texture analyzer device (2) connected to said measuring means, the first needle (10) and the second needle (11) being mounted on the texture analyzer device (2), the measuring means being configured to acquire second measurement data (D2).relating to the penetration force of the first needle (10) and the second needle (11) during their insertion through the tissues. Figure to be published with the abbreviation: Figure 1,

Description

Title of the invention: System for characterizing the tissue structure of a living organism Technical field of the invention

[0001] The invention relates to a system for characterizing the tissue structure of a living being. State of the art

[0002] In certain applications, it is relevant to know the structure of a living organism's tissues, particularly the different layers that make up these tissues. This is the case, for example, when one wishes to inject a compound such as a therapeutic agent at a specific depth under the skin of the living organism. It is then useful to know the histology of the living organism's skin, that is, the different layers of the skin and the thickness of each layer. When this data is known, it is thus easier to administer a product at the desired depth.

[0003] Currently, it is known to use a microneedle patch to administer appropriate therapeutic agents when necessary, taking into account the physiological parameters of the living organism. This principle is described in the referenced publication:

[0004] C. OMahony et al., "Embedded sensors for Micro Transdermal Interface Platforms (MicroTIPs), " 2016 Symposium on Design, Test, Integration and Packaging of MEMS / MOEMS (DTIP), Budapest, Hungary, 2016, pp. 1-5, doi: 10.1109 / DTIP.2016.7514859.

[0005] This type of device is in the form of a patch and is suitable for delivering therapeutic agents into the first layers of the skin of a living being. It is not suitable for determining the depth to which the microneedles should be inserted, in order to ensure that the therapeutic agents are administered at the appropriate depth.

[0006] The aim of the invention is therefore to provide a suitable solution for characterizing the tissues of a living organism, for example the different layers of the skin of a living organism. It is then possible, for example, to detect the presence of an infection and, ultimately, to administer a therapeutic agent or other compound at the desired depth. Description of the invention

[0007] This goal is achieved by a system for characterizing the tissue structure of a living being, comprising: - A tissue perforation device comprising at least a first needle and a second needle, the first and second needles being intended to be inserted through said tissues, the first and second needles each being instrumented with a first and second electrode respectively, - Measuring means to which the first and second electrodes are connected, the measuring means being configured to acquire initial measurement data for at least one parameter measured between the first and second electrodes, when the first and second needles are inserted through the tissues, - A processing unit configured to process said initial measurement data,

[0008] The system comprising: - A texture analyzer device connected to said measuring means, the first needle and the second needle being mounted on the texture analyzer device, the measuring means being configured to acquire second measurement data, relating to the penetration force of the first and second needles during their insertion through the tissues, - The processing unit being configured to process said second measurement data in conjunction with said first measurement data in order to determine the structure of said tissues.

[0009] According to a particular embodiment, the system includes at least one needle which is hollow.

[0010] According to another particular embodiment, the first needle and the second needle are positioned in parallel.

[0011] According to another particular embodiment, the first needle and the second needle are arranged concentrically.

[0012] According to another particular embodiment, the first needle and the second needle are mounted on the same support element adapted to the texturer device.

[0013] According to another particular embodiment, the first measurement data are impedance data measured between the first electrode and the second electrode.

[0014] According to another particular embodiment, the second measurement data are data relating to the penetration force of the first needle and the second needle in the tissues.

[0015] The invention also relates to a method for determining the tissue structure of a living being, said method being implemented using the system as defined above.

[0016] According to a particular embodiment, the process includes a step of determining a change in layer by detecting a sharp drop in said second measurement data.

[0017] According to another particular embodiment, the first measurement data are impedance data measured between the first electrode and the second electrode, the method comprising a step of determining the depth of a layer by detecting an impedance plateau in the first measurement data.

[0018] The invention is particularly advantageous because it allows for the determination of the skin histology of a living organism. This will be especially useful for applications involving the identification of a type of carcinoma, by evaluating the thicknesses of the constituent layers of the skin and the layers of cancerous cells. This makes it possible to determine the depth of the infection, thereby identifying the type of carcinoma and ultimately tailoring the treatment accordingly. Brief description of the figures

[0019] Other features and advantages will appear in the detailed description that follows, made in conjunction with the figures listed below: - Fig. 1 schematically represents the characterization system according to the invention; - Fig. 2 shows an alternative embodiment of the perforation device that can be used in the system of the invention; - Fig. 3 shows the characterization system of the invention of Fig. 1 in interaction with tissues of a living being, composed of several superimposed layers possibly with distinct mechanical and electrical properties; - Fig. 4 shows two diagrams illustrating the measurement data collected using the characterization system of the invention;

[0020] Detailed description of at least one embodiment

[0021] With reference to figures 1 to 3, the invention relates to a system for characterizing the tissue structure of a living being.

[0022] The system comprises: - A tissue perforation device 1, - A texture analyzer device 2, - Measurement means, configured to acquire first measurement data DI from the perforation device 1 and second measurement data D2 from the texture analyzer device 2, - A processing unit (PU) responsible for processing the first measurement data and the second measurement data, in order to characterize the structure of the tissues of the living being.

[0023] More precisely, the perforation device 1 comprises a first needle 10 and a second needle 11. Each needle is advantageously of the microneedle type, i.e. with a diameter of less than one millimeter.

[0024] The two needles are, for example, identical in cross-section and length, positioned adjacently and in parallel ([Fig. 1]). The two needles are positioned sufficiently close to each other so as to perforate the same layer simultaneously, under the same conditions.

[0025] The two needles 10, 11 can also be of distinct shapes. They can, for example, be integrated concentrically, one of them being arranged on the periphery of the other. [Fig. 2] shows this particular configuration.

[0026] Each needle can have a solid or hollow configuration, i.e., with a longitudinal axial channel. This channel can allow the injection of a therapeutic agent or other compound.

[0027] The two needles 10, 11 are advantageously supported by the same support element 3.

[0028] According to a particular feature of the invention, each needle 10, 11 carries at least one electrode. The first needle 10 thus carries a first electrode 100 and the second needle 11 carries a second electrode 110. Each needle is thus instrumented with its electrode. The electrode is advantageously arranged as close as possible to the perforation end of the needle. Advantageously, the electrode is made on a small surface area so as to localize the measurement on a specific layer, without extending into an adjacent layer.

[0029] The two electrodes 100, 110 are, for example, connected to measuring means, including, for example, a potentiostat, adapted to perform an impedance measurement between the two electrodes. Alternatively, the two electrodes can be used to measure any other parameter, such as an electrochemical parameter (pH, for example). In this case, each electrode is functionalized according to the electrochemical parameter to be measured.

[0030] It is also possible to instrument each needle with several electrodes, in order to measure several distinct parameters (impedance, pH,...).

[0031] Each electrode can be made by depositing a conductive layer. Depending on the parameter being measured, the material of the layer will be chosen differently.

[0032] For measuring an electrochemical parameter, one of the two electrodes is a measuring electrode and the other is a reference electrode. To form the measuring electrode, the conductive layer can be an ion-based conductive ink. metallic or conductive organic polymers such as polythiophene (PT), poly(octylthiophene) (POT), polyaniline (PANI) possibly doped with dodecylbenzenesulfonic acid (DBSA), poly(3,4-ethylenedioxythiophene) coupled to sodium poly(styrene sulfonate) (PEDOT:PSS), polypyrrole, or polyphthalocyanine. The reference electrode used is, for example, made by depositing an Ag / AgCl type ink.

[0033] The ends of the needles 10, 11 are advantageously positioned at the same height so that the two needles penetrate each layer of the tissues simultaneously.

[0034] Furthermore, it should be noted that the perforation device 1 can have more than two needles and therefore possibly more than two electrodes, in order to increase the number of measurements and / or the number of parameters measured.

[0035] The system of the invention has the particularity of having a texturer device 2. Such a texturer device 2 is used to measure the rheological properties and the geometric structures composing the texture of a compound.

[0036] In this particular case, it involves, for example, measuring the texture of living tissues, for example skin, in order to deduce the mechanical properties of its different layers, and in particular the differences in structures that may exist from one layer to another.

[0037] The texturer device 2 is associated with the perforation device to deduce the variation of the force applied during penetration through the tissues.

[0038] The measurement means are configured to acquire the second measurement data D2 provided by the texturer device 2.

[0039] Advantageously, the support element 3 of the needles is mounted directly on the texturer device 2 in order to measure a single penetration force of the assembly formed by the two needles.

[0040] The system also includes a processing unit UC. This processing unit UC is responsible for processing the first measurement data DI and the second measurement data D2. The processing unit UC is capable of correlating the first measurement data DI and the second measurement data D2 to deduce the topology of the different layers traversed by the needles. Figure 3 thus shows the perforation device 1 used in the invention, which penetrates several superimposed layers C1, C2, and C3 of different hardnesses and compositions.

[0041] Figure 4 shows two diagrams illustrating the correlation implemented between the first measurement data (the impedance in Ohms in this case) and the second measurement data (the force in N applied for needle penetration), as a function of time. The needles are moved at a constant speed, thus allowing to correlate the time and distance traveled by each needle and thus determine their depth of penetration.

[0042] Between T0 and Tl: The two needles 10, 11 are still in the air. The measured impedance is therefore very high and the force applied to move the perforation device in the air is almost zero, without any resistance.

[0043] A Tl: The needles penetrate a first layer. The force required to perforate this first layer increases progressively and it is observed that the measured impedance decreases sharply, synonymous with a change of medium.

[0044] Between T1 and T2: The impedance is mostly on a plateau, indicating that the needles are still in the first layer. The force exerted to cross this first layer remains low, indicating that this first layer is made of a rather soft material.

[0045] At T2: The needles reach a second layer, harder than the first. Indeed, an increase in impedance and an increase in the force required to penetrate through this second layer are observed.

[0046] Between T2 and T3: The needles pass through this second layer.

[0047] At T3: The needles reach a third layer. Indeed, the impedance reaches a new plateau, while the penetration force increases. The force required to penetrate this new layer is greater than that applied to penetrate the previous layers.

[0048] Between T3 and T4: The needles are always in this third layer, the impedance remaining constant and the force required for penetration increasing over time.

[0049] At T4: A surface is perforated by the needles. Indeed, a sudden drop in the applied force is observed, indicating perforation. Furthermore, the impedance also drops sharply.

[0050] Between T4 and T5: After perforation, the needles penetrate through a fourth layer.

[0051] Between T5 and T6 and between T6 and T7: once the fourth layer has been crossed, there is again a progressive increase in the force required for penetration as well as a rise in impedance, up to a new plateau.

[0052] At T7: A new perforation is observed, as at T4. Indeed, a sudden drop in applied force and impedance is observed.

[0053] After T7: The impedance is on a new plateau, synonymous with remaining in the same medium.

[0054] The correlation of data provided by the texture analyzer and data provided by impedance measurement makes it possible to confirm the presence of a change in layer and medium. Indeed, a change in layer by perforation is indicated by a sudden decrease in the force required for perforation, while a change in medium is symbolized by a variation in impedance. Furthermore, an impedance plateau indicates that the needles are still within the same layer and that it is simply a mechanical deformation of the layer traversed.

[0055] The two types of data acquired thus make it possible to distinguish between the deformation of a layer and the perforation of a layer. Indeed, with a single impedance measurement, it would not necessarily be possible to distinguish a change in layer. The abrupt variation in the penetration force makes it possible to detect the change in layer via perforation.

[0056] The processing unit is configured to correlate the first measurement data DI and the second measurement data D2. As an output, it is thus able to determine the number of distinct layers traversed by the needles, as well as an estimate of the thickness of each layer taking into account the depth of penetration of each needle into the tissues.

[0057] Once the tissue structure is characterized, it is possible to use the information relating to this structure to detect the presence of an infection (presence of cancer cells) and potentially to administer a compound, for example a therapeutic agent, at the desired depth. Indeed, thanks to the invention, based on the number of layers in the structure and the thickness of each layer, it is possible to adjust the insertion depth of a needle used to administer the desired compound.

[0058] It should be noted that in the case where at least one needle of the piercing device is hollow, it can be used directly for the administration of the compound.

Claims

Demands

1. A system for characterizing the tissue structure of a living organism, comprising: - A tissue perforation device (1) comprising at least a first needle (10) and a second needle (11), the first and second needles being intended to be inserted through said tissues, the first needle (10) and the second needle (11) each being instrumented with a first electrode (100) and a second electrode (110) respectively, - Measuring means to which the first electrode (100) and the second electrode (110) are connected, the measuring means being configured to acquire first measurement data (Dl) of at least one parameter measured between the first electrode and the second electrode, when the first needle (10) and the second needle (11) are inserted through the tissues, - A processing unit (PU) configured to process said initial measurement data, characterized in that the system comprises: - A texture analyzer device (2) connected to said measuring means, the first needle (10) and the second needle (11) being mounted on the texture analyzer device (2), the measuring means being configured to acquire second measurement data (D2), relating to a penetration force of the first needle (10) and the second needle (11) during their insertion through the tissues, - The processing unit (PU) being configured to process said second measurement data in conjunction with said first measurement data in order to determine the structure of said tissues.

2. System according to claim 1, characterized in that at least one needle (10) is hollow.

3. System according to claim 1 or 2, characterized in that the first needle (10) and the second needle (11) are positioned in parallel.

4. System according to claim 1 or 2, characterized in that the first needle (10) and the second needle (11) are arranged concentrically.

5. System according to any one of claims 1 to 4, characterized in that the first needle (10) and the second needle (11) are mounted on the same support element (3) adapted to the texturer device (2).

6. System according to any one of claims 1 to 5, characterized in that the first measurement data (Dl) are impedance data measured between the first electrode (100) and the second electrode (110).

7. A method for determining the tissue structure of a living being, characterized in that it is implemented using the system as defined in any one of claims 1 to 6.

8. Method according to claim 7, characterized in that it comprises a step of determining a change of layer by detecting a sharp drop in said second measurement data (D2).

9. A method according to claim 7 or 8, characterized in that the first measurement data are impedance data measured between the first electrode (100) and the second electrode (110) and in that the method includes a step of determining the depth of a layer by detecting an impedance plateau in the first measurement data (Dl).

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