Manufacturing process for a microneedle and in particular metallization of the tip of a microneedle

Abstract

Manufacturing process for a micro-needle and in particular metallization of the tip of a micro-needle.The invention relates to a method for manufacturing a microneedle (10), the microneedle (10) comprising a base (12) and a tip (11), the method comprising the following steps: - supplying (E0) a barrel (1) with a tip; - deposition (E1') of a conductive layer (2) covering the barrel (1); - deposition (E2) of an insulating layer (3) having a thickness x on the conductive layer (2); - removal (E3) of the insulating layer (3) so as to define a conductive tip (11) of the microneedle (10) by means of a laser (5), the laser (5) being configured to remove a thickness y greater than or equal to the thickness x so as to expose the tip (11) of the entire thickness of the second insulating layer (3) and a portion of the thickness of the conductive layer (2), so that the tip (11) is exposed of the entire thickness x of the insulating layer (3), the microneedle (10) thus obtained comprising an insulating base (12) and a conductive tip (11). Figure for the abbreviation: Fig. 2.

Description

Description Title of the invention: TITLE OF THE INVENTION Process for manufacturing a microneedle and in particular metallization of the tip of a microneedle. GENERAL TECHNICAL FIELD The present invention relates to the manufacture of microneedles of a body monitoring device via the analysis of body fluid, typically interstitial, using such microneedles. It relates more specifically to the formation of the tip of a microneedle and in particular its metallization. STATE OF THE ART Certain pathologies such as diabetes require daily monitoring of biochemical parameters of the human body, that is to say concentrations of certain compounds (blood sugar in the example of glucose). Today, we know of advanced systems that simply analyze interstitial fluid, that is, the fluid that fills the space between blood capillaries and cells. It has an ionic composition close to that of blood plasma. These advanced systems thus make it possible to monitor the desired biochemical parameters transcutaneously, i.e. without the need to regularly pierce the skin and take samples. We know of devices with microneedles, which have the advantage of being less invasive than conventional needles. However, it is important that these microneedles remain in place. There are permanent devices for this purpose, where microneedles are held on the skin with an adhesive strip. However, continuous or near-continuous monitoring is desired, which requires autonomous devices. One example is the GlucoWatch device, which uses iontophoresis (rather than needles). However, when such a device includes microneedles, there may be interference from sweat on the skin. Sweat can come into contact with the base of the microneedle and therefore distort the measurements. To solve this, there are solutions aimed at masking certain parts of the microneedles, for example the base, to prevent them from interfering. In this respect, the document US 2014 / 0275897 describes the use of an insulating coating to mask certain parts of the microneedles. And one of the techniques used to remove the thickness of this insulating coating from the head of the microneedle is to put in place a cap or a mask covering the head of the microneedle before the application of the insulating layer and to remove this cap afterwards (mechanical cap or chemical). However, using a cap is not very practical. PRESENTATION OF THE INVENTION One aim of the invention is to propose a simple and precise solution for obtaining a microneedle which makes it possible to avoid interference linked to sweat by using an insulator on only part of the microneedle. In this respect, the invention relates, according to a first aspect, to a method of manufacturing a microneedle, the microneedle comprising a base and a tip, the method comprising the following steps: - supply of a pointed barrel; - deposit of a conductive layer covering the barrel; - depositing an insulating layer having a thickness x on the conductive layer; - removing the insulating layer so as to define a conductive tip of the microneedle by means of a laser, the laser being configured to remove a thickness y greater than or equal to the thickness x so as to strip the tip of the entire thickness of the second insulating layer and a portion of the thickness of the conductive layer, so that the tip is stripped of the entire thickness x of the insulating layer, the microneedle thus obtained comprising an insulating base and a conductive tip. The invention is advantageously supplemented by the following characteristics, taken alone or in any of their technically possible combinations: - the laser comprises a tolerance interval t, the conductive layer having a thickness greater than 0.1 #7” than the tolerance interval of the laser used during the removal step so that the conductive layer at the end of the removal step has a thickness greater than or equal to 0.1 #7; - the conductive layer comprises at least a first conductive sub-layer covering the barrel and at least a second conductive sub-layer covering the first conductive sub-layer, the second sub-layer having a thickness greater than the thickness of the first sub-layer; - the second conductive sub-layer is deposited using a process different from that used to deposit the first conductive sub-layer; - the conductive layer comprises an intermediate sub-layer arranged between the first conductive sub-layer and the second conductive sub-layer, the intermediate sub-layer is made of a material identical to that of the second conductive sub-layer and has a thickness less than the thickness of the second conductive sub-layer; - the intermediate sub-layer is deposited using a process identical to that used to deposit the first conductive sub-layer; - the conductive layer has a thickness between 0.1 #7" and 7 #FM: - the insulating layer is made of electrically insulating and biocompatible material with a thickness between 1 and 20 #1; The invention relates, according to a second aspect, to a microneedle, capable of being obtained by a method according to the first aspect of the invention. The microneedle is such that the conductive layer has a thickness 0.1 #77 greater than the tolerance interval of the laser used during the removal step. The laser allows the insulating layer to be removed from the tip of the microneedle in a single step, eliminating the need for masking and unmasking. And to ensure that the laser removes the entire thickness of this insulating layer, the conductive layer is thick enough to take into account the uncertainties induced by the laser while ensuring that a certain thickness of the conductive layer is maintained. Additionally, having a sufficiently thick conductive tip provides a microneedle that is resistant to wear over time. In one embodiment, the conductive layer is a simple conductive monolayer of thickness greater than the tolerance range of the laser. In one embodiment, the conductive layer is composed of two sub-layers to promote the retention of the conductive layer on the pointed shaft. In one embodiment, the conductive layer is composed of two sub-layers with an intermediate sub-layer disposed between the two conductive sub-layers in order to ensure a thickness of the layer greater than the tolerance interval of the laser and to prevent delamination between the sub-layers. PRESENTATION OF THE FIGURES Other characteristics and advantages of the present invention will appear on reading the following description of a preferred embodiment. This description will be given with reference to the appended drawings in which: [Fig. 1] illustrates a body monitoring device according to one embodiment of the invention. [Fig.2] illustrates steps of a method of forming the tip of a microneedle according to one embodiment; [Fig.3] schematically illustrates steps of the method according to the invention; [Fig.4] illustrates a microneedle whose tip is obtained according to an embodiment in which the conductive layer is made up of two conductive sub-layers; [Fig.5] illustrates a microneedle whose tip is obtained according to an embodiment in which the conductive layer is made up of sub-layers drivers; [Fig.6] illustrates a microneedle whose tip is obtained according to an embodiment in which the conductive layer consists of two conductive sub-layers and an intermediate sub-layer; [Fig.7] illustrates a microneedle whose tip is obtained according to an embodiment in which it is made up of conductive sub-layers and an intermediate sub-layer. In all figures, similar elements bear identical references. DETAILED DESCRIPTION general of a device of ill it [Fig. 1] illustrates a body monitoring device 100 comprising a housing 200, a sensor 30 and an adhesive patch 40. The sensor 30 is here a needle sensor intended to provide a measurement of electric current within the interstitial liquid of the wearer of the device 100. Needles 10 are advantageously arranged on an inner face 31 of the sensor 30. This inner face 31 is intended to be placed on the wearer's skin. The sensor 30 is assembled to the adhesive patch 40 and together constitute a capsule. The sensor 30 can also be removable relative to the patch 40. Such a capsule is advantageously removably mounted with the housing 200. In particular, the capsule and therefore the sensor 30 preferably engages in a cavity 210 of the housing 200 located on its face intended to be in contact with the skin. The sensor 30 comprises an outer face 32 opposite the inner face 31. The housing 200 and the capsule may have complementary shapes, which limits the effort required for proper insertion of the capsule against the housing 200. The patch 40 comprises an adhesive layer, or is itself formed from an adhesive material. The patch therefore allows the capsule to be attached to the wearer's skin, and helps maintain the needles 10 in the interstitial fluid. The patch 40 has, for example, an annular shape, and covers the capsule. The sensor 30 illustrated here is circular in shape with a central orifice 33 but it can take other shapes: rectangular, oblong, ellipsoidal with or without a central orifice. The central orifice 33 makes it possible to correctly position the sensor 30 in the cavity 210 of the housing which includes a central positioning stud (not shown). The sensor 30 therefore comprises elements which make it possible to sample the liquid or to bring the signals detected by each microneedle to the box 200 for processing (not described here). The sensor 30 can take the form of a plastic plate, a printed circuit (rigid or flexible silicon), a non-conductive metal plate such as aluminum. The adhesive patch 40 is adapted to be stuck to the skin and supports the sensor 30 and allows the housing 200 to be detached without removing the sensor 30 while keeping it stuck to the body. Such a configuration makes it possible to avoid removing the sensor for certain operations which only involve the housing: recharging the battery, repair, replacement, extraction of data to a computer. The case 200 is advantageously in the form of a watch case and comprises means 230 for attaching the device to a user's wrist. This is in particular a bracelet adapted to surround a user's wrist. The bracelet is preferably adjustable. The housing 200 houses several elements for analyzing or extracting interstitial fluid. In this respect, reference may be made to document WO 2019 / 141743 in the name of the applicant, which describes in detail the measurement and detection of a physical quantity using microneedles in contact with a bodily fluid that may or may not be sampled. Advantageously, the watch further comprises a wireless communication interface, for example via a 3G and / or 4G and / or 5G and / or Wi-Fi and / or Bluetooth and / or NFC and / or DECT type telecommunications network. Also, the watch may include a light indicator such as a diode, which may be used to signal the end of a sensor preparation operation. The needles 10 are advantageously micro-needles. The sensor 30 preferably comprises between four and fifty micro-needles or even four hundred micro-needles. Of course, a different number can be considered without this limiting the description of the invention given here. A microneedle is understood to mean a needle having a low height, preferably between 10 µm and 1000 µm, preferably between 0.3 mm and 0.8 mm. The height of the microneedles is low enough to avoid contact with a mechanical pain nerve of the wearer when the device is worn. 10 microneedles are used to measure body fluid. The microneedles 10 are solid to directly analyze the liquid. To analyze liquid, the microneedles do not sample liquid and integrate the sensor on their surface in the form of a coating such as a biochemical material capable of reacting with the analysis to be carried out on the liquid. The length of the needles 10 is thus sufficiently reduced to avoid contact with a nerve of the user, to limit the pain caused by wearing the device 100. For example, each needle has a pyramidal shape. In the present example, each needle 10 comprises on its surface at least one chemical or biochemical material capable of reacting with the bodily analyte for which a measurement is desired (i.e., here, glucose). A material capable of reacting with the bodily analyte is, for example, an enzyme capable of oxidizing the bodily analyte. Advantageously, the sensor 30 comprises several microneedles which consist of a network of microneedles in that they are electrically connected to each other in groups. The microneedles pierce the skin to come into contact with the interstitial fluid when the sensor is in contact with the skin. General description of a method for forming the tip of a microneedle [Fig. 2] describes a method for manufacturing a microneedle according to an embodiment in which the microneedle 10 is made up of a pointed barrel 1 and comprises a base 12 and a tip 11. The pointed barrel 1 is, as will be seen later, a support on which different layers of materials are deposited to define the microneedle 10 for the sensor 30. The base 12 is the lower part of the microneedle and represents between 1 / 2 and 4 / 5 of the total size of the microneedle 10, the tip 11 represents the upper part of the microneedle 10 and therefore represents between 1 / 5 and 1 / 2 of the total height of the microneedle 10. The upper part of the microneedle is the one which is intended to be in contact with the user's skin. Such a method makes it possible to obtain a microneedle 10 whose tip 11 is conductive and whose base 12 is insulating. Also in relation to [Fig.3], the method comprises providing a tip barrel 1 made of, for example, silicon, polymer, plastic or metal (step E0). Other materials are possible. A conductive layer of metal 2 is applied uniformly to the barrel at tip 1 (step E1). The thickness of this conductive layer 2 is between 0.1 um and 7 um. As will be seen later, the metal layer 2 can be obtained in different ways. Then, an insulating layer 3 of thickness x is applied uniformly above the conductive layer 2 (step E2). The insulating layer 3 therefore covers the previously deposited conductive layer 2. The insulating layer 3 is a polymer (for example parylene). This layer is deposited using a coating method known to those skilled in the art. This may be spray deposition, bath deposition, or vacuum deposition. This insulating layer 3 isolates the base of the microneedle from the tip. Indeed, there may be interference related to sweat present on the skin when the microneedle is inserted. Sweat may indeed come into contact with the base of the microneedle and therefore distort the measurements. Then a removal (step E3) of the insulating layer 3 to obtain a conductive tip 11 of the microneedle 10 is implemented. In particular, the removal consists of removing a thickness y greater than or equal to the thickness x so as to strip the tip 11 of the entire thickness of the insulating layer 3 and a portion of thickness of the conductive layer 2, so that the tip 11 is stripped of the entire thickness x of the insulating layer 3, the microneedle 10 thus obtained comprising an insulating base 12 and a conductive tip 11. Such removal is advantageously implemented by means of a laser. In a known manner, the laser has an inaccuracy of + t / 2 # defining a tolerance interval t mm. Furthermore, as will have been understood, the laser must make it possible to remove the entire thickness of the insulating layer 3 of the tip portion 11 of the microneedle 10 in order to be certain of obtaining a conductive tip 11. Thus, to ensure the effectiveness of this step, the laser is configured to remove a layer of thickness y greater than the thickness x of the insulating layer 3 and therefore makes it possible, in addition to the insulating layer 3, to remove a portion of the thickness of the conductive layer 2 of the tip 11 of the microneedle 10. The laser and its parameters are adapted to the type of layer to be removed and are known to those skilled in the art. However, since the tip 11 must be conductive, it must be ensured that the laser does not remove the entire thickness of the conductive layer 2 during the laser removal step. Indeed, the minimum thickness of the conductive layer 2 must be greater than or equal to a minimum thickness Emin typically equal to 0.1 μm in order to have a sufficiently conductive microneedle 10. The minimum thickness can of course be defined differently. It is therefore necessary to take into account the uncertainties associated with laser removal. The lower limit yt / 2 of the removed thickness, due to the uncertainty of the laser during material removal, must be greater than the thickness x um of the insulating layer 3. It is therefore necessary to provide a conductive layer 2 with a thickness greater than or equal to the tolerance interval t plus a value at least equal to the minimum thickness Emin, i.e. here 0.1 um. The conductive layer 2 must therefore have a thickness greater than or equal to t + Emin, i.e. here t + 0.1 um. The thickness of the conductive layer 2 is such that it promotes electrical conductivity and is compatible with the active layer which must cover at least partially the tip of the microneedle and that it allows removal, in particular by laser, of the insulating layer 3. The active layer is a biochemical layer capable of reacting with analytes whose concentration is to be analyzed. At the end of the removal step (step E3), a microneedle 10 is obtained as illustrated in [Fig.2] above step E3. The use of a laser during this step makes it possible to obtain a clean cut of the insulating layer 3 at the level of the limit between base 11 and tip 12. The precision of the clean cut is between 0.1um and 0.9um. The microneedle 10 comprises a tip shank 1 uniformly covered by a conductive layer 2, itself uniformly covered by an insulating layer 3 of thickness x. The tip 11 of the microneedle 10 is stripped of the entire thickness of the insulating layer 3 and of a portion of the thickness of the conductive layer 2 as illustrated in [Fig. 2]. The tip shank 1 of the microneedle 10 remains intact, its thickness is not affected. The thickness of the conductive layer 2 is sufficiently large to guarantee a minimum thickness, for example, of 0.1μm after removal of the entire thickness x of the insulating layer 3 of the tip 11 of the microneedle 10. The conductive layer 2 is advantageously made up of one or more layers superimposed on each other. Conductive layer 2 According to one embodiment and as illustrated in [Fig.4], the conductive layer 2 is advantageously made up of two conductive sub-layers 21, 23: a first conductive sub-layer 21 and a second conductive sub-layer 23. In this case, the insulating layer 3 covers the second conductive sub-layer 23. By suitably choosing the materials and thicknesses of the first and second conductive sub-layers 21, 23, a conductive layer 2 is obtained which is compatible with the shaft 1 and the insulating layer 3 in terms of adhesion between the layers. A delamination phenomenon is thus avoided between the conductive layer thus obtained, the shaft 1 and the insulating layer 3. Indeed, having a single layer for the conductive layer 2 can lead to an adhesion problem with the barrel 1 or with the insulating layer 3, a problem accentuated given the thickness required for the conductive layer 2. Thus, it is expected that the thickness of the first conductive sub-layer 21 is less than that of the second conductive sub-layer 23. In this way, the first sub-layer 21 promotes the maintenance of the thicker second conductive sub-layer 23 and therefore of the conductive layer 2 while allowing the maintenance of the insulating layer 3 on the second conductive sub-layer 23. The deposition of the conductive layer 2 here consists of the uniform deposition of a first conductive sub-layer 21 (step E11) according to a first method and the uniform deposition of a second conductive sub-layer 23 covering the first conductive sub-layer 21 (step E12) according to a second method. The first method and the second method may be identical. However, depending on the type of method used and the thickness to be deposited, it may be advantageous to implement different methods. Thus and preferably, the first method is such that it allows layers of a first thickness to be deposited while the second method is such that it allows layers of a second thickness different from the first thickness to be deposited. Thus, the second method allows layers of a thickness greater than those deposited by the first method to be deposited. For example, the first method allows layers of a thickness between 0.1 μm and 0.2 μm to be deposited while the second method allows layers of a thickness between 0.5 μm and 7 μm to be deposited. According to this embodiment, a second conductive sub-layer 23 is then obtained with a thickness greater than that of the first conductive sub-layer 21. At the end of the step of removing the insulating layer, a microneedle is obtained as illustrated in [Fig. 5]. In this figure, the microneedle 10 comprises a pointed shaft 1 uniformly covered by a conductive layer 2, itself uniformly covered by an insulating layer 3 of thickness x. According to one embodiment, the second conductive sub-layer 23 is made of the same conductive material as that constituting the first conductive sub-layer 21. This promotes adhesion between the two layers. According to one embodiment, the second conductive sub-layer 23 is made of a conductive material different from that constituting the first conductive sub-layer 21. In this case, care will be taken to ensure that the materials chosen are compatible for adhering to each other. In the case where the materials of the first sub-layer 21 or of the second sub-layer 23 are different, care will be taken to ensure that the material of the second conductive sub-layer 23 is made of a more conductive material than that of the first conductive sub-layer 21. For example, the first sub-layer 21 and / or the second sub-layer 21 are made of copper, nickel, gold, silver or titanium, etc. The first underlayer 21 is made of a material chosen to adhere to the pointed shaft while allowing the second underlayer 23 to adhere to the first underlayer 21. Additionally, to avoid a delamination phenomenon between the first conductive sub-layer 21 and the second conductive sub-layer 23 caused by the superposition of layers of different thicknesses and / or different materials, one or the other of the surfaces of these sub-layers 21, 23 in contact have a surface roughness to improve the adhesion between the two. At the end of the removal step (step E3), preferably by laser, as illustrated in [Fig. 5], the tip 11 of the microneedle 10 is stripped of the entire thickness x of the insulating layer 3 and part of the thickness of the conductive layer 2. The thickness of the conductive layer 2 is sufficiently large to guarantee a minimum thickness Emin (for example 0.1jm) after the removal of the insulating layer 3 from the tip 11 of the microneedle 10; the shaft at the tip 1 of the microneedle 10 remains intact, its thickness is not affected. As stated previously, and in order to take into account the uncertainty t of the laser while guaranteeing the presence of a minimum thickness of conductive layer after the removal of the entire thickness x of the insulating layer 3, the thickness of the conductive layer is greater than or equal to t + Emin; t being the total tolerance interval of the laser used during step E3. According to an embodiment illustrated in [Fig.6], the conductive layer 2 consists of the first conductive sub-layer 21 and the second conductive sub-layer 23 and an intermediate sub-layer 22 arranged between the first conductive sub-layer 21 and the second conductive sub-layer 23. Consequently, the deposition of the conductive layer 2 comprises the deposition of the first conductive sub-layer 21 (step E11”) followed by the deposition of the intermediate sub-layer 22 (step E12”) followed by the deposition of the second conductive sub-layer 23 (step E13”). The intermediate layer 22 is preferably deposited just after the deposition of the first conductive layer 21 to avoid oxidation of the first conductive sub-layer 21. The addition of the intermediate layer 22 further reduces the delamination phenomenon, in particular that between the first and second conductive sub-layers 21, 23. In particular, it is expected that the thickness of the intermediate sub-layer 22 is substantially identical to that of the first sub-layer 21. Furthermore, this intermediate sub-layer 22 is made of a material identical to that of the second sub-layer 23. As previously, the first conductive sub-layer 21 is deposited according to a first method and the second conductive sub-layer is deposited according to a second method in order to obtain a second conductive sub-layer 23 of thickness greater than that of the first conductive sub-layer 21. Is the intermediate sub-layer 22 deposited using the first process identical to that used to deposit the first sub-layer 21? Finally, here again it can be provided that the contact surfaces between the layers have a surface roughness to improve the adhesion between the layers. The fact that the intermediate sub-layer 22 and the first conductive sub-layer 21 have a substantially similar thickness makes it possible to avoid delamination between these sub-layers 22, 21. And the fact that the second conductive sub-layer 23 and the intermediate sub-layer 22 are made of the same material makes it possible to avoid delamination while allowing the creation of an excess thickness thanks to the deposition of the second conductive sub-layer 23. According to this embodiment, the delamination phenomenon is particularly reduced. At the end of the removal step, a microneedle is obtained as illustrated in [Fig.7]. In this figure, the tip 11 of the microneedle 10 is stripped of the entire thickness x of the insulating layer 3 according to the method of [Fig.2] and a part of the thickness of the conductive layer 2. The thickness of the conductive layer 2 is sufficiently large to guarantee a minimum thickness of 0.1 μm after the removal of the insulating layer 3 from the tip 11 of the microneedle 10; the tip 1 of the microneedle 10 remains intact, its thickness is not affected. As previously stated, and in order to take into account the uncertainty of the laser while guaranteeing the presence of a minimum thickness of 0.1 mm of conductive layer after removal of the entire thickness x of the insulating layer 3, the thickness of the conductive layer is greater than or equal to t + Emin; t being the total tolerance interval of the laser used during step E3.

Claims

Claims

1. A method of manufacturing a microneedle (10), the microneedle (10) comprising a base (12) and a tip (11), the method comprising the next steps: - supply (EO) of a barrel (1) at the tip; - deposition (El, El1, E12, El1l', El2', E13') of a conductive layer (2) covering the barrel (1); - deposition (E2) of an insulating layer (3) having a thickness x on the conductive layer (2); - removal (E3) of the insulating layer (3) so as to define a tip (11) conducting the microneedle (10) by means of a laser (5), the laser (5) being configured to remove a thickness y greater than or equal to to the thickness x so as to strip the tip (11) of the entire the thickness of the second insulating layer (3) and a portion thickness of the conductive layer (2), so that the tip (11) is stripped of the entire thickness x of the insulating layer (3), the microneedle (10) thus obtained comprising an insulating base (12) and a tip (11) driver.

2. A method according to claim !, wherein the laser comprises an in- tolerance interval t, the conductive layer (2) having a thickness su- 0.1 mm outside the tolerance interval of the laser used during the removal step (E3) so that the conductive layer (2) at the outcome of the removal step has a thickness greater than or equal to 0.1 one

3. A method according to any preceding claim, in which the conductive layer (2) comprises at least a first sub conductive layer (21) covering the barrel (1) and at least a second conductive sub-layer (23) covering the first sub-layer (21) conductive, the second sub-layer (23) having a thickness su- greater than the thickness of the first sub-layer (21).

4. A method according to claim 3, wherein the second sub-layer (23) conductive is deposited using a process different from that used in work for depositing the first conductive underlayer (21).

5. Method according to claim 4, in which the conductive layer (2) comprises an intermediate sub-layer (22) arranged between the first conductive sub-layer (21) and the second sub-layer (23) conductive, the intermediate sub-layer (22) is made of identical material to that of the second conductive sub-layer (23) and has a thickness less than the thickness of the second sub-layer (23) driver.

6. The method of claim 5, wherein the inter-sublayer mediator (22) is deposited using a process identical to that used in work for depositing the first conductive underlayer (21).

7. Method according to any one of the preceding claims, in in which the conductive layer (2) has a thickness of between 0.1 HA and 7 HIHI

8. A method according to any preceding claim, in which the insulating layer (3) is made of electrically insulating material and biocompatible having a thickness between 1 #7 and 20 / 9

9. Microneedle (10) obtained by a method according to any one of the previous claims,