METHOD FOR MANUFACTURING AN ELEMENTARY MODULE OF A MICRONEEDLE SENSOR

Abstract

The invention relates to a method for manufacturing an elementary module (6) of a microneedle sensor, comprising a step of assembling a support (7) with at least one staple (8), the assembly consisting of introducing the staple (8) into an opening (71) formed in the entire thickness of the support (7), the staple forming microneedles.

Description

TECHNICAL FIELD

[0001] The invention relates to ready-to-wear or "wearables" devices used in body monitoring systems, for example for the recording and monitoring of biochemical parameters of the human body, such devices comprising a microneedle sensor.

[0002] The invention relates more particularly to the manufacture of an elementary module comprising at least two microneedles of such a sensor. STATE OF THE ART

[0003] Monitoring many known chronic diseases in humans requires daily recording of biochemical parameters. The concentration level of a bodily analyte in a bodily fluid, for example in blood plasma or in the interstitial fluid of the body's cells, can be measured.

[0004] As a common example, monitoring diabetes in a patient requires an accurate daily reading of the patient's blood glucose level.

[0005] One solution for monitoring diabetes is to perform a puncture, for example at the tip of the finger, to draw a drop of blood, and then to perform a daily measurement of blood glucose in the drop of blood thus obtained.

[0006] Continuous glucose monitoring (CGM) systems have been proposed to eliminate the need for manual blood glucose sampling, making blood glucose measurement less laborious and less invasive.

[0007] Some of these CGM systems perform regular blood glucose measurements in the interstitial fluid between skin cells. Interstitial fluid glucose levels are very close to blood plasma glucose levels. Interstitial fluid measurements allow for simple and minimally invasive monitoring of patients' blood glucose levels; these measurements can be performed using needle sensors, transcutaneously, or non-invasively, such as by iontophoresis or implantable devices with chemofluorescence measurement.

[0008] The international application published under number WO 2019 / 141743 describes a body monitoring system, particularly for blood glucose monitoring. This monitoring system comprises an electronic watch that can be attached to the wrist using a strap. The watch has a case into which is inserted a removable, interchangeable capsule containing a microneedle sensor and an adhesive patch for securing the sensor to the wrist. The case includes a battery that powers the sensor, and the sensor is automatically controlled by the case's electronics to perform a transcutaneous measurement. The blood glucose measurement by the sensor is an electrochemical measurement.

[0009] Manufacturing such a sensor requires a microneedle array. However, obtaining these arrays is a laborious process and often results in a high defect rate during manufacturing. This leads to increased production costs. DESCRIPTION OF THE INVENTION

[0010] The invention proposes to simplify the manufacture of microneedle arrays.

[0011] In this respect, the invention proposes a method for manufacturing an elementary module of a microneedle sensor, comprising a step of assembling a support with at least one staple, the assembly consisting of introducing the staple into an opening formed in the entire thickness of the support, the staple forming microneedles.

[0012] The invention is advantageously complemented by the following features, taken alone or in any technically feasible combination thereof: The staple is U-shaped and comprises an arm and two prongs extending from the arm; inserting the staple into the opening involves more or less aligning a lower surface of the arm with a lower surface of the support; the prongs of the staple are pointed or beveled to facilitate insertion of the staples into a user's skin; the staple is attached to the support by force into the opening, by gluing, or by clipping; the staple is obtained by carrying out the following steps: cutting a strip of staples from a plate, each staple being attached to a strip by a cutting foot; depositing at least one conductive layer on the staple strip, the feet, and the strip; separating each staple at the cutting foot;The cutting foot extends from a central area of ​​the arm of each clip towards the strip, the foot being attached to the arm on a bonding area smaller than the length of the arm; the conductive layer is gold or palladium or titanium; a substrate comprising an array of supports for elementary modules, the process comprising, after the assembly of the elementary modules, cutting each elementary module; the clip has a thickness of between 100 microns and 600 microns, preferably 250 microns, an arm width of between 1500 and 3000 microns, preferably 2000 microns, an arm height of between 200 microns and 1500 microns, preferably 800 microns.

[0013] The invention also proposes an elementary module comprising a support and at least one clip, the elementary module being obtained by means of a process according to the invention.

[0014] The invention also proposes a microneedle sensor comprising a plate and at least one elementary module obtained by means of a process according to the invention.

[0015] The invention makes it possible to easily obtain microneedle arrays.

[0016] With such a process there is no limitation for the height of the staples, other micro-needle manufacturing techniques simply do not allow to obtain heights greater than 500 microns. PRESENTATION OF THE FIGURES

[0017] Other features, purposes and advantages of the invention will become apparent from the following description, which is purely illustrative and not limiting, and which should be read in conjunction with the accompanying drawings on which: there figure 1 illustrates an overview of a device for monitoring a body analyte there figure 2 illustrates a schematic view of a needle sensor according to the invention; the figure 3aand the figure 3b illustrate an elementary module according to two embodiments of the invention; the figure 4a and the figure 4b illustrate a support for an elementary module according to two embodiments of the invention; the figure 5a and the figure 5b illustrate respectively a staple of an elementary module according to one embodiment of the invention and two cross-shaped staples according to another embodiment of the invention; the figure 6a , there figure 6b and the figure 6c illustrate different variants of a staple of an elementary module according to an embodiment of the invention; the figure 7 illustrates the steps in a manufacturing process for an elementary module according to an embodiment of the invention: the figure 8 a substrate comprising several supports for elementary modules according to an embodiment of the invention; the figure 9illustrates manufacturing steps of a staple of an elementary module according to an embodiment of the invention.

[0018] Across all figures, similar elements bear identical references. DETAILED DESCRIPTION General architecture of a body surveillance device

[0019] There figure 1 illustrates a body monitoring device 1 comprising a housing 2, a sensor 3 and an adhesive patch 4.

[0020] Sensor 3 here is a needle sensor designed to provide an electrical current measurement within the interstitial fluid of the wearer of device 1.

[0021] Needles 5 are advantageously arranged on an inner face 31 of the sensor 3. This inner face 31 is intended to be placed on the skin of the wearer.

[0022] The sensor 3 is assembled with the adhesive patch 4, together forming a capsule. The sensor 3 can also be removable from the patch 4. Such a capsule is advantageously mounted as removable with the housing 2. In particular, the capsule, and therefore the sensor 3, preferably engages in a cavity 21 of the housing 2 located on its face intended to be in contact with the skin. The sensor 3 comprises an outer face 32 opposite the inner face 31.

[0023] Housing 2 and the capsule may have complementary shapes, which limits the effort required for proper insertion of the capsule against housing 2.

[0024] Patch 4 has an adhesive layer, or is itself made of an adhesive material. The patch thus allows the capsule to attach to the wearer's skin and helps retain the needles 5 in the interstitial fluid. Patch 4, for example, has a ring shape and covers the capsule.

[0025] The sensor 3 shown here is circular with a central opening 33, but it can take other shapes: rectangular, oblong, ellipsoidal, with or without a central opening. The central opening 33 allows the sensor 3 to be correctly positioned in the cavity 21 of the housing, which includes a central positioning pin (not shown).

[0026] Sensor 3 therefore includes elements which allow the liquid to be collected or the signals detected by each microneedle to be brought to housing 2 for processing (not described here).

[0027] The sensor 3 can take the form of a plastic plate, a printed circuit board (rigid or flexible silicon), a non-conductive metal plate such as aluminum.

[0028] The adhesive patch 4 is designed to adhere to the skin and supports the sensor 3, allowing the device 2 to be detached without removing the sensor 3, keeping it attached to the body. This configuration avoids removing the sensor for certain operations that only involve the device: battery charging, repair, replacement, and data transfer to a computer.

[0029] The housing 2 is advantageously shaped like a watch case and includes means 23 for attaching the device to a user's wrist. This includes a suitable strap to encircle the user's wrist. The strap is preferably adjustable.

[0030] Housing 2 contains several components for analyzing or extracting interstitial fluid. In this regard, reference can be made to document WO 2019 / 141743, filed on behalf of the applicant, which describes in detail the measurement and detection of a physical quantity using microneedles in contact with a bodily fluid, whether or not it is sampled.

[0031] Advantageously, the watch also includes 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.

[0032] Also, the watch may include a light indicator such as an LED, which can be used to signal the end of a sensor preparation operation.

[0033] The needles 5 are advantageously microneedles. The sensor 3 preferably comprises between four and fifty microneedles, or even four hundred microneedles. Of course, a different number can be considered without limiting the description of the invention given here.

[0034] A microneedle is defined as a needle with a small height, preferably between 10 µm and 1000 µm, and preferably between 0.3 mm and 0.8 mm. The height of the microneedles is sufficiently small to avoid contact with a mechanical pain nerve in the wearer when the device is worn.

[0035] The 5 microneedles allow for the measurement of body fluid.

[0036] The 5 microneedles are solid for direct liquid analysis. To analyze liquid, the microneedles do not draw up any liquid and instead incorporate the sensor on their surface in the form of a coating such as a biochemical material capable of reacting with the analysis to be performed on the liquid.

[0037] The length of the needles 5 is thus sufficiently reduced to avoid contact with a nerve of the user, to limit the pain caused by wearing the device 1.

[0038] Each needle, for example, has a pyramidal shape.

[0039] In this example, each needle 5 has on its surface at least one chemical or biochemical material capable of reacting with the body analyte whose measurement is to be obtained (i.e., glucose in this case). A material capable of reacting with the body analyte is, for example, an enzyme capable of oxidizing the body analyte.

[0040] Advantageously, sensor 3 comprises several microneedles, which form a network of microneedles electrically connected to each other in groups. The microneedles pierce the skin to make contact with the interstitial fluid when the sensor is in contact with the skin.

[0041] Sensor 3 illustrated on the figure 2 It comprises a substrate 311 with several elementary modules 6, each elementary module comprising a support 61 and at least two microneedles (not visible). The elementary modules are connected to each other by means of metallic tracks. Advantageously, each elementary module 6 is positioned in a housing 312 and is connected to the substrate 311, for example, by gluing.

[0042] Thus, sensor 3 comprises electrodes, each consisting of at least one microneedle. In particular, sensor 3 includes a working conductivity electrode and a reference conductivity electrode 314.

[0043] During the use of sensor 3 to perform a measurement, a voltage is generated between several needles. At least some of the needles 5 of sensor 3 are at least partially immersed in the interstitial fluid. The chemical or biochemical material present on the surface of the needles 5 reacts with the glucose in the interstitial fluid.

[0044] Sensor 3 thus provides an electrical current measurement, representative of the glucose concentration in the interstitial fluid.

[0045] The substrate 311 and the needles 5 are preferentially arranged on a single face of the sensor 3, which is the face facing upwards according to the orientation of the figure 2This upper surface is intended to be placed against the user's skin.

[0046] Each needle extends from the upper face in a Z direction, from its base to its tip. The Z direction is preferably orthogonal to a plane of the upper face.

[0047] The central aperture 33 is circular in shape. The sensor 3 thus has, in this example, a generally annular shape. Elementary Module

[0048] There figure 3a illustrates an elementary module 6 comprising a support 7 and a clip 8 positioned in an opening formed in the entire thickness of the support 7. The clip 8 forms two microneedles for the sensor 3 described above.

[0049] There figure 3b illustrates an elementary module 6 comprising a support 7 and two staples 8 positioned in a cross within an opening formed through the entire thickness of the support 7.

[0050] As illustrated on the figures 4a and 4b ,support 7 and the opening are for example parallelepiped in shape but other shapes are possible.

[0051] There figure 5a illustrates a clip 8 according to an embodiment. The clip 8 is preferably U-shaped and comprises an arm 81 and two branches 82 extending from the arm 81. Preferably, the branches 82 extend from the ends of the arm 81. On the figure 5b when it comes to positioning two staples in a cross, steps 813 are provided on the arms 81, these steps are complementary.

[0052] The arm 81 comprises a thickness X less than or equal to the thickness X' of the substrate.

[0053] Furthermore, the clip 8 is positioned in the opening 71 so as to align as closely as possible the lower surface 811 of the arm with the lower surface 73 of the support 7, while also ensuring that the arm 81 does not protrude beyond the upper surface 72 of the support 7, the surface that is intended to be in contact with the user's skin. Indeed, the elementary module 6 is designed to be in contact with the user's skin, and the arm 81 must not extend beyond the opening 71, as this could injure the user. Moreover, at the lower surface 73 of the support 7, the elementary module 6 must be securely fixed to the substrate 311 of the sensor 3, with the contact surfaces being as flat as possible to optimize the fixing of the elementary module 6.

[0054] The U-shaped staple 8 has parallel or nearly parallel arms 82. The concept of a staple is well known to those skilled in the art, so the structure of the staple itself is also well known to them.

[0055] In particular, the section of arm 81 and the branches is rectangular as visible on the figure 5a which illustrates a staple.

[0056] As illustrated on the figures 6a, 6b and 6c The prongs 82 of the staple 8 are pointed or beveled to facilitate insertion of the staples into the user's skin. In the case of beveled prongs, it is the free end of the prongs 82 that is beveled. This bevel can be oriented either outwards or inwards towards the arm 81.

[0057] The shape of the end of the staple 8 is adapted for insertion into the user's skin since it has the function of a micro-needle.

[0058] Staple 8 has dimensions adapted to its function as a microneedle and has a thickness between 100 microns and 600 microns, preferably 250 microns, an arm width between 1500 and 3000 microns, preferably 2000 microns, an arm height between 200 microns and 1500 microns, preferably 800 microns.

[0059] The clip 8 has a metallic base and a conductive coating of gold, platinum, or titanium. Since these are microneedles for a biochemical sensor, a layer is required to allow an enzyme to bind to the clip.

[0060] The use of a clip 8 is advantageous because the electrical connection between the branches 82 and the arm 81 is continuous. The branches 82 are designed to be in contact with the liquid containing the analyte to be measured; a current is then generated at the clip 8, which must be carried to the sensor housing 3 for processing. Using the clip 8 eliminates the need for complex electrical connections. Manufacturing a basic module

[0061] There figure 7 illustrates steps in a manufacturing process for an elementary module conforming to an embodiment of the invention.

[0062] In relation to the figure 8 ,To manufacture an elementary module 6, we start with a substrate S comprising a network of supports 7 for elementary modules 6 (step E0). Each support 7 includes a rectangular (or more or less rectangular) opening 71. The opening 71 is adapted to receive a clip 8 as previously described.

[0063] Of course, we can also start from a single support 7 to obtain only an elementary module 6.

[0064] A staple 8 is inserted into each opening (step E1). The staple 8 can be forced in so that the single insertion secures the staple to the substrate. Alternatively, after insertion, the staple is attached to the substrate by gluing or clipping (step E2). The staples are preferably obtained beforehand through specific manufacturing (step E4) (see below).

[0065] Once the staples are inserted into the supports, a cut is made from each 6-element module of the substrate (step E3)

[0066] We then obtain elementary modules as described above.

[0067] These different steps apply to an elementary module comprising two staples as shown above. Staple manufacturing

[0068] The staples are obtained in a simple and uncomplicated way.

[0069] Indeed, as illustrated on the figure 9We start with a metal plate 9 (step E41). A strip of staples is cut from this metal plate 9 (step 42). Each staple 8 is attached to a strip 92 by a cutting foot 93, the cutting foot extending from the staple arm in the opposite direction to the arms. The cutting foot 93 extends from a central area of ​​the arm 81 of each staple 8 towards the strip 92, the foot 93 being attached to the arm 81 at a connection point smaller than the length of the arm 82.

[0070] Next, a deposit of at least one conductive layer 10 is made on the staple tape, feet and strip (step E43). Here, a conductor such as gold, platinum or titanium is deposited.

[0071] Next, each staple 9 is separated at the cutting foot (step E44).

[0072] The advantage of providing a cutting foot is that the deposition step is carried out widely over the entire ribbon and that at the time of separation of the staple 8, only the part of the staple 8 connected to the cutting foot 93 no longer has the additional conductive deposit 10. Thus, the electrical connection from the branches to the arm is ensured.

[0073] In figure 9 the conductive deposit has been represented by a line wider than that of the central area of ​​arm 81. We see the part in thin line which corresponds to the part without additional deposit and which corresponds to the cutting area allowing to separate each staple 8.

Claims

1. Method of manufacturing an elementary module (6) of a microneedle sensor, comprising a step of assembling a support (7) with at least one clip (8), the support comprising an upper surface (72) intended to be in contact with the skin of a user and a lower surface (73), the clip is U-shaped and comprises an arm (81) and two branches (82) extending from each end of the arm (81), the ends of the branches being adapted to be inserted into the skin of a user and forming two microneedles, the assembly consisting of inserting the clip (8) into a rectangular opening (71) formed in the entire thickness of the support (7) so as to position the clip so that the arm (81) does not protrude from the upper surface (72) of the support (7), the clip forming microneedles, an elementary module comprising at least two solid microneedles.

2. Method according to claim 1, wherein the introduction of the clip (8) into the opening (71) consists of aligning a lower surface of the arm with a lower surface of the support.

3. Method according to claim 2, wherein the arms (82) of the staple (8) are pointed or beveled so as to facilitate the insertion of the staples into the skin of a user.

4. A method according to any one of the preceding claims, wherein the staple (8) is fixed to the support by force-fitting into the opening (71) or by gluing or by clipping.

5. A method according to any one of the preceding claims, wherein the staple (8) is obtained by carrying out the following steps: - cutting (E42) from a plate (9) a strip (91) of staples (8), each staple (8) being attached to a strip (91) by a cutting foot (93); - depositing (E43) at least one conductive layer (10) on the strip of staples, the feet and the strip; - separating (E44) each staple (8) at the cutting foot.

6. Method according to the preceding claim, wherein the cutting foot (93) extends from a central area of ​​the arm (81) of each staple (8) to the strip (92), the foot (93) being attached to the arm (81) on a linkage area smaller than the length of the arm (82).

7. A method according to any one of claims 5 to 6, wherein the conductive layer (10) is gold or palladium or titanium.

8. A method according to any one of the preceding claims, wherein the assembly is carried out on a substrate (11) comprising a network of supports for elementary modules, the method comprising, after the assembly of the elementary modules, a cutting of each elementary module.

9. A method according to any one of claims 2 to 8, wherein the clip (8) has a thickness of between 100 microns and 600 microns, preferably 250 microns, an arm width of between 1500 and 3000 microns, preferably 2000 microns, and an arm height of between 200 microns and 1500 microns, preferably 800 microns.

10. Elementary module comprising a support and at least one clip (8), the elementary module being obtained by means of a process according to any of the preceding claims.

11. Microneedle sensor comprising a stage and at least one elementary module obtained by means of a method according to any one of the preceding claims.