METHOD FOR PRODUCING AN ANALYTE SENSOR, AN ANALYTE SENSOR, AND A USE THEREOF

Abstract

A method for producing an analyte sensor is disclosed. A first substrate having a first side and a second side is provided. The second side has a first layer having a first conductive material. A second substrate having a first side and a second side is provided. The first side has a second layer having a second conductive material. The second side of the second substrate has a third layer having a third conductive material. A conductive preparation is applied onto at least one of the first side of the first substrate and the third layer or a portion thereof to form a conductive preparation layer. The conductive preparation has conductive particles and a polymeric binder. The first side of the first substrate is laminated with the second side of the second substrate. An analyte sensor is obtained.

Claims

1. A method for producing an analyte sensor, comprising: a) providing a first substrate having a first side and a second side, wherein the second side has a first layer comprising a first conductive material; b) providing a second substrate having a first side and a second side, wherein the first side has a second layer comprising a second conductive material and the second side has a third layer comprising a third conductive material; c) applying a conductive preparation onto at least one of the first side of the first substrate and the third layer or a portion thereof to form a conductive preparation layer, wherein the conductive preparation comprises a plurality of conductive particles and a polymeric binder; d) laminating the first side of the first substrate with the second side of the second substrate; and e) obtaining the analyte sensor.

2. The method according to claim 1, wherein the conductive particles comprise carbon, Ag, AgCl or Ag/AgCl.

3. The method according to claim 1, wherein the at least one polymeric binder is selected from at least one of a thermoplastic polyurethane and an acrylate.

4. The method according to claim 1, wherein the conductive preparation is applied until the layer of the conductive preparation has a thickness of 5 μm to 20 μm.

5. The method according to claim 1, wherein a first electrode is formed on the first layer or the first layer is the first electrode.

6. The method according to claim 5, wherein the first electrode is a first working electrode.

7. The method according to claim 1, wherein a second electrode is formed on the second layer or the second layer is the second electrode.

8. The method according to claim 7, wherein the second electrode is a second working electrode or a counter electrode.

9. The method according to claim 1, wherein an interlayer is formed by the third layer and the conductive preparation layer.

10. The method according to claim 9, wherein the interlayer comprises a third electrode.

11. The method according to claim 10, wherein the third electrode is a combined counter/reference electrode or a reference electrode.

12. The method according to claim 1, wherein a laminated substrate is obtained by step d), wherein the laminated substrate is cut after step d) and prior to step e).

13. The method according to claim 12, wherein the laminated substrate is cut by laser cutting or dye cutting.

14. An analyte sensor made by the method of claim 1.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0150] The above-mentioned aspects of exemplary embodiments will become more apparent and will be better understood by reference to the following description of the embodiments taken in conjunction with the accompanying drawings, wherein:

[0151] FIGS. 1A, 1B, 1C, 1D and 1E each schematically illustrates preferred embodiments of the method for producing an analyte sensor according to this disclosure; and

[0152] FIGS. 2A, 2B, 2C, 2D and 2E each schematically illustrates preferred embodiments of the method for producing an analyte sensor according to this disclosure.

DESCRIPTION

[0153] The embodiments described below are not intended to be exhaustive or to limit the invention to the precise forms disclosed in the following detailed description. Rather, the embodiments are chosen and described so that others skilled in the art may appreciate and understand the principles and practices of this disclosure.

[0154] FIGS. 1 and 2 each schematically illustrates a preferred embodiment of the method 110 for producing an analyte sensor 112, in particular a portion thereof, according to this disclosure in cross-sectional views which are not to scale. The analyte sensor 112 may be a fully or partially implantable analyte sensor for continuously monitoring an analyte, in particular by performing a continuous measurement of the analyte in a subcutaneous tissue, preferably in a body fluid, especially in an interstitial fluid or in blood. For this purpose, the analyte sensor 112 may be configured to convert the analyte into an electrically charged entity by using an enzyme. Specifically, the analyte may comprises glucose, which may be converted into an electrically charged entity by using at least one of glucose oxidase (GOD) or glucose dehydrogenase (GHD) as the enzyme. As an alternative, the analyte sensor 112 may be configured to specifically detect two or more analytes in a concurrent or consecutive manner. Specifically, the analyte sensor 112 may be configured to detect glucose and, concurrently or consecutively, a further analyte, preferably selected from lactate or ketones, in a specific fashion. However, the analyte sensor 112 according to this disclosure may also be applicable to other kinds of analytes as well as to other processes for monitoring an analyte. In the particular example of FIGS. 1 and 2, the implantable portion of the analyte sensor 112 as depicted there comprises an elongate analyte sensor; however, other forms of the analyte sensor 112 may also be feasible.

[0155] As illustrated in FIGS. 1a) and 2a), a first substrate 114 is provided in accordance with step a) of the method 110. Herein, the first substrate 114 has a first side 116 and a second side 118. Further, the second side 118 of the first substrate 114 has a first layer 120 which comprises a first conductive material 122, while the first side 116 of the first substrate 114 remains blank. Instead of having an uncoated insulating surface as depicted in FIGS. 1a) and 2a), the first side 116 of the first substrate 114 may, in an alternative embodiment not depicted here, comprise at least one electrically insulating layer. As further schematically shown in FIGS. 1a) and 2a), the first side 116 and the second side 118 of the first substrate 114 are arranged in an opposing fashion with respect to each other and the first substrate 114.

[0156] As illustrated in FIGS. 1b) and 2b), a second substrate 124 is provided in accordance with step b) of the method 110. Herein, the second substrate 124 has a first side 126 and a second side 128. Further, the first side 126 of the second substrate 124 has a second layer 130 which comprises a second conductive material 132 while the second side 128 of the second substrate 124 has a third layer 134 which comprises a third conductive material 136. As further schematically shown in FIGS. 1b) and 2b), the first side 126 and the second side 128 of the second substrate 124 are arranged in an opposing fashion with respect to each other and the second substrate 124.

[0157] In the particular examples of FIGS. 1 and 2, each of the first substrate 114 and the second substrate 124 is a planar substrate; however, each substrate 114, 124 may also have a different form. Further, each of the first substrate 114 and the second substrate 124 as illustrated there has an elongated shape, in particular a bar shape; however, other kinds of shapes may also be feasible. Preferably, each substrate 114, 124 may have a lateral extension of 1 mm to 500 mm, preferably of 10 mm to 100 mm, more preferred of 20 mm to 50 mm, and a thickness of 10 μm to 100 μm, preferably of 20 μm to 80 μm, more preferred of 50 μm to 80 μm; however, a different value for the lateral extension and/or the thickness may also be feasible.

[0158] In particular, each of the first substrate 114 and the second substrate 124 may be an electrically insulating substrate which may, preferably, comprise at least one electrically insulating material, especially to avoid unwanted currents between the second layer 120 and the third layer 134. Herein, the electrically insulating material may, preferably, be selected from polyethylene terephthalate (PET) or polycarbonate (PC); however, other kinds of electrically insulating materials, such as the insulating materials as indicated above, may also be feasible.

[0159] Further, each of the first conductive material 122 as comprised by the first layer 120, the second conductive material 132 as comprised by the second layer 130, and the third conductive material 136 as comprised by third layer 134 as shown in the particular examples of FIGS. 1 and 2 may, preferably, comprise an electrically conductive material. In particular, the conductive material may be selected from a noble metal, especially gold; or from an electrically conductive carbon material; however, further kinds of conductive materials may also be feasible. The layers 120, 130, 134 may, specifically, have an elongated shape, such as a strip shape or a bar shape; however, other kinds of shapes may also be feasible. In general, the layers 120, 132, 134 may, partially or completely, cover the respective sides 118, 126, 128 of the corresponding substrate 114, 124. In a preferred embodiment, in which the layers 120, 132, 134 may only partially cover a portion of the respective sides 118, 126, 128 of the corresponding substrate 114, 124, an insulating layer (not depicted here) may, partially or completely, cover the remaining portion of the corresponding substrate 114, 124. In particular, the layers 120, 132, 134 may, preferably, be produced, prior to steps a) and b), using an additive process by applying, especially by depositing, the conductive material to the respective sides 118, 126, 128 of the corresponding substrate 114, 124; however, a further process of producing the layers 120, 132, 134 may be feasible. In particular, the additive process may be selected from at least one process as indicated above, wherein sputtering may particularly be preferred.

[0160] As illustrated in FIG. 1c), a layer 138 of a conductive preparation 140 is, according to step c), applied onto the third layer 134 or a portion thereof. In an alternative embodiment as illustrated in FIG. 2c), the layer 138 of the conductive preparation 140 is applied onto the first side 116 of the first substrate 114 or a portion thereof. It is emphasized here that selecting either the procedure as shown in FIG. 1c) or the procedure as shown in FIG. 2c) may not result in a difference in the analyte sensor as obtained by the method 110.

[0161] The conductive preparation 140 comprises at least one first component and at least one second component, wherein the at least one first component is or comprises a plurality of conductive particles, wherein the at least one second component is or comprises at least one polymeric binder. However, further types of components may also be conceivable, in particular at least one solvent. In a particularly preferred embodiment, the conductive particles comprise carbon, Ag, AgCl or Ag/AgCl. In a further preferred embodiment, the at least one polymeric binder may be selected from at least one of a thermoplastic polyurethane (TPU) or an acrylate, wherein the thermoplastic polyurethane (TPU) may particularly be preferred. For further kinds of suitable polymeric binders, reference can be made to the description above. The layer 138 of the conductive preparation 140 may be applied by any suitable additive process which may be selected from at least one process as indicated above, wherein a deposition process may particularly be preferred. In a particularly preferred embodiment, the conductive preparation 140 may applied onto the third layer 134 or a portion thereof, or on the first side 116 of the first substrate 114 or a portion thereof, respectively, until the layer 138 of the conductive preparation 140 may have a thickness of 5 μm to 20 μm, preferably of 10 μm±2 μm.

[0162] As illustrated in FIGS. 1d) and 2d), the first side 116 of the first substrate 114 is, according to step d), laminated with the second side 128 of the second substrate 124. In the embodiment as shown in FIG. 1d) in which the layer 138 of a conductive preparation 140 is applied onto the third layer 134 or the portion thereof, the first side 116 of the first substrate 114 is laminated onto the second side 128 of the second substrate 124. In the alternative embodiment as illustrated in FIG. 2d), in which the layer 138 of the conductive preparation 140 is applied onto the first side 116b of the first substrate 114 or the portion thereof, the second side 128 of the second substrate 114 is laminated onto the first side 116 of the first substrate 114 in a laminating process indicated by arrows carrying reference sign 142. Independently of the embodiment as selected during step d), the process of joining the adjacent sides 116, 128 of the two individual substrates 114, 124 results in a permanently assembled object, also denoted as a “sandwich,” which constitutes the desired analytical sensor 144 as illustrated in FIGS. 1e) and 2e).

[0163] In a particular embodiment, at least one further process may, in addition, be applied prior to the laminating process 142, especially, to improve at least one property of at least one of the sides 116, 128 as affected by the laminating process 142. Herein, the at least one further process may, specifically, be selected from at least one of pre-processing or pre-coating; however, at last one further process may also be feasible. In a further particular embodiment, at least one further process may, in addition, be applied during or after the laminating process 142, especially, to improve the permanent assembly of the analyte sensor 112. Herein, the at least one further process may, specifically, be or comprise finishing and/or smoothing the analyte sensor 112 by applying a calendering process; however, at last one further process may also be feasible.

[0164] In a particular embodiment, TPU which is not sticky at room temperature can be used as the polymeric binder in the conductive preparation 140. In a first embodiment, solvent-free TPU and a solvent-free TPU-based Ag/AgCl paste, which are solid at room temperature, are heated up to a temperature of 80° C. to 100° C. to reach a liquid state. Both molten masses are transferred to one of the substrates 114, 124, especially, by using a slit die. While the coating is still hot and sticky, the other one of the substrates 114, 124 is applied to the conductive preparation 140, whereby the laminated analyte sensor 112 is obtained. Optionally, calendering can be used. In an alternative embodiment, both materials the TPU and the TPU-based Ag/AgCl paste are solutions. Both solutions are transferred to one of the substrates 114 124, especially, by using a slit die. Both solutions are dried in order to solidify, whereby the solvent is removed, at least to a large extent. In order to generate the laminated analyte sensor 112, hot laminating can be applied using a temperature which is sufficient to melt both solutions. In a still further embodiment, the conductive preparation may comprise acrylate-based Ag/AgCl, which is sticky also at room temperature, such that cold laminating can be used. However, further embodiments may also be feasible.

[0165] As schematically illustrated in FIGS. 1e) and 2e), the analyte sensor 112 as obtained during step e) comprises: [0166] a first electrode 144 which corresponds here to the first layer 120; [0167] a second electrode 146 which corresponds here to the first layer 130; and [0168] a third electrode 148 which corresponds here to an interlayer 150 which is formed by the third layer 134 and the layer 138 of the conductive preparation 140 in a fashion that the interlayer 150 is electrically conductive.

[0169] Herein, the electrodes 144, 146, 148 are arranged in a stack 152 as schematically depicted in FIGS. 1e) and 2e). In a further embodiment (not depicted here), the first electrode 144 may, alternatively or in addition, be formed as an additional conductive layer which may be attached to the first layer 120 and/or the second electrode 146 may, alternatively or in addition, be formed as a further additional conductive layer which may be attached to the second layer 130. Herein, each electrode 144, 146, 148 may have a lateral extension of 1 mm to 25 mm, preferably of 2 mm to 20 mm, more preferred of 5 mm to 20 mm, and a thickness of 5 μm to 20 μm, preferably of 10 μm±2 μm. However, further embodiments of the electrodes may also be feasible.

[0170] In a preferred embodiment as schematically shown in FIG. 1e), the first electrode 144 corresponding to the first layer 120 may be or comprise a first working electrode 154 and the second electrode 146 corresponding to the second layer 130 may be or comprise a second working electrode 156 while the third electrode 148 as provided by the interlayer 150 may, preferably, be or comprise a combined counter/reference electrode 158.

[0171] In an alternative embodiment as schematically shown in FIG. 2e), the first electrode 144 corresponding to the first layer 120 may be or comprise the working electrode 160 and the second electrode 146 corresponding to the second layer 130 may be or comprise a counter electrode 162, while the third electrode 148 as provided by the interlayer 150 may be a reference electrode 164. However, further kinds of embodiments with respect to the electrodes 144, 146, 148 may also be feasible, in particular a further embodiment in which the electrodes 144, 146, 148 as used in the stack 152 of FIG. 2e) may comprise the same assignment as the corresponding electrodes 144, 146, 148 as used in the stack 152 of FIG. 1e), or vice-versa.

[0172] While exemplary embodiments have been disclosed hereinabove, the present invention is not limited to the disclosed embodiments. Instead, this application is intended to cover any variations, uses, or adaptations of this disclosure using its general principles. Further, this application is intended to cover such departures from the present disclosure as come within known or customary practice in the art to which this invention pertains and which fall within the limits of the appended claims.

LIST OF REFERENCE NUMBERS

[0173] 110 method for producing an analyte sensor [0174] 112 analyte sensor [0175] 114 first substrate [0176] 116 first side [0177] 118 second side [0178] 120 first layer [0179] 122 first conductive material [0180] 124 second substrate [0181] 126 first side [0182] 128 second side [0183] 130 second layer [0184] 132 second conductive material [0185] 134 third layer [0186] 136 third conductive material [0187] 138 layer [0188] 140 conductive preparation [0189] 142 laminating process [0190] 144 first electrode [0191] 146 second electrode [0192] 148 third electrode [0193] 150 interlayer [0194] 152 stack [0195] 154 first working electrode [0196] 156 second working electrode [0197] 158 counter/reference electrode [0198] 160 working electrode [0199] 162 counter electrode [0200] 164 reference electrode