Implantable sensor element

• US 9,826,926 B2
• Filed: 10/02/2009
• Issued: 11/28/2017
• Est. Priority Date: 10/02/2008
• Status: Active Grant

• Current Assignee: EyeSense AG
• Original Assignee: EyeSense AG
• Inventors: Mller, Achim, Herbrechtsmeier, Peter
• Primary Examiner(s): Winakur, Eric
• Assistant Examiner(s): Fardanesh, Marjan
• Application Number:
  US13/122,087
• Publication Number:
  US 20110224514A1
• Time in Patent Office: 2,979 Days
• Field of Search: 600310-344
• CPC Class Codes: A61B 2562/0238 Optical sensor arrangements for performing transmission measurements on body tissue
• CPC Class Codes: A61B 2562/12 Manufacturing methods specially adapted for producing sensors for in-vivo measurements
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/1459 invasive, e.g. introduced into the body by a catheter A61B5/1464 takes precedence
• CPC Class Codes: A61B 5/14735 comprising an immobilised reagent
• CPC Class Codes: A61B 5/685 Microneedles
• CPC Class Codes: B29C 39/006 Monomers or prepolymers by reaction injection moulding B29C67/246
• CPC Class Codes: B29C 39/021 by casting in several steps
• CPC Class Codes: B29C 39/023 for making multicoloured articles
• CPC Class Codes: B29C 39/025 for making multilayered articles
• CPC Class Codes: B29C 39/028 having an axis of symmetry
• CPC Class Codes: B29C 39/10 incorporating preformed parts or layers, e.g. casting around inserts or for coating articles coating a surface by casting in general B05D1/30, B29C39/126 takes precedence
• CPC Class Codes: B29C 39/24 Feeding the material into the mould

Abstract

The invention relates to a sensor element for detecting at least one analyte in a body fluid or in a body tissue, particularly for determining at least one metabolite concentration in a body fluid. The sensor element comprises an implantable, one-piece shaped body, which comprises a sensor end and a coupling end. The shaped body comprises, in the area of the sensor end, at least one sensor area, which comprises at least one sensor material. The sensor material changes at least one optically measurable property in the presence of the analyte. The shaped body also has at least one optically transparent coupling part, which is designed to transmit electromagnetic radiation in at least one spectral range between the sensor area and the coupling end. In the sensor area, the shaped body has at least one optically transparent matrix material, and the analyte can at least partially diffuse through the matrix material to the sensor material. The sensor material is embedded in the matrix material. The coupling part is formed at least partially by the matrix material.

Claims

1. Sensor element for detecting at least one analyte in a body fluid or in a body tissue, particularly for determining at least one metabolite concentration in a body fluid, wherein the sensor element comprises an implantable, one-piece shaped body, wherein the shaped body comprises a sensor end and a coupling end, wherein the shaped body comprises, in the area of the sensor end, at least one sensor area, wherein the sensor area comprises at least one sensor material which changes at least one optically measurable property in the presence of the analyte, wherein the shaped body also has at least one optically transparent coupling part, wherein the coupling part is designed to transmit electromagnetic radiation in at least one spectral range between the sensor area and the coupling end, wherein the shaped body has, in the sensor area, at least one optically transparent matrix material, wherein the analyte can at least partially diffuse through the matrix material to the sensor material, wherein the sensor material is embedded in the matrix material, wherein the coupling part has a length between 1 millimeter and 8 millimeters and is formed at least partially by the matrix material, wherein the sensor material is at least partially embedded in the matrix material in microcapsules, wherein the matrix material comprises at least one curable plastic comprising a crosslinkable plastic.

2. Sensor element according to claim 1, wherein the coupling part is substantially free of sensor material and the crosslinkable plastic comprises a biocompatible crosslinkable plastic in cured form.

3. Sensor element according to claim 1, wherein the sensor material is immobilized in the matrix material.

4. Sensor element according to one of the claim 1, wherein the matrix material in the sensor area, in the implanted state of the sensor element, is configured to be in direct contact with the body fluid and/or the body tissue.

5. Sensor element according to claim 1, wherein the coupling part is an elongate coupling part with a substantially homogeneous refractive index.

6. Sensor element according to claim 1, wherein the crosslinkable plastic comprises at least one hydrogel and/or at least one random copolymer.

7. Sensor element according to claim 1, wherein the crosslinkable plastic is produced using at least one of the following materials:

a nelfilcon polymer;

a crosslinkable polyvinyl acetate or a crosslinkable derivative of the polyvinyl acetate;

a crosslinkable polyvinyl alcohol or a crosslinkable derivative of the polyvinyl alcohol;

a crosslinkable polymer based on polyethylene glycol, in particular based on at least one of the following polymers;

bis(acryloyl) polyethylene glycol, bis(acrylamido) polyethylene glycol, a polyurethane based on polyethylene glycol, a bis- or tris-isocyanate, an acryloyl isocyanate;

a crosslinkable polymer based on crosslinkable silicone hydrogel copolymers, in particular based on co-polycondenates of bis(aminodimethyl) siloxanes and/or hydrophilic di- and/or tri-isocyanates and/or acryloyl isocyanates;

a telechelic polymer and/or a multivalent hydrophilic polymer.

8. Sensor element according to claim 1, wherein the shaped body is provided completely or partially with a biocompatible coating, a multi-layer coating and/or a plasma coating.

9. Sensor element according to claim 1, wherein the shaped body also comprises at least one active substance that promotes healing.

10. Sensor element according to claim 9, wherein the active substance that promotes healing is arranged in and/or on the shaped body in such a way as to be able to diffuse into the surrounding body tissue.

11. Sensor element according to claim 1, wherein at least one reference material in the form of reference particles is also embedded in the sensor area, and wherein the reference material has at least one optically measurable reference property that does not substantially change in the presence of the analyte.

12. Sensor arrangement comprising at least one sensor element according to claim 1 and at least one optical detector, designed for coupling optically to the coupling end, when the sensor element is implanted in a body tissue, and for measuring the at least one optically measurable property of the sensor material.

13. Method for manufacturing a sensor element for detecting at least one analyte in a body fluid or in a body tissue, the method comprising:

introducing a first prepolymer liquid with at least one first curable prepolymer for producing an optically transparent coupling part into a cannula;

introducing a second prepolymer liquid with at least one second curable prepolymer for producing a sensor area into the cannula;

introducing at least one sensor material into the second prepolymer liquid, wherein the sensor material changes at least one optically measurable property in the presence of the analyte; and

crosslinking the first prepolymer liquid and the second prepolymer liquid, such that a shaped body with a sensor end and a coupling end is obtained.

14. Method according to claim 13, wherein the crosslinking comprises at least one of the following types of crosslinking:

a photochemical crosslinking, or, a thermal crosslinking.

15. Method according to claim 13, wherein the first curable prepolymer and the second curable prepolymer are at least partially chemically identical and comprise a curable matrix material.

16. Method according to claim 13, wherein the shaped body at least partially corresponds, in terms of its outer shape, to the shape of the inner lumen of the cannula.

17. Method according to claim 13, wherein the cannula is at least partially transparent.

18. Method according to claim 13, wherein the first prepolymer liquid and/or the second prepolymer liquid are introduced into the cannula from at least one prepolymer reservoir, by being sucked in by means of an underpressure and/or by being forced in by means of an overpressure.

19. Method according to claim 13, wherein the shaped body is additionally provided with a coating comprises at least one of

a biocompatible coating, in particular a hydrogel coating;

a multi-layer coating;

a coating with at least one active substance that promotes healing; and

a coating with at least one second sensor material that changes at least one optically measurable property in the presence of the analyte.

20. Method according to claim 19, wherein the coating is applied by means of at least one of the following:

an immersion method;

an immersion method with at least one subsequent crosslinking step in order to crosslink the coating; and

a co-extrusion method by means of a cannula with at least two extrusion lumens, wherein at least a first of the extrusion lumens is used to generate the coating and at least a second of the extrusion lumens is used to generate the coupling part and/or the sensor area.

21. Method according to claim 20, wherein at least one preliminary treatment step is performed prior to the application of the coating to improve the adherence of the coating to the shaped body.