Electrochemical and luminescent sensor structures integrated on common substrate

• US 9,993,187 B2
• Filed: 01/22/2015
• Issued: 06/12/2018
• Est. Priority Date: 01/23/2014
• Status: Active Grant

• Current Assignee: Joanneum Research Forschungsgesellschaft MbH & Co. KG, JOANNEUM RESEARCH Forschungsgesellschaft mbH (Province of Styria)
• Original Assignee: Joanneum Research Forschungsgesellschaft MbH & Co. KG
• Inventors: Hajnsek, Martin
• Primary Examiner(s): Natnithithadha, Navin
• Assistant Examiner(s): Shostak, Andrey
• Application Number:
  US14/603,157
• Publication Number:
  US 20150223742A1
• Time in Patent Office: 1,237 Days
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/1455 using optical sensors, e.g. spectral photometrical oximeters
• CPC Class Codes: A61B 5/14556 by fluorescence A61B5/14555 takes precedence
• CPC Class Codes: A61B 5/1459 invasive, e.g. introduced into the body by a catheter A61B5/1464 takes precedence
• CPC Class Codes: A61B 5/1468 using chemical or electrochemical methods, e.g. by polarographic means A61B5/1486 takes precedence
• CPC Class Codes: A61B 5/1473 invasive, e.g. introduced into the body by a catheter A61B5/1482 takes precedence
• CPC Class Codes: A61B 5/14735 comprising an immobilised reagent
• CPC Class Codes: A61B 5/1486 using enzyme electrodes, e.g. with immobilised oxidase
• CPC Class Codes: A61B 5/14865 invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors
• CPC Class Codes: A61B 5/4839 combined with drug delivery
• CPC Class Codes: A61B 5/6852 Catheters
• CPC Class Codes: C12Q 1/006 for glucose
• CPC Class Codes: G01N 21/64 Fluorescence; Phosphorescence
• CPC Class Codes: G01N 21/6428 Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: G01N 21/6486 Measuring fluorescence of biological material, e.g. DNA, RNA, cells G01N21/6428 takes precedence

Abstract

A sensor arrangement for detecting information indicative of a physiological substance in a body material of a physiological subject, wherein the sensor arrangement comprises a substrate, a first sensor structure connected to the substrate and being configured for sensing the physiological substance electrochemically, and a second sensor structure connected to the substrate and being configured for sensing the physiological substance by a luminescence detection.

Claims

1. A sensor arrangement for detecting information indicative of a physiological substance in a body material of a physiological subject, the sensor arrangement comprising:

a substrate;

a first sensor structure connected to the substrate and being configured for sensing the physiological substance electrochemically; and

a second sensor structure connected to the substrate and being configured for sensing the physiological substance by a luminescence detection,

wherein the first sensor structure comprises an electrode and an enzyme comprising structure, the electrode being configured for electrically detecting a product of an enzyme-catalyzed chemical reaction between the physiological substance and an educt,

wherein the second sensor structure comprises a luminescent substance having luminescent properties which change upon change of an amount of the educt of the enzyme-catalyzed chemical reaction, and

wherein the electrode is arranged directly on the substrate, the luminescent substance is arranged in a surface portion of the sensor arrangement and is configured to contact the body material, and the enzyme comprising structure is arranged between the electrode and the luminescent substance.

2. The sensor arrangement of claim 1, wherein at least one of the first sensor structure and the second sensor structure is configured as at least one layer formed in and/or on and/or above the substrate, and wherein the first sensor structure and the second sensor structure together constitute a layer sequence on the substrate.

3. The sensor arrangement of claim 1, wherein the second sensor structure comprises a permeable membrane in which the luminescent substance is embedded.

4. The sensor arrangement of claim 1, wherein at least a part of the first sensor structure and at least a part of the second sensor structure are integrated into a common physical body so that a sensor event detectable by the first sensor structure and a sensor event detectable by the second sensor structure both occur within the common physical body.

5. The sensor arrangement of claim 1, wherein the second sensor structure is formed directly on the first sensor structure and the first sensor structure is formed directly on the substrate to thereby space the substrate with regard to the second sensor structure.

6. The sensor arrangement of claim 1, wherein both the first sensor structure and the second sensor structure are configured for detecting glucose as the physiological substance.

7. A monitoring system for monitoring a physiological substance in a body material of a physiological subject, the monitoring system comprising:

a catheter being implantable in the physiological subject;

a sensor arrangement integrated with the catheter, the sensor arrangement having a substrate, a first sensor structure connected to the substrate and a second sensor structure connected to the substrate, the sensor arrangement arranged such that the first sensor structure and the second sensor structure interact with a body material comprising the physiological substance in the physiological subject when the catheter is implanted in the physiological subject, the first sensor structure having an electrode and a structure comprising an enzyme, the electrode configured to electrochemically detect a product of an enzyme-catalyzed chemical reaction between the physiological substance and an educt, the second sensor structure having a luminescent substance having properties that change upon change of an amount of the educt of the enzyme-catalyzed chemical reaction, the second sensor configured to sense the physiological substance by a luminescence detection, wherein the electrode is arranged directly on the substrate, the luminescent substance is arranged in a surface portion of the sensor arrangement and is configured to contact the body material, and the enzyme comprising structure is arranged between the electrode and the luminescent substance; and

an evaluation unit configured for evaluating a first sensor signal and a second sensor signal of the sensor arrangement in common, wherein the first sensor signal is detected as an electrochemical response of the first sensor structure upon interaction of the physiological substance with the first sensor structure, and the second sensor signal is detected as a response of luminescence properties of the second sensor structure upon interaction with the physiological substance.

8. The monitoring system of claim 7, wherein the catheter is a catheter tube, and wherein the sensor arrangement is arranged circumferentially at the catheter tube.

9. The monitoring system of claim 7, further comprising:

a supply unit configured for supplying a physiologically active substance to the physiological subject in a quantity depending on a result of the evaluation of the evaluation unit.

10. The monitoring system of claim 9, wherein the supply unit is configured for supplying the physiologically active substance to the physiological subject via a permeable section of the catheter.

11. The monitoring system of claim 7, further comprising:

an electrically conductive signal supply structure configured for transmitting an electric stimulus signal to the first sensor structure; and

an electrically conductive detection structure configured for transmitting an electric detection signal to the evaluation unit, the electric detection signal being generated at the first sensor structure in response to the electric stimulus signal upon interaction of the sensor arrangement with the physiological substance.

12. The monitoring system of claim 7, further comprising:

an electromagnetic radiation source configured for transmitting primary electromagnetic radiation to the second sensor structure; and

an electromagnetic radiation detector configured for detecting secondary electromagnetic radiation generated at the second sensor structure in response to the primary electromagnetic radiation upon interaction of the sensor arrangement with the physiological substance, and configured for transmitting a corresponding detection signal to the evaluation unit.

13. The monitoring system of claim 7, further comprising:

an insertion needle configured to be selectively insertable into the catheter for inserting the catheter into the physiological subject or retractable out of the catheter after the insertion of the catheter into the physiological subject.

14. The monitoring system of claim 7, further comprising:

a hollow insertion needle configured so that the catheter is selectively insertable into the insertion needle for inserting the catheter into the physiological subject and that the insertion needle is retractable relative to the catheter after the insertion of the catheter into the physiological subject.

15. A method of manufacturing a sensor arrangement for detecting information indicative of a physiological substance in a body material, the method comprising:

connecting a first sensor structure to a substrate and configuring the first sensor structure for sensing the physiological substance electrochemically; and

connecting a second sensor structure with the substrate and configuring the second sensor structure for sensing the physiological substance by a luminescence detection,

wherein the first sensor structure is arranged with an electrode and a structure comprising an enzyme, the electrode configured to electrochemically detect a product of an enzyme-catalyzed chemical reaction between the physiological substance and an educt, the second sensor structure having a luminescent substance with properties that change upon change of an amount of the educt of the enzyme-catalyzed chemical reaction, the second sensor structure configured to sense the physiological substance by a luminescence detection, and

wherein the electrode is arranged directly on the substrate, the luminescent substance is arranged in a surface portion of the sensor arrangement and is configured to contact the body material, and the enzyme comprising structure is arranged between the electrode and the luminescent substance.

16. The method of claim 15, wherein the first sensor structure comprises an enzyme layer and an electrode, and wherein the electrode is deposited on the substrate.