WO1996026668A1 - Systeme de detection implantable pour determiner des concentrations de substances dans des organismes vivants - Google Patents

Systeme de detection implantable pour determiner des concentrations de substances dans des organismes vivants Download PDF

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Publication number
WO1996026668A1
WO1996026668A1 PCT/DE1996/000356 DE9600356W WO9626668A1 WO 1996026668 A1 WO1996026668 A1 WO 1996026668A1 DE 9600356 W DE9600356 W DE 9600356W WO 9626668 A1 WO9626668 A1 WO 9626668A1
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WO
WIPO (PCT)
Prior art keywords
substance
sensor system
capillary membrane
living organisms
implantable sensor
Prior art date
Application number
PCT/DE1996/000356
Other languages
German (de)
English (en)
Inventor
Meinhard Knoll
Original Assignee
Meinhard Knoll
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Meinhard Knoll filed Critical Meinhard Knoll
Priority to EP96904719A priority Critical patent/EP0812147A1/fr
Priority to JP8525962A priority patent/JPH11501234A/ja
Publication of WO1996026668A1 publication Critical patent/WO1996026668A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/68—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
    • A61B5/6846—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive
    • A61B5/6847—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive mounted on an invasive device
    • A61B5/6865—Access ports
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/14525—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using microdialysis
    • A61B5/14528—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using microdialysis invasively
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/14532—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue for measuring glucose, e.g. by tissue impedance measurement
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/48—Other medical applications
    • A61B5/4836—Diagnosis combined with treatment in closed-loop systems or methods
    • A61B5/4839—Diagnosis combined with treatment in closed-loop systems or methods combined with drug delivery
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/68—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
    • A61B5/6846—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive
    • A61B5/6847—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive mounted on an invasive device
    • A61B5/686—Permanently implanted devices, e.g. pacemakers, other stimulators, biochips

Definitions

  • Implantable sensor system for determining substance concentrations in living organisms
  • the invention relates to an implantable sensor system for determining substance concentrations in living organisms and to methods for its production.
  • Such sensors can be used for the continuous measurement of the concentration of glucose, lactate and other analytes in the tissue or blood vessels of humans, animals and other organisms.
  • ERSATZBLAH (REGEL26) Rajotte, HP Baltes: A biocompatible enzyme electrode for continuous in vivo glucose monitoring in whole blood, Sensors and Actuators, Bl, 561-564, 1990).
  • microdialysis systems with an implantable microdialysis needle are used to determine the glucose concentration in the patient (see, for example: FJ Schmidt et al .: Calibration of a wearable glucose sensor, The International Journal of Artificial Organs, Vol. 15, No. 1, pp 055-061, 1992).
  • Body fluids using an implantable dialysis probe using an implantable dialysis probe.
  • a disadvantage of the prior art is that the known enzyme electrodes have low enzyme stability when in contact with blood or other body fluids and therefore do not have a sufficient lifespan for use as fully implantable sensors. There are also problems of biocompatibility with regard to the materials used. There is also a morphological incompatibility, i.e. a contact problem between the often very small sensor surface and relatively inhomogeneous tissue.
  • ERSATZBLAH ERSATZBLAH (REGEL26)
  • the known microdialysis systems are suitable for short-term use on patients, but do not offer the possibility of full implantation of the overall system.
  • the invention is therefore based on the object of integrating substance-detecting sensors into an implantable sensor system such that the sensor system has the following properties:
  • the substance-recognizing surface of at least one sensor is connected to at least one micro-tube-like permeable and flexible capillary membrane, which makes good contact with the living organism after the implantation,
  • REPLACEMENT BLA ⁇ (RULE 26) that the capillary membrane is also filled with a substance which allows the transport of the analyte which has entered the inside of the capillary membrane to the substance-recognizing sensor surface, and that the capillary membrane is connected to at least one septum by means of a channel in a holder in such a way that with the help of an injection needle, substances can be added to and removed from the interior of the capillary membrane through the septum.
  • the sensor is connected to a signal processing electronics and a battery for energy supply and is housed together with a telemetry device in a housing which is connected to the holder.
  • the telemetry device is used for data exchange with external signal electronics. This can be found in a patient's wristwatch, for example.
  • the advantages achieved by the invention are, in particular, that there is no direct contact between the substance-recognizing sensor surface and the living organism.
  • the capillary membrane is very thin and flexible and can therefore make good contact with the tissue of the living organism. All biocompatible materials which are sufficiently permeable for the substance to be measured can be used for the capillary membrane.
  • the septa can be used to remove or add substances to the capillary membrane.
  • REPLACEMENT BLA ⁇ (RULE 26) membrane can also be rinsed. In this way, calibration fluids, medication, disinfectants or other substances can be flushed through the interior of the capillary membrane with the help of two injection needles. This means that recalibrations of the sensor take place during long-term operation and substances in the capillary membrane can be renewed.
  • FIG. 1 shows a simple embodiment of the sensor system in plan view and FIG. 2 shows the same in section.
  • the substance-recognizing surface 1, 1 'of at least one sensor 2, 2' is connected to at least one micro-tube-like permeable and flexible capillary membrane 3, 3 ', which makes good contact with the living organism after the implantation.
  • the sensor 2, 2 ' All embodiments that are suitable for measuring the concentration of the desired analyte are possible for the sensor 2, 2 '. These are, for example, potentiometric, ion-selective electrodes that are used to determine blood electrolyte concentrations. Likewise, amperometric sensors can be used to measure blood gas concentrations (for example dissolved oxygen, CO 2, etc.), but also enzyme electrodes (for example for measuring glucose concentrations) and other biosensors. The electrical sensor signal is supplied to signal electronics in a known manner.
  • potentiometric, ion-selective electrodes that are used to determine blood electrolyte concentrations.
  • amperometric sensors can be used to measure blood gas concentrations (for example dissolved oxygen, CO 2, etc.), but also enzyme electrodes (for example for measuring glucose concentrations) and other biosensors.
  • the electrical sensor signal is supplied to signal electronics in a known manner.
  • the capillary membrane 3, 3 ' has a length between 0.1 mm and 1 m, preferably a few cm.
  • REPLACEMENT BLA ⁇ (RULE 26) knife is a few 100 ⁇ m to a few mm.
  • the wall thickness of the capillary membrane is a few ⁇ m to a few 100 ⁇ m.
  • All materials which are permeable to the substance to be measured can be used for the capillary membrane.
  • Such materials are e.g. Polycarbonate, cellulose acetate, cellulose hydrate, regenerated cellulose, cuprophan, Thomapor, polyacrylonitrile, polysulfone, polyamide, polyethyl methacrylate, Teflon.
  • the capillary membrane can also be coated with other substances such as polyurethane, silicone or others which increase the biocompatibility.
  • the capillary membrane is filled with a substance 4 which facilitates the transport of the outside, i.e. Analytes which have entered the interior of the capillary membrane 3, 3 'from the tissue of the living organism to the substance-recognizing sensor surface 1, 1' are permitted. In the simplest case, this transport takes place by diffusion.
  • the substance 4 can consist of liquid materials such as sodium chloride solution, buffered sodium chloride solution and other solutions. Medicinal products such as heparin, antibiotics or disinfectants can also be added to these solutions, which have a stabilizing effect on the interface between the capillary membrane and living tissue and substance 4 itself.
  • the capillary membrane is by means of a channel 11,
  • REPLACEMENT BLA ⁇ (RULE 26)
  • the holder 5, 5 'can consist of all biocompatible materials such as polyurethane, polyethylene, titanium or others.
  • the septum 6, 6 ' can be made of all known biocompatible materials such as silicone, natural rubber, natural rubber with a Teflon coating, Viton-TefIon, silicone-rubber-Teflon, PTFE-coated Teflon, butyl rubber, polyetheride ( PEI) exist.
  • the septum has a diameter between a few mm and a few cm. Its thickness is a few 100 ⁇ m to a few mm.
  • the system can also be constructed in such a way that the brackets 5, 5 'are connected to a common carrier plate (not shown).
  • FIGS. 3 and 4 show a sensor system which is expanded compared to the illustration in FIG. 1.
  • the sensor 2, 2 ' is connected to a signal processing electronics 7 and a battery 8 for energy supply and is housed together with a telemetry device 9 in a housing 10 which is connected to the holder 5, 5'.
  • the telemetry device 9 is used for data exchange with external signal electronics. This can be found in a patient's wristwatch, for example.
  • the housing 10 can consist of the same material as the holder 5, 5 '.
  • FIG. 5 shows a section of a sensor system in plan view (FIG. 5a) and in section (FIG. 5b), the sensor of which is modified compared to the representations from FIGS.
  • ERSATZBLAH ERSATZBLAH
  • the channel 11 in the holder 5 ′′ is in contact with a membrane 12 which is permeable to the substance to be measured.
  • a membrane 12 On the side of the membrane 12 opposite the channel 11 there is a substance 13 which enters into a chemical or biochemical reaction with the analyte diffused through the membrane.
  • the sensor 17 measures the change in the composition of the substance 13 caused by the chemical and biochemical reaction.
  • the substance 13 can be removed and replaced with an injection needle through at least one septum 15.
  • the membrane 12 is e.g. made of polycarbonate, cellulose acetate, cellulose hydrate, regenerated cellulose, cuprophan, Thomapor, polyacrylonitrile, polysulfone, polyamide, polyethyl methacrylate, HEMA, poly-HEMA or other suitable substances.
  • the substance 13 consists of a saline solution, KCl solution or another inorganic or organic solution, to which the enzyme glucose oxidase is added.
  • the oxygen concentration or H : 0 -.- concentration changed by the enzymatic reaction can be measured with the aid of a sensor 17, which is designed as an oxygen sensor or H 2 0 -, - sensor.
  • the sensor signal is supplied to signal electronics in a known manner.
  • the septum 15 can be made from all known biocompatible materials such as silicone, natural rubber, natural rubber with a Teflon coating, Viton-TefIon, silicone
  • REPLACEMENT BLA ⁇ (RULE 26) Con-rubber TefIon, PTFE-coated Teflon, butyl rubber, polyetherimide (PEI) exist.
  • FIG. 6 shows a sensor system in the top view, shown in section in FIG. 7, which is expanded by a pump 16 compared to the embodiment of FIG. 3.
  • This pump 16 pumps the liquid substance 4, which is located in the capillary membrane in the circuit through the channel 11 "and past the sensors 2, 2 '.
  • This has the advantage that the analyte that gets into the interior of the capillary membrane is transported to the sensor more quickly than would be possible by diffusion alone.
  • the pump 16 can operate both in continuous operation and in interval operation.
  • FIGS. 8 and 9 A very simple embodiment of part of a sensor system is shown in FIGS. 8 and 9. Here is at least one micro tube-like permeable and flexible capillary membrane 3 ′′ with one
  • Substance 4 ' which allows the transport of the analyte which has entered the inside of the capillary membrane 3 "from the outside and which connects the capillary membrane to at least one septum 6'" with the aid of the channel 11 '"in a holder 5'" that substances can be added and removed from the inside of the capillary membrane through the septum with the aid of an injection needle.
  • This arrangement can be implanted as part of a sensor system. With the help of two injection needles or cannulas, the tissue of the living organism and then the septa 6 '"are pierced from the outside, so that there is an inflow and an outflow for the liquid substance 4' through the capillary membrane
  • This arrangement can be used in the same way as a microdialysis needle and works with a measuring system arranged outside the organism. With the help of this measuring system, the substance 4 'is pumped through the capillary membrane and the concentration of substances such as glucose, lactate, blood electrolytes etc. measured.
  • a device according to FIGS. 8 and 9 has the particular advantage that it can be used as a preliminary stage for fully implantable sensor systems for clinical examinations and system developments and optimizations.

Abstract

L'invention concerne un système de détection implantable pour déterminer des concentrations de substances dans des organismes vivants, ainsi que son procédé de production. Ledit système se caractérise en ce que la surface (1, 1') de reconnaissance des substances concernées d'au moins un détecteur (2, 2') est reliée à au moins une membrane capillaire (3, 3') perméable et souple, sous forme de microtube, qui induit un bon contact avec l'organisme vivant, après implantation. La membrane capillaire est en outre remplie d'une substance (4) qui permet à la substance à détecter, passée de l'extérieur à l'intérieur de la membrane capillaire (3, 3'), d'être acheminée jusqu'à la surface du détecteur (1, 1') de reconnaissance des substances. La membrane capillaire est reliée à l'aide d'un canal (11, 11'), dans un support (5, 5'), à au moins un septum (6, 6'), de manière à ce que des substances puissent être introduites, à travers le septum, à l'intérieur de la membrane capillaire, à l'aide d'une aiguille d'injection, et en être extraites. Ces détecteurs s'utilisent pour mesurer en continu les concentrations en glucose, en lactate et en d'autres substances à détecter, présentes dans des tissus ou des vaisseaux sanguins, chez l'homme, l'animal et dans d'autres organismes.
PCT/DE1996/000356 1995-03-01 1996-02-27 Systeme de detection implantable pour determiner des concentrations de substances dans des organismes vivants WO1996026668A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
EP96904719A EP0812147A1 (fr) 1995-03-01 1996-02-27 Systeme de detection implantable pour determiner des concentrations de substances dans des organismes vivants
JP8525962A JPH11501234A (ja) 1995-03-01 1996-02-27 生物体内の物質の濃度を決定する埋め込み型センサ・システム

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE19507107.7 1995-03-01
DE1995107107 DE19507107C1 (de) 1995-03-01 1995-03-01 Implantierbares Sensorsystem zur Bestimmung von Stoffkonzentrationen in lebenden Organismen

Publications (1)

Publication Number Publication Date
WO1996026668A1 true WO1996026668A1 (fr) 1996-09-06

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Application Number Title Priority Date Filing Date
PCT/DE1996/000356 WO1996026668A1 (fr) 1995-03-01 1996-02-27 Systeme de detection implantable pour determiner des concentrations de substances dans des organismes vivants

Country Status (4)

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EP (1) EP0812147A1 (fr)
JP (1) JPH11501234A (fr)
DE (1) DE19507107C1 (fr)
WO (1) WO1996026668A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006122554A2 (fr) 2005-05-17 2006-11-23 Radiometer Medical Aps Detecteur d'enzymes pourvu d'une couche membranaire de couverture recouverte par un polymere hydrophile

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Publication number Priority date Publication date Assignee Title
US6331163B1 (en) * 1998-01-08 2001-12-18 Microsense Cardiovascular Systems (1196) Ltd. Protective coating for bodily sensor
DE10119036C1 (de) * 2001-04-18 2002-12-12 Disetronic Licensing Ag Tauchsensor zur Messung der Konzentration eines Analyten mit Hilfe einer Oxidase
CA2458966C (fr) * 2001-10-23 2013-02-26 Medtronic Minimed, Inc. Procede et systeme d'implantation d'une sonde non vasculaire
DE10241071B4 (de) * 2002-09-05 2010-01-14 Aesculap Ag Vorrichtung zum Lokalisieren bestimmter Substanzen in einem tierischen oder menschlichen Körper
US7736309B2 (en) 2002-09-27 2010-06-15 Medtronic Minimed, Inc. Implantable sensor method and system

Citations (4)

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Publication number Priority date Publication date Assignee Title
EP0183351A1 (fr) * 1984-09-28 1986-06-04 Vladimir Feingold Dispositif implantable d'administration de médicaments par perfusion
WO1986007150A1 (fr) * 1985-05-21 1986-12-04 Brian John Bellhouse Dispositif de test de liquides
EP0243854A1 (fr) * 1986-05-02 1987-11-04 Siemens Aktiengesellschaft Appareil implantable étalonnable pour la mesure d'une substance corporelle
EP0245073A2 (fr) * 1986-05-06 1987-11-11 The Regents Of The University Of California Système complet de surveillance du glucose avec module de captage implantable pour la mesure à distance

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DE3700119A1 (de) * 1987-01-03 1988-07-14 Inst Diabetestechnologie Gemei Implantierbarer elektrochemischer sensor
DE3933373A1 (de) * 1989-10-06 1991-04-18 Thomas Hoell Blutsensorsystem fuer die analytische in-vivo bestimmung eines blutbestandteils
DE4405149C2 (de) * 1993-02-25 1998-11-26 Daimler Benz Aerospace Ag Anordnung zum Bestimmen der Konzentration von Inhaltsstoffen in Körperflüssigkeiten

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0183351A1 (fr) * 1984-09-28 1986-06-04 Vladimir Feingold Dispositif implantable d'administration de médicaments par perfusion
WO1986007150A1 (fr) * 1985-05-21 1986-12-04 Brian John Bellhouse Dispositif de test de liquides
EP0243854A1 (fr) * 1986-05-02 1987-11-04 Siemens Aktiengesellschaft Appareil implantable étalonnable pour la mesure d'une substance corporelle
EP0245073A2 (fr) * 1986-05-06 1987-11-11 The Regents Of The University Of California Système complet de surveillance du glucose avec module de captage implantable pour la mesure à distance

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
P. ATANASOV: "Biosensor for Continuous Glucose Monitoring", BIOTECHNOLOGY AND BIOENGINEERING INCLUDING: SYMPOSIUM BIOTECHNOLOGY IN ENERGY PRODUCTION AND CONSERVATION., vol. 43, no. 3, 5 February 1994 (1994-02-05), NEW YORK US, pages 262 - 266, XP000417475 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006122554A2 (fr) 2005-05-17 2006-11-23 Radiometer Medical Aps Detecteur d'enzymes pourvu d'une couche membranaire de couverture recouverte par un polymere hydrophile

Also Published As

Publication number Publication date
DE19507107C1 (de) 1996-08-14
EP0812147A1 (fr) 1997-12-17
JPH11501234A (ja) 1999-02-02

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