EP3010399A1 - Cathéter comprenant un dispositif de détection pour déceler en temps réel une matière d'échantillon - Google Patents

Cathéter comprenant un dispositif de détection pour déceler en temps réel une matière d'échantillon

Info

Publication number
EP3010399A1
EP3010399A1 EP14734078.0A EP14734078A EP3010399A1 EP 3010399 A1 EP3010399 A1 EP 3010399A1 EP 14734078 A EP14734078 A EP 14734078A EP 3010399 A1 EP3010399 A1 EP 3010399A1
Authority
EP
European Patent Office
Prior art keywords
catheter
sample material
detection device
signal
detection
Prior art date
Legal status (The legal status 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 status listed.)
Withdrawn
Application number
EP14734078.0A
Other languages
German (de)
English (en)
Inventor
Andreas Bollman
Robert Niestroj
Klaus LÜCKE
Solveigh KRUSEKOPF
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Gilupi GmbH
Original Assignee
Gilupi GmbH
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 Gilupi GmbH filed Critical Gilupi GmbH
Publication of EP3010399A1 publication Critical patent/EP3010399A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • 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
    • A61B5/14503—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 invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors
    • 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
    • A61B5/6852—Catheters
    • 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
    • A61B5/14546—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 analytes not otherwise provided for, e.g. ions, cytochromes
    • 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
    • A61B5/1455—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 optical sensors, e.g. spectral photometrical oximeters
    • A61B5/1459—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 optical sensors, e.g. spectral photometrical oximeters invasive, e.g. introduced into the body by a catheter
    • 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
    • A61B5/1468—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 chemical or electrochemical methods, e.g. by polarographic means
    • A61B5/1473—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 chemical or electrochemical methods, e.g. by polarographic means invasive, e.g. introduced into the body by a catheter
    • 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
    • A61B5/1486—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 enzyme electrodes, e.g. with immobilised oxidase
    • A61B5/14865—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 enzyme electrodes, e.g. with immobilised oxidase invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/41—Detecting, measuring or recording for evaluating the immune or lymphatic systems
    • A61B5/412—Detecting or monitoring sepsis

Definitions

  • the present invention relates to a catheter.
  • Catheters are tubes or tubes of various diameters, with which hollow organs such as bladder, stomach, intestine and blood vessels, but also the ear or heart can be probed, emptied, filled or rinsed. Catheters are used during surgery and patients are placed in intensive care units, for example, to supply them with vital medicines or, in the case of a balloon catheter, to keep cardiac vessels open.
  • the object of the present invention is thus to provide a device which makes it possible to detect and detect sample material virtually in real time.
  • the present invention achieves this object by means of a catheter having at least one detection device for the real-time detection of a sample material, wherein the at least one detection device converts a functionalized surface for enriching the sample material, a signal transducer, which converts the enrichment of the sample material on the functionalized surface into a binding signal, and a signal conductor for transmitting the binding signal comprises.
  • the inventive combination of catheter and sensor allows real-time detection of the sample material also in vivo.
  • the catheter according to the invention like a conventional catheter, can be catheterized to a patient, ie introduced and fulfill its proper function.
  • the catheter according to the invention has at least one detection device for the real-time detection of a sample material, it is not necessary to wait for externally recognizable symptoms in the case of infectious disease, in particular sepsis, before sepsis is detected. Rather, the at least one detection device continuously detects the presence of a specific sample material, for example an injection germ. Once the sample material is present, it is enriched at the functionalized surface of the detection device of the catheter of the invention. The enrichment is converted directly by the signal transducer into a binding signal, which is then transmitted via the signal conductor and can be read outside the catheter as an indicative signal that the predetermined sample material is present. In this way, there is no loss of time and it can be recognized early on whether harmful sample material, for example infectious bacteria, is present in the bloodstream of intensive care patients or in the catheter itself.
  • harmful sample material for example infectious bacteria
  • the functionalized surface may be arranged on an outer side and / or on an inner side of the catheter.
  • the placement of the functionalized surface on the outside of the catheter allows specimens of the environment in which the catheter is placed to be detected. For example, if it is a venous catheter or a cardiac catheter, sample material from the bloodstream can be detected in real time by means of the catheter according to the invention.
  • the functionalized surface By disposing the functionalized surface on an inner side of the catheter, it is possible to detect sample material in the fluid flow within the catheter. In this way, for example, it can be immediately recognized whether an infection or contamination is present in the catheter and the catheter has to be exchanged. Contaminations of the fluid administered or withdrawn via the catheter can also be detected.
  • the at least one detection device can be connected captively to the catheter, which facilitates the handling of the catheter with detection device.
  • the at least one detection device may preferably be formed integrally with the catheter.
  • Such a one-piece embodiment can be achieved, for example, by integrating the at least one detection device into the catheter. Integration may be such that only the functionalized surface on an outside and / or on an inside of the catheter is exposed to interact with the outside environment or interior of the catheter and to allow sample material to attach to the functionalized surface ,
  • the catheter according to the invention can also have a detection device with a plurality of functionalized surfaces.
  • a first functionalized area on an outer side of the catheter and a further, second functionalized area on an inner side of the catheter Catheter may be arranged so that an interaction of the functionalized surface with both fluid flowing in the catheter as well as with the outer environment of the catheter is possible.
  • the catheter can have more than one detection device comprising a functionalized surface, a signal converter and a signal conductor, of which, for example, the one detection device is arranged on an outer side of the catheter and a second detection device on an inner side of the catheter.
  • the catheter according to the invention with more than one detection device, it is also possible to detect different sample materials. In this way, not only will information about receiving an infection be available. In addition, a more detailed classification of the infectious germ, for example a determination as to whether it is a gram-negative or a gram-positive pathogen, can be made.
  • the catheter according to the invention is suitable for any application for which conventional catheters are suitable.
  • the catheter according to the invention is also suitable for any technique of catheterization and may for example be a disposable catheter and in particular a permanent or indwelling catheter, as it is placed in the context of operations, patient monitoring and / or intensive medical measures in accordance with precaution.
  • the catheter of the invention may have any diameter and be made of various materials, such as plastic, rubber, silicone, metal or glass, for cost and sterility reasons steel or plastic catheters are particularly well suited.
  • the functionalized surface can be equipped at least in sections with detection molecules.
  • Detection molecules are molecules that specifically bind sample material.
  • a specific binding in the context of the present invention is understood as meaning a bond whose affinity is so high that it has an association constant of at least 10 4 mol -1, preferably 10 5 mol -1 and in particular above 10 6 mol -1 .
  • the detection molecules may preferably be antibodies, specifically binding fragments of antibodies, antigens, peptides, proteins, nucleic acids, inhibitors, enzymes, endotoxins, substrates of an enzyme, cofactors of an enzyme, ligands, receptors, chelates, in particular metal ion chelates or other molecules, which specifically bind the sample material, ie bind with specific affinity.
  • sample material of specific target molecules and / or target cells of various kinds can be detected in real time.
  • the sample material may be, for example, a specific membrane structure or a surface protein of a particular pathogen, or a disease-specific or pathogen-derived metabolite that is typically not present in the fluid flowing in the catheter or in the catheter surrounding tissue occurs.
  • the detection molecules can bind pathogen-specific and / or pathogen-associated sample material. These include special antigens or structures on the surfaces of pathogens, but also detectable nucleic acid structures or substances of pathogens secreted into the environment.
  • the detection molecules can bind sample-specific and / or infection-associated sample material, preferably sepsis-specific and / or sepsis-associated sample material.
  • a detection molecule can specifically bind O, H and pili antigens or core polysaccharides of the cell membranes, thus making it possible to detect infection microorganisms. Endotoxins produced by gram-negative pathogens, for example lipid A, or clumping factor A are also possible pathogen-specific sample material.
  • the detection molecules specifically bind so-called quorum sensing molecules.
  • the quorum sensing molecules for example, homoserine lactone, such as homoserine lactone (HSL) 1 to 4 (HSL1: N- (1-1-carboxy-3-oxoundecanoyl) -L-homoserine lactone; HSL2: N- (5-carboxypentanoyl) -L-homoserine lactone; HSL3: N- (1 1 -carboxy-3-hydroxyundecanoyl) -L-homoserine lactone; HSL4: N- (9-carboxynonanoyl) -L-homoserine lactone).
  • HSL homoserine lactone
  • quorum sensing oligopeptides which are summarized as autoinducer peptides, serve the chemical communication of unicellular organisms.
  • an increased concentration of quorum sensing molecules is a strong indication of a risk of sepsis, so that quorum sensing molecules are sepsis-specific samples.
  • a catheter according to the invention which is equipped with a functionalized surface for the enrichment of quorum sensing molecules, can therefore very quickly and reliably indicate a strong suspicion of sepsis.
  • An advantage of detection molecules that specifically detect quorum sensing mo- Forming molecules is that in this way one can not only detect the presence of an infection in real time, but also make statements about the gram status of the pathogens, because the homoserine lactones only from gram-negative pathogens and the autoinducer peptides only produced by gram-positive pathogens.
  • sepsis-associated sample material can also be detected in real time by means of the catheter according to the invention.
  • certain enzymes are altered in their activity by the increased concentration of quorum sensing molecules which occurs during an infection.
  • a functionalized surface with detection molecules which detect a change in the activity of such sepsis-associated enzymes also makes it possible to detect sepsis in real time by means of the catheter according to the invention.
  • the increased concentration of quorum sensing molecules in the case of sepsis means that the enzymes beta-galactosidase, beta-hexosaminidase and arylsulphatase A have a higher activity and the enzyme paraxonase 1 (also: paraoxonase 1) has a reduced enzyme activity.
  • the signal converter and / or the catheter can be coated at least in sections by a polymer, preferably a biocompatible polymer. Due to their versatile properties, polymer-coated surfaces are well suited for modifying surfaces of the catheter or signal converter, and the large number of different polymers and possibilities for modifying these polymers permit a polymer coating which is suitable for the particular application in question. When coating, it is useful in the case of the catheter according to the invention to use a protein and / or cell repellent polymer in order to exclude undesired deposits on the catheter according to the invention.
  • hydrophobic polymers and copolymers such as polyethylene glycol, polystyrene or its derivative, as well as hydrophilic polymers such as polyacrylates and polyamides, as well as natural polymers such as polylysine or polysaccharides such as alginate and chitosan.
  • the detection molecules can be attached directly covalently. It is also possible to couple the detection molecules to the desired site via linking molecules (so-called linkers) and to form them into a structured functionalized surface.
  • Alginate is an example of a functionalized natural polymer which is protein and / or cell repellent.
  • the coating of a biocompatible polymer may preferably fulfill one of the following requirements:
  • the biocompatible polymer is formed as a coherent polymer layer. This allows the entire surface of the catheter to be covered or shielded by the polymer layer.
  • the thickness of the polymer layer is preferably in the range of 0.1 to 10 ⁇ m, preferably in the range of 0.5 to 5 ⁇ m, particularly preferably in the range of 1 to 2 ⁇ m.
  • the biocompatible polymer has a three-dimensional, preferably filamentous and / or porous structure.
  • the biocompatible polymer has a carbon-containing, branched molecular structure. These structures are ideal for binding the detection molecules and increase the effective binding area. In the area of the boundary layer on a surface occupied by this molecular structure, the flow around a sample liquid is considerably slowed down. This promotes the enrichment of the ligands.
  • Possible advantageous embodiments of the structured functional surface are a functional surface with elevations, depressions and / or branches, and / or a functional surface that at least partially has a helical, helical, helical, wavy, helical, filamentous, brush-shaped, comb-shaped, reticulated, porous, spongy structure includes.
  • the biocompatible polymer is preferably operably linked via functional groups to the carrier, for example the catheter or signal transducer, preferably by chemical bonding, more preferably by covalent bonding.
  • the biocompatible polymer is a hydrogel.
  • the biocompatible polymer includes saturated atomic groups and covalently bound detection receptors to prevent unwanted interactions with blood components and the attachment of nonspecific cells and molecules.
  • the biocompatible polymer is crosslinked.
  • the biocompatible polymer comprises or forms the functional surface.
  • the functional surface is preferably located on the surface of the biocompatible polymer.
  • the biocompatible polymer can be equipped directly with the detection molecules.
  • the biocompatible polymer can form a matrix that prevents binding of nonspecific cells or interactions with body fluids.
  • the functionalized surface and / or the polymer may be coated with a protective layer which protects the functionalized surface, in particular its Dektetechnischmiesmoleküle, and / or the Bioplymer against external factors that occur during sterilization.
  • the protective layer may preferably satisfy at least one of the following requirements:
  • the protective layer is soluble in liquids, especially in body fluids, preferably in blood. This allows the functional surface to be automatically exposed as soon as the protective layer comes into contact with the sample fluid.
  • the protective layer is biocompatible. As a result, defense reactions of the body during the in vivo application of the detection device are largely prevented.
  • the protective layer is organic crystalline.
  • the protective layer comprises at least one of the following components: alginates, preferably high-purity alginates, polyethylene glycols, cyclic and non-cyclic oligosaccharides, polysaccharides, antioxidant amino acids, proteins or vitamins. Such components are biocompatible and readily soluble.
  • the detection molecules can be coupled directly, for example via a covalent bond or indirectly via a linking molecule, to the signal transducer or a polymer coating the signal transducer. In this way a reliable and secure connection of the functionalized surface with the signal converter is ensured.
  • the at least one detection device of the catheter according to the invention may comprise an electrochemical signal converter, an optical signal converter, an acoustic signal converter, an electrical signal converter, a thermal signal converter and / or piezoelectric signal converter.
  • an electrochemical signal transducer can convert the bond into a change in resistance, impedance, or current flow.
  • An optical signal converter can output a change in the refraction of light, as occurs in surface plasmon resonance spectroscopy, as a binding signal.
  • the signal converter may according to one embodiment comprise at least one electrode or at least one prism or at least one light guide section.
  • the light guide section may comprise an optical fiber core coated with a metal layer.
  • the metal layer may be coupled to the functionalized surface.
  • the change of the resistance or the impedance can be tapped and output as a binding signal.
  • the prism or at the light guide section the change in the refraction of light can be output as a binding signal.
  • the catheter according to the invention comprises detection molecules and / or a functionalized surface, which structurally change upon binding of the sample material, and whose structural change causes a change in the current flow or results in the refraction of light.
  • detection molecules which are modifiable substances, can be immobilized, for example, via a linker system on a carrier, the signal converter directly, or a coating of the signal converter.
  • the catheter according to the invention has a signal conductor.
  • the signal conductor may be, for example, an electrical conductor that transports a change in the current flow or the resistance / impedance.
  • the signal conductor may be a light guide, guided by the light to the signal converter and, for example, a change in the refraction of light as a binding signal is directed away from the transducer back to the outside.
  • the signal conductor can be arranged on the catheter and / or enclosed in the catheter.
  • the catheter itself serves as a carrier material for the signal conductor. Since in particular electrical conductors, such as metallic wires and optical fibers, for example glass fibers, can now be produced very flexibly and with small diameters, an arrangement or integration of the signal conductor on or into the catheter is possible in a simple manner.
  • the signal conductor may be co-extruded together with the catheter, or inserted, braided or cast into the catheter.
  • the at least one detection device of the catheter according to the invention may comprise a shield blocking off interfering signals, such as when using the catheter near the catheter Heart can occur.
  • a shield blocking off interfering signals such as when using the catheter near the catheter Heart can occur.
  • Another possibility is to equip the at least one detection device with at least one reference measuring device.
  • the reference measuring device detects the background noise or interfering signal and also makes it possible to filter out the interference factors or the background noise and in this way to make a reliable statement that actual enrichment of the sample material on the functionalized surface has taken place.
  • FIG. 1 is a schematic perspective view of a first embodiment of the catheter according to the invention, housed in a lumen;
  • FIG. 2 is a schematic representation of a detection device
  • FIG. 3 is a schematic representation of a detection device according to an alternative embodiment
  • 4 shows a cross-section of a catheter according to the invention placed in a lumen according to a second embodiment
  • FIG. 5 shows a cross section of a catheter according to the invention placed in a lumen according to a third embodiment
  • FIG. 6 is a cross-sectional view of a catheter of the invention placed in a lumen according to a fourth embodiment
  • FIG. 7 shows a schematic perspective embodiment of a catheter according to the invention according to a fifth embodiment.
  • FIG. 8 is a cross-sectional view of a catheter of the invention placed in a lumen according to a sixth embodiment.
  • the catheter 1 according to the invention and its individual components will be described in detail below with reference to the accompanying drawings.
  • the catheter 1 according to the invention makes it possible in vivo and intravascularly to detect the binding of a sample material 2 in real time, without it being necessary to remove the catheter 1 from the body.
  • FIG. 1 shows how the catheter 1 according to the invention is placed in a lumen 3, which is shown by way of example and may for example be a blood vessel.
  • the drawings generally represent the sizes of catheter 1, lumen 3 and the detection device 4 of the catheter only schematically and not to scale.
  • the catheter 1 comprises a detection device 4 for the real-time detection of the sample material 2, for example certain pathogen cells such as Staphylococcus aureus or other infectious bacteria or infectious fungi.
  • the detection device 4 comprises a functionalized surface 5 for enrichment of the sample material 2.
  • the functionalized surface will be discussed in more detail below with reference to FIGS. 2 and 3.
  • the detection device 4 further comprises a signal converter 6, which converts the enrichment of the sample material 2 on the functionalized surface 5 into a binding signal 7.
  • the detection device 4 of the catheter 1 according to the invention comprises a signal conductor 8 for transmitting the binding signal 7, which is indicated by an arrow in FIG. 1 by way of example.
  • the signal conductor 8 which may be, for example, an electrical conductor 8a or an optical conductor 8b
  • the binding signal 7 is transported away from the detection device 4 and outside of the body lumen 3, the binding of the sample material 2 to the functionalized surface 5 of the catheter 1 according to the invention Spend real time. This makes it possible, for example, to detect infectious bacteria in the bloodstream at a very early stage, which can provide the decisive time advantage, in particular in the presence of sepsis, in order to initiate the life-saving countermeasures in a timely manner.
  • the functionalized surface 5 is arranged on the inner side 9 of the catheter.
  • This arrangement on the inner side 9 of the catheter 1 makes it possible to detect infections or other undesired sample material in the interior 10 of the catheter in real time and to take appropriate precautions, for example the infiltration of the catheter. replace the catheter so that the infection does not enter the body via the catheter.
  • the detection device 4 is connected captively to the catheter 1 by the detection device 4 being formed integrally with the catheter 1.
  • the detection device is fused to the inner side 9 of the catheter 1 or embedded in this.
  • FIGS. 2 and 3 two exemplary embodiments of a detection device 4, as can be used in the catheter 1 according to the invention, are discussed in more detail.
  • the detection device 4 comprises a functionalized surface 5 for accretion of the sample material 2, a signal converter 6 and a signal conductor 8.
  • the signal conductor 8 is an electrical conductor 8a, with which an electrical binding signal 7, which is generated by the signal converter 6, transmitted can be.
  • the electrical conductor 8a is the guide wire, which is also used to insert the catheter 1 into the corresponding body lumen 3 at the same time.
  • FIG. 2 omits the illustration of the lumen 3 and of the catheter jacket.
  • the signal converter 6 is an electrochemical signal converter which is formed by a gold-coated surface 11 of the electrical conductor 8a.
  • the gold-coated surface 1 1 forms an electrode 15.
  • the functionalized surface 5 comprises detection molecules 13, which in the illustrated embodiment are formed by antibodies against infectious fungi or bacteria as sample material 2.
  • the detection molecules 13 are coupled to the signal converter 6.
  • a polymer 12 is provided in the illustrated embodiment.
  • the polymer 12 coats the signal converter 6 so that on the one hand it is protected against external influences and on the other hand non-specific and undesired interactions of the signal converter 6 with sample material 2 are excluded.
  • a functionalized hydrogel such as a functionalized alginate gel, represents the polymer 12 which coats the signal transducer 6.
  • the detection molecules 13 of the functionalized surface 5 are coupled to the polymer 12.
  • the antibodies which form the detection molecules 13 can be bound to the functional groups of the alginate.
  • the binding can be For example, carried out by the fact that the antibody is chemically bonded directly via formation of a covalent bond with the functional groups of the alginate.
  • a linking molecule 14 also called a linker, can be used, which is connected on the one hand to the polymer 12 and on the other hand to the detection molecules 13.
  • sample material 2 to be detected by the catheter 1 according to the invention binds to the detection molecules 13 of the detection device 4 specific for this purpose.
  • the binding of the sample material 2 to the antibodies is carried out in the gold layer 11, which has an electrode 15 of the Signal converter 6, converted into a binding signal 7.
  • the conversion takes place in the exemplary embodiment shown in that the binding of the sample material 2 to the antibodies as detection molecules 13 leads to a change in the current flow and ultimately the resistance in the electrode 15, which is formed by the gold coating 11. This change in resistance is subsequently transported away as a binding signal 7 via the electrical conductor 8a and indicates, outside the lumen 3, in real time that binding of the sample material 2 is present.
  • FIG. 3 shows an alternative embodiment of the detection device 4 from FIG. 2.
  • the same reference symbols are used for elements whose function and / or construction is identical to the elements of the previous figures.
  • the detection device 4 from FIG. 3 comprises, like the detection device 4 from FIG. 2, an electrical conductor 8 a as signal conductor 8, a signal converter 6 coated with a polymer 12 and a functionalized surface 5 which comprises antibodies as detection molecules 13.
  • the antibody 13 is not bound directly to the polymer 12 but is coupled via a linking molecule 14.
  • linker small molecules are referred to, for example, have two identical (homobifunctional) or two different (heterobifunctional) functional groups.
  • the length of the linker is relevant to the function.
  • Zero-length crosslinkers are used for a two-molecule connection without a spacer.
  • the use of a linker may, in particular in the case of complex molecules such as enzymes or antibodies, have a beneficial effect on the biological activity of the immobilized structure.
  • the active center or active domain of the molecule is brought farther away from the parent structure to which the molecule is immobilized by the linker. This reduces the risk of inactivation by the im- mobilization.
  • Another possibility is to choose the linker so that it binds only to a specific structure in the target molecule and thus leaves the active region of the molecule intact.
  • the linker For the coupling of an IgG antibody to carboxyl groups in the polymer, one can use the zero-length crosslinker EDC (1-ethyl-3- [3-dimethylaminopropyl] carbodiimide hydrochloride) which inhibits the formation of a peptide bond between a primary amino group in the antibody and a carboxyl group of the Polymers catalysed.
  • EDC 1-ethyl-3- [3-dimethylaminopropyl] carbodiimide hydrochloride
  • the signal converter 6 comprises an electrode arrangement 15 ', which causes a change in the resistance which is caused by the binding of the sample material 2 to the antibody 13 and a structural change of the linking molecule 14 associated therewith.
  • the resistance change is output by the signal converter 6 as a binding signal 7 and transported via the electrical conductor 8a as a signal conductor 8 to the outside.
  • the binding 2 of the sample material 2 to the antibodies thus causes a modification of the functionalized surface 5 or of the linking molecules 14, which is reflected in a current flow change, which can be output as a change of the resistance or the impedance as a binding signal 7.
  • a second embodiment of a catheter 1 according to the invention is discussed in more detail with reference to FIG. 2, the catheter 1 according to the invention, as placed in a lumen 3, is shown schematically in a cross section.
  • the catheter 1 of the second embodiment according to the invention compared to the catheter of the first embodiment, as shown in Fig. 1, will be discussed.
  • the catheter 1 of the second embodiment has arranged the detection device 4 not on the inside 9 but on the outside 16 of the catheter. In this way, the functionalized surface 5 of the detection device 4 is arranged in the lumen 3.
  • sample material 2 from the lumen 3, such as a blood vessel can be detected in real time.
  • infectious agents associated with sepsis can be detected at a very early stage and in real time with the catheter 1 of the present invention without having to remove a sample or previously remove the catheter 1 from the lumen 3.
  • FIG. 5 shows a cross-section of a catheter 1 according to the invention placed in a lumen 3, which essentially corresponds to the representation from FIG. 4.
  • the inventive catheter 1 according to the third embodiment is characterized in that the detection device 4 has a first functional surface 5, which is arranged on the outside of the catheter 1, and has a second functionalized surface 5a, which on the inside 9 of the catheter 1 is arranged.
  • the detection device 4 is integrated into the catheter 1.
  • the detection device 4 may be cast into the catheter body such that only the first functionalized surface 5 or the second functionalized surface 5a is exposed on the outside 16 or inner side 9 of the catheter 1 and is freely accessible. In this way it can be demonstrated whether sample material 2 is present in the lumen 3 and / or in the interior 10 of the catheter.
  • the functionalized surface 5 has detection molecules 13 which differ from the detection molecules 13 'of the second functionalized surface 5a.
  • different sample materials 2 can be detected. If the first functionalized surface 5 and the second functionalized surface 5a are coupled to the signal converter 6 so that different binding signals 7 are output, depending on whether binding of the sample material 2 on the first functionalized surface 5, on the second functionalized surface 5a or both functional surfaces 5 and 5a takes place, a statement can be made as to where the sample material binds, ie if, for example, there is an infection in the lumen, in the catheter or in the lumen and catheter.
  • the catheter 1 according to the fourth embodiment is also capable of detecting the accumulation of sample material 2 both inside the catheter 10 and in the lumen 3.
  • the catheter 1 of the fourth embodiment according to FIG. 6 has two detection devices 4 and 4a.
  • the first detection device 4 is arranged on the outside 9 of the catheter and can thus detect the presence of the sample material 2 in the lumen 3.
  • the second detection device 4a is arranged on the inner side 9 of the catheter 1 and thus can detect the presence of pro- Benmaterial 2, which binds specifically to detection molecules of the second detection device 4a, inside of the catheter 10 detect.
  • the detection devices 4, 4a of the fourth embodiment of FIG. 6 are optical detection devices which use the measuring principle of surface plasmon resonance.
  • the detection devices 4, 4a of the fourth embodiment have an optical conductor 8b, for example a fiber optic cable, which has an optical waveguide section 17, which is metallized, as optical signal converter 6.
  • Polarized light in total reflection is fed through the optical waveguide 8b and reaches the metal-coated optical waveguide section 17 on which the functionalized surface 5 is arranged. If no sample material 2 binds to the functionalized surface, the angle spectrum of the totally reflected polarized light has a minimum at a certain angle.
  • sample material 2 binds to the functionalized surface 5
  • a prism of a surface plasmon resonance detector may also be used as the optical signal converter 6.
  • FIG. 7 a fifth embodiment of a catheter 1 according to the invention is shown with reference to FIG.
  • the illustration of FIG. 7 essentially corresponds to FIG. 1, wherein in the following only the differences between the catheter 1 of the first embodiment of FIG. 1 and the catheter 1 of the fifth embodiment of FIG. 7 will be discussed.
  • a shield 18 which isolates the detection device 4, more precisely its signal converter 6 together with functionalized surface 5 against external interference factors.
  • the shielding 18 ensures that external factors which could undesirably influence the binding of the sample material 2 or distort the conversion of the binding by the signal converter 6 into the binding signal 7 are reduced.
  • the catheter 1 according to the fifth embodiment of Fig. 7 does not include a shield 18 but instead a reference measuring device 19.
  • the reference measuring device 19 is also located on the inside 9 of the catheter 1 and makes it possible to take a reference measurement which is representative of background noise. By subtracting the background signal 20 output from the reference measuring device 19 from the binding signal 7, the signal actually characteristic of the binding of the sample material 2 can be isolated.
  • the reference measuring device 19 may be constructed, for example, identically to the detection device 4, with the only difference that the functionalized surface 5 either has no detection molecules 13 or only reference molecules which do not bind the sample material 2 to be detected.
  • FIG. 8 shows a catheter 1 according to the invention in accordance with a sixth embodiment.
  • FIG. 8 again shows a schematic cross-section of a catheter 1 according to the invention placed in a lumen 3, as shown for example in the same way for the catheter 1 of the second embodiment in FIG. 4.
  • the sixth embodiment of the catheter 1 according to the invention is a modification of the fifth embodiment of Fig. 7. Also in the sixth embodiment of Fig. 8 on the inside 9 of the catheter 1 both an electrochemical detection device 4 and a reference measuring device 19 for filtering the background noise are arranged ,
  • the catheter 1 according to the sixth embodiment from FIG. 8 has a further electrochemical detection device 4 a on the outer side 16 of the catheter 1 and a further reference measuring device 19 a, which is also placed on the outer side 16 of the catheter 1.
  • a binding signal 7 from the inner space 10 which images the binding of sample material 2 in the catheter, filtered by the background noise.
  • sample material can also be detected in the lumen 3, in which also the binding signal 7 is isolated and reduced by the background noise.

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Abstract

La présente invention concerne un cathéter (1). Pour produire un dispositif qui permet de dépister et de déceler de la matière d'échantillon (2) en temps réel, le cathéter (1) selon l'invention comprend au moins un dispositif de détection (4, 4a) pour déceler en temps réel la matière d'échantillon (2), ledit dispositif de détection (4, 4a) comportant une surface fonctionnalisée (5, 5a) pour enrichir la matière d'échantillon (2), un convertisseur de signal (6) qui convertit l'enrichissement de la matière d'échantillon (2) sur la surface fonctionnalisée (5, 5a) en un signal de liaison (7), et un conducteur de signal (8) pour transmettre le signal de liaison (7).
EP14734078.0A 2013-06-21 2014-06-23 Cathéter comprenant un dispositif de détection pour déceler en temps réel une matière d'échantillon Withdrawn EP3010399A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102013211837.6A DE102013211837A1 (de) 2013-06-21 2013-06-21 Katheter mit Detektionsvorrichtung zum Echtzeitnachweis eines Probenmaterials
PCT/EP2014/063165 WO2014202783A1 (fr) 2013-06-21 2014-06-23 Cathéter comprenant un dispositif de détection pour déceler en temps réel une matière d'échantillon

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EP3010399A1 true EP3010399A1 (fr) 2016-04-27

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US (1) US20160135721A1 (fr)
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CN (1) CN105592776A (fr)
DE (1) DE102013211837A1 (fr)
WO (1) WO2014202783A1 (fr)

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US20050153309A1 (en) 2003-12-22 2005-07-14 David Hoon Method and apparatus for in vivo surveillance of circulating biological components
WO2017100823A1 (fr) * 2015-12-18 2017-06-22 Macquarie University Système de détection biologique
SG10202012275PA (en) 2016-06-09 2021-01-28 Haimachek Inc Collector for detection and reversible capturing of cells from body fluids in vivo
TWI586391B (zh) * 2016-06-23 2017-06-11 何中庸 一種氣囊管裝置與運作方法
US11633129B2 (en) 2019-04-05 2023-04-25 Cambridge Medical Technologies LLC Non-invasive transdermal sampling and analysis device incorporating redox cofactors
US11375931B2 (en) * 2019-08-08 2022-07-05 Cambridge Medical Technologies LLC Non-invasive transdermal sampling and analysis device incorporating an electrochemical bioassay

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CN105592776A (zh) 2016-05-18
WO2014202783A1 (fr) 2014-12-24
DE102013211837A1 (de) 2014-12-24

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