WO2024099566A1

WO2024099566A1 - Catheter system and method for the detection of bacterial infection and/or thrombus

Info

Publication number: WO2024099566A1
Application number: PCT/EP2022/081428
Authority: WO
Inventors: Fearghal O'Connor; Ciaran GILES; Eoin CONNAUGHTON; Derek Doyle; John O'shea; Christina STEPHENSON
Original assignee: ClearStream Technologies Ltd
Current assignee: ClearStream Technologies Ltd
Priority date: 2022-11-10
Filing date: 2022-11-10
Publication date: 2024-05-16
Anticipated expiration: 2025-05-10
Also published as: EP4598429A1

Abstract

A system comprising a catheter having an enzymatic sensor positioned at or adjacent the distal end thereof, said enzymatic sensor comprising an enzyme capable of reacting with a biomarker indicative of the presence of bacterial infection and/or of a thrombus in a patient's vessel.

Description

CATHETER SYSTEM AND METHOD

FOR THE DETECTION OF BACTERIAL INFECTION AND/OR THROMBUS

TECHNICAL FIELD

The present disclosure relates to catheter systems and methods, and more particularly to systems with a catheter comprising an enzymatic sensor and to methods using the same.

BACKGROUND

Catheter systems are well-known and catheters, such as central veinous catheters (CVCs) and peripherally inserted central catheters (PICCs), are routinely used to administer medication, nutrition and/or fluids, or to obtain blood samples and biopsies. These catheters may remain in place for the short-, medium or long-term.

The patient may suffer complications, such as an infection or thrombosis, and prompt action is required to avoid further complications or, in certain cases, death of the patient. The catheter may need to be removed or replaced, and further treatments, such as the administration of medication or surgery, may be required.

However, often these conditions remain undetected until the patient shows symptoms of infection or the thrombus once it is formed. The later the infection or thrombus formation is detected, the more drastic or invasive the corrective treatment becomes.

SUMMARY OF THE INVENTION

It is an object of this invention to mitigate problems such as those described above. In particular, there is a need for a system capable of early detection of infection and of thrombosis and emboli formation, so as to minimise the risk of further complications without the need for intensive curative and corrective treatments.

According to a first aspect of the disclosure, there is provided a system comprising a catheter having an enzymatic sensor positioned at or adjacent the distal end thereof, said enzymatic sensor comprising an enzyme capable of reacting with a biomarker indicative of the presence of bacterial infection and/or of a thrombus in a vessel. In some embodiments, the biomarker is polysaccharides. The enzymatic sensor may comprise an enzyme capable of reacting with polysaccharides, and selected from one or more of glucose oxidase, protease, DNase, alginate ligase, amylase and cellulase.

In some embodiments, the biomarker is fibrin. The enzymatic sensor may comprise an enzyme capable of reacting with fibrin, such as trypsin.

In some embodiments, the system comprises an electrode coupled to the catheter. The electrode may be in contact with the fluid and/or solids present in the patient’s vessel.

In some embodiments, the enzyme is immobilised on the surface of said electrode.

In some embodiments, the system comprises a conductive braid coupled with said electrode and extending in the lumen of the catheter, at least from the electrode to the proximal end of the catheter.

In some embodiments, the system comprises a control hub.

The control hub may be configured to measure the electrical signal generated at the electrode; and to compare the intensity of the electrical signal with a predetermined intensity value indicative of the presence of the biomarker.

The control hub may be configured to measure the electrical signal generated at the electrode; to correlate the intensity of the electrical signal with intensity values indicative of the amount of biomarker; and to determine the concentration of biomarker.

In some embodiments, the catheter is a single-lumen or a multi-lumen catheter.

In a second aspect of the disclosure, there is provided a method for detecting a bacterial infection in a patient’s vessel, wherein the method comprises the step of inserting a catheter as described herein above into a patient’s vessel.

In some embodiments, the biomarker is polysaccharides. The enzymatic sensor may comprise one or more of glucose oxidase, protease, DNase, alginate ligase, amylase and cellulase. In some embodiments, the method comprises the steps of measuring an electrical signal generated at an electrode in contact with the fluid and/or solids in the patient’s vessel; and comparing the intensity of the electrical signal with a predetermined intensity value indicative of the presence of the biomarker.

In some embodiments, the method comprises the steps of measuring an electrical signal generated at an electrode in contact with the fluid and/or solids in the patient’s vessel; correlating the intensity of the electrical signal with intensity values indicative of the amount of biomarker; and determining the concentration of biomarker.

In a third aspect of the invention, there is provided a method for detecting a thrombus wherein the method comprises the step of inserting a catheter as described herein above into a patient’s vessel.

In some embodiments, the biomarker is fibrin. The enzymatic sensor may comprise trypsin.

In some embodiments, the method comprises the steps of measuring an electrical signal generated at an electrode in contact with the fluid and/or solids in the patient’s vessel; and comparing the intensity of the electrical signal with a predetermined intensity value indicative of the presence of the biomarker.

These and other features of the concepts provided herein will become more apparent to those of skill in the art in view of the following description, which describe particular embodiments of such concepts in greater detail.

BRIEF DESCRIPTION OF THE DRAWINGS

To enable better understanding of the present disclosure, and to show how the same may be carried into effect, reference will now be made, by way of example only, to the accompanying drawings, in which: FIG. 1 shows a catheter system comprising an enzymatic sensor for detecting a bacterial infection in a vessel;

FIG. 2 shows an alternative embodiment of a catheter system comprising an enzymatic sensor for detecting a bacterial infection in a vessel;

FIG. 3 shows a catheter system comprising an enzymatic sensor for detecting a thrombus in a vessel;

FIG. 4 shows a catheter system comprising an enzymatic sensor for detecting a bacterial infection and an enzymatic sensor for detecting a thrombus in a vessel; and

FIG. 5 shows an alternative catheter system comprising an enzymatic sensor for detecting a bacterial infection and an enzymatic sensor for detecting a thrombus in a vessel.

DETAILED DESCRIPTION

The embodiments described herein are provided as exemplary and non-limiting embodiments of the present invention.

The system according to the present disclosure comprises a catheter. For example, the catheter may be a central veinous catheter (CVC), a peripherally inserted central catheter (PICC) or any intravenous (IV) line.

The catheter comprises at least one enzymatic sensor (also referred to as “enzymatic biosensor”). The enzymatic sensor is capable of real-time measurements of an enzymatic activity. Enzymatic sensors are advantageously used for they high sensitivity and high selectivity towards their target biomarker(s).

The enzymatic sensor may comprise a transducer or an electrode. In some embodiments, the enzyme is immobilised on or within a surface of the transducer or electrode. For the example, the enzyme may be immobilised on an active site or surface of the electrode. Some enzymes naturally exist on the surface of cells exposed to blood and other fluids so that there is a degree of natural resistance to fouling. Immobilisation of the enzymes onto the sensor or electrode may also increase resistance to fouling. The enzyme acts as a catalyst, so that it does not change or deplete and may therefore be used multiple times. Consequently, the catheter is suitable for medium- to long-term use.

The electrode may be positioned to detect the presence of the relevant biomarker(s) in the fluid outside the catheter, or in the fluid inside the catheter. When the system is used to deliver a drug, it may be advantageous to monitor the fluid outside the catheter; whereas when the system is used to retrieve blood, it is possible to monitor blood flowing through the catheter.

The transducer or electrode may be electrically coupled to a conductive strip, such as a wire or braid. The conductive braid may extend through (a lumen of) the catheter. The conductive braid may be coupled to a control hub. An enzymatic reaction occurs at the sensor, which is converted by the transducer or electrode into an electrical current which travels from the electrode, along the conductive braid to the control hub. The sensor may be an amperometric sensor, an electrochemical sensor, or any sensor capable of translating an enzymatic activity into an electrical signal.

The intensity of the electrical signal is indicative of the concentration of biomarker. Therefore, the present system may be used to detect the presence or absence of an infection and/or thrombosis biomarker, for example by comparing the measured biomarker concentration with a biomarker concentration indicative of the presence of an infection and/or of a thrombi. The presence of a biomarker may be monitored within a patient’s blood vessels, arteries or veins, or in a patient’s organ. The present system may be used to monitor the increase of decrease of enzymatic activity, and therefore allow early detection of the development of an infection or of the formation of a thrombi. Although the present system is described with reference to the detection of a thrombi or thrombosis, the system may be used for the detection of any solid or deposit, such an embolus or embolism.

The enzymatic sensor comprises an enzymatic sensor comprising an enzyme capable of reacting with a biomarker indicative of the presence of bacterial infection. For example, the enzyme is capable of reacting with a polysaccharide in a bacterial biofilm. An enzyme may be selected which oxidises the polysaccharides present in the bacterial biofilm. Enzymes capable of reacting with a polysaccharide include, but are not limited to, glucose oxidase, protease, DNase, alginate ligase, amylase and cellulase.

Alternatively or additionally, the sensor comprises an enzymatic sensor comprising an enzyme capable of reacting with a biomarker indicative of the presence of a thrombus (or embolus) in a vessel. For example, the enzyme is capable of reacting with prothrombin, which is present during thrombus formation. In a preferred embodiment, the enzyme is trypsin, which can proteolytically cleave prothrombin.

The catheter device may comprise one or more additional sensors. The additional sensor(s) may be selected from biosensors, such as enzymatic sensors, antibody sensors, or aptasensors, sensors to detect the concentration of an electrolyte, an analyte, a drug and/or a biomarker, and sensors configured to detect other physiological parameters. Other sensors may be considered such as temperature sensors and pressure sensors.

The catheter has a distal and a proximal end, the distal end being opposite the proximal end. The distal end is the end of the catheter inserted into the patient; whereas the proximal end is the end of the catheter usually outside the patient and closer the medical professional. The enzymatic sensor is positioned at or adjacent the distal end of the catheter. The enzymatic sensor may be positioned at or adjacent the distal tip of the catheter. Appropriately placed sensors on the device can detect the early stages of bacterial infection and or the early stage of thrombus formation and communicate that to the health care worker/ patient.

The catheter may comprise a distal opening to allow the delivery and/or the retrieval of components. Such components may be, for example, a medical device (such as an occlusion implant or a thrombectomy device), fluid (such as blood or plasma), a drug, and the like. The distal opening may be positioned at or adjacent the distal tip of the catheter.

The electrode may be positioned at or adjacent the distal opening of the catheter. When the system is used to detect the presence of a thrombus, the electrode may be positioned at the distal opening so as to directly come into contact with the thrombus as the catheter is advanced. However, when the system is used to deliver a drug, the electrode may be a distance apart from the catheter opening or drug delivery outlet, so that the measurement is a true measurement of the content of the patient’s vessel.

The catheter device may comprise a single lumen or two or more lumens. Where the catheter device comprises multiple lumens, the lumens may divide the inner space of the catheter into sections. For example, the lumens may be positioned in a concentric manner. Each lumen of the catheter may receive different elements of the system. For example, the catheter may comprise lumens configured to contain a conductive braid coupled with a sensor to detect a bacterial infection, a conductive braid coupled with a sensor to detect a thrombus, a sensor system for detecting and/or monitoring any other physiological parameter(s), as well as lumens configured to receive a medical device (such as an implant), a device for the delivery of a medical device or of medication, a device for the retrieval of fluids, and the like.

The sensor may be a low-profile sensor. The sensor may be incorporated into the lumen of the catheter or may be partly or completely embedded in the catheter. For example, the conductive wire, strip or braid may be embedded within the wall of the catheter, i.e., between the outer and inner wall surfaces of the catheter. The wire, strip or braid comprises a conductive material which allows communication between the sensor and the control hub, but also provides skin resistance to the catheter.

The control hub may comprise a housing. The housing may be configured to receive an electrical feed, such as an electrical lead or a battery, for example a coin battery. The control hub may comprise a display and/or alarm to provide information regarding the biomarker. For example, the control hub may comprise an alarm in the form of an LED light, which may flash when a predetermined concentration of marker is detected by the sensor. The system may comprise a plurality of alarms, each connected to an individual sensor for detecting a specific biomarker.

Although the present system is described with reference to a system with a catheter having an enzymatic sensor, it is envisaged that the enzymatic sensor is alternatively comprised by a sheath or a needle of the system. For example, a system comprising a sheath or needle having an enzymatic sensor positioned at or adjacent the distal end thereof, said enzymatic sensor comprising an enzyme capable of reacting with a biomarker indicative of the presence of bacterial infection and/or of a thrombus in a vessel, is considered.

According to an embodiment, the method for detecting and/or monitoring a biomarker comprises the step of introducing the catheter into a patient’s vessel or organ. The catheter system may be used specifically in the context of the treatment of an infection and/or of the removal of a thrombus. Alternatively, the treatment of the infection and/or thrombus formation may be achieved in the context of a treatment of a different condition. For example, the patient may require the administration of fluid through an IV, and an infection or a thrombus may be detected using the present system during the fluid administration procedure. The enzymatic sensor, and more particularly its electrode, is configured to be in fluid contact with the fluid in the patient’s vessel. If the patient suffers from an infection, a bacterial biofilm is formed comprising for example polysaccharides. These polysaccharides may be selected as the biomarker for bacterial infection. When the enzyme of the enzymatic sensor comes into contact with the polysaccharides, a biochemical reaction (such as the oxidation of the polysaccharides) occurs.

Similarly, prothrombin is naturally present in the patient to help blood clotting. Therefore, the presence, at certain concentration levels, of prothrombin in a patient’s vessel may be indicative of the formation of a thrombus. Therefore, prothrombin may be selected as the biomarker for thrombus formation. When the enzyme of the enzymatic sensor comes into contact with the polysaccharides, a biochemical reaction (such as the cleavage of prothrombin) occurs.

The enzymatic reaction is converted into an electrical current by a transducer or electrode of the sensor. The intensity of the electrical signal corresponds to the biomarker concentration. The electrical current thus generated travels from the electrode to the control hub, via a conductive wire, strip or braid in electrical communication with the electrode and the control hub.

The control hub is configured to receive and process the electrical signal. The control hub may be programmed to include information relating to clinical concentrations of specific biomarkers. For example, the threshold biomarker concentration or biomarker concentration range indicative of the development or presence of infection and/or of the formation and/or presence of thrombosis may be entered. The electrical signal generated at the active site of the electrode may be compared against the relevant threshold or range. Once predetermined clinical concentration is reached, a signal may be sent to the user (for example, a LED or sound alarm may trigger).

With reference to FIG. l, there is illustrated a system comprising a catheter (100) having an enzymatic sensor (130) positioned at or adjacent the distal end thereof, said enzymatic sensor (130) comprising an enzyme capable of reacting with a biomarker indicative of the presence of bacterial infection and/or of a thrombus in a vessel.

More specifically, FIG.1 depicts a catheter system for detecting a bacterial infection in a vessel. The system may include a catheter 100 and a control hub 600 disposed at a proximal end of the catheter 100. The catheter 100 may include a catheter body 110, with a peripheral wall surrounding a catheter lumen 120. The catheter body 110 may have an inner wall surface 111 that is adjacent to the catheter lumen 120, and an outer wall surface 112 that is, in use, adjacent to a vessel wall. The catheter body 110 may further comprise one or more openings 114. An enzymatic sensor 130 for detecting bacterial biomarkers may be positioned within the catheter lumen 120 and adjacent or at the opening 114. The sensor 130 may comprise an electrode and enzymes immobilised on the surface of the electrode that react with bacterial biomarkers. In some embodiments, the enzymatic sensor 130 may extend, at least partially, into the opening 114 of the catheter body. In this configuration, the enzymatic sensor 130 may be in contact with the fluids/solids in the patient’s vessel and the catheter lumen so as to react with bacterial biomarkers contained therein. The enzymatic sensor 130 may be connected to a conductive element 131, which may be embedded within the wall of the catheter body 110, i.e., between the inner wall surface 111 and the outer wall surface 112. Alternatively, the conductive element may be positioned along the inner wall surface 111 or outer wall surface 112 of the catheter body 110 with or without a protective surface layer. The conductive element may be a wire, braid or strip that is electrically connected to the control hub 600.

The control hub 600 may comprise a control hub housing 610 for containing components of the control hub 600. Such components may include a receptor 620, an alarm 630 and a battery 640 (such as a small coin battery) which may power the receptor 620, the alarm 630 and any other electrical component. The alarm 630 may be a visual alarm (e.g., in the form of an LED) and/or an audio alarm. A reaction of the enzymes of the sensor 130 with a bacterial biomarker may generate an electrical current signal that travels from the sensor 130 to the receptor 620 of the control hub 600 via the conductive element 131. The intensity of the signal may correspond with the concentration of the bacterial biomarker in the fluid of the vessel. The receptor 620 may measure the intensity of the signal. If the signal intensity is at or above a predetermined clinical concentration, the receptor 620 may trigger the alarm 620.

FIG.2 generally depicts a catheter system with a configuration that is similar to that of the system of FIG 1. However, according to this embodiment, the catheter body 110 of the catheter 200 may comprise a recess 115 in the wall of the catheter body 110. The recess 115 may be formed in the outer wall surface 112 of the catheter body such that the enzymatic sensor 230 may be exposed to the fluids/solids in the patient’s vessel. Alternatively, the recess 115 may be formed in the inner surface of the catheter body 110 such that the enzymatic sensor 230 may be exposed to the fluids/solids in the catheter lumen 120. The enzymatic sensor 230 may also have a low profile so that the sensor 230 does not or does not substantially extend beyond the surface in which the recess 115 is formed. Similar to the embodiment of FIG. 1, the enzymatic sensor 230 may be connected to a control hub 600 via a conductive element 131 that is embedded in the wall of the catheter body 110. Lighting of the LED alarm 630 to signal the detection of a bacterial infection may occur following the same process as described above.

FIG.3 depicts a catheter system comprising an enzymatic sensor for detecting a thrombus in a vessel. The catheter system may have the same configuration as described previously for FIG. 1 and FIG.2. However, according to this embodiment, the catheter 300 may comprise an enzymatic sensor 320 for detecting thrombus biomarkers. The sensor 320 may comprise an electrode and enzymes immobilised on the surface of the electrode that react with the thrombus biomarkers to generate an electrical current. The enzymatic sensor 320 may be positioned at/or adjacent to the distal end of the catheter 300 so that the sensor 320 may come into direct contact with a thrombus when the catheter is advanced distally. The system may comprise a component to facilitate contact between the electrode and the thrombus biomarkers. For example, the system may comprise a penetrating, cutting, shearing or fragmenting component. The thrombus sensor 320 may be connected to a conductive element 321, which may be embedded within the wall of the catheter body 110, i.e., between the inner wall surface 111 and the outer wall surface 112. The conductive element 321 may be connected to a control hub 600'. The control hub 600' is the same as the control hub 600, except that control hub 600' comprises receptor 620' and alarm 630' that are associated with signals generated by the thrombus biomarker sensor 320 and communicated to the control hub 600' via conductive element 321.

FIG. 4 depicts a catheter system comprising an enzymatic sensor 130 for detecting a bacterial infection, such as that described with reference to FIG.l, and an enzymatic sensor 320 for detecting a thrombus in a vessel, such as that described with reference to FIG.3. In this embodiment, the control hub 600" receives signals from the conductive elements 131 and 321 that are respectively linked to the bacterial sensor 130 and thrombus sensor 320. The control hub 600" comprises the receptor 620 and alarm 630 for measuring and signalling detection of bacterial biomarkers by the bacterial sensor 130, as well as the receptor 620' and alarm 630' for measuring and signalling detection of thrombus biomarkers by the thrombus sensor 320. It is envisaged that the enzymatic sensors 130,320 are aligned with each other, adjacent to each other or separated from each other, for example so as to be positioned on diametrically opposed sides of the catheter body 110. Similarly, it is envisaged that the conductive elements 131,321 are aligned with each other, adjacent to each other or separated from each other, for example so as to be positioned on diametrically opposed sides of the catheter body 110.

FIG. 5 depicts an alternative catheter system with a configuration that is identical or similar to that illustrated in FIG.4. However, according to this embodiment, the system comprises the enzymatic sensor 230, as described with reference to FIG.2, for detecting a bacterial infection and the enzymatic sensor 320, as described with reference to FIG.3, for detecting a thrombus in a vessel.

In some embodiments, the catheter may be used in the method for detecting bacterial biomarkers. The method may comprise the step of inserting a catheter (100, 200, 400, 500) into a patient’s vessel. The bacterial biomarkers to be detected may be polysaccharides. The enzymatic sensor (130, 230) may comprise one or more of glucose oxidase, protease, DNase, alginate ligase, amylase and cellulase. The method may further comprise the steps of measuring an electrical signal generated at an electrode in contact with the fluid and/or solids in the patient’s vessel and comparing the intensity of the electrical signal with a predetermined intensity value indicative of the presence of the biomarker. The method may also comprise the steps of measuring an electrical signal generated at an electrode in contact with the fluid and/or solids in the patient’s vessel, correlating the intensity of the electrical signal with intensity values indicative of the amount of biomarker, and determining the concentration of biomarker.

In some embodiments, the catheter may be used in the method for detecting thrombus biomarkers. The method may comprise the step of inserting a catheter (300, 400, 500) into a patient’s vessel. The thrombus biomarker may be fibrin. The enzymatic sensor (320) may comprise trypsin. The method may further comprise the steps of measuring an electrical signal generated at an electrode in contact with the fluid and/or solids in the patient’s vessel and comparing the intensity of the electrical signal with a predetermined intensity value indicative of the presence of the biomarker. The method may also comprise the steps of measuring an electrical signal generated at an electrode in contact with the fluid and/or solids in the patient’s vessel, correlating the intensity of the electrical signal with intensity values indicative of the amount of biomarker, and determining the concentration of biomarker. Thus, the present invention provides a minimally invasive catheter system capable of early or real-time indication of the presence of bacteria and/or thrombus formation, thereby allowing for earlier intervention. Early intervention, particularly with infections, can significantly improve mortality rates. Earlier administration of anti-thrombic medications can reduce the catheter failure/replacement rate.

Claims

1. A system comprising a catheter having an enzymatic sensor positioned at or adjacent the distal end thereof, said enzymatic sensor comprising an enzyme capable of reacting with a biomarker indicative of the presence of bacterial infection and/or of a thrombus in a vessel.

2. The system according to claim 1, wherein the biomarker is polysaccharides.

3. The system according to claim 2, wherein the enzymatic sensor comprises one or more of glucose oxidase, protease, DNase, alginate ligase, amylase and cellulase.

4. The system according to any preceding claim, wherein the biomarker is fibrin.

5. The system according to claim 4, wherein the enzymatic sensor comprises trypsin.

6. The system according to any preceding claim, further comprising an electrode coupled to the catheter, wherein said electrode is in contact with the fluid and/or solids present in the vessel.

7. The system according to claim 6, wherein the enzyme is immobilised on the surface of said electrode.

8. The system according to claim 6 or 7, further comprising a conductive braid coupled with said electrode and extending in the lumen of the catheter, at least from the electrode to the proximal end of the catheter.

9. The system according to any preceding claim, further comprising a control hub.

10. The system according to claim 9, wherein the control hub is configured to measure the electrical signal generated at the electrode; and to compare the intensity of the electrical signal with a predetermined intensity value indicative of the presence of the biomarker.

11. The system according to claim 9 or 10, wherein the control hub is configured to measure the electrical signal generated at the electrode; to correlate the intensity of the electrical signal with intensity values indicative of the amount of biomarker; and to determine the concentration of biomarker.

12. The system according to any preceding claim, wherein the catheter is a multi-lumen catheter.

13. A method for detecting a bacterial infection in a patient’s vessel, wherein the method comprises the step of inserting a catheter according to any one of claims 1 to 3 and 6 to 12 into a patient’s vessel.

14. The method according to claim 13, wherein the biomarker is polysaccharides.

15. The method according to claim 14, wherein the enzymatic sensor comprises one or more of glucose oxidase, protease, DNase, alginate ligase, amylase and cellulase.

16. The method according any one of claims 13 to 15, comprising the steps of measuring an electrical signal generated at an electrode in contact with the fluid and/or solids in the patient’s vessel; and comparing the intensity of the electrical signal with a predetermined intensity value indicative of the presence of the biomarker.

17. The method according any one of claims 13 to 16, comprising the steps of measuring an electrical signal generated at an electrode in contact with the fluid and/or solids in the patient’s vessel; correlating the intensity of the electrical signal with intensity values indicative of the amount of biomarker; and determining the concentration of biomarker.

18. A method for detecting a thrombus wherein the method comprises the step of inserting a catheter according to any one of claims 1 and 4 to 12 into a patient’s vessel.

19. The method according to claim 18, wherein the biomarker is fibrin.

20. The method according to claim 19, wherein the enzymatic sensor comprises trypsin.

21. The method according to any one of claims 18 to 20, comprising the steps of measuring an electrical signal generated at an electrode in contact with the fluid and/or solids in the patient’s vessel; and comparing the intensity of the electrical signal with a predetermined intensity value indicative of the presence of the biomarker.

22. The method according to any one of claims 18 to 21, comprising the steps of measuring an electrical signal generated at an electrode in contact with the fluid and/or solids in the patient’s vessel; correlating the intensity of the electrical signal with intensity values indicative of the amount of biomarker; and determining the concentration of biomarker.