WO2016000756A1

WO2016000756A1 - Measuring device for detecting ammonia in gastric juice

Info

Publication number: WO2016000756A1
Application number: PCT/EP2014/063923
Authority: WO
Inventors: Patrick Fröse; Erhard Magori; Roland Pohle; Angelika Tawil; Oliver von Sicard
Original assignee: Siemens Aktiengesellschaft
Priority date: 2014-07-01
Filing date: 2014-07-01
Publication date: 2016-01-07

Abstract

The invention relates to a measuring device for detecting ammonia in gastric juice, in particular capsule, catheter, gastroscope or biopsy forceps, having a sensor, wherein the sensor comprises: - a reference electrode comprising a noble metal that is impervious to acid present in gastric juice, - a first measuring electrode having a silver chloride layer, - at least one second measuring electrode having a silver chloride layer, wherein the silver chloride layer of the second measuring electrode and the silver chloride layer of the first measuring electrode have thicknesses and/or layer morphologies that are different from each other, - means for determining a first electrical variable between the first measuring electrode and the reference electrode and a second electrical variable between the second measuring electrode and the reference electrode, wherein the electrical variables are influenced by the presence of ammonia in the region of the electrodes.

Description

description

The invention relates to a measuring device for ammonia detection in gastric juice.

A common cause of discomfort in the upper gastrointestinal tract is a bacterial infestation of its organs. For example, Helicobacter pylori infestation is believed to be responsible for a whole range of gastric disorders associated with increased gastric acid secretion. These include, for example, type B gastritis, about 75% of gastric ulcers, and almost all twelve-finger gut ulcers. The investigation of the hollow organs of the gastrointestinal tract on colonization with bacteria, in particular on colonization with Helicobacter pylori, is therefore an important part of the diagnosis of gastric diseases.

One possibility for examining the stomach for colonization with Helicobacter pylori is the so-called gastroscopy ("gastroscopy")

WO 2010/094650 Al described, a gastroscope used at the end of which are two electrodes with which a measurement for the detection of Helicobacter pylori is made possible.

An alternative to gastroscopy is the use of a

Endoscopy capsule, as shown in more detail in WO 2009/127528, for example. In this case, the endoscopy capsule is guided to a point to be examined in the gastrointestinal tract and a determination for Helicobacter pylori is carried out "on site." WO 2010/094649 describes another method for the determination of Helicobacter pylori. A disadvantage of the known in-vivo measuring devices is that the intensity and timing of the characteristic signal which arises when the AgCl layer is detached by ammonia can be unfavorable at very low ammonia concentrations or very high ammonia concentrations. For example, with thinly selected AgCl layers, a signal may unfavorably occur immediately when contact with the gastric juice is made. The actual signal is disadvantageously superimposed by the other effects of immersion on the sensor. If the AgCl layer is made thicker, at low ammonia concentrations the signal may be delayed significantly.

It is an object of the present invention to provide a measuring device and a method with which an improved determination of a bacterial infestation, such as

Helicobacter pylori, in vivo.

This object is achieved by a measuring device having the features of claim 1 or by a method having the features of claim 5. Further developments of the invention can be found in the dependent claims.

The measuring device according to the invention is in particular a gastric capsule, a catheter, a gastroscope or a biopsy forceps and comprises a sensor which has a reference electrode, a first measuring electrode and at least one second measuring electrode. The reference electrode comprises a noble metal which is not attackable by gastric acid. The first measuring electrode comprises a silver chloride layer. The second measuring electrode likewise comprises a silver chloride layer. In this case, the silver chloride layer of the second measuring electrode has one and the silver chloride layer of the first measuring electrode mutually different thicknesses and / or

Layer morphology on. Finally, the sensor comprises means for determining a first electrical variable between the first measuring electrode and the reference electrode and a second electrical variable between the second measuring element Electrode and the reference electrode, wherein the electrical quantities are influenced by the presence of ammonia in the region of the electrodes. The method according to the invention for ammonia detection in gastric juice comprises the following steps:

Providing a measuring device, in particular capsule, catheter, gastroscope or biopsy forceps, with a sensor, the sensor comprising:

a reference electrode with a noble metal which is not attackable by gastric acid,

a first measuring electrode with a silver chloride layer, at least one second measuring electrode with a

Silver chloride layer, the silver chloride layer of the second measuring electrode having one and the silver chloride layer of the first measuring electrode having mutually different thicknesses and / or layer morphology,

- Determining at least a first electrical variable between the first measuring electrode and the reference electrode and a second electrical variable between the second measuring electrode and the reference electrode, wherein the electrical quantities are influenced by the presence of ammonia in the region of the electrodes , The invention is based on the finding that an improvement of the detection with respect to greatly varying ammonia concentrations can be achieved by using at the location of only one measuring electrode a plurality of measuring electrodes in which a different functionalization is present. The functionalization, i. the silver chloride layer is different so that the time until dissolution of the entire layer by the ammonia is different. This can be achieved by different thicknesses of AgCl layers, but also by a different microstructure.

Advantageously, the measuring device allows in a simple manner, during the examination directly in Gastrointestinal tract of a patient and without taking a tissue sample to detect ammonia (NH3). The measuring device thus makes it possible to examine the gastric acid and the tissue of the gastric mucosa for Helicobacter pylori only to a low degree.

Advantageous embodiments of the invention are:

The measuring device can be designed to apply a voltage before a measurement which is suitable for preventing the formation of a silver chloride layer on the measuring electrodes in the gastric juice. As a result, it is achieved particularly advantageously that even in gastric juice the measuring electrodes remain largely unchanged and a well-defined initial state of the sensor is maintained for the measurement.

- As precious metals that are not attacked by hydrochloric acid and thus are suitable for the reference electrode, for example, platinum (Pt) and gold (Au) come into question.

- The measuring device may be configured to apply no voltage during a measurement. Thus no current flows between the measuring electrodes and the reference electrode. Between the measuring electrodes and the reference electrode, the potential, that is to say without current, is thus advantageously measured. This hardly causes ion migration in the stomach acid.

- The measuring device may be configured to apply a DC electrical voltage during a measurement for a predeterminable time. The predeterminable time for which a voltage can be applied by the user between the first electrode and the second electrode can be between zero seconds and continuously, wherein the user-selected electrical voltage can be zero volts or higher. At a

Time of zero seconds or a voltage of zero volts is a passive measurement. For deviating values, an active measurement is available. For example, potentials, electrical currents or electrical resistances or their changes or quantities derived from the electrical variables (for example electrical conductivity or impedance) or changes thereof can be measured as the electrical variable.

The measuring device may have a single reference electrode, so that pairs of electrodes are formed with this reference electrode. Alternatively, the measuring device may comprise a plurality of, preferably exactly two, reference electrodes, so that a separate reference electrode is available for each measuring electrode. The invention and further advantageous embodiments are explained in more detail below with reference to an embodiment in the drawing. 1 schematically shows a gastroscope with an ammonia sensor,

2 shows the ammonia sensor.

FIG. 1 shows a gastroscope 1, which is a flexible endoscope and is used to examine the upper gastrointestinal tract. The gastroscope 1 comprises an insertion tube, in which a working channel 2 is arranged, and a sensor 4, which is guided over a guide wire 3 in the working channel 2. The sensor 4 comprises a first electrode 5 (reference electrode) made of gold. In addition, the sensor 4 comprises a first measuring electrode 6 and a second measuring electrode 7. The first measuring electrode 6 is a silver electrode with an overlying silver chloride layer 61. The second measuring electrode 7 is also a silver electrode with an overlying silver chloride layer 71. In the exemplary embodiment shown, the measuring electrodes 6, 7 have the same and constant distance from the reference electrode 5. It is the Thickness of the silver chloride layer 61 of the first measuring electrode 6 is about twice as thick as the thickness of the silver chloride layer 71 of the second measuring electrode 7. FIG. 2 shows the measuring electrodes 6, 7 and the reference electrode in a highly schematic and not to scale side view for clarification The different structure of the silver chloride layers 61, 71. To the pairs of the first measuring electrode 6 and reference electrode 5 and the second measuring electrode 7 and reference electrode 5 each a separate electrical voltage can be applied, whereby in the presence of ammonia in the region of the first Electrode 6 and the second electrode 7, a change in electrical size, such as potential, electrical current or electrical resistance, can be measured.

In the gastroscope 1 shown in the drawing, further elements, such as e.g. Fiber optic bundle (with a

Light source coupled fiber bundle) and image guide bundle (bundled with a camera fiber bundle) and

Abwinkelungszüge (running in the flexible outer casing of the gastroscope) may be arranged. The other elements, the arrangement of which is known per se, are not shown in the drawing for reasons of clarity.

Furthermore, the gastroscope 1 can have a supply line for urea. Urea is converted from Helicobacter pylori to ammonia. By targeted addition of urea, therefore, an amplification of the measured effect can be achieved.

After the introduction of the gastroscope 1 according to the invention, the sensor 4 detects ammonia (NH3) present in the stomach acid and in the tissue of the gastric mucosa on the stomach inner wall. This results in an infection of the tissue (gastric mucous membrane) with Helicobacter pylori by the detection of ammonia (NH3). knows. This is done without biopsy and is thus much less stressful for the patient.

The detection of ammonia is a very strong indication of the presence of Helicobacter pylori, since ammonia is produced by the Helicobacter pylori bacteria by a cleavage of urea by urease to the acidic environment of the gastrointestinal tract, in particular the high acid concentration in the stomach , to protect. The salt AgCl (silver chloride) is split by ammonia into the silver-diamine complex [Ag (NH3) 2] + and chlorine Cl-. [Ag (NH3) 2] + is highly soluble in water as a cation and is absorbed by the stomach acid. In the given embodiment, two electrical variables are measured and logged. These electrical variables (potential, electrical current, electrical resistance) relate to the first measuring electrode 6 and the reference electrode 5 as well as the second measuring electrode 7 and the reference electrode 5. For example, the electrical voltage between the first measuring electrode 6 and the reference electrode 5 are recorded and stored as a first electrical quantity. As a second electrical variable, the electrical voltage between the second measuring electrode 7 and the reference electrode 5 is used.

In the state before the measurement, the two measured electrical variables can reflect the different structure of the two measuring electrodes 6, 7. The immersion in the stomach acid can influence the structure of the measuring electrodes. If a measurement is not yet desired, since, for example, no suitable location has yet been activated, a countervoltage can be applied to the second measuring electrode in the gastroscope 1 shown, which prevents further buildup of an AgCl layer together with the stomach acid. Thereby, the initial state of the measuring electrodes 6, 7 is obtained and the accuracy of the measurement is improved. In the extreme cases of particularly low ammonia concentration or in the complete absence of ammonia or particularly high ammonia concentration, the advantages of the sensor show. At very low ammonia concentration, if only the thick silver chloride layer 61 were present, it would take a long time to wait for the signal to appear when the AgCl layer was completely dissolved. As a result of the sensor 4 also having a thinner silver chloride layer 71, the waiting time can be shortened since the thinner layer 71 would show a signal more quickly.

Conversely, if only the thin layer of silver chloride 71 were present, a very high concentration of ammonia would only give a bad signal, as it would then be dissolved almost simultaneously with immersion in the gastric juice.

Here, the thick silver chloride layer 61, which generates a signal only delayed, allows a much more accurate measurement that is unaffected by the immersion process. An analogous effect can be achieved if the silver chloride layers 61, 71 also have a different microstructure instead of or in addition to the different thickness. For example, a higher porosity can lead to an increased reaction with the ammonia and thus to an accelerated degradation of the silver chloride layer 61, 71.

It is also advantageous if a third or fourth or further measuring electrodes are used in which there are further different thicknesses and / or morphologies. Thus, further ranges of ammonia concentration can be tapped for accurate measurement.

Claims

claims

1. Measuring device (1) for ammonia detection in gastric juice or in the stomach, in particular capsule, catheter, gastroscope (1) or biopsy forceps, with a sensor (4), wherein the sensor (4) comprises:

a reference electrode (5) with a precious metal which is not vulnerable to acid present in gastric juice,

- A first measuring electrode (6) with a

Silver chloride layer (61),

- At least a second measuring electrode (7) with a

Silver chloride layer (71), wherein the silver chloride layer (71) of the second measuring electrode (7) and the

Silver chloride layer (61) of the first measuring electrode (6) have mutually different thicknesses and / or layer morphology,

- means for determining a first electrical quantity between the first measuring electrode (6) and the reference electrode (5) and a second electrical variable between the second measuring electrode (7) and the reference electrode (5), wherein the electrical quantities are influenced by the presence of ammonia in the region of the electrodes (6, 7).

2. Measuring device (1) according to one of the preceding claims che, in which the sensor (4) comprises means for applying an electrical voltage between at least one of the measuring electrodes (6, 7) and the reference electrode (5).

3. Measuring device (1) according to one of the preceding claims che, wherein the reference electrode (5) made of platinum or from

Gold exists.

4. Measuring device (1) according to one of the preceding claims, wherein the sensor (4) has at least one second reference electrode.

5. Method for ammonia detection in gastric juice or in the stomach with the steps: - Providing a measuring device (1), in particular capsule, catheter, gastroscope (1) or biopsy forceps, with a sensor (4), wherein the sensor (4) comprises:

a reference electrode (5) with a noble metal which is not attackable by gastric acid,

- A first measuring electrode (6) with a

Silver chloride layer (61),

- At least a second measuring electrode (7) with a

- Determining at least a first electrical variable between the first measuring electrode (6) and the reference electrode (5) and a second electrical variable between the second measuring electrode (7) and the reference electrode

(5), wherein the electrical quantities are influenced by the presence of ammonia in the region of the electrodes (6, 7).