SWALLOWABLE ELECTROCHEMICAL SENSOR

Description

[0001] The invention relates to an electrochemical sensor characterized by being swallowable and usable for detecting gases in the intestinal tract of a human being.

[0002] Electrochemical sensors are generally known. These are electrochemical cells that have at least one working electrode and one counter electrode. An electric current can flow between the electrodes via a conductive liquid, the so-called electrolyte, provided that certain analytes enter the area of ​​the electrodes. These analytes are usually gases.

[0003] However, a disadvantage of conventional electrochemical sensors is that the materials usually required for the electrochemical reaction, i.e., both electrolyte and electrodes, are often toxic or at least harmful to organisms.

[0004] The application range of conventional electrochemical sensors is therefore limited.

[0005] Nevertheless, from a medical perspective, it is of interest to be able to detect certain gases within an organism. For example, in connection with inflammatory bowel diseases, it can be useful to monitor the development of H₂S or NO gas. The severity of a corresponding disease, which often progresses in waves, could potentially be predicted based on the development of these gases.

[0006] Swallowable sensors are known, for example, from US 10,326,139 B2. However, these are mostly either optical or pH sensors. These are only suitable to a limited extent for detecting gases. While optical sensors can be used to detect methane in high concentrations, they are more commonly used for imaging the gastrointestinal tract. pH sensors, on the other hand, are mostly used to monitor the pH value of the stomach.

[0007] From Yoshida, S., Miyaguchi, H. & Nakamura, T. (2018). Proof of Concept for Tablet-Shaped Ingestible Core-Body Thermometer with Gastric Acid Battery. IEEE Sensors Journal; 18(23), 9755-9762; doi: 10.1109 / JSEN.2018.2871064, a battery is also known that can be used to power swallowable electronics. A battery is also an electrochemical cell. In this case, however, the electrodes, in the form of metal plates, are exposed on the surface. The battery function occurs as soon as these exposed electrodes come into contact with gastric juice from the surrounding environment. It should be noted that although this is an electrochemical cell with gastric juice as the electrolyte, the general operating principle differs fundamentally between batteries and electrochemical gas sensors. The battery described by Yoshida, S., Miyaguchi, H. & Nakamura, T.The battery proposed in 2018 is therefore in no way suitable for the detection of gases.

[0008] An electrochemical sensor according to the preamble of claim 1 is known from document US2013 / 289368 A1. Another electrochemical sensor is disclosed in document US2020 / 182823 A1.

[0009] The object of the present invention is therefore to provide an electrochemical gas sensor that can be used to detect gases in the digestive tract of an individual.

[0010] The main features of the invention are specified in the characterizing part of claim 1. Embodiments are the subject of claims 2 to 14.

[0011] An electrochemical gas sensor comprising a housing, at least one working electrode, and a counter electrode is proposed, wherein the housing has a gas inlet sealed by a gas-permeable membrane. The electrochemical gas sensor is characterized in that the housing has at least one electrolyte inlet filled with a hydrophilic sealant. The electrochemical gas sensor is preferably a swallowable gas sensor for detecting gases in the human intestinal tract.

[0012] Such a gas sensor can be swallowed by the individual being examined, thus entering the gastrointestinal tract. In other words, it is a swallowable sensor device. In the gastrointestinal tract, preferably in the stomach, the hydrophilic sealant allows gastric juice to pass through the electrolyte inlet into the interior of the housing, preferably into the interior described below. For this purpose, it is advantageous if the hydrophilic sealant is permeable to aqueous liquids, such as gastric juice, but impermeable to particles, for example, food particles. In this way, the gastric juice can come into contact with the electrodes, in particular the working electrode and the counter electrode, and subsequently serve as the electrolyte inside the gas sensor.The flow of gastric juice through the electrolyte inlet creates a fully functional electrochemical gas sensor inside the individual's body after the device according to the invention is swallowed. In other words, the device according to the invention can also be described as a swallowable, instant electrochemical gas sensor. This offers the significant advantage that, with the aid of the device according to the invention, the use of conventional electrolytes, especially toxic and / or harmful electrolytes, can be avoided when operating the electrochemical gas sensor inside the body of the individual being examined. This is a major advantage of the invention.

[0013] In any case, the casing is a hollow body with an outer surface and an inner surface. The components of the electrochemical cell are arranged in the inner surface. When operational, the gastric juice, which serves as the electrolyte, is also located in the inner surface.

[0014] It is advantageous if the housing also has a gas inlet separate from the electrolyte inlet. This gas inlet allows the gas to enter the electrochemical cell and subsequently react at the working electrode.

[0015] It is evident that it is advantageous for the housing to have multiple openings, namely at least one gas inlet and at least one electrolyte inlet. The gas inlet is a hole in the housing wall through which gas can enter the interior. To prevent liquid from entering through the gas inlet, it is advisable to seal it with a membrane that is gas-permeable but forms a barrier against liquid and particles. The electrolyte inlet is also a hole in the housing wall.

[0016] Inside the chamber, the gas can then come into contact with the working electrode and the electrolyte flowing in through the electrolyte inlet, resulting in an electrochemical reaction. This electrochemical reaction causes a current to flow between the working and counter electrodes. This current flow can then be detected.

[0017] To detect the electrochemical reaction, measuring electronics are also arranged in the housing, preferably in an electronics compartment separate from the interior. The measuring electronics are connected via precious metal wires to the electrodes of the electrochemical cell located inside the housing. They can be configured to wirelessly transmit a measurement signal, for example via Bluetooth or a similar wireless signal transmission, to a receiver located outside the body of the individual who has swallowed the sensor.

[0018] The electrolyte inlet is an opening in the housing of the electrochemical sensor. This opening connects the interior of the housing to the external environment of the electrochemical sensor. A fluid, preferably gastric juice, can flow into the interior of the housing through this opening.

[0019] The hydrophilic sealant is, for example, a glass fleece, hydrophilic PTFE (polytetrafluoroethylene), functionalized PO (polyolefin), or similar material. Due to its hydrophilic properties, it absorbs gastric juice from the sensor's surroundings. At the same time, it prevents larger particles from entering the housing. The sealant thus ensures that the gastric juice is transported through the electrolyte inlet into the housing's interior.

[0020] In other words, the invention relates to a swallowable electrochemical sensor characterized by the fact that its housing has electrolyte inlets through which an aqueous electrolyte, for example gastric acid, can penetrate from the sensor's environment into the interior and serve there as an electrolyte. The electrochemical sensor is thus brought into an operational state by being swallowed and the gastric acid penetrating the sensor.

[0021] In an initial embodiment, the interior of the housing is filled with a hydrophilic filler. This hydrophilic filler can then act as a wick, selectively transporting gastric juice from the external environment of the swallowed sensor to the electrodes. The hydrophilic filler can be made of the same material as the hydrophilic sealant. This ensures that the gastric juice, acting as the electrolyte, is not only drawn into the electrolyte inlet but also actually fills the interior of the housing. Furthermore, such a wick made of hydrophilic filler material ensures that the three-phase boundary necessary for an electrochemical reaction to detect gases forms correctly.The wick, formed from the hydrophilic filler and filling the interior of the housing, ensures that sufficient, but not excessive, electrolyte is transported from the outside through the electrolyte inlet to the electrodes. The hydrophilic filler is preferably designed such that the electrolyte transport is influenced by both the hydrophilicity of the material and by capillary forces. The strength of the capillary forces can be influenced, for example, by selecting the pore size of the filler. Glass fiber systems, such as glass fiber fleeces, have proven particularly suitable in this regard.

[0022] Furthermore, it is conceivable that the casing has multiple electrolyte inlet openings. This offers the advantage that gastric juice has several entry points into the interior of the casing. In this way, it is ensured that even if one of the inlet openings is blocked by food particles or similar, sufficient gastric juice can still reach the interior of the casing. It is also conceivable that all openings and the entire capsule are filled with hydrophilic fibers.

[0023] It is evident that a capsule-shaped sensor is advantageous. A capsule is generally understood to be a small, round container used to transport objects requiring protection. Such a container typically has a housing, inside which the object to be transported is located. The capsule's housing can also serve as the housing for the electrochemical sensor; the remaining structure of the sensor corresponds to that described above and in the following sections. Alternatively, the sensor could also be tablet-shaped. In any case, the sensor can be described as an encapsulated sensor.

[0024] It is conceivable that the housing is made of inert plastic. For example, the housing could be made of medical-grade polypropylene or polyethylene. An inert material reacts, if at all, only to a negligible degree, preferably not at all, with reagents and substances in the environment. It is therefore particularly advantageous if the inert plastic is one that is inert to gastric juice. A plastic inert to gastric juice is especially inert to hydrochloric acid and digestive enzymes.

[0025] The sensor could also have a soft, inert material as its casing. Such a casing could, for example, be applied as a coating to the outside of the housing. This casing can serve to improve the sensor's swallowability. It is conceivable, for instance, that the casing is made of silicone or another medically inert material. A medically inert material is one that does not react with bodily fluids, such as gastric juices or other digestive juices, and is therefore not absorbed by the body but excreted unchanged. Provided the casing is made of a suitable, durable, and inert material, it is, of course, designed so that the inlet openings in the housing—that is, the gas inlet and electrolyte inlet—do not obstruct them.

[0026] Alternatively, the sensor could have a casing made of a soft, absorbable material. Gelatin, for example, could be such a material. This type of casing would further improve the sensor's swallowability. The absorbable material could be dissolved by gastric juices, for instance. In this case, the casing could initially cover the inlet openings in the housing. This could be advantageous during the manufacturing process, as the sensor could then simply be completely immersed in gelatin.

[0027] In any case, it is advantageous for the gas inlet to be located directly in front of the working electrode. This minimizes the distance the gas has to travel within the sensor before reacting at the working electrode. It is beneficial to have a hydrophobic membrane positioned in front of the gas inlet and the working electrode. Such a membrane can serve as a physical barrier, preventing the ingress of food particles. Furthermore, the hydrophobic membrane can prevent gastric juice from entering through the gas inlet. The hydrophobic membrane can be designed with a narrow pore size to further impede the ingress of materials other than gas. A narrow pore size is defined as a membrane with a pore size of no more than 5 µm. It is advantageous if the pore size is less than 5 µm, preferably less than 4 µm, particularly preferably less than 3 µm, and most preferably 2 µm or less.

[0028] In addition to the working and counter electrodes, the sensor can also have a reference electrode. The reference electrode is also located inside the housing and thus also comes into electrically conductive contact with the electrolyte. It can be used for calibrating and verifying the functionality of the sensor according to the invention. This is particularly advantageous because the swallowed sensor is not readily accessible from the outside for calibration or maintenance.

[0029] In any case, the electrode material can be selected from palladium, platinum, rhodium, iridium, carbon, and / or gold. Mixtures of the aforementioned materials are also conceivable. Carbon and gold, in particular, offer the additional advantage of being inert materials. The other electrode materials can also be used without hesitation due to the sensor's design according to the invention, since they are located exclusively inside the sensor and therefore cannot come into contact with body tissue. It is evident that the sensor's design as an encapsulated sensor offers a further advantage in this respect.

[0030] It is also conceivable that two working electrodes are present. This is advantageous, for example, when several different gases need to be detected. The first working electrode could be made of iridium. Such an iridium electrode can be used selectively for the detection of H₂S. The second working electrode could be made of carbon. A carbon electrode could then be used for the selective detection of NO. Therefore, a sensor with a first working electrode made of iridium and a second working electrode made of carbon can be used for the selective detection of H₂S and NO. This is helpful, for example, when an impending inflammatory wave needs to be detected during the course of chronic colitis.

[0031] In one embodiment, the sensor can be filled with an electrolyte, which is selected from the group consisting of citric acid, formic acid, acetic acid, hydrochloric acid, or phosphoric acid. The sensor can be filled with the electrolyte, particularly before ingestion. For this purpose, the provided, electrolyte-free sensor is placed in an electrolyte bath. The electrolyte bath consists, for example, of a solution of citric acid, formic acid, acetic acid, or the like. It is particularly advantageous if the electrolyte bath consists of a citric acid solution. The citric acid is preferably an aqueous solution, with the citric acid present in a concentration in the range of 0.1 molar to 2 molar, preferably 0.5 molar to 1 molar, and most preferably 0.75 molar. In another embodiment, it is particularly advantageous if the electrolyte bath consists of a hydrochloric acid solution.The hydrochloric acid solution is an aqueous solution, wherein the hydrochloric acid is present in a concentration range of 0.1 molar to 2 molar, preferably from 0.5 molar to 1 molar, and most preferably 1 molar. It goes without saying that tight tolerances of the concentration range are also included in the corresponding embodiments. In yet another embodiment, it is particularly advantageous if the electrolyte bath consists of a phosphoric acid solution. The phosphoric acid solution is an aqueous solution, wherein the phosphoric acid is present in a concentration range of 0.1 molar to 2 molar, preferably from 0.5 molar to 1 molar, and most preferably 1 molar. It goes without saying that tight tolerances of the concentration range are also included in the corresponding embodiments.

[0032] It can be seen that, in the context of the present solution, a method for providing a swallowable electrochemical sensor is also advantageous, wherein the method comprises the following steps: a. Providing an unfilled electrochemical sensor b. Providing an electrolyte solution c. Immersing the unfilled electrochemical sensor in the electrolyte solution d. Providing the pre-filled electrochemical sensor.

[0033] Optionally, the sensor can also be coated between steps c and d, i.e., after it has been pre-filled by immersion in the electrolyte solution and before it is prepared for ingestion. For example, the gelatin coating described above can be applied. Other coating materials are, of course, also conceivable. Therefore, the procedure can also include the following step e: e. Coating the pre-filled sensor (10) with a self-dissolving layer upon contact with gastric acid.

[0034] Step e is preferably executed after step c but before step d.

[0035] In any case, it is advantageous if the pre-filling of the electrochemical sensor according to step c also includes a brief rinsing of the sensor after bathing the unfilled electrochemical sensor. Rinsing can be done, for example, by briefly rinsing under running water immediately before ingestion. However, it is preferable to briefly immerse the sensor, bathed in the electrolyte solution, in a rinsing bath. The rinsing bath can contain, for example, distilled water or a physiological saline solution.

[0036] It is particularly advantageous if the electrolyte bath provided according to step b comprises an electrolyte selected from the group containing citric acid, formic acid, acetic acid, hydrochloric acid, phosphoric acid, preferably citric acid, formic acid, hydrochloric acid or phosphoric acid, most preferably citric acid, hydrochloric acid or phosphoric acid.

[0037] For example, it is conceivable that the unfilled sensor is first provided to medical or pharmaceutical personnel. They then carry out the necessary steps for pre-filling and coating the sensor. The coating could be done, for instance, by immersing the pre-filled sensor in a gelatin solution or similar substance. The personnel can then give the prepared sensor to a patient, who would then swallow it.

[0038] After ingestion, in addition to the electrolyte already present in the sensor, stomach acid can flow into the sensor through one or more of the electrolyte inlets, as described above.

[0039] In a further advantageous embodiment, the solution to the problem also includes a kit for the detection of intestinal gases, wherein the kit comprises an unfilled electrochemical sensor corresponding to the one described above, as well as an electrolyte preparation.

[0040] The electrolyte preparation can be supplied as a ready-to-use liquid, a concentrated liquid, or a powder. Using the kit, medical or pharmaceutical personnel, or even a patient themselves, can pre-fill the swallowable electrochemical sensor immediately before use. If the electrolyte preparation is in powder form, it can be dissolved in a specified amount of liquid, such as tap water or distilled water as indicated in the instructions. If the electrolyte preparation is in concentrated liquid form, it can be diluted according to the instructions before immersing the empty sensor in the electrolyte solution until the desired concentration is reached.

[0041] Furthermore, such a kit could also provide a suitable rinsing solution. It is also conceivable that the kit includes appropriate containers in which the electrolyte preparation and the rinsing solution for immersing the sensor can be provided.

[0042] Further features, details and advantages of the invention will become apparent from the wording of the claims and from the following description of exemplary embodiments with reference to the drawings. The drawings show: Fig. 1 a schematic cross-section through a sensor according to the invention. Fig. 2 a further schematic cross-section through a sensor according to the invention. Fig. 3 a schematic overview of a method for providing a swallowable electrochemical sensor.

[0043] Both in Fig. 1 as well as in Fig. 2A cross-section through a gas sensor 10 is visible. The gas sensor 10 has a housing 11. The housing 11 has an interior 20. A first working electrode 14 and a second working electrode 14' are arranged in the interior 20. It is also conceivable that the sensor has only one working electrode 14. Furthermore, a counter electrode 15 and a reference electrode 16 are arranged in the interior 20.

[0044] An electronic unit 21 is arranged on the outside of the housing 11. The electronic unit 21 is installed in a sealed capsule. The electrodes 14, 14', 15, 16 are connected to the electronic unit 21 via wire connections 22, which extend from the electronic unit 21 and through the housing 11, as shown in particular in Fig. 2 This wire connection is not suitable for all electrodes in the Fig. 1 and 2This is visible because it lies partially outside the cross-sectional plane of the illustration. However, a corresponding wire connection 22 is naturally provided for each of the electrodes.

[0045] It can be seen that the housing 11 has several openings, namely openings that serve as gas inlet 12 and openings that serve as electrolyte inlet 17.

[0046] The gas inlet 12 is arranged such that a working electrode 14, 14' is located on the inside of the housing 11, directly behind the gas inlet 12. Furthermore, each gas inlet 12 is sealed by a hydrophobic membrane 13. In this way, only gas can enter the sensor through the gas inlet 12 and reach the working electrode 14, 14'. Aqueous liquids are repelled due to the hydrophobic properties of the membrane. Solid particles, e.g., food particles, are prevented from entering by the physical barrier effect of the membrane. In the example shown, the Figure 1 and 2 The hydrophobic membrane 13 is located on the outside of the housing 12. It is also conceivable that it is arranged on the inside of the housing 12, although the embodiment shown in the figures is preferred. Furthermore, it can be seen that in the Figure 1 and 2 A hydrophobic membrane 13 covers all gas inlets 12. It is of course also conceivable that each gas inlet 12 is closed with its own hydrophobic membrane 13, although the embodiment shown in the figures is preferred.

[0047] The openings, which serve as electrolyte inlets 17, are each fitted with hydrophilic seals 18. Due to their hydrophilic properties, these seals direct aqueous liquids into the interior 20 of the housing 11. However, the hydrophilic seals 18, like the hydrophobic membrane 13, prevent solid particles from entering the interior 20.

[0048] The interior 20 of the housing 11 is filled with a hydrophilic filler 19. This can act like a sponge or wick and, for example, facilitate the penetration of gastric acid, which serves as an electrolyte. Furthermore, the hydrophilic filler 19 can retain the successfully penetrated electrolyte within the interior 20 of the housing 11.

[0049] One can further recognize in the Figure 1 and 2 The entire device 10 is surrounded by a shell 30. The shell 30 forms a capsule around the sensor 10. The shell 30 consists, for example, of a soft, inert material, as described above. It can be seen that the shell 30 also encloses the hydrophobic membrane. The shell 30 also has openings only at the locations where the gas inlets 12 and the electrolyte inlets 17 are formed.

[0050] In Fig. 3It can be seen that a suitable swallowable electrochemical sensor can be provided by first providing an unfilled sensor 10. This unfilled sensor 10 corresponds to the one described above and in the Figure 1 and 2The sensor 10 shown is described. To avoid repetition, reference is made to the above description for all features of the provided unfilled sensor 10. In a further step b, an electrolyte solution is provided. This can, for example, contain citric acid, formic acid, or acetic acid as the electrolyte. According to step c of the procedure, the provided unfilled sensor 10 is then immersed in the provided electrolyte solution. The sensor is thereby pre-filled with the appropriate electrolyte. According to step e, the pre-filled sensor 10 can optionally be coated if required, before it is in any case made available for further use according to step d.

[0051] In a preferred embodiment, the electrolyte solution provided according to step b is a solution of 0.75 molar citric acid in water.

[0052] In another embodiment, the electrolyte solution provided according to step b is an aqueous solution of 1 molar hydrochloric acid.

[0053] In yet another embodiment, the electrolyte solution provided according to step b is an aqueous solution of 1 molar phosphoric acid.

[0054] The invention is not limited to one of the embodiments described above, but can be modified in many ways.

[0055] All features and advantages arising from the claims, the description and the drawing, including design details, spatial arrangements and process steps, can be essential to the invention both individually and in various combinations.

[0056] In any case, an electrochemical sensor 10 is provided with a housing 11, with at least one working electrode 14 and with a counter electrode 15, wherein the housing 11 has an interior space 20 in which the working electrode 14 and the counter electrode 15 are arranged, and wherein the housing 11 has at least one gas inlet 12, each gas inlet 12 being closed with a gas-permeable membrane 13, and wherein the housing 11 has at least one electrolyte inlet 17, each electrolyte inlet 17 being filled with a hydrophilic sealant 18. It is advantageous if the interior space 20 of the housing 20 is filled with a hydrophilic filler 19 and / or if the housing 20 has several electrolyte inlet openings 17. It is also advantageous if the sensor 10 is a capsule, if the housing 20 is made of inert plastic and / or if the sensor 10 has a soft, inert material as a casing 30.Advantageously, the gas inlet 12 is located directly in front of the working electrode 14, with a hydrophobic membrane 13 arranged in front of the gas inlet 12.

[0057] Furthermore, it is advantageous if the sensor 10 has a reference electrode 16. The electrode material can be selected from palladium, platinum, rhodium, iridium, carbon, and / or gold. Preferably, two working electrodes 14, 14' are provided. The first working electrode 14 can be made of iridium. The second working electrode 14' can be made of carbon. Reference symbol list

[0058] 10 Gas sensor 11 Housing 12 Gas inlet 13 Hydrophobic membrane 14 Working electrode 14' Working electrode 15 Counter electrode 16 Reference electrode 17 Electrolyte inlet 18 Hydrophilic sealant 19 Hydrophilic filler 20 Interior 21 Electronic unit 22 Wire connection 30 Sheath

Claims

1. Ingestible electrochemical sensor (10) for detecting gases in the intestinal tract of a human, comprising a housing (11), at least one working electrode (14) and a counter electrode (15), the housing (11) comprising an interior space (20) in which the working electrode (14) and the counter electrode (15) are arranged, and the housing (11) having at least one gas inlet (12), each gas inlet (12) being closed by a gas-permeable membrane (13), characterized in that the housing (11) has at least one electrolyte inlet (17), each electrolyte inlet (17) being filled with a hydrophilic sealant (18).

2. Electrochemical sensor according to claim 1, characterized in that the interior (20) of the housing (11) is filled with a hydrophilic filler (19).

3. Electrochemical sensor according to either of the preceding claims, characterized in that the housing (11) comprises a plurality of electrolyte inlet openings (17).

4. Electrochemical sensor according to any of the preceding claims, characterized in that the sensor (10) is a capsule.

5. Electrochemical sensor according to any of the preceding claims, characterized in that the housing (11) is made of inert plastics material.

6. Electrochemical sensor according to any of the preceding claims, characterized in that the sensor (10) comprises a soft, inert material as a casing (30).

7. Electrochemical sensor according to any of the preceding claims, characterized in that the gas inlet (12) is located directly in front of the working electrode (14).

8. Electrochemical sensor according to any of the preceding claims, characterized in that a hydrophobic membrane (13) is arranged in front of the gas inlet (12) in front of the working electrode (14).

9. Electrochemical sensor according to any of the preceding claims, characterized in that two working electrodes (14, 14') are present.

10. Electrochemical sensor according to any of the preceding claims, characterized in that the sensor can be filled with an electrolyte, the electrolyte being selected from the group containing citric acid, formic acid, acetic acid, hydrochloric acid, phosphoric acid.

11. Method for providing an ingestible electrochemical sensor according to any of claims 1 to 10, characterized in that the method comprises the steps of: a. providing an unfilled electrochemical sensor (10); b. providing an electrolyte solution; c. bathing the unfilled electrochemical sensor (10) in the electrolyte solution; d. providing the prefilled electrochemical sensor (10).

12. Method according to claim 11, characterized in that the method also comprises the step of e. coating the prefilled sensor (10) with a layer that dissolves upon contact with gastric acid.

13. Method according to either of claims 11 or 12, characterized in that the electrolyte bath provided according to step b comprises an electrolyte which is selected from the group containing citric acid, formic acid, acetic acid, hydrochloric acid, phosphoric acid, preferably citric acid, formic acid, hydrochloric acid or phosphoric acid, particularly preferably citric acid, hydrochloric acid or phosphoric acid.

14. Kit for detecting intestinal gases, wherein the kit comprises an unfilled electrochemical sensor according to at least one of claims 1 to 10, and an electrolyte preparation.

15. Kit according to claim 14, characterized in that the electrolyte preparation is available as a ready-to-use liquid preparation, as a concentrated liquid preparation or as a powder.