Collection module delivery capsule for multi-collection of intestinal biological substances

Abstract

The capsule module for multi-collection of intestinal biological substances according to the present invention can collect intestinal samples in various places within the gastrointestinal tract by means of the administration of a single capsule without the aid of an external system and thus can improve the accessibility and convenience of intestinal microorganism research.

Description

Delivery capsule for collection module for multiple collections of intestinal biological materials

[0001] This invention was made under the support of the Korea Health Industry Development Institute under the project identification number 2023080014, project number 2023080014, and the research management specialized institution of the said project is the Daegu Gyeongbuk Institute of Science and Technology, the research project name is “Development of advanced technology for common base module of micro medical robot and commercialization of medical product”, the research project name is “Development of advanced technology for microbial collection module to prevent cross-contamination in (primary) digestive organs”, the main institution is the Daegu Gyeongbuk Institute of Science and Technology, and the research period is from 2023.08.01 to 2023.12.31.

[0002] The present invention was made under the support of the Korea Institute of Industrial Technology Planning and Evaluation, under the grant number 2022040050, and the research management specialized institution of the said project is the Daegu Gyeongbuk Institute of Science and Technology, the research project name is “Bioindustry Technology Development”, the research project name is “Development of a convergence medical device for active precision delivery of embolic particles for transarterial chemoembolization for the treatment of liver tumors and a simulator for embolization training”, the main institution is the Daegu Gyeongbuk Institute of Science and Technology, and the research period is from 2023.03.01 to 2023.12.31.

[0003] The present invention relates to a collection module delivery capsule for multiple collection of intestinal biological materials, and more particularly, to a device capable of multiple collection of biological materials from multiple locations in the intestine of a subject through a plurality of collection modules included in a capsule module, and a collection method using the same.

[0004] Gut microbes play a crucial role in human health. They are essential for the digestive process and play a crucial role in regulating the immune system. Furthermore, gut microbes help maintain our body's balance by contributing to the synthesis of vitamins and essential nutrients. When this microbial balance is disrupted, various health problems can arise. For example, an imbalance in the gut microbiome can increase the risk of chronic diseases such as obesity, diabetes, and autoimmune diseases. It can even affect mental health, with research linking it to conditions like stress, anxiety, and depression.

[0005] Previous studies of the gut microbiome have primarily relied on stool samples. While stool samples provide information on the diversity and composition of the gut microbiome, they typically only provide a limited overview of microbes in the rectum, the distal part of the colon. They are limited in their ability to fully assess the microbial composition of other areas, such as the proximal colon or small intestine. However, these areas are closely linked to the immune system and are where a significant amount of nutrients are absorbed. Therefore, existing studies using stool samples have presented challenges in accurately assessing the microbiome of the target organism.

[0006] Endoscopy is a method for collecting gut microbiota samples from specific areas of the gastrointestinal tract. However, endoscopic methods have several drawbacks: they are invasive, uncomfortable for the patient, expensive, time-consuming, and carry a risk of sample contamination. In particular, collecting intestinal samples using endoscopy presents a limitation: it is difficult to obtain samples from the distal small intestine or the proximal colon.

[0007] To overcome these limitations, a noninvasive technique for collecting gut microbiota samples from within the gastrointestinal tract is needed. Among the various techniques developed to date, no technique has been reported that allows for the collection of gut microbiota samples from multiple locations within the gastrointestinal tract using a single capsule, while preventing microbial cross-contamination before and after collection. Such a technique could significantly expand the accuracy and scope of gut microbiota research and lead to significant advancements in the diagnosis and treatment of gut-related diseases.

[0008] Against this backdrop, the present invention proposes a novel technique for efficiently and accurately collecting gut microbiota samples from various locations within the gastrointestinal tract. This technique is non-invasive, rapid, cost-effective, and minimizes the risk of sample contamination. This will enable more precise and comprehensive gut microbiota research and is expected to have a significant impact on the diagnosis and treatment of gut-related diseases.

[0009] The inventors of the present invention have fabricated a capsule module comprising a plurality of collection modules and have confirmed that the collection modules can move along the body of a subject, specifically the digestive tract, to collect biological samples at different locations.

[0010] Accordingly, an object of the present invention is to provide a capsule module including a plurality of collection modules.

[0011] Another object of the present invention is to provide a method for collecting an intestinal biological sample using a capsule module.

[0012] One aspect of the present invention is a capsule module for multiple sampling of intestinal biological materials, wherein the capsule module comprises two or more sampling modules connected to each other by a connecting member, the sampling module comprising: a module body, an opening for introducing a sample into an internal region of the module body, and a sampling member for collecting a sample introduced through the opening, wherein the connecting member is dissolved by intestinal fluid, and the two or more sampling modules are separated according to the dissolution of the connecting member.

[0013] In one embodiment of the present invention, the collection module may further include a cover member disposed adjacent to the opening and dissolved by the liquid.

[0014] In one embodiment of the present invention, the capsule module may further include a head module connected to any one of the two or more harvesting modules.

[0015] In one embodiment of the present invention, the head module may include an inwardly retractable receiving groove.

[0016] In one embodiment of the present invention, the collection module may further include a sealing member disposed above the collection member to block the opening according to expansion of the collection member.

[0017] In one embodiment of the present invention, the sealing member may include one or more materials selected from the group consisting of polydimethylsiloxane (PDMS), Ecoflex, and silicone elastomer.

[0018] In one embodiment of the present invention, the capsule module may be coated with an enteric cover.

[0019] In one embodiment of the present invention, the enteric cover may include one or more materials selected from the group consisting of guar gum, methyl methacrylate-methacrylic acid copolymers, starch, pectin, chitosan, guar gum, and dextran.

[0020] In one embodiment of the present invention, the extraction module may further include a magnetic body.

[0021] In one embodiment of the present invention, the harvesting module may include a plurality of sub-harvesting modules.

[0022] In one embodiment of the present invention, the plurality of sub-sampling modules may each include a module body, an opening, and a sampling member.

[0023] In one embodiment of the present invention, the collection module may include a porous member positioned adjacent to the opening.

[0024] In one embodiment of the present invention, the collection module may include one or more materials selected from the group consisting of cellulose, cellulose ester, polysulfone, polytetrafluoroethylene (PTFE), polydimethylsiloxane (PDMS), polyvinylidene fluoride (PVDF), polyethersulfone (PES), etched polycarbonates, or collagen.

[0025] In one embodiment of the present invention, the extraction member may include an expandable material.

[0026] In one embodiment of the present invention, the expandable material is selected from the group consisting of hydrogels, hydrocolloids, croscarmellose sodium, cross-linked polyvinyl pyrrolidone, ethylene maleic anhydride copolymer, carboxymethylcellulose, hydroxypropyl cellulose, polyvinyl alcohol copolymers, hydrophilic polyurethane, hydroxyethylmethacrylate (HEMA), sodium starch glycolate, crospovidone, cellulose, pectin, alginate, It may be at least one selected from the group consisting of agar, collagen, glycosaminoglycan, agarose, superabsorbent polymers, sponge, sodium polyacrylate, polyacrylamide, compressed rayon or starches at various levels of crosslinking.

[0027] In one embodiment of the present invention, the cover member may include a water-decomposable material.

[0028] Hydrodegradable materials include polyvinyl alcohol (PVA), polyvinyl acetate phthalate (PVAP), polyvinyl chloride (PVC), polyvinylpyridine acrylic acid, fatty acids, waxes, shellac, plant fibers, paper, cellulosic materials, starch, methyl acrylate-methacrylic acid copolymers, and cellulose acetate phthalate.CAP), Cellulose Acetate Succinate, Hydroxypropyl Methyl Cellulose Phthalate, Hydroxypropyl Methyl Cellulose Acetate Succinate, Methyl Methacrylate, Methacrylic Acid, Polyacryl, Cellulose Acetate, Trimellitate, Sodium Alginate, Zein, Starch, Pectin, Gelatin, Cross-Linked Gelatin, Carbohydrates, Gum Arabic, Salts, Sodium Hypochlorite, Lithium Hypochlorite It may be one or more selected from the group consisting of Lithium Hypochlorite, Calcium Hypochlorite, Dichlor, Trichlor, Sugars, Proteins and Hydrogels.;

[0029] In one embodiment of the present invention, the connecting member may include a long-lasting material.

[0030] In one embodiment of the present invention, the enteric material is Eudragit L100-55, Eudragit S100, Cellulose Acetate Phthalate, Hydroxypropyl Methyl Cellulose Phthalate, Kollicoat MAE 100 P, Methyl Methacrylate Methacrylic Acid Copolymer, Methyl Acrylate-Methacrylic Acid Copolymers, Cellulose Acetate Phthalate (CAP), Cellulose Acetate Succinate, Hydroxypropyl Methyl Cellulose Phthalate Methyl Cellulose Phthalate), Hydroxypropyl Methyl Cellulose Acetate Succinate, Hypromellose Acetate Succinate, Polyvinyl Acetate Phthalate (PVAP), Methyl Methacrylate-Methacrylic Acid Copolymers, Shellac, Cellulose Acetate Trimellitate, Sodium Alginate, and Zein.

[0031] In one embodiment of the present invention, the capsule module may include a first collection module, a second collection module connected to the first collection module via a first connecting member, and a third collection module connected to the second collection module via a second connecting member.

[0032] In one embodiment of the present invention, the first connecting member and the second connecting member may be dissolved at different locations within the intestine.

[0033] In one embodiment of the present invention, the cover members of the first collection module, the second collection module, and the third collection module may be dissolved at different locations or at different decomposition times within the intestine.

[0034] In one embodiment of the present invention, the cover members of the first extraction module, the second extraction module, and the third extraction module may have different thicknesses or different shapes.

[0035] In one embodiment of the present invention, the head module may include a camera module.

[0036] In one embodiment of the present invention, the head module may include a magnetic body.

[0037] In one embodiment of the present invention, the head module may include a sensor.

[0038] In one embodiment of the present invention, the head module may comprise a genetically recombinant microorganism.

[0039] The capsule module for multiple sampling of intestinal biological materials according to the present invention can collect intestinal samples from various parts of the gastrointestinal tract through a single capsule intake without the aid of an external system, thereby improving accessibility and convenience of intestinal microbiota research.

[0040] FIG. 1 is an exploded perspective view of a capsule module for multiple sampling of intestinal biological materials according to one embodiment of the present invention.

[0041] Figure 2 is a cross-sectional view of a first extraction module according to one embodiment of the present invention.

[0042] Figure 3 is a perspective view of a first extraction module according to one embodiment of the present invention.

[0043] FIGS. 4 to 6 are drawings for explaining a process of collecting an intestinal biological sample of a collection module or a sub-collection module according to one embodiment of the present invention.

[0044] FIG. 7 is an exploded perspective view of a capsule module for multiple sampling of intestinal biological materials according to another embodiment of the present invention.

[0045] Figure 8 is a cross-sectional view of a first sub-collection module according to another embodiment of the present invention.

[0046] FIGS. 9 to 14 are drawings for explaining a process of collecting samples from the intestines of a capsule module for multiple sampling of intestinal biological materials according to one embodiment of the present invention.

[0047] FIGS. 15 to 20 are drawings illustrating a process for collecting samples from the intestines in different ways using a capsule module for multiple sampling of intestinal biological materials according to one embodiment of the present invention.

[0048] In a capsule module for multiple sampling of intestinal biological materials,

[0049] The capsule module comprises two or more collection modules connected to each other by a connecting member,

[0050] The harvesting module:

[0051] It comprises a module body, an opening for introducing a sample into an internal area of ​​the module body, and a sampling member for collecting a sample introduced through the opening.

[0052] A capsule module in which the connecting member is dissolved by the liquid and two or more collection modules are separated according to the dissolution of the connecting member.

[0053] Hereinafter, the present invention will be described with reference to the attached drawings. However, the present invention can be implemented in various different forms and is therefore not limited to the embodiments described herein. In the drawings, irrelevant parts have been omitted for clarity of description, and similar parts have been designated with similar reference numerals throughout the specification.

[0054] Throughout the specification, when a part is said to be "connected (connected, contacted, or coupled)" to another part, this includes not only cases where it is "directly connected," but also cases where it is "indirectly connected" with another part in between. Furthermore, when a part is said to "include" a component, this does not exclude other components, but rather implies that it may include other components, unless otherwise specifically stated.

[0055] The terminology used herein is merely used to describe specific embodiments and is not intended to limit the present invention. The singular expression includes the plural expression unless the context clearly indicates otherwise. In this specification, it should be understood that the terms "comprises" or "has" indicate the presence of a feature, number, step, operation, component, part, or combination thereof described in the specification, but do not exclude in advance the possibility of the presence or addition of one or more other features, numbers, steps, operations, components, parts, or combinations thereof.

[0056]

[0057] Hereinafter, embodiments of the present invention will be described in detail with reference to the attached drawings.

[0058]

[0059] FIG. 1 is an exploded perspective view of a capsule module for multiple sampling of intestinal biological materials according to one embodiment of the present invention.

[0060] Referring to FIG. 1, a capsule module (hereinafter, capsule module) for multiple sampling of intestinal biological materials according to one embodiment of the present invention may include a head module (100), a first sampling module (200), a second sampling module (300), and a third sampling module (400).

[0061] A capsule module (1000) according to one embodiment may include one or more collection modules (200, 300, 400). The capsule module (1000) may include two or more, three or more, four or more, or five or more collection modules, and may be configured with a number of collection modules appropriately according to the number of areas from which biological samples are to be collected. For example, the capsule module (1000) may include three collection modules, namely a first collection module (200), a second collection module (300), and a third collection module (400), as illustrated in FIG. 1.

[0062] Two or more harvesting modules (200, 300, 400) included in a capsule module (1000) can be connected to each other. One harvesting module can be connected to another harvesting module, or can be connected to two or more harvesting modules simultaneously. The harvesting modules can be connected linearly as illustrated in FIG. 1, or can be connected non-linearly, with multiple other harvesting modules simultaneously connected to a specific harvesting module. For example, as illustrated in FIG. 1, within the capsule module (1000), a first harvesting module (200) can be connected to a second harvesting module (300), a second harvesting module (400) can be connected to the first harvesting module (200) and a third harvesting module (400), and a third harvesting module (400) can be connected to the second harvesting module (300).

[0063] The collection module (200, 300, 400) may have various shapes without limitation as long as it has a suitable structure for collecting intestinal biological samples. The collection module (200, 300, 400) may have various shapes such as a cylinder, a square cylinder, a pentagonal cylinder, a sphere, etc. For example, the collection module may have a cylindrical shape as illustrated in FIG. 1.

[0064] The collection module (200, 300, 400) may include a material suitable for collecting a biological sample without causing a rejection in the subject when entering the body, for example, the collection module may include a material including cellulose, cellulose ester, polysulfone, polytetrafluoroethylene (PTFE), polydimethylsiloxane (PDMS), polyvinylidene fluoride (PVDF), polyethersulfone (PES), etched polycarbonates or collagen.

[0065] The collection modules (200, 300, 400) can be connected to each other by a connecting member (not shown). In this case, the connecting member (not shown) may include a long-lasting material.

[0066] Enteric materials may be substances that are dependent on the pH of the external environment and are soluble. For example, enteric materials are compounds that are made to be broken down or absorbed in the small intestine without being broken down by gastric acid, and are stable under the pH conditions of gastric acid but can be dissolved or activated under the alkaline pH conditions of the small intestine.

[0067] Accordingly, as the capsule module moves within the digestive tract of the subject, the connecting member may pass through without being decomposed, maintaining its entire form. Upon entering the small or large intestine, the connecting member may be decomposed and separated in the pH environment of each organ. When the connecting member is decomposed after the capsule module enters the small or large intestine, the means connecting each collection module disappears, separating each collection module, allowing the user to begin collecting biological samples at the desired location.

[0068] A biological sample is a sample collected by a capsule module for examining or measuring the intestinal environment of a subject, and may include liquids, digestive fluids, mucus, microorganisms, metabolites, cells, cell fragments, carbohydrates, fats, lipids, proteins, peptides, immune system molecules, immune system cells, blood, hemoglobin, food particles, acids, bases, gases, small molecules, hormones, nucleic acids, drugs, prodrugs, drug metabolites, volatile molecules, gases, and other molecules present in the gastrointestinal tract from mouth to anus. For example, the biological sample may be a microorganism, and the microorganism may include one or more species or strains of microscopic organisms from the domains eukaryotes, prokaryotes, archaea, and viruses (e.g., bacteriophages).

[0069] As an enteric material, any material that is decomposed depending on specific pH conditions, for example, an enterolytic material known in the art to be decomposed in the small intestine without being decomposed by gastric acid, may be used without limitation.For example, enteric materials include Eudragit L100-55, Eudragit S100, Cellulose Acetate Phthalate, Hydroxypropyl Methyl Cellulose Phthalate, Kollicoat MAE 100 P, Methyl Methacrylate Methacrylic Acid Copolymer, Methyl Acrylate-Methacrylic Acid Copolymers, Cellulose Acetate Phthalate (CAP), Cellulose Acetate Succinate, Hydroxypropyl Methyl Cellulose Phthalate Examples of such materials include, but are not limited to, Cellulose Phthalate, Hydroxypropyl Methyl Cellulose Acetate Succinate, Hypromellose Acetate Succinate, Polyvinyl Acetate Phthalate (PVAP), Methyl Methacrylate-Methacrylic Acid Copolymers, Shellac, Cellulose Acetate Trimellitate, Sodium Alginate, and Zein.

[0070] When the capsule module (1000) includes three or more collection modules (200, 300, 400), each collection module (200, 300, 400) can be connected by different connecting members. For example, when the capsule module (1000) includes a first collection module (200), a second collection module (300), and a third collection module (400), the first collection module (200) can be connected to the second collection module (300) by the first connecting member, and the second collection module (300) and the third collection module (400) can be connected by the second connecting member.

[0071] The first connecting member and the second connecting member may be degraded under different conditions. That is, the first connecting member and the second connecting member may contain different enteric materials. When each connecting member contains an enteric material that degrades under different conditions, the positions at which the respective collection modules (200, 300, 400) of the capsule module (1000) are separated from each other may be different.

[0072] For example, the first connecting member and the second connecting member may include an enteric material that dissolves under different conditions, and specifically, the first connecting member and the second connecting member may include an enteric material that dissolves at different pHs. Generally, the human digestive tract, such as the duodenum, small intestine, and large intestine, have different pHs. The duodenum has a pH of approximately 6.0 to 7.4, the small intestine has a pH of 6.0 to 7.4, and the large intestine has a pH of 5.5 to 7.0. Accordingly, when the first connecting member is configured to decompose at a pH of 6.0 to 7.4 and the second connecting member is configured to decompose between 5.5 and 6.0, the first collection module (200) can collect a sample by separating from the duodenum or small intestine as the first connecting member dissolves in the duodenum or small intestine, and the second collection module (300) and the third collection module (400) can collect a sample from the large intestine as the second connecting member dissolves in the large intestine. Meanwhile, the pH of the digestive tract may be different even in the same organ. For example, if the capsule module (1000) is to collect biological samples from the proximal, middle, and distal portions of the small intestine, the first connecting member may be configured to be decomposed in the proximal region of the small intestine, and the second connecting member may be configured to be decomposed in the middle portion of the small intestine, so that the first collection module (200) can be separated from the proximal region of the small intestine, and the second collection module (300) and the third collection module (400) can be separated from the middle portion of the small intestine.

[0073] The connecting member may be a member in various forms including an enteric material, for example, a film, a coating, or a cured solid. When the connecting member is configured in the form of an enteric film, the first collection module (200) and the second collection module (300) may be connected to each other while the side portion (230) of the first collection module and the side portion (330) of the second collection module are simultaneously wrapped by the first connecting member having a film form, and the second collection module (300) and the third collection module (400) may be connected to each other while the side portion (330) of the second collection module and the side portion (430) of the third collection module are simultaneously wrapped by the second connecting member.

[0074] Meanwhile, when the connecting member is in the form of a film, long-lasting films having different decomposition conditions can be laminated to form a connecting member in the form of a film having multiple layers. For example, as illustrated in FIG. 1, when a capsule module includes a first collection module (200), a second collection module (300), and a third collection module (400), and the first collection module (200) and the second collection module (300) are connected by a first connecting member, and the second collection module (300) and the third collection module (400) are connected by a second connecting member, the first connecting member may be configured as a single layer of an enteric film that decomposes at a pH of 6.0 to 7.4, and the second connecting member may be configured by overlapping an enteric film that decomposes at a pH of 6.0 to 7.4 and an enteric film that decomposes at a pH of 5.5 to 6.0, so that the positions at which the first collection module (200) and the second collection module (300) are separated and the positions at which the second collection module (300) and the third collection module (400) are separated can be set differently.

[0075] The capsule module (1000) may include a head module (100) connected to at least one collection module (200, 300, 400).

[0076] The head module (100) may be placed at the end when a plurality of harvesting modules (200, 300, 400) are linearly connected within the capsule module (1000), or may be placed between harvesting modules.

[0077] The head module (100) can be connected to one or more collection modules by a third connection member (not shown), which is a separate connection member. At this time, the third connection member connecting the head module (100) and the collection module can include a material including the same enteric material as the connection members (the first connection member and the second connection member) connecting the aforementioned collection modules. For example, the third connection member connecting the head module (100) and the collection module can be an enteric film, and the head module and the collection module can be connected in a form that simultaneously wraps the side portion of the head module (100) and the side portion of the collection module. Therefore, when configuring the capsule module, the user can set the position at which the head module and the collection module are separated differently depending on the type of the enteric material used in the first connection member, the second connection member, and the third connection member, the thickness of the connection member including the enteric material, and the use of enteric materials laminated in multiple layers. For example, if the third connecting member is set to dissolve at the proximal end of the small intestine, the second connecting member is set to dissolve at the distal end of the small intestine, and the first connecting member is set to dissolve at the proximal end of the large intestine, the head module (100) can be detached from the capsule module (1000) at the proximal end of the small intestine, the first collection module (200) can be detached at the middle end of the small intestine, and the second collection module (300) and the third collection module (400) can be detached at the distal end of the small intestine.

[0078] The head module (100) may include a curved portion (120). When the curved portion (120) is included in the head module (100), when the capsule module (1000) moves within the digestive tract of a subject, the capsule module can move along the digestive tract with less resistance, thereby minimizing unnecessary stimulation or discomfort to the subject.

[0079] The head module (100) may include a material that does not cause rejection in the subject when entering the body, and for example, the head module (100) may include a material including cellulose, cellulose ester, polysulfone, polytetrafluoroethylene (PTFE), polydimethylsiloxane (PDMS), polyvinylidene fluoride (PVDF), polyethersulfone (PES), etched polycarbonates, or collagen.

[0080] The head module (100) may include an inwardly retractable receiving groove (110). The receiving groove (110) may contain a biological sample as the head module (100) moves within the digestive tract of the subject, and additional samples separate from the biological sample collected by the collection member may be collected. For example, a stool sample of the subject may be collected in the receiving groove (110), and an amount of the stool sample suitable for analysis may be collected in the receiving groove (110) and discharged to the outside as the head module moves within the colon of the subject.

[0081] The head module (100) may include a camera module. The camera module may be disposed in the internal space of the head module (100) or disposed on the surface of the head module (100) to capture images while moving along the digestive tract of the subject. When the camera module is disposed within the head module (100), the head module (100) may additionally include a power supply for driving the camera module. The power supply may be a battery, and the battery may be disposed within the head module (100) so as to be electrically connected to the camera module. In addition, images captured by the camera module may be transmitted to the outside, and electrodes for transmitting image data to the outside may be additionally included in the head module (100). A portion of the electrode may be exposed on the surface of the head module (100).

[0082] A sensor may be additionally placed in the head module (100). The sensor may be a sensor for measuring pH, temperature, hormones, or minerals. The sensor may be placed in the receiving groove (110) of the head module (100) or on the surface of the head module (110). As with the camera module, when the head module (100) includes a sensor, a power supply for operating the sensor and a transmission means for transmitting data measured by the sensor to the outside, such as an electrode, may be placed in the head module (100).

[0083] A means for detecting a biomarker may be placed in the receiving groove (110) of the head module (100) or on the surface of the head module (100). For example, a genetically recombinant microorganism may be placed in the receiving groove (110), or a kit device including the same may be included in the receiving groove (110) so that the head module (100) can detect a biomarker as it moves along the digestive tract of the subject.

[0084] A capsule module (1000) according to one embodiment can be driven in a passive manner, and can collect biological samples by moving through movements such as peristalsis of the digestive tract of a subject without active driving by a power supply or by applying a magnetic field from an external system. However, in order to increase the efficiency of collection and to control the capsule module more precisely, biological samples can be collected actively in addition to the passive manner.

[0085] In a non-limiting embodiment of the present invention, the head module (100) and the collection module (200, 300, 400) may include a magnetic material. The magnetic material may be a permanent magnet, an electromagnet, or magnetic nanoparticles (MNPs).

[0086] When a magnetic body is included in the capsule module (1000), the user can move the capsule module (1000) to a desired position more precisely by using an external magnetic field driving system. Specifically, the user can use the external magnetic field driving system to generate a uniform magnetic field and / or a gradient magnetic field to move the capsule module (1000) in a direction in which a biological sample is to be collected from a target. In addition, the magnetic body inside the capsule module (1000) and the magnetic field applied from the outside interact with each other, so that the posture and position of the capsule module (1000) can be precisely controlled.

[0087] The capsule module (1000) may include a communication element. For example, the head module (100) and / or the collection module (200, 300, 400) may include a communication element. The communication element may include a signal generator that generates an externally recognizable position signal. The position of the capsule module (1000) may be detected based on the position signal generated from the signal generator. For example, a device capable of generating a radio frequency signal (RF signal) or a permanent magnet or electromagnet capable of generating a magnetic field may be disposed inside the capsule module (1000), and the position and orientation of the capsule module (1000) may be determined through an external receiver such as an RF receiver or a magnetic field sensor.

[0088] Additionally, the capsule module (1000) can be detected from inside the subject by an external signal. For example, the capsule module (1000) can be detected moving along the subject's digestive organ by an external X-ray or ultrasound.

[0089] The capsule module (1000) may be coated with an enteric cover (not shown). The enteric cover may include an enteric material, similar to the connecting member. In addition to the above-described enteric material, the material for forming the enteric cover may be one or more selected from the group consisting of guar gum, methyl methacrylate-methacrylic acid copolymers, starch, pectin, chitosan, guar gum, and dextran, or a combination thereof.

[0090] When the capsule module (1000) is coated with an enteric cover, the time at which the connecting member of the capsule module (1000) is exposed to the environment within the digestive organ of the subject may be delayed. Specifically, since the enteric cover is not decomposed in the stomach of the subject, the connecting member of the capsule module (1000) is not exposed to the gastric environment, and upon reaching the small or large intestine, the enteric cover may dissolve and be exposed to the intestinal environment, thereby being decomposed. In one embodiment, when the capsule module (1000) is mechanically incorrectly coupled or there is a problem with the concentration of the enteric material of the connecting member, a situation may occur in which the capsule module (1000) is arbitrarily decomposed in the stomach before reaching the intestine, even though it is unwanted. However, when the enteric cover is additionally included in the capsule module (1000), the probability of the connecting member being arbitrarily decomposed at an undesired location in the stomach can be reduced.

[0091]

[0092] FIG. 2 is a cross-sectional view of a first collection module according to one embodiment of the present invention, FIG. 3 is a perspective view of a collection module according to one embodiment of the present invention, and FIG. 4 is a drawing for explaining a process of collecting an intestinal biological sample of a collection module or a sub-collection module according to one embodiment of the present invention.

[0093] Referring to FIGS. 2 and 3, the first collection module (200) may include a module body (280), an opening (260), a collection member (240), a cover member (210), and a sealing member (250).

[0094] The module body (280) may include a main body (270) and a side body (290). The main body (270) and the side body (290) may be manufactured as an integral body by curing the components of the module body through a mold, or the main body (270) and the side body (290) may be manufactured separately and then joined to form the module body.

[0095] The side body (290) may extend upwardly from the main body (270). Specifically, the side body (290) may not be joined to the main body (270) to have the same height as the main body (270), but a portion of the side body may protrude upwardly from the main body (270), and a receiving portion (220) may be formed through the protruding portion.

[0096] When the cover member (210) is placed on the upper side of the opening (260), the portion extending from the side body (290) to the upper side of the main body (270) forms a side, and the cover member (210) forms a lower surface to form a bowl-shaped receiving portion (220).

[0097] Alternatively, when the cover member (210) is disposed on the lower side of the opening (260), a portion extending upward from the side body (290) to the main body (270) may form a side surface, and a portion of the cover member (210) exposed by the upper surface of the main body and the opening may form a lower surface to form a receiving portion. In this way, the receiving portion (210) forming the side surface and the lower surface may accommodate an intestinal biological sample and an intestinal fluid containing the sample. At this time, since the intestinal fluid comes into contact with the cover member (210) in a form contained in the receiving portion (210), the contact time between the intestinal fluid and the cover member (210) may be extended, and the cover member (210) may be dissolved according to a dissolution time of the cover member (210) intended by the user.

[0098] The module body (280) can protect the collection member (240) from exposure to the intestinal environment and can be made of a material that does not cause a rejection reaction in the body. The module body (280) can include a material such as cellulose, cellulose ester, polysulfone, polytetrafluoroethylene (PTFE), polydimethylsiloxane (PDMS), polyvinylidene fluoride (PVDF), polyethersulfone (PES), etched polycarbonates, or collagen.

[0099] The module body (280) may include a magnetic material. When the module body (280) includes a magnetic material, the first collection module (200) collects an intestinal biological sample from the digestive tract of the subject, and when the sample is discharged to the outside, the collection modules can be more easily obtained from the stool using a magnet, and the sample can be separated from the collection module for analysis. The magnetic material may be a permanent magnet or magnetic nanoparticles.

[0100] An opening (260) may be arranged in the module body (280). The opening (260) may allow an intestinal biological sample and intestinal fluid to enter the internal space (20) of the module body (280). One opening (260) may be included in the module body (280), or two or more openings may be arranged in the module body (280). When multiple openings are arranged, the cover member (210) may be arranged adjacent to the openings in a manner that blocks all of the openings simultaneously, or the cover members may be arranged adjacent to each opening so that each of the openings is blocked.

[0101] The first collection module (200) may include a porous member. The porous member may be positioned adjacent to the opening (260). The porous member may block large impurities such as food in the intestinal biological sample flowing through the opening (260). The porous member may be made of any material having an open space, but may be, for example, one or more selected from the group consisting of cell foams, fibers, channeled materials, papers, cellulosics, acetates, cotton, cloth, gauze, sponges, and polymer membranes, or a combination thereof.

[0102] The first extraction module (200) may include a cover member (210).

[0103] The cover member (210) may be arranged adjacent to the opening (260). At this time, the cover member (210) may be arranged on the upper side of the opening (260) and placed in the receiving portion (220), or may be arranged on the lower side of the opening (260) and placed in the internal space (20) of the module body (280).

[0104] The cover member (210) may include a material that can dissolve upon contact with a water-soluble substance. Unlike the connecting member or the enteric cover, the cover member (210) may include a water-dissolvable material rather than an enteric material. Therefore, a material that can dissolve independently without being affected by the pH of the external environment may be used as the material for the cover member (210).

[0105] The water-decomposable material that can be used as the cover member (210) is a material that can be dissolved upon contact with intestinal fluid and can be used without limitation, for example, polyvinyl alcohol (PVA), polyvinyl acetate phthalate (PVAP), polyvinyl chloride (PVC), polyvinylpyridine acrylic acid, fatty acids, waxes, shellac, plant fibers, paper, cellulosic material, starch, methyl acrylate-methacrylic acid copolymers, cellulose acetate phthalate (Cellulose Acetate Phthalate;CAP), Cellulose Acetate Succinate, Hydroxypropyl Methyl Cellulose Phthalate, Hydroxypropyl Methyl Cellulose Acetate Succinate, Methyl Methacrylate, Methacrylic Acid, Polyacryl, Cellulose Acetate, Trimellitate, Sodium Alginate, Zein, Starch, Pectin, Gelatin, Cross-Linked Gelatin, Carbohydrates, Gum Arabic, Salts, Sodium Hypochlorite, Lithium Hypochlorite (Lithium Hypochlorite), Calcium Hypochlorite, Dichlor, Trichlor, Sugars, Proteins and Hydrogels, or a combination thereof.;

[0106] As the capsule module (1000) moves within the digestive organ of the subject, and as the capsule module (1000) reaches a specific location (e.g., the small intestine) within the digestive organ, the connecting member connecting the enteric cover on the outside of the capsule module (1000) and the collection module is disintegrated. The portion of the collection module that was not exposed within the intestine because it was connected to another collection module or a head module is directly exposed to the intestinal environment as the individual collection module is detached from the entire capsule module. At this time, the intestinal fluid and the cover member of the collection module come into direct contact, and the water-dissolvable material contained in the cover member is decomposed upon contact with the intestinal fluid, and thus the entire cover member (210) is dissolved by the intestinal fluid. As the cover member (210) is dissolved, the opening (260) is completely opened to the external area of ​​the first collection module (200), and thus, the intestinal biological sample along with the intestinal fluid flows into the internal space of the module body, thereby initiating sample collection. That is, rather than the liquid and sample flowing into the collection module immediately upon dissolution of the intestinal cover or connecting member, the time for collecting the sample can be set more precisely by setting the time for dissolution of the cover member.

[0107] As described above, the capsule module (1000) may include a plurality of collection modules, and at this time, the cover member of each collection module may be dissolved under the same conditions or may be dissolved under different conditions. The dissolution time of the cover member may be set differently depending on the thickness of the cover member, the type or concentration of the water-degradable material included in the cover member, and the shape of the cover member. As illustrated in FIG. 1, when the capsule module (1000) includes a first collection module (200), a second collection module (300), and a third collection module (400), the thickness or shape of the cover member included in each collection module may be different, and accordingly, the dissolution time of the cover member included in each collection module may be set differently, and as the dissolution times are different, the time and position at which each collection module starts collecting an intestinal biological sample may be different.

[0108] For example, if the connecting members connecting each collection module and the head module are all set to dissolve under the same conditions, and the cover member of the first collection module is configured to be the thickest and the cover member of the third collection module is configured to be the thinnest, the cover member of the first collection module dissolves the last, so that the time required for the intestinal biological sample to be introduced is the longest (samples are collected from the digestive tract location furthest from the mouth), and the cover member of the third collection module dissolves the fastest, so that the intestinal biological sample can be collected the fastest (samples are collected from the digestive tract location closest to the mouth).

[0109] In this way, the capsule module (1000) for collecting intestinal biological material according to one embodiment can individually set the dissolution conditions of the cover member and the connecting member, and can set the location where each collecting member collects a sample differently.

[0110] When configuring capsule modules, the user can set the cover members of the collection modules to disintegrate over the same period of time, and set different conditions for the disintegration of the connecting members. In this case, the time for the cover members to dissolve is the same for all, but the location and time for the connecting members to dissolve are different. Therefore, the cover member of the collection module that is separated first is directly exposed to the intestinal environment the fastest and dissolves, collecting the sample first. The cover member of the collection module that is separated last is exposed to the intestinal environment the last and collecting the sample last, allowing samples to be collected from different locations in the intestine through a single capsule module.

[0111] In addition, when configuring capsule modules, the user can set the conditions for dissolving each connecting member to be the same, while setting the times for dissolving the cover members of the collection modules to be different. In this case, since the dissolution start positions of the connecting members are all the same, all collection modules are separated from the entire capsule module at the same time. However, since the dissolving conditions of the cover members used in each collection member are all different, even if the time points at which each cover member is exposed to the intestinal environment are the same, the intestinal biological samples begin to be collected at different locations due to the difference in the dissolving times, and thus, samples from different locations may be collected.

[0112] Finally, when configuring a capsule module, the user can set different conditions for dissolution of each connecting member, and also set different times for dissolution of each covering member. In this case, as the connecting members dissolve at different locations, the collection modules sequentially detach from the capsule module, and intestinal biological samples can be collected at different locations depending on the time it takes for each covering member to disintegrate.

[0113] In this way, the capsule module (1000) for collecting an intestinal biological sample according to one embodiment individually sets the dissolution condition of the connecting member and the dissolution time of the cover member of the collection module, thereby enabling multiple collection of samples from different locations in the digestive tract of a subject through one capsule module (1000).

[0114] A sampling member (240) may be placed in the internal space of the module body (280). An intestinal biological sample introduced through an opening (260) may be collected from the sampling member (240).

[0115] The collection member (240) may include an expandable material that expands upon absorption of liquid. Examples of expandable materials include hydrogels, hydrocolloids, croscarmellose sodium, cross-linked polyvinyl pyrrolidone, ethylene maleic anhydride copolymer, carboxymethylcellulose, hydroxypropyl cellulose, polyvinyl alcohol copolymers, hydrophilic polyurethane, hydroxyethylmethacrylate (HEMA), sodium starch glycolate, crospovidone, cellulose, pectin, alginate, and agar. (Agar), Collagen, Glycosaminoglycan, Agarose, Superabsorbent Polymers, Sponge, Sodium Polyacrylate, Polyacrylamide, Compressed Rayon or Starches at Various Levels of Crosslinking, but are not limited thereto.

[0116] The collection member (240) may include a reagent required for cell lysis. When the collection member (240) includes a cell lysis reagent, enzymatic activity may be stopped after the intestinal biological sample is introduced into the collection member (240), and the cellular contents within the biological sample may be analyzed after the capsule module is discharged outside the subject body. The cell lysis reagent may be sodium dodecyl carbonate, tris (2-carboxyethyl) phosphine, 2-chloroacetamide, or a tris buffer.

[0117] The collection member (240) may include a reagent necessary for protein digestion. If the collection member (240) includes a protein digestion reagent, enzymatic activity within the intestinal biological sample may be inhibited, and cellular components may be analyzed after the capsule module is excreted from the body. The protein digestion reagent may be trypsin or Lys-C protease.

[0118] The collection kit (240) may include reagents necessary for real-time reverse transcription of RNA. Unstable RNA within intestinal biological samples, which is unstable and may degrade before subsequent collection and analysis, can be synthesized into much more stable cDNA using reverse transcription reagents. Reagents necessary for reverse transcription include reverse transcriptase, random or specific primers, ligase, deoxynucleotides (dNTPs), RNase inhibitors, salts, and buffers.

[0119] The collection module (200) may include a sealing member (250). The sealing member (250) may be disposed in the internal space (20) of the module body (280). The sealing member (250) may be disposed at a position capable of blocking the opening (260) as the collection member (240) expands. For example, as illustrated in FIG. 2, the sealing member (250) may be disposed on the upper side of the collection member (240) so that as the collection member (240) expands, the sealing member (250) gradually moves toward the opening (260) to physically block the opening (260) and seal the collection module (200) from the outside. In addition, when the collection module (200) includes a plurality of openings as described above, the sealing member (250) may also be positioned to block the openings according to the expansion of the collection member (240) in the internal space (20) of the module body (280) in a number corresponding to the openings (260).

[0120] Materials that can be used as the sealing member (250) include biocompatible, elastic, and non-degradable materials. For example, polydimethylsiloxane (PDMS), Ecoflex, and silicone elastomer can be used as the sealing member (250), but are not limited thereto.

[0121] FIGS. 4 to 6 are drawings for explaining a process of collecting an intestinal biological sample of a collection module or a sub-collection module according to one embodiment of the present invention.

[0122] As the capsule module (1000) passes through the digestive tract of the subject, the connecting member connecting the collection module (200) and the collection module (or head module) dissolves, thereby separating the collection module (200), and the cover member (210) of the collection module is exposed to the intestinal fluid. As the cover member is exposed to the intestinal fluid, the cover member dissolves, and the intestinal fluid flows into the collection module. At this time, the collection member (240) may be arranged to entirely cover the bottom surface of the module body (280), as shown in FIG. 4, or may be arranged to partially cover the bottom surface of the module body, as shown in FIG. 5. A sealing member (250) may be positioned on the upper side of the collection member (240), and as the intestinal fluid flows into the collection module, as shown in FIG. 6, the collection member (240) swells, allowing the sealing member (250) to move toward the opening (260). When the collection of the intestinal biological sample through the collection member (240) is completed and the collection member (240) is fully inflated due to intestinal fluid absorption, the sealing member (250) moves to the maximum toward the opening (260) and stops by contacting and engaging with the module body adjacent to the opening (260) to completely block the opening (260). In this way, since the collection module can be blocked from the outside through the sealing member (250) at the same time as the sample collection is completed, it is possible to prevent contaminants from entering the inside of the collection module after the sample is collected and damaging the sample.

[0123]

[0124] FIG. 7 is an exploded perspective view of a capsule module for multiple sampling of intestinal biological materials according to another embodiment of the present invention, and FIG. 8 is a cross-sectional view of a sub-sampling module according to another embodiment of the present invention.

[0125] Referring to FIGS. 7 and 8, a capsule module (2000) according to another embodiment may include a collection module (500, 600, 700) including a plurality of sub-collection modules. Specifically, the capsule module (2000) according to another embodiment may include a head module (100), a fourth collection module (500), a fifth collection module (600), and a sixth collection module (700), wherein the fourth collection module (500) may include a first sub-collection module (500(a)) and a second sub-collection module (500(b)), the fifth collection module (600) may include a third sub-collection module (600(a)) and a fourth sub-collection module (600(b)), and the fourth collection module (700) may include a fifth sub-collection module (700(a)) and a sixth sub-collection module (700(b)).

[0126] Referring to FIG. 8, the first sub-collection module (500(a)) may each include a module body (580(a)), an opening (560(a)), and a collection member (540(a)). The module body of the sub-collection module may include a main body (570(a)) and a side body (590(a)), and a sealing member (550(a)) may be arranged on the collection member (540(a)).

[0127] The collection module may include two sub-collection modules, three sub-collection modules, or four or more collection modules. When one collection module includes multiple sub-collection modules, biological samples can be collected from a wider variety of locations in the digestive tract of the subject while maintaining the size of the entire capsule module (2000). At this time, the user can adjust the dissolution time of the cover member included in each sub-collection module differently while connecting the head module or other collection modules through a connecting member. As described above, the capsule module for collecting intestinal biological samples can diversify the sample collection location by adjusting the dissolution condition of the connecting member and the dissolution time of the cover member included in each collection module. In this way, when one collection module includes multiple sub-collection modules, like the capsule module (2000) of another embodiment, it is possible to diversify the intestinal sample collection location by appropriately adjusting the connecting member and the cover member differently.

[0128] In a capsule module (2000) according to another embodiment, the collection module may include a sub-collection module, but may also include a collection module that does not include a sub-collection module. Therefore, as illustrated in FIG. 7, not all collection modules include sub-collection modules, and collection modules without sub-collection modules may be connected in a complex manner to collect more samples from a specific location within the digestive organ than from other locations. For example, as illustrated in FIG. 7, the fourth collection module (500) and the fifth collection module (600) are each configured as collection modules that include sub-collection modules, and the sixth collection module (700) is configured as a single collection module, unlike in FIG. 7, so that more samples can be collected from a location where the sixth collection module collects samples than from other locations, as needed.

[0129]

[0130] FIGS. 9 to 14 are drawings for explaining a process of collecting samples from the intestines of a capsule module for multiple collections of intestinal biological materials according to one embodiment of the present invention.

[0131] Referring to FIGS. 9 to 14, the connecting member of the capsule module according to one embodiment can be set to dissolve under different conditions to collect multiple biological samples from the intestine.

[0132] The capsule module enters and passes through the subject's mouth into the digestive tract. The capsule module can passively move within the digestive tract by the peristaltic motion of the digestive tract and gravity, or it can be actively moved by applying an external magnetic field by placing a magnetic material within the capsule module.

[0133] The capsule module first passes through the stomach. At this time, an external enteric film (enteric cover) can be attached to the capsule module, and the enteric cover can prevent the collection module (collection module) from being separated in the stomach (Fig. 9). Even when an external enteric film is not used, an enteric material can be used in the connecting member (enteric film) that connects the head module and the collection modules, respectively, to prevent them from being randomly separated during passage through the stomach.

[0134] Afterwards, the capsule module passes through the stomach and reaches the proximal small intestine (Duodenum), where the outer enteric film set to dissolve dissolves, exposing the capsule module to the intestinal environment, and thus the first enteric film (connector) connecting the collection module dissolves (Fig. 10).

[0135] As the outer enteric film and the first enteric film dissolve, the first collection module (first collection module) separates from the capsule module, and the water-soluble film (cover member) inside the collection module begins to dissolve (Fig. 11).

[0136] As the water-soluble film of the first collection module dissolves, the fluid and sample flow into the collection module, and as the sample is collected by the collection member placed inside, the collection member swells (Fig. 12).

[0137] As the sampling member swells due to the intestinal fluid flowing into the sampling module, the sealing member placed on the sampling member moves toward the opening (opening), and when the sampling by the sampling member is completed, the sealing member completely blocks the opening, thereby preventing unnecessary contamination of the sample after sampling (Fig. 13). Thereafter, the above process is repeated so that the second sampling module (second sampling module) and the third sampling module (third sampling module) also collect intestinal biological samples from their respective set locations (Fig. 14).

[0138]

[0139] FIGS. 15 to 20 are drawings illustrating a process for collecting samples from the intestines in different ways using a capsule module for multiple sampling of intestinal biological materials according to one embodiment of the present invention.

[0140] Referring to FIGS. 15 to 20, the enteric film (connecting member) of the capsule module according to one embodiment is set to dissolve under the same conditions, and the time for which the water-soluble film (covering member) included in each collection module (collection module) decomposes is set differently, thereby allowing multiple biological samples to be collected from the intestine.

[0141] The capsule module passes through the stomach, and the collection module (collection module) is prevented from being arbitrarily separated by an external enteric film (enteric cover) as shown in Fig. 9 (Fig. 15).

[0142] Afterwards, the capsule module passes through the stomach and reaches the small intestine, where all enteric films (connecting members) connecting each collection module and head module together with the external enteric film are exposed to the intestinal fluid and dissolve (Fig. 16).

[0143] As the entire water-soluble film is dissolved, the first collection module (first collection module), the second collection module (second collection module), the third collection module (third collection module) and the head module are all separated, and the water-soluble film (cover member) of each collection module is exposed to the intestinal fluid, and the dissolution of the water-soluble film begins (Fig. 17).

[0144] At this time, the thickness of the water-soluble film of the first collection module is set to the thinnest, so that the water-soluble film of the first collection module dissolves as quickly as possible, so that the intestinal sample is collected from the first collection module first after all collection modules are separated simultaneously. However, since the second and third collection modules are still not decomposed, sample collection does not occur, and samples are collected from different locations from the first collection module (Fig. 18).

[0145] As the fluid flows into the first collection module, the collection member expands, and the sealing member blocks the opening to prevent contamination (Fig. 19).

[0146] Thereafter, the process is repeated as above so that intestinal biological samples are collected from the second and third collection modules, and all three collection modules collect samples from different locations before excreting them from the subject's body, where the samples can be individually analyzed (Fig. 20).

[0147]

[0148] The foregoing description of the present invention is for illustrative purposes only, and those skilled in the art will readily appreciate that the present invention can be readily modified into other specific forms without altering the technical spirit or essential characteristics of the present invention. Therefore, the embodiments described above should be understood as illustrative in all respects and not restrictive. For example, each component described as a single entity may be implemented in a distributed manner, and similarly, components described as distributed may be implemented in a combined manner.

[0149] The scope of the present invention is indicated by the claims set forth below, and all changes or modifications derived from the meaning and scope of the claims and their equivalent concepts should be interpreted as being included in the scope of the present invention.

[0150] The capsule module for multiple sampling of intestinal biological materials according to the present invention can collect intestinal samples from various parts of the gastrointestinal tract through a single capsule intake without the aid of an external system, thereby improving accessibility and convenience of intestinal microbiota research.

Claims

1. In a capsule module for multiple sampling of intestinal biological materials, The above capsule module includes two or more collection modules connected to each other by a connecting member, The above extraction module: It comprises a module body, an opening for introducing a sample into an internal region of the module body, and a sampling member for collecting a sample introduced through the opening. A capsule module in which the above connecting member is dissolved by the liquid, and the two or more collection modules are separated according to the dissolution of the connecting member.

2. In paragraph 1, A capsule module, wherein the above-mentioned collection module further includes a cover member disposed adjacent to the opening and dissolved by the liquid.

3. In paragraph 1, A capsule module, wherein the capsule module further includes a head module connected to one of the two or more collection modules.

4. In paragraph 3, A capsule module, wherein the head module includes a receiving groove introduced inwardly.

5. In paragraph 1, A capsule module, wherein the above-mentioned collection module further includes a sealing member disposed above the collection member to block the opening according to expansion of the collection member.

6. In paragraph 1, A capsule module, wherein the capsule module is coated with an enteric cover.

7. In paragraph 1, A capsule module wherein the above-mentioned collection module further includes a magnetic material.

8. In paragraph 1, The above extraction module includes multiple sub-extraction modules, A capsule module, wherein the plurality of said sub-collection modules each include the module body, the opening, and the collection member.

9. A capsule module according to claim 1, wherein the collection module includes a porous member positioned adjacent to the opening.

10. In paragraph 1, The above capsule module: A capsule module comprising a first extraction module, a second extraction module connected to the first extraction module via a first connecting member, and a third extraction module connected to the second extraction module via a second connecting member.

11. In paragraph 10, A capsule module wherein the first connecting member and the second connecting member are dissolved at different locations within the intestine.

12. In paragraph 10, A capsule module wherein the cover members of the first collection module, the second collection module, and the third collection module are dissolved at different locations or at different decomposition times within the intestine.

13. In paragraph 12, A capsule module, wherein the cover members of the first extraction module, the second extraction module, and the third extraction module have different thicknesses or different shapes.

14. In the third paragraph, the head module comprises one or more of the following: a capsule module: camera module; magnetic material; sensor; and Genetically recombinant microorganisms.

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