Capsule structure for collecting biological material, and method of driving same

Abstract

The capsule structure according to various embodiments of the present invention may comprise: a body; a collection module accommodated in the body and collecting a biological material; and a magnetic body accommodated in the body, wherein the collection module includes one or more collection modules. The method of driving a capsule structure may comprise the steps of: dissolving an external protective layer of collection module 1; moving the capsule structure up to a target position; applying a first external signal to heat a heating layer of collection module 1; dissolving an internal protective layer of collection module 1; and adsorbing a biological material by a polymer layer of collection module 1, wherein the capsule structure comprises: a body; a collection module accommodated in the body and collecting a biological material; and a magnetic body accommodated in the body, wherein the collection module includes collection modules from collection module 1 to collection module n (where n is an integer greater than or equal to 2).

Description

Biological material collection capsule structure and driving method thereof

[0001] Various embodiments of the present invention relate to a capsule structure for active collection of biological material and a method for operating the same. More specifically, the present invention relates to a biological material collection capsule structure capable of selectively collecting biological material from the digestive organs and a method for operating the same.

[0002] The human intestine is home to over 500 species and 10 trillion intestinal bacteria, weighing up to 2 kg. Research has revealed that the microorganisms residing in the human body have a significant impact on the human body, leading to active research on intestinal microorganisms, which analyze the genetic information of microorganisms. It is known that various microorganisms in the human body influence all functions of the body, including regulating metabolism, digestive function, and various diseases, as well as genetic mutations due to environmental changes and the process of passing them on to the next generation. In particular, it has been reported that various metabolic and immune diseases related to allergies, rhinitis, atopy, obesity, enteritis, and heart disease are related to these intestinal microorganisms.

[0003] Stool analysis is a method for collecting biological substances, such as microorganisms, proteins, and metabolites, from the digestive tract. While stool samples offer the advantages of easy accessibility, low cost, and non-invasive collection, they primarily reflect the microbial composition of colonic contents, a limitation.

[0004] Meanwhile, an endoscopic collection method can be adopted to investigate the composition of intestinal microorganisms according to the location of the digestive organ, but it is expensive, invasive, prone to contamination, and difficult to collect samples from the small intestine.

[0005] To overcome these limitations, many non-invasive sampling methods have been proposed, but most devices are passively moved by intestinal peristalsis and the sampling mechanism depends on the intestinal environment such as pH, making selective sampling impossible and multiple sampling from multiple locations within the gastrointestinal tract impossible.

[0006] The present invention has been devised to solve the above-mentioned problems, and aims to provide a biological material collection capsule structure and an operating method thereof that can selectively and multiple-collect various intestinal biological materials and are operated according to various collection activation conditions.

[0007] A capsule structure according to various embodiments of the present invention comprises a main body; a collection module accommodated in the main body and collecting biological material; and a magnetic body accommodated in the main body, wherein at least one collection module may be included.

[0008] The extraction module of the capsule structure according to various embodiments of the present invention may include an outer protective layer, an inner protective layer, a polymer layer, and a heating layer.

[0009] In the collection module of the capsule structure according to various embodiments of the present invention, the outer protective layer, the inner protective layer, the polymer layer, and the heating layer can be sequentially arranged along the inside from the surface of the main body.

[0010] In the collection module of the capsule structure according to various embodiments of the present invention, the outer protective layer may include a pH-responsive polymer.

[0011] In the collection module of the capsule structure according to various embodiments of the present invention, the outer protective layer may include at least one selected from the group consisting of Eudragit EPO, Eudragit L100-55, ShinEtsu HP-55, Chemie HPP-55, and Cellulose Acetate Phthalate.

[0012] In the extraction module of the capsule structure according to various embodiments of the present invention, the inner protective layer may be provided to have a target melting point.

[0013] In the collection module of the capsule structure according to various embodiments of the present invention, the inner protective layer may include at least one selected from the group consisting of soy wax, bees wax, paraffin wax, palm wax, carnauba wax, paraffin oil, and polyethylene glycol (PEG).

[0014] In the extraction module of the capsule structure according to various embodiments of the present invention, the melting point of the inner protective layer is characterized by being 39°C to 65°C.

[0015] In a collection module of a capsule structure according to various embodiments of the present invention, the polymer layer is characterized by comprising a mixture of a polymer monomer, a crosslinking agent, and a reaction initiator, or a dried hydrogel.

[0016] In the collection module of the capsule structure according to various embodiments of the present invention, the polymer monomer is characterized in that it includes at least one selected from the group consisting of acrylamide, N-isopropylacrylamide (NIPAM), acrylic acid, poly(ethylene glycol) diacrylate (PEGDA), hexane-1,6-diol diacrylate (HDDA), ethoxylated trimethylolpropane triacrylate (ETTA), and ethylene carbonate (EC).

[0017] In the collection module of the capsule structure according to various embodiments of the present invention, the crosslinking agent may include at least one selected from the group consisting of N, N' methylene bis-acrylamide (BIS), carboxymethylcellulose (CMC), polyethylene glycol, and the like.

[0018] In the collection module of the capsule structure according to various embodiments of the present invention, the reaction initiator may include at least one selected from the group consisting of ammonium persulfate (APS), potassium persulfate (KPS), azobisisobutyronitrile (AIBN), ascorbic acid + ferric chloride, Irgacure 2959, and the like.

[0019] A method for driving a capsule structure including a main body; a collection module accommodated in the main body and collecting biological material; and a magnetic body accommodated in the main body, wherein the collection module includes collection module 1 to collection module n (wherein n is an integer of 2 or more), and may include a step of dissolving an outer protective layer of the collection module 1; a step of moving the capsule structure to a target position; a step of applying a first external signal to heat a heating layer of the collection module 1; a step of dissolving an inner protective layer of the collection module 1; and a step of adsorbing a biological material by a polymer layer of the collection module 1.

[0020] In a method for driving a capsule structure according to various embodiments of the present invention, after the step of the polymer layer of the collection module n-1 adsorbing a biological substance, the method may include the step of heating the heating layer of the collection module n by applying an nth external signal; the step of dissolving the inner protective layer of the collection module n; and the step of adsorbing the biological substance by the polymer layer of the collection module n.

[0021] In a method for driving a capsule structure according to various embodiments of the present invention, the inner protective layer of each extraction module is characterized in that it has a different melting point.

[0022] The capsule structure according to various embodiments of the present invention can selectively collect multiple biological materials according to the collection activation conditions, so that biological materials can be collected from various locations inside an organ and used for research or diagnosis.

[0023] Additionally, the capsule structure according to various embodiments of the present invention allows for control of the capsule's position and location. The capsule structure of the present invention can be used not only for collecting biological materials, but also as a structure for drug / probiotic delivery or for biomarker measurement.

[0024] The capsule structure according to various embodiments of the present invention can be used for research, diagnosis, and treatment of the distribution of biological substances in the intestine through sequencing analysis or genetic analysis related to microorganisms, proteins, metabolites, viruses, etc.

[0025] FIG. 1 is a perspective view of a capsule structure for collecting biological material according to various embodiments of the present invention.

[0026] Fig. 2 is a cross-sectional view showing a cross-section taken along line I-I' of Fig. 1.

[0027] FIG. 3 is a drawing confirming the melting point of the inner protective layer according to various embodiments of the present invention.

[0028] FIGS. 4 and 5 are drawings for explaining a method for actively collecting biological material according to various embodiments of the present invention.

[0029] Hereinafter, various embodiments of this document are described with reference to the attached drawings. The embodiments and terminology used herein are not intended to limit the technology described in this document to specific embodiments, but should be understood to encompass various modifications, equivalents, and / or alternatives of the embodiments.

[0030] Hereinafter, embodiments of the present invention will be described in detail with reference to the attached drawings.

[0031]

[0032] FIG. 1 is a perspective view of a capsule structure for collecting biological material according to various embodiments of the present invention. FIG. 2 is a cross-sectional view taken along line I-I' of FIG. 1.

[0033] Referring to FIGS. 1 and 2, a capsule structure (10) for collecting biological material according to various embodiments of the present invention may include a main body (100), a collection module (200), and a magnetic body (300).

[0034] The main body (100) can accommodate at least one collection module (200). The main body (100) can include a receiving space for accommodating the collection module (200). The main body (100) can be composed of a biocompatible resin or medical plastic with confirmed biological stability. The medical plastic can be Acrylonitrile Butadiene Styrene (ABS), Polyamide (PA), Polycarbonate (PC), Poly vinyl chloride (PVC), Polypropylene (PP), Polystyrene (PS), Thermoplastic Elastomer (TPE), etc. A magnetic body (300) can be arranged in the core of the main body (100).

[0035] At least one collection module (200) may be provided on the main body (100). A plurality of collection modules (200) may be provided along the surface of the main body (100). The collection modules (200) may be mounted within the receiving space of the main body (100).

[0036] The harvesting module (200) can be operated according to different harvesting activation conditions. That is, whether the harvesting module (200) is activated can be determined based on pH and / or temperature.

[0037] Specifically, referring to FIG. 2, the collection module (200) may include a collection module 1 (210) and a collection module 2 (230). The following description will be based on the collection module 1 (210).

[0038] The collection module (210) may be composed of multiple layers. The collection module (210) may include an outer protective layer (211), an inner protective layer (213), a polymer layer (215), and a heating layer (217). The outer protective layer (211), the inner protective layer (213), the polymer layer (215), and the heating layer (217) may be sequentially arranged along the inside from the surface of the main body (100).

[0039] The outer protective layer (211) may include a pH-responsive polymer. Specifically, the outer protective layer (211) may include any one selected from the group consisting of Eudragit EPO, which is a methacrylate copolymer, Eudragit L100-55, which is an anionic copolymer based on methacrylic acid and ethyl acrylate, Eudragit S 100, which is an anionic copolymer based on methacrylic acid and methyl methacrylate, ShinEtsu HP-55, which is hypromellose phthalate (HPMCP), Chemie HPP-55, which is hypromellose phthalate (HPMCP), and cellulose acetate phthalate.

[0040] At this time, Eudragit EPO can be used to target drug release in the stomach and is dissolved at pH 5.0 or lower. Eudragit L100-55 can be used to target drug release in the proximal and / or mid-small intestine and is dissolved at pH 5.5 or higher. Eudragit S 100 can be used to target drug release in the distal small intestine and is dissolved at pH 7.0 or higher. ShinEtsu HP-55 is dissolved at pH 5.0 to 5.5. Chemie HPP-55 can be used to target drug release in the proximal and / or mid-small intestine and is dissolved at pH 5.5 or higher. Cellulose acetate phthalate is dissolved at pH 5.5 or higher. Therefore, the material of the outer protective layer (211) can be changed depending on the target area of ​​the collection module (210).

[0041] The outer protective layer (211) may be maintained until the capsule structure (10) reaches a specific organ region after being administered to a subject requiring microbial collection. The outer protective layer (211) may prevent the collection module (210) from operating until the target region is reached. The outer protective layer (211) may protect the inner protective layer (213) and the polymer layer (215) until the target region is reached. The outer protective layer (211) may be dissolved when the target region is reached. For example, the outer protective layer (211) may not be dissolved in the stomach, but may be dissolved in regions of interest such as the proximal small intestine, the middle small intestine, the distal small intestine, and the proximal large intestine.

[0042] The inner protective layer (213) may be positioned beneath the outer protective layer (211). The inner protective layer (213) may be provided to have a target melting point. The inner protective layer (213) does not melt due to body temperature of the human body, but may melt when a specific temperature is reached by the heating layer (217). Since the inner protective layer (210) melts at a specific melting point to expose the polymer layer (215), it may not melt until it reaches the target location. In other words, sampling may be prevented until the capsule structure (10) reaches the region of interest and reaches a specific temperature.

[0043] The inner protective layer (213) may include at least one selected from the group consisting of soy wax, beeswax, paraffin wax, palm wax, carnauba wax, paraffin oil, and polyethylene glycol (PEG). The inner protective layer (213) may have various melting points through specific combinations of various materials. In this case, the melting point of the inner protective layer may be 40° C. to 60° C.

[0044] For example, the inner protective layer (213) may include paraffin wax and paraffin oil. At this time, referring to FIG. 3, various melting points can be implemented by controlling the mixing amount of paraffin wax and paraffin oil. In FIG. 3, '100 %' is an example of mixing 100 % (v / v) of paraffin wax and 0 % (v / v) of paraffin oil, '50 %' is an example of mixing 50 % (v / v) of paraffin wax and 50 % (v / v) of paraffin oil, and '25 %' is an example of mixing 25 % (v / v) of paraffin wax and 75 % (v / v) of paraffin oil.

[0045] Referring to (b) of FIG. 3, when the total weight of the inner protective layer (213) includes 25% (v / v) of paraffin wax and 75% (v / v) of paraffin oil (25%), a melting point of 39°C can be achieved. When the total weight of the inner protective layer (213) includes 50% (v / v) of paraffin wax and 50% (v / v) of paraffin oil (50%), a melting point of 49.9°C can be achieved. When the total weight of the inner protective layer (213) includes 100% (v / v) of paraffin wax and 0% (v / v) of paraffin oil (100%), a melting point of 64.7°C can be achieved.

[0046] Alternatively, the inner protective layer (213) may include polyethylene glycol. At this time, various melting points can be achieved by controlling the average molecular weight of the polyethylene glycol. When the inner protective layer (213) includes polyethylene glycol having an average molecular weight of 600, a melting point of 22.2° C. can be achieved. When the inner protective layer (213) includes polyethylene glycol having an average molecular weight of 1000, a melting point of 35 to 40° C. can be achieved. When the inner protective layer (213) includes polyethylene glycol having an average molecular weight of 600 and polyethylene glycol having an average molecular weight of 1000, a melting point of 23 to 26° C. can be achieved. When the inner protective layer (213) includes polyethylene glycol having an average molecular weight of 2000, a melting point of 35.93° C. can be achieved. When the inner protective layer (213) includes polyethylene glycol having an average molecular weight of 6000, a melting point of 39.6°C can be achieved. When the inner protective layer (213) includes polyethylene glycol having an average molecular weight of 1500, a melting point of 47.23°C can be achieved. When the inner protective layer (213) includes polyethylene glycol having an average molecular weight of 4000, a melting point of 55.95°C can be achieved. When the inner protective layer (213) includes polyethylene glycol having an average molecular weight of 8000, a melting point of 59.74°C can be achieved. When the inner protective layer (213) includes polyethylene glycol having an average molecular weight of 10000, a melting point of 58.01°C can be achieved. When the inner protective layer (213) includes polyethylene glycol having an average molecular weight of 12,000, a melting point of 60.93°C can be achieved. When the inner protective layer (213) includes polyethylene glycol having an average molecular weight of 20,000, a melting point of 92.27°C can be achieved.

[0047] The polymer layer (215) may be positioned beneath the inner protective layer (213). When exposed to an area of ​​interest, the polymer layer (215) may hydrogel or absorb external fluids to collect biological materials, such as intestinal microorganisms. When in contact with fluids within a specific organ, the polymer layer (215) may form a hydrogel structure, thereby storing biological materials within the formed structure.

[0048] The polymer layer (215) may include a mixture of a polymer monomer, a crosslinking agent, and a reaction initiator, or a dried hydrogel.

[0049] The polymer monomer may be at least one selected from the group consisting of poly(ethylene glycol) diacrylate (PEGDA), acrylamide, N-isopropylacrylamide (NIPAM), acrylic acid, hexane-1,6-diol diacrylate (HDDA), ethoxylated trimethylolpropane triacrylate (ETTA), and ethylene carbonate (EC). The polymer monomer can synthesize a hydrogel through a radical polymerization reaction induced by a reaction initiator.

[0050] The crosslinking agent may be at least one selected from the group consisting of N, N' methylene bis-acrylamide (BIS), carboxymethylcellulose (CMC), polyethylene glycol, and the like.

[0051] The reaction initiator may be at least one selected from the group consisting of ammonium persulfate (APS), potassium persulfate (KPS), azobisisobutyronitrile (AIBN), ascorbic acid + ferric chloride, Irgacure 2959, etc. The reaction initiator can induce self-assembly by causing a radical polymerization reaction upon contact with moisture in the intestinal fluid.

[0052] At this time, the reaction initiator and the polymer monomer may have a molar ratio of 1:0.5 to 1.5. When the reaction initiator and the polymer monomer have the above molar ratio, when the capsule structure (10) is positioned in the region of interest and the polymer layer (215) is exposed, hydrogelation or volume expansion may be facilitated, and biological materials may be easily collected.

[0053] Meanwhile, the inner protective layer (213) and / or the polymer layer (215) may include a visualization reagent. This allows for confirmation that the sample collection has been successfully performed at the target location.

[0054] The heating layer (217) may be placed under the polymer layer (215). The heating layer (217) may melt the inner protective layer (213). The heating layer (217) may be activated by an external signal such as an alternating magnetic field, near-infrared rays, or ultrasonic waves, and may generate heat. The heating layer (217) may be made of various metal materials. For example, it may be made of a metal material such as Al or Fe. The heating amount of the heating layer (217) may be controlled by the intensity, frequency, irradiation time, distance, etc. of the external signal. Alternatively, the heating amount of the heating layer (217) may be controlled by changing the material, size, shape, etc. of the heating element.

[0055] The harvesting module 2 (230) may have the same or similar configuration as the harvesting module 1 (210) described above. That is, the harvesting module 2 (230) may include an outer protective layer (231), an inner protective layer (233), a polymer layer (235), and a heating layer (237) arranged sequentially along the inside of the surface of the main body (100).

[0056] The outer protective layers (211, 231) included in the collection module 1 (210) and the collection module 2 (230) may each include different pH-responsive polymers. Accordingly, the collection module 1 (210) and the collection module 2 (230) may be controlled according to the pH of the external environment of the main body (100) and the target pH of the outer protective layers (211, 231), so that the collection activation conditions may vary.

[0057] The inner protective layers (213, 233) included in each of the extraction modules 1 (210) and 2 (230) may have different melting points. Accordingly, the extraction triggering conditions may vary depending on the heat generation amount of the heating layers (217, 237) included in each of the extraction modules 1 (210) and 2 (230) and the melting points of the inner protective layers (213, 233).

[0058] Meanwhile, a magnetic body (300) is arranged in the core of the main body (100) so that the capsule structure (10) can be moved using an external magnetic field. To generate a magnetic field, an electromagnetic coil system composed of a plurality of coils and an electromagnet drive system composed of an electromagnet and a high-degree-of-freedom robotic arm can be used. Therefore, using the capsule structure (10) of the present invention, microorganisms can be collected from various locations inside an organ and used for research or diagnosis. However, the embodiment is not limited thereto, and the capsule structure (10) can also be manually moved by the peristaltic movement of the intestine without including a separate magnetic body (300).

[0059] The capsule structure (10) of the present invention has a very small size, making it easy to directly ingest. For example, the capsule structure (10) of the present invention may have a diameter of 9 to 12 mm and a length of 24 to 30 mm.

[0060] The capsule structure (10) of the present invention may include a fluorescent dye. This allows the capsule structure (10) to be easily identified during the subsequent recovery process after collecting microorganisms.

[0061] An imaging module may be integrated into the capsule structure (10) of the present invention. Through this, the posture and position of the capsule structure (10) can be estimated. For example, an image can be obtained using external equipment such as X-ray or ultrasound to determine the position of the capsule, and equipment generally used in hospitals can be utilized. Alternatively, a permanent magnet or electromagnet capable of generating an RF signal or magnetic field may be built into the capsule structure (10). Through this, the position of the capsule can be recognized using an external receiver (RF receiver or magnetic field sensor). Alternatively, a three-axis coil capable of generating a magnetic induction signal by an external magnetic field may be built into the capsule structure (10). Through this, the posture and position of the capsule can be estimated using magnetic field measurements.

[0062] Meanwhile, communication and control can be performed between an external device and the capsule structure (10) to collect samples at a desired location. That is, after the posture and location of the capsule structure (10) are identified and it reaches the desired location, a sample collection measurement operation signal of the capsule structure (10) can be transmitted to the outside via an RF or magnetic signal.

[0063] Although the above capsule structure (10) is described as a structure for collecting biological materials, the embodiment is not limited thereto, and may be used as a structure for drug / probiotics delivery or a structure for biomarker measurement.

[0064] Specifically, when the capsule structure according to the embodiment is used as a structure for drug / probiotics delivery, a hydrogel structure loaded with the drug / probiotics may be used instead of the polymer layer of the collection module. Meanwhile, magnetic nanoparticles may be additionally included in the hydrogel structure to maximize performance, such as drug / probiotics delivery efficiency, measurement sensitivity, and precision targeting. Furthermore, an additional coating may be formed on the outer surface of the hydrogel structure to prevent drug leakage and increase drug / bacteria loading efficiency.

[0065] Meanwhile, when the capsule structure according to the embodiment is used as a structure for biomarker measurement, a hydrogel structure containing genetically engineered bacteria may be used instead of the polymer layer of the collection module.

[0066]

[0067] Hereinafter, with reference to FIGS. 4 and 5, a driving method of a capsule structure according to various embodiments of the present invention will be described in detail.

[0068] Referring to FIG. 4, a method for driving a capsule structure may include a step of preparing a capsule structure, a step of administering the capsule structure, a step of dissolving an outer protective layer of a collection module, a step of moving the capsule structure to a target position, a step of applying an external signal to heat a heating layer of the collection module, a step of dissolving an inner protective layer of the collection module, and a step of adsorbing a biological substance by a polymer layer of the collection module.

[0069] Specifically, the capsule structure (10) may include collection modules 1 to n (where n is an integer greater than or equal to 2). These multiple collection modules may be sequentially driven. First, collection module 1 may be driven. At this time, the driving method of the capsule structure of the present invention may include a step of dissolving an outer protective layer of collection module 1; a step of moving the capsule structure to a target position; a step of heating a heating layer of collection module 1 by applying a first external signal; a step of dissolving an inner protective layer of collection module 1; and a step of adsorbing a biological material by a polymer layer of collection module 1.

[0070] These steps can be performed for each harvesting module. Meanwhile, after the step of the polymer layer of the harvesting module n-1 adsorbing the biological material, the step of heating the heating layer of the harvesting module n by applying the nth external signal; the step of dissolving the inner protective layer of the harvesting module n; and the step of adsorbing the biological material by the polymer layer of the harvesting module n can be performed.

[0071] Hereinafter, with reference to FIG. 4, a method for operating a capsule structure according to one embodiment of the present invention will be described. First, in the step of preparing a capsule structure, the capsule structure (10) described above can be prepared. That is, a capsule structure (10) including a plurality of collection modules (200) can be prepared.

[0072] In the step of administering the capsule structure, the capsule structure can be directly administered to the subject requiring biological material collection through the esophagus, etc.

[0073] Referring to (a) and (b) of FIG. 4, the outer protective layer of the capsule structure does not dissolve from above, so sample collection from above can be prevented, and the outer protective layer can be dissolved in the target area such as the small intestine or large intestine, thereby preparing for sample collection.

[0074] Referring to (c) of Fig. 4, in the step of moving the capsule structure to the target location, the capsule structure can be moved to the target location within the organ from which the biological material is desired to be collected using an external magnetic field (magnetic force).

[0075] Referring to (d) of Fig. 4, in the step of heating the heating layer (heating element) by applying an external signal, after removing the external magnetic field, a first external signal such as an alternating magnetic field (AMF), near infrared (NIR), or ultrasound may be applied to the capsule structure (10). Through this first external signal, heat may be generated in the heating layer of the collection module 1. At this time, the external signal may control the amount of heat generated so that the internal protective layer of the collection module 1 having a specific melting point may be melted.

[0076] Referring to (e) of Fig. 4, at the stage where the inner protective layer of the collection module is dissolved, the inner protective layer of collection module 1 may be dissolved due to heat generation of the heating layer caused by an external signal, thereby exposing the polymer layer of collection module 1 to the intestinal fluid. Accordingly, biological materials such as microorganisms can be collected by forming a hydrogel through a reaction between the external environment and the polymer layer. At this time, the inner protective layers of collection modules other than collection module 1 may not be dissolved.

[0077] Referring to (f) of Fig. 4, multiple sampling can be performed using each sampling module by repeating the above processes (c) to (e). For example, if the capsule structure has six sampling modules (n=6), six samplings can be performed by varying the sampling trigger conditions.

[0078] Meanwhile, although not shown in the drawing, in the stage where the capsule structure to which microorganisms are adsorbed is discharged, the capsule structure to which microorganisms are adsorbed can pass through the digestive organs through the peristaltic movement of the organs and be discharged as feces.

[0079] Next, in the step of recovering the capsule structure, the discharged stool is collected and diluted, and then an external magnetic field is used to easily recover the capsule structure to which the intestinal biological substances have been adsorbed. After the capsule structure is recovered, the recovered biological substances can be analyzed using kits or reagents to prevent the death of anaerobic microorganisms, prevent changes in microbial composition, block microbial metabolic activity, and preserve dietary components within the sample. The capsule structure containing the recovered biological substances can be utilized for research, diagnosis, and treatment of the distribution of intestinal biological substances through sequencing or genetic analysis related to microorganisms, proteins, metabolites, and viruses.

[0080]

[0081] Example 1: Multiple sampling method

[0082] Hereinafter, with reference to FIG. 5, a method for multiple extraction using the capsule structure of the present invention will be described.

[0083] The capsule structure of the present invention includes six collection modules, and the target collection areas of collection modules 1 and 2 are the proximal (or stomach) small intestine, the target collection areas of collection modules 3 and 4 are the middle small intestine, and the target collection areas of collection modules 5 and 6 are the distal small intestine, so that each collection module is configured.

[0084] To harvest biological material from multiple locations within a target area, the capsule structure can be moved actively by an external magnetic field or passively by peristalsis of the intestine.

[0085] Meanwhile, the target area of ​​each collection module, the dissolution pH of the outer protective layer, the outer protective layer material, and the inner protective layer material were configured as shown in Table 1 below.

[0086] Target areaDissolution pH of the outer protective layerOuter protective layer materialInner protective layer materialSampling module 1Proximal small intestine (or stomach)Less than 5.0Eudragit EPOParaffin wax 25% (v / v) and paraffin oil 75% (v / v) (melting point 39 ℃)Sampling module 2Proximal small intestine (or stomach)Less than 5.0Eudragit EPOParaffin wax 50% (v / v) and paraffin oil 50% (v / v) (melting point 49.9 ℃)Sampling module 3Middle small intestineLess than 5.5Eudragit L100-55Paraffin wax 25% (v / v) and paraffin oil 75% (v / v) (melting point 39 ℃)Sampling module 4Middle small intestineLess than 5.5Eudragit L100-55Paraffin wax 50% (v / v) and paraffin oil 50 %(v / v) (melting point 49.9 ℃) Collection module 5 Distal small intestine 7.0 or moreEudragit S 100Paraffin wax 25 %(v / v) and paraffin oil 75 %(v / v)(melting point 39 ℃) Collection module 6 Distal small intestine 7.0 or moreEudragit S 100Paraffin wax 50 %(v / v) and paraffin oil 50 %(v / v) (melting point 49.9 ℃)

[0087] Referring to (a) of Fig. 5, the capsule structure is moved to the first target area, the proximal small intestine (or stomach), and the outer protective layers included in the collection modules 1 and 2 can be dissolved. In order to activate the collection module 1, an external signal is applied so that the heating layer included in the collection module 1 is heated to a temperature of 39°C or higher, and the inner protective layer included in the collection module 1 is dissolved. Therefore, the polymer layer of the collection module 1 is exposed, and the collection of biological materials can occur. That is, the collection module 1 is activated so that the biological materials can be collected. Referring to (b) of Fig. 5, in order to activate the collection module 2, an external signal is applied so that the heating layer included in the collection module 2 is heated to a temperature of 49.9°C or higher, and the inner protective layer included in the collection module 2 is dissolved. Therefore, the polymer layer of the collection module 2 is exposed, and the collection of biological materials can occur.

[0088] Referring to (c) of FIG. 5, the capsule structure is moved to the second target area, the middle part of the small intestine, and the outer protective layer included in the collection modules 3 and 4 may be dissolved. To activate the collection module 3, an external signal is applied so that the heating layer included in the collection module 3 is heated to a temperature of 39°C or higher, and the inner protective layer included in the collection module 3 is dissolved. Accordingly, the polymer layer of the collection module 3 is exposed, so that the collection of biological material can occur.

[0089] Referring to (d) of Fig. 5, in order to activate the sampling module 4, an external signal is applied, the heating layer included in the sampling module 4 is heated to a temperature of 49.9°C or higher, and the internal protective layer included in the sampling module 4 is melted. Accordingly, the polymer layer of the sampling module 4 is exposed, so that the sampling of biological material can occur.

[0090] Referring to (e) of FIG. 5, the capsule structure is moved to the third target area, the distal small intestine, and the outer protective layer included in the collection modules 5 and 6 may be dissolved. To activate the collection module 5, an external signal is applied so that the heating layer included in the collection module 5 is heated to a temperature of 39°C or higher, and the inner protective layer included in the collection module 5 is dissolved. Accordingly, the polymer layer of the collection module 5 is exposed, so that the collection of biological material can occur.

[0091] Referring to (f) of Fig. 5, in order to activate the sampling module 6, an external signal is applied, the heating layer included in the sampling module 6 is heated to a temperature of 49.9°C or higher, and the internal protective layer included in the sampling module 6 is melted. Accordingly, the polymer layer of the sampling module 6 is exposed, so that the sampling of biological material can occur.

[0092]

[0093] Example 2: Multiple sampling method

[0094] The capsule structure of the present invention includes six collection modules, and the target collection areas of collection modules 1 to 3 are the proximal / middle small intestine, and the target collection areas of collection modules 4 to 6 are the distal small intestine / proximal large intestine, so that each collection module is configured.

[0095] As in Example 1, the capsule structure within the area can be actively or passively moved to collect biological material from multiple locations within the target area.

[0096] Meanwhile, the target area of ​​each collection module, the dissolution pH of the outer protective layer, the outer protective layer material, and the inner protective layer material were configured as shown in Table 2 below.

[0097] Target areaDissolution pH of the outer protective layerExternal protective layer materialInner protective layer materialSampling module 1 Proximal / mid-small intestine 5.5 or moreEudragit L100-55 Paraffin wax 25 % (v / v) and paraffin oil 75 % (v / v) (melting point 39 ℃)Sampling module 2 Proximal / mid-small intestine 5.5 or moreEudragit L100-55 Paraffin wax 50 % (v / v) and paraffin oil 50 % (v / v) (melting point 49.9 ℃)Sampling module 3 Proximal / mid-small intestine 5.5 or moreEudragit L100-55 Paraffin wax 100 % (v / v) (melting point 64.7 ℃)Sampling module 4 Distal small intestine / proximal large intestine 7.0 or moreEudragit S 100 Paraffin wax 25 % (v / v) and paraffin oil 75 % (v / v) (melting point 39 ℃) Collection module 5 Distal small intestine / proximal large intestine 7.0 or more Eudragit S 100 Paraffin wax 50 % (v / v) and paraffin oil 50 % (v / v) (melting point 49.9 ℃) Collection module 6 Distal small intestine / proximal large intestine 7.0 or more Eudragit S 100 Paraffin wax 100 % (v / v) (melting point 64.7 ℃)

[0098] The capsule structure is moved to the first target area, the proximal (or middle) small intestine, and the outer protective layer included in the collection modules 1 to 3 can be dissolved. To activate the collection module 1, an external signal is applied so that the heating layer included in the collection module 1 is heated to a temperature of 39°C or higher, and the inner protective layer included in the collection module 1 is dissolved. Therefore, the polymer layer of the collection module 1 is exposed, and the collection of biological material can occur. That is, the collection module 1 is activated so that the biological material can be collected. Next, to activate the collection module 2, an external signal is applied so that the heating layer included in the collection module 2 is heated to a temperature of 49.9°C or higher, and the inner protective layer included in the collection module 2 is dissolved. Therefore, the polymer layer of the collection module 2 is exposed, and the collection of biological material can occur.

[0099] Next, to activate the harvesting module 3, an external signal is applied so that the heating layer included in the harvesting module 3 heats up to a temperature of 64.7°C or higher, and the internal protective layer included in the harvesting module 3 melts. Accordingly, the polymer layer of the harvesting module 3 is exposed, allowing the harvesting of biological material to occur.

[0100] The capsule structure is moved to the second target area, the distal small intestine (or the proximal large intestine), and the outer protective layer included in the collection modules 4 to 6 may be dissolved. To activate the collection module 4, an external signal is applied so that the heating layer included in the collection module 4 is heated to a temperature of 39°C or higher, and the inner protective layer included in the collection module 4 is dissolved. Accordingly, the polymer layer of the collection module 4 is exposed, so that collection of biological material can occur.

[0101] Next, to activate the harvesting module 5, an external signal is applied so that the heating layer included in the harvesting module 5 heats to a temperature of 49.9°C or higher, and the internal protective layer included in the harvesting module 5 melts. Accordingly, the polymer layer of the harvesting module 5 is exposed, allowing the harvesting of biological material to occur.

[0102] Next, to activate the harvesting module 6, an external signal is applied so that the heating layer included in the harvesting module 6 heats to a temperature of 64.7°C or higher, and the internal protective layer included in the harvesting module 6 melts. Accordingly, the polymer layer of the harvesting module 6 is exposed, allowing the harvesting of biological material to occur.

[0103]

[0104] The features, structures, effects, etc. described in the above-described embodiments are included in at least one embodiment of the present invention, and are not necessarily limited to just one embodiment. Furthermore, the features, structures, effects, etc. exemplified in each embodiment can be combined or modified in other embodiments by those skilled in the art to which the embodiments pertain. Therefore, the contents related to such combinations and modifications should be construed as falling within the scope of the present invention.

[0105] In addition, although the above description focuses on embodiments, these are merely examples and do not limit the present invention. Those skilled in the art to which the present invention pertains will appreciate that various modifications and applications not exemplified above are possible without departing from the essential characteristics of the present embodiments. For example, each component specifically shown in the embodiments can be modified and implemented. In addition, differences related to such modifications and applications should be interpreted as being included within the scope of the present invention defined in the appended claims.

Claims

1. Main body; A collection module accommodated in the above body and collecting biological material; and Contains a magnetic material accommodated in the above body, A capsule structure characterized in that it includes at least one above-mentioned collection module.

2. In paragraph 1, The above extraction module, A capsule structure comprising an outer protective layer, an inner protective layer, a polymer layer, and a heating layer.

3. In paragraph 2, A capsule structure in which the outer protective layer, inner protective layer, polymer layer and heating layer are sequentially arranged along the inside from the surface of the main body.

4. In paragraph 2, The above outer protective layer is, A capsule structure characterized by comprising a pH-responsive polymer.

5. In paragraph 2, The above outer protective layer is, A capsule structure characterized in that it comprises at least one selected from the group consisting of Eudragit EPO, Eudragit L100-55, Eudragit S 100, ShinEtsu HP-55, Chemie HPP-55, and Cellulose Acetate Phthalate.

6. In paragraph 2, The above inner protective layer is, A capsule structure characterized in that it is provided to have a target melting point.

7. In paragraph 2, The above inner protective layer is, A capsule structure characterized by comprising at least one selected from the group consisting of soy wax, bees wax, paraffin wax, palm wax, carnauba wax, paraffin oil, and polyethylene glycol (PEG).

8. In paragraph 2, A capsule structure, characterized in that the melting point of the inner protective layer is 39°C to 65°C.

9. In paragraph 2, A capsule structure, characterized in that the polymer layer comprises a mixture comprising a polymer monomer, a crosslinking agent, and a reaction initiator, or a dried hydrogel.

10. In paragraph 9, A capsule structure characterized in that the polymer monomer comprises at least one selected from the group consisting of poly(ethylene glycol) diacrylate (PEGDA), acrylamide, N-isopropylacrylamide (NIPAM), acrylic acid hexane-1,6-diol diacrylate (HDDA), ethoxylated trimethylolpropane triacrylate (ETTA), and ethylene carbonate (EC).

11. In paragraph 9, A capsule structure characterized in that the reaction initiator comprises at least one selected from the group consisting of ammonium persulfate (APS), potassium persulfate (KPS), azobisisobutyronitrile (AIBN), ascorbic acid, ferric chloride (ascorbic acid + ferric chloride), and Irgacure 2959.

12. In paragraph 1, The above collection module is provided in multiple units, A capsule structure characterized in that the melting points of the inner protective layers included in a plurality of extraction modules are each different.

13. A method for driving a capsule structure including a main body; a collection module accommodated in the main body and collecting biological material; and a magnetic body accommodated in the main body, The above-mentioned collection module includes collection module 1 to collection module n (where n is an integer greater than or equal to 2), Step of dissolving the outer protective layer of the extraction module 1; A step of moving the capsule structure to a target position; A step of heating the heating layer of the collection module 1 by applying a first external signal; The step of dissolving the inner protective layer of the extraction module 1; and A method of operating a capsule structure comprising a step of adsorbing a biological material by a polymer layer of a collection module 1.

14. In paragraph 13, After the polymer layer of the collection module n-1 adsorbs the biological material, A step of heating the heating layer of the sampling module n by applying an external signal n; A step in which the inner protective layer of the extraction module n is dissolved; and A method of operating a capsule structure comprising a step of adsorbing a biological material by a polymer layer of a collection module n.

15. In paragraph 1, A method for driving a capsule structure, characterized in that the inner protective layer of each of the above-mentioned extraction modules has a different melting point.

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