WO2018133660A1 - Gastrointestinal microorganism collection capsule and collection system - Google Patents

Gastrointestinal microorganism collection capsule and collection system Download PDF

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Publication number
WO2018133660A1
WO2018133660A1 PCT/CN2018/000024 CN2018000024W WO2018133660A1 WO 2018133660 A1 WO2018133660 A1 WO 2018133660A1 CN 2018000024 W CN2018000024 W CN 2018000024W WO 2018133660 A1 WO2018133660 A1 WO 2018133660A1
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WIPO (PCT)
Prior art keywords
capsule
collection
gastrointestinal
gastrointestinal microbial
sample
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PCT/CN2018/000024
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French (fr)
Chinese (zh)
Inventor
王邦茂
王罡
曹海龙
荆洋
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天津医科大学总医院
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Publication of WO2018133660A1 publication Critical patent/WO2018133660A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B10/00—Other methods or instruments for diagnosis, e.g. instruments for taking a cell sample, for biopsy, for vaccination diagnosis; Sex determination; Ovulation-period determination; Throat striking implements
    • A61B10/02—Instruments for taking cell samples or for biopsy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B10/00—Other methods or instruments for diagnosis, e.g. instruments for taking a cell sample, for biopsy, for vaccination diagnosis; Sex determination; Ovulation-period determination; Throat striking implements
    • A61B10/0038—Devices for taking faeces samples; Faecal examination devices
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B10/00—Other methods or instruments for diagnosis, e.g. instruments for taking a cell sample, for biopsy, for vaccination diagnosis; Sex determination; Ovulation-period determination; Throat striking implements
    • A61B10/0045—Devices for taking samples of body liquids
    • A61B2010/0061—Alimentary tract secretions, e.g. biliary, gastric, intestinal, pancreatic secretions

Definitions

  • the present invention relates to the field of other methods or instruments for diagnosis, and in particular to a gastrointestinal microbial collection capsule and collection system.
  • fecal analysis is commonly used in the diagnosis of infectious gastroenteritis, and fecal analysis works well in this application.
  • fecal analysis has a significant impact on analytical results such as microbial composition and abundance due to differences in the collection, storage, and processing of samples during the study or diagnosis of other diseases.
  • An ideal specimen was obtained by a simple and standardized collection method, and there was no damage to the microbial sample during the process.
  • fecal samples are usually collected by patients at home, and the home environment can cause potential impact on the sample or even contamination, thus obstructing the clinical application of microbial sample analysis.
  • the results of the fecal analysis are only representative of the microbial samples in the colon and rectum. It is impossible to obtain the difference in microbial composition and abundance of each segment of the gastrointestinal tract of each subject by fecal analysis.
  • the second method is to use a rectal swabbing, swab the swab (swab) into the anus about 5 cm, and collect a sample for analysis.
  • This method is more acceptable to patients than gastrointestinal mirrors.
  • This method has been widely used for the screening of some rectal microorganisms, but it cannot be widely extended to sample collection in other segments of the gastrointestinal tract.
  • the third method is to collect a small sample of the gastrointestinal epithelium by endoscopic biopsy. Although such methods are highly standardized, their high invasiveness makes them unusable for screening and follow-up. It is particularly worth mentioning that the cleansing enema step prior to the endoscope affects the number and diversity of microorganisms in the gut. As a result, there is still a large doubt about the representativeness of the microbial samples on the collected epidermis. In addition, both the gastroscope and the colonoscope have their distance limitations, and the epidermis specimens of the entire small intestine cannot be collected from either side.
  • the fourth method is to collect intestinal fluid specimens in the gastrointestinal tract using intestinal collection capsules developed based on microelectromechanical technology.
  • the advantage of such a method is that it is minimally invasive.
  • the leading company in this field is the Dutch-based Medimetrics, which developed the Intellicap capsule system including an MEMS-based orally available electronic capsule.
  • the electronic capsule After being orally administered by the patient, the electronic capsule has a built-in micro-detector that can detect the pH and temperature status in the gastrointestinal tract in real time, and can transmit signals to the external controller through its built-in wireless transmitter in real time; at the same time, its built-in wireless receiver It is also possible to receive commands from the external controller for real-time transmission, thereby controlling the operation of a built-in micropump.
  • Its micropump includes an electric motor, a piston and a reservoir.
  • the electric motor can advance the piston forward or backward in a straight line, and the volume of its reservoir is determined by the position of the piston.
  • the liquid storage chamber is sealed by the capsule shell and the piston, and only communicates with the external through a small hole in the capsule shell. When the electric motor pushes the piston backwards, the volume in the liquid storage chamber becomes larger, thereby forming a negative pressure, and a suction force is generated through the small hole to absorb the liquid in the outer gastrointestinal tract of the capsule into the liquid storage chamber.
  • capsules use MEMS technology and require a staff member to continuously monitor the pH and temperature status of the detector to determine the position of the capsule in the gastrointestinal tract to control the operation of the capsule to activate its micropump.
  • the manufacturing cost and the use cost are extremely high, and it is difficult to widely spread and apply in scientific research and clinical practice.
  • the gastrointestinal tract often has solid matter such as food, biological tissue and other components, when the diameter of the pores of such capsules is too small, it will cause the solid matter sucked by the negative pressure to block the pores, and even the sample sucked into the reservoir. The number is small and the representativeness is lost.
  • the diameter of the pores of such capsules is too large, the microbial sample inhaled into the reservoir cavity will exchange and exchange microorganisms in the environment of the whole gastrointestinal region, so that the sample is contaminated. Loss of representation.
  • Another type of electronic capsule technology for gastrointestinal diseases such as gastrointestinal bleeding
  • electronic capsules developed based on such techniques such as Nemiroski, et al. "Swallowable Fluorometric Capsule for Wireless Triage of Gastrointestinal Bleeding," Lab Chip 15,4479 (2015), has the function of collecting and fixing the liquid sample in the gastrointestinal tract in a semi-closed capsule cavity; a micro blood detector based on photoelectric technology is provided in the capsule cavity for instantaneous detection of red blood cell content in the liquid sample The test results are sent to the outside of the body through wireless transmission technology.
  • such capsules do not function to isolate specimens. Specimens are highly contaminated by microorganisms in other gastrointestinal tract environments during passage through the gastrointestinal tract and excreted from the body, and therefore do not apply to gastrointestinal microbes. Sample collection.
  • electronic capsules based on MEMS technology including electronic gastroscope capsules and drug delivery capsules, have a risk of gastrointestinal retention after being taken by the patient.
  • the risk of retention is as high as 15%.
  • Electronic capsules contain toxic substances due to their internal micro-electromechanical components and structures, such as batteries.
  • the gastrointestinal motility promotes the drug and promotes gastrointestinal motility to expel the capsule. If the drug stimulation still does not promote the exclusion of the capsule, the doctor will remove the capsule by gastrointestinal endoscopy or even open surgery according to the position of the capsule.
  • the invention is to solve the problem that the existing gastrointestinal microbial ecological sample collection methods have limitations and cannot be applied to a large area of healthy people, and provides a gastrointestinal microbial collection capsule and an acquisition system.
  • a gastrointestinal microbial collection capsule comprising one or more sets of spontaneous collection and separation devices, the collection and separation device comprising a capsule shell and a capsule shell bottom cover, wherein the capsule shell and the capsule shell bottom cover form a capsule cavity Forming at least one liquid flow channel on the capsule shell;
  • the sample shell is provided with a sample separation device, and the sample separation device comprises a piston on one side of the liquid flow channel between the piston and the capsule shell or the capsule bottom cover a spring and a limiter attached to the piston.
  • the limiting device comprises a soluble body and a linkage extending through the through hole of the soluble body and the capsule shell top and movably connected to the piston.
  • linkage is a screw or a closed traction belt/rope.
  • a bottom of the piston is provided with a piston base, and the limiting device is connected to the piston base.
  • the capsule shell and the capsule bottom cover are in a plug-in connection or a threaded connection.
  • the spring is a coil spring, a tension spring or a compression spring.
  • a hydrophilic fibrous material is provided in the capsule cavity on the side where the liquid flow path is formed.
  • the spring or the linkage is made of metal.
  • the material of the capsule shell, the capsule bottom cover and the piston base is wholly or partially made of a bioabsorbable material.
  • the exterior of the collecting and separating device is coated with a sample collecting and starting component, and the sample collecting and starting component comprises an outer capsule body and an enteric coating.
  • outer capsule body and the capsule bottom cover are plug-in or screwed.
  • sample collection and activation assembly further includes an outer capsule cap disposed on the outer capsule body, the outer capsule body being in a plug-in connection or a threaded connection with the outer capsule cap.
  • dissolution rate of the sample separation device and the sample collection initiation assembly is related to the material, the pH of the gastrointestinal tract, temperature, and gastric motility.
  • a gastrointestinal microbial collection capsule comprises two sets of collecting and separating devices, and two sets of collecting and separating devices share a capsule bottom cover.
  • the collection capsule further includes a detection system including a micro controller and an antenna and a sensor connected to the micro controller.
  • the detection system further includes a magnet.
  • the senor includes an image sensor, a pH sensor, a temperature sensor, a humidity detector, and a pressure sensor.
  • the humidity detector and the pressure sensor pass through the capsule bottom cover and are placed in a capsule cavity forming a side of the liquid flow channel.
  • a gastrointestinal microbial collection system comprising at least one gastrointestinal microbial collection capsule and a capsule collection detection device.
  • the capsule collection detecting device comprises a container and a metal detector.
  • the metal detector is placed in a sealed cavity at the bottom of the container; the metal detector includes a first coil and a second coil, and the first coil and the second coil are respectively connected to the signal transmitter and the signal receiver in the sealed box
  • the signal transmitter and the signal receiver are both connected to the main controller, and the main controller is connected to the buzzer.
  • the present invention achieves the following advantageous effects.
  • the capsule of the invention can automatically complete the collection of gastric juice or intestinal fluid sample and sample isolation after reaching the different specific positions of the gastrointestinal tract in the whole collection process, and is painless and non-invasive, and is easily accepted by the user; Collecting samples extending to the distal end of the small intestine and the segments of the large intestine that are inaccessible to the endoscope; after collecting the gastric or intestinal fluid sample, the liquid flow channel is completely closed and cannot be in contact with the external environment, ensuring that the sample is isolated and not contaminated; The gastric juice or intestinal fluid sample is excreted through the capsule, does not cause intestinal obstruction, and is safe; after the capsule is discharged from the body, it enters the capsule collection and detection device, and the metal detector activates the buzzer after detecting the metal component in the capsule, notifying The user collects the capsule in time; the collected intestinal fluid is used to analyze the composition of the microbial components, and the results can be widely used for basic research and clinical diagnosis and treatment related to gastrointestinal microorganisms, and to establish a
  • the capsule If the capsule is retained in the gastrointestinal tract for a long time, the capsule can be slowly degraded in the gastrointestinal tract and decomposed into several smaller diameter structures, so that it can be excreted through the stenosis in the gastrointestinal tract, so that the capsule user can avoid suffering from the gastroscope or The risk of open surgery.
  • Embodiment 1 is a schematic structural view of the inside of a capsule before collecting a liquid sample in Embodiment 1 of the present invention
  • FIG. 2 is a schematic structural view of the inside of a capsule in a process of collecting a liquid sample in Embodiment 1 of the present invention
  • Figure 3 is a schematic view showing the structure of the inside of the capsule after the liquid sample is collected in the first embodiment of the present invention
  • Figure 5 is a schematic view showing the structure of the capsule in the first embodiment of the present invention after long-term retention in the gastrointestinal tract;
  • Figure 6 is a schematic view showing the structure of the inside of the capsule before collecting the liquid sample in Embodiment 2 of the present invention
  • Figure 7 is a schematic view showing the structure of the inside of the capsule in the process of collecting a liquid sample in Embodiment 2 of the present invention.
  • Figure 8 is a schematic view showing the structure of the inside of the capsule after the liquid sample is collected in the second embodiment of the present invention.
  • Figure 9 is a schematic view showing the structure of the inside of the capsule when the sample is disassembled in the second embodiment of the present invention.
  • Figure 10 is a schematic view showing the structure of the inside of the capsule before collecting the liquid sample in Embodiment 3 of the present invention.
  • Figure 11 is a schematic view showing the internal structure of the capsule during the process of collecting intestinal juice by the first collecting and separating device in Embodiment 3 of the present invention.
  • Figure 12 is a schematic view showing the internal structure of the capsule after the collection of intestinal fluid by the first collecting and separating device in the third embodiment of the present invention.
  • Figure 13 is a schematic view showing the internal structure of the capsule during the process of collecting intestinal juice by the second collecting and separating device in Embodiment 3 of the present invention.
  • Figure 14 is a schematic view showing the internal structure of the capsule after the collection of intestinal fluid by the second collecting and separating device in the third embodiment of the present invention.
  • Figure 15 is a schematic view showing the structure of the inside of the capsule before collecting the liquid sample in Embodiment 4 of the present invention.
  • Figure 16 is a schematic view showing the structure of the inside of the capsule in the process of collecting a liquid sample in Embodiment 4 of the present invention.
  • Figure 17 is a schematic view showing the structure of the inside of the capsule after the liquid sample is collected in the fourth embodiment of the present invention.
  • Figure 18 is a schematic view showing the structure of the capsule collecting and detecting device of the present invention.
  • Figure 19 is a schematic structural view of a metal detector of the present invention.
  • Figure 20 is a block diagram showing the system structure of the metal detector of the present invention.
  • outer capsule body 1. outer capsule body; 2. outer capsule cap;
  • Figures 1-5 depict the first structure of a gastrointestinal microbial collection capsule.
  • the outer capsule body 1 and the outer capsule cap 2 constitute the outer casing of the entire outermost collection capsule, and the outer capsule body 1 and the outer capsule cap 2 are first locked by the locking structure 3.
  • the outer capsule body 1 and the outer capsule cap 2 after the closure are coated with one or more layers of the enteric coating 4 to achieve a targeted dissolution function.
  • the outer capsule body 1 and the outer capsule cap 2 were made of AAA DBcaps (inner diameter 11.39 mm, capsule length 16.31 mm, capsule cap length 14.84 mm) produced by Suzhou Capsule (Capsugel).
  • the enteric coating 4 is a composite jejunal targeting enteric material based on Eudragit L100-55 produced by Evonik.
  • the preparation method is as follows:
  • the closed outer capsule cap 2 was immersed in the above-mentioned coating reagent for 15 seconds, taken out and baked in a baking oven at 50 degrees Celsius for 20 minutes. After the coating-bake step was repeated 10 times, the outer capsule 1 was coated and baked 10 times in the same manner.
  • the inside of the sample collection and starting assembly 16 is a spontaneous collecting and separating device.
  • the bottom of the main body of the capsule shell 6 is screwed to the capsule bottom cover 5 by internal and external threads, so that the bottom of the capsule shell 6 is completely sealed.
  • the interior of the capsule shell 6 is a capsule chamber of hollow structure.
  • the side wall of the capsule shell 6 has four apertures penetrating the capsule shell wall, which is a preferred implementation of the liquid flow channel 7.
  • the capsule shell bottom cover 5 and the capsule shell 6 are simple in design, and are manufactured by a precision machine tool PEEK material in a prototype that has been produced on a small scale. In the mass production stage, the capsule shell bottom cover 5 and the capsule shell 6 can also be produced by a compression molding method.
  • the piston 8 is located on the upper side of the liquid flow passage 7 in the capsule chamber, further separating the capsule chamber into a first sub-chamber 9 and a second sub-chamber 10, and isolating the liquid flow between the two sub-chambers.
  • the piston 8 uses a piston element in a Luer-Lok 3 mL needle tube manufactured by BD Corporation.
  • the soluble body 11 is a disc-shaped sugar piece
  • the spring 12 is a compression spring in a high energy storage state
  • the linkage 13 is a flat head screw; after the piston 8 is inserted into the piston base 14 and fixed, the linkage 13 is sequentially worn.
  • the piston base 14 is screwed, and the structural bearing pressure of the soluble body 11 and the energy storage of the compression spring are fixed.
  • the piston 8 is in an initial position on the upper side of the liquid flow path 7 in the capsule chamber.
  • the piston 8 is inserted into the piston base 14, and then inserted into the capsule cavity from the bottom of the capsule shell 6 with the compression spring; then the piston 8 is pushed upward from the bottom of the capsule shell 6, and the piston 8 is placed against the elastic force of the compression spring.
  • the gastrointestinal microbial collection capsule is first contacted with the liquid in the gastrointestinal tract after the user enters the gastrointestinal tract orally; in the prototype that has been produced, the sample collection activation component 16 is a duodenum target. To the coating material Eudragit L100-55. Therefore, the sample collection activation assembly 16 should remain structurally intact and insoluble in the stomach.
  • the sample collection activation assembly 16 dissolves.
  • the intestinal fluid surrounding the capsule passes through the liquid flow channel 7 penetrating the capsule shell wall, and flows into the second sub-chamber 10 by its own gravity, intestinal peristalsis, and suction of the hydrophilic fiber 15, and is fixed in the hydrophilicity by adsorption.
  • the surface of the fiber 15 is.
  • the soluble body 11 in the sample separation device is melted, and its structural disintegration causes the compression spring to exert its energy storage, and the force released when the high energy storage form changes to the low energy storage form moves the position of the piston 8 to Between the liquid flow channel 7 and the capsule bottom cover 5, a certain amount of liquid sample 17, i.e., intestinal fluid, is enclosed in the second sub-chamber 10.
  • the capsule bottom cover 5 is unscrewed to complete the disassembly.
  • the hydrophilic fibers 15 in the capsule shell 6 and the intestinal fluid sample attached thereto can be easily taken out for biochemical detection in the laboratory, such as 16s rRNA detection.
  • the material of the capsule shell 6, the capsule shell bottom cover 5, and the piston base 14 can be slowly degraded in the gastrointestinal tract and decomposed into several diameters.
  • the small structure facilitates passage through the stenosis in the gastrointestinal tract and is thereby excreted, so that the capsule user avoids the risk of endoscopic or open surgery.
  • the material of the capsule shell 6, the capsule shell bottom cover 5, and the piston base 14 may be a bioabsorbable material such as bioabsorbable polydioxanone.
  • Bioabsorbable poly(dioxa) is a new synthetic material, and because of its robust structure, it has been used as a degradable scaffold for the treatment of esophageal stricture. It degrades slowly after several weeks of implantation (Dhar , et al.”Biodegradable stent or balloon dilatation for benign
  • FIG. 6-9 Depicted in Figures 6-9 is a second configuration of a gastrointestinal microbial collection capsule.
  • the spring 12 is located in the second sub-chamber 10 and is in a stretched state.
  • the piston 8 is moved between the liquid flow path 7 and the capsule bottom cover 5 to close a certain amount of the liquid sample 17.
  • FIG. 10-14 Depicted in Figures 10-14 is a third configuration of a gastrointestinal microbial collection capsule.
  • one collection capsule of the embodiment includes two sets of spontaneous collection and separation devices, and the soluble body 11 of the two collection and separation devices is made of different materials, so that the dissolution time is different, so Digestion samples can be taken separately at different locations in the gastrointestinal tract.
  • the soluble body 11 in the sample separation device can be coated with an enteric coating material (such as Eudragit L100) for a common candy piece, and the sample collection starter assembly 16 can be applied to another enteric coating material for standard gelatin capsules.
  • enteric coating material such as Eudragit L100
  • the sample collection starter assembly 16 can be applied to another enteric coating material for standard gelatin capsules.
  • S100 is suitable for decomposition in the colon; the gastrointestinal microbial collection capsules achieved by this combination are kept intact in the stomach and duodenum after oral administration by the user.
  • the liquid flow channel 7 remains closed, and the gastrointestinal fluid of this segment cannot flow into the second sub-chamber 10 via the liquid flow channel 7; in a later jejunum, the sample collection starter assembly 16 dissolves rapidly, causing the liquid flow channel 7 to open, the jejunum The liquid enters the second sub-chamber 10 via the liquid flow channel 7; in a later colon, the sample separation device dissolves rapidly, thereby causing the spring 12 to release its potential energy, pushing the piston 8 to move and The liquid flow path 7 is closed.
  • the intestinal fluid sample in the second sub-chamber 10 is isolated from the outside world, and thus its components, such as, but not limited to, microorganisms and compound components, represent intestinal fluid components from the jejunum to the colon segment.
  • the soluble body 11 in the sample separation device can be a common candy piece, and the sample collection and activation assembly 16 can be removed from the design, and the liquid flow channel 7 of the gastrointestinal microbial collection capsule realized by the combination is initially In the open state, the gastric juice is immediately absorbed into the stomach by the user; the sample separation device rapidly dissolves in the stomach, thereby causing the spring 12 to release its potential energy, pushing the piston 8 to move and closing the liquid flow channel 7 .
  • the gastric juice sample in the second sub-chamber 10 is isolated from the outside, so its composition represents the gastric juice component.
  • the capsule is further provided with a detection system.
  • the detection system has a microcontroller 18 as a main control unit, and externally connects various sensors, an antenna 19 and a magnet 30.
  • the sensor is one or more miniature sensors including, but not limited to, humidity, pressure, pH, temperature, and image sensors.
  • the microsensor simultaneously detects the physiological condition of the gastrointestinal tract section of the capsule and the state of the gastrointestinal fluid collection and separation device, and inputs a detection signal to the microcontroller 18 built into the capsule.
  • the microcontroller 18 transmits the collected signals to the outside of the body through a miniature antenna built into the capsule.
  • the capsule can control the magnet 30 based on the signal feedback of the sensor by an external magnetic control platform to control the fixation and movement of the capsule in the gastrointestinal tract.
  • Figure 18 is a schematic view showing the structure of a capsule collection detecting device.
  • the structure of the capsule collection detecting device is divided into two parts: a barrel container 25 at the top and a sealing chamber 26 at the bottom, and a sealed metal chamber is built in the sealing chamber 26.
  • the capsule collection and detection device can be placed in a sitting toilet as a whole, so that the user can use the defecation within a few days after the oral gastrointestinal fluid collection capsule. Because each user's gastrointestinal motility is different, the time for capsules to be excreted through the gastrointestinal tract is different. At the same time, capsules are less likely to be visually observed by the user after being excreted with the feces.
  • the metal detector in the capsule collection detecting device can automatically detect whether the capsule is excreted after each defecation: when the capsule stays in the body, it is far from the metal detector, and the signal generated by the metal detector changes little.
  • the buzzer will not be triggered to start; when the capsule is discharged from the anus and then falls into the container 25, close to the metal detector, the signal generated by the metal detector changes significantly; the signal change activates the buzzer, notifying the user that the capsule has been discharged in vitro.
  • the sealed case 27 has built-in electronic components such as a metal detector and a buzzer; both ends of the first coil 28 and the second coil 29 are also connected to the sealed case 27.
  • the sealing chamber 26 is a water-tight structure, and the capsule collecting and detecting device is placed in the sitting toilet, and the electronic components inside can also operate normally.
  • Figure 20 is a block diagram illustration showing the implementation principle of the capsule collection detecting device of the present invention.
  • the main controller control signal transmitter generates a current through the first coil 28 to generate electromagnetic induction to generate a first magnetic field; the first magnetic field passes through the compartment of the container 25 and the sealed chamber 26 via electromagnetic induction, in the compartment A vortex is created in the metal part in the upper capsule.
  • the eddy current again generates a second magnetic field via electromagnetic induction; the second magnetic field creates another eddy current within the second coil 29.
  • the signal receiver receives this eddy current and transmits the signal to the main controller.
  • the intestinal fluid collection capsule stays in the body, it is far from the metal detector, and the flow of the eddy current in the capsule is small, and further, the second magnetic field generated by the capsule and the second magnetic field generated by the second magnetic field are smaller. .
  • the gastrointestinal fluid collection capsule is discharged outside the body, staying in the container 25, closer to the metal detector, the eddy current flow in the capsule is larger, and further, the second magnetic field generated by the second magnetic field and the second magnetic field are in the second coil 29. The resulting current flow is large.
  • the main controller starts the buzzer alarm.
  • the capsule collection detecting device described in the present invention can be applied not only to the detection of the gastrointestinal fluid collection capsule described in the present invention, but also to the collection and detection of any capsule discharge containing metal components because of its basic electromagnetic induction principle.
  • the bottom of the container 25 of the capsule collection and detection device described in the present invention is a sealed structure, and the discharged feces and capsules are not in contact with the surrounding environment, and the intestinal flora carried by the capsule is carried out. It will not be polluted by the micro-ecological environment in the surrounding environment, so that the sample of intestinal flora collected by the capsules of the present invention is more accurate and representative, and can satisfy the clinical and scientific research needs, and has broad application prospects. .

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Abstract

Disclosed are a gastrointestinal microorganism collection capsule and a collection system. The gastrointestinal microorganism collection capsule comprises one or more autonomous sample collecting and separating apparatuses. The collecting and separating apparatus comprises a capsule shell (6) and a capsule shell bottom cap (5), with at least one fluid flow channel (7) being formed on the capsule shell (6). A sample separating apparatus is provided in the capsule shell (6), and the sample separating apparatus comprises a piston (8) located on one side of the fluid flow channel (7), a spring (12) located between the piston (8) and the capsule shell (7) or the capsule shell bottom cap (5), and a limiting apparatus connected to the piston (8). The collection system comprises at least one gastrointestinal microorganism collection capsule and a capsule collection and detection apparatus. The gastrointestinal microorganism collection capsule can collect samples as far as the distal small intestine and proximal colon sections; samples of gastric fluid or intestinal fluid are automatically collected after the capsule reaches different positions in the gastrointestinal tract; after collecting samples of gastric fluid or intestinal fluid, the fluid flow channel (7) is completely closed, ensuring that microorganism samples are not contaminated; and after the capsule is excreted, the capsule collection and detection apparatus can notify a user to gather the capsule.

Description

胃肠道微生物采集胶囊及采集***Gastrointestinal microbial collection capsule and collection system 技术领域Technical field
本发明涉及用于诊断的其他方法或仪器领域，具体是一种胃肠道微生物采集胶囊及采集***。The present invention relates to the field of other methods or instruments for diagnosis, and in particular to a gastrointestinal microbial collection capsule and collection system.
背景技术Background technique
在过去一个世纪以来，对胃肠道微生物生态的研究一直在稳步进行，但进展较为缓慢。近期研究结果表明，肠道微生物与包括炎症性肠病(IBD)，肥胖，和营养不良等在内的多种疾病都有关联性。但针对大面积健康人群的胃肠道微生物样本的全面研究少之又少。一个原因是全面采集健康人群胃肠道微生物样本极为困难，有理论提出“健康”的个体必然拥有一个稳定的胃肠道微生物生态平衡，然而个体之间的生态也有显著的差异。因此，目前缺少一个对“正常”或“健康”的胃肠道微生物生态的定义，这也是目前相关科研的一个主要方向。阻碍胃肠道微生物研究的另一个重要原因是缺乏一种简易，全面和有效的采集胃肠道微生物样本的标准方法。In the past century, research on the microbial ecology of the gastrointestinal tract has been steadily progressing, but progress has been slow. Recent studies have shown that intestinal microbes are associated with a variety of diseases including inflammatory bowel disease (IBD), obesity, and malnutrition. However, there has been little thorough research on gastrointestinal microbial samples for large healthy populations. One reason is that it is extremely difficult to collect gastrointestinal microbial samples from healthy people. It is theoretically suggested that “healthy” individuals must have a stable gastrointestinal microbial ecological balance, but the ecology between individuals is also significantly different. Therefore, there is currently no definition of a “normal” or “healthy” gastrointestinal microbial ecology, which is currently a major direction of related research. Another important reason for hindering gastrointestinal microbiology research is the lack of a simple, comprehensive and effective standard method for collecting gastrointestinal microbial samples.
现有的四种采集胃肠道微生物样本的方法：第一种，也是最常见的一种，是粪便采集与分析。粪便分析常用于感染性胃肠炎的诊断，粪便分析在这一应用上效果极好。然而，粪便分析在研究或诊断其他疾病的应用中，由于存在样本的采集，储存和处理过程中的差异，使得其对分析结果如微生物组成和丰度都有显著影响。一个理想的标本是通过简易且标准化的采集方法获得的，而且其过程中并无对微生物样本的破坏。然而现实中，粪便样本通常是由病人在家采集，住家环境会导致对样本的潜在影响甚至污染，从而阻挠了微生物样本分析在临床当中的应用。另一方面，粪便分析的研究结果只是对结肠和直肠内的微生物样本具有代表性，人们无法通过粪便分析获取每个实验对象胃肠道各区段的微生物组成和丰度的差异。There are four existing methods for collecting gastrointestinal microbial samples: the first and most common one is fecal collection and analysis. Fecal analysis is commonly used in the diagnosis of infectious gastroenteritis, and fecal analysis works well in this application. However, fecal analysis has a significant impact on analytical results such as microbial composition and abundance due to differences in the collection, storage, and processing of samples during the study or diagnosis of other diseases. An ideal specimen was obtained by a simple and standardized collection method, and there was no damage to the microbial sample during the process. However, in reality, fecal samples are usually collected by patients at home, and the home environment can cause potential impact on the sample or even contamination, thus obstructing the clinical application of microbial sample analysis. On the other hand, the results of the fecal analysis are only representative of the microbial samples in the colon and rectum. It is impossible to obtain the difference in microbial composition and abundance of each segment of the gastrointestinal tract of each subject by fecal analysis.
第二种方法是采用直肠拭子(rectal swabbing)，将拭子(棉签)探入***约5公分，采集小样用于分析。相较胃肠镜，此方法较易被病人接受。此方法已被广泛用于一些直肠微生物的筛查，但其无法被广泛推广至胃肠道其他区段的样本采集。The second method is to use a rectal swabbing, swab the swab (swab) into the anus about 5 cm, and collect a sample for analysis. This method is more acceptable to patients than gastrointestinal mirrors. This method has been widely used for the screening of some rectal microorganisms, but it cannot be widely extended to sample collection in other segments of the gastrointestinal tract.
第三种方法是通过内窥镜活检采集一小块胃肠道表皮样本，尽管此类方法标准化很高，但是其极高的侵入性使其无法被应用于筛查和随访。特别值得提出的是，内窥镜之前的清洁灌肠步骤会影响肠道内微生物的数量和多元化结构。其结果为，所采集的表皮上的微生物样本的代表性仍存有较大的疑 问。此外，胃镜及肠镜都有其距离限制，从任何一侧皆无法采集到小肠全区域的表皮标本。The third method is to collect a small sample of the gastrointestinal epithelium by endoscopic biopsy. Although such methods are highly standardized, their high invasiveness makes them unusable for screening and follow-up. It is particularly worth mentioning that the cleansing enema step prior to the endoscope affects the number and diversity of microorganisms in the gut. As a result, there is still a large doubt about the representativeness of the microbial samples on the collected epidermis. In addition, both the gastroscope and the colonoscope have their distance limitations, and the epidermis specimens of the entire small intestine cannot be collected from either side.
第四种方法是应用基于微机电技术开发的肠道采集胶囊采集胃肠道中的肠液标本。此类方法的优点为其侵入性极小。在这一领域的领军企业是总部位于荷兰的Medimetrics，其开发的Intellicap胶囊***包括一个基于微机电***的可口服的电子胶囊。经由患者口服之后，此电子胶囊内置微型探测器可实时探测胃肠道内的pH和温度状态，并且可以通过其内置的无线发射器向体外的控制器实时传输信号；同时，其内置的无线接收器也可以接收体外的控制器实时传输的命令，进而控制其内置的一个微型泵运作。其微型泵包括一个电动马达，一个活塞和储液腔。电动马达可以沿直线向前或向后推进活塞，而其储液腔的体积由活塞的位置决定。储液腔由胶囊壳和活塞密封，只有经胶囊壳上的一个小孔与外接联通。当电动马达向后推进活塞时，储液腔内体积变大，进而形成一个负压，经由小孔产生一个吸力吸收胶囊外胃肠道内的液体进入储液腔内。然而，此类胶囊由于采用微机电技术，且操作时需有工作人员持续监控探测器传输的pH和温度状态以判断胶囊在胃肠道内的位置来控制胶囊启动其微型泵的运作，因此，其制造成本和使用成本极高，较难于科研和临床上广泛推广应用。另外，因胃肠道内常有固态物如积食，生物组织等成分，当此类胶囊的小孔直径过小时，会导致通过负压吸入的固态物堵住小孔，以至吸入储液腔的样本数量较少，失去代表性；而当此类胶囊的小孔直径过大时，吸入储液腔的微生物样本会在全胃肠道区域环境下的微生物发生流动交换，而使样本被污染，亦失去代表性。The fourth method is to collect intestinal fluid specimens in the gastrointestinal tract using intestinal collection capsules developed based on microelectromechanical technology. The advantage of such a method is that it is minimally invasive. The leading company in this field is the Dutch-based Medimetrics, which developed the Intellicap capsule system including an MEMS-based orally available electronic capsule. After being orally administered by the patient, the electronic capsule has a built-in micro-detector that can detect the pH and temperature status in the gastrointestinal tract in real time, and can transmit signals to the external controller through its built-in wireless transmitter in real time; at the same time, its built-in wireless receiver It is also possible to receive commands from the external controller for real-time transmission, thereby controlling the operation of a built-in micropump. Its micropump includes an electric motor, a piston and a reservoir. The electric motor can advance the piston forward or backward in a straight line, and the volume of its reservoir is determined by the position of the piston. The liquid storage chamber is sealed by the capsule shell and the piston, and only communicates with the external through a small hole in the capsule shell. When the electric motor pushes the piston backwards, the volume in the liquid storage chamber becomes larger, thereby forming a negative pressure, and a suction force is generated through the small hole to absorb the liquid in the outer gastrointestinal tract of the capsule into the liquid storage chamber. However, such capsules use MEMS technology and require a staff member to continuously monitor the pH and temperature status of the detector to determine the position of the capsule in the gastrointestinal tract to control the operation of the capsule to activate its micropump. The manufacturing cost and the use cost are extremely high, and it is difficult to widely spread and apply in scientific research and clinical practice. In addition, because the gastrointestinal tract often has solid matter such as food, biological tissue and other components, when the diameter of the pores of such capsules is too small, it will cause the solid matter sucked by the negative pressure to block the pores, and even the sample sucked into the reservoir. The number is small and the representativeness is lost. When the diameter of the pores of such capsules is too large, the microbial sample inhaled into the reservoir cavity will exchange and exchange microorganisms in the environment of the whole gastrointestinal region, so that the sample is contaminated. Loss of representation.
另有一类电子胶囊技术在胃肠道疾病，如胃肠道出血方面的应用，基于此类技术开发的电子胶囊，如Nemiroski，et al.″Swallowable Fluorometric Capsule for Wireless Triage of Gastrointestinal Bleeding，″Lab Chip 15，4479(2015)，已有采集和固定胃肠道内液体标本于一个半封闭的胶囊腔的功能；胶囊腔内设有基于光电技术的微型血液检测器用于即时检测液体标本内的血红细胞含量并通过无线传输技术将检测结果发送至体外。然而，此类胶囊并未实现隔离标本的功能，标本在穿过胃肠道并排出体外的过程中极易被其他胃肠道区域环境下的微生物所污染，因此也不适用于胃肠道微生物样本采集。Another type of electronic capsule technology for gastrointestinal diseases, such as gastrointestinal bleeding, electronic capsules developed based on such techniques, such as Nemiroski, et al. "Swallowable Fluorometric Capsule for Wireless Triage of Gastrointestinal Bleeding," Lab Chip 15,4479 (2015), has the function of collecting and fixing the liquid sample in the gastrointestinal tract in a semi-closed capsule cavity; a micro blood detector based on photoelectric technology is provided in the capsule cavity for instantaneous detection of red blood cell content in the liquid sample The test results are sent to the outside of the body through wireless transmission technology. However, such capsules do not function to isolate specimens. Specimens are highly contaminated by microorganisms in other gastrointestinal tract environments during passage through the gastrointestinal tract and excreted from the body, and therefore do not apply to gastrointestinal microbes. Sample collection.
最后，基于微机电技术开发的电子胶囊，包括电子胃镜胶囊和释药胶囊，在被患者服用后均具有胃肠滞留的风险。在某些特定胃肠疾病患者人群当中，滞留风险率高达15％.电子胶囊因其内部微机电元件及结构，如电池等，含有有毒性物质，通常当滞留发生7天后，患者需服用医生开具的胃肠动力促 进药物，促进胃肠蠕动排出胶囊。如药物刺激仍无法促进胶囊排除体外，则医生会根据胶囊的位置，通过胃肠镜甚至开腹手术取出胶囊。Finally, electronic capsules based on MEMS technology, including electronic gastroscope capsules and drug delivery capsules, have a risk of gastrointestinal retention after being taken by the patient. In some patients with certain gastrointestinal diseases, the risk of retention is as high as 15%. Electronic capsules contain toxic substances due to their internal micro-electromechanical components and structures, such as batteries. Usually, 7 days after the retention occurs, patients need to take a doctor. The gastrointestinal motility promotes the drug and promotes gastrointestinal motility to expel the capsule. If the drug stimulation still does not promote the exclusion of the capsule, the doctor will remove the capsule by gastrointestinal endoscopy or even open surgery according to the position of the capsule.
综上所述，现有针对特定属性人群的胃肠道微生物生态样本采集方法皆有较大的局限性，无法被广泛推广于大面积人群的研究，用于建立一套人类微生物分布图谱，这也必是将肠道菌群应用于临床诊断的一个先决条件。In summary, the existing methods for collecting gastrointestinal microbial ecological samples for specific populations have great limitations and cannot be widely extended to large-area populations for establishing a set of human microbial distribution maps. It must also be a prerequisite for the application of intestinal flora to clinical diagnosis.
发明内容Summary of the invention
本发明就是为了解决现有的胃肠道微生物生态样本采集方法均具有局限性，不能应用于大面积健康人群的问题，所提供了一种胃肠道微生物采集胶囊及采集***。The invention is to solve the problem that the existing gastrointestinal microbial ecological sample collection methods have limitations and cannot be applied to a large area of healthy people, and provides a gastrointestinal microbial collection capsule and an acquisition system.
本发明是按照以下技术方案实现的。The present invention has been achieved in accordance with the following technical solutions.
一种胃肠道微生物采集胶囊，包括一套及以上的自发性采集及分离装置，所述采集及分离装置包括胶囊壳和胶囊壳底盖，所述胶囊壳和胶囊壳底盖内形成胶囊腔，所述胶囊壳上至少形成一个液体流动通道；所述胶囊壳内设有样本分离装置，样本分离装置包括位于液体流动通道一侧的活塞，位于活塞与胶囊壳或胶囊壳底盖之间的弹簧以及连接在活塞上的限位装置。A gastrointestinal microbial collection capsule comprising one or more sets of spontaneous collection and separation devices, the collection and separation device comprising a capsule shell and a capsule shell bottom cover, wherein the capsule shell and the capsule shell bottom cover form a capsule cavity Forming at least one liquid flow channel on the capsule shell; the sample shell is provided with a sample separation device, and the sample separation device comprises a piston on one side of the liquid flow channel between the piston and the capsule shell or the capsule bottom cover a spring and a limiter attached to the piston.
进一步的，所述限位装置包括可溶体以及贯穿可溶体和胶囊壳顶部通孔并与活塞活动连接的联动件。Further, the limiting device comprises a soluble body and a linkage extending through the through hole of the soluble body and the capsule shell top and movably connected to the piston.
进一步的，所述联动件为螺丝或封闭的牵引带/绳。Further, the linkage is a screw or a closed traction belt/rope.
进一步的，所述活塞的底部设有活塞底座，所述限位装置连接在活塞底座上。Further, a bottom of the piston is provided with a piston base, and the limiting device is connected to the piston base.
进一步的，所述胶囊壳和胶囊壳底盖为***式连接或通过螺纹连接。Further, the capsule shell and the capsule bottom cover are in a plug-in connection or a threaded connection.
进一步的，所述弹簧为螺旋弹簧，拉伸弹簧或压缩弹簧。Further, the spring is a coil spring, a tension spring or a compression spring.
进一步的，在形成液体流动通道一侧的胶囊腔内设有亲水性纤维物。Further, a hydrophilic fibrous material is provided in the capsule cavity on the side where the liquid flow path is formed.
进一步的，所述弹簧或联动件为金属材质。Further, the spring or the linkage is made of metal.
进一步的，所述胶囊壳、胶囊壳底盖和活塞底座的材质全部或局部采用生物可吸收材质。Further, the material of the capsule shell, the capsule bottom cover and the piston base is wholly or partially made of a bioabsorbable material.
进一步的，所述采集及分离装置的外部包覆有样本采集启动组件，样本采集启动组件包括外胶囊体和肠溶包衣。Further, the exterior of the collecting and separating device is coated with a sample collecting and starting component, and the sample collecting and starting component comprises an outer capsule body and an enteric coating.
进一步的，所述外胶囊体与胶囊壳底盖为***式连接或通过螺纹连接。Further, the outer capsule body and the capsule bottom cover are plug-in or screwed.
进一步的，所述样本采集启动组件还包括设置在外胶囊体上的外胶囊帽，所述外胶囊体与外胶囊帽为***式连接或通过螺纹连接。Further, the sample collection and activation assembly further includes an outer capsule cap disposed on the outer capsule body, the outer capsule body being in a plug-in connection or a threaded connection with the outer capsule cap.
进一步的，所述样本分离装置和样本采集启动组件的溶化速率与材料、胃肠道的pH值，温度和胃动力有关。Further, the dissolution rate of the sample separation device and the sample collection initiation assembly is related to the material, the pH of the gastrointestinal tract, temperature, and gastric motility.
一种胃肠道微生物采集胶囊，包括两套采集及分离装置，两套采集及分离装置共用胶囊壳底盖。A gastrointestinal microbial collection capsule comprises two sets of collecting and separating devices, and two sets of collecting and separating devices share a capsule bottom cover.
进一步的，所述采集胶囊还包括检测***，所述检测***包括微型控制器以及与微型控制器相连的天线和传感器。Further, the collection capsule further includes a detection system including a micro controller and an antenna and a sensor connected to the micro controller.
进一步的，所述检测***还包括磁体。Further, the detection system further includes a magnet.
进一步的，所述传感器包括图像传感器、pH传感器、温度传感器、湿度探测器和压力传感器。Further, the sensor includes an image sensor, a pH sensor, a temperature sensor, a humidity detector, and a pressure sensor.
进一步的，所述湿度探测器和压力传感器穿过胶囊壳底盖并置于形成液体流动通道一侧的胶囊腔内。Further, the humidity detector and the pressure sensor pass through the capsule bottom cover and are placed in a capsule cavity forming a side of the liquid flow channel.
一种胃肠道微生物采集***，包括至少一个胃肠道微生物采集胶囊和胶囊收集检测装置。A gastrointestinal microbial collection system comprising at least one gastrointestinal microbial collection capsule and a capsule collection detection device.
进一步的，所述胶囊收集检测装置包括容器和金属探测器。Further, the capsule collection detecting device comprises a container and a metal detector.
进一步的，所述金属探测器置于容器底部的密封腔内；金属探测器包括第一线圈和第二线圈，第一线圈和第二线圈分别与密封盒中的信号发射器和信号接收器相连；信号发射器和信号接收器均与主控制器相连，主控制器连接蜂鸣器。Further, the metal detector is placed in a sealed cavity at the bottom of the container; the metal detector includes a first coil and a second coil, and the first coil and the second coil are respectively connected to the signal transmitter and the signal receiver in the sealed box The signal transmitter and the signal receiver are both connected to the main controller, and the main controller is connected to the buzzer.
本发明获得了如下有益效果。The present invention achieves the following advantageous effects.
本发明所述胶囊在整个采集过程无体外遥控即可实现在抵达胃肠道不同的特定位置后自动完成胃液或肠液样本采集及样本隔离，无痛无创，极易被使用者接受；本发明可采集延伸至小肠远端和大肠近段那些内镜无法到达的区段的样本；采集胃液或肠液样本后，液体流动通道被完全封闭无法与外界环境接触，保证样本被隔离不被污染；采集到的胃液或肠液样本经由胶囊排出体外，不会造成肠梗阻，安全性强；胶囊排出体外后，进入胶囊收集检测装置，金属探测器在探测到胶囊内的金属元件后，启动蜂鸣器，通知使用者及时收集胶囊；采集到的胶囊内的肠液用于分析其微生物成份构成，其结果可广泛用于与胃肠道微生物相关的基础研究和临床诊断及治疗，以及建立一套完整的人类肠道微生物分布图谱。如若胶囊长期滞留胃肠道时，所述胶囊可在胃肠道内缓慢降解，分解为数个直径较小的结构，便于其通过胃肠道内狭窄处进而被排出体外，使胶囊使用者避免承受胃镜或开腹手术的风险。The capsule of the invention can automatically complete the collection of gastric juice or intestinal fluid sample and sample isolation after reaching the different specific positions of the gastrointestinal tract in the whole collection process, and is painless and non-invasive, and is easily accepted by the user; Collecting samples extending to the distal end of the small intestine and the segments of the large intestine that are inaccessible to the endoscope; after collecting the gastric or intestinal fluid sample, the liquid flow channel is completely closed and cannot be in contact with the external environment, ensuring that the sample is isolated and not contaminated; The gastric juice or intestinal fluid sample is excreted through the capsule, does not cause intestinal obstruction, and is safe; after the capsule is discharged from the body, it enters the capsule collection and detection device, and the metal detector activates the buzzer after detecting the metal component in the capsule, notifying The user collects the capsule in time; the collected intestinal fluid is used to analyze the composition of the microbial components, and the results can be widely used for basic research and clinical diagnosis and treatment related to gastrointestinal microorganisms, and to establish a complete human intestine Trace microbial distribution map. If the capsule is retained in the gastrointestinal tract for a long time, the capsule can be slowly degraded in the gastrointestinal tract and decomposed into several smaller diameter structures, so that it can be excreted through the stenosis in the gastrointestinal tract, so that the capsule user can avoid suffering from the gastroscope or The risk of open surgery.
附图说明DRAWINGS
图1是本发明实施例1中收集液体样本前胶囊内部的结构示意图；1 is a schematic structural view of the inside of a capsule before collecting a liquid sample in Embodiment 1 of the present invention;
图2是本发明实施例1中收集液体样本过程中胶囊内部的结构示意图；2 is a schematic structural view of the inside of a capsule in a process of collecting a liquid sample in Embodiment 1 of the present invention;
图3是本发明实施例1中收集液体样本结束后胶囊内部的结构示意图；Figure 3 is a schematic view showing the structure of the inside of the capsule after the liquid sample is collected in the first embodiment of the present invention;
图4是本发明实施例1中拆解取样时胶囊内部的结构示意图；4 is a schematic structural view of the inside of the capsule when the sample is disassembled in Embodiment 1 of the present invention;
图5是本发明实施例1中胶囊长期滞留胃肠道中缓慢降解后的结构示意图；Figure 5 is a schematic view showing the structure of the capsule in the first embodiment of the present invention after long-term retention in the gastrointestinal tract;
图6是本发明实施例2中收集液体样本前胶囊内部的结构示意图；Figure 6 is a schematic view showing the structure of the inside of the capsule before collecting the liquid sample in Embodiment 2 of the present invention;
图7是本发明实施例2中收集液体样本过程中胶囊内部的结构示意图；Figure 7 is a schematic view showing the structure of the inside of the capsule in the process of collecting a liquid sample in Embodiment 2 of the present invention;
图8是本发明实施例2中收集液体样本结束后胶囊内部的结构示意图；Figure 8 is a schematic view showing the structure of the inside of the capsule after the liquid sample is collected in the second embodiment of the present invention;
图9是本发明实施例2中拆解取样时胶囊内部的结构示意图；Figure 9 is a schematic view showing the structure of the inside of the capsule when the sample is disassembled in the second embodiment of the present invention;
图10是本发明实施例3中收集液体样本前胶囊内部的结构示意图；Figure 10 is a schematic view showing the structure of the inside of the capsule before collecting the liquid sample in Embodiment 3 of the present invention;
图11是本发明实施例3中第一采集及分离装置收集肠液过程中胶囊内部结构示意图；Figure 11 is a schematic view showing the internal structure of the capsule during the process of collecting intestinal juice by the first collecting and separating device in Embodiment 3 of the present invention;
图12是本发明实施例3中第一采集及分离装置收集肠液结束后胶囊内部结构示意图；Figure 12 is a schematic view showing the internal structure of the capsule after the collection of intestinal fluid by the first collecting and separating device in the third embodiment of the present invention;
图13是本发明实施例3中第二采集及分离装置收集肠液过程中胶囊内部结构示意图；Figure 13 is a schematic view showing the internal structure of the capsule during the process of collecting intestinal juice by the second collecting and separating device in Embodiment 3 of the present invention;
图14是本发明实施例3中第二采集及分离装置收集肠液结束后胶囊内部结构示意图；Figure 14 is a schematic view showing the internal structure of the capsule after the collection of intestinal fluid by the second collecting and separating device in the third embodiment of the present invention;
图15是本发明实施例4中收集液体样本前胶囊内部的结构示意图；Figure 15 is a schematic view showing the structure of the inside of the capsule before collecting the liquid sample in Embodiment 4 of the present invention;
图16是本发明实施例4中收集液体样本过程中胶囊内部的结构示意图；Figure 16 is a schematic view showing the structure of the inside of the capsule in the process of collecting a liquid sample in Embodiment 4 of the present invention;
图17是本发明实施例4中收集液体样本结束后胶囊内部的结构示意图；Figure 17 is a schematic view showing the structure of the inside of the capsule after the liquid sample is collected in the fourth embodiment of the present invention;
图18是本发明胶囊收集检测装置的结构示意图；Figure 18 is a schematic view showing the structure of the capsule collecting and detecting device of the present invention;
图19是本发明金属探测器的结构示意图；Figure 19 is a schematic structural view of a metal detector of the present invention;
图20是本发明金属探测器的***结构框图。Figure 20 is a block diagram showing the system structure of the metal detector of the present invention.
其中，1.外胶囊体；     2.外胶囊帽；Among them, 1. outer capsule body; 2. outer capsule cap;
      3.锁合结构；     4.肠溶包衣；3. Locking structure; 4. Enteric coating;
      5.胶囊壳底盖；   6.胶囊壳；5. Capsule shell bottom cover; 6. Capsule shell;
      7.液体流动通道； 8.活塞；7. Liquid flow path; 8. Piston;
      9.第一分腔；     10.第二分腔；9. The first sub-cavity; 10. the second sub-cavity;
      11.可溶体；      12.弹簧；11. soluble body; 12. spring;
      13.联动件；      14.活塞底座；13. Linkage; 14. Piston base;
      15.亲水性纤维；  16.样本采集启动组件；15. Hydrophilic fiber; 16. Sample collection starter component;
      17.液体样本；    18.微型控制器；17. Liquid sample; 18. Microcontroller;
      19.天线；        20.图像传感器；19. an antenna; 20. an image sensor;
      21.pH传感器；    22.温度传感器；21. pH sensor; 22. temperature sensor;
      23.湿度探测器；  24.压力传感器；23. Humidity detector; 24. Pressure sensor;
      25.容器；        26.密封腔；25. container; 26. sealed cavity;
      27.密封盒；      28.第一线圈；27. a sealed box; 28. a first coil;
      29.第二线圈；    30.磁体。29. Second coil; 30. Magnet.
具体实施方式detailed description
以下参照附图及实施例对本发明的一种胃肠道微生物采集胶囊及采集 ***进行技术说明。A gastrointestinal microbial collection capsule and collection system of the present invention will now be described with reference to the accompanying drawings and embodiments.
实施例1Example 1
图1-5描述的是胃肠道微生物采集胶囊的第一种结构。Figures 1-5 depict the first structure of a gastrointestinal microbial collection capsule.
外胶囊体1和外胶囊帽2构成了整个采集胶囊最外层的外壳，外胶囊体1与外胶囊帽2首先通过锁合结构3锁合。锁合之后的外胶囊体1与外胶囊帽2的表面被涂装一层或多层肠溶包衣4以达到靶向溶解的功能。在已生产的样机中，外胶囊体1与外胶囊帽2采用苏州胶囊(Capsugel)所生产的AAA DBcaps(内径11.39mm，胶囊体长16.31mm，胶囊帽长14.84mm)。实验证明，未涂抹肠溶包衣4的AAA DBcaps在37度温水中，2分钟(±0.2分钟，N＝10)内会迅速溶解。在已生产的样机中，肠溶包衣4采用基于赢创公司(Evonik)所生产的Eudragit L100-55的复合空肠靶向肠溶材料。其制备方法如下：The outer capsule body 1 and the outer capsule cap 2 constitute the outer casing of the entire outermost collection capsule, and the outer capsule body 1 and the outer capsule cap 2 are first locked by the locking structure 3. The outer capsule body 1 and the outer capsule cap 2 after the closure are coated with one or more layers of the enteric coating 4 to achieve a targeted dissolution function. In the prototype produced, the outer capsule body 1 and the outer capsule cap 2 were made of AAA DBcaps (inner diameter 11.39 mm, capsule length 16.31 mm, capsule cap length 14.84 mm) produced by Suzhou Capsule (Capsugel). Experiments have shown that AAA DBcaps without application of enteric coating 4 dissolve rapidly in 37 degrees warm water for 2 minutes (± 0.2 minutes, N = 10). In the prototype that has been produced, the enteric coating 4 is a composite jejunal targeting enteric material based on Eudragit L100-55 produced by Evonik. The preparation method is as follows:
按照以下比例制备液体涂装试剂：Prepare liquid coating reagents in the following proportions:
EUDRAGIT L100-55，9.0g；EUDRAGIT L100-55, 9.0g;
polyethylene glycol(PEG)400，1.4g；Polyethylene glycol (PEG) 400, 1.4g;
Tween 80，0.1g；Tween 80, 0.1g;
丙酮(Acetone)，38ml；Acetone, 38ml;
无水药用酒精(Isopropyl alcohol)，57ml；Isopropyl alcohol, 57ml;
蒸馏水，5ml。Distilled water, 5ml.
在室温环境下搅动均匀后，将锁合后的外胶囊帽2浸入以上所述涂装试剂中15秒，取出后在50摄氏度烘培箱中烘培20分钟。如此涂装-烘培步骤重复10次后，再将外胶囊体1按照同样步骤涂装-烘培10次。After the agitation was uniform at room temperature, the closed outer capsule cap 2 was immersed in the above-mentioned coating reagent for 15 seconds, taken out and baked in a baking oven at 50 degrees Celsius for 20 minutes. After the coating-bake step was repeated 10 times, the outer capsule 1 was coated and baked 10 times in the same manner.
样本采集启动组件16内部为自发性采集及分离装置，胶囊壳6主体底部与胶囊壳底盖5通过内外螺纹相旋合，使胶囊壳6底部完全密封。胶囊壳6的内部为空心结构的胶囊腔。胶囊壳6的侧壁有四个穿透胶囊壳壁的小孔，即为所述液体流动通道7的优先实现方式。所述胶囊壳底盖5和胶囊壳6设计简单，在已小规模生产的样机中，均由精密机床加工PEEK材料制成。在量产阶段，所述胶囊壳底盖5和胶囊壳6亦可用压模方法制作。The inside of the sample collection and starting assembly 16 is a spontaneous collecting and separating device. The bottom of the main body of the capsule shell 6 is screwed to the capsule bottom cover 5 by internal and external threads, so that the bottom of the capsule shell 6 is completely sealed. The interior of the capsule shell 6 is a capsule chamber of hollow structure. The side wall of the capsule shell 6 has four apertures penetrating the capsule shell wall, which is a preferred implementation of the liquid flow channel 7. The capsule shell bottom cover 5 and the capsule shell 6 are simple in design, and are manufactured by a precision machine tool PEEK material in a prototype that has been produced on a small scale. In the mass production stage, the capsule shell bottom cover 5 and the capsule shell 6 can also be produced by a compression molding method.
活塞8位于所述胶囊腔内液体流动通道7的上侧，将胶囊腔进一步分隔为第一分腔9与第二分腔10，并隔离两个分腔之间的液体流动。在已生产的样机中，活塞8采用BD公司所生产的Luer-Lok3mL针管内的活塞元件。The piston 8 is located on the upper side of the liquid flow passage 7 in the capsule chamber, further separating the capsule chamber into a first sub-chamber 9 and a second sub-chamber 10, and isolating the liquid flow between the two sub-chambers. In the prototype that has been produced, the piston 8 uses a piston element in a Luer-Lok 3 mL needle tube manufactured by BD Corporation.
样本分离装置中可溶体11为圆盘形糖片，弹簧12为高储能状态下的压缩弹簧，联动件13为平头螺丝；所述活塞8套入活塞底座14固定之后，联动件13依次穿过可溶体11中心的钻孔、胶囊壳顶部的小孔、高储能状态下的压缩弹簧之后，与活塞底座14旋合，经由可溶体11的结构承压力和压缩弹簧的储能，固定所述活塞8于所述胶囊腔内液体流动通道7上侧的一个初始 位置。在已生产的样机中，作为可溶体11的圆盘形糖片为压缩糖片(直径11mm，高4mm)；所述压缩弹簧采用力司百灵(Lee Springs)生产的LC032D01S(直径7.6mm，自由高度11.125mm，完全压缩后高度4.3mm)；作为联动件13的平头螺丝为不锈钢美制螺丝(#2-56，1/2英寸)；活塞底座14在已小规模生产的样机中，由精密机床加工PEEK材料制成；在量产阶段，所述活塞底座14亦可用压模方法制作。体外实验证明，未涂抹肠溶包衣4的可溶体11糖片在37度温水中，平均在10分钟内(±0.7分钟，N＝10)溶解。In the sample separation device, the soluble body 11 is a disc-shaped sugar piece, the spring 12 is a compression spring in a high energy storage state, and the linkage 13 is a flat head screw; after the piston 8 is inserted into the piston base 14 and fixed, the linkage 13 is sequentially worn. After drilling through the center of the soluble body 11, the small hole at the top of the capsule shell, and the compression spring in the high energy storage state, the piston base 14 is screwed, and the structural bearing pressure of the soluble body 11 and the energy storage of the compression spring are fixed. The piston 8 is in an initial position on the upper side of the liquid flow path 7 in the capsule chamber. In the prototype produced, the disc-shaped syrup as the soluble body 11 is a compressed syrup (diameter 11 mm, height 4 mm); the compression spring is made of Lee Springs LC032D01S (diameter 7.6 mm, free The height is 11.125mm, the height is 4.3mm after full compression; the flat head screw as the linkage 13 is stainless steel American screw (#2-56, 1/2 inch); the piston base 14 is in the prototype of small scale production, by precision machine tool The PEEK material is processed; in the mass production stage, the piston base 14 can also be fabricated by a compression molding method. In vitro experiments showed that the soluble 11 sugar tablets which were not coated with the enteric coating 4 were dissolved in 37 degrees of warm water on average within 10 minutes (±0.7 minutes, N=10).
整机组装的步骤具体如下：The steps of assembly of the whole machine are as follows:
首先，将活塞8套入活塞底座14，再与压缩弹簧先后从胶囊壳6底部置入胶囊内腔；然后从胶囊壳6底部将活塞8向上推动，克服压缩弹簧的弹力，将活塞8置入其初始位置；之后，联动件13穿过可溶体11中心的钻孔和胶囊壳6顶部的小孔，与高储能状态(压缩状态)下的压缩弹簧之后，与活塞底座14旋合，经由可溶体11的结构承压力和压缩弹簧的储能，固定所述活塞8于所述胶囊腔内液体流动通道7上侧的初始位置；之后，将少量亲水性纤维15置入胶囊壳底盖5，并将胶囊壳底盖5与胶囊壳6旋合，使亲水性纤维15处于第二分腔10内；然后，将组装好的组件置入外胶囊体1内，再将外胶囊帽2与外胶囊体1锁合；最后按照所述涂装方法，涂装肠溶包衣4于外胶囊表面并烘培完毕，形成一个完整的胃肠道微生物采集胶囊。First, the piston 8 is inserted into the piston base 14, and then inserted into the capsule cavity from the bottom of the capsule shell 6 with the compression spring; then the piston 8 is pushed upward from the bottom of the capsule shell 6, and the piston 8 is placed against the elastic force of the compression spring. Its initial position; after that, the linkage 13 passes through the bore of the center of the soluble body 11 and the small hole at the top of the capsule shell 6, and after the compression spring in the high energy storage state (compressed state), is screwed with the piston base 14 via The structural bearing pressure of the soluble body 11 and the energy storage of the compression spring fix the initial position of the piston 8 on the upper side of the liquid flow passage 7 in the capsule chamber; thereafter, a small amount of hydrophilic fibers 15 are placed in the capsule bottom cover 5, and the capsule shell bottom cover 5 and the capsule shell 6 are screwed together, so that the hydrophilic fiber 15 is placed in the second sub-chamber 10; then, the assembled component is placed in the outer capsule body 1, and then the outer capsule cap 2 is locked with the outer capsule body 1; finally, according to the coating method, the enteric coating 4 is coated on the surface of the outer capsule and baked to form a complete gastrointestinal microbial collection capsule.
本胃肠道微生物采集胶囊在使用者口服进入胃肠道之后，其样本采集启动组件16首先接触胃肠道内的液体；在已生产的样机中，样本采集启动组件16主体为十二指肠靶向包衣材料Eudragit L100-55。因此，样本采集启动组件16在胃内应保持结构完整，不溶解。The gastrointestinal microbial collection capsule is first contacted with the liquid in the gastrointestinal tract after the user enters the gastrointestinal tract orally; in the prototype that has been produced, the sample collection activation component 16 is a duodenum target. To the coating material Eudragit L100-55. Therefore, the sample collection activation assembly 16 should remain structurally intact and insoluble in the stomach.
如图2所示，胶囊进入肠道后，样本采集启动组件16发生溶解。胶囊周边的肠液沿穿透胶囊壳壁的液体流动通道7，依靠其自身重力，肠道蠕动，还有亲水性纤维15的吸力，流入第二分腔10内，并在吸附固定在亲水性纤维15表面。As shown in Figure 2, after the capsule enters the intestine, the sample collection activation assembly 16 dissolves. The intestinal fluid surrounding the capsule passes through the liquid flow channel 7 penetrating the capsule shell wall, and flows into the second sub-chamber 10 by its own gravity, intestinal peristalsis, and suction of the hydrophilic fiber 15, and is fixed in the hydrophilicity by adsorption. The surface of the fiber 15 is.
如图3所示，样本分离装置中的可溶体11溶化，其结构崩解导致压缩弹簧施放出其储能，由高储能形态变化为低储能形态时释放的力移动活塞8的位置至液体流动通道7和胶囊壳底盖5之间，从而在第二分腔10内封闭一定量的液体样本17，即肠液。As shown in FIG. 3, the soluble body 11 in the sample separation device is melted, and its structural disintegration causes the compression spring to exert its energy storage, and the force released when the high energy storage form changes to the low energy storage form moves the position of the piston 8 to Between the liquid flow channel 7 and the capsule bottom cover 5, a certain amount of liquid sample 17, i.e., intestinal fluid, is enclosed in the second sub-chamber 10.
如图4所示，胃肠道微生物采集胶囊排出体外后，拧下胶囊壳底盖5完成拆解。胶囊壳6内的亲水性纤维15及附着在上的肠液样本可轻易从中取出，用于实验室内的生化检测，如16s rRNA检测。As shown in Fig. 4, after the gastrointestinal microbial collection capsule is discharged from the body, the capsule bottom cover 5 is unscrewed to complete the disassembly. The hydrophilic fibers 15 in the capsule shell 6 and the intestinal fluid sample attached thereto can be easily taken out for biochemical detection in the laboratory, such as 16s rRNA detection.
如图5所示，胃肠道微生物采集胶囊如若长期滞留胃肠道时，所述胶囊壳6、胶囊壳底盖5、活塞底座14的材料可在胃肠道内缓慢降解，分解为数个 直径较小的结构，便于其通过胃肠道内狭窄处进而被排出体外，使胶囊使用者避免承受胃镜或开腹手术的风险。所述胶囊壳6、胶囊壳底盖5、活塞底座14的材料可采用生物可吸收材质(bioabsorbable material)，如生物可吸收聚对二氧六环酮(bioabsorbable polydioxanone)。生物可吸收聚对二氧六环酮为一种新型合成材料，又因其结构坚固，已开始被用于制成治疗食管狭窄症状的可降解支架，在植入试管后数周缓慢降解(Dhar，et al.”Biodegradable stent or balloon dilatation for benignAs shown in FIG. 5, if the gastrointestinal microbial collecting capsule is retained in the gastrointestinal tract for a long time, the material of the capsule shell 6, the capsule shell bottom cover 5, and the piston base 14 can be slowly degraded in the gastrointestinal tract and decomposed into several diameters. The small structure facilitates passage through the stenosis in the gastrointestinal tract and is thereby excreted, so that the capsule user avoids the risk of endoscopic or open surgery. The material of the capsule shell 6, the capsule shell bottom cover 5, and the piston base 14 may be a bioabsorbable material such as bioabsorbable polydioxanone. Bioabsorbable poly(dioxa) is a new synthetic material, and because of its robust structure, it has been used as a degradable scaffold for the treatment of esophageal stricture. It degrades slowly after several weeks of implantation (Dhar , et al."Biodegradable stent or balloon dilatation for benign
oesophageal stricture：Pilot randomised controlled trial”，W J.Gastroenterol，Vol.20，No.48，2014)。Oesophageal stricture: Pilot randomised controlled trial", W J. Gastroenterol, Vol. 20, No. 48, 2014).
实施例2Example 2
图6-9中描述的是胃肠道微生物采集胶囊的第二种结构。与实施例1的不同之处在于，弹簧12位于第二分腔10内，并且处于拉伸状态。当可溶体11溶解后，弹簧12的储能释放并收缩，带动活塞8移动至液体流动通道7和胶囊壳底盖5之间，封闭一定量的液体样本17。Depicted in Figures 6-9 is a second configuration of a gastrointestinal microbial collection capsule. The difference from Embodiment 1 is that the spring 12 is located in the second sub-chamber 10 and is in a stretched state. When the soluble body 11 is dissolved, the stored energy of the spring 12 is released and contracted, and the piston 8 is moved between the liquid flow path 7 and the capsule bottom cover 5 to close a certain amount of the liquid sample 17.
实施例3Example 3
图10-14中描述的是胃肠道微生物采集胶囊的第三种结构。与实施例1相比，本实施例的一个采集胶囊中包含了两套自发性采集及分离装置，两套采集及分离装置中的可溶体11选用不同的材质，因而其溶解时间存在差别，故可以在胃肠道的不同位置分别提取消化液样本。Depicted in Figures 10-14 is a third configuration of a gastrointestinal microbial collection capsule. Compared with the first embodiment, one collection capsule of the embodiment includes two sets of spontaneous collection and separation devices, and the soluble body 11 of the two collection and separation devices is made of different materials, so that the dissolution time is different, so Digestion samples can be taken separately at different locations in the gastrointestinal tract.
实施例4Example 4
样本分离装置中的可溶体11可为普通的糖块涂抹一种肠溶包衣材料(如Eudragit L100)，所述样本采集启动组件16可为标准的明胶胶囊涂抹另一种肠溶包衣材料(如Eudragit S100)。根据Eudragit官网，S100适用于在结肠内分解；由这种搭配实现的所述胃肠道微生物采集胶囊在使用者口服后，在胃内和十二指肠内，样本采集启动组件16保持结构完整，液体流动通道7保持关闭，此段的胃肠液无法经由液体流动通道7流入第二分腔10；在稍后的空肠内，样本采集启动组件16迅速溶解，导致液体流动通道7打开，空肠的液体经由液体流动通道7进入所述第二分腔10内；在更稍后的结肠内，所述样本分离装置迅速溶解，进而导致所述弹簧12释放其势能，推动所述活塞8移动并封闭所述液体流动通道7。所述第二分腔10内的肠液样本则与外界隔离，因此其成分，例如但不限于微生物和化合物成分，代表空肠至结肠段的肠液成分。The soluble body 11 in the sample separation device can be coated with an enteric coating material (such as Eudragit L100) for a common candy piece, and the sample collection starter assembly 16 can be applied to another enteric coating material for standard gelatin capsules. (eg Eudragit S100). According to Eudragit's official website, S100 is suitable for decomposition in the colon; the gastrointestinal microbial collection capsules achieved by this combination are kept intact in the stomach and duodenum after oral administration by the user. The liquid flow channel 7 remains closed, and the gastrointestinal fluid of this segment cannot flow into the second sub-chamber 10 via the liquid flow channel 7; in a later jejunum, the sample collection starter assembly 16 dissolves rapidly, causing the liquid flow channel 7 to open, the jejunum The liquid enters the second sub-chamber 10 via the liquid flow channel 7; in a later colon, the sample separation device dissolves rapidly, thereby causing the spring 12 to release its potential energy, pushing the piston 8 to move and The liquid flow path 7 is closed. The intestinal fluid sample in the second sub-chamber 10 is isolated from the outside world, and thus its components, such as, but not limited to, microorganisms and compound components, represent intestinal fluid components from the jejunum to the colon segment.
实施例5Example 5
样本分离装置中的可溶体11可为普通的糖块，所述样本采集启动组件16可从设计中删除掉，由这种搭配实现的所述胃肠道微生物采集胶囊的液体 流动通道7初始即为打开状态，在使用者口服进入胃内即刻吸收胃液；所述样本分离装置迅速在胃内溶解，进而导致所述弹簧12释放其势能，推动所述活塞8移动并封闭所述液体流动通道7。所述第二分腔10内的胃液样本则与外界隔离，因此其成分代表胃液成分。The soluble body 11 in the sample separation device can be a common candy piece, and the sample collection and activation assembly 16 can be removed from the design, and the liquid flow channel 7 of the gastrointestinal microbial collection capsule realized by the combination is initially In the open state, the gastric juice is immediately absorbed into the stomach by the user; the sample separation device rapidly dissolves in the stomach, thereby causing the spring 12 to release its potential energy, pushing the piston 8 to move and closing the liquid flow channel 7 . The gastric juice sample in the second sub-chamber 10 is isolated from the outside, so its composition represents the gastric juice component.
实施例6Example 6
图15-17中描述的是胃肠道微生物采集胶囊的第四种结构。与实施例1相比，胶囊中还设有检测***，检测***以一个微型控制器18为主控制单元，外部连接多种传感器，天线19和磁体30。传感器是一个或多个微型传感器，包括但不限于，湿度，压强，pH，温度，和图像传感器。所述微型传感器同时检测胶囊所处胃肠道区段的生理情况和胃肠液采集及分离装置的状态，并输入探测信号至胶囊内置的微型控制器18。所述微型控制器18将收集到的信号通过胶囊内置的微型天线传输至体外。胶囊可藉由一个体外的磁控平台根据传感器的信号反馈控制磁体30进而控制胶囊在胃肠道内的固定和移动。Depicted in Figures 15-17 is a fourth configuration of a gastrointestinal microbial collection capsule. Compared with the first embodiment, the capsule is further provided with a detection system. The detection system has a microcontroller 18 as a main control unit, and externally connects various sensors, an antenna 19 and a magnet 30. The sensor is one or more miniature sensors including, but not limited to, humidity, pressure, pH, temperature, and image sensors. The microsensor simultaneously detects the physiological condition of the gastrointestinal tract section of the capsule and the state of the gastrointestinal fluid collection and separation device, and inputs a detection signal to the microcontroller 18 built into the capsule. The microcontroller 18 transmits the collected signals to the outside of the body through a miniature antenna built into the capsule. The capsule can control the magnet 30 based on the signal feedback of the sensor by an external magnetic control platform to control the fixation and movement of the capsule in the gastrointestinal tract.
实施例7Example 7
图18为胶囊收集检测装置的结构示意图。胶囊收集检测装置的结构分为两部分：包括位于顶部的桶状容器25和位于底部的密封腔26，密封腔26内置金属探测器。此胶囊收集检测装置可以整体放入一个坐式马桶内，方便使用者在口服胃肠液采集胶囊后的数天内使用排便。因每一位使用者的胃肠动力情况不同，胶囊通过胃肠道排出体外的时间亦不同；同时，胶囊因体积较小，在随粪便排出体外后，较难为使用者肉眼观察发现。胶囊收集检测装置中的金属探测器可以自动检测到每次排便后胶囊是否排出体外：当所述胶囊停留在体内时，距离金属检测器较远，所述金属探测器产生的信号变化较小，蜂鸣器不会被触发启动；当胶囊由***排出体外后掉入所述容器25，接近金属检测器，金属探测器产生的信号变化明显；信号变化启动蜂鸣器，通知使用者胶囊已排出体外。Figure 18 is a schematic view showing the structure of a capsule collection detecting device. The structure of the capsule collection detecting device is divided into two parts: a barrel container 25 at the top and a sealing chamber 26 at the bottom, and a sealed metal chamber is built in the sealing chamber 26. The capsule collection and detection device can be placed in a sitting toilet as a whole, so that the user can use the defecation within a few days after the oral gastrointestinal fluid collection capsule. Because each user's gastrointestinal motility is different, the time for capsules to be excreted through the gastrointestinal tract is different. At the same time, capsules are less likely to be visually observed by the user after being excreted with the feces. The metal detector in the capsule collection detecting device can automatically detect whether the capsule is excreted after each defecation: when the capsule stays in the body, it is far from the metal detector, and the signal generated by the metal detector changes little. The buzzer will not be triggered to start; when the capsule is discharged from the anus and then falls into the container 25, close to the metal detector, the signal generated by the metal detector changes significantly; the signal change activates the buzzer, notifying the user that the capsule has been discharged in vitro.
图19为密封腔26的横切面图，用以展示密封腔26的内部结构示意图。其中密封盒27内置有金属探测器和蜂鸣器等电子元件；第一线圈28和第二线圈29的两端也连入密封盒27内。密封腔26为隔水结构，胶囊收集检测装置被放入坐式马桶中，里面的电子元件也可以正常运作。19 is a cross-sectional view of the sealed chamber 26 for illustrating the internal structure of the sealed chamber 26. The sealed case 27 has built-in electronic components such as a metal detector and a buzzer; both ends of the first coil 28 and the second coil 29 are also connected to the sealed case 27. The sealing chamber 26 is a water-tight structure, and the capsule collecting and detecting device is placed in the sitting toilet, and the electronic components inside can also operate normally.
图20为本发明中所述胶囊收集检测装置的实现原理的框图说明。其中主控制器控制信号发射器产生一个穿过第一线圈28的电流，产生电磁感应，生成第一磁场；第一磁场经由电磁感应，穿过容器25和密封腔26的隔层，在隔层上方的胶囊内的金属零件中产生一个涡流。所述涡流再次经由电磁感应，产生第二磁场；第二磁场在第二线圈29内产生另一个涡流。信号接收 器接收到这个涡流，并将信号传输给主控制器。当肠液采集胶囊停留在体内时，距离金属检测器较远，胶囊内的涡流电流流量较小，进而，其产生的第二磁场和由第二磁场在第二线圈29内产生的电流流量较小。当胃肠液采集胶囊排出体外，停留在容器25内，距离金属检测器较近，胶囊内的涡流电流流量较大，进而，其产生的第二磁场和由第二磁场在第二线圈29内产生的电流流量较大。当信号接收器检测的电流流量较大时，主控制器启动蜂鸣器报警。本发明中所述的胶囊收集检测装置，因为其基本的电磁感应原理，不仅可以应用于检测本发明中所述的胃肠液采集胶囊，亦可以应用于收集及检测任何含有金属元件的胶囊排出体外，方便使用者寻找收集胶囊；并且，本发明中所述的胶囊收集检测装置的容器25底部为密封结构，所排出粪便及胶囊不会与周边环境所接触，其所携带的肠道菌群不会被周边环境中的微生态环境所污染，从而使由本发明中的胶囊所采集到的肠道菌群样本更加精准，具有代表性，能充足的满足临床及科研需要，具有广阔的应用前景。Figure 20 is a block diagram illustration showing the implementation principle of the capsule collection detecting device of the present invention. Wherein the main controller control signal transmitter generates a current through the first coil 28 to generate electromagnetic induction to generate a first magnetic field; the first magnetic field passes through the compartment of the container 25 and the sealed chamber 26 via electromagnetic induction, in the compartment A vortex is created in the metal part in the upper capsule. The eddy current again generates a second magnetic field via electromagnetic induction; the second magnetic field creates another eddy current within the second coil 29. The signal receiver receives this eddy current and transmits the signal to the main controller. When the intestinal fluid collection capsule stays in the body, it is far from the metal detector, and the flow of the eddy current in the capsule is small, and further, the second magnetic field generated by the capsule and the second magnetic field generated by the second magnetic field are smaller. . When the gastrointestinal fluid collection capsule is discharged outside the body, staying in the container 25, closer to the metal detector, the eddy current flow in the capsule is larger, and further, the second magnetic field generated by the second magnetic field and the second magnetic field are in the second coil 29. The resulting current flow is large. When the current flow detected by the signal receiver is large, the main controller starts the buzzer alarm. The capsule collection detecting device described in the present invention can be applied not only to the detection of the gastrointestinal fluid collection capsule described in the present invention, but also to the collection and detection of any capsule discharge containing metal components because of its basic electromagnetic induction principle. In vitro, it is convenient for the user to find the collection capsule; and the bottom of the container 25 of the capsule collection and detection device described in the present invention is a sealed structure, and the discharged feces and capsules are not in contact with the surrounding environment, and the intestinal flora carried by the capsule is carried out. It will not be polluted by the micro-ecological environment in the surrounding environment, so that the sample of intestinal flora collected by the capsules of the present invention is more accurate and representative, and can satisfy the clinical and scientific research needs, and has broad application prospects. .

Claims (21)

  1. 一种胃肠道微生物采集胶囊，包括一套及以上的自发性采集及分离装置，所述采集及分离装置包括胶囊壳(6)和胶囊壳底盖(5)，所述胶囊壳(6)和胶囊壳底盖(5)内形成胶囊腔，其特征在于：所述胶囊壳(6)上至少形成一个液体流动通道(7)；所述胶囊壳(6)内设有样本分离装置，样本分离装置包括位于液体流动通道(7)一侧的活塞(8)，位于活塞(8)与胶囊壳(6)或胶囊壳底盖(5)之间的弹簧(12)以及连接在活塞(8)上的限位装置。A gastrointestinal microbial collection capsule comprising one or more sets of spontaneous collection and separation devices, the collection and separation device comprising a capsule shell (6) and a capsule shell bottom cover (5), the capsule shell (6) Forming a capsule cavity in the capsule bottom cover (5), characterized in that: at least one liquid flow channel (7) is formed on the capsule shell (6); a sample separation device is arranged in the capsule shell (6), the sample The separating device comprises a piston (8) on one side of the liquid flow channel (7), a spring (12) between the piston (8) and the capsule shell (6) or the capsule bottom cover (5) and a piston (8) The limit device on the).
  2. 根据权利要求1所述的一种胃肠道微生物采集胶囊，其特征在于：所述限位装置包括可溶体(11)以及贯穿可溶体(11)和胶囊壳(6)顶部通孔并与活塞(8)活动连接的联动件(13)。A gastrointestinal microbial collection capsule according to claim 1, wherein said stopper means comprises a soluble body (11) and a through hole passing through the top of the soluble body (11) and the capsule shell (6) and the piston (8) Linkage of the active connection (13).
  3. 根据权利要求2所述的一种胃肠道微生物采集胶囊，其特征在于：所述联动件(13)为螺丝或封闭的牵引带/绳。A gastrointestinal microbial collection capsule according to claim 2, characterized in that the linkage (13) is a screw or a closed traction belt/rope.
  4. 根据权利要求1所述的一种胃肠道微生物采集胶囊，其特征在于：所述活塞(8)的底部设有活塞底座(14)，所述限位装置连接在活塞底座(14)上。A gastrointestinal microbial collection capsule according to claim 1, characterized in that the bottom of the piston (8) is provided with a piston base (14), and the limiting device is connected to the piston base (14).
  5. 根据权利要求1所述的一种胃肠道微生物采集胶囊，其特征在于：所述胶囊壳(6)和胶囊壳底盖(5)为***式连接或通过螺纹连接。A gastrointestinal microbial collection capsule according to claim 1, characterized in that the capsule shell (6) and the capsule shell bottom cover (5) are plug-in connections or by screw connections.
  6. 根据权利要求1所述的一种胃肠道微生物采集胶囊，其特征在于：所述弹簧(12)为螺旋弹簧，拉伸弹簧或压缩弹簧。A gastrointestinal microbial collection capsule according to claim 1, wherein the spring (12) is a coil spring, a tension spring or a compression spring.
  7. 根据权利要求1所述的一种胃肠道微生物采集胶囊，其特征在于：在形成液体流动通道(7)一侧的胶囊腔内设有亲水性纤维物。A gastrointestinal microbial collection capsule according to claim 1, wherein a hydrophilic fibrous material is provided in the capsule cavity on the side where the liquid flow path (7) is formed.
  8. 根据权利要求1所述的一种胃肠道微生物采集胶囊，其特征在于：所述弹簧(12)或联动件(13)为金属材质。The gastrointestinal microbial collection capsule according to claim 1, characterized in that the spring (12) or the linkage (13) is made of metal.
  9. 根据权利要求1所述的一种胃肠道微生物采集胶囊，其特征在于：所述胶囊壳(6)、胶囊壳底盖(5)和活塞底座(14)的材质全部或局部采用生物可吸收材质。The gastrointestinal microbial collection capsule according to claim 1, characterized in that the material of the capsule shell (6), the capsule bottom cover (5) and the piston base (14) are all or partially bioabsorbable. Material.
  10. 根据权利要求1所述的一种胃肠道微生物采集胶囊，其特征在于：所述采集及分离装置的外部包覆有样本采集启动组件(16)，样本采集启动组件(16)包括外胶囊体(1)和肠溶包衣(4)。A gastrointestinal microbial collection capsule according to claim 1, wherein the exterior of the collection and separation device is coated with a sample collection activation component (16), and the sample collection activation component (16) comprises an outer capsule body. (1) and enteric coating (4).
  11. 根据权利要求10所述的一种胃肠道微生物采集胶囊，其特征在于：所述外胶囊体(1)与胶囊壳底盖(5)为***式连接或通过螺纹连接。A gastrointestinal microbial collection capsule according to claim 10, characterized in that the outer capsule body (1) is in a plug-in connection or a screw-on connection to the capsule shell bottom cover (5).
  12. 根据权利要求10所述的一种胃肠道微生物采集胶囊，其特征在于：所述样本采集启动组件(16)还包括设置在外胶囊体(1)上的外胶囊帽(2)，所述外胶囊体(1)与外胶囊帽(2)为***式连接或通过螺纹连接。A gastrointestinal microbial collection capsule according to claim 10, wherein said sample collection activation assembly (16) further comprises an outer capsule cap (2) disposed on the outer capsule body (1), said outer The capsule body (1) and the outer capsule cap (2) are either plug-in or threaded.
  13. 根据权利要求10所述的一种胃肠道微生物采集胶囊，其特征在于：所述样本分离装置和样本采集启动组件(16)的溶化速率与材料、胃肠道的pH值，温度和胃动力有关。A gastrointestinal microbial collection capsule according to claim 10, characterized in that the dissolution rate of the sample separation device and the sample collection starter assembly (16) and the material, the pH of the gastrointestinal tract, the temperature and the gastric motility related.
  14. 根据权利要求1所述的一种胃肠道微生物采集胶囊，其特征在于：包括两套采集及分离装置，两套采集及分离装置共用胶囊壳底盖(5)。A gastrointestinal microbial collection capsule according to claim 1, comprising two sets of collecting and separating devices, and the two sets of collecting and separating devices share a capsule bottom cover (5).
  15. 根据权利要求1-13任一所述的一种胃肠道微生物采集胶囊，其特征在于：所述采集胶囊还包括检测***，所述检测***包括微型控制器(18)以及与微型控制器(18)相连的天线(19)和传感器。A gastrointestinal microbial collection capsule according to any of claims 1-13, wherein said collection capsule further comprises a detection system comprising a microcontroller (18) and a microcontroller ( 18) Connected antenna (19) and sensor.
  16. 根据权利要求15所述的一种胃肠道微生物采集胶囊，其特征在于：所述检测***还包括磁体(30)。A gastrointestinal microbial collection capsule according to claim 15 wherein said detection system further comprises a magnet (30).
  17. 根据权利要求15所述的一种胃肠道微生物采集胶囊，其特征在于：所述传感器包括图像传感器(20)、pH传感器(21)、温度传感器(22)、湿度探测器(23)和压力传感器(24)。A gastrointestinal microbial collection capsule according to claim 15, wherein said sensor comprises an image sensor (20), a pH sensor (21), a temperature sensor (22), a humidity detector (23) and a pressure Sensor (24).
  18. 根据权利要求17所述的一种胃肠道微生物采集胶囊，其特征在于：所述湿度探测器(23)和压力传感器(24)穿过胶囊壳底盖(5)并置于形成液体流动通道(7)一侧的胶囊腔内。A gastrointestinal microbial collection capsule according to claim 17, wherein said humidity detector (23) and pressure sensor (24) pass through the capsule bottom cover (5) and are placed in a liquid flow path. (7) Inside the capsule cavity on one side.
  19. 一种胃肠道微生物采集***，其特征在于：包括至少一个胃肠道微生物采集胶囊和胶囊收集检测装置。A gastrointestinal microbial collection system comprising at least one gastrointestinal microbial collection capsule and a capsule collection and detection device.
  20. 根据权利要求19所述的一种胃肠道微生物采集***，其特征在于：所述胶囊收集检测装置包括容器(25)和金属探测器。A gastrointestinal microbial collection system according to claim 19, wherein said capsule collection detecting means comprises a container (25) and a metal detector.
  21. 根据权利要求20所述的一种胃肠道微生物采集***，其特征在于：所述金属探测器置于容器(25)底部的密封腔(26)内；金属探测器包括第一线圈(28)和第二线圈(29)，第一线圈(28)和第二线圈(29)分别与密封盒(27)中的信号发射器和信号接收器相连；信号发射器和信号接收器均与主控制器相连，主控制器连接蜂鸣器。A gastrointestinal microbial collection system according to claim 20, wherein said metal detector is placed in a sealed chamber (26) at the bottom of the container (25); the metal detector comprises a first coil (28) And a second coil (29), the first coil (28) and the second coil (29) are respectively connected to the signal transmitter and the signal receiver in the sealed box (27); the signal transmitter and the signal receiver are both controlled by the main control The device is connected and the main controller is connected to the buzzer.
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