JP6739782B2 - Pretreatment kit for gene analysis, nucleic acid analysis chip, gene analysis system - Google Patents

Description

The present invention relates to a pretreatment kit for gene analysis for extracting a biological substance from a sample collected from any one of a human body, excrement and soil, and a nucleic acid analysis for analyzing a target nucleic acid to be detected from the sample. The present invention relates to a chip and a gene analysis system.

Conventionally, medical examinations have been performed exclusively in specialized medical institutions such as hospitals, but with the advent of a super-aging society in Japan, the burden of examinations at medical institutions is becoming serious. For this reason, tests that require a dedicated device such as X-ray photography and electrocardiogram measurement, and tests that require a syringe such as blood tests continue to be performed at medical institutions, while the user can easily perform tests. It is also necessary to consider that it is possible to reduce the burden of medical examinations at medical institutions by using self-examinations performed at home. If it is possible to establish such self-examination at home, it is possible to enhance therapeutic and preventive medical care even in developing countries where necessary medical services are insufficient.

In such a situation, in order to enable the next-generation self-examination, in addition to downsizing, general-purpose, and low cost of the inspection device, it can be realized even by a user who has no specialized knowledge about medical care. Some degree of ease of handling is required.

In response to such social needs, in recent years, gene analysis using a nucleic acid analysis chip (DNA chip) has been realized. Nucleic acid analysis chips are used in various fields such as medical fields, chemical fields, drug discovery fields, clinical test fields, food fields, agricultural fields, engineering fields, forensic fields, and criminal forensics fields. For example, medical fields In general, medical examinations for various diseases such as cancer are generally performed by tests using biochemical samples such as blood.

A nucleic acid analysis chip is a device in which nucleic acid probes are immobilized at high density on a glass or silicon substrate. When highly accurate gene analysis is performed using a nucleic acid analysis chip, gene amplification is required in advance. When the nucleic acid amplified in this way has a complementary base sequence with the nucleic acid probe on the substrate in the next hybridization step, it binds to the nucleic acid probe. Next, in a washing step, the nucleic acid analysis chip after the hybridization reaction is washed with a predetermined washing solution. As a result, all DNA samples that have not bound to the nucleic acid probe on the substrate are washed away.

Subsequently, the presence and/or amount of the target nucleic acid is detected by scanning the hybridization signal from the washed nucleic acid analysis chip. In this scanning, laser light having a wavelength suitable for exciting the fluorescent substance is irradiated onto the substrate of the nucleic acid analysis chip and scanned. As a result, the luminescence amount of the nucleic acid bound to each spotted nucleic acid probe is measured, and the analysis process can be performed based on the measured luminescence amount.

For the nucleic acid analysis chip as described above, for example, a technique disclosed in Patent Document 1 is disclosed for the purpose of meeting the needs for self-examination performed at home. This Patent Document 1 discloses a nucleic acid analysis chip which can detect a reaction instantaneously, has a small-sized and portable analyzer configuration, and which stores a reaction reagent in advance and can dispose of it together with the reagent after analysis. Patent Document 2 also proposes a disposable paper-based microfluidic device for detecting and analyzing a sample in blood or urine collected from a subject.

JP, 2004-28589, A Special table 2014-529083 gazette

However, in the above-described conventional nucleic acid analysis chip, there is room for further improvement from the viewpoint of improving the accuracy of biochemical tests. In addition, when fixing a nucleic acid analysis chip to an analyzer and performing an enzymatic reaction or a biochemical reaction, it may be difficult to control the temperature of the nucleic acid analysis chip with high accuracy, and the desired reaction may not proceed sufficiently. there were.

Patent Document 1 proposes that a chip for nucleic acid analysis is provided with an adsorption groove, and the chip is adsorbed and fixed at a desired position by vacuum suction through the adsorption groove by a vacuum exhaust pump. However, when such a configuration is adopted, it becomes a big obstacle in downsizing the analyzer.

Therefore, the present invention has been devised in view of the above-mentioned problems, and an object of the present invention is to reduce the size of a testing device and make it more versatile in a nucleic acid analysis chip that enables next-generation self-checking. In addition to cost reduction, the ease of handling that can be realized even by users who do not have specialized knowledge about medical treatment is ensured, and the accuracy of biochemical tests can be improved, and nucleic acid analysis chips and gene analysis are also possible. The object of the present invention is to provide a pretreatment kit for gene analysis for extracting a biological material from a system and a sample collected from any one of a human body, excrement, and soil at a stage before the analysis.

The pretreatment kit for gene analysis according to the first invention is a pretreatment kit for gene analysis for extracting a biological substance from a sample collected from any one of a human body, excrement, and soil. In addition, the liquid is dipped in the granular body, and when the rod-shaped body having the collected matter attached to the tip is inserted, the collected matter is collected by bringing the tip into contact with the granular body and A collecting cartridge to be impregnated with the liquid, a discharging means for discharging the liquid sent from the collecting cartridge to the outside, and at least serum is separated from the liquid sent from the mounted collecting cartridge. And a pretreatment main body having the discharge means. The discharge means discharges the liquid having passed through the first filter to the outside, and collects the cartridge for collection and the pretreatment. When mounted on the main body, the container filled with the granular material and the first filter are provided with a mesh body through which the liquid can pass and a laminated body in which the film through which the liquid cannot pass is laminated. When the liquid is delivered from the collection cartridge, the film is formed with holes for passing the liquid to allow the liquid to pass therethrough and the granular body is held by the mesh body. And

Gene pre for analysis kit according to the second invention, in the first invention, the liquid is characterized bactericidal component, gene detection primer, and this formed by incorporating a polymerase enzyme.

A pretreatment kit for gene analysis according to a third invention is the pretreatment body according to the second invention, wherein the pretreatment main body further comprises a second filter for separating at least viruses and bacteria from the liquid that has passed through the first filter. However, the discharging means discharges the liquid having passed through the second filter to the outside.

A pretreatment kit for gene analysis according to a fourth invention is the pretreatment kit for gene analysis according to any one of the first to third inventions, wherein the collection cartridge is pre-biased in a direction of narrowing and the tip of the rod-shaped body is It is characterized in that it has an insertion port for insertion, the inside of the insertion port is filled with the granular material, and the liquid is immersed therein.

The pretreatment kit for gene analysis according to the fifth invention is the pretreatment kit for gene analysis according to the fourth invention, wherein the rod-shaped body has a protrusion having a root portion of the tip to which the sample is attached is protruded outward, and the protrusion is It is characterized in that it is locked in the insertion opening.

A pretreatment kit for gene analysis according to a sixth invention is the pretreatment kit for gene analysis according to any one of the first invention to the fifth invention, wherein the granular body is composed of any of metal, ceramics and resin, and the surface thereof is It is characterized in that any one of zeolite, emulsion gel, hydrophilic polymer and amino acid substance is formed.

According to the present invention having the above-described configuration, the user collects a sample from a human body, excrement, or soil with a rod-shaped body, and the sample is attached to the tip of the collecting cartridge in which the liquid is immersed. Insert the rod. Other than that, simply attach the collection cartridge to the pretreatment main body and connect the tip of the outlet of the pretreatment main body to the sample injection port of the nucleic acid analysis chip. Analysis will be performed.

Therefore, even a user who does not have specialized knowledge about medical treatment can perform gene analysis by himself/herself with an extremely simple operation.

Moreover, since the pretreatment kit for gene analysis, the nucleic acid analysis chip, and the chip measuring device are not complicated in device configuration, they can be downsized, and have a structure suitable for self-examination at home. In addition, since it can be provided at a low price, it can be purchased by an individual.

Furthermore, according to the present invention, nucleic acids can be extracted from collected samples with high efficiency, and serum, bacteria, and viruses are previously removed through a pretreatment kit for gene analysis in order to identify nucleic acids with high accuracy. Further, these operations can be performed very easily without any special skill or knowledge.

In addition, the washing liquid can be washed by flowing the washing liquid from the wash flow passage to the hybridization flow passage, and since the nucleic acid analysis chip can be used repeatedly, it has a very excellent cost performance. Therefore, this cleaning work can be performed very easily.

In addition, the accuracy of the biochemical test can be maintained at the same level as before, while simplifying the device configuration, improving the ease of handling, and improving the cost performance as described above. It becomes possible to realize the gene analysis of at home.

It is a figure which shows the system configuration of the gene analysis system to which this invention is applied. It is a figure for explaining the composition of the collection cartridge. It is a figure for demonstrating the detail of the laminated body comprised by the two-layered structure of a net-like body and a film. It is a figure for demonstrating the structure of the pre-processing main body. It is a figure for demonstrating the structure of the chip for nucleic acid analysis. It is a system configuration diagram of a chip measuring device. It is a figure which shows the block configuration of the control block in a chip measuring device. It is a figure for demonstrating the method of analyzing a gene using the gene analysis system to which this invention is applied. FIG. 3 is a diagram showing a state in which a collecting cartridge is mounted in a cartridge housing portion of the pretreatment main body. It is a figure which shows the state which passed the film about liquid and made it flow down to the separation part side in the main body for pretreatment. It is a figure which shows the external appearance of a case accommodation type gene analysis system. It is a development view of a case-accommodating gene analysis system.

Hereinafter, modes for carrying out a gene analysis system to which the present invention is applied will be described in detail with reference to the drawings.

FIG. 1 shows the system configuration of a gene analysis system 1 to which the present invention is applied. The gene analysis system 1 can communicate with the gene analysis pretreatment kit 2, a nucleic acid analysis chip (DNA chip) 3, a chip measuring device 4 on which the nucleic acid analysis chip 3 is mounted, and the chip measuring device 4. The mobile terminal 5 includes a portable terminal 5, a server 7 connected to the portable terminal 5 via a public communication network 6, and a central controller 8 connected to the public communication network 6.

The mobile terminal 5 is, for example, a mobile phone, a smartphone, a tablet type terminal, a wearable terminal, a laptop personal computer (PC), or the like, and is a device capable of communicating via the public communication network 6 based on at least a user's operation. is there. The mobile terminal 5 is a device that can be carried by the user at all times, but is not limited to this, and is a concept including any electronic device such as a desktop PC.

The mobile terminal 5 can download the examination application via the public communication network 6. Thus, the user can activate the examination app by operating the mobile terminal 5 to check the examination record of himself/herself or various suggestions for future health maintenance. In the following example, a case where a smartphone is applied to the mobile terminal 5 will be described as an example.

The public communication network 6 is an internet network or the like in which the mobile terminal 5, the server 7, and the central control device 8 are connected via a communication line. The public communication network 6 may be a so-called optical fiber communication network. The public communication network 6 is not limited to the wired communication network, but may be realized by a wireless communication network.

A predetermined database is built in the server 7. Information sent via the public communication network 6 is accumulated in this database. The server 7 also transmits the stored information to the mobile terminal 5 via the public communication network 6 based on the request from the mobile terminal 5.

The central controller 8 is composed of an electronic device such as a personal computer, accesses the server 7 via the public communication network 6, and analyzes the information accumulated therein. Further, the central control device 8 may be operated by an expert such as a doctor, or the information accumulated in the server 7 may be utilized. The knowledge obtained by the information analysis by the central controller 8 or the analysis result itself may be transmitted to the mobile terminal 5 via the public communication network 6. The mobile terminal 5 can display various information sent from the central control device 8 to the user via the examination application.

The gene analysis pretreatment kit 2 roughly includes a plunger 21, a collection cartridge 22, and a pretreatment main body 23.

The plunger 21 is inserted into the sampling cartridge 22 and is provided to push out the liquid contained therein. The plunger 21 has an inner cylinder portion 211 and a pusher 212. The inner tubular portion 211 is extended in the longitudinal direction, and a rubber portion 213 is provided at the extended end thereof. The pusher 212 is provided on the other end side of the plunger 21, which is different from the extension end on which the rubber portion 213 is provided, and presses the user's finger against the inner cylinder portion 211 to collect it. It is configured so that it can be inserted into the unit 22.

As shown in FIG. 2, the collection cartridge 22 has a container 220 filled with a plurality of particles 223. The granular body 223 is immersed in the liquid L. The sampling cartridge 22 further includes an inner wall 221 bulging inward, and a laminated body 26 provided on the bottom surface of the container 220.

The granular body 223 may be made of any material such as resin, ceramics, and metal. When the granular material 223 is made of metal, it may be made of die casting, and when it is made of resin, it may be made of polystyrene, for example. Further, in the granular body 223, these materials may be laminated in a two-layer structure, and for example, a resin layer may be coated on the outer shell of a metal core made of die casting.

The granular body 223 will be described by taking as an example the case of being composed of spherical beads, but the granular body 223 is not limited to this, and may be composed of any polyhedron such as a cube or a rectangular parallelepiped. Alternatively, they may be configured in a random three-dimensional shape. Further, the granular body 223 may be configured in a peculiar shape such as a hook shape.

The surface of the granular body 223 may be further coated with calcium phosphate. Through this calcium phosphate layer, it becomes possible to act so that the pH of the container 220 approaches neutral. The surface of the granular body 223 is coated with any one of zeolite, emulsion gel, hydrophilic polymer, and amino acid substance so that feces or solid matter as excrement is adsorbed to the granular body 223, It becomes possible to take extra things easily with a filter.

The liquid L is preliminarily injected into the container 220 filled with the granular material 223 having the above-described configuration. The components of this liquid may have the composition shown in Table 1 below, for example, if the collected material from which the genomic DNA as the biological substance is extracted is feces. Further, in the case of extracting RNA, the liquid may have a composition shown in Table 2. The volume of each component composition is expressed by weight% with respect to the total weight of the liquid L.

Here, the lysis buffer is a stabilizing substance for preventing the oxidation of feces, and consists of HCl, EDTA, NaCl, SDS and the like. The DNase buffer is a solution for preventing the degradation and inactivation of genomic DNA, and comprises DNase A (deoxyribonuclease) for inhibiting DNA degradation, sodium acetate containing EDTA, and the like. The DNase/RNase-treated water is water from which DNase, which is a DNA degrading enzyme, has been removed, and is composed of water from which a DNA degrading enzyme and an RNA degrading enzyme have been removed.

If the target sample is blood or urine, the composition may be configured as shown in Table 3 below.

Further, in the case of extracting RNA, the liquid may have a composition shown in Table 4.

Here, the adjustment buffer is a stabilizing substance for preventing blood coagulation, and is composed of EDTA, SDS and the like. The buffer solution is a solution for preventing the decomposition and inactivation of genomic DNA, and is composed of a mixture of citric acid and disodium hydrogen phosphate. The DNase/RNase-treated water is water from which DNAse, which is a DNA degrading enzyme, has been removed, and is composed of water from which a DNA degrading enzyme and an RNA degrading enzyme have been removed.

If the target sample is saliva, it may be configured with the composition shown in Table 5 below.

Further, in the case of extracting RNA, the liquid may have a composition shown in Table 6.

Here, the buffer solution is a solution for preventing the decomposition and inactivation of genomic DNA, and is composed of a mixture of citric acid and disodium hydrogenphosphate. The DNase/RNase-treated water is water from which DNAse, which is a DNA degrading enzyme, has been removed, and is composed of water from which a DNA degrading enzyme and an RNA degrading enzyme have been removed. The pronase solution is a solution for removing a protein called mucin contained in saliva, and is composed of lactose, hydroxypropyl cellulose, pronase and the like.

The inner wall 221 is made of an elastic body such as rubber and is elastically expandable and contractible in the radial direction of the container 220. The inner diameter of the inner wall 221 is gradually reduced from the upper end of the storage container 220 to the lower side, and the inner diameter is smallest in the middle stage. In the middle stage where the inner diameter is the smallest, an insertion port 229 surrounded by a protrusion 222 that further protrudes inward is provided. It is formed so that the inner diameter thereof gradually expands downward from the insertion port 229. As a result, the container 220 is divided into two chambers, the upper chamber 220a and the lower chamber 220b, with the insertion port 229 as a boundary via the inner wall 221.

The inner cylinder portion 211 of the plunger 21 described above can be inserted into the upper chamber 220a. The lower chamber 220b is filled with the granular material 223, and the liquid L is further injected. The granular material 223 and the liquid L are basically charged in the lower chamber 220b, but a part thereof may overflow into the upper chamber 220a.

The insertion port 229 formed by the inner wall 221 may be pre-biased in the direction in which the inner diameter is narrowed. That is, the insertion opening 229 may be pre-biased in the direction of the arrow in FIG.

By the way, the structure of the inner wall 221 is not limited to the above-described structure, and may not be a shape that bulges inward. That is, the inner wall 221 may be configured to have the same inner diameter without changing the inner diameter.

As shown in FIG. 3, the laminate 26 has a two-layer structure including a mesh body 224 and a film 225, and these layers are attached to each other.

The net-like body 224 is formed of, for example, a mesh structure or a net in which a warp yarn and a weft yarn are woven, and the mesh of the net is formed to have a diameter that allows the liquid L to pass therethrough. However, the mesh-like body 224 is required to have a mesh whose diameter is such that the above-mentioned granular body 223 cannot pass through. As a result, even if the liquid L passes through the mesh body 224, it is possible to prevent the granular body 223 from passing therethrough, and to hold the granular body 223.

The film 225 is made of, for example, a resin, and is made of a material such as polyimide, polyethylene, polypropylene, polyester, polyvinyl chloride, or polycarbonate. The film 225 has a function of preventing the passage of the liquid L as well as the granular material 223.

The mesh body 224 and the film 225 may be laminated by being adhered to each other, or may be integrated and laminated. Further, only the peripheral ends of the mesh body 224 and the film 225 may be attached to each other. Further, the reticulate body 224 and the film 225 are not limited to the case where they are laminated by being adhered to each other, and they may be separated from each other.

Such a laminated body 26 is attached to the lower end of the lower chamber 220b of the storage container 220. As a result, the laminated body 26 serves as the bottom of the container 220. The planar shape of the net-like body 224 and the film 225 that form the laminated body 26 corresponds to the planar view of the lower chamber 220b to which the net-like body 224 and the film 225 are attached.

As shown in FIG. 4, the pretreatment main body 23 has a cartridge housing portion 231 and a separating portion 233 extending downward from the cartridge housing portion 231. The separation unit 233 has a first filter 234 and a second filter 235 provided on the downstream side of the first filter 234, in other words, on the lower side. The lower end of the separating portion 233 is continuous with the discharge port 236, and the discharge port 236 is usually sealed with a cap 237. The pretreatment main body 23 may be made of any material such as glass, resin, metal, or ceramics.

The cartridge accommodating portion 231 is configured such that the periphery thereof is surrounded by the peripheral wall 232, and has a shape into which the sampling cartridge 22 can be inserted and mounted.

The separation portion 233 is configured such that the inner diameter gradually decreases downward, but the invention is not limited to this, and the inner diameters may all be the same. The separation part 233 is formed in a tubular shape that is continuous from the cartridge storage part 231 and can guide the liquid to the discharge port 236 provided at the lower end thereof.

A first filter 234 is provided in order in the separation unit 233 from above, and a second filter 235 is provided at a distance from the first filter 234 toward the lower side.

The first filter 234 is composed of a film capable of separating at least serum from the liquid L. That is, in the chamber R1 separated upward through the first filter 234 and the chamber R2 separated downward, the serum separated from the liquid L is retained in the chamber R1, and the liquid separated from the serum. It serves to transmit L to the room R2.

As the first filter 234, "Microza MF" manufactured by Asahi Kasei Chemicals Co., Ltd., "silicone hollow fiber" manufactured by Fuji Systems Co., Ltd., "Zaltoclear depth filter 290-C4" manufactured by Sarutrius Stedum Biotech, etc. should be used. May be. The first filter 234 is composed of a hollow fiber membrane, and separates the serum from the liquid L via the holes formed between the continuous tissues of the membrane.

The second filter 235 is composed of a film capable of separating at least viruses and bacteria from the liquid L. Specifically, the second filter 235 is composed of a membrane capable of separating various viruses such as Gram-positive cocci, MRSA, SARS, and influenza virus. That is, in the chamber R2 separated upward through the second filter 235 and the chamber R3 separated downward, the viruses and bacteria separated from the liquid L are retained in the chamber R2, and It plays a role of transmitting the separated liquid L to the chamber R3.

As the second filter 235, "Microza UF" manufactured by Asahi Kasei Chemicals Corporation, "Zaltoclear depth filter 290-F7H" manufactured by Sarutrius Stedum Biotech, or the like may be used. The configuration of the second filter 235 is not essential and may be omitted.

The discharge port 236 is continuous from the chamber R3 in the separation unit 233, and the liquid L from which viruses and microbes have been separated is delivered. Since the discharge port 236 is formed at the tip projecting downward in a tubular shape, it is possible to improve convenience when the liquid L is injected toward the nucleic acid analysis chip 3.

The cap 237 is usually attached to the discharge port 236 to seal it. When actually injecting the liquid L toward the nucleic acid analysis chip 3, the cap 237 is opened and the discharge port 236 is opened.

Incidentally, the nucleic acid analysis chip 3 is not limited to the case where the collection cartridge 22 and the pretreatment main body 23 are configured to be separated from each other, and these are configured to be integrated with each other. Good. Further, the configuration of the first filter 234 and the second filter 235 may be omitted in the pretreatment main body, and in such a case, at least only the means for discharging the liquid from the sampling cartridge 22 is mounted. Good. Specifically, the sampling cartridge 22 and the pretreatment main body 23 are integrally configured, and by omitting the configurations of the first filter 234 and the second filter 235, this is realized.

Next, the structure of the nucleic acid analysis chip 3 will be described. As shown in FIG. 5, the nucleic acid analysis chip 3 is connected to an air pump connection port 31, a wash channel 32 continuous from the air pump connection port 31, a sample injection port 33, and a sample injection port 33. The PCR flow path 34, the heating wire 35 provided close to the PCR flow path 34, the open/close switch 36 provided at the downstream end of the wash flow path 32, and the wash flow path 32 and the PCR flow path 34. A hybridization flow channel 37 provided on the further downstream side where each downstream is merged, a waste liquid storage reservoir 38 provided on the downstream side of the hybridization flow channel 37, and a discharge port 39 continuous to the waste liquid storage reservoir 38. Equipped with.

An air pump (not shown) is connected to the air pump connection port 31 to feed air. The air and the cleaning liquid sent to the air pump connection port 31 are guided to the wash channel 32. The air pump connection port 31 may be closed by a lid (not shown) when not in use.

The wash flow path 32 is a flow path for alternately flowing air and a cleaning liquid. In order to alternately flow such air and cleaning liquid, a bifurcated branch air tube is attached to the inlet of the wash channel 32. Then, the cleaning liquid is caused to flow from one of the branched tubes, and air is sent from the tube to the other branched tube via a micro pump. By increasing the atmospheric pressure of the air sent from the micropump, the air enters between the cleaning liquids, and the air and the cleaning liquid flow alternately. This can also be realized by periodically changing the amount of air sent from the micropump or the atmospheric pressure.

The intervals of the air and the cleaning liquid that are alternately flown may be arbitrary. The wash flow channel 32 is not limited to the case where the air and the cleaning liquid flow alternately. That is, the wash flow path 32 may be a flow path for only the cleaning liquid. The wash flow channel 32 may be omitted.

The tip of the discharge port 236 in the main body 23 for pretreatment described above can be connected to the sample injection port 33. The liquid L is injected into the sample injection port 33 via the connected discharge port 236. The sample inlet 33 may be closed by a lid (not shown) when not in use. The sample injection port 33 is not necessarily limited to the case where the tip of the discharge port 236 in the pretreatment main body 23 can be connected. In such a case, the discharge port 236 in the main body 23 for pretreatment may be positioned directly above the sample injection port 33 in a state of being separated from the sample injection port 33, and the liquid L may be dropped into the sample injection port 33. That is, the sample injection port 33 may have any structure as long as the liquid L can be sent from the discharge port 236 of the pretreatment main body 23. The liquid L sent to the sample injection port 33 is guided to the PCR channel 34.

The PCR flow path 34 amplifies the nucleic acid fragment in the target nucleic acid in the process of flowing the liquid L toward the downstream. The cross-sectional shape of the PCR flow path 34 may be any shape such as a circular shape or a polygonal shape, but it is desirable that the diameter thereof is set to a micron order of less than 1 mm. As a result, the liquid L passing through the PCR channel 34 is in a so-called microfluidic state, and conversely, the PCR channel 45 that allows such a microfluid to flow down is in a so-called microfluidic state. It should be noted that, in order to allow the liquid L to efficiently flow downstream in a microfluidic state, the height may be set to gradually decrease as the PCR flow path 34 moves downstream.

The PCR flow path 34 may have any route, but for example, as shown in FIG. 5, after being straightened for a predetermined distance, it is folded back to make a U-turn, and then again directed in the opposite direction to a predetermined direction. The vehicle may be straightened over a distance and then folded back to make a U-turn and repeated. At this time, the number of U-turns may be set to any number. The end of such a PCR flow path 34 joins the wash flow path 32.

In the present invention, instead of containing the bactericidal component, the gene detection primer, and the polymerase enzyme in the liquid injected from the sample injection port 33, these substances are sprayed in advance on the inner wall of the PCR channel 34 or the like. You may make it apply. This makes it possible to omit the sterilizing component, the gene detection primer, and the polymerase enzyme from being contained in the liquid injected from the sample injection port 33, and the liquid may be composed of water or the like. When a solvent composed of such a liquid composed of water is injected from the sample injection port 33, the bactericidal component, the gene detection primer, and the polymerase enzyme applied on the inner wall of the PCR channel 34 are dissolved. Therefore, the desired amplification of the nucleic acid fragment can be realized. In such a case, it is desirable that the structure be such that turbulent flow occurs in the PCR flow path 34 and stirring is possible. Further, it is possible to omit containing the sterilizing component, the gene detecting primer, and the polymerase enzyme in the liquid injected from the sample inlet 33, and to separately add the sterilizing component, the gene detecting primer, and the polymerase enzyme from the sample inlet 33. You may make it inject.

In addition, when the substances in Table 1 or Table 2 are applied to the surface of the PCR channel 34 in advance and the PCR channel 34 has a structure that causes turbulent flow and allows stirring, the solution L Alternatively, the substance applied to the surface of the channel may be dissolved and mixed. As a result, the process for detecting RNA by DNA amplification or cDNA synthesis can be performed in the PCR flow path 34.

The heating wire 35 is provided below the PCR flow path 34. The heating wire 35 is extended so that its longitudinal direction is orthogonal to the straight traveling direction of the PCR flow path 34. The heating wire 35 is set so that the heating temperature thereof is 90 to 95°C. However, the heating temperature is not limited to this, and may be between 30 and 150°C. The heating wire 35 is not limited to being formed in one row and may be formed in a plurality of rows. In the example of FIG. 5, the heating wire 35 has a width of 5 mm, and the interval between the heating wires adjacent to each other is 5 mm. The PCR flow path 45 passing over the heating wire 35 passes through in the direction orthogonal to the heating wire 35 provided at a predetermined interval and then is folded back and further passes over each heating wire 35 and is further folded back. And passing over each heating wire 35 is repeated. As a result, the PCR flow path 34 is heated at 90 to 95° C. on the heating wire 35, then cooled until it passes over the next heating wire 35, and the temperature is lowered to about 55° C. As the next heating wire 35 approaches, the temperature rises and is heated to 90 to 95°C. In the process of flowing through the PCR flow path 34, such heating and cooling via the heating wire 35 will be repeated.

The open/close switch 36 controls the washing liquid flowing from the wash flow channel 32 to the hybridization flow channel 37 by making the wash flow channel 32 openable and closable. As a specific configuration of the open/close switch 36, the wash flow path 32 is formed of a resin tube body, while only the position of the open/close switch 36 is formed of a film tube body that is elastically deformable. External pressure may be applied to the pipe body. By receiving such an external pressure, the tubular body made of film is elastically deformed so as to be reduced in diameter, so that the passage of the cleaning liquid from the wash channel 32 can be suppressed. On the other hand, by not applying an external pressure to the film tube body, the film tube body does not reduce its diameter, and in such a case, the cleaning liquid passes through the open/close switch 36 and passes through the hybridization flow path 37. It will flow to. In order to apply this external pressure, for example, an air pump may be installed at the location where the opening/closing switch 36 is provided, and the external pressure may be applied by supplying air to the film tube body.

A nucleic acid probe is previously formed on the bottom surface of the hybridization channel 37. In the hybridization channel 37, a nucleic acid probe having a base sequence complementary to the target nucleic acid to be detected is formed in advance.

In the hybridization flow channel 37, for example, when analysis is performed based on a certain sample from excrement, the following bacteria in the intestinal bacterial flora (Bifidobacteria, lactic acid bacteria, Faicari bacteria, Leishonomycetes, Fragilis bacteria, Butyricum bacteria, equol production A nucleic acid probe suitable for identifying a bacterium, a Clostridium perfringens, a Solderie bacterium, a Nucletam bacterium, a Bacillus cereus, a Copribacterium, etc. may be arranged.

The hybridization flow channel 37 needs to be made of, for example, a light-transmissive material in order to allow the light emitted from the outside to reach and to allow the light emission to reach the outside. For example, it is made of a transparent plastic material.

From the hybridization flow channel 37, a waste liquid containing nucleic acids other than the target nucleic acid flows into the waste liquid storage reservoir 38. The waste liquid storage reservoir 38 is composed of a water storage tank having a storage space in which the waste liquid can be temporarily stored.

The discharge port 39 is provided to discharge the waste liquid accumulated in the waste liquid storage reservoir 38. The discharge port 39 is usually closed by a cap (not shown), but by opening the cover, the waste liquid accumulated in the waste liquid storage reservoir 38 can be discharged.

Next, the configuration of the chip measuring device 4 will be described. FIG. 6 is a system configuration diagram of the chip measuring device 4.

The chip measuring device 4 includes an illuminating section 41 and a detecting section 42 which are respectively connected to the control block 46, and a chip mounter 43 provided so as to face the illuminating section 41 and the detecting section 42. And a heat dissipation plate 45 provided on the back side of the chip mounter 43. The heating wire 35 described above is attached to the chip mounter 43. The nucleic acid analysis chip 3 is detachably attached to the chip mounter 43.

FIG. 7 shows a block configuration of the control block 46. The control block 46 includes a central control unit 61, a communication unit 62 connected to the central control unit 61, a display panel 63, an air pump control unit 64, a power stabilization unit 65, an operating unit 66, and a heating wire control. And a section 67. The detection unit 42 and the illumination unit 41 are connected to the central control unit 61. An air pump 91 and a sensor 92 are connected to the air pump controller 64. The heating wire 35 is connected to the heating wire control unit 67.

The illumination unit 41 is an illumination that irradiates the nucleic acid analysis chip 3 attached to the chip mounter 43 with light, and is composed of, for example, an LED (blue LED or the like). The illumination unit 41 is arranged so that the irradiated light directly reaches the hybridization flow channel 37 in the nucleic acid analysis chip 3. The central control unit 61 controls the illumination unit 41 such as ON/OFF of light emission, emission intensity, emission wavelength, emission time, and the like.

The detection unit 42 is a device for receiving a hybridizing signal including light emission from the nucleic acid analysis chip 3 attached to the chip mounter 43, converting the hybridizing signal into an electric signal, and transmitting the electric signal to the central control unit 61. is there. The detector 42 is composed of a solid-state image sensor such as a photomultiplier tube or a CCD image sensor. The detection unit 42 is arranged at a position where light emitted from the hybridization flow channel 37 in the nucleic acid analysis chip 3 can be directly received. In the detection unit 42, the central control unit 61 controls ON/OFF of light reception, light reception time, and the like.

Note that the detection unit 42 is not limited to receiving light in the visible light region, and may also receive and measure light in the infrared region, near infrared region, and ultraviolet region. In such a case, the detection unit 42 uses a small spectroscope (C12666MA/C12800MA) manufactured by Hamamatsu Photonics or the like to absorb the light in the infrared region and the near infrared region from the hybridization channel 37. Alternatively, the molecular vibration may be measured to identify the substance. Further, in order to detect a minute light such as an ultraviolet region from the hybridization flow channel 37, a photomultiplier tube of Hamamatsu Photonics (example: R11265U-200) is used for the detection unit 42 for measurement. Good.

The chip mounter 43 is provided with a mounting table on which the nucleic acid analysis chip 3 can be mounted and a fixing device such as a magnet or an attachment so that the chip can be detachably fixed. The chip mounter 43 is configured so that the nucleic acid analysis chip 3 can be fixed so that the hybridization flow path 37 is oriented exactly in the direction of the illumination unit 41 and the detection unit 42.

The heat radiating plate 45 is provided in the vicinity of the heating wire 35, and has a shape provided with unevenness so as to increase the outer surface area in order to easily dissipate the heat generated from the heating wire 35. It is desirable that the heat radiating plate 45 be made of a material such as aluminum which is lightweight and easy to process.

Under the control of the central control unit 61, the heating wire control unit 67 performs feedback control so that the temperature of the heating wire 35 falls within a predetermined range.

The communication unit 62 converts the communication signal sent from the central control unit 61 into a radio signal and controls the transmission to the mobile terminal 5 via the antenna. The communication unit 62 also has a role of receiving a radio signal transmitted from the mobile terminal 5, converting the radio signal into an electric signal, and supplying the electric signal to the central control unit 61. The communication unit 62 is premised on transmitting and receiving radio signals to and from the mobile terminal 5, but the present invention is not limited to this, and communicates with the public communication network 6 without going through the mobile terminal 5. You may do it. Further, the communication unit 62 is not limited to the case of transmitting and receiving a signal by wireless communication, and it may be replaced by wired communication.

The display panel 63 is composed of, for example, a liquid crystal display panel or the like, and is a device for displaying various information to the user.

The operation unit 66 is composed of buttons, a mouse, a touch panel and the like for the user to operate and control the chip measuring device 4. The input information input by the operation unit 66 is transmitted to the central control unit 61, and the central control unit 61 performs various controls based on the input information. By the way, when the operation unit 66 is configured by a touch panel, it may be configured integrally with the display panel 63.

The power supply stabilizing unit 65 performs control for stabilizing the power supply of the control block 46, the heating wire 35, and the like in the chip measuring device 4.

The central control unit 61 is a central control unit for controlling the entire chip measuring device 4, and includes, for example, a CPU (Central Processing Unit). The central control unit 61 transmits various control commands to each unit via the operation unit 66 according to a user's operation. Further, the central control unit 61 controls ON/OFF of light emission, light emission intensity, light emission wavelength, light emission time, etc. for the illumination unit 41. In addition, the central control unit 61 controls the detection unit 42 such as ON/OFF of light reception and light reception time. The central control unit 61 receives the light reception information received by the detection unit 42 from the hybridization flow channel 37. The central control unit 61 displays such received light information on the display panel 63 or transmits it to the outside via the communication unit 62. The central controller 61 also controls opening/closing by the opening/closing switch 36. The central control unit 61 executes each of these controls based on a program stored in a ROM (not shown) or the like.

The air pump control unit 64 controls air supply via the air pump 91 connected to the air pump connection port 31. The air supply amount and the air supply timing of the air pump control unit 64 may be controlled based on the detection information of the sensor 92, for example.

The sensor 92 is composed of, for example, a motion sensor or an infrared sensor, detects a movement of the user's hand, generates detection information based on the movement, and transmits the detection information to the air pump control unit 64. As a result, the air supply control of the air pump 91 by the air pump control unit 64 can be realized based on the movement of the user.

The air pump 91 is an air tank that stores air to be sent by sucking air from the outside, and a tube that supplies the air stored in the air tank to the wash flow passage 32 through the air pump connection port 31. It can be classified into and. The air pump 91 is not limited to the case where it operates by automatic control, and air may be manually supplied to the wash passage 32 through the air pump connection port 31. In such a case, the configurations of the air pump control unit 64 and the sensor 92 can be omitted.

Next, a method of analyzing a gene using the gene analysis system 1 to which the present invention is applied will be described.

First, the user collects a sample collected from any of the human body, excrement, and soil. The collection target here is blood, sweat, saliva or the like for the human body, and feces or urine for excrement.

When collecting such a sample, the sample is attached to the tip of a rod-shaped body such as a cotton swab. Next, as shown in FIG. 8, a rod-shaped body 9 having a tip 94 on which a sample 95 is attached is attached to a sampling cartridge 22 in which a plurality of granular bodies 223 are filled in a container 220 and the liquid L is immersed therein. insert. The tip portion 94 of the rod-shaped body 9 may be slightly thickened like a cotton swab, but is not limited to this and may be all rod-shaped bodies having the same diameter.

As the rod-shaped body 9 is inserted into the accommodation container 220 from its tip 94, the tip of the rod-shaped body 9 is directed toward the insertion port 229 through the inner diameter of the inner wall 221 whose diameter is gradually reduced from the upper end. You will be guided naturally. By further pushing down the tip portion 94 of the rod-shaped body 9 from the insertion opening 229, the tip portion 94 is inserted into the insertion opening 229 and enters the lower chamber 220b. At this time, a protrusion 96 protruding outward may be formed in advance at a root portion of the rod-shaped body 9 slightly separated from the tip end portion 94 toward the root side. As a result, the protruding portion 96 is locked to the protruding portion 222 of the insertion opening 229, whereby the pushing depth of the rod-shaped body 9 can be controlled to an appropriate position, and thus the rod-shaped body 9 can be set in the storage container 220. It is possible to prevent it from being pushed too far and reaching the laminated body 26. Further, the rod-shaped body 9 may be preliminarily formed with a fold line, a kerf, or the like so that it can be easily folded in the vicinity of the protruding portion 96 and easily separated from the tip portion 94.

Since the insertion opening 229 formed by the inner wall 221 is pre-biased in the direction in which the inner diameter thereof is narrowed, in the process of pushing the thickened tip portion 94 of the rod-shaped body 9 into the insertion opening 229. An operation of inserting this into the lower chamber 220b side while expanding the insertion opening 229 to the outside is performed. Then, when the thickened tip portion 94 is completely in the lower chamber 220b side, the insertion opening 229 once expanded is urged in the direction in which the inner diameter is narrowed again. The root portion of the tip portion 94 of the rod-shaped body 9 closes the protruding portion 222 of the insertion port 229. As a result, it is possible to create a state in which the user cannot directly see the tip 94. For this reason, if the collected material 95 is excrement, the user cannot directly visually recognize the collected material, which makes it possible to give a clean impression.

Further, when pulling out the rod-shaped body 9 from the lower chamber 220b, in the process of pushing out the thickened tip portion 94 from the insertion port 229, the insertion port 229 is expanded outward while being pulled toward the upper chamber 220a side. Will be done. At this time, if the sample 95 is attached to the tip portion 94, the sample 95 can be dropped into the lower chamber 220b by applying the inner wall 221 to which the biasing force is applied to the sample 95. It will be possible.

Further, since the insertion port 229 formed by the inner wall 221 is pre-biased in the direction in which the inner diameter thereof is narrowed, the lower chamber 220b is in a state close to a closed state, so that the liquid L in the inside is closed. It is possible to make the granular material 223 last longer.

In this way, the periphery of the tip 94 of the rod-shaped body 9 that has entered the lower chamber 220b is surrounded by the granular body 223. As a result, since the granular body 223 comes into contact with the tip 94, the sample 95 attached to the tip 94 also comes into contact with the granular body 223. As a result, the sample 95 is wiped off and collected by the contacted granular body 223. Since the granular material 223 is impregnated with the liquid L, the collected sample is dissolved in the liquid L.

The user may stir the rod-shaped body 9 in the lower chamber 220b, or may slightly vibrate vertically. As a result, the collected material 95 attached to the tip portion 94 comes into contact with the granular body 223 several times and is rubbed, and the collected material 95 can be dissolved more effectively by wiping the collected material 95 more effectively.

Next, the user pulls out the rod-shaped body 9 including the tip portion 94 after the sample 95 is removed from the housing container 220. Next, as shown in FIG. 9, the sampling cartridge 22 is mounted in the cartridge housing portion 231 of the pretreatment main body 23. As a result, when the collecting cartridge 22 and the pretreatment main body 23 are mounted, the container 220 filled with the granular material 223 and the first filter 234 are separated from each other by the laminate 26. It becomes a state. In this state, the liquid L is in a state of being held by the film 225 through which the liquid itself cannot pass.

Next, by making a hole in the film 225, the liquid L is made to flow down to the separation section 233 side in the pretreatment main body 23. Any method may be used to make a hole in the film 225. For example, a plurality of long needles are installed upward in a chamber R1 that is separated from the upper side by a first filter 234. Incidentally, when the collection cartridge 22 is mounted, this long needle pierces the film 225, and the liquid L flows down from the hole formed in the film 225 to the separation section 233 side of the pretreatment main body 23. Becomes On the other hand, since the granular body 223 cannot pass through the mesh body 224, the granular body 223 is held by the granular body 223 and does not fall into the separation unit 233.

FIG. 10 shows the state in which the liquid L has passed through the film 225 and has flowed down to the separation section 233 side of the pretreatment main body 23. The liquid L first flows down into the chamber R1 and passes through the first filter 234. In the first filter 234, the serum is separated from the liquid L via the holes formed between the continuous tissues of the membrane. That is, the serum is accumulated in the chamber R1, and the liquid L from which the serum has been removed passes through the first filter 234 and flows down into the chamber R2.

The liquid L flowing down into the chamber R2 will be separated by the second filter 235 into at least viruses and bacteria. Only the liquid L from which viruses and bacteria have been separated passes through the second filter 235 and flows down into the chamber R3.

After accumulating the liquid that has flowed down into the chamber R3, the user opens the cap 237 and connects the tip of the discharge port 236 in the pretreatment main body 23 to the sample injection port 33 in the nucleic acid analysis chip 3. As a result, the liquid L is injected into the sample injection port 33 via the discharge port 236 in the pretreatment main body 23. The liquid L sent to the sample injection port 33 is guided to the PCR channel 34.

The liquid L guided to the PCR flow path 34 gradually flows down toward the downstream of this flow path 34. At this time, the liquid L flows through the PCR channel 34 in a microfluidic state by flowing through the PCR channel 34 having a reduced diameter. The liquid L causes a polymerase chain reaction while flowing through the PCR flow path 34. Specifically, when the PCR flow path 34 is flowing on the heating wire 35, it is in a state of being heated at 90 to 95° C. Therefore, at this stage, the nucleic acid is thermally denatured and the double-stranded nucleic acid The hydrogen bond is cleaved and dissociated into single-stranded nucleic acid.

As the liquid L containing such single-stranded nucleic acid passes over the heating wire 35 and further separates from the heating wire 35, the temperature decreases. Since this liquid L contains a primer, when the temperature is lowered to about 55° C., a complementary bond with the primer occurs with respect to the single-stranded nucleic acid.

Next, the temperature starts to rise again as the liquid L containing the single-stranded nucleic acid complementary to such a primer gradually approaches the heating wire 35. As the temperature increases, the primer begins to extend and becomes a double-stranded nucleic acid. Then, the liquid L again reaches the heating wire 35 and is heated at a temperature of 90 to 95° C., so that denaturation occurs and the hydrogen bond of the double-stranded nucleic acid is broken to dissociate into the single-stranded nucleic acid. It will be.

In the process in which the liquid L flows through the PCR flow path 34, as a result of the above-described process being repeated, it becomes possible to flow the nucleic acid fragment downstream while amplifying it.

The liquid L will be guided to the hybridization flow channel 37 after exiting the PCR flow channel 34. At the stage when the liquid L flows through the hybridization flow channel 37, at least the illumination light from the illumination unit 41 needs to reach this hybridization flow channel 37, and light emission from the hybridization flow channel 37 occurs. In this case, the central controller 61 in the control block 46 needs to be controlled in advance so that the detector 42 can detect this.

In the hybridization flow channel 37, if the target nucleic acid is contained in the liquid L, it becomes possible to form a stable double strand between this and the nucleic acid probe. As a result, only the target nucleic acid remains in the hybridization flow channel 37 as it is by forming a complementary double strand with the nucleic acid probe, and any nucleic acid other than the target nucleic acid remains in the hybridization flow channel 37. It flows and is sent to the waste liquid storage reservoir 38.

The presence or absence of the target nucleic acid bound to the nucleic acid probe remaining in the hybridization channel 37 will be identified by the chip measuring device 4. The hybridization performed in the hybridization channel 37 may be performed by any known method. For example, when fluorescence in situ hybridization is adopted, a nucleic acid probe labeled with a fluorescent substance, an enzyme, or the like is used, and the hybridization signal emitted by hybridization with the target nucleic acid is detected by the detection unit 42 as a fluorescence microscope. You may make it detect by.

In this way, hybridization is carried out in the hybridization channel 37. In order to perform the hybridization in the hybridization channel 37 more preferably, the temperature, pH, cation concentration and the like need to be adjusted in advance. The temperature may be adjusted by using a Peltier element or a heating wire. The temperature may be about 37° C. and the pH may be about 7.

After the completion of hybridization, the opening/closing switch 36 may be opened to flow the washing liquid from the wash flow channel 32 to the hybridization flow channel 37. As a result, the nucleic acid analysis chip 3 can be used to identify the nucleic acid multiple times. When flowing the cleaning liquid from the wash channel 32, the air pump 91 is operated via the air pump control unit 64 and the cleaning liquid is alternately supplied. The cleaning liquid flows through the wash channel 32 toward the downstream side, and then flows into the hybridization channel 37 as it is. The washing liquid that has reached the hybridization channel 37 flows all the remaining nucleic acid and sends it to the waste liquid storage reservoir 38.

When the detection unit 42 can detect the luminescence indicating the presence of the target nucleic acid, the detection unit 42 outputs this to the central control unit 61. The central control unit 61 acquires the detection result and then displays the detected data via the display panel 63, or transmits the detected data to the mobile terminal 5 via the communication unit 62.

When the mobile terminal 5 receives the above-mentioned data via the communication unit 62, the mobile terminal 5 uses the examination application stored in itself to analyze the data to identify the nucleic acid and perform the gene analysis. .. The form terminal 5 displays the analysis result to the user, or displays various suggestions for future health maintenance to the user. The mobile terminal 5 may further transmit the data received via the communication unit 62 to the public communication network 6. The data transmitted to the public communication network 6 is stored in the server 7. The data stored in the server 7 is analyzed by the central controller 8 and confirmed by a doctor or the like. Further, the knowledge obtained by the information analysis by the central controller 8 and the analysis result may be transmitted to the mobile terminal 5 via the public communication network 6.

According to the present invention having the above-described configuration, the user collects a sample from the human body, excrement, or soil with the rod-shaped body 9 and collects the sample into the collecting cartridge 22 in which the liquid L is dipped and into the tip 94. The rod-shaped body 9 to which the object 95 is attached is inserted. Other than that, the work of mounting the collection cartridge 22 to the pretreatment main body 23 and connecting the tip of the discharge port 236 of the pretreatment main body 23 to the sample injection port 33 of the nucleic acid analysis chip 3 are performed. Will be automatically subjected to gene analysis.

Therefore, even a user who does not have specialized knowledge about medical treatment can perform gene analysis by himself/herself with an extremely simple operation.

In addition, since the gene analysis pretreatment kit 2, the nucleic acid analysis chip 3, and the chip measuring device 4 are not complicated in device configuration, they can be downsized and are suitable for self-examination at home. Since it has a different structure and can be provided at a low price, it can be purchased by individuals.

Further, according to the present invention, nucleic acid can be extracted from a collected sample with high efficiency, and serum, bacteria, and viruses are previously removed through the pretreatment kit 2 for gene analysis in order to identify nucleic acid with high accuracy. Further, these operations can be performed very easily without any special skill or knowledge.

In addition, the washing liquid can be washed by flowing the washing liquid from the wash flow passage 32 to the hybridization flow passage 37, and the nucleic acid analysis chip 3 can be used repeatedly many times, which is very excellent in cost performance. With this configuration, the cleaning work can be performed very easily.

In addition, the accuracy of the biochemical test can be maintained at the same level as before, while simplifying the device configuration, improving the ease of handling, and improving the cost performance as described above. It becomes possible to realize the gene analysis of at home.

The present invention is not limited to the above embodiment. The granular body 223 may be configured by previously filling the liquid L in the skin made of an elastic material. In such a case, it is not essential to impregnate the liquid L in the container 220. When the rod-shaped body 9 having the sample attached to the tip is inserted, the sample is collected by bringing the tip into contact with the granular body 223 in the same manner as described above. In addition to this, the liquid L is caused to flow out by breaking the surface of the granular body 223 by the tip of the rod-shaped body 9. This makes it possible to impregnate the tip of the rod 9 with the liquid L that has flowed out.

Further, the gene analysis system 1 to which the present invention is applied may be configured as a case-housing type as shown in FIGS. The components and members of the case-accommodating gene analysis system 1 ′ are the same as those in the above-described embodiment, and therefore, the same reference numerals are given and the description is omitted.

FIG. 11 shows the appearance of the case-accommodating gene analysis system 1'. In the case-accommodating gene analysis system 1', one end is joined by a hinge (not shown), and the case 100a and the case 100b are configured to be openable/closable with respect to the hinge (not shown) as a rotation center. A handle 101 and a lock mechanism 102 are provided on the upper surfaces of the cases 100a and 100b. A display 103 and a touch panel 104 may be provided outside the case-accommodating gene analysis system 1'. Incidentally, the display 103 corresponds to the display panel 63, and the touch panel 104 corresponds to the operation unit 66.

FIG. 12 shows a state in which the cases 100a and 100b are expanded. The chip measuring device 4 described above is disposed on the side of the case 100a, a personal computer (PC) 50 is connected to the chip measuring device 4, and a battery 105 is connected to the PC 50. The PC 50 operates by the power supplied from the battery 105. The measurement result by the chip measuring device 4 is sent to the PC 50. The PC 50 has the same function as the mobile terminal 5 described above.

A nucleic acid analysis chip 3 is arranged on the case 100b side, and a pretreatment main body 23 is connected to the nucleic acid analysis chip 3. The nucleic acid analysis chip 3 is provided at a position just facing the chip measurement device 4 when the cases 100a and 100b are closed. This enables the above-mentioned measurement. The sample injection port 33 of the nucleic acid analysis chip 3 is directly connected to the discharge port 236 of the pretreatment main body 23 to send the liquid L. The pretreatment main body 23 and the nucleic acid analysis chip 3 may be arranged in plural sets. A sample can be introduced into the pretreatment main body 23 from the sample introduction port 108 through the branch tube 111. The structure of the sample introduction port 108 is similar to that of the sampling cartridge 22. The liquid L from the sampling cartridge 22 is sent to the pretreatment main body 23 via the branch tube 111. Incidentally, the power for sending the liquid L from the sampling cartridge 22 to the branch tube 111 is assumed to be carried out via the pump 109. The insides of the cases 100a and 100b are covered with a reinforced plastic or a reinforced protective film except for the sample introduction port 108, so that scattering of the sample can be prevented.

According to such a case-accommodating gene analysis system 1', the system can be compactly packed in a case having a size such as a suitcase. In addition, high-risk viruses and illnesses (HIV, Marburg virus, Ebola virus, smallpox, Lassa fever, etc.) can be quickly measured without having to entrust them to special management facilities each time. It is possible to detect trends and the like quickly and prevent the damage from spreading. In particular, according to this case-accommodating gene analysis system 1 ′, since the rod-shaped body 9 to which the sample 95 is attached can be inserted into the sample introduction port 108 and the rest can be measured fully automatically, the operability is improved. Can be further improved and can be disposed of without any human touch from the start to the end of the measurement, which is excellent in hygiene.

Further, according to the present invention, in addition to the nucleic acid measurement, biological substances such as peptides, exosomes, biomarkers and antibodies can be similarly measured. In such a case, the liquid L injected through the discharge port 236 in the pretreatment main body 23 will flow into the hybridization flow channel 37 as it is without nucleic acid amplification in the PCR flow channel 34. All other steps are similar to those of the above-described embodiment. That is, when biological substances such as peptides, exosomes, biomarkers, and antibodies are also measured in the same manner, an injection flow channel that simply flows the injected liquid L into the hybridization flow channel 37 instead of the PCR flow channel 34. It should have been done.

1 Gene Analysis System 2 Pretreatment Kit for Gene Analysis 3 Nucleic Acid Analysis Chip 4 Chip Measuring Device 5 Mobile Terminal 6 Public Communication Network 7 Server 8 Central Control Unit 9 Rod 12 Public Communication Network 21 Plunger 22 Collection Cartridge 23 Pretreatment Main body 26 Laminated body 31 Air pump connection port 32 Wash flow channel 33 Sample injection port 34 PCR flow channel 35 Heating wire 36 Open/close switch 37 Hybridization flow channel 38 Waste liquid storage reservoir 39 Discharge port 41 Illumination unit 42 Detection unit 43 Chip mounter 45 Heat dissipation Plate 45 Flow path 46 Control block 61 Central control unit 62 Communication unit 63 Display panel 64 Air pump control unit 65 Power supply stabilization unit 66 Operation unit 67 Heating wire control unit 91 Air pump 92 Sensor 95 Sample 96 Protrusion 211 Inner cylinder 212 Pusher 213 Rubber part 220 Storage container 220a Upper chamber 220b Lower chamber 221 Inner wall 222 Protruding part 223 Granular body 224 Net body 225 Film 229 Insertion port 231 Cartridge accommodating part 232 Circumferential wall 233 Separation part 234 First filter 235 Second filter 236 Discharge Outlet 237 cap

Claims (6)

In a pretreatment kit for gene analysis for extracting a biological substance from a sample collected from a human body, excrement, or soil,
With a plurality of granular bodies being filled, a liquid is immersed in the granular body, and when a rod-shaped body having the collected material attached to the tip is inserted, the tip is brought into contact with the granular body. A collecting cartridge for collecting a sample and impregnating the sample with the liquid,
Discharge means for discharging the liquid sent from the sampling cartridge to the outside ,
A first filter for separating at least serum from the liquid delivered from the mounted collection cartridge; and a pretreatment main body having the discharge means,
The discharge means discharges the liquid passing through the first filter to the outside,
When the collecting cartridge and the pretreatment main body are mounted, the container filled with the granular material and the first filter are a mesh body through which the liquid can pass and a film through which the liquid cannot pass. Are separated from each other by a laminated body laminated with each other,
When delivering the liquid from the collecting cartridge, a hole is formed in the film to allow the liquid to pass therethrough, and the liquid is allowed to pass through, and the granular material is retained by the reticulate body. Pretreatment kit. The liquid is sterilized components, genetic detection primer according to claim 1, before a gene analysis according treatment kit, characterized in that formed by incorporating a polymerase enzyme. The main body for pretreatment further includes a second filter for separating at least viruses and bacteria from the liquid that has passed through the first filter, and the discharging means externally discharges the liquid that has passed through the second filter. The pretreatment kit for gene analysis according to claim 2, wherein the pretreatment kit is for excretion. The sampling cartridge has an insertion opening that is pre-biased in the direction of narrowing and the tip of the rod-shaped body is inserted, and the inside of the insertion opening is filled with the granular material. The pretreatment kit for gene analysis according to any one of claims 1 to 3 , wherein the liquid is immersed therein. The said rod-shaped body has a protrusion part which made the root part of the front-end|tip to which the said sample adheres protrude outside, and the said protrusion part is latched by the said insertion opening, The claim 4 characterized by the above-mentioned. Pretreatment kit for gene analysis. The granular material is made of any one of metal, ceramics, and resin, and on the surface thereof, any one of zeolite, emulsion gel, hydrophilic polymer, and amino acid substance is formed. A pretreatment kit for gene analysis according to any one of items 1 to 5 .

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