Patent Publication Number: US-2023137860-A1

Title: Integrated molecular diagnosis apparatus

Description:
CROSS REFERENCE TO RELATED APPLICATION 
     The present application claims priority to Korean Patent Application Nos. 10-2021-0149875, 10-2021-0151223, and 10-2022-0005099 filed Nov. 3, 2021, Nov. 5, 2021, and Jan. 13, 2022, respectively, the entire contents of which is incorporated herein for all purposes by this reference. 
     BACKGROUND OF THE INVENTION 
     Field of the Invention 
     The present disclosure relates to an integrated molecular diagnosis apparatus and, more particularly, to an integrated molecular diagnosis apparatus capable of independently performing a process from pretreatment of a collected sample to molecular diagnosis thereof with a user&#39;s involvement being minimized. Furthermore, the integrated molecular diagnosis apparatus is capable of being manufactured in a small size and thus performing point-of-care testing. 
     STATEMENT OF GOVERNMENTAL SUPPORT 
     Individual Project Number: 1465032760 
     Project Number: HW20C2068 
     Government Ministry: Ministry of Health and Welfare 
     Institution: Korea Health Industry Development Institute 
     Research Project Title: Disinfection Technology Development Project 
     Research Project Title: Development of Integrated LAMP-type Molecular Diagnosis 
     Apparatus for Sample Pretreatment, Capable of Quick Diagnosis on the Spot 
     Contribution Ratio: 1/1 
     Project Researcher Institute: WIZBIOSOLUTIONS INC. 
     Project Period: 2020 Sep 1˜2023 Feb 28 
     DESCRIPTION OF THE RELATED ART 
     Usually, a molecular diagnostic method directly performs genetic testing of harmful bacteria or viruses. Thus, the molecular diagnostic method has an advantage in precision and more accurate diagnosis of causative organisms of infectious diseases over an immunodiagnostic method. However, a diagnosis procedure is complex because the molecular diagnostic method sequentially performs sample collection, cell destruction, nucleic acid extraction, and nucleic acid amplification. Furthermore, it takes a long time of approximately 30 minutes to 2 hours to obtain a result of diagnosis. 
     Therefore, research has been conducted on quick pretreatment of a sample in order to shorten a testing time taken for the molecular diagnosis method and to find application in point-of-care testing (POCT). Usually, a pretreatment of sample is to extract nucleic acids (DNA, RNA, and the like) in a cell for amplifying the nucleic acids on a polymerase chain reaction (PCR) process. Specifically, a component that interrupts or suppresses an amplification reaction is removed, and only target nucleic acids are purified to a greater level of purity. 
     A sample pretreatment method in the related art extracts nucleic acids using a centrifugal separator. However, in recent years, technologies have been developed that automate a sample pretreatment process without using the centrifugal separator. Accordingly, cartridge integrated molecular diagnosis apparatuses that independently perform a process from sample pretreatment to molecular diagnosis have been commercialized. 
     Usually, the cartridge integrated molecular diagnosis apparatuses control a fluid with a mechanical method, using a valve or a motor in order to transport a sample during a process from the sample pretreatment to the amplification. Therefore, a cartridge structure or a control method is complex. In addition to this method, there is an electrowetting method that is used to control a small volume of fluid. However, an electrode array that is required to complicate manufacturing process is essential, thereby increasing the cost of a cartridge. Furthermore, the reliability of a result of diagnosis is relatively low. 
     The foregoing is intended merely to aid in the understanding of the background of the present disclosure, and is not intended to mean that the present disclosure falls within the purview of the related art that is already known to those skilled in the art. 
     SUMMARY OF THE INVENTION 
     An objective of the present disclosure is to provide an integrated molecular diagnosis apparatus capable of independently performing a process from pretreatment of a collected sample to molecular diagnosis thereof with a user&#39;s involvement being minimized. Furthermore, the integrated molecular diagnosis apparatus is capable of being manufactured in a small size and thus performing point-of-care testing. 
     According to an aspect of the present disclosure, there is provided an integrated molecular diagnosis apparatus comprising: a buffer tube into which a sample collection tool collecting a sample is inserted, the buffer preparing a sample solution that contains nucleic acid extracted from the collected sample; a cartridge combined with the buffer tube and supplied with the sample solution, the cartridge transporting the sample solution to a reaction chamber through a fluid channel and performing a nucleic acid amplification reaction; and a diagnosis module main body detachably combined with the cartridge, the diagnosis module main body supplying heat at a predetermined temperature to the reaction chamber, detecting the nucleic acid amplification reaction, and determining whether or not a diagnosis target is present. 
     The disclosed technology may have the following effects. However, a specific implementation example of the integrated molecular diagnosis apparatus is not meant to be acquired to achieve all the following effects or only the following effects, and therefore should not be understood as imposing any limitation on the claimed scope of the present disclosure. 
     An integrated molecular diagnosis apparatus according to an embodiment of the present disclosure can independently perform a process from pretreatment of a collected sample to molecular diagnosis thereof with a user&#39;s involvement being minimized. The integrated molecular diagnosis apparatus can be manufactured in a small size, and thus can perform point-of-care testing. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The above and other objectives, features, and other advantages of the present disclosure will be more clearly understood from the following detailed description when taken in conjunction with the accompanying drawings, in which: 
         FIG.  1    is a block diagram illustrating an integrated molecular diagnosis system according to a first embodiment of the present disclosure; 
         FIG.  2    is a view illustrating an implementation example of an integrated molecular diagnosis apparatus illustrated in  FIG.  1   ; 
         FIGS.  3 A to  3 C  are views each illustrating a buffer tube illustrated in  FIG.  1   ; 
         FIGS.  4 A to  4 C  are views each illustrating an opening and closing body illustrated in  FIGS.  3 A to  3 C ; 
         FIG.  5    is a view illustrating a cartridge illustrated in  FIG.  1   ; 
         FIGS.  6 A to  6 D  are views each illustrating a cartridge main body illustrated in  FIG.  5   ; 
         FIGS.  7 A and  7 B  are views each illustrating a cartridge holder illustrated in  FIG.  5   ; 
         FIG.  8    is a block diagram illustrating a diagnosis module main body illustrated in  FIG.  1   ; 
         FIG.  9    is a view illustrating a body of the diagnosis module main body illustrated in  FIG.  8   ; 
         FIG.  10    is a view illustrating a heat supply module illustrated in  FIG.  8   ; 
         FIG.  11    is a view illustrating a detection module illustrated in  FIG.  8   ; 
         FIG.  12    is a flowchart for a molecular diagnostic method according to a second embodiment of the present disclosure; 
         FIG.  13    is a view illustrating a movement of an inlet-port plugging member of a buffer tube; 
         FIG.  14    is a view illustrating a path along which a sample solution flows; 
         FIGS.  15 A and  15 B  are graphs each illustrating a result of diagnosis; 
         FIG.  16    is a block diagram illustrating an integrated molecular diagnosis system according to a third embodiment of the present disclosure; 
         FIGS.  17 A to  17 C  are views each illustrating a cartridge illustrated in  FIG.  16   ; 
         FIG.  18    is a block diagram illustrating a diagnostic module main body illustrated in  FIG.  16   ; 
         FIG.  19    is a view illustrating a heat supply module illustrated in  FIG.  18   ; 
         FIGS.  20 A and  20 B  are views each illustrating a detection module illustrated in  FIG.  18   ; and 
         FIG.  21    is a view illustrating a detection signal that is output from the detection module illustrated in  FIG.  18   . 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     An embodiment of the present disclosure will be described below in an exemplary manner in terms of structures and functions. Therefore, the claimed scope of the present disclosure should not be construed as being limited by the embodiment of the present disclosure. That is, various modifications can be made to the embodiment, and the embodiment can take various forms. Therefore, equivalents of the embodiment that can realize the technical idea of the present disclosure should be understood as falling within the scope of the present disclosure. In addition, a specific embodiment is not meant to be required to achieve all the objectives of the present disclosure or all the effects thereof or to achieve only all the effects, and therefore should not be understood as imposing any limitation on the claimed scope of the present disclosure. 
     The terms used through the present application should be understood as having the following meanings. 
     The terms “first”, “second”, and so on are intended to distinguish among constituent elements and therefore should not be construed as imposing any limitation on the claimed scope of the present disclosure. For example, a first constituent element may be named a second constituent element. In the same manner, the second constituent element may also be named the first constituent element. 
     A constituent element, when described as being “connected to” a different constituent element, should be understood as being connected directly to the different constituent element or as being connected to the different constituent element with a third intervening constituent element interposed therebetween. By contrast, a constituent element, when described as being “connected directly to” a different constituent element, should be understood as being connected to the different constituent element without any third intervening constituent element interposed therebetween. Expressions such as “between” and “directly between” and expressions such as “adjacent to” and “directly adjacent to” that are used to describe a relationship between constituent elements should also be construed in the same manner. 
     The term used in the present specification, although expressed in the singular, is construed to have a plural meaning, unless otherwise explicitly meant in context. It should be understood that the terms “include”, “have”, and the like are intended to indicate that a feature, a number, a step, an operation, a constituent element, a component, or any combination thereof is present, without precluding the possible presence or addition of one or more other features, numbers, steps, operations, constituent elements, or any combination thereof. 
     Identification characters (for example, a, b, c, and so forth) are assigned to steps for convenience of description. The identification characters do not indicate the order of steps. Unless otherwise stated in context, steps may be performed in a different order of steps than in the mentioned order of steps. That is, steps may be performed in the mentioned order of steps. Steps may be performed substantially at the same time and may be performed in reverse order of the steps. 
     The present disclosure may be realized as computer-readable codes recorded on a computer-readable recording medium. Computer-readable recording media include all types of recording devices on which data readable by a computer system are stored. Examples of the computer-readable recording medium include a ROM, a RAM, a CD-ROM, a magnetic tape, a floppy disk, an optical data storage device, and the like. In addition, codes that are distributed to computer systems connected through a network and are readable by a computer in a distributed manner may be stored on the computer-readable medium and may be executed therefrom. 
     Unless otherwise defined, each of all terms used throughout the present specification has the same meaning as is normally understood by a person of ordinary skill in the art to which the present disclosure pertains. A term as defined in a commonly used dictionary should be construed as having the same meaning as that in context in the related art and, unless otherwise explicitly defined in the present application, should not be construed as having an excessively implied meaning or a purely literal meaning. 
       FIG.  1    is a block diagram illustrating an integrated molecular diagnosis system according to a first embodiment of the present disclosure.  FIG.  2    is a view illustrating an implementation example of an integrated molecular diagnosis apparatus illustrated in  FIG.  1   . 
     With reference to  FIGS.  1  and  2   , the integrated molecular diagnosis system according to the first embodiment of the present disclosure may include an integrated molecular diagnosis apparatus  1  and a user terminal  2 . The integrated molecular diagnosis apparatus  1  may communicate with the user terminal  2  through a network. The networks here may include wired communication networks, wireless communication networks employing communication standards, such as a wireless LAN, Wi-Fi, Bluetooth, and Zigbee, and various types of mobile communication networks employing communication standards, such as 2G, 3G, 4G, 5G, and LTE. 
     The integrated molecular diagnosis apparatus  1  may automatically pretreat a sample that is collected from a user subject to diagnostic testing and then is injected thereinto. From the pretreated sample, the integrated molecular diagnosis apparatus  1  may determine in real time whether or not a diagnosis target is present. The diagnosis target according to the present disclosure may be bacteria or virus that cause a respiratory disease. Examples of the diagnosis target may include the bacteria or virus that cause a respiratory disease, such as a respiratory syncytial virus (RSV), a COVID-19, and a delta COVID-19. The integrated molecular diagnosis apparatus  1  may transmit a result of the diagnosis to the user terminal  2 . 
     The integrated molecular diagnosis apparatus  1  may include a sample collection tool  100 , a buffer tube  200 , a cartridge  300 , and a diagnosis module main body  400 . In this case, the sample collection tool  100 , the buffer tube  200 , and the cartridge  300  are disposable, and may be disposed of after use. The sample collection tool  100  collects a sample from the user subject to diagnostic testing. The sample collection tool  100  may collect a sample from a mucous membrane on an inner wall of a nasal cavity or oral cavity of the user subject to diagnostic testing. The sample collection tool  100  may be formed to have a shape for easily collecting a sample from the user subject to diagnostic testing and may be formed of a material for easily collecting a sample from the user subject to diagnostic testing. For example, the sample collection tool  100  may be formed to have the shape of a swab in such a manner as to be insertable into the nasal cavity or oral cavity of the user subject to diagnostic testing. 
     The sample collection tool  100  is accommodated in the buffer tube  200  into which a buffer solution is pre-injected, for being immersed into the buffer solution. The buffer solution here is obtained by mixing a lysis buffer, which is a buffer solution that is used when breaking a cell membrane, or with micro-particles or the like for improving lysis efficiency. This buffer solution may be pre-injected into the buffer tube  200 . 
     The buffer tube  200  extracts nucleic acid from the sample collected through the sample collection tool  100  and prepares a sample solution. Generally, methods of destroying a cell membrane of a sample include a chemical method of adjusting pH of a buffer solution, a method of heating a buffer solution to a predetermined temperature 60 to 95□ C and thus removing a large protein molecule through protein denaturation, a method of applying a physical impact using an ultrasonic wave, and the like. 
     A sample containing bacteria or virus that causes a respiratory disease has a relatively smaller number of impurities than blood or other samples. For this reason, according to the first embodiment of the present disclosure, the method of destroying a cell membrane by shaking the buffer tube  200  to apply a physical and chemical impact on a sample is employed. That is, in a state where the sample collection tool  100  is inserted into the buffer tube  200  and where the buffer tube  200  is sealed, the sample collection tool  100  is shaken in such a manner that the buffer solution is together shaken. With this motion, the cell membrane of the sample is destroyed, and thus the nucleic acid may be extracted. The first embodiment of the present disclosure is not limited to this extraction method. At least one of a method of applying a physical impact by heating a buffer solution and a method of applying a physical impact using an ultrasonic wave may be employed together to extract nucleic acid. 
     The buffer tube  200  may be inserted into the cartridge  300  for being mounted therein and may supply to the cartridge  300  the sample solution from which the nucleic acid is extracted. The buffer tube  200 , when inserted into the cartridge  300 , may discharge the sample solution to the outside by drilling a hole in the bottom surface of the buffer tube  200 . To this end, the buffer tube  200  may be formed of a non-rigid plastic material having excellent chemical resistance. For example, the buffer tube  200  may be formed of polypropylene (PP), polycarbonate (PC), or the like. 
     The cartridge  300  is combined with the buffer tube  200  and is supplied with the sample solution from the buffer tube  200 . The cartridge  300  extracts a fixed amount of sample solution through at least one fluid channel and mixes the extracted amount of sample solution with a pre-injected reagent. Then, the cartridge  300  is supplied with heat at a predetermined temperature from the diagnosis module main body  400  and performs a nucleic acid amplification reaction. 
     The reagent here serves to detect the diagnosis target by amplifying the nucleic acid contained in the sample and may be pre-injected into the cartridge  300  in a frozen and dry state. The cartridge  300  may be formed of a non-rigid transparent material having excellent chemical resistance. For example, the cartridge  300  may be formed of polypropylene (PP), polycarbonate (PC), acryl, or the like. 
     The diagnosis module main body  400  may be detachably combined with the cartridge  300 . According to a preset operating condition, the diagnosis module main body  400  may supply heat at a predetermined temperature, which is necessary for the nucleic acid amplification reaction, to the cartridge  300 . Then, the diagnosis module main body  400  may measure color or a fluorescent magnitude of the sample solution that varies with the nucleic acid amplification reaction and thus may determine whether or not the diagnosis target is present. The operating condition here may be set as a state where the sample solution is mixed with the reagent within the cartridge  300  in preparation for performing the nucleic acid amplification reaction after the cartridge  300  is inserted into the diagnosis module main body  400 . 
     Under the control of the user terminal  2 , the diagnosis module main body  400  may communicate with the user terminal  2  to transmit a result of diagnosing the diagnosis target. That is, in the integrated molecular diagnosis apparatus  1  according to the first embodiment of the present disclosure, a procedure in which a user transfers the sample solution into the cartridge  300 , and so on are omissible. Thus, a pretreating process of collecting the sample and extracting and amplifying the nucleic acid and a diagnosis process may be independently performed in one apparatus in a state where user&#39;s involvement is minimized. 
     The user terminal  2  may communicate with the integrated molecular diagnosis apparatus  1  to control operation of the integrated molecular diagnosis apparatus  1 . The user terminal  2  may display on a screen the result of the diagnosis supplied from the integrated molecular diagnosis apparatus  1 . The result of the diagnosis may be displayed as negative or positive. In addition, the user terminal  2  may provide a screen on which the time required for the diagnosis and the result of the diagnosis are displayed. For storage, the user terminal  2  may transmit the place and the date and time of the diagnosis and the like to a database, along with the result of the diagnosis. The database here may be located inside or outside the user terminal  2  and may be managed by a separate server. 
     The user terminal  2  may be a computing apparatus that is used by a user who uses the integrated molecular diagnosis apparatus  1 . For example, the user terminal  2  may be a computing apparatus, such as a smartphone, a tablet PC, or a desktop PC, but is not limited to these apparatuses. An application that is to be executed in conjunction with the integrated molecular diagnosis apparatus  1  may be installed on the user terminal  2 . 
       FIGS.  3 A to  3 C  are views each illustrating the buffer tube  200  illustrated in  FIG.  1   .  FIGS.  4 A to  4 C  are views each illustrating an opening and closing body illustrated in  FIGS.  3 A to  3 C .  FIG.  3 C  is a vertically cross-sectional view illustrating a state where the buffer tube  200  in  FIG.  1    is combined with a cartridge body illustrated in  FIG.  5   .  FIG.  4 B  is a bottom view illustrating the opening and closing body illustrated in  FIG.  4 A .  FIG.  4 C  is a top view illustrating the opening and closing body illustrated in  FIG.  4 A . 
     With reference to  FIG.  3 A , the buffer tube  200  may include a tube body  210 , an opening and closing body  220 , and an inlet-port plugging member  230 . The tube body  210  is formed to have the shape of a cylinder and has an internal space in which the buffer solution is accommodated. The tube body  210  is open at the top. The opening and closing body  220  is connected to an upper end of the tube body  210 . The sample collection tool  100  may be accommodated in the internal space in the tube body  210 . 
     The top here of the tube body  210  may be sealed with a sealing film (not illustrated), and the sealing film may be removed when molecular diagnostic testing is performed. A stepped jaw  211  may be formed on an outer circumferential surface of the tube body  210 , and a concave groove  213  may be formed in the outer circumferential surface thereof. With the stepped jaw  211  and the concave groove  213 , the tube body  210  are hooked onto the cartridge  300  for being combined therewith. The stepped jaw  211  is formed to have a diameter relatively greater than a diameter of the tube body  210 . When the tube body  210  is seated in the cartridge  300 , the stepped jaw  211  is hooked onto an insertion hall  331  in a cartridge holder  330  for combining the tube body  210  with the cartridge  300 . Thus, the tube body  210  can be prevented from deviating from the cartridge  300 . 
     The concave groove  213  is formed along the outer circumferential surface of the tube body  210  in such a manner as to have a diameter relatively smaller than the diameter of the tube body  210 . The concave groove  213  is formed at a position corresponding to a combination protrusion  335  of the cartridge holder  330 . The combination protrusion  335  is hooked onto the concave groove  213  for combining the tube body  210  with the cartridge  300 . Accordingly, with an elastic force of an elastic member  333  provided on the combination protrusion  335 , the tube body  210  is pressed against the cartridge  300  in a state of being inserted thereinto. Thus, the buffer tube  200  may be fixed together with the cartridge  300 . 
     The tube body  210 , as illustrated in  FIG.  3 B , may include a backward-flowing prevention jaw  215  on the bottom surface. The backward-flowing prevention jaw  215  here may be formed to have the shape of a ring in such a manner as to protrude from the bottom surface of the tube body  210 . The backward-flowing prevention jaw  215  may be formed in such a manner as to have a smaller width than the bottom surface of the tube body  210 . As illustrated in  FIG.  3 C , the backward-flowing prevention jaw  215  may be formed in such a manner as to have a height at which one portion of an inlet port  310  is blocked when the tube body  210  is combined with the cartridge  300 . In addition, it is desirable that the backward-flowing prevention jaw  215  is formed in such a manner that an outer diameter thereof is equal to an inner diameter of a support jaw  311   a  of the tube accommodation body  311 . 
     Accordingly, when the sample solution accommodated within the tube body  210  is discharged, the sample solution flows through the inlet port  310  only to a plurality of fluid channels  315 , and a flow of the sample solution between an outer wall of the tube body  210  and an inner wall of the cartridge  300  is limited. Thus, the sample solution can be prevented from flowing backward along an outer lateral surface of the tube body  210 . In addition, the sample solution is not brought into contact with the outer lateral surface of the tube body  210 . Thus, the sample solution can be prevented from coming into contact with a contamination source that may be present on an outer wall of the tube body  210 . 
     The opening and closing body  220  is combined with the upper end of the tube body  210  and opens and closes the internal space in the tube body  210 . The opening and closing body  220 , as illustrated in  FIG.  4 A to  4 C , may include a concave-convex pattern  221 , a protrusion jaw  223 , a through-hole  225 , a plurality of vent holes  227 , and a hook jaw  229 . The concave-convex pattern  221  is formed on an upper surface of the opening and closing body  220 . The concave-convex pattern  221  can minimize an area of the opening and closing body  220  with which a user&#39;s hand comes into contact during an operation of opening and closing the diagnosis module main body  400  and while the buffer tube  200  is inserted into the cartridge  300 . Thus, the sample can be prevented from being contaminated. 
     The protrusion jaw  223  is formed to have the shape of a ring in such a manner as to protrude from a bottom surface of the opening and closing body  220 . An outer circumferential surface of the protrusion jaw  223  is inserted into an inner circumferential surface of the tube body  210 . The through-hole  225  is formed in a central area of the opening and closing body  220  in a manner that passes therethrough from the upper surface to the lower surface. 
     Each of the plurality of vent holes  227  is formed in the lower surface of the opening and closing body  220  between a lateral surface of the through-hole  225  and the protrusion jaw  223 . The plurality of vent holes  227  may be formed in such a manner as to be spaced apart a predetermined distance from each other. 
     The hook jaw  229  extends inward from the lateral surface of the through-hole  225  and thus supports the inlet-port plugging member  230 . At this point, when the inlet-port plugging member  230  is moved, a shape of a curved surface of the hook jaw  229  may be changed by a pressing pressure transferred through the inlet-port plugging member  230  and thus may support the inlet-port plugging member  230  in a state where the inlet-port plugging member  230  is no longer moved. 
     The inlet-port plugging member  230  is inserted into the through-hole  225  in the opening and closing body  220  and seals the internal space in the tube body  210 . At this point, the inlet-port plugging member  230  may be supported by the hook jaw  229 . The inlet-port plugging member  230 , when pressed by the operation of opening and closing the diagnosis module main body  400 , is moved toward the internal space in the tube body  210  and thus opens the plurality of vent holes  227 . That is, by the operation of opening and closing the diagnosis module main body  400 , the inlet-port plugging member  230  forms an air introduction path along which air flows into the internal space. 
     The inlet-port plugging member  230  may be formed of a material that can allow air to pass through and can block passage of the sample solution (or the buffer solution). That is, the inlet-port plugging member  230  may be formed of a hydrophobic material in such a manner that the sample solution is prevented from flowing to the outside even when the buffer tube  200  or the cartridge  300  is turned upside down. The inlet-port plugging member  230  may be formed to a predetermined length in such a manner as to perform a plugging function. 
       FIG.  5    is a view illustrating an implementation example of the cartridge  300  illustrated in  FIG.  1   .  FIGS.  6 A to  6 D  are views each illustrating a cartridge main body illustrated in  FIG.  5   .  FIGS.  7 A and  7 B  are views each illustrating the cartridge holder  330  illustrated in  FIG.  5   .  FIG.  6 C  is a top view illustrating a cartridge main body illustrated in  FIG.  6 A .  FIG.  6 D  is a cross-sectional view taken along line A-A′ on  FIG.  6 A . 
     With reference to  FIG.  5   , the cartridge  300  may include a cartridge body  310 , a plurality of outlet-port plugging members  320 , and the cartridge holder  330 . The cartridge body  310  here, as illustrated in  FIG.  6 A to  6 D , is formed in a manner that is based on the shape of a plate with a front surface and a rear surface and may include the tube accommodation body  311 , an inlet port  313 , the plurality of fluid channels  315 , a plurality of reaction chambers  317 , and a plurality of outlet ports  319 . 
     The tube accommodation body  311  is formed to have a protruding shape in such a manner as to constitute a front portion of the cartridge body  310 . The tube accommodation body  311  is open at the top and has an internal space into which the buffer tube  200  is inserted. The internal space here may be formed to have the same shape and size as the buffer tube  200 . Thus, when the tube body  210  is combined with the cartridge  300 , the sample solution may be limited to flowing only to the inlet port  310 . 
     The tube accommodation body  311  may include a combination hole  311   a , a hole drilling member  311   b , and the support jaw  311   c . The combination hole  311   a  here may be formed in a front surface of the tube accommodation body  311  in a manner that passes through the tube accommodation body  311  from a front surface thereof to the inside at a position corresponding to the combination protrusion  335  of the cartridge holder  330   
     The hole drilling member  311   b  may be formed on a support surface of the tube accommodation body  311 . The hole drilling member  311   b  drills a hole in a bottom surface of the buffer tube  200  using a pressure applied with an operation of inserting the buffer tube  200 . The hole drilling member  311   b  may be formed in such a manner as to protrude upward from the support surface of the tube accommodation body  311  and to have a pointed end portion. 
     The support jaw  311   c  may be formed in such a manner as to protrude toward the internal space along with an inner lateral surface of the tube accommodation body  311  other than the inlet port  313  and may be formed to a predetermined height from the support surface of the tube accommodation body  311 . That is, the support jaw  311   c  may be formed to have the shape of a ring in such a manner as to surround the support surface of the tube accommodation body  311 . 
     The support jaw  311   c  supports the backward-flowing prevention jaw  215  of the tube body  210 , when the tube body  210  is inserted into the internal space in the tube accommodation body  311 . That is, the backward-flowing prevention jaw  215  is combined with the support jaw  311   c  in such a manner that an outer lateral surface thereof is brought into contact with an inner lateral surface of the support jaw  311   c . Accordingly, the sample solution is limited to flowing only to the inlet port  313 . 
     The inlet port  313  is formed in a rear surface of the cartridge body  310  in a manner that passes through the cartridge body  310  from a rear surface thereof to the outside on the support surface of the tube accommodation body  311 . Through the inlet port  313 , the sample solution discharged from the bottom surface of the buffer tube  200  is introduced into each of the plurality of the fluid channels  315 . 
     Each of the plurality of the fluid channels  315  may be formed in the rear surface of the cartridge body  310 . Along the plurality of the fluid channels  315 , the sample solution may be transported from the inlet port  313  through the corresponding reaction chamber  317  to the corresponding outlet port  319 . Each of the plurality of fluid channels  315  here may include a first flow path  315   a  and a second flow path  315   b.    
     The first flow path  315   a  may be formed in such a manner as to branch out to each of the plurality of reaction chambers  317  from the inlet port  313 . The second flow path  315   b  may be formed between the corresponding reaction chamber  317  and the outlet port  319 . The second flow path  315   b  may be formed in such a manner as to be curved in a zigzag fashion when viewed from above in order to increase fluid resistance. Accordingly, the flow resistance of the sample solution flowing along the second flow path  315   b  is increased, and thus a flowing speed can be uniformly maintained. 
     The plurality of reaction chambers  317  are formed in the rear surface of the cartridge body  310  and accommodate the sample solution transported along the plurality of fluid channels  315 , respectively. Each of the plurality of reaction chambers  317  here may include the pre-injected reagent. Each of the plurality of reaction chambers  317  may be supplied with heat at a predetermined temperature from the diagnosis module main body  400  and may perform the nucleic acid amplification reaction on the sample solution. Each of the plurality of reaction chambers  317  may be formed in such a manner as to be of sufficient size to contain a fixed amount of sample solution. 
     According to the first embodiment of the present disclosure, as an example, the case where three reaction chambers  317  are provided is described above, but the present disclosure is not limited to this case. The number of reaction chambers  317  can be increased or decreased according to the number of diagnosis targets. 
     Each of the plurality of outlet ports  319  is formed in a front surface of the cartridge body  310  in such a manner as to be positioned between the corresponding reaction chamber  317  and the tube accommodation body  311 . That is, each of the plurality of outlet ports  319  is positioned more upward than the corresponding reaction chamber  317 . Thus, a state where each of the plurality of reaction chambers  317  is filled with the sample solution can be maintained. 
     The cartridge body  310  according to the first embodiment of the present disclosure may further include a sealing member (not illustrated) sealing the inlet port  313 , the plurality of fluid channels  315 , and the plurality of reaction chambers  317  on the rear surface. The sealing member may be formed as a transparent thin film. 
     The plurality of outlet-port plugging members  320  may be inserted into the plurality of outlet ports  319 , respectively. Each of the plurality of outlet-port plugging members  320  can allow air to pass through and can block discharge of the sample solution flowing along each of the plurality of fluid channels  315 . Each of outlet-port plugging members  320  may be formed of a porous material, for example, porous polyethylene or porous hydrogel. Therefore, the fluid channel  315  can be kept stationary within the plurality of fluid channels without being discharged to the outside. 
     The cartridge holder  330  is combined with the front surface of the cartridge body  310  and thus holds the buffer tube  200  in place within the cartridge body  310 . The cartridge holder  330 , as illustrated in  FIGS.  7 A and  7 B , may have the internal space into which the cartridge body  310  is inserted and may include the insertions hole  331 , the elastic member  333 , and the combination protrusion  335 . 
     The insertion hole  331  is formed at a position corresponding to an upper end portion of the tube accommodation body  311 . Through the insertion hole  331 , the internal space of the tube accommodation body  311  is exposed. The elastic member  333  has the shape of a plate spring and is positioned on an inner lateral surface of the cartridge holder  330  that faces the tube accommodation body  311 . With a sliding motion due to the insertion of the buffer tube  200 , the elastic member  333  is elastically deformed and thus provides an elastic force to the combination protrusion  335 . 
     The combination protrusion  335  is formed in such a manner as to protrude from the elastic member  333  at a position corresponding to the combination hole  311   a  in the tube accommodation body  311  and is inserted into the combination hole  311   a . The combination protrusion  335  has an inclined surface and causes the elastic member  333  to be maximally elastically deformed at an end of the inclined surface. Thus, a restoring force that acts when the elastic member  333  is restored to its original position can be increased. With the sliding motion due to the insertion of the buffer tube  200 , the combination protrusion  335  reaches the concave groove  213 . At this time, the combination protrusion  335  is supplied with the elastic force from the elastic member  333 . Thus, the combination protrusion  335  is hooked onto the concave groove  213  for being fastened thereto, making a slight sharp “click” sound. 
     That is, when hooked onto the concave groove  213  for being combined therewith, the combination protrusion  335  makes a slight sharp “click” sound. Thus, it can be ensured that the tube body  210  is completely combined with the cartridge body  310  in such a manner as to be positioned at its home position. Once the combination protrusion  335  combines the buffer tube  200  and the cartridge body  310  into one piece, the buffer tube  200  is not allowed to be separated from the cartridge body  310 . 
       FIG.  8    is a block diagram illustrating the diagnosis module main body  400  illustrated in  FIG.  1   .  FIG.  9    is a view illustrating a body illustrated in  FIG.  8   .  FIG.  10    is a view illustrating a heat supply module illustrated in  FIG.  8   .  FIG.  11    is a view illustrating a detection module illustrated in  FIG.  8   . 
     With reference to  FIG.  8   , the diagnosis module main body  400  may include a body  410 , a heat supply module  420 , a detection module  430 , a power supply module  440 , a sensing module  450 , and an integrated control module  460 . The body  410  accommodates the cartridge  300 , the heat supply module  420 , the detection module  430 , the power supply module  440 , and the integrated control module  460 . The body  410 , as illustrated in  FIG.  9   , may include the lower body  411  and the opening and closing body  413 . The lower body  411  may be formed to have the shape of a rectangle and has an internal space of predetermined size. The lower body  411  may include an insertion hole  411   a . The insertion hole  411   a  may be formed in an upper surface of the lower body  411 . The insertion hole  411   a  may be formed to have a shape and size corresponding to the cartridge  300  so that the cartridge  300  can be inserted into the insertion hole  411   a.    
     The opening and closing body  413  is combined with the lower body  411  and opens and closes the internal space in the lower body  411 . The opening and closing body  413  may include a pressing member  413   a . The pressing member  413   a  may be formed in such a manner as to protrude from an inner surface corresponding to the upper surface of the lower body  411  and may be formed at a position corresponding to the inlet-port plugging member  230  of the buffer tube  200 . The pressing member  413   a  may press the inlet-port plugging member  230  for movement thereof. 
     The heat supply module  420  is detachably combined with the cartridge  300 . Under the control of the integrated control module  460 , the heat supply module  420  supplies heat at a predetermined temperature, which is necessary for the nucleic acid amplification reaction, to each of the plurality of reaction chambers  317 . 
     The heat supply module  420 , as illustrated in  FIG.  10   , may include a thermal conductivity body  421  and a heating unit  423 . The thermal conductivity body  421  is combined with the cartridge  300 . The thermal conductivity body  421  is supplied with heat at a temperature from the heating unit  423  and transfers the heat to the cartridge  300 . The thermal conductivity body  421  accommodates the cartridge  300  and the heating unit  423  and may include a cartridge insertion groove  421   a , a plurality of first holes  421   b , and a plurality of second holes  421   c.    
     The cartridge insertion groove  421   a  may be formed at a position corresponding to the insertion hole  411   a  in the lower body  411 . The cartridge insertion groove  421   a  may be formed in such a manner that an inner surface thereof is brought into contact with a front surface, a rear surface, and a bottom surface of a portion of the cartridge  300 , the portion including the plurality of reaction chambers  317 . 
     Each of the plurality of first holes  421   b  is formed in the cartridge insertion groove  421   a  in a manner that passes therethrough from the one-side inner surface to the outside. The plurality of first holes  421   b  may be formed at positions, respectively, that correspond to the plurality of reaction chambers  317 . 
     Each of the plurality of second holes  421   c  is formed in the cartridge insertion groove  421   a  in a manner that passes through a bottom surface thereof. The plurality of second holes  421   c  may be formed at positions, respectively, that correspond to the plurality of reaction chambers  317 . 
     The heating unit  423  is arranged within the thermal conductivity body  421  and generates heat at a predetermined temperature. Examples of the heating unit  423  may include a resistive heater, a thermoelectric element, and the like. 
     The first embodiment of the present disclosure is not limited to this heating unit  423 . The heat supply module  420  may further include a heat sink or the like that dissipates heat of the thermal conductivity body  421  to the outside. 
     The detection module  430  is arranged adjacent to the heat supply module  420 . Under the control of the integrated control module  460 , the detection module  430  emits light to each of the plurality of reaction chambers  317 , detects light that passes through each of the plurality of reaction chambers  317 , and generates a detection signal. 
     The detection module  430 , as illustrated in  FIG.  11   , may include a plurality of light sources  431  and a plurality of light detectors  433 . Under the control of the integrated control module  460 , the plurality of light sources  431  may emit light to the plurality of reaction chambers  317 , respectively. Each of the plurality of light sources  431  may be formed as a light emitting diode (LED) or a laser diode (LD). 
     The plurality of light sources  431  here may be arranged adjacent to the plurality of second holes  421   c , respectively, in the thermal conductivity body  421 . The plurality of light sources  431  may be arranged in a direction horizontal or vertical to the light detectors  433 , respectively, with reference to the cartridge  300 . According to the first embodiment of the present disclosure, as an example, the case where the plurality of light sources  431  are arranged in the direction vertical to the plurality of light detectors  433 , respectively, but the first embodiment of the present disclosure is not limited to this case. The plurality of light sources  431  may be arranged in the direction horizontal to the plurality of light detectors  433 , respectively, with reference to the cartridge  300 . 
     It is desirable that the light source  431  may be arranged in the direction horizontal to the light detector  433  in a case where the light detector  433  detects color of the sample solution. Furthermore, it is desirable that the light source  431  may be arranged in the direction vertical to the light detector  433  in a case where the light detector  433  detects fluorescent of the sample solution. 
     The plurality of light detectors  433  may detect light that passes through the plurality of reaction chambers  317 , respectively. Then, the light detectors  433  may generate the detection signal and may transmit the generated detection signal to the integrated control module  460 . The plurality of light detectors  433  may be arranged in such a manner as to face the plurality of reaction chambers  317 , respectively. The plurality of light detectors  433  may be arranged adjacent to the plurality of first holes  421   b , respectively, in the thermal conductivity body  421 . Each of the plurality of light detectors  433  here may include a photodiode (PD), a photo multiplier tube (PMT), a phototransistor, a charge-coupled device (CCD) image sensor, or a complementary metal-oxide semiconductor (CMOS) image sensor. 
     The power supply module  440  may supply electric power to each of the heat supply module  420 , the detection module  430 , and the integrated control module  460 . The power supply module  440  may include a battery, a power button, a power terminal, and the like. 
     The sensing module  450  may sense a closed state of the body  410  and may generate an opening and closing sensing signal. Furthermore, the sensing module  450  may sense temperature of the heat supply module  420  and may generate a temperature sensing signal. The sensing module  450  may include a plate spring member (not illustrated) supporting the opening and closing body  413 , a pressure sensor (not illustrated), and a temperature sensor (not illustrated). 
     Through the pressure sensor, the sensing module  450  may sense an elastic force that is generated from the plate spring member when the opening and closing body  413  is closed, and may generate an opening and closing sensing signal. In addition, through the temperature sensor, the sensing module  450  may sense the temperature of the heat supply module  420  and may generate a temperature sensing signal. 
     According to the detection signal and the opening and closing sensing signal that are transmitted from the detection module  430 , the integrated control module  460  may determine whether or not the preset operating condition is satisfied. Specifically, according to the detection signal, the integrated control module  460  may determine whether or not the cartridge  300  is inserted or whether or not the sample solution is transported into the plurality of reaction chambers  317 . That is, the integrated control module  460  according to the first embodiment of the present disclosure may determine the operating condition by utilizing the detection module  430  as the sensor for determining whether or not the cartridge  300  is inserted into the body  410  and the sensor for determining whether or not the sample solution is injected into each of the reaction chambers  317 . 
     In addition, according to the opening and closing sensing signal, the integrated control module  460  may determine whether the body  410  is opened or closed. That is, in a case where the cartridge  300  is inserted, where the sample solution is transported into the plurality of reaction chambers  317 , and where the body  410  is in a closed state, the integrated control module  460  may determine that all operating conditions are satisfied. 
     When the operating condition is satisfied, the integrated control module  460  supplies heat at a predetermined temperature, which is necessary for the nucleic acid amplification reaction, to each of the plurality of reaction chambers  317  through the heat supply module  420 . According to the temperature sensing signal, the integrated control module  460  may control the temperature of the heat supply module  420  in a manner that is uniformly maintained. 
     When heat at a predetermined temperature is supplied to each of the plurality of reaction chambers  317 , the integrated control module  460  may detect a change in color or in a fluorescent magnitude due to the nucleic acid amplification reaction from the sample solution in each of the plurality of reaction chambers  317  and may determine whether or not the diagnosis target is present. The integrated control module  460  may communicate with the user terminal  2  to transmit the result of diagnosing the diagnosis target. The integrated control module  460  may be controlled by the user terminal  2  and may be realized as a printed circuit board (PCB). 
       FIG.  12    is a flowchart for a molecular diagnostic method according to a second embodiment of the present disclosure.  FIG.  13    is a view illustrating a movement of the inlet-port plugging member  230  of the buffer tube  200 .  FIG.  14    is a view illustrating a path along which the sample solution flows.  FIGS.  15 A and  15 B  are graphs each illustrating the result of the diagnosis. 
     With reference to  FIG.  12   , a sample is collected from a user using the sample collection tool  100  (Step S 110 ). Subsequently, the sample collection tool  100  is placed into the tube body  210  of the buffer tube  200  (Step S 120 ). At this time, the sample collection tool  100  is immersed in the buffer solution pre-injected into the buffer tube  200 . Subsequently, the opening and closing body  220  is closed. At this time, the inlet-port plugging member  230  is in a state of being fittingly inserted into the through-hole  225  in the opening and closing body  220 . Therefore, when the opening and closing body  220  is closed, the tube body  210  is sealed. 
     Subsequently, the buffer tube  200  is shaken. Then, a cell membrane of the sample collected through the sample collection tool  100  is destroyed, and thus nucleic acid is extracted (Step S 130 ). Accordingly, a sample solution that is obtained by mixing the buffer solution with the nucleic acid is prepared. 
     In this state, the cartridge  300  is mounted in the diagnosis module main body  400  through the insertion hole  411   a  in the lower body  411  (Step S 140 ). Then, the buffer tube  200  is inserted into the tube accommodation body  311  of the cartridge  300 . At this time, the hole driving member  311   b  drills a hole in the bottom surface of the tube body  210  (Step S 150 ). Then, the sample solution is discharged from the tube body  210 . At this time, the plurality of vent holes  227  are in a state of being closed by the inlet-port plugging member  230  of the buffer tube  200 . Therefore, the sample solution is not introduced into the inlet port  313 . 
     In this state, when the opening and closing body  413  is closed, as illustrated in  FIG.  13   , the pressing member  413   a  of the opening and closing body  413  presses the inlet-port plugging member  230  of the buffer tube  200 , and the inlet-port plugging member  230  is moved downward. Thus, the plurality of vent holes  227  are opened. Accordingly, an air introduction path A along which air is introduced into the internal space in the tube body  210  is formed. 
     Then, as illustrated in  FIG.  14   , air flows at both ends of each of the plurality of fluid channels  315 . In this state, due to a capillary force, the sample solution flows along a path B from the inlet port  313  through the corresponding reaction chamber  317  to the corresponding the outlet port  319 . At this time, each of the plurality of outlet ports  319  is in a state of being closed by the corresponding outlet-port stopper member  320 . The sample solution is accommodated in a stationary state within the reaction chamber  317 . In this manner, the sample solution is transported into the corresponding reaction chamber  317  along each of the plurality of fluid channels  315  (Step S 160 ). 
     At this time, according to the detection signal and the opening and closing sensing signal, the integrated control module  460  determines whether or not the operation condition is satisfied. For example, according to the detection signal, the integrated control module  460  may determine whether or not the cartridge  300  is inserted into the body  410  and may determine whether or not the sample solution is injected into each of the reaction chambers  317 . Then, according to the opening and closing sensing signal, the integrated control module  460  may determine whether the body  410  is opened or closed. At this point, when the cartridge  300  is inserted into the diagnosis module main body  400  and when the sample solution is injected into each of the reaction chambers  317  in a state where the body  410  is closed, the integrated control module  460  may determine that all the operating conditions are satisfied. 
     When all the operating conditions are satisfied in this manner, the integrated control module  460  supplies heat at a predetermined heat to the plurality of reaction chambers  317  through the heat supply module  420 . Accordingly, the nucleic acid amplification reaction is performed on the sample solution accommodated in each of the plurality of reaction chambers  317 . At this time, the detection module  430  detects color or a fluorescent magnitude of the sample solution, generates the detection signal, and transmits the generated detection signal to the integrated control module  460 . 
     Subsequently, according to the detection signal, the integrated control module  460  detects a change in color or in a fluorescent magnitude due to the nucleic acid amplification reaction from the sample solution in each of the plurality of reaction chambers  317  and finds out whether or not the diagnosis target is present. 
     For example, in a case where there are three reaction chambers  317 , that is, reaction chambers A, B, and C, reagents for detecting first type and second type genes for diagnosing COVID-19 may be contained in the reaction chamber A and the reaction chamber B, respectively. An internal control (IC) reagent for checking whether or not the apparatus operates properly and whether or not sample collection is sufficient may be contained in the reaction chamber C. The internal control (IC) regent here is a material for identifying RNA of epithelial tissue. In a case where the sample collection is insufficient, or in a case where the apparatus does not operate properly, a negative response appears. 
     In this state, when a change in color due to a change in pH before or after the nucleic acid amplification reaction occurs in the sample solution accommodated in each of the reaction chambers A, B, and C, the integrated control module  460  may determine that the diagnosis target is present. To this end, a phenol red indicator or a purple indicator of which color is changed due to the nucleic acid amplification reaction may be contained in the sample solution accommodated in each of the reaction chambers A, B, and C. 
     For example, as illustrated in  FIG.  15 A , in a case where color of the sample solution accommodated in each of the reaction chamber A and the reaction chamber B is changed after the nucleic acid amplification reaction, but where color of the sample solution accommodated in the reaction chamber B is not changed, the detection signal corresponding to the change in color in each of the reaction chambers A and C, that is, an electrical output (electrical signal) value is increased in a manner that is higher than an electrical output value (indicated by a dotted line) that is obtained before the nucleic acid amplification reaction. Then, the integrated control module  460  may verify that the sample is appropriately collected and that the apparatus operates and may determine that first type COVID-19 virus is present (a positive response). 
     Alternatively, the integrated control module  460  may detect the fluorescent magnitude of the sample solution through the nucleic acid amplification reaction and may determine whether or not the diagnosis target is present. For example, as illustrated in  FIG.  15 B , in a case where, unlike in the reaction chamber B, the fluorescent magnitude of the sample solution accommodated in each of the reaction chamber A and the reaction chamber C is increased, the integrated control module  460  may verify that the sample is appropriately collected and that the apparatus operates properly and may determine that the first type COVID-19 virus is present (a positive response). 
     Next, the integrated control module  460  provides the result of diagnosing the diagnosis target to the user terminal  2  (Step S 170 ). Subsequently, the buffer tube  200  and the cartridge  300  may be disposed of in a sealed state. 
     The second embodiment of the present disclosure is not limited to Step S 140 . In Step S 140 , when the cartridge  300  is inserted into the diagnosis module main body  400 , the cartridge  300  may be inserted into the diagnosis module main body  400  in a state where the buffer tube  200  is inserted into the cartridge  300 . That is, the buffer tube  200  may be first inserted into the cartridge  300 , and then the cartridge  300  may be inserted into the diagnosis module main body  400 , together with the buffer tube  200 . 
       FIG.  16    is a block diagram illustrating an integrated molecular diagnosis system according to a third embodiment of the present disclosure.  FIGS.  17 A to  17 C  are views each illustrating a cartridge illustrated in  FIG.  16   .  FIG.  18    is a block diagram illustrating a diagnostic module main body illustrated in  FIG.  16   .  FIG.  19    is a view illustrating a heat supply module illustrated in  FIG.  18   .  FIGS.  20 A and  20 B  are views each illustrating a detection module illustrated in  FIG.  18   .  FIG.  21    is a view illustrating a detection signal that is output from the detection module illustrated in  FIG.  18   . 
     With reference to  FIG.  16   , an integrated molecular diagnosis system according to a third embodiment may include an integrated molecular diagnosis apparatus  3  and a user terminal  4 . The integrated molecular diagnosis apparatus  3  may include a sample collection tool  100 ′, a buffer tube  200 ′, a cartridge  300 ′, and a diagnosis module main body  400 ′. In this case, the sample collection tool  100 ′ and the buffer tube  200 ′ have the same configurations as the sample collection tool  100  and the buffer tube  200 , respectively, and therefore descriptions thereof are omitted. 
     The cartridge  300 ′ is the same as the cartridge  300  according to the first embodiment, except that the cartridge  300 ′ further includes a sensing unit  340 . Accordingly, the same constituent elements are given the same reference numeral, and descriptions of the same constituent elements are not repeated for convenience of description. The sensing unit  340  here reacts with hydrogen ions contained in the sample solution in each of the plurality of reaction chambers  317  and senses a hydrogen ion concentration (pH). The sensing unit  340 , as illustrated in  FIGS.  17 A to  17 C , may include a reference electrode  341  and a plurality of sensing electrodes  343 . 
     The reference electrode  341  may be formed to have the shape of a plate in such a manner as to cover the respective tops of the inlet port  313 , the plurality of fluid channels  315 , and the plurality of reaction chamber  317 . The reference electrode  341  may be combined with the rear surface of the cartridge body  310 . That is, the reference electrode  341  according to the third embodiment of the present disclosure may serve as the sealing member sealing the rear surface of the cartridge body  310 . 
     The reference electrode  341  may include an electrode terminal surface  341   a  extending downward toward a bottom surface of the cartridge body  310  and may be electrically connected to the diagnosis module main body  400  through the electrode terminal surface  341   a.    
     The reference electrode  341  has a surface that is brought into contact with the top of each of the plurality of reaction chambers  317 . This surface may be brought into contact with the sample solution. The reference electrode  341  has predetermined reference potential that results from a change in a hydrogen-ion concentration (pH) of the sample solution. The reference electrode  341  may be formed of a half-cell reactive material that is stable to a range of pH and provides high reproducibility. For example, the reference electrode  341  may be formed of Ag/AgCl. 
     A half cell here means a cell in which a potential difference resulting from an oxidation half reaction or a reduction half reaction occurs. That is, when an oxidation reaction or a reduction reaction occurs according to a value of the hydrogen-ion concentration (pH) of the sample solution in each of the plurality of sensing electrodes  343 , the reference electrode  341  may operate as a reduction electrode or an oxidation electrode that is different from the plurality of sensing electrodes  343 . 
     Each of the plurality of sensing electrodes  343  is spaced apart from the reference electrode  341  and is brought into contact with the sample solution in the internal space in each of the plurality of reaction chambers  317 . Each of the plurality of sensing electrodes  343  may be formed in a manner that passes through the cartridge body  310  in order to be positioned in the internal space in the each of the plurality of reaction chambers  317 . That is, each of the plurality of sensing electrodes  343  may be formed in such a manner as to be inserted from the bottom surface of the cartridge body  310  into the internal space in each of the plurality of reaction chambers  317 . Therefore, first end portions of the plurality of sensing electrodes  343  may be arranged in the internal spaces, respectively, in the plurality of reaction chambers  317  and may be brought into contact with the sample solution. Second end portions thereof may be exposed at the bottom surface of the cartridge body  310  and may be electrically connected to the diagnosis module main body  400 . 
     Each of the plurality of the sensing electrodes  343  has sensing potential that varies with a change in the hydrogen-ion concentration (pH) of the sample solution. That is, the reference electrode  341  and both ends of each of the plurality of sensing electrodes  343  operate as a potential condenser. The sensing potential of each of the plurality of sensing electrodes  343  varies with respect to reference potential of the reference electrode  341 . Each of the plurality of sensing electrodes  343  here may be formed of a metal oxide material sensitive to the hydrogen ion concentration (pH), for example, ITO, SiO2, or the like. 
     The diagnosis module main body  400 ′ may be detachably combined with the cartridge  300 ′. The diagnosis module main body  400 ′ may supply heat at a predetermined temperature, which is necessary for the nucleic acid amplification reaction, to the cartridge  300 ′ and may convert a change in the hydrogen ion concentration, which results from the nucleic acid amplification reaction, into an electrical signal. Thus, the diagnosis module main body  400 ′ may determine whether or not the diagnosis target is present. 
     The diagnosis module main body  400 ′, as illustrated in  FIG.  18   , may include a body  410 ′, a heat supply module  420 ′, a detection module  430 ′, a power supply module  440 ′, a sensing module  450 ′, and an integrated control module  460 ′. The body  410 ′ and the power supply module  440 ′ have the same configurations as the body  410  and the power supply module  440 , respectively, according to the first embodiment of the present disclosure, and thus detailed descriptions thereof are omitted. 
     The heat supply module  420 ′ is detachably combined with the cartridge  300 ′. Under the control of the integrated control module  460 ′, the heat supply module  420 ′ supplies heat at a predetermined temperature, which is necessary for the nucleic acid amplification reaction, to each of the plurality of reaction chambers  317 . 
     The heat supply module  420 ′, as illustrated in  FIG.  19   , may include a thermal conductivity body  421 ′ and a heating unit  423 ′. The thermal conductivity body  421 ′ is inserted into the cartridge  300 ′. The thermal conductivity body  421 ′ is supplied with heat at a predetermined temperature from the heating unit  423 ′ and transfers the heat to the cartridge  300 ′. 
     The thermal conductivity body  421 ′ may accommodate the cartridge body  310  and the heating unit  423  and may include the cartridge insertion groove  421   a′  and first and second connector insertion holes  421   b′  and  421   c′ . The cartridge insertion groove  421   a′  may be formed at a position corresponding to the insertion hole  411   a  in the lower body  411  and may be formed in such a manner that an inner surface thereof is brought into contact with a front surface, a rear surface, and a bottom surface of a portion of the cartridge body  310 , the portion including the plurality of reaction chambers  317 . The cartridge insertion groove  421   a′  may be formed in such a manner that a bottom surface thereof is stepped in a manner that corresponds to the electrode terminal surface  341   a  of the reference electrode  341 . 
     The first connector insertion hole  421   b′  may be formed in a bottom surface of the cartridge insertion groove  421   a′  in a manner that passes through the cartridge insertion hole  421   a′  from top to bottom. The second connector insertion hole  421   c′  may be formed in the bottom surface of the cartridge insertion groove  421   a′  in a manner that is spaced apart a predetermined distance from the first connector hole  421   b′  and in a manner that passes through the cartridge insertion groove  421   a′  from top to bottom. 
     The heating unit  423 ′ is arranged within the thermal conductivity body  421 ′. Under the control of the integrated control module  460 ′, the heating unit  423 ′ generates heat at a predetermined temperature. Example of the heating unit  423 ′ may include a resistor heater, a thermoelectric element, or the like. The first embodiment of the present disclosure is not limited to this heating unit  423 ′. The heat supply module  420 ′ may further include a cooling unit dissipating heat generated from the thermal conductivity body  421 ′ to the outside, and the like. 
     The detection module  430 ′ is electrically connected to a sensing unit  340 ′ of the cartridge  300 ′ and supplies a reference voltage of predetermined magnitude to the reference electrode  341 . The detection module  430 ′ measures a sensing voltage of each of the plurality of sensing electrodes  343  and generates a plurality of detection signals. The detection module  430 ′ transmits the detection signal to the integrated control module  460 ′. 
     The detection module  430 ′, as illustrated in  FIG.  20 A , may include a reference electrode connector  431 ′, a plurality of sensing electrode connectors  433 ′, a reference voltage supply unit  435 , and a hydrogen-ion concentration detection unit  437 . The reference electrode connector  431 ′ is inserted into the first connector insertion hole  421   b′  in the thermal conductivity body  421 ′ and is brought into contact with the reference electrode  341 . 
     The reference electrode connector  431 ′ has an insertion groove  431   a  into which the electrode terminal surface  341   a  of the reference electrode  341  is inserted, and may be brought into surface contact with the electrode terminal surface  341   a . The third embodiment of the present disclosure is not limited to this shape of the reference electrode connect  431 ′. The reference electrode connector  431 ′ may be bent in the form of ¬ and thus may be brought into contact with the electrode terminal surface  341   a  of the reference electrode  341 . 
     The plurality of sensing electrode connectors  433 ′ are inserted into the plurality of second connector insertion holes  421   c′ , respectively, in the thermal conductivity body  421 ′ and is brought into contact with the plurality of sensing electrodes  343 , respectively. The plurality of sensing electrode connectors  433 ′ may be brought into contact with the plurality of sensing electrodes  343 , respectively, at the bottom surface of the cartridge body  310 . 
     The reference voltage supply unit  435  supplies predetermined voltage potential to the reference electrode  341  through the reference electrode connector  431 ′. 
     The hydrogen-ion concentration detection unit  437  is electrically connected to the plurality of sensing electrodes  343  through the plurality of sensing electrode connectors  433 ′, respectively. The hydrogen-ion concentration detection unit  437  detects the sensing potential of each of the plurality of sensing electrodes  343  and generates the plurality of detection signals. 
     The hydrogen-ion concentration detection unit  437  may include a plurality of non-inverting operational amplifiers (AP). Each of the plurality of non-inverting operational amplifiers (AP), as illustrated in  FIG.  20 B , may include a non-inverting input terminal (+), an inverting input terminal (−), and an output terminal. The non-converting input terminal (+) is connected to each of the plurality of sensing electrode connectors  433 ′. A ground voltage is applied to the inverting input terminal (−). The output terminal outputs a detection signal Vout. 
     According to a change in the hydrogen-ion concentration (pH) of the sample solution (SS), sensing potential Vs of the sensing electrode  343  may change by ΔVs from reference potential Vr. The non-inverting operational amplifiers (AP) may output an amount of the change in the sensing potential Vs as the detection signal Vout. That is, the hydrogen-ion concentration detection unit  437  may detect the change in the hydrogen-ion concentration (pH) of the sample solution within each of the plurality of reaction chambers  317  and may generate the detection signal Vout. 
     For example, from  FIG.  21   , it can be seen that, as indicated by C, a voltage level of the detection signal Vout changes according to the change in hydrogen-ion concentration. The third embodiment of the present disclosure is not limited to this change in the voltage level of the detection signal Vout. The reference electrode  341  may be formed of the material of each of the plurality of sensing electrodes  343 , and conversely, each of the plurality of sensing electrodes  343  may be formed of the material of the reference electrode  341 . In this case, it can be seen that, as indicated by D, the detection signal Vout changes in a direction opposite to a direction of the change in the hydrogen-ion concentration (pH). 
     The sensing module  450 ′ may sense temperature of the heat supply module  420 ′ and may generate a sensing signal. Then, the sensing module  450 ′ may transmit the generated sensing signal to the integrated control module  460 ′. The sensing module  450 ′ may include a temperature sensor. 
     The integrated control module  460 ′ supplies heat at a predetermined temperature, which is necessary for the nucleic acid amplification reaction, to each of the plurality of reaction chambers  317  through the heat supply module  420 ′. The integrated control module  460 ′ here may control the temperature of the heat supply module  420 ′ in a manner that is uniformly maintained. 
     When the heat at the predetermined temperature is supplied to each of the plurality of reaction chambers  317 , according to the plurality of detection signals, the integrated control module  460 ′ finds out whether the diagnosis target is present. According to the plurality of detection signals, the integrated control module  460 ′ may determine whether or not the hydrogen-ion concentration of the sample solution in each of the plurality of reaction chambers  317  changes. When the hydrogen-ion concentration changes, the integrated control module  460 ′ may determine that the diagnosis target is present. 
     The integrated control module  460 ′ may communicate with the user terminal  4  to transmit the result of diagnosing the diagnosis target. The integrated control module  460 ′ may be controlled by the user terminal  4  and may be realized as a printed circuit board (PCB). 
     As described above, only with one integrated molecular diagnosis apparatus  1  or  3  according to the first or third embodiment of the present disclosure, a process from the pretreatment of the collected sample to the transmission of the result of the diagnosis can be performed. Therefore, the result of the diagnosis can be obtained simply and quickly. In addition, the result of the diagnosis can be obtained by employing an optical method or a method that uses an electrochemical sensor. Thus, the integrated molecular diagnosis apparatus can be simply manufactured in a small size and thus can be used for point-of-care testing. The result of the diagnosis can be obtained from the user terminal  2 , and thus convenience can be improved. 
     Although the specific embodiment of the present disclosure has been described for illustrative purposes, those skilled in the art will appreciate that various modifications, additions and substitutions are possible, without departing from the scope and spirit of the disclosure as disclosed in the accompanying claims.