Integrated molecular diagnostic device

Abstract

The present invention relates to an integrated molecular diagnostic device, which includes a buffer tube into which a sampling tool taking a sample is inserted to generate a sample solution containing a nucleic acid extracted from the taken sample; a cartridge combined with the buffer tube to receive the sample solution, to transfer the sample solution to a reaction chamber through a fluid passage, and to receive heat of a prescribed temperature to perform a nucleic acid amplification reaction; and a diagnostic module body combined with the cartridge in a detachable manner to supply the heat of the prescribed temperature to the reaction chamber and to diagnose the presence or absence of a diagnosis object by detecting the nucleic acid amplification reaction.

Description

TECHNICAL FIELD

[0001] The present application relates to an integrated molecular diagnostic device, and more particularly, to an integrated molecular diagnostic device that minimizes the intervention of a user to perform operations from pre-processing of a taken sample to molecular diagnosis through one device and can be manufactured in a small size to implement on-site diagnosis.

[0002] The Korean national research and development project supporting the present application is as follows.

[0003] Subject inherent number: 1465032760

[0004] Subject number: HW20C2068

[0005] Ministry name: Ministry of Health and Welfare

[0006] Subject management (specialized) agency name: Korea Health Industry Development Institute

[0007] Research project name: Development of infectious disease epidemic prevention technology

[0008] Research subject name: Development of a sample pre-processing integrated LAMP method-based molecular diagnostic device that can rapidly diagnose on-site

[0009] Contribution rate: 1 / 1

[0010] Subject implementing agency name: Wizbiosolutions Inc.

[0011] Research period: September 1, 2020 to February 28, 2023 BACKGROUND

[0012] Generally, in a molecular diagnostic method, a gene of a harmful bacterium or virus is directly detected, and compared to an immunodiagnostic method, the accuracy is high, and the infection pathogen can be more accurately diagnosed. However, the molecular diagnostic method sequentially performs sampling, cell disruption, nucleic acid extraction, and nucleic acid amplification processes, and thus the process is relatively complex, and it takes a relatively long time of about 30 minutes to 2 hours to derive a result.

[0013] Accordingly, research is being conducted to shorten the examination time of the molecular diagnostic method and rapidly pre-process a sample for on-site examination (Point Of Care Testing (POCT)). Generally, sample pre-processing is a process of amplifying nucleic acids (deoxyribonucleic acid (DNA), ribonucleic acid (RNA), etc.) in cells through a polymerase chain reaction (PCR) and extracting the same to remove components that hinder or inhibit the amplification reaction and purify target nucleic acids at a high purity.

[0014] A conventional sample pretreatment method is a method of extracting nucleic acids using a centrifuge. However, a technique of automating a sample pretreatment process without using a centrifuge is being developed recently. Thus, a cartridge-integrated molecular diagnostic device that performs a process from sample pretreatment to molecular diagnosis through one diagnostic device has been commercialized.

[0015] Generally, the cartridge-integrated molecular diagnostic device controls fluid in a mechanical method using a valve or a motor in order to transfer a sample from sample pretreatment to an amplification process. Thus, a structure or a control method of a cartridge is complicated. In addition to the above-described method, there is a method of controlling a small volume of fluid using an electrowetting method, but an electrode array needs to be manufactured, a cost of a cartridge is expensive, and reliability of a diagnostic result is relatively low. SUMMARY

[0016] An embodiment of the present application provides a cartridge-integrated molecular diagnostic device that can minimize intervention of a user to perform a process from sample pretreatment to molecular diagnosis through one device and can be manufactured in a small size to implement a point-of-care test.

[0017] In an embodiment, the cartridge-integrated molecular diagnostic device includes a buffer tube into which a sampling tool that takes a sample is inserted to generate a sample solution containing nucleic acids extracted from the taken sample, a cartridge that receives the sample solution in combination with the buffer tube to transfer the sample solution to a reaction chamber through a fluid channel to perform a nucleic acid amplification reaction, and a diagnostic module body that is combined with the cartridge in a detachable manner to supply heat of a prescribed temperature to the reaction chamber to diagnose presence or absence of a diagnosis object by detecting the nucleic acid amplification reaction.

[0018] The disclosed technology can have the following effects. However, it does not mean that a specific embodiment must include all of the following effects or only include the following effects, and the scope of the invention of the disclosed technology should not be interpreted as being limited by the following effects.

[0019] The cartridge-integrated molecular diagnostic device of an embodiment of the present application can minimize intervention of a user to perform a process from sample pretreatment to molecular diagnosis through one device and can be manufactured in a small size to implement a point-of-care test. BRIEF DESCRIPTION OF DRAWINGS

[0020] Figure 1 A block diagram of a molecular diagnostic system of an embodiment of the present application is shown.

[0021] Figure 2 An embodiment of the cartridge-integrated molecular diagnostic device is shown. Figure 1

[0022] Figures 3a to 3c An embodiment of the cartridge-integrated molecular diagnostic device is shown.​Figure 1 The diagram shows the buffer tube.

[0023] Figures 4a to 4c This is a diagram used to illustrate the opening and closing mechanism shown in Figure 3.

[0024] Figure 5 For illustrative purposes Figure 1 The image shows a diagram of the card box.

[0025] Figures 6a to 6d For illustrative purposes Figure 5 The image shown is of the card box itself.

[0026] Figure 7a and Figure 7b For illustrative purposes Figure 5 The diagram shows the card holder support.

[0027] Figure 8 For illustrative purposes Figure 1 The diagram shown is a block diagram of the diagnostic module body.

[0028] Figure 9 For illustrative purposes Figure 8 The diagram shows the main body.

[0029] Figure 10 For illustrative purposes Figure 8 The diagram shows the heat supply module.

[0030] Figure 11 For illustrative purposes Figure 8 The diagram shows the detection module.

[0031] Figure 12 The flowchart illustrates a molecular diagnostic method according to an embodiment of the present invention.

[0032] Figure 13 This diagram illustrates the movement of the inlet cap component of the buffer tube.

[0033] Figure 14 This is a diagram used to illustrate the movement path of the sample solution.

[0034] Figure 15a and Figure 15b This is a diagram used to illustrate the diagnostic results.

[0035] Figure 16 To show Figure 1 A diagram of another embodiment of the integrated molecular diagnostic system shown.

[0036] Figures 17a to 17c For illustrative purposes Figure 16 The image shows a diagram of the card box.

[0037] Figure 18 For illustrative purposes Figure 16A diagram of the diagnostic module body shown.

[0038] Figure 19 For the purpose of Figure 18 A diagram of the heat supply module shown.

[0039] Figure 20a And Figure 20b For the purpose of Figure 18 A diagram of the detection module shown.

[0040] Figure 21 For the purpose of Figure 18 A diagram of the detection signal output from the detection module shown. DETAILED DESCRIPTION

[0041] The description of the present application is only for the purpose of structural and functional explanation of the embodiments, and the scope of the invention claimed by the present application should not be interpreted as being limited to the embodiments described herein. That is, the embodiments can be changed in various ways and have various embodiments, and therefore, it should be understood that the scope of the invention claimed by the present application includes equivalent technical solutions capable of achieving the technical idea. Also, the objects or effects proposed by the present application do not mean that the specific embodiments must include the above objects or effects, or only include the above objects or effects, and the scope of the invention claimed by the present application should not be interpreted as being limited to these embodiments.

[0042] On the other hand, the meaning of the terms described in the present application should be understood as follows.

[0043] The terms "first", "second", and the like are used to distinguish one structural element from other structural elements, and are not intended to limit the scope of the invention claimed by the present application by these terms. For example, a first structural element can be named as a second structural element, and similarly, a second structural element can be named as a first structural element.

[0044] It should be understood that when referring to a certain structural element "connected" to another structural element, it can be directly connected to the other structural element, or there can be other structural elements in between. In contrast, when referring to a certain structural element "directly connected" to another structural element, it should be understood that there are no other structural elements in between. On the other hand, the expressions used to explain the relationship between structural elements, i.e., "between" and "just between" or "adjacent to" and "directly adjacent to" and the like should also be interpreted in the same way.

[0045] Unless explicitly defined otherwise in the context, singular expressions shall be understood to encompass plural expressions, and "comprising" or "having" and the like shall be understood to denote the presence of the stated features, numbers, steps, operations, structural elements, components, or combinations thereof, without excluding the presence or additional possibility of one or more other features, numbers, steps, operations, structural elements, components, or combinations thereof.

[0046] The identification symbols (e.g., a, b, c, etc.) in each step are used for convenience of explanation, and are not used to explain the order of the steps, and unless the specific order of the steps is explicitly described in the context, the steps can be performed in a different order from the order described. That is, the steps can be performed in the same order as described, can be performed substantially simultaneously, or can be performed in the reverse order.

[0047] The present application can be implemented in a computer readable code in a computer readable recording medium including all kinds of recording devices storing data readable by a computer system. Examples of the computer readable recording medium are read only memory (ROM), random access memory (RAM), compact disc read only memory (CD-ROM), magnetic tape, floppy disk, optical data storage device, etc. Also, the computer readable recording medium can be distributed in computer systems connected through a network, and the computer readable code can be stored and executed in a distributed manner.

[0048] Unless otherwise defined, all terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. Terms generally used in dictionaries are to be interpreted as having the same meaning as the context of the relevant technology, and unless explicitly defined in the present application, no ideal or formal meaning is to be given.

[0049] Figure 1 To show a block diagram of a molecular diagnostic system according to an embodiment of the present application, Figure 2 To show Figure 1 a diagram of an embodiment of the integrated molecular diagnostic device shown.

[0050] Referring to Figure 1 and Figure 2 , an integrated molecular diagnostic system according to an embodiment of the present application can include an integrated molecular diagnostic device 1 and a user terminal 2. The integrated molecular diagnostic device 1 can communicate with the user terminal 2 through a network. The network can include a wired communication network, a wireless local area network, a wireless network communication technology (Wi-Fi), Bluetooth, Zigbee, or various mobile communication networks such as 2G, 3G, 4G, 5G, long term evolution (LTE), etc.

[0051] The integrated molecular diagnostic device 1 can automatically pre-process a test sample taken from a test subject and injected by a user, and can diagnose in real time whether a diagnostic object exists in the test sample. The diagnostic object of an embodiment of the present application can be a pathogenic bacterium of a respiratory disease. For example, the diagnostic object can be a pathogenic bacterium molecule of a respiratory disease such as respiratory syncytial virus (RSV), COVID-19, Delta COVID-19, etc. The integrated molecular diagnostic device 1 can transmit a diagnostic result to the user terminal 2.

[0052] The integrated molecular diagnostic device 1 can include a sampling tool 100, a buffer tube 200, a cartridge 300, and a diagnostic module body 400. Among them, the sampling tool 100, the buffer tube 200, and the cartridge 300 are disposable and can be disposed of after use. The sampling tool 100 takes a test sample from a test subject user. The sampling tool 100 can take a test sample from the mucosa of the inner wall of the nasal cavity or oral cavity of the test subject user in order to diagnose a pathogenic bacterium of a respiratory disease. The sampling tool 100 can be formed of a shape and material that is easy to take a test sample from a test subject user, for example, can be formed in a cotton swab shape that can be inserted into the nasal cavity or oral cavity of the test subject user.

[0053] The buffer tube 200 contains a buffer solution pre-injected therein, receives the sampling tool 100, and immerses it in the buffer solution. Among them, the buffer solution is a lysis buffer used as a buffer solution when a cell membrane is destroyed, and can be mixed with microparticles for improving lysis efficiency and pre-injected into the buffer tube 200.

[0054] The buffer tube 200 generates a test sample solution by extracting nucleic acid from a test sample taken by the sampling tool 100. In general, methods of destroying a cell membrane of a test sample include a chemical method of adjusting the pH of a buffer solution, or a method of removing large protein molecules by heating a buffer solution to a prescribed temperature (60℃ to 95℃) to cause protein denaturation, or a method of applying physical impact using ultrasonic waves, etc.

[0055] Compared to blood or other test samples, a respiratory pathogenic bacterium test sample has less impurities, and an embodiment of the present application adopts a method of destroying a cell membrane by applying physical impact to a test sample by shaking the buffer tube 200. That is, the buffer tube 200 is shaken together with the buffer solution in a state in which the sampling tool 100 is inserted and sealed, and can extract nucleic acid by destroying a cell membrane of a test sample by the operation of shaking. An embodiment of the present application is not limited thereto, and can extract nucleic acid by mixing at least one of a method of heating a buffer solution or a method of applying physical impact using ultrasonic waves.

[0056] The buffer tube 200 is inserted into the cartridge 300, and can supply the sample solution for extracting nucleic acid to the cartridge 300. The buffer tube 200 can discharge the sample solution to the outside through the perforation of the bottom surface when the buffer tube 200 is inserted into the cartridge 300. To this end, the buffer tube 200 can be formed of a plastic material having excellent chemical resistance and not being hard. For example, the buffer tube 200 can be formed of polypropylene (PP), polycarbonate (PC), or the like.

[0057] The cartridge 300 receives the sample solution supplied from the buffer tube 200 in combination with the buffer tube 200. The cartridge 300 extracts a predetermined amount of the sample solution through at least one fluid passage, mixes the sample solution with a reagent previously injected, and receives heat of a predetermined temperature supplied from the diagnostic module body 400 to perform a nucleic acid amplification reaction.

[0058] The reagent for amplifying nucleic acid contained in the sample solution to detect a diagnostic object can be previously injected into the cartridge 300 in a freeze-dried state. The cartridge 300 can be formed of a transparent plastic material having excellent chemical resistance and not being hard. For example, the cartridge 300 can be formed of polypropylene (PP), polycarbonate (PC), acryl, or the like.

[0059] The diagnostic module body 400 is combined with the cartridge 300 in a detachable manner, can supply heat of a predetermined temperature required for a nucleic acid amplification reaction to the cartridge 300 according to a preset operation condition, and can diagnose whether or not a diagnostic object exists by detecting a color or a fluorescence intensity of the sample solution changed by the nucleic acid amplification reaction. The operation condition can be set such that the sample solution is mixed with the reagent in the cartridge 300 to be in a state in which the nucleic acid amplification reaction is completed after the cartridge 300 is inserted into the diagnostic module body 400.

[0060] The diagnostic module body 400 can be controlled by the user terminal 2, and can transmit a diagnosis result regarding a diagnostic object by communicating with the user terminal 2. That is, the integrated molecular diagnostic apparatus 1 according to an embodiment of the present application can omit a process of moving the sample solution to the cartridge 300 and loading the cartridge 300 or the like by a user, and can implement a pre-treatment process of sampling, nucleic acid extraction, and amplification and a diagnosis process in a state in which intervention of the user is minimized by one apparatus.

[0061] The user terminal 2 can control the operation of the integrated molecular diagnostic device 1 by communicating with the integrated molecular diagnostic device 1. The user terminal 2 can receive the diagnostic result provided from the integrated molecular diagnostic device 1 to show in a screen. Among them, the diagnostic result can be shown as negative or positive. Also, the user terminal 2 can provide a screen showing the time required for diagnosis and the diagnostic result. The user terminal 2 can transmit the diagnosis place, date, diagnosis time, etc. to the database together with the diagnostic result and store. Among them, the database can be located inside or outside of the user terminal 2, and can be managed through a separate server.

[0062] The user terminal 2 can be a computing device used by a user who uses the integrated molecular diagnostic device 1. For example, the user terminal 2 can be a smart phone, a tablet PC, a desktop computer, a notebook computer, etc. computing device, but is not limited thereto. An application program linked with the integrated molecular diagnostic device 1 can be installed in the user terminal 2.

[0063] Figures 3a to 3c For explanation of Figure 1 the buffer tube shown in FIG. 1, Figures 4a to 4c For explanation of the opening and closing body shown in FIG. 3. Among them, Figure 3c For explanation of Figure 1 the buffer tube shown in FIG. 1 and Figure 5 the state in which the cartridge body shown in FIG. 2 is combined with the buffer tube, Figure 4b For explanation of Figure 4a the bottom view of the opening and closing body shown in FIG. 3, Figure 4c For explanation of Figure 4a the top view of the opening and closing body shown in FIG. 3.

[0064] Referring to Figure 3a , the buffer tube 200 can include a tube body 210, an opening and closing body 220, and a flow inlet cover member 230. The tube body 210 is formed in a cylindrical shape, and includes an internal space in which a buffer solution is accommodated. The tube body 210 can accommodate the sampling tool 100 in the internal space by opening the upper end through the opening and closing body 220.

[0065] Among them, the upper end of the tube body 210 can be sealed using a sealing film (not shown), and the sealing film can be removed at the time of molecular diagnostic examination. The tube body 210 can include a stepped portion 211 and a groove 213 formed in the outer peripheral surface to be combined with the cartridge 300. The stepped portion 211 is formed in a manner that the diameter is relatively larger than that of the tube body 210. The stepped portion 211 can be combined with the insertion hole 331 of the cartridge holder 330 to prevent the tube body 210 from being separated when the tube body 210 is installed in the cartridge 300.

[0066] The groove 213 is formed along the outer peripheral surface with a diameter relatively smaller than that of the tube body 210. The groove 213 is formed at a position corresponding to the engagement protrusion 335 of the card holder support 330 to engage with the engagement protrusion 335. Thus, the tube body 210 is pressed into the card holder 300 by the elastic force provided by the elastic member 333 to the engagement protrusion 335. Therefore, the buffer tube 200 can be fixed together with the card holder 300.

[0067] Moreover, such as Figure 3b As shown, the tube body 210 may include an anti-backflow portion 215 on its bottom surface. The anti-backflow portion 215 protrudes from the bottom surface of the tube body 210 and may be formed in a ring shape. The anti-backflow portion 215 may be formed with a width narrower than the bottom surface of the tube body 210. For example... Figure 3c As shown, the anti-backflow section 215 can be formed by the height of a portion of the flow inlet 313 when the tube body 210 is combined with the cartridge 300. Furthermore, preferably, the outer diameter of the anti-backflow section 215 can be formed to be the same size as the inner diameter of the support portion 311c of the tube housing body 311.

[0068] Therefore, when the sample solution contained inside the tube body 210 is discharged, the movement of the sample solution is only transmitted to the multiple fluid channels 315 through the inlet 313, while the flow is restricted to the space between the outer wall of the tube body 210 and the inner wall of the cartridge 300. This prevents the sample solution from flowing back along the outer surface of the tube body 210. Furthermore, the outer surface of the tube body 210 does not contact the sample solution, thus preventing any contaminants that may exist on the outer wall of the tube body 210 from contacting the sample solution.

[0069] The opening / closing body 220 is attached to the upper end of the tube body 210 to open and close the internal space of the tube body 210. For example... Figures 4a to 4c As shown, the opening / closing body 220 may include a textured surface 221, a boss 223, a through hole 225, multiple vent holes 227, and a locking part 229. The textured surface 221 is formed on the upper surface of the opening / closing body 220, which can minimize the contact area of ​​the user's hand during opening / closing operations and during the insertion of the buffer tube 200 into the cartridge 300, thereby preventing sample contamination.

[0070] The boss 223 protrudes from the bottom surface of the opening / closing body 220, forming a ring shape so that its outer peripheral surface is inserted into the inner peripheral surface of the tube body 210. The through hole 225 is formed by penetrating the upper and lower surfaces corresponding to the central region of the opening / closing body 220.

[0071] Multiple vent holes 227 are formed on the lower surface of the opening / closing body 220 between the side of the through hole 225 and the boss 223. The multiple vent holes 227 can be formed at a predetermined interval.

[0072] The locking part 229 bends inward on the side of the through hole 225 to support the inlet cover component 230. When the inlet cover component 230 moves, the bent surface of the locking part 229 deforms under the pressure transmitted through the inlet cover component 230, thereby supporting the inlet cover component 230 in a state that stops its movement.

[0073] The inlet cap component 230 seals the internal space of the tube body 210 by being inserted into the through hole 225 of the opening / closing body 220. The inlet cap component 230 can be supported by the locking part 229. The inlet cap component 230 is pressurized by the opening and closing operation of the diagnostic module body 400, moving towards the internal space of the tube body 210 to open multiple vent holes 227. That is, the inlet cap component 230 forms an air inflow path through the opening and closing operation of the diagnostic module body 400, allowing air to pass through the internal space.

[0074] The inlet cap component 230 can be formed of a material that allows air to pass through while blocking the sample solution (or buffer solution). That is, the inlet cap component 230 can be formed of a hydrophobic material, so that the sample solution will not flow out even if the buffer tube 200 or the cartridge 300 is inverted, and can be formed to a specified length that can function as a stopper.

[0075] Figure 5 For illustrative purposes Figure 1 The diagram shows one embodiment of the card box. Figures 6a to 6d For illustrative purposes Figure 5 The image shown is of the card box itself. Figure 7a and Figure 7b For illustrative purposes Figure 5 The diagram shows the card holder bracket. Among them, Figure 6c for Figure 6a The top view of the card box body shown. Figure 6d According to Figure 6a The AA' cutting line shows the cross-sectional view.

[0076] Reference Figure 5 The card holder 300 may include a card holder body 310, multiple outlet cover components 320, and a card holder support 330. For example, Figures 6a to 6d As shown, the cartridge body 310 is formed into a plate shape including a front surface and a rear surface, and may include a tube housing body 311, an inlet 313, multiple fluid channels 315, multiple reaction chambers 317 and multiple outlets 319.

[0077] The tube accommodating body 311 is formed in a shape protruding from the front surface of the cartridge body 310, and includes an internal space open at the upper end to allow insertion of the buffer tube 200. The internal space is formed in the same shape and size as the buffer tube 200, and can be restricted to allow only the sample solution to flow to the flow inlet 313 when the tube body 210 is combined with the cartridge 300.

[0078] The tube accommodating body 311 can include a combination hole 311a, a perforating member 311b, and a support portion 311c. The combination hole 311a can be formed through the front surface of the tube accommodating body 311 at a position corresponding to the combination protrusion 335 of the cartridge holder 330.

[0079] The perforating member 311b is formed on the support surface of the tube accommodating body 311, and can perforate the bottom surface of the buffer tube 200 using pressure applied by the operation of inserting the buffer tube 200. The perforating member 311b can protrude upward from the support surface of the tube accommodating body 311, and can be formed in a shape having a sharp end.

[0080] The support portion 311c can be formed to protrude in the direction of the internal space along the inner side of the tube accommodating body 311 except for the flow inlet 313, and can be formed at a predetermined height with reference to the support surface of the tube accommodating body 311. That is, the support portion 311c can be formed in a ring shape surrounding the support surface of the tube accommodating body 311.

[0081] The support portion 311c supports the anti-backflow portion 215 of the tube body 210 when the tube body 210 is inserted into the internal space of the tube accommodating body 311. That is, the anti-backflow portion 215 is combined in a manner in which the outer side surface thereof is in contact with the inner side surface of the support portion 311c, and thus the sample solution is restricted to flow only to the flow inlet 313.

[0082] The flow inlet 313 is formed through the rear surface of the cartridge body 310 at the support surface of the tube accommodating body 311. The flow inlet 313 allows the sample solution discharged from the bottom surface of the buffer tube 200 to flow into the plurality of fluid passages 315, respectively.

[0083] The plurality of fluid passages 315 are formed in the rear surface of the cartridge body 310, respectively, and can transfer the sample solution from the flow inlet 313 to the corresponding flow outlet 319 via the corresponding reaction chamber 317. The plurality of fluid passages 315 can include a first flow path 315a and a second flow path 315b, respectively.

[0084] The first flow paths 315a can be branched from the flow inlet 313 to the plurality of reaction chambers 317, respectively. The second flow paths 315b can be formed between the corresponding reaction chambers 317 and the flow outlets 319. The second flow paths 315b can be formed in a zigzag shape to increase fluid resistance. Thus, the fluid resistance of the sample solution flowing through the second flow paths 315b can be increased to maintain a constant moving speed.

[0085] The plurality of reaction chambers 317 can be formed in the rear surface of the cartridge body 310 to receive the sample solution transferred through the plurality of fluid paths 315, respectively. The plurality of reaction chambers 317 can contain a reagent injected in advance, respectively, to perform a nucleic acid amplification reaction on the sample solution by receiving heat of a predetermined temperature supplied from the diagnostic module body 400. The plurality of reaction chambers 317 can be formed in a size capable of receiving a predetermined amount of the sample solution, respectively.

[0086] An embodiment of the present application illustrates a case where the plurality of reaction chambers 317 is three, but an embodiment of the present application is not limited thereto, and the number of the reaction chambers 317 can be increased or decreased according to the number of target diagnostic objects.

[0087] The plurality of flow outlets 319 can be formed in the front surface of the cartridge body 310 between the corresponding reaction chambers 317 and the tube receiving body 311, respectively. That is, the plurality of reaction chambers 317 can be maintained in a state filled with the sample solution by locating the plurality of flow outlets 319 above the corresponding reaction chambers 317, respectively.

[0088] On the other hand, the cartridge body 310 of an embodiment of the present application can further include a sealing member (not shown) for sealing the flow inlet 313, the plurality of fluid paths 315, and the plurality of reaction chambers 317 in the rear surface. The sealing member can be formed of a transparent and thin film.

[0089] The plurality of flow outlet cover members 320 can be inserted into the plurality of flow outlets 319, respectively. The plurality of flow outlet cover members 320 can allow air to pass therethrough and block the sample solution flowing in the plurality of fluid paths 315, respectively. The plurality of flow outlet cover members 320 can be formed of a porous material, such as porous polyethylene or porous hydrogel material, respectively. Thus, the sample solution can not be discharged to the outside and can be maintained in a state of stopping flowing in the plurality of fluid paths 315.

[0090] The cartridge holder 330 can be coupled to the front surface of the cartridge body 310 to fix the buffer tube 200 in the cartridge body 310. As Figure 7a and Figure 7bAs shown, the cartridge holder 330 includes an inner space into which the cartridge body 310 is inserted, and can include an insertion hole 331, an elastic member 333, and a coupling protrusion 335.

[0091] The insertion hole 331 is formed at a position corresponding to the upper end of the tube accommodation body 311 to expose the inner space of the tube accommodation body 311. The elastic member 333 is a plate spring formed on the inner side surface facing the tube accommodation body 311. The elastic member 333 is elastically deformed by the sliding operation of the insertion buffer tube 200 to provide an elastic force to the coupling protrusion 335.

[0092] The coupling protrusion 335 is formed to protrude from the elastic member 333 at a position corresponding to the coupling hole 311a of the tube accommodation body 311 and is inserted into the coupling hole 311a. The coupling protrusion 335 has an inclined surface inclined, and can guide the elastic deformation of the elastic member 333 to the greatest extent at the end of the inclined surface to increase the elastic restoring force caused by the recovery of the elastic member 333. When the coupling protrusion 335 reaches the groove 213 by the sliding operation of the insertion buffer tube 200, the elastic restoring force provided from the elastic member 333 is received, and is fastened to the groove 213 with a "click" sound.

[0093] That is, it can be known that the tube body 210 is completely coupled with the cartridge body 310 in the correct position by the "click" sound emitted when the coupling protrusion 335 is coupled with the groove 213. Also, the coupling protrusion 335 makes the buffer tube 200 not to be separated from the cartridge body 310 after the buffer tube 200 is integrated with the cartridge body 310 and is fastened at one time.

[0094] Figure 8 for explanation Figure 1 a block diagram of a diagnostic module body, Figure 9 for explanation Figure 8 a diagram of a body, Figure 10 for explanation Figure 8 a diagram of a heat supply module, Figure 11 for explanation Figure 8 a diagram of a detection module.

[0095] Referring to Figure 8 , the diagnostic module body 400 can 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. As shown in FIG. 4, Figure 9As shown, the main body 410 may include a lower body 411 and an opening / closing body 413. The lower body 411 may be formed into a quadrilateral shape, including an internal space of a predetermined size. The lower body 411 may include an insertion hole 411a. The insertion hole 411a is formed on the upper surface of the lower body 411 and can be formed into a shape and size corresponding to the card holder 300, so as to insert the card holder 300.

[0096] The opening / closing body 413 is combined with the lower body 411 to open and close the internal space of the lower body 411. The opening / closing body 413 may include a pressing member 413a. The pressing member 413a is formed protruding from an internal surface corresponding to the upper surface of the lower body 411 and can be formed at a position corresponding to the inlet cap member 230 of the buffer tube 200. The pressing member 413a can be moved by applying pressure to the inlet cap member 230.

[0097] The heat supply module 420 is detachably combined with the cartridge 300 and supplies heat to multiple reaction chambers 317 to the specified temperature required for nucleic acid amplification reaction under the control of the integrated control module 460.

[0098] like Figure 10 As shown, the heat supply module 420 may include a heat conduction body 421 and a heating unit 423. The heat conduction body 421 is combined with the card holder 300 and receives heat at a predetermined temperature supplied from the heating unit 423 to transfer it to the card holder 300. The heat conduction body 421 houses the card holder 300 and the heating unit 423, and may include a card holder insertion slot 421a, a plurality of first holes 421b, and a plurality of second holes 421c.

[0099] The cartridge insertion slot 421a is formed at a position corresponding to the insertion hole 411a of the lower body 411, and is formed in such a way that its inner surface is in contact with the front surface, rear surface and bottom surface of the cartridge 300, which includes a region of multiple reaction chambers 317.

[0100] Multiple first holes 421b are formed by passing through the inner surface of one side of the cartridge insertion slot 421a. The multiple first holes 421b can be formed at positions corresponding to the multiple reaction chambers 317.

[0101] Multiple second holes 421c are formed by penetrating the bottom surface of the card insert slot 421a. The multiple second holes 421c can be formed at positions corresponding to the multiple reaction chambers 317.

[0102] The heating unit 423 is disposed within the heat conduction body 421 and generates heat at a specified temperature. The heating unit 423 may include a resistance heater, a thermoelectric device, etc.

[0103] One embodiment of the present invention is not limited thereto; the heat supply module 420 may also include a heat sink or the like that releases heat from the heat conduction body 421 to the outside.

[0104] The detection module 430 is configured adjacent to the heat supply module 420. Under the control of the integrated control module 460, light is irradiated onto multiple reaction chambers 317 respectively, and detection signals are generated by the light from the multiple reaction chambers 317 respectively.

[0105] like Figure 11 As shown, the detection module 430 may include multiple light sources 431 and multiple photodetectors 433. The multiple light sources 431 can respectively irradiate light onto multiple reaction chambers 317 under the control of the integrated control module 460. The multiple light sources 431 can be formed by light-emitting diodes (LEDs) or laser diodes (LDs).

[0106] In this embodiment, multiple light sources 431 can be arranged adjacent to multiple second holes 421c of the heat conduction body 421. The multiple light sources 431 can be arranged horizontally or vertically relative to the multiple photodetectors 433, with the cartridge 300 as a reference. One embodiment of the present invention shows an example of multiple light sources 431 arranged vertically relative to the multiple photodetectors 433; however, one embodiment of the present invention is not limited to this, and the multiple light sources 431 can be arranged horizontally relative to the multiple photodetectors 433, with the cartridge 300 as a reference.

[0107] Preferably, when the photodetector 433 detects the color of the sample solution, the light source 431 can be arranged in a direction horizontal to the photodetector 433; when the photodetector 433 detects the fluorescence of the sample solution, the light source 431 can be arranged in a direction perpendicular to the photodetector 433.

[0108] Multiple photodetectors 433 can detect light passing through each reaction chamber 317 to generate detection signals and transmit them to the integrated control module 460. The multiple photodetectors 433 can be respectively configured opposite to the multiple reaction chambers 317. The multiple photodetectors 433 can be respectively configured adjacent to the multiple first holes 421b of the heat conduction body 421. The multiple photodetectors 433 can each include an image sensor such as a photodiode (PD), photomultiplier tube (PMT), phototransistor, charge-coupled device (CCD), or complementary metal-oxide semiconductor (CMOS).

[0109] The power module 440 can supply power to the heat supply module 420, the detection module 430, and the integrated control module 460, respectively. The power module 440 can include a battery, a power button, a power terminal, etc.

[0110] The sensing module 450 can generate an opening / closing sensing signal by sensing the closed state of the body 410, and can generate a temperature sensing signal by sensing the temperature of the heat supply module 420. The sensing module 450 can include a leaf spring part (not shown) supporting the opening / closing body 413, a pressure sensor (not shown), and a temperature sensor (not shown).

[0111] The sensing module 450 can generate an opening / closing sensing signal by sensing the elastic force generated from the leaf spring part when the opening / closing body 413 is closed, through the pressure sensor. Also, the sensing module 450 can generate a temperature sensing signal by sensing the temperature of the heat supply module 420 through the temperature sensor.

[0112] The integrated control module 460 can determine whether the preset operation conditions are satisfied according to the detection signal and the opening / closing sensing signal transmitted from the detection module 430. Specifically, the integrated control module 460 can determine whether the cartridge 300 is inserted and the sample solution is delivered into the plurality of reaction chambers 317 according to the detection signal. That is, the integrated control module 460 of the present embodiment can determine the operation conditions by using the detection module 430 as a sensor for determining whether the cartridge 300 is inserted into the body 410 and as a sensor for determining whether the sample solution is injected into each of the reaction chambers 317.

[0113] Also, the integrated control module 460 can determine whether the body 410 is opened / closed according to the opening / closing sensing signal. That is, in the case where the cartridge 300 is inserted and the sample solution is delivered into the plurality of reaction chambers 317 and the body 410 is in the closed state, the integrated control module 460 can determine that all of the operation conditions are satisfied.

[0114] If the operation conditions are satisfied, the integrated control module 460 supplies heat of a prescribed temperature required for the nucleic acid amplification reaction to the plurality of reaction chambers 317 through the heat supply module 420, respectively. The integrated control module 460 can control the temperature of the heat supply module 420 to be within a constant level according to the temperature sensing signal.

[0115] When the heat of the prescribed temperature is supplied to the plurality of reaction chambers 317, respectively, the integrated control module 460 diagnoses the presence or absence of the diagnosis object by detecting the change in the color or the fluorescence intensity due to the nucleic acid amplification reaction from each of the sample solutions of the plurality of reaction chambers 317. The integrated control module 460 can communicate with the user terminal 2 to transmit the diagnosis result regarding the diagnosis object. The integrated control module 460 can be controlled by the user terminal 2, and can be implemented by a printed circuit board (PCB).

[0116] Figure 12 FIG. 1 is a flowchart showing a molecular diagnostic method according to an embodiment of the present application, Figure 13 FIG. 4 is a diagram for explaining a moving operation of an inlet cover member of a buffer tube, Figure 14 FIG. 5 is a diagram for explaining a moving path of a sample solution, Figure 15a and Figure 15b FIG. 6 is a diagram for explaining a diagnosis result.

[0117] Referring to Figure 12 , first, the sample is taken from a user by using the sampling tool 100 (step S110). Then, the sampling tool 100 is put into the tube body 210 of the buffer tube 200 (step S120). In this case, the sampling tool 100 is dipped in the buffer solution that is previously injected into the buffer tube 200. Then, the opening and closing body 220 is closed. In this case, the inlet cover member 230 is inserted into the through hole 225 of the opening and closing body 220, and when the opening and closing body 220 is closed, the tube body 210 is sealed.

[0118] Then, the buffer tube 200 is shaken. Thus, the cell membrane of the sample taken by the sampling tool 100 is broken to extract the nucleic acid (step S130). Thereby, the sample solution in which the nucleic acid is mixed in the buffer solution is prepared.

[0119] In this state, the cartridge 300 is mounted to the diagnosis module body 400 through the insertion hole 411a of the lower body 411 (step S140). Also, the buffer tube 200 is inserted into the tube housing body 311 of the cartridge 300. In this case, the bottom surface of the tube body 210 is perforated by the perforating member 311b (step S150). Thus, the sample solution is discharged from the tube body 210. In this case, the plurality of vent holes 227 are in a closed state by the inlet cover member 230 of the buffer tube 200, so that the sample solution does not flow into the inlet 313.

[0120] In this state, as Figure 13As shown, if the opening and closing body 413 is closed, the pressing member 413a of the opening and closing body 413 presses the flow inlet cover member 230 of the buffer tube 200, and the flow inlet cover member 230 moves to the lower side to open the plurality of air holes 227. Thus, an air inflow path A is formed in which air flows into the internal space of the tube body 210.

[0121] As shown, in a state in which air passes through both ends of the plurality of fluid channels 315, the sample solution moves along a path B from the flow inlet 313 through the corresponding reaction chamber 317 and to the flow outlet 319 by capillary force. In this case, the plurality of flow outlets 319 are each in a state of being closed by the corresponding flow outlet cover member 320, and the sample solution is stored in the reaction chamber 317 in a state of stopping flowing. In this way, the sample solution is transferred to the corresponding reaction chamber 317 through the plurality of fluid channels 315 (step 160). Figure 14

[0122] In this case, the integrated control module 460 determines whether the operation conditions are satisfied based on the detection signal and the opening and closing sensing signal. For example, the integrated control module 460 can determine whether the cartridge 300 is inserted into the body 410 based on the detection signal, and determine whether the sample solution is injected into each reaction chamber 317. Also, the integrated control module 460 can determine whether the body 410 is opened and closed based on the opening and closing sensing signal. When the cartridge 300 is inserted into the diagnostic module body 400 and the body 410 is closed to inject the sample solution into each reaction chamber 317, the integrated control module 460 can determine that all operation conditions are satisfied.

[0123] In this way, when all operation conditions are satisfied, the integrated control module 460 supplies heat of a predetermined temperature to the plurality of reaction chambers 317 through the heat supply module 420. Thus, the nucleic acid amplification reaction of the sample solution stored in each reaction chamber 317 is performed. In this case, the detection module 430 generates a detection signal by detecting the color or the fluorescence intensity of the sample solution and transmits the detection signal to the integrated control module 460.

[0124] Then, the integrated control module 460 diagnoses whether the diagnosis object exists or not based on the detection signal from each sample solution of the plurality of reaction chambers 317 by detecting the change in the color or the fluorescence intensity caused by the nucleic acid amplification reaction.

[0125] ​For example, reaction chambers 317 are divided into three sections: A, B, and C. Reaction chambers A and B may contain reagents for detecting type I and type II genes, respectively, which are diagnostic for COVID-19. Reaction chamber C may contain an internal control (IC) reagent to confirm whether the device is operating correctly and whether the sampling is adequate. The internal control (IC) is used to confirm the ribonucleic acid of epithelial cells; if the sampling is insufficient or the device is not operating correctly, it will show a negative result.

[0126] In this state, if the integrated control module 460 detects a color change in the sample solutions contained in reaction chambers A, B, and C, respectively, due to the pH change before and after the nucleic acid amplification reaction, it can be determined that a diagnostic target is present. Therefore, the sample solutions contained in reaction chambers A, B, and C may contain a phenol red indicator or a purple indicator that changes color through the nucleic acid amplification reaction.

[0127] For example, such as Figure 15a As shown, when the color of the sample solutions contained in reaction chambers A and C changed after the nucleic acid amplification reaction, while the color of the sample solution contained in reaction chamber B remained unchanged, the detection signals corresponding to the color changes in reaction chambers A and C, i.e., the electrical signal values, increased compared to the electrical output values ​​before the nucleic acid amplification reaction (represented by the dashed line). This confirms that the integrated control module 460 sampled appropriately and the device is operating normally, and it can be determined that the first type of novel coronavirus pneumonia virus is present (positive).

[0128] In contrast, the integrated control module 460 can diagnose the presence of a diagnostic target by detecting the fluorescence intensity of the sample solution through a nucleic acid amplification reaction. For example, as Figure 15b As shown, when the fluorescence intensity of the sample solutions contained in reaction chambers A and C increases differently than that in reaction chamber B, it can be confirmed that the integrated control module 460 sampling is appropriate and the device is operating normally, and it can be determined that the first type of novel coronavirus pneumonia virus is present (positive).

[0129] Then, the integrated control module 460 provides the user terminal 2 with the diagnostic results of the diagnostic object (step S170). After that, the buffer tube 200 and the card holder 300 can be sealed and disposed of.

[0130] On the other hand, an embodiment of the present application is not limited to this, and in step S140, when the cartridge 300 is inserted into the diagnostic module body 400, the cartridge 300 can be inserted into the diagnostic module body 400 in a state in which the buffer tube 200 is inserted into the cartridge 300. That is, the buffer tube 200 can be inserted into the cartridge 300 first, and then the buffer tube 200 and the cartridge 300 can be inserted into the diagnostic module body 400 together.

[0131] Figure 16 FIG. 2 is a diagram for explaining a cartridge according to an embodiment of the present application, Figures 17a to 17c FIG. 3 is a diagram for explaining a diagnostic module body according to an embodiment of the present application, Figure 16 FIG. 4 is a diagram for explaining a cartridge according to an embodiment of the present application, Figure 18 FIG. 5 is a diagram for explaining a diagnostic module body according to an embodiment of the present application, Figure 16 FIG. 6 is a diagram for explaining a cartridge according to an embodiment of the present application, Figure 19 FIG. 7 is a diagram for explaining a diagnostic module body according to an embodiment of the present application, Figure 18 FIG. 8 is a diagram for explaining a cartridge according to an embodiment of the present application, Figure 20a FIG. 9 is a diagram for explaining a diagnostic module body according to an embodiment of the present application, Figure 20b FIG. 10 is a diagram for explaining a cartridge according to an embodiment of the present application, Figure 18 FIG. 11 is a diagram for explaining a diagnostic module body according to an embodiment of the present application, Figure 21 FIG. 12 is a diagram for explaining a detection signal output from a detection module according to an embodiment of the present application. Figure 18 Referring to FIG. 1,

[0132] , an integrated molecular diagnostic system according to another embodiment of the present application can include an integrated molecular diagnostic device 3 and a user terminal 4. The integrated molecular diagnostic device 3 can include a sampling tool 100`, a buffer tube 200`, a cartridge 300`, and a diagnostic module body 400`. Among them, the sampling tool 100` and the buffer tube 200` are the same structure as the sampling tool 100 and the buffer tube 200 of the embodiment of the present application, and thus the detailed description thereof will be omitted. Figure 16 The cartridge 300` is the same as the cartridge 300 of the embodiment of the present application, but further includes a sensing unit 340. Thus, the same structure will be described with the same reference numerals, and the detailed description thereof will be omitted for convenience of explanation. Among them, the sensing unit 340 senses the hydrogen ion concentration (pH) in reaction with the hydrogen ion contained in each of the sample solutions of the plurality of reaction chambers 317. As

[0133] shown in FIG. 3, the sensing unit 340 can include a reference electrode 341 and a plurality of sensing electrodes 343. Figures 17a to 17c The reference electrode 341 is coupled to the rear surface of the cartridge body 310, and the reference electrode 341 can be formed in a plate shape covering all of the opening surfaces of the flow inlet 313, the plurality of fluid passages 315, and the plurality of reaction chambers 317. That is, the reference electrode 341 of the embodiment of the present application can function as a sealing member that seals the rear surface of the cartridge body 310.

[0134]

[0135] ​The reference electrode 341 includes an electrode terminal surface 341a extending downward from the bottom surface of the cartridge body 310, and can be electrically connected to the diagnostic module body 400 via the electrode terminal surface 341a.

[0136] The reference electrode 341 can be in contact with the sample solution via a surface corresponding to each of the opening surfaces of the plurality of reaction chambers 317. The reference electrode 341 has a prescribed reference potential in changes in the hydrogen ion concentration (pH) of the sample solution. The reference electrode 341 can be formed of a half-cell reactant material having pH stability and high reproducibility. For example, the reference electrode 341 can be formed of Ag / AgCl.

[0137] The half-cell refers to a cell that generates a potential difference according to an oxidation or reduction reaction. That is, when oxidation or reduction reactions occur in the plurality of sensing electrodes 343 according to the hydrogen ion concentration (pH) of the sample solution, respectively, the reference electrode 341 can operate as a reduction electrode or an oxidation electrode different from the plurality of sensing electrodes 343.

[0138] The plurality of sensing electrodes 343 are in contact with the sample solution in each of the internal spaces of the plurality of reaction chambers 317 in a manner spaced apart from the reference electrode 341, respectively. The plurality of sensing electrodes 343 can be formed to penetrate the cartridge body 310 in the internal spaces of the plurality of reaction chambers 317, respectively. That is, the plurality of sensing electrodes 343 can be formed to be inserted into the internal spaces of the plurality of reaction chambers 317 from the bottom surface of the cartridge body 310, respectively. Thus, one end of each of the plurality of sensing electrodes 343 can be disposed in the internal spaces of the plurality of reaction chambers 317 to be in contact with the sample solution, and the other end can be exposed on the bottom surface of the cartridge body 310 and electrically connected to the diagnostic module body 400.

[0139] The plurality of sensing electrodes 343 each have a sensing potential that varies according to changes in the hydrogen ion concentration (pH) of the sample solution. That is, the two ends of the reference electrode 341 and the plurality of sensing electrodes 343 each operate as a potential capacitor, and the sensing potential of each of the plurality of sensing electrodes 343 can vary with the reference potential of the reference electrode 341 as a reference. The plurality of sensing electrodes 343 can each be formed of a metal oxide material sensitive to the hydrogen ion concentration (pH), such as indium tin oxide (ITO), SiO2, or the like.

[0140] The diagnostic module body 400' is coupled to the cartridge 300' in a detachable manner, supplies heat of a prescribed temperature required for a nucleic acid amplification reaction to the cartridge 300', and can diagnose the presence or absence of a diagnosis target by detecting changes in the hydrogen ion concentration caused by the nucleic acid amplification reaction via an electrical signal.

[0141] As Figure 18As shown, the diagnostic module 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' and power supply module 440' have the same structure as the body 410 and power supply module 440 of one embodiment of the present invention, therefore their detailed description will be omitted.

[0142] The heat supply module 420' is detachably connected to the cartridge 300' and, under the control of the integrated control module 460', supplies heat to multiple reaction chambers 317 to the specified temperature required for nucleic acid amplification reactions.

[0143] like Figure 19 As shown, the heat supply module 420' may include a heat conduction body 421' and a heating unit 423'. The heat conduction body 421' has a card holder 300' inserted into it, and receives heat at a specified temperature supplied from the heating unit 423' to transfer to the card holder 300'.

[0144] The heat conduction body 421' houses the card holder body 310 and the heating unit 423, and may include a card holder insertion slot 421a', a first connector insertion hole 421b', and a second connector insertion hole 421c'. The card holder insertion slot 421a' is formed at a position corresponding to the insertion hole 411a of the lower body 411, and can be formed such that its inner surface is in contact with the front surface, rear surface, and bottom surface of the card holder body 310, which includes a region of multiple reaction chambers 317. The card holder insertion slot 421a' can be formed such that its bottom surface has a corresponding height difference with the electrode terminal surface 341a of the reference electrode 341.

[0145] The first connector insertion hole 421b' can be formed by penetrating the bottom surface of the card holder insertion slot 421a', and the second connector insertion hole 421c' can be formed by being spaced apart from the first connector insertion hole 421b' by a specified distance and penetrating the bottom surface of the card holder insertion slot 421a'.

[0146] The heating unit 423' is disposed within the heat conduction body 421' and heats up at a predetermined temperature under the control of the integrated control module 460'. The heating unit 423' may include a resistance heater, a thermoelectric device, etc. One embodiment of the present invention is not limited thereto, and the heat supply module 420' may also include a cooling unit, etc., for dissipating heat generated in the heat conduction body 421' to the outside.

[0147] The detection module 430' is electrically connected to the sensing unit 340' of the cartridge 300' to supply a reference voltage of a specified magnitude to the reference electrode 341, and detects the sensing voltages of the multiple sensing electrodes 343 to generate multiple detection signals. The detection module 430' can transmit the detection signals to the integrated control module 460'.

[0148] like Figure 20a As shown, the detection module 430' may include a reference electrode connector 431', multiple sensing electrode connectors 433', a reference voltage supply unit 435, and a hydrogen ion concentration detection unit 437. The reference electrode connector 431' contacts the reference electrode 341 by being inserted into the first connector insertion hole 421b' of the heat conduction body 421'.

[0149] The reference electrode connector 431' may include an insertion groove 431a for inserting the electrode terminal face 341a of the reference electrode 341, which can contact the reference terminal face 341a. One embodiment of the present invention is not limited thereto, and the reference electrode connector 431' may be bent into a "┐" shape to contact the electrode terminal face 341a of the reference electrode 341.

[0150] Multiple sensing electrode connectors 433' are respectively inserted into multiple second connector insertion holes 421c' of the heat conduction body 421' to contact multiple sensing electrodes 343 respectively. Multiple sensing electrode connectors 433' can contact multiple sensing electrodes 343 respectively on the bottom surface of the cartridge body 310.

[0151] The reference voltage supply unit 435 supplies a voltage at a specified potential to the reference electrode 341 through the reference electrode connector 431'.

[0152] The hydrogen ion concentration detection unit 437 is electrically connected to multiple sensing electrodes 343 through multiple sensing electrode connectors 433', and generates multiple detection signals by detecting the sensing potential of each of the multiple sensing electrodes 343.

[0153] The hydrogen ion concentration detection unit 437 may include multiple in-phase operational amplifiers (APs). For example... Figure 20b As shown, the multiple non-inverting operational amplifiers AP may include a non-inverting input terminal (+) connected to multiple sensing electrode connectors 433', an inverting input terminal (-) for receiving ground voltage, and an output terminal for outputting a detection signal Vout.

[0154] The sensing potential Vs of the sensing electrode 343 can change ΔVs based on the change in hydrogen ion concentration (pH) of the sample solution SS with reference potential Vr as the reference. The positive operational amplifier AP can output the change in sensing potential Vs through the detection signal Vout. That is, the hydrogen ion concentration detection unit 437 can generate the detection signal Vout by detecting the change in hydrogen ion concentration (pH) of the sample solution in multiple reaction chambers 317.

[0155] For example, such as Figure 21As shown, it can be seen that the voltage level of the detection signal Vout changes to the level of (C) as the hydrogen ion concentration (pH) changes. An embodiment of the present application is not limited thereto, and the reference electrode 341 and the plurality of sensing electrodes 343 can interchange materials, in which case the detection signal Vout can show a tendency to change in the opposite direction to the change in the hydrogen ion concentration (pH) as shown in (D).

[0156] The sensing module 450` can sense the temperature of the heat supply module 420` to generate a temperature sensing signal and transmit it to the integrated control module 460`. The sensing module 450` can include a temperature sensor.

[0157] The integrated control module 460` supplies heat of a prescribed temperature required for a nucleic acid amplification reaction to the plurality of reaction chambers 317 through the heat supply module 420`, respectively. Herein, the integrated control module 460` can control the temperature of the heat supply module 420` to be within a constant level according to the temperature sensing signal.

[0158] When heat of a prescribed temperature is supplied to the plurality of reaction chambers 317, respectively, the integrated control module 460` diagnoses whether a diagnosis object exists according to the plurality of detection signals. The integrated control module 460` can determine whether the hydrogen ion concentration of each of the sample solutions of the plurality of reaction chambers 317 changes according to the plurality of detection signals, and if the hydrogen ion concentration changes, determine that a diagnosis object exists.

[0159] The integrated control module 460` can transmit a diagnosis result regarding a diagnosis object by communicating with the user terminal 4. The integrated control module 460` can be controlled through the user terminal 4, and can be implemented through a printed circuit board.

[0160] As described above, the integrated molecular diagnosis apparatus 1 according to an embodiment of the present application can implement a process from pre-processing of a taken sample to a diagnosis result in one apparatus. Accordingly, a diagnosis result can be obtained simply and quickly. Also, since a diagnosis result is obtained through an optical method or an electrochemical sensor method, an instrument can be miniaturized and simplified, and thus can be used in a field diagnosis. Also, a diagnosis result can be obtained through the user terminal 2, and thus convenience can be improved.

Claims

1. An integrated molecular diagnostic device, comprising: a buffer tube into which a sampling tool that takes a sample is inserted, generating a sample solution containing nucleic acids extracted from the taken sample; a cartridge that receives the sample solution in conjunction with the buffer tube, moving the sample solution to a reaction chamber through a fluid passage to perform a nucleic acid amplification reaction; and a diagnostic module body that, in a detachable manner, is combined with the cartridge to supply heat of a prescribed temperature to the reaction chamber, diagnosing the presence or absence of a diagnosis object by detecting the nucleic acid amplification reaction, wherein the buffer tube is pre-injected with a buffer solution, and in a state in which the sampling tool is inserted, the nucleic acids are extracted by a shaking operation that disrupts the cell membrane of the sample, wherein the buffer tube includes: a tube body that houses the sampling tool, including an internal space into which the buffer solution is pre-injected; an opening and closing body that opens and closes the internal space in conjunction with the tube body; and a flow inlet cover member that is inserted through the opening and closing body, selectively allowing air to flow into the internal space of the tube body by moving in response to an applied pressure force from the diagnostic module body, wherein the opening and closing body includes: a boss that protrudes from a lower surface, is formed in a ring shape, and has an outer circumferential surface that is inserted into an inner circumferential surface of the tube body; a through hole that is formed in a manner that passes through between an upper surface and the lower surface, for insertion of the flow inlet cover member; and a plurality of vent holes that are formed on the lower surface between a side surface of the through hole and the boss, formed apart from each other, wherein the diagnostic module body includes a pressing member that is formed at a position corresponding to the flow inlet cover member, wherein the pressing member applies the pressure force to the flow inlet cover member by an opening and closing operation of the diagnostic module body, wherein the plurality of vent holes are in a state of being sealed by the flow inlet cover member, and when the diagnostic module body is closed such that the pressing member applies the pressure force to the flow inlet cover member, the flow inlet cover member moves in the direction of the internal space of the tube body, causing the plurality of vent holes to open, wherein the buffer tube is formed of a plastic material that includes at least one of polypropylene and polycarbonate, wherein the cartridge includes: a cartridge body that is formed in a plate shape including a front surface and a rear surface; and a cartridge holder that is combined to the front surface of the cartridge body, wherein the cartridge body includes: a tube housing body that is formed on the front surface of the cartridge body, including an internal space into which the buffer tube is inserted; a flow inlet that is formed through the rear surface of the cartridge body from a support surface of the tube housing body that is in contact with a bottom surface of the buffer tube; a flow outlet that is formed on the front surface of the cartridge body, disposed between the flow inlet and the reaction chamber; a fluid passage that is formed on the rear surface of the cartridge body, moving the sample solution from the flow inlet to the flow outlet; the reaction chamber that is formed within the fluid passage on the rear surface of the cartridge body, houses the sample solution, contains a pre-injected reagent, and receives the heat of the prescribed temperature to perform the nucleic acid amplification reaction; and a flow outlet cover member that is inserted into the flow outlet to allow air to pass through, blocking the sample solution. ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ 2. The integrated molecular diagnostic device of claim 1, wherein ​ 3. The integrated molecular diagnostic device of claim 1, wherein ​ ​ ​ 4. The integrated molecular diagnostic device of claim 3, wherein ​ ​ ​ ​ ​ ​ ​ 5. The integrated molecular diagnostic device of claim 4, wherein The fluid passage includes: a first flow path formed from the flow inlet to the reaction chamber; and a second flow path formed from the reaction chamber to the flow outlet.

6. The integrated molecular diagnostic device of claim 5, wherein The second flow path is formed in a zigzag curved shape.

7. The integrated molecular diagnostic device of claim 4, wherein The flow outlet cover member is formed of at least one of porous polyethylene and porous hydrogel.

8. The integrated molecular diagnostic device of claim 4, wherein, The tube housing body includes: a coupling hole formed in the front surface; and a perforating member formed on the support surface to perforate the bottom surface of the buffer tube.

9. The integrated molecular diagnostic device of claim 8, wherein, The cartridge holder includes: a resilient member formed on the inner side surface of the tube housing body to be elastically deformed by a sliding operation of inserting the buffer tube; and a coupling protrusion formed to protrude from the resilient member at a position corresponding to the coupling hole, having an inclined surface inclined.

10. The integrated molecular diagnostic device according to claim 9, wherein the buffer tube includes a groove formed in an outer circumferential surface at a position corresponding to the coupling hole, the coupling protrusion is inserted into the coupling hole to be engaged with the groove, and receives an elastic restoring force of the resilient member to press the buffer tube.

11. The integrated molecular diagnostic device of claim 3, wherein The cartridge includes a sensing unit that senses a hydrogen ion concentration of the sample solution in the reaction chamber.

12. The integrated molecular diagnostic device of claim 11, wherein, The sensing unit includes: a reference electrode that contacts the sample solution and has a prescribed reference potential in a change in the hydrogen ion concentration of the sample solution; and a sensing electrode that contacts the sample solution in a manner spaced apart from the reference electrode and has a sensing potential that changes in the change in the hydrogen ion concentration of the sample solution.

13. The integrated molecular diagnostic device of claim 12, wherein, The reference electrode is formed of Ag / AgCl.

14. The integrated molecular diagnostic device of claim 12, wherein, The reference electrode includes an electrode terminal surface formed in a plate shape to cover an opening surface of the reaction chamber, to be engaged with the cartridge body, and to be electrically contacted with the diagnostic module body, with a bottom surface of the cartridge body as a reference.

15. The integrated molecular diagnostic device of claim 12, wherein, The sensing electrode is formed to pass through the cartridge body from an inner space of the reaction chamber.

16. The integrated molecular diagnostic device of claim 12, wherein, The diagnostic module body includes: a detection module that is electrically connected to the reference electrode and the sensing electrode, respectively, detects a sensing potential of the sensing electrode, and generates a detection signal; and an integrated control module that diagnoses whether the diagnostic object exists or not, based on a change in the hydrogen ion concentration of the sample solution, according to the detection signal.

17. The integrated molecular diagnostic device of claim 1, wherein, The cartridge is formed of a transparent plastic material including at least one of polypropylene, polycarbonate, and acrylic acid.

18. The integrated molecular diagnostic device of claim 1, wherein, The diagnostic module body includes: a body including an internal space of a prescribed size, including a lower body in which an insertion hole into which the cartridge is inserted is formed in an upper surface, and an opening and closing body that is engaged with the lower body to open and close the internal space; a heat supply module that is disposed in the internal space of the body, is detachably engaged with the cartridge through a cartridge insertion slot formed at a position corresponding to the insertion hole, and supplies heat of the prescribed temperature to the reaction chamber; a detection module that is disposed in the internal space of the body to irradiate light to the reaction chamber, detects a color or a fluorescence intensity of the sample solution, and generates a detection signal; and An integrated control module is disposed in the internal space of the body and diagnoses the presence or absence of the diagnosis object by judging the color or fluorescence intensity of the sample solution changed by the nucleic acid amplification reaction based on the detection signal.

19. The integrated molecular diagnostic device of claim 18, wherein, The detection module includes: A light source that irradiates light to the reaction chamber; and A light detector that detects the color or fluorescence intensity of the sample solution irradiated by the light to generate the detection signal.

20. The integrated molecular diagnostic device of claim 18, wherein, The integrated control module communicates with a user terminal and transmits the diagnosis result of the diagnosis object to the user terminal.

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