A molecular diagnostic system

Abstract

This invention provides a molecular diagnostic system comprising a nucleic acid extraction and dispensing system, a sample loading system, an injection system, a nucleic acid amplification system, and a gripper and detection system. The sample loading system is located above the injection system, and the gripper and detection system is located above the nucleic acid amplification system. These systems cooperate in a mechanized and automated manner to achieve molecular diagnostics. The injection system includes a molecular detection card, which further includes a non-deformable card body. This system achieves a fully automated molecular diagnostic system with minimal contamination and simultaneously supports multiple amplification types and multiple tests.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of in vitro diagnostic molecular detection instruments, and more particularly, to a molecular diagnostic system. BACKGROUND

[0002] The existing in vitro diagnostic molecular detection instrument is mainly used for molecular diagnosis, and the molecular diagnosis is a technology of making a diagnosis by detecting the changes in the structure or expression level of genetic material in the body of a patient by using molecular biology methods. The molecular diagnosis is a main method of predictive diagnosis, and can be used for diagnosing individual genetic diseases and prenatal diagnosis. The molecular diagnosis mainly refers to the detection of genes encoding various structural proteins, enzymes, antigens and antibodies, and immunologically active molecules related to diseases.

[0003] Since the molecular detection plate of the in vitro diagnostic molecular detection instrument is frequently replaced, the use frequency is high, and the sealing requirement in the application to the in vitro diagnostic molecular detection instrument is relatively high.

[0004] The existing molecular diagnostic system is a single item test or a multi-item test, and none of the systems is an instrument and system capable of testing single items and multiple items (more than 6 items).

[0005] The existing molecular system is either a single-step amplification or a two-step amplification, and there is no detection system compatible with both.

[0006] The existing automatic high-throughput analysis instrument cannot work in a general laboratory environment due to the problem of pollution control, and needs to solve the problem of pollution to achieve use in a general laboratory environment.

[0007] Due to the randomness (unplanned nature) of hospital projects, a project cannot be detected on the same machine as multiple projects.

[0008] In order to solve the unplanned nature of precision requirements, both single-step amplification and secondary amplification of some high-precision projects are supported, and both nested PCR and ordinary PCR are supported.

[0009] Therefore, a new molecular diagnostic system needs to be proposed. SUMMARY

[0010] The present application provides a molecular diagnostic system to at least solve the technical problems of pollution and inability to meet the full automation of multiple projects and multiple amplification types of the existing molecular diagnostic system.

[0011] The application provides a molecular diagnostic system, which comprises a nucleic acid extraction and liquid adding system, a sample adding system, a sample feeding system, a nucleic acid amplification system, and a gripper and detection system, the sample adding system is located above the sample feeding system, the gripper and detection system is located above the nucleic acid amplification system, and the nucleic acid extraction and liquid adding system, the sample adding system, the sample feeding system, the nucleic acid amplification system and the gripper and detection system are cooperated with each other in the mechanical automation of the molecular diagnostic system to realize molecular diagnosis.

[0012] The sample feeding system comprises a molecular detection card, the molecular detection card comprises a first liquid suction port, a second liquid suction port, a third liquid suction port and a molecular detection card cavity, the first liquid suction port, the second liquid suction port and the third liquid suction port are connected with the molecular detection card cavity respectively, the molecular detection card further comprises a card body which cannot be deformed, and the molecular detection card cavity is arranged in the card body which cannot be deformed.

[0013] Optionally, the sample feeding system further comprises a transport ship, a sample rack, a sample tube, a vacuum cavity, a first heat gun and a second heat gun, the sample tube and the molecular detection card are arranged in the sample rack, the sample rack is arranged in the transport ship, the transport ship transports the sample rack to the vacuum cavity, after the first liquid suction port and the second liquid suction port are filled with the sample to be detected required by the molecular detection card, the transport ship transports the sample rack to the vacuum cavity, and the vacuum cavity and the transport ship form a vacuum chamber, and the first liquid suction port and the second liquid suction port containing the sample to be detected are vacuumized to negative pressure in the vacuum chamber.

[0014] Optionally, the first heat gun can move to the third liquid suction port to heat seal the third liquid suction port, and the second heat gun can move to the first liquid suction port and the second liquid suction port to heat seal the first liquid suction port and the second liquid suction port.

[0015] Optionally, the nucleic acid extraction and liquid adding system comprises a molecular detection plate, a dovetail groove is arranged on the molecular detection plate, the dovetail groove is located at the tail of the molecular detection plate, the molecular detection plate further comprises a cover plate, the cover plate is connected with the dovetail groove in cooperation, the cover plate and the dovetail groove are connected in cooperation in two gears, the two-gear cooperation connection comprises an open cover connection and a closed cover connection, the cover plate changes from the open cover connection to the closed cover connection under the action of external force, and the dovetail groove and the molecular detection plate are fixedly connected as an integrated structure.

[0016] Optionally, the molecular detection card cavity includes a liquid storage chamber, a mixing chamber, a first amplification chamber, and a second amplification chamber. The first aspiration port is connected to the first amplification chamber, the second aspiration port is connected to the liquid storage chamber, the liquid storage chamber is connected to the mixing chamber, the mixing chamber is connected to the first amplification chamber, the mixing chamber is connected to the second amplification chamber, and the third aspiration port is connected to the second amplification chamber; and / or

[0017] In the initial state, the liquid storage chamber is connected to but not communicating with the mixing chamber; the mixing chamber is connected to but not communicating with the first amplification chamber; and the mixing chamber is connected to and communicating with the second amplification chamber; and / or

[0018] In operation, the liquid storage chamber is connected to the mixing chamber, the mixing chamber is connected to the first amplification chamber, and the mixing chamber is connected to the second amplification chamber.

[0019] Optionally, the liquid storage chamber and / or the mixing chamber and / or the first amplification chamber are deformable chambers.

[0020] Optionally, the aforementioned non-deformable card body is provided with a pressing shell, which is positioned outside the liquid storage cavity and / or the first amplification cavity. When the pressing shell is subjected to force, it acts on the liquid storage cavity and / or the first amplification cavity, causing deformation of the liquid storage cavity and / or the first amplification cavity; and / or

[0021] The number of the above-mentioned mixing cavities is greater than 1, and the above-mentioned mixing cavities with a number greater than 1 are connected in series.

[0022] Optionally, the borders of the aforementioned liquid storage chamber, mixing chamber, first amplification chamber, and second amplification chamber must not be deformed;

[0023] The liquid storage chamber is connected to the mixing chamber via a first reaction liquid valve V1, the mixing chamber is connected to the first amplification chamber via a second amplification valve V2, and the mixing chamber is connected to the second amplification chamber via a third valve V3.

[0024] Optionally, the above-mentioned nucleic acid amplification system includes a temperature control system and a valve control system. The first amplification is completed in the first amplification chamber. After the first reaction liquid valve V1 and the second amplification valve V2 are opened, the test sample to be detected by the molecular detection card is mixed in the mixing chamber. The third valve V3 is opened, so that the mixed test sample enters the second amplification chamber for the second amplification.

[0025] Optionally, the aforementioned molecular diagnostic system is a fully automated, integrated molecular diagnostic system that evacuates the molecular diagnostic card during real-time detection.

[0026] The molecular diagnostic system provided by this invention is compatible with both single-item and multi-item test tubes. It supports both single-step and two-step amplification for each test, and is compatible with nested PCR and conventional PCR technologies. It also features a comprehensive anti-contamination system: negative pressure draws nucleic acid extraction and reagents into the reaction consumables; the nucleic acid extraction chamber and sample chamber have sealed lids; reagents for dissolving nucleic acid are added to the nucleic acid transfer cup; the entire machine is under negative pressure and uses a filter membrane; and it includes an ultraviolet disinfection system. The machine can be cascaded on a large scale to achieve high-throughput, multi-item simultaneous testing.

[0027] Nested PCR technology can minimize interference from other non-specific pathogen nucleic acid substances, while two-step PCR amplification can ensure rapid detection even at extremely low pathogen concentrations, thereby improving detection sensitivity.

[0028] For samples with high abundance, conventional PCR can solve cost issues and save detection time. The molecular diagnostic system provided by this invention can perform both conventional PCR and nested PCR, meeting different needs within a single system and solving the contamination problem. This enables automated molecular diagnostic instruments to be used in ordinary laboratory environments. Consumables and samples can be automatically loaded and unloaded, and the machines can be cascaded on a large scale to achieve high-throughput, multi-sample simultaneous detection. Attached Figure Description

[0029] The above and other objects, features, and advantages of exemplary embodiments of the present invention will become readily apparent from the following detailed description taken in conjunction with the accompanying drawings. Several embodiments of the invention are illustrated in the drawings by way of example and not limitation, wherein:

[0030] Figure 1 This is a schematic diagram of an optional molecular diagnostic system according to an embodiment of the present invention;

[0031] Figure 2 This is a schematic diagram of one possible form of a molecular detection card according to an embodiment of the present invention;

[0032] Figure 3 A schematic diagram of an optional sample introduction system provided in an embodiment of the present invention;

[0033] Figure 4 A schematic diagram of an optional sample introduction system transportation process provided for an embodiment of the present invention;

[0034] Figure 5 A schematic diagram of an optional sample introduction system for vacuuming, provided for an embodiment of the present invention;

[0035] Figure 6 A schematic diagram of an optional sample introduction system heat sealing process provided in an embodiment of the present invention;

[0036] Figure 7 A schematic diagram of the structure of a sample tube for an optional sample introduction system provided in an embodiment of the present invention;

[0037] Figure 8 This is an enlarged schematic diagram of the molecular detection plate 11;

[0038] Figure 9 This is an enlarged schematic diagram of another structure of the nested PCR detection card included in the molecular detection card;

[0039] Figure 10 for Figure 9 A three-dimensional schematic diagram;

[0040] Figure 10-1 for Figure 9 Schematic diagram of a partial explosion structure;

[0041] Figure 11 This is a schematic diagram of an optional nucleic acid extraction and liquid addition system provided in an embodiment of the present invention.

[0042] The following detailed embodiments are used to further illustrate, but are not limited to, the present invention. The following examples are only one preferred embodiment of the present invention. Detailed Implementation

[0043] The principles and spirit of the invention will now be described with reference to several exemplary embodiments. It should be understood that these embodiments are provided merely to enable those skilled in the art to better understand and implement the invention, and are not intended to limit the scope of the invention in any way. Rather, these embodiments are provided to make this disclosure more thorough and complete, and to fully convey the scope of this disclosure to those skilled in the art.

[0044] like Figure 1 As shown, Figure 1 This is a schematic diagram of a molecular diagnostic system provided in an embodiment of the present invention. The molecular diagnostic system includes a nucleic acid extraction and liquid addition system 1, a sample addition system 2, a sample injection system 3, a nucleic acid amplification system 4, and a gripper and detection system 5. The sample addition system 2 is located above the sample injection system 3, and the gripper and detection system 5 is located above the nucleic acid amplification system 4. The nucleic acid extraction and liquid addition system 1, the sample addition system 2, the sample injection system 3, the nucleic acid amplification system 4, and the gripper and detection system 5 cooperate with each other in the mechanical automation of the molecular diagnostic system to achieve molecular diagnosis.

[0045] The aforementioned sample introduction system 3 includes a molecular detection card 34, such as... Figure 2 As shown, Figure 2This is a schematic diagram of one manifestation of the molecular diagnostic card provided in an embodiment of the present invention. The molecular diagnostic card 34 includes a first suction port 341, a second suction port 342, a third suction port 347, and a molecular diagnostic card cavity. The first suction port 341, the second suction port 342, and the third suction port 347 are respectively connected to the molecular diagnostic card cavity. The molecular diagnostic card 34 also includes a non-deformable card body 348, and the molecular diagnostic card cavity is placed inside the non-deformable card body 348. The present invention uses a molecular diagnostic card with a non-deformable card body, which makes it possible to automate the transportation, packaging, and testing of the molecular diagnostic card in the molecular diagnostic system. The unique structure of the molecular diagnostic card allows it to perform real-time detection, real-time sample injection, and real-time vacuum negative pressure in the molecular diagnostic system, all of which are completed by the mechanical system in the molecular diagnostic system. This results in low cost, less pollution, and full automation.

[0046] Furthermore, such as Figure 3 As shown, Figure 3 This is a schematic diagram of the sample introduction system provided in an embodiment of the present invention. The sample introduction system 3 further includes a transport vessel 31, a sample rack 32, a sample tube 33, a vacuum chamber 35, and as shown in the figure. Figure 6 The first heat gun 36 and the second heat gun 37 are shown. The sample tube 33 and the molecular detection card 34 are placed in the sample holder 32. The sample holder 32 is placed in the transport ship 31. The transport ship 31 transports the sample holder 32 to the vacuum chamber 35. Figure 4 As shown, Figure 4 This is a schematic diagram of the sample introduction system transportation process provided in an embodiment of the present invention, such as... Figure 5 As shown, Figure 5 This is a schematic diagram of the vacuuming of the sample introduction system provided in an embodiment of the present invention. After the sample to be tested by the molecular detection card 34 is loaded into the first liquid suction port 341 and the second liquid suction port 342, the transport ship 31 transports the sample rack 32 to the vacuum chamber 35. The vacuum chamber 35 and the transport ship 31 form a vacuum chamber. In the vacuum chamber, the first liquid suction port 341 and the second liquid suction port 342 containing the sample to be tested are evacuated to a negative pressure. This scheme further illustrates how the unique structure of the molecular detection card enables it to evacuate to a negative pressure in the sample introduction system in real time, with low cost, less pollution, and full automation.

[0047] Furthermore, such as Figure 6 As shown, Figure 6The above-mentioned first hot gun 36 can move to the third liquid suction port 347 to heat seal the third liquid suction port 347. The above-mentioned second hot gun 37 can move to the first liquid suction port 341 and the second liquid suction port 342 to heat seal the first liquid suction port 341 and the second liquid suction port 342.

[0048] Furthermore, such as Figure 7 As shown, Figure 7 The above-mentioned sample tube of the sample introduction system provided in the embodiment of the present invention is a schematic diagram of the structure. The sample tube 33 is provided with a spout-shaped avoidance structure 331. The spout-shaped avoidance structure 331 can effectively avoid collision with the sample tube of the consumable molecular detection card during sample addition. The above-mentioned liquid inlets are the liquid inlets of the sample tube of the molecular detection card.

[0049] Furthermore, the aforementioned nucleic acid extraction and dispensing system 1 includes a molecular detection plate 11, such as... Figure 8 As shown, Figure 8 The diagram above shows an enlarged view of the molecular detection plate 11. The molecular detection plate 11 has a dovetail groove 112 located at the tail end of the molecular detection plate 11. The molecular detection plate 11 also includes a cover plate 111, which is connected to the dovetail groove 112 in a two-position connection. This two-position connection includes an open-lid connection and a closed-lid connection. Under external force, the cover plate 111 changes from the open-lid connection to the closed-lid connection. The dovetail groove 112 and the molecular detection plate 11 are fixedly connected as an integral structure. This integral structure provides the possibility for fully automated integration, as manual operation of opening and closing the lid is no longer required. For disposable molecular detection plates, the initial state can be open. After sample addition, the system, such as a mechanical baffle, applies external force to the cover plate 111, changing the connection from open to closed, thus replacing manual sample addition and lid closing operations.

[0050] Furthermore, such as Figure 9 As shown, Figure 9 This is an enlarged schematic diagram of another structure of the nested PCR detection card included in the above-mentioned molecular detection card. The cavity of the molecular detection card includes a liquid storage cavity 343, a mixing cavity 344, a first amplification cavity 345, and a second amplification cavity 346. The first aspiration port 341 is connected to the first amplification cavity 345, the second aspiration port 342 is connected to the liquid storage cavity 343, the liquid storage cavity 343 is connected to the mixing cavity 344, the mixing cavity 344 is connected to the first amplification cavity 345, the mixing cavity 344 is connected to the second amplification cavity 346, and the third aspiration port 347 is connected to the second amplification cavity 346.

[0051] In the initial state, the liquid storage chamber 343 is connected to the mixing chamber 344 but not connected, the mixing chamber 344 is connected to the first amplification chamber 345 but not connected, and the mixing chamber 344 is connected to and connected to the second amplification chamber 346.

[0052] In operation, the liquid storage chamber 343 is connected to the mixing chamber 344, the mixing chamber 344 is connected to the first amplification chamber 345, and the mixing chamber 344 is connected to the second amplification chamber 346.

[0053] Furthermore, such as Figure 9 and Figure 10-1 The liquid storage chamber 343, the mixing chamber 344, and the first amplification chamber 345 shown above are deformable cavities. That is, when the liquid storage chamber 343, the mixing chamber 344, and the first amplification chamber 345 are subjected to external force, they can deform and squeeze out the liquid in the cavity, allowing the liquid to flow into the next cavity. This external force can come from the force applied by a mechanical arm or a hard object such as a baffle in the system. Since the molecular detection card is a consumable disposable detection card, it can be made in a cost-effective connection method. For example, in the initial state (before use), it can be made into a state in which two membranes are stuck together to block the connection between the two cavities. When a fluid flows through, the state of sticking together changes to a state in which the two membranes separate and the two cavities are connected.

[0054] Furthermore, such as Figure 9 , Figure 10 and Figure 10-1 As shown, Figure 10 for Figure 9 A three-dimensional diagram, Figure 10-1 for Figure 9 A schematic diagram of a partial explosion structure shows that the aforementioned non-deformable card body is equipped with a first pressing shell 3431 and a second pressing shell 3451. The first pressing shell 3431 and the second pressing shell 3451 are placed as follows: Figure 9 The liquid storage chamber 343 and the first amplification chamber 345 shown above are located outside the liquid storage chamber 343 and the first amplification chamber 345, respectively. After being subjected to force, the first pressing shell 3431 and the second pressing shell 3451 act on the outside of these chambers. Figure 9 The liquid storage chamber 343 and the first amplification chamber 345 shown are deformed, causing the fluid inside the chambers to flow and generate an impact force that breaks through the state where, for example, the two membranes are stuck together and blocking the connection between the two chambers. The number of the above-mentioned mixing chambers 344 is greater than one, for example, there can be eight or more. The above-mentioned mixing chambers 344, which are more than one in number, are connected in series to achieve a thorough mixing effect, which can fully prepare for the second amplification of nested PCR. The above-mentioned adhesion can be manifested as follows: Figure 10-1 The origin is shown as 349.

[0055] Furthermore, such as Figure 2 The frames of the liquid storage chamber 343, mixing chamber 344, first amplification chamber 345, and second amplification chamber 346 shown must not deform, achieving fully automated mechanization; as shown... Figure 2 As shown, the liquid storage chamber 343 and the mixing chamber 344 are connected through the first reaction liquid valve V1, the mixing chamber 344 and the first amplification chamber 345 are connected through the second amplification valve V2, and the mixing chamber 344 and the second amplification chamber 346 are connected through the third valve V3. The flow of liquid in the chamber is controlled by the valves. Although the cost is slightly higher, it can reduce contamination and achieve a fully automated sample introduction system with real-time detection and real-time vacuuming.

[0056] Furthermore, the aforementioned nucleic acid amplification system 4 includes a temperature control system and a valve control system. The first amplification is completed in the first amplification chamber 345. After the first reaction liquid valve V1 and the second amplification valve V2 are opened, the test sample to be detected by the molecular detection card 34 is mixed in the mixing chamber 344. The third valve V3 is opened, allowing the mixed test sample to enter the second amplification chamber 346 for the second amplification.

[0057] Furthermore, the liquid storage chamber 343 and / or the mixing chamber 344 and / or the first amplification chamber 345 are soft air-filled chambers, and the molecular detection card is a molecular detection card for nested PCR detection of multiple items.

[0058] Furthermore, the aforementioned molecular diagnostic system is a fully automated, integrated molecular diagnostic system that evacuates the molecular diagnostic card during real-time detection.

[0059] The working principle of the whole machine is as follows:

[0060] like Figures 1 to 11 As shown, Figure 11This is an enlarged schematic diagram of the above-mentioned nucleic acid extraction and liquid dispensing system 1. The integrated reagent consumable, such as the molecular detection plate 11, is added to the nucleic acid extraction and liquid dispensing system 1. The molecular detection card, such as the nested PCR detection card 34, is placed in the sample rack of the sample introduction system 3. The machine is started, and the machine adds the sample into the nucleic acid extraction well for nucleic acid extraction. After extraction, the multi-head liquid dispensing system adds the system solution to the reaction vessel. The sample dispensing system 2 adds the nucleic acid extract and system solution mixture to sample tube 33. Another sample tube contains the PCR-II reaction solution. The sample introduction system... The transport vessel 31 transports the sample holder 32 to the vacuum chamber 35. The vacuum chamber 35 descends and is pressed by the sealing ring of the transport vessel 31 to form a sealed vacuum chamber. The vacuum system draws negative pressure, and the first hot gun 36 descends to the third suction port 347 of the molecular detection card. The third suction port 347 is heat-sealed, the vacuum chamber 35 rises, and the transport vessel 31 is connected to the atmosphere. The liquid in the sample tube 33 enters the cavity of the molecular detection card along the first suction port 341 and the second suction port 342, respectively. The second hot gun 37 descends to the first suction port 341 and the second suction port 342 and heat-seales them. The transport vessel 31 transports the sample holder 32 to the amplification position. The gripper of the gripper and detection system 5 places the molecular detection card 34 into the nucleic acid amplification position of the nucleic acid amplification system 4. This nucleic acid amplification supports two-step amplification and is adapted to nested PCR. The gripper has a detection system for detecting the fluorescence signal on each consumable.

[0061] The core improvement of the aforementioned nucleic acid extraction and liquid addition system 1 lies in the adoption of the molecular detection plate 11, an integrated reagent consumable. The molecular detection plate 11 consists of a reaction cup, a reaction chamber, a magnetic bead position, a reagent position, a magnetic sleeve, a sample tube position, a tip position, and a cover plate. The biggest improvement is as described above, which adopts a dovetail groove and cover plate structure. For disposable molecular detection plates, the initial state can be an open state. After sample addition, the system, such as a mechanical baffle, applies external force to the cover plate 111, changing the open connection to a closed connection. This replaces the manual sample addition and closing operation, thus incorporating the detection of single-tube reagent cards into the entire system and realizing the possibility of full automation.

[0062] Insert the integrated reagent consumable, place the sample tube into the sample position of the consumable, start the detection, and the instrument will extract nucleic acid according to the nucleic acid extraction process. Then, the multi-head liquid addition system will add the reagent system to the reaction tube.

[0063] The sample introduction system 3 includes a sample rack, sample tubes, molecular detection consumables, a transport system, a hot gun, a vacuum chamber, and a vacuuming system. The sample tubes have a spout-shaped avoidance structure to prevent collision with the sample tubes of the consumables during sample addition. The liquid suction tube on the molecular detection consumables is inserted into the sample tubes, and the liquid level is always higher than the suction port. The transport vessel transports the sample rack, the sample tubes on it, and the molecular detection consumables to the vacuuming position. The vacuum chamber is pressed tightly against the transport vessel by a sealing ring under the action of the motion mechanism. The vacuum system evacuates the chamber. After all the chambers in the molecular consumables are evacuated, the third suction port 347 of the PCR-II reaction chamber (the second amplification chamber 346) is heat-sealed by the first hot gun 36. The vacuum chamber opens, and the sample and PCR-II reaction solution are drawn into the corresponding chambers. The transport system transports the sample rack to the heat-sealing position. The second hot gun 37 heat-seals the first suction port 341 and the second suction port 342, thereby sealing the suction tubes. The transport vessel 31 continues to move to the PCR amplification position.

[0064] The sampling tube is inserted into the sample tube 33. Consumables and sample tubes are transported to the vacuum chamber and evacuated. The first hot gun 36 heat-seals the third suction port 347. After the vacuum chamber is opened to the atmosphere, the sample flows from the first suction port 341 into each PCR-I reaction chamber (first amplification chamber 345), and the PCR-II reaction solution flows from the second suction port 342 into the PCR-II storage chamber (liquid storage chamber 343). The second hot gun 37 heat-seals the first suction port 341 and the second suction port 342. The PCR-I reaction chamber contains lyophilized probes, primers, Taq polymerase, and four types of DNTP. Then, PCF amplification is performed. After completing the first amplification step, open the PCR-II reaction solution valve V1 (first reaction solution valve V1) and the valve V2 for the first PCR-I amplification (second amplification valve V2) in the consumables. Mix the two liquids in the mixing chamber, close the above two valves, and open the third valve V3 (third valve V3). The mixture flows into the PCR-II reaction chamber (second amplification chamber 346). The reaction chamber contains lyophilized probes, nested primers, Taq polymerase, and four types of DNTP. After closing the third valve V3, perform PCR amplification and fluorescence detection.

[0065] The above-mentioned detection positions are compatible with single-item and multi-item detection tubes. The detection of each item supports both single-step and two-step amplification. It is compatible with nested PCR technology and ordinary PCR technology. The complete anti-contamination system is reflected in the negative pressure to draw nucleic acid extraction and reagents into the reaction consumables. The nucleic acid extraction chamber and sample chamber have sealed lids. The nucleic acid transfer cup is filled with reagents to dissolve nucleic acid. The whole machine is under negative pressure and filtered by a filter membrane. It also has an ultraviolet disinfection system.

[0066] Anti-contamination system: The integrated reagent strip has a mechanism to seal the sample and nucleic acid extraction chamber. The sample tube can be disposed of in the solid-liquid waste bin in time. The PCR amplification consumables are heat-sealed and negative pressure injection is used. The top of the machine has a negative pressure system and filter membrane, and the top of the machine also has an ultraviolet disinfection system.

[0067] The core improvement of the technical solution of this invention lies in the negative pressure aspiration during sample addition, which reduces the number of consumables and pollution. The molecular detection plate with the dovetail groove cover structure can better achieve automation and less pollution. When molecular diagnosis is required, it can perform fully automated vacuum sample addition and detection. It can also perform multiple projects and realize the shared functions of microfluidic technology and fully automated nucleic acid extraction, making nested PCR fully automated for the first time.

Claims

1. A molecular diagnostic system, characterized in that, The molecular diagnostic system includes a nucleic acid extraction and liquid addition system (1), a sample addition system (2), an injection system (3), a nucleic acid amplification system (4), and a gripper and detection system (5). The sample addition system (2) is located above the injection system (3), and the gripper and detection system (5) is located above the nucleic acid amplification system (4). The nucleic acid extraction and liquid addition system (1), the sample addition system (2), the injection system (3), the nucleic acid amplification system (4), and the gripper and detection system (5) cooperate with each other in the mechanical automation of the molecular diagnostic system to achieve molecular diagnosis. The sample introduction system (3) includes a molecular detection card (34), which includes a first suction port (341), a second suction port (342), a third suction port (347), and a molecular detection card cavity. The first suction port (341), the second suction port (342), and the third suction port (347) are respectively connected to the molecular detection card cavity. The molecular detection card (34) also includes a non-deformable card body, and the molecular detection card cavity is placed inside the non-deformable card body. The sample introduction system (3) also includes a transport ship (31), a sample rack (32), a sample tube (33), a vacuum chamber (35), a first hot gun (36), and a second hot gun (37). The sample tube (33) and the molecular detection card (34) are placed in the sample rack (32). The sample rack (32) is placed in the transport ship (31). The transport ship (31) transports the sample rack (32) to the vacuum chamber (35). After the sample to be tested by the molecular detection card (34) is loaded into the first suction port (341) and the second suction port (342), the transport ship (31) transports the sample rack (32) to the vacuum chamber (35). The vacuum chamber (35) and the transport ship (31) form a vacuum chamber. In the vacuum chamber, the first suction port (341) and the second suction port (342) containing the sample to be tested are evacuated to negative pressure. The first heat gun (36) can move to the third suction port (347) to heat seal the third suction port (347), and the second heat gun (37) can move to the first suction port (341) and the second suction port (342) to heat seal the first suction port (341) and the second suction port (342). The molecular detection card cavity includes a liquid storage cavity (343), a mixing cavity (344), a first amplification cavity (345), and a second amplification cavity (346). The first aspiration port (341) is connected to the first amplification cavity (345), the second aspiration port (342) is connected to the liquid storage cavity (343), the liquid storage cavity (343) is connected to the mixing cavity (344), the mixing cavity (344) is connected to the first amplification cavity (345), the mixing cavity (344) is connected to the second amplification cavity (346), and the third aspiration port (347) is connected to the second amplification cavity (346). In the initial state, the liquid storage cavity (343) is connected to the mixing cavity (344) but not in communication, the mixing cavity (344) is connected to the first amplification cavity (345) but not in communication, and the mixing cavity (344) is connected to and in communication with the second amplification cavity (346). In the working state, the liquid storage chamber (343) is connected to the mixing chamber (344), the mixing chamber (344) is connected to the first amplification chamber (345), and the mixing chamber (344) is connected to the second amplification chamber (346); The liquid storage chamber (343), the mixing chamber (344), and the first amplification chamber (345) are deformable chambers.

2. The molecular diagnostic system according to claim 1, characterized in that, The nucleic acid extraction and liquid addition system (1) includes a molecular detection plate (11), on which a dovetail groove (112) is provided. The dovetail groove (112) is located at the tail of the molecular detection plate (11). The molecular detection plate (11) also includes a cover plate (111). The cover plate (111) is connected to the dovetail groove (112). The connection between the cover plate (111) and the dovetail groove (112) is a two-stage connection. The two-stage connection includes an open-top connection and a closed-top connection. Under the action of external force, the cover plate (111) changes from the open-top connection to the closed-top connection. The dovetail groove (112) and the molecular detection plate (11) are fixedly connected as an integral structure.

3. The molecular diagnostic system according to claim 1, characterized in that, The non-deformable card body is provided with a pressing shell, which is placed outside the liquid storage cavity (343) and / or the first amplification cavity (345). When the pressing shell is subjected to force, it acts on the liquid storage cavity (343) and / or the first amplification cavity (345), causing the liquid storage cavity (343) and / or the first amplification cavity (345) to deform; and / or The number of mixing cavities (344) is greater than 1, and the mixing cavities (344) with a number greater than 1 are connected in series.

4. The molecular diagnostic system according to claim 1, characterized in that, The borders of the liquid storage chamber (343), the mixing chamber (344), the first amplification chamber (345), and the second amplification chamber (346) must not be deformed; The liquid storage chamber (343) is connected to the mixing chamber (344) via a first reaction liquid valve (V1), the mixing chamber (344) is connected to the first amplification chamber (345) via a second amplification valve (V2), and the mixing chamber (344) is connected to the second amplification chamber (346) via a third valve (V3).

5. The molecular diagnostic system according to claim 4, characterized in that, The nucleic acid amplification system (4) includes a temperature control system and a valve control system. The first amplification is completed in the first amplification chamber (345). After the first reaction liquid valve (V1) and the second amplification valve (V2) are opened, the test sample to be detected by the molecular detection card (34) is mixed in the mixing chamber (344). The third valve (V3) is opened so that the mixed test sample enters the second amplification chamber (346) for the second amplification.

6. The molecular diagnostic system according to any one of claims 1 to 5, characterized in that, The molecular diagnostic system is a fully automated, integrated system that evacuates the molecular diagnostic card during real-time detection.

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