A fully sealed thermal cover system with an external heating component and a driving method thereof

Abstract

The present invention relates to a fully sealed thermal cover system with an external heating component and a driving method. The system comprises a cover module and a heating module that are not fixedly connected to each other. By externalizing the heating component and part of the driving function, the thermal cover functional components can be reused, thereby reducing the production cost of the cartridge. At the same time, a connection method containing a sealing ring is adopted to ensure that the thermal cover does not damage the overall sealing of the cartridge under any displacement state, thus achieving a balance between the sealing performance of the cartridge and the production cost. The system is particularly suitable for application in the field of NGS library preparation.

Description

Technical Field

[0001] The present invention relates to the technical field of gene detection, and in particular to a fully sealed heat cover system with an external heating component and a driving method thereof. Background Art

[0002] During library preparation PCR, heating the PCR tube cap is often necessary to prevent water from evaporating from the sample in the main reaction well and condensing on the cap. Using a heated cap to prevent evaporation is a common solution, as it avoids the difficulty of removing the paraffin oil after the reaction is complete.

[0003] Most of the hot covers used in the prior art come from the thermal cycler structure, corresponding to the fixed structure of 96-well plates or PCR strip tubes. When heating is required, the motor drives the movable structure to compress the PCR tube cover and utilizes the hot cover (such as PI heating film) to heat the PCR tube cover. The hot cover structure used in the prior art can well realize the heating of the PCR tube cover, but it cannot be directly applied in the library preparation process. Compared with the simple PCR thermal cycle process, the library preparation process is more complicated. In addition to heating, it is also necessary to use components such as pipettes to perform operations such as adding samples and pipetting. It is obviously necessary to control the opening and closing of the hot cover according to the operating steps and provide available operating space for other functional components (such as pipettes), and the heating effect of the hot cover cannot be considered alone. On the other hand, in order to ensure the reliability of the prepared library, the entire library preparation process needs to be kept in a sealed state and completely isolated from the external environment to ensure that the sample will not be contaminated. Therefore, the opening and closing actions of the hot cover are required not to destroy the sealing of the entire cassette.

[0004] From a functional perspective, a thermal cover primarily consists of a cover body for sealing the reaction wells and a heating assembly for heating. Obviously, placing the thermal cover entirely inside the cartridge can completely ensure the cartridge's seal is intact. However, for disposable cartridges, excessively high production costs are unacceptable. Therefore, the thermal cover design should minimize disposable structures and make as many functional components as possible reusable, ensuring low production costs and processing difficulty. While meeting the functional requirements of the thermal cover, balancing the cartridge's seal with production costs is a major technical challenge. Summary of the Invention

[0005] To address the shortcomings of the existing technology, the present invention proposes a fully sealed thermal cover system with an external heating component and a driving method. By externalizing the heating component and part of the driving function, the thermal cover functional components can be reused, reducing the cost of cartridge production. At the same time, a connection method containing a sealing ring is used to ensure that the thermal cover does not damage the overall sealing of the cartridge under any displacement state, achieving a balance between cartridge sealing and production cost. The system is particularly suitable for applications in the field of NGS library preparation.

[0006] To achieve the above objectives, the technical solutions adopted by the present invention include:

[0007] A fully sealed thermal cover system with an external heating assembly, characterized in that it comprises a cover module and a heating module which are not fixedly connected to each other;

[0008] The cover module includes a sliding seat and a cover assembly arranged on the bottom surface of the sliding seat; at least one annular sealing ring is provided on the outer surface of the sliding seat, and the sliding seat can be horizontally slidably installed in the thermal cover installation groove corresponding to the card cartridge through the annular sealing ring to maintain the sealed state of the card cartridge, and the side of the sliding seat facing the outside of the card cartridge is set to be open; the cover assembly is sealed and installed on the bottom surface of the sliding seat by an elastic element and remains parallel to the reaction hole in the card cartridge. When the cover assembly is subjected to a vertical downward external force, it is vertically displaced downward relative to the sliding seat and is vertically moved upward and reset by the elastic restoring force of the elastic element after the external force is removed;

[0009] The heating module is arranged outside the card box, and includes a driving arm that supports at least horizontal displacement and vertical displacement, and a heating component arranged at the end of the bottom surface of the driving arm; the driving arm horizontally enters the sliding seat from the open opening of the sliding seat and contacts and pushes against the vertical surface inside the sliding seat, and when the driving arm horizontally enters and contacts the vertical surface inside the sliding seat, the heating component is aligned with the cover body component.

[0010] Furthermore, two annular sealing rings are sequentially provided on the outer surface of the sliding seat.

[0011] Furthermore, a return spring is connected between the sliding seat and the wall of the cartridge, and the sliding seat is pushed by the driving arm to perform horizontal entry displacement and pulled by the return spring to perform horizontal exit displacement.

[0012] Furthermore, the lower portion of the cover assembly protrudes from the outer surface of the sliding seat when not subject to vertical external force; the bottom surface of the thermal cover mounting groove includes a cover assembly accommodating section and a sealing sliding section in sequence, and the distance between the cover assembly accommodating section and the outer surface of the sliding seat is greater than the protruding length of the cover assembly when not subject to vertical external force.

[0013] Furthermore, the bottom of the heating component includes a connecting head, and the top of the cover component includes a connecting hole corresponding to the connecting head; the connecting head is vertically displaced downward and inserted into the connecting hole, and there is a removable interference fit between the connecting head and the connecting hole.

[0014] Furthermore, the cover assembly includes a sealing cover at the bottom; when the cover assembly is displaced vertically downward, the sealing cover is inserted into the reaction hole, and the resistance overcome by the sealing cover when being pulled out of the reaction hole is smaller than the resistance overcome by the connector when being pulled out of the connection hole.

[0015] Furthermore, the heat source used by the heating component includes a PI heating film, a ceramic heating sheet, a Peltier, a silicone heating sheet or a mica heating sheet.

[0016] Furthermore, the heating component also includes a temperature sensor.

[0017] The present invention also relates to a method for driving a fully sealed heat cover of an external heating assembly, which is characterized by comprising:

[0018] The driving arm moves horizontally into the sliding seat and pushes against the vertical surface inside the sliding seat through the open opening of the sliding seat, thereby driving the sliding seat to move horizontally into the sliding seat;

[0019] The driving arm moves vertically downward and pushes against the cover assembly, driving the cover assembly to move vertically downward and close the reaction hole;

[0020] The driving arm moves vertically upward and out of contact with the cover assembly, and the cover assembly moves vertically upward and resets under the elastic reset force of the elastic element;

[0021] The driving arm is disengaged horizontally to disengage from the vertical surface inside the sliding seat, and the sliding seat is pulled by the return spring to perform the horizontal withdrawal displacement.

[0022] Furthermore, the vertical upward displacement of the driving arm to disengage from the cover assembly comprises:

[0023] The driving arm moves vertically upward, and the sealing cover is pulled out of the reaction hole;

[0024] The driving arm continues to move vertically upward, and the connector is pulled out of the connecting hole.

[0025] The beneficial effects of the present invention are:

[0026] The fully sealed thermal cover system and driving method with an external heating component of the present invention are used to cover and heat the reaction wells during the library preparation process. This ensures the integrity of the cartridge seal while enabling the thermal cover structure to move horizontally and vertically according to operational needs. This does not affect the operation of the reaction wells by other functional components within the cartridge, thereby avoiding external contamination of the sample due to thermal cover displacement. Furthermore, there is no rigid connection between the heating module and the thermal cover, allowing the relatively expensive heating module to be easily and independently disposed outside the cartridge, thereby significantly reducing the manufacturing cost and difficulty of the cartridge and making it more suitable for producing disposable cartridges. Furthermore, a more precise driving component can be used as needed to improve the efficiency and accuracy of library preparation experiments. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 This is a three-dimensional schematic diagram of a preferred embodiment of a fully sealed thermal cover system with an external heating component of the present invention.

[0028] Figure 2 This is a schematic diagram of the internal structure of a preferred embodiment of the present invention from the first perspective.

[0029] Figure 3 This is a schematic diagram of the internal structure of a preferred embodiment of the present invention from a second perspective.

[0030] Figure 4 Schematic diagram of the return spring in a preferred embodiment of the present invention.

[0031] Figure 5 Schematic diagram of the cover assembly according to a preferred embodiment of the present invention.

[0032] Figure 6 This is a schematic diagram of a heating component according to a preferred embodiment of the present invention.

[0033] Figure 7a This is a schematic diagram of the hot cover in the open state according to a preferred embodiment of the present invention.

[0034] Figure 7b This is a schematic diagram of the hot cover entering the horizontal displacement state in a preferred embodiment of the present invention.

[0035] Figure 7c This is a schematic diagram of the state of the reaction hole closed by the hot cover in a preferred embodiment of the present invention.

[0036] Figure 8a This is a schematic diagram of the position of the cover assembly relative to the reaction wells when the hot cover is open in a preferred embodiment of the present invention. Figure 8b This is a schematic diagram of the position of the cover assembly relative to the reaction well when the hot cover is in a horizontal displacement state according to a preferred embodiment of the present invention.

[0037] Figure 8c This is a schematic diagram of the position of the cover assembly relative to the reaction well when the reaction well is closed by the thermal cover in a preferred embodiment of the present invention.

[0038] Explanation of the accompanying figures: 11-sliding seat, 111-annular sealing ring, 112-reset spring, 12-cover assembly, 121-connecting hole, 122-sealing cover, 13-elastic element, 21-driving arm, 22-heating assembly, 221-connector, 3-card box, 31-hot cover mounting slot, 32-reaction hole. DETAILED DESCRIPTION

[0039] In order to more clearly understand the content of the present invention, it will be described in detail with reference to the accompanying drawings and embodiments.

[0040] During the library preparation process, using a heated lid system to heat the reaction wells must simultaneously ensure the integrity of the library preparation cartridge's seal and not affect the operability of other functional components. This essentially requires the heated lid (cover assembly) to not only undergo a single-dimensional vertical displacement to properly close and open the heated lid, but also provide an appropriate displacement method to ensure that when the heated lid is open, it can provide operating space directly above the reaction well for other functional components in the cartridge (such as a pipette) to operate the reaction well. More complex displacement requirements not only pose problems for the cartridge seal, but also directly lead to a more complex and costly heated lid structure, making it unsuitable for single-use cartridges.

[0041] In order to solve the relative contradiction between the complex displacement, sealing and low cost of the thermal cover system, the present invention adopts a solution in which the thermal cover and the heating module are set separately. The thermal cover is directly set on the card box by an elastic seal, forming a whole with the card box (card box wall), ensuring the sealing of the card box, and using an external heating module to drive the thermal cover to perform the required displacement to realize the thermal cover function. While solving the complex displacement and sealing problems, the external heating module can be reused, reducing the cost of the card box part (disposable part). The premise of breaking away from cost constraints also facilitates the use of more efficient drive components as needed, which helps to improve the efficiency and accuracy of library preparation.

[0042] like Figure 1 A three-dimensional schematic diagram of a preferred embodiment of a fully sealed thermal cover system with an external heating assembly according to the present invention is shown, primarily illustrating the overall exterior design of the lower cartridge 3 using this preferred embodiment. Significantly different from the prior art, this preferred embodiment features a thermal cover mounting groove 31 on the sidewall of the lower cartridge 3. A sliding seat 11 is mounted within this groove. Both the sliding seat 11 and the thermal cover mounting groove 31 are open outward, allowing the drive arm 21 to extend into the sliding seat 11. The thermal cover mounting groove 31 is preferably an integrally formed part of the cartridge 3 to ensure its sealing.

[0043] like Figure 2 and Figure 3The figure shows the internal structure of the preferred embodiment. By partially viewing the wall of the cartridge 3, etc., the preferred embodiment of the thermal cover system of the present invention can be reflected. Two annular sealing rings 111 are sequentially provided on the outer surface of the sliding seat 11, so that the cartridge 3 can still maintain a sealed state when the cartridge 3 is horizontally moved into and out of the thermal cover mounting groove 31. A heating assembly 22 is provided at the end of the driving arm 21 extending into the sliding seat 11. In particular, when the end of the driving arm 21 is horizontally moved into contact with the vertical surface inside the sliding seat 11, the position of the heating assembly 22 corresponds to the cover assembly 12 provided on the sliding seat 11. The heat generated by the heat source of the heating assembly 22 (such as a PI heating film, a ceramic heating plate, a Peltier, a silicone heating plate or a mica heating plate) can be conducted to the cover assembly 12. At the same time, the driving arm 21 pushes against the vertical surface of the sliding seat 11 to drive the sliding seat 11 to move horizontally inward, thereby achieving vertical alignment between the heating assembly 22, the cover assembly 12 and the reaction well 32. At this time, the driving arm 21 can be further moved vertically downward to push the cover assembly 12 to move vertically downward and close the reaction well 32. Preferably, in order to ensure that the cover assembly 12 can better seal the reaction well 32, the cover assembly 12 may remain in a state of protruding from the surface of the sliding seat 11 under normal conditions. Therefore, a redundant space is provided at the corresponding position of the hot cover mounting groove 31 to accommodate the cover assembly 12, so that when the sliding seat 11 performs horizontal entry and horizontal exit displacements, there will be no interference caused by the cover assembly 12 contacting the hot cover mounting groove 31.

[0044] On the basis of achieving horizontal entry displacement of the sliding seat 11 and vertical downward displacement of the cover assembly 12 by pushing through the driving arm 21, it is also necessary to provide driving modes for horizontal exit displacement and vertical upward displacement for the sliding seat 11 and the cover assembly 12 respectively, so as to realize the complete displacement capability of the hot cover system.

[0045] In a preferred embodiment, if Figure 4 As shown, a return spring 112 is employed to achieve horizontal withdrawal of the sliding seat 11. The return spring 112 is preferably a preloaded spring and can be symmetrically positioned one on each side of the sliding seat 11. One end of the return spring 112 is fixedly connected to the sliding seat 11, and the other end is fixedly connected to the wall of the cartridge 3. When the driving arm 21 pushes against the sliding seat 11 to cause it to move horizontally, the sliding seat 11 actually moves relative to the cartridge 3, thus stretching and accumulating the return spring 112. When the driving arm 21 releases contact with the sliding seat 11 during its horizontal withdrawal, the sliding seat 11, under the tension of the return spring 112, continues its horizontal withdrawal.

[0046] like Figure 5The figure shows a structural schematic diagram of the cover assembly 12 in a preferred embodiment. A connecting head 221 is provided at the lower part of the heating assembly 22. Corresponding to the connecting head 221, a connecting hole 121 is provided on the cover assembly 12. When the driving arm 21 performs a vertical downward displacement, the connecting head 221 is correspondingly inserted into the connecting hole 121 and further pushes the cover assembly 12 as a whole to move vertically downward; a sealing cover 122 is provided at the lower part of the cover assembly 12. The size of the sealing cover 122 corresponds to the reaction hole 32. When the cover assembly 12 moves vertically downward, the sealing cover 122 is inserted into and closes the reaction hole 32. At this time, the heating assembly 22, the cover assembly 12 and the reaction hole 32 are contact-connected through the connecting head 221, the connecting hole 121 and the sealing cover 122 to form a heat-conducting whole, so that the heat generated by the heat source on the heating assembly 22 can be conducted to the reaction hole 32 to achieve a heating effect. During this process, the cover assembly 12 needs to perform a vertical displacement relative to the sliding seat 11 structure. In order to maintain the sealing of the interior of the card box 3 during this displacement process, the cover assembly 12 is connected to the sliding seat 11 via an elastic element 13. When the cover assembly 12 is vertically displaced, the elastic element 13 is elastically deformed and maintains the sealing state. Preferably, if necessary, the sliding seat 11 and the elastic element 13 can be connected by an additional structural member to improve the connection strength and sealing reliability. When the drive arm 21 performs a vertical upward displacement, the cover assembly 12 can be displaced upward and returned to its original position due to the elastic force accumulated by the elastic element 13 during the elastic deformation process. In order to ensure the reliability of the reset of the cover assembly 12, it is preferred to increase the friction between the connecting head 221 and the connecting hole 121, for example, setting the end of the connecting head 221 to a slightly larger diameter, so that the force required for the connecting head 221 and the connecting hole 121 to disengage from each other is greater than the force required for the sealing cover 122 and the reaction hole 32 to disengage from each other. When the driving arm 21 performs a vertical upward displacement, the sealing cover 122 and the reaction hole 32 will be disengaged first, and then the connecting head 221 and the connecting hole 121 will be disengaged from each other, thereby ensuring the reset of the cover assembly 12.

[0047] like Figure 6 Shown is a schematic diagram of a heating assembly 22 in a preferred embodiment of the present invention. The heating assembly 22 is arranged at the end of the driving arm 21, and a connector 221 is provided at the lower end. The specific structure of the connector 221 needs to correspond to the number and size of the connecting holes 121 on the cover assembly 12, and further form a corresponding relationship with the number of reaction holes 32 that need to be heated. The displacement of the driving arm 21 can be driven by any suitable conventional power source, such as a motor drive or a pneumatic drive. Preferably, the heating assembly 22 can also be matched with a temperature sensor for detecting the temperature and providing feedback to assist in controlling the heating process.

[0048] Figures 7a to 7c as well as Figures 8a to 8cThe specific position relationship changes between system components at each stage of displacement in the preferred embodiment are shown. Figure 7a and Figure 8a This is a schematic diagram of the hot cover being open. At this time, the driving arm 21 can be in a position that just contacts the vertical wall surface inside the sliding seat 11, but does not push the sliding seat 11. The heating component 22 is vertically aligned with the cover component 12 and both are deviated from the position of the reaction hole 32. Figure 7b and Figure 8b The heat cover is shown in the horizontal displacement state. The driving arm 21 performs the horizontal displacement and pushes the sliding seat 11 to perform the horizontal displacement synchronously until Figure 7b and Figure 8b The heating assembly 22, the cover assembly 12 and the reaction hole 32 shown in the figure are all aligned vertically. According to the structural description of the preferred embodiment above, the reset spring 112 is in a stretched state at this time. Figure 7c and Figure 8c The figure shows the state of the hot cover closing the reaction hole 32. The driving arm 21 performs a vertical downward displacement and pushes the cover body assembly 12 to move vertically downward synchronously, thereby closing the reaction hole 32. Specifically, the connecting head 221 is first inserted into the connecting hole 121 and further pushes the cover body assembly 12 to move vertically downward. At this time, the elastic element 13 undergoes elastic deformation until the sealing cover 122 completely closes the reaction hole 32. At this time, the reaction hole 32 can be heated.

[0049] The above description is merely a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any changes or substitutions that can be easily conceived by a person skilled in the art within the technical scope disclosed in the present invention are intended to be covered by the scope of protection of the present invention. Therefore, the scope of protection of the present invention should be based on the scope of protection of the claims.

Claims

1. A fully sealed thermal cover system with an external heating component, characterized in that: It includes a cover module and a heating module that are not fixedly connected to each other; The cover module includes a sliding seat and a cover assembly arranged on the bottom surface of the sliding seat; at least one annular sealing ring is provided on the outer surface of the sliding seat, and the sliding seat can be horizontally slidably installed in the thermal cover installation groove corresponding to the card cartridge through the annular sealing ring to maintain the sealed state of the card cartridge, and the side of the sliding seat facing the outside of the card cartridge is set to be open; the cover assembly is sealed and installed on the bottom surface of the sliding seat by an elastic element and remains parallel to the reaction hole in the card cartridge. When the cover assembly is subjected to a vertical downward external force, it is vertically displaced downward relative to the sliding seat and is vertically moved upward and reset by the elastic restoring force of the elastic element after the external force is removed; The heating module is disposed outside the cartridge and includes a driving arm capable of at least horizontal and vertical displacements and a heating assembly disposed at an end portion of a bottom surface of the driving arm; the driving arm horizontally enters the sliding seat from an open opening of the sliding seat and contacts and pushes against a vertical surface within the sliding seat, and when the driving arm horizontally enters and contacts the vertical surface within the sliding seat, the heating assembly is aligned with the cover assembly; The driving arm pushes against the vertical surface of the sliding seat to drive the sliding seat to move horizontally, thereby achieving vertical alignment between the heating assembly, the cover assembly and the reaction well. At this time, the driving arm further moves vertically downward to push the cover assembly vertically downward and close the reaction well. The bottom of the heating component includes a connecting head, and the top of the cover component includes a connecting hole corresponding to the connecting head; the connecting head is vertically displaced downward and inserted into the connecting hole, and the connecting head and the connecting hole are in an interference fit that can be pulled out; The cover assembly includes a sealing cover at the bottom; when the cover assembly moves vertically downward, the sealing cover is inserted into the reaction hole, and the resistance overcome by the sealing cover when being pulled out of the reaction hole is smaller than the resistance overcome by the connector when being pulled out of the connection hole.

2. The system according to claim 1, wherein Two annular sealing rings are sequentially arranged on the outer surface of the sliding seat.

3. The system according to claim 1, wherein: A return spring is further connected between the sliding seat and the wall of the cartridge. The sliding seat is pushed by the driving arm to perform horizontal entry displacement and is pulled by the return spring to perform horizontal exit displacement.

4. The system according to claim 3, wherein: The lower portion of the cover assembly protrudes from the outer surface of the sliding seat when not subject to vertical external force; the bottom surface of the thermal cover mounting groove includes a cover assembly accommodating section and a sealing sliding section in sequence, and the distance between the cover assembly accommodating section and the outer surface of the sliding seat is greater than the protruding length of the cover assembly when not subject to vertical external force.

5. The system according to any one of claims 1 to 4, characterized in that The heat source used by the heating component includes a PI heating film, a ceramic heating sheet, a Peltier, a silica gel heating sheet or a mica heating sheet.

6. The system according to any one of claims 1 to 4, characterized in that The heating assembly also includes a temperature sensor.

7. A method for driving a fully sealed heat cover with an external heating assembly, characterized in that: include: The driving arm moves horizontally into the sliding seat and pushes against the vertical surface inside the sliding seat through the open opening of the sliding seat, thereby driving the sliding seat to move horizontally into the sliding seat; The driving arm moves vertically downward and pushes against the cover assembly, driving the cover assembly to move vertically downward and close the reaction hole; The driving arm moves vertically upward and out of contact with the cover assembly, and the cover assembly moves vertically upward and resets under the elastic reset force of the elastic element; The driving arm is disengaged horizontally and disengages from the vertical surface inside the sliding seat, and the sliding seat is pulled by the return spring to perform the horizontal withdrawal displacement; The driving arm pushes against the vertical surface of the sliding seat to drive the sliding seat to move horizontally, thereby achieving vertical alignment between the heating assembly, the cover assembly and the reaction well. At this time, the driving arm further moves vertically downward to push the cover assembly vertically downward and close the reaction well. The method is used to execute the system according to any one of claims 1 to 6.

8. The method according to claim 7, wherein The vertical upward displacement of the driving arm out of contact with the cover assembly comprises: The driving arm moves vertically upward, and the sealing cover is pulled out of the reaction hole; The driving arm continues to move vertically upward, and the connector is pulled out of the connecting hole.

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