Gene sequencing device

Abstract

The invention discloses a gene sequencing device. The gene sequencing device comprises a chip table, a refrigeration system, a fluid system and an optical detection system, the chip table is used for bearing a biochip, the refrigeration system is used for refrigerating a sample and / or a sequencing reagent, the refrigeration system comprises a reagent bearing module, and the reagent bearing module is used for placing a liquid container for storing the refrigerated sample and / or the sequencing reagent; the fluid system is used for extracting a refrigerated sample and / or a sequencing reagent in the refrigeration system; the optical detection system is used for detecting an optical signal emitted by a sample in the biological chip; the gene sequencing device has a liquid pumping state for the fluid system to pump a refrigerated sample and / or a sequencing reagent in the refrigeration system, and in the liquid pumping state, the reagent bearing module is higher than the chip table, so that the liquid level in the liquid container is higher than the biochip. The technical problem that the sequencing performance is affected due to the fact that bubbles are easily generated in a fluid system of a gene sequencing device is mainly solved.

Description

Technical Field

[0001] The present application relates to a gene sequencing device. Background Art

[0002] Gene sequencing devices can use biochips to carry samples to be tested, and then flow different reagents through the circulation pool of the biochip. Different reagents react with different base sequences in the genetic material to emit specific light. The base sequence can then be obtained by detecting the above light through an optical detection system.

[0003] An important system in a gene sequencing device is the fluid system, which needs to use a liquid power device (such as a pump) to transport samples and / or different reagents to the biochip in sequence through fluid pipelines.

[0004] However, soluble gases usually exist in liquid samples and / or reagents. When the gases precipitate and gather together, they will generate bubbles in the fluid system. When the bubbles pass through or stay in the biochip, they will have a significant impact on the sequencing performance of the gene sequencing device. Summary of the Invention

[0005] The main technical problem solved by this application is that bubbles are easily generated in the fluid system of a gene sequencing device, which affects the sequencing performance.

[0006] The present application provides a gene sequencing device, comprising: A chip stage, used to carry a biochip; A refrigeration system for refrigerating samples and / or sequencing reagents, the refrigeration system comprising a reagent carrying module for placing liquid containers for storing the refrigerated samples and / or sequencing reagents; a fluid system for extracting refrigerated samples and / or sequencing reagents from the refrigeration system and transporting them to the biochip on the chip stage; and an optical detection system for detecting light signals emitted by samples within the biochip; The gene sequencing device has a liquid extraction state for the fluid system to extract refrigerated samples and / or sequencing reagents from the refrigeration system. In the liquid extraction state, there is a height difference between the reagent carrying module and the chip stage. The reagent carrying module is higher than the chip stage so that the liquid level in the liquid container is higher than the biochip.

[0007] In one embodiment, the refrigeration system includes a refrigeration box, the reagent carrying module is arranged in the refrigeration box, and the bottom wall height of the refrigeration box is the same as that of the chip table.

[0008] In one embodiment, the fluid system includes a reagent needle located above the reagent carrying module, and the reagent needle is used to extract the sample and / or sequencing reagent; The reagent carrying module is movably arranged in the vertical direction, and has a liquid aspiration position for inserting the reagent needle into the liquid container on its movable stroke.

[0009] In one embodiment, the lowest position of the reagent carrying module in its movable travel is higher than the chip stage.

[0010] In one embodiment, the height of the chip stage is no more than half the height of the main body of the gene sequencing device.

[0011] In one embodiment, at least two refrigeration systems are included, and at least two refrigeration systems are located on both sides of the chip table in the horizontal direction.

[0012] In one embodiment, a display module is included, and the display module is located above the chip stage.

[0013] In one embodiment, the optical detection system is located above the chip stage, and the display module is located above the optical detection system.

[0014] In one embodiment, a computer module is further included, which is used to control the gene sequencing device. The computer module is located in the upper half of the gene sequencing device, and the computer module and the display module are respectively located on two opposite sides of the gene sequencing device.

[0015] In one embodiment, a circuit module for supplying power to the gene sequencing device is included, and the circuit module is centrally arranged on one side surface of a device frame of the gene sequencing device.

[0016] In one embodiment, the fluid system includes a fluid control component, which is centrally arranged on another side of the device frame; the fluid control component includes at least one of a fluid pressure sensor, a fluid control plate, a bubble sensor, and a pump device.

[0017] In one embodiment, the device frame includes a chassis, and at least a portion of the fluid control components are disposed on the chassis.

[0018] In one embodiment, a gene sequencing device includes a device frame, which includes a frame body and a chassis. The chassis is fixed to the bottom of the frame body. The device frame has an operating side for an operator to operate. Lifting brackets are provided on both sides of the operating side in a horizontal direction on the chassis. The position of the bearing surface formed by the lifting brackets is higher than the surface of the chassis. The refrigeration system is provided on each of the two lifting brackets. The lifting brackets have a space for installing parts.

[0019] In one embodiment, the chip stage is located between the two lifting supports in the horizontal direction.

[0020] In one embodiment, the optical detection system is located between the two refrigeration systems in the horizontal direction, and a display module is provided above the optical detection system between the two refrigeration systems.

[0021] In one embodiment, mounting plates are provided on both sides of the device frame in the horizontal direction adjacent to the operating side, wherein the mounting plate on one side is provided with a circuit module, and the mounting plate on the other side is provided with a fluid control component. In one embodiment, the device further comprises a degassing module, which is arranged on the infusion tube between the liquid pipetting module and the chip carrier system. In one embodiment, the device further includes a degassing module, which is disposed on the infusion tube between the refrigeration system and the chip carrying system.

[0022] In one embodiment, the device further includes a waste liquid box, which is disposed at the bottom of one of the lifting supports.

[0023] In one embodiment, the device also includes a whole-machine heat dissipation system, which includes a whole-machine air inlet, a whole-machine air outlet and a chip stage air outlet. The whole-machine air inlet is arranged in the middle of the front side of the outer shell of the device, the whole-machine air outlet is arranged at the lower part of the rear side of the outer shell of the device, and the chip stage air outlet is arranged at the lower part of the rear side of the outer shell of the device.

[0024] In one embodiment, the heat dissipation system further includes an industrial computer module air outlet, and the industrial computer module air outlet is arranged on the top of the housing of the device.

[0025] In one embodiment, the refrigeration system includes a refrigeration box and a TEC radiator, the TEC radiator is installed on the back of the refrigeration box, and the heat dissipation system also includes a refrigeration system air inlet and a refrigeration system air outlet, the refrigeration system air inlet is arranged opposite to the TEC radiator, and the refrigeration system air outlet is arranged above and / or below the refrigeration system air outlet.

[0026] In one embodiment, the heat dissipation system further includes a circuit module air inlet and a circuit module air outlet, the circuit module air inlet is arranged at the lower portion of the one side surface, and the circuit module air outlet is arranged at the upper portion of the circuit module air inlet.

[0027] In one embodiment, the circuit module air inlet and the circuit module air outlet are arranged diagonally, and a cooling fan is provided at the circuit module heat dissipation outlet.

[0028] According to the above-mentioned gene sequencing device, by making the height of the reagent carrying module higher than the chip stage and making the liquid level in the liquid container higher than the biochip, when the fluid system transports liquid samples and / or sequencing reagents, a certain liquid positive pressure can be formed in the fluid pipeline by relying on the height difference. The liquid positive pressure can limit or avoid the precipitation of bubbles, thereby avoiding the impact of bubbles on sequencing performance, and is conducive to the liquid samples and / or sequencing reagents filling the circulation pool on the biochip, ensuring the accuracy and reliability of sequencing. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 A stereoscopic representation of an embodiment of a gene sequencer in this application Figure 1 ; Figure 2 A stereoscopic representation of an embodiment of a gene sequencer in this application Figure 2 ; Figure 3 A stereoscopic representation of an embodiment of a gene sequencer in this application Figure 3 ; Figure 4 A stereoscopic representation of an embodiment of a gene sequencer in this application Figure 4 ; Figure 5 This is a front view of an embodiment of a gene sequencer in the present application; Figure 6 for Figure 5 A top view of Figure 7 for Figure 5 Left view of; Figure 8 for Figure 5 Right view; Figure 9 for Figure 1 Schematic diagram of the external appearance of the intermediate refrigeration system; Figure 10 for Figure 9 Schematic diagram of the arrangement of the internal components and the outer shell of the refrigeration system, with a portion of the refrigeration box body cut away; Figure 11 for Figure 10 A three-dimensional image with the shell hidden in the middle; Figure 12 for Figure 11 A stereogram from another perspective; Figure 13 for Figure 11 A three-dimensional diagram of a refrigerated box with a refrigeration system hidden in it; Figure 14 for Figure 12 A three-dimensional diagram of a refrigerated box with a refrigeration system hidden in it; Figure 15 for Figure 1 The three-dimensional structure of the central device frame Figure 1 ; Figure 16 for Figure 1 The three-dimensional structure of the central device frame Figure 2 ; Figure 17 for Figure 1 A perspective view of the main body of the device frame; Figures 18 to 21 This is a heat dissipation diagram of another embodiment of the gene detection device of the present application.

[0030] Reference numerals: 100, device frame; 110, chassis; 120, frame body; 130, lifting bracket; 140, mounting plate; 150, waste liquid box; 200, chip table; 300, aspiration module; 310, aspiration base; 320, reagent needle; 330, degassing module; 400, refrigeration system; 410, refrigeration box; 411, article access port; 420, reagent carrying module; 431, first reagent area; 432, second reagent area; 440, lifting device frame; 441, bottom support plate; 442, vertical guide frame; 443, vertical guide rail; 444, top mounting seat; 450, bearing seat; 451, seat body; 452, bearing arm; 461, lead screw; 462, drive motor; 471, transverse guide rail; 472, transverse motor; 473, driving pulley; 474, driven pulley; 475, transmission belt; 480, radiator; 500. Optical detection system; 600, display module; 700, circuit module; 710, switching power supply; 720, circuit board; 730, power switch; 800, computer module; 910. Fluid pressure sensor; 920. Fluid control board; 930. Bubble sensor; 940. Pump device.

[0031] 1010 Whole machine air inlet; 1020 Whole machine air outlet; 1030 Chip station air outlet; 1040 Refrigeration system air inlet; 1050 Refrigeration system air outlet; 1060 Circuit module air inlet; 1070 Circuit module air outlet; 1080 Industrial computer module air outlet. DETAILED DESCRIPTION

[0032] The present application is further described in detail below by means of specific embodiments in conjunction with the accompanying drawings. Similar elements in different embodiments are numbered with associated similar elements. In the following embodiments, many detailed descriptions are provided to enable the present application to be better understood. However, those skilled in the art will readily appreciate that some of the features may be omitted in different circumstances, or may be replaced by other elements, materials, or methods. In some cases, some operations related to the present application are not shown or described in the specification. This is to avoid the core portion of the present application being overwhelmed by excessive descriptions. For those skilled in the art, it is not necessary to describe these related operations in detail. They can fully understand the related operations based on the description in the specification and the general technical knowledge in the art.

[0033] In addition, the features, operations, or characteristics described in the specification may be combined in any appropriate manner to form various embodiments. Furthermore, the steps or actions in the method description may be reordered or adjusted in a manner readily apparent to those skilled in the art. Therefore, the various sequences in the specification and drawings are provided solely for the purpose of clearly describing a particular embodiment and are not intended to be mandatory, unless otherwise specified.

[0034] Component numbers used herein, such as "first" and "second," are used solely to distinguish the components being described and do not convey any sequential or technical meaning. References to "connection" and "coupling" herein, unless otherwise specified, include both direct and indirect connections (couplings).

[0035] This embodiment provides a gene sequencing device.

[0036] Please refer to Figure 1-8 The gene sequencing device includes a device frame 100, a chip carrying system, a fluid system, a refrigeration system 400, an optical detection system 500, and also includes a control system and a processing system.

[0037] In order to more clearly illustrate the specific implementation and technical solutions of this application, Figure 1 The upper, lower, left, right, front and back directions shown in the middle coordinates are described. Of course, the direction limitation in the embodiment is only to more clearly illustrate the positional relationship between the various components, and does not limit the application to be arranged in this way.

[0038] The chip carrying system is used to carry the biochip and can realize the positioning and clamping of the biochip. Since the biochip generally needs to be loaded with the sample to be tested when in use, a fluid interface generally needs to be provided on the chip carrying system. The fluid interface can be connected to the fluid system and docked with the flow pool interface on the biochip after the biochip is loaded. Specifically, the chip carrying system may include a chip stage 200, on which a chip positioning structure and a clamping structure are provided. The biochip is positioned in the horizontal and vertical directions by the chip positioning structure and fixed by the clamping structure. The specific structure of the chip carrying system can adopt the existing technology and will not be described in detail here.

[0039] In one embodiment, please refer to Figure 1 、 2 5. The chip carrier system is positioned in the middle of the gene sequencing apparatus in the left-right direction, and is located in the lower-middle portion of the apparatus. The height of the chip stage 200 does not exceed half the height of the main body of the gene sequencing apparatus. Placing the chip carrier system in the lower-middle portion of the apparatus facilitates increasing the height difference between the biochip and the test sample and / or sequencing reagents in the reagent carrier module 420 (described below), thereby further preventing bubbles in the fluid system. Furthermore, by rationally designing the height of the chip carrier system, it is easier for the operator to access the biochip, improving the operator experience and work efficiency.

[0040] It should be noted that the setting position of the chip carrying system can also be adjusted, for example, it can be set on the left or right side of the gene sequencing device, or in the upper middle part in the height direction of the gene sequencing device. However, considering the convenience of operation and the improvement of the bubble problem in the fluid system, it is more advantageous to choose a relatively low setting position for the chip carrying system. At the same time, considering that the vertical space in the device frame 100 is limited, the refrigeration system 400 itself needs to occupy a large space, and it is necessary to form a height difference between the biochip and the reagent carrying module 420 so that the liquid level in the liquid container is higher than the biochip, it is more reasonable to set the chip carrying system in the lower middle part of the gene sequencing device.

[0041] Please refer to Figures 15 to 18In one embodiment, the device frame 100 of the chip carrier system includes a main frame 120 and a chassis 110, which is fixed to the bottom of the main frame 120. The chassis 110 may be a plate-shaped structure that stably supports the components thereon. The device frame 100 has an operating side for operators to operate, which in the illustrated embodiment is the front side. Lifting brackets 130 are provided on both sides of the chassis 110 (the left and right sides in the illustrated embodiment) in a horizontal direction relative to the operating side. The supporting surface formed by the lifting brackets 130 is positioned higher than the surface of the chassis. A refrigeration system is provided on each of the two lifting brackets 130, which conveniently places the refrigeration system at a higher position, facilitating the generation of positive pressure in the liquid circuit. Furthermore, the presence of two refrigeration systems allows for the storage of a larger number of reagents and facilitates their removal. The lifting brackets 130 contain space for component installation, which not only allows for the refrigeration system to be elevated, but also fully utilizes the space within the device frame 100, resulting in a compact structure.

[0042] Furthermore, the gene sequencing device also includes a waste liquid box, which is arranged at the lower part of the left lifting bracket 130 and is connected to the biochip through an infusion tube. It is used to collect the waste liquid discharged from the biochip during the sequencing process. The setting position of the waste liquid box can also be adjusted. For example, it can be set on the lower right side of the gene sequencing device, or in the lower middle part of the height direction of the gene sequencing device. In order to effectively utilize the installation space of the device, improve the integrity of the instrument, and consider the convenience of operation, it is more reasonable to set the waste liquid box at the lower left part of the gene sequencing device. The waste liquid box also has position detection and liquid volume detection functions, which further improve the convenience of human-computer interaction.

[0043] Furthermore, the chip stage 200 is horizontally located between the two lifting brackets 130, making it easier for operators to clamp / remove chips. Additionally, the optical inspection system 500 is horizontally located between the two refrigeration systems 400, also fully utilizing the space within the device frame 100.

[0044] Please refer to Figures 10 to 14 In one embodiment, the refrigeration system 400 includes a refrigeration box 410 and a reagent carrying module 420. The refrigeration system 400 is used to refrigerate samples and / or sequencing reagents. The sequencing reagents include reaction reagents and non-reaction reagents. The reaction reagents are suitable for reacting with the samples attached to the biochip to generate specific light for optical detection; non-reaction reagents, such as buffer solutions, can be used to clean the liquid circuit of the fluid system.

[0045] In a specific embodiment, the refrigeration box 410 of the refrigeration system 400 may include an insulation layer, which can enclose a low-temperature space that is relatively isolated from the outside world, which is conducive to maintaining a constant temperature and preventing the test samples and / or sequencing reagents from becoming ineffective. A radiator 480 is provided at the rear of the refrigeration system 400. For example, a cooling fan can be used to achieve heat dissipation through air cooling. In other embodiments, liquid cooling can also be used for heat dissipation. In order to place the test samples and / or sequencing reagents into the reagent carrying module 420 and take them out from the reagent carrying module 420, please refer to Figures 1 to 10 The front side of the refrigeration box 410 of the refrigeration system 400 is provided with an item access opening 411. When the reagent carrying module 420 moves vertically to the item access opening 411, the reagent carrying module 420 can be pulled out of the access opening, thereby performing the access operation. Of course, in some other embodiments, the refrigeration system 400 can also be provided with a door body, and the door body can be opened when materials need to be taken out.

[0046] The reagent carrying module 420 is used for placing liquid containers for storing refrigerated samples and / or sequencing reagents. The reagent carrying module 420 can be a box structure with a container holding space, and the reagent carrying module 420 can also have a cover or be set as an open structure. When the fluid system adopts a reagent needle 320 to aspirate, in order to facilitate sampling, a clearance port for the aspiration needle to pass through should be provided on the reagent carrying module 420 with a cover. It should be noted that the structure of the reagent carrying module 420 is not limited to the above-mentioned box structure. For example, it can also be a frame structure, a tray structure, etc. with multiple storage positions. The reagent carrying module 420 is provided with a positioning structure, which can be used for positioning different liquid containers at corresponding positions in the horizontal coordinate system, so that the reagent needle 320 is accurately inserted into the liquid container.

[0047] The reagent carrying module 420 is disposed within the refrigerated housing 410. The reagent carrying module 420 can be fixed at a fixed height within the refrigerated housing 410, and this height enables the liquid level in the liquid container to be higher than the biochip. In addition, the height of the reagent carrying module 420 within the refrigerated housing 410 can also be adjustable, that is, the reagent carrying module 420 can be raised and lowered within the refrigerated housing 410. When the gene sequencing apparatus is in a state where the fluid system extracts refrigerated samples and / or sequencing reagents from the refrigerated system 400, there is a height difference between the reagent carrying module 420 and the chip stage 200. This can also cause the fluid in the fluid system to form a positive pressure due to the liquid level difference, thereby reducing or eliminating the generation of bubbles in the fluid system.

[0048] Preferably, the bottom wall of the cold storage box 410 is higher than the chip stage 200, thereby ensuring that the height of the reagent carrying module 420 is always higher than the biochip. It should be noted that in some other embodiments, when the height of the reagent carrying module 420 is adjustable, before the liquid is withdrawn, the lowest position of the reagent carrying module 420 in its movable range is higher than the chip stage 200, which facilitates the placement and removal of test samples and / or sequencing reagents into and from the reagent carrying module 420 at a lower position.

[0049] In order to adjust the height of the reagent carrying module 420, in one embodiment, please refer to Figures 10 to 14 The refrigeration system 400 also includes a reagent carrying module lifting device, which is used to achieve the lifting and lowering of the reagent carrying module 420. The refrigeration system 400 can be placed as a modular device in the device frame 100 of the gene sequencing device. In this way, the refrigeration system 400 can be independently manufactured and assembled, which facilitates the assembly of the entire device and also ensures the refrigeration performance of the reagent carrying module 420.

[0050] It should be noted that in the above embodiment, the lifting device frame 440 of the reagent carrying module lifting device is set in the refrigeration box 410 of the refrigeration system 400 and is in a refrigeration environment with a lower temperature. In some other embodiments, the reagent carrying module 420 itself can be equipped with refrigeration components, and the reagent carrying module lifting device does not need to be in a refrigeration environment with a lower temperature at this time.

[0051] Please refer to Figure 10 、 Figure 11 In one embodiment, the reagent carrying module lifting device includes a lifting device frame 440, a bearing seat 450 and a lifting drive mechanism. The lifting device frame 440 is used to support the bearing seat 450 and install the guide members, driving members, etc. required for realizing the lifting and lowering of the bearing seat 450. The bearing seat 450 is movably arranged on the lifting device frame 440. A lifting space is provided on one side of the horizontal direction of the lifting drive mechanism, and the bearing seat 450 is arranged on the horizontal side of the lifting drive mechanism. The bearing seat 450 is arranged on the horizontal side of the lifting drive mechanism to facilitate full utilization of the space in the gene sequencing device, so that the reagent carrying module 420 is lowered to a lower height, which is convenient for taking and placing samples. If the space is suitable, the lifting drive mechanism can also be arranged above, below, on the left or on the right side of the bearing seat 450.

[0052] When the article access port 411 on the front side of the refrigeration box 410 of the refrigeration system 400 is taken in and put in, in order to avoid hindering the movement of the reagent carrying module 420, the bearing seat 450 is a cantilever structure, the rear end of the bearing seat 450 is assembled on the lifting device frame 440, and the front end is suspended. Specifically, the bearing seat 450 includes a box-shaped seat body 451, a storage chamber for the reagent carrying module 420 to be placed in the seat body 451, and an inlet and outlet are provided at the front end of the storage chamber. The reagent carrying module 420 can be moved in and out of the storage chamber by pulling, similar to a drawer. In order to facilitate the entry and exit of the reagent carrying module 420, the inlet and outlet at the front end of the storage chamber are provided with a guide slope arranged in an inclined manner to form a flared structure. The bottom of the seat body 451 is fixedly connected to the carrying arm 452, which is a variable cross-section shape with a bottom side as an inclined side, tilted downward from front to back, which is conducive to reducing weight while ensuring sufficient bearing capacity. In other embodiments, the bearing seat 450 can also be supported on the lifting drive mechanism in the middle of the front and rear directions.

[0053] Please refer to Figures 10 to 13 To ensure the stability of the reagent carrying module lifting device, in one embodiment, the lifting device frame 440 of the reagent carrying module lifting device includes a bottom support plate 441 and a vertical guide frame 442. The vertical guide frame 442 is fixed to one side of the bottom support plate 441 in the horizontal direction. The bearing seat 450 is movably arranged on the vertical guide frame 442. The bearing seat 450 and the bottom support plate 441 are located on the same side of the vertical guide frame 442 in the horizontal direction. Specifically, two vertical guide rails 443 extending in the vertical direction are provided on both sides of the vertical guide frame 442 in the left and right directions. The bearing seat 450 is movably assembled on the vertical guide rails 443 in the vertical direction.

[0054] By providing the bottom support plate 441, the center of gravity of the carrier 450 and the reagent carrying module 420 can be located above the bottom support plate 441, thereby improving the load stability of the lifting device frame 440 and preventing the reagent carrying module lifting device from tipping over. It should be noted that in some other embodiments, the lifting device frame 440 can also adopt other structures, such as omitting the bottom support plate 441 and directly fixing it to the side wall of the refrigeration box 410 of the refrigeration system 400.

[0055] In order to achieve precise driving of the reagent carrying module 420, in one embodiment, the lifting drive device is in the form of a screw-nut mechanism, which includes a screw 461 and a transmission nut (not shown in the figure), the screw 461 is connected to the drive motor 462, and the transmission nut is fixed on the support seat 450. Specifically, the screw 461 is arranged in the vertical direction in the middle of the left and right directions of the vertical guide frame 442 and is rotatably assembled on the vertical guide frame 442. The screw 461 can only rotate under the drive of the drive motor 462; the transmission nut is fixed to the rear end of the support seat 450. The drive motor 462 drives the screw 461 to rotate forward and backward to achieve the lifting and lowering of the support seat 450.

[0056] Considering that the drive motor 462 generates heat during operation, and to prevent this heat from affecting the temperature within the refrigeration system 400, in one specific embodiment, the drive motor 462 is fixed to the top of the refrigeration box 410 of the refrigeration system 400 via a connecting bracket. In other embodiments, when the lifting drive device utilizes a screw-nut mechanism, the drive motor 462 may also be located at the bottom of the refrigeration box 410 of the refrigeration system 400, or may be located on the left or right side of the refrigeration box 410 of the refrigeration system 400 and achieve reversing via a reversing mechanism such as bevel gears. Furthermore, in some other embodiments, the lifting drive device may be replaced with other mechanisms, such as a pneumatic cylinder or an electric push rod.

[0057] The fluid system of the gene sequencing device can achieve fluid delivery, such as delivering test samples and / or sequencing reagents to the biochip. The fluid system can include a pump device, a rotary valve, an infusion tube, a liquid pipetting module 300, etc. The liquid pipetting module 300 includes a plurality of reagent needles 320, which are used to extract the test samples and / or sequencing reagents from the liquid container to supply the biochip. The number of reagent needles 320 can be determined according to the type of reagents required for gene sequencing. Each reagent needle 320 is simultaneously fixed to the liquid pipetting base 310 and can correspond to each liquid container placement position on the reagent holding module 420.

[0058] In order to realize the installation of the reagent needle 320, in a specific embodiment, please refer to Figures 11 to 14 , a top mounting seat 444 is provided at the top of the vertical guide frame 442, and the top mounting seat 444 can be a plate-like structure, and the liquid aspiration base 310 is arranged on the top mounting seat 444 and fixed in the vertical direction. When the reagent carrying module 420 is driven by the reagent carrying module lifting device to rise, the reagent carrying module 420 can move upward until the reagent needle 320 is inserted into the liquid container on the reagent carrying module 420, and the insertion depth can be set as needed. It should be noted that the lengths of the reagent needles 320 can be equal, or they can be designed to be unequal in length according to different insertion depth requirements.

[0059] Each aspiration needle is connected to a rotary valve through its corresponding infusion tube. The rotary valve can be a multi-input and one-output structure, which is used to connect the output infusion tube to the chip carrier system and finally selectively connect to the corresponding flow channel on the corresponding biochip.

[0060] In order to generate liquid driving force, a pump device can be provided at the liquid outlet of the biochip to draw the sample to be tested and / or sequencing reagents by negative pressure. It should be noted that in some other embodiments, the pump device can also be a positive pressure delivery pump.

[0061] The above-mentioned pump device, rotary valve, infusion tube, suction module 300, etc. of the fluid system can adopt the structure of the existing technology, and will not be described in detail here.

[0062] To further avoid bubbles from being generated during the process of delivering the sample to be tested and / or the sequencing reagent to the biochip, in one embodiment, please refer to Figure 4 The fluid system also includes a degassing module 330. The degassing module 330 is arranged on the infusion tube between the liquid aspiration module 300 and the chip carrier system, and can also be arranged on the infusion tube between the refrigeration system 400 and the chip carrier system. It can be understood that the degassing module 330 can be arranged on the infusion tube of the biochip, so that the sample to be tested and / or sequencing reagents pass through the degassing module 330 before entering the biochip, filtering out the dissolved gas in the liquid, avoiding the generation of bubbles during the sequencing process, and thus improving the sequencing quality and performance.

[0063] In one embodiment, the degassing module 330 can be set on an infusion tube near the pipetting module 300 or the cold storage box 410, with one end connected to the pipetting needle and the other end connected to the rotary valve. The degassing module 330 can also be set on an infusion tube near the rotary valve, with one end connected to the liquid outlet of the rotary valve and the other end connected to the liquid inlet of the biochip.

[0064] In one embodiment, the degassing module 330 may be an independent degassing chamber component, or a degasser device with a degassing chamber.

[0065] In the initial state, the reagent carrying module 420 can be located at the bottom edge of the refrigeration system 400 and at the same height as the article access port 411 on the refrigeration system 400 under the drive of the reagent carrying module lifting device. When it is necessary to inject the test sample or sequencing reagent into the biochip, the reagent carrying module lifting device drives the reagent carrying module 420 to rise to the liquid suction position. The liquid suction position is a position that enables the reagent needle 320 to enter the liquid container to suck the test sample and / or sequencing reagent. When the reagent carrying module 420 is in the liquid suction position, the liquid level in the liquid container is higher than the chip carrying system. Then, the fluid system can extract the liquid from the liquid container through the reagent needle 320 and then transport it to the biochip. After the test sample is attached to the inner wall of the circulation pool of the biochip, the sequencing reagent is sequentially introduced into the biochip through the fluid system. The test sample reacts with the various reagents introduced in sequence. After each reaction, the optical detection system 500 can be used for optical detection to ultimately achieve gene sequencing.

[0066] Please refer to Figure 1 and Figure 9 To ensure sufficient storage for a large number of reagent cartridges for refrigerated samples and / or sequencing reagents while minimizing the size of the refrigeration system 400, in one embodiment, the gene sequencing apparatus includes two refrigeration systems 400, located at a certain height on the left and right sides of the gene sequencing apparatus. This facilitates easy access to reagent cartridges and provides favorable conditions for generating positive pressure in the fluid system, thereby improving the overall performance of the gene sequencing apparatus. In other embodiments, depending on the reagent storage requirements, a single refrigeration system 400 may be provided, or three or more refrigeration systems may be provided.

[0067] When the gene sequencing device is working, after the reagent carrying module 420 rises, it not only meets the liquid aspiration needs of the liquid aspiration module 300, but also can raise the height of the sample to be tested and the sequencing reagents in the vertical direction, so that the fluid system between the chip carrying system and the reagent carrying module 420 has a greater liquid pressure, which is conducive to avoiding the generation of bubbles and filling the biochip.

[0068] After the gene sequencing device completes sequencing, the reagent needles 320 need to be cleaned before the run ends. Currently, most traditional cleaning methods involve replacing the liquid container in the reagent carrying module 420. The new liquid container contains a reagent capable of cleaning the reagent needles 320, and then each reagent needle 320 is cleaned. However, this operation requires manual intervention, cannot achieve fully automatic cleaning, and is cumbersome to operate.

[0069] In order to solve the above problem, in one embodiment, please refer to Figure 11The reagent carrying module 420 is provided with a first reagent area 431 and a second reagent area 432. The first reagent area 431 and the second reagent area 432 are arranged in parallel in the horizontal direction, for example, in parallel in the left-right direction. The liquid aspiration module 300 is movably arranged along the arrangement direction of the first reagent area 431 and the second reagent area 432. The reagent needle 320 has two working positions, and the two working positions are aligned with the first reagent area 431 and the second reagent area 432 respectively. The first reagent area 431 can be used to place sequencing reagents for gene sequencing, while the second reagent area 432 can be used to place reagents for cleaning the reagent needle 320. With the above-mentioned reagent partitioning structure, after the gene sequencing device completes sequencing, the working position of the reagent needle 320 can be directly replaced, and it can be moved in the horizontal direction to a position aligned with the second reagent area 432 in the vertical direction. The cleaning work of the reagent needle 320 can be directly performed without replacing the liquid container in the reagent carrying module 420.

[0070] In a specific embodiment, please refer to Figures 11 to 14 The pipette base 310 for carrying each reagent needle 320 is movably arranged in the horizontal direction, for example, by being movably assembled to the top mounting seat 444 of the vertical guide frame 442 via a transverse guide rail 471. In order to control the movement of the pipette base 310 carrying each reagent needle 320, in one embodiment, the refrigeration system 400 further includes a transverse motor 472. The transverse motor 472 is fixed to the top of the refrigeration box 410 of the refrigeration system 400, corresponding to the right side of the lifting bracket. At the same time, the drive shaft connected to the transverse motor 472 is provided with a driving pulley 473, and the left side of the lifting device frame 440 is rotatably equipped with a driven pulley 474. A transmission belt 475 is wound around the driving pulley 473 and the driven pulley 474. The pipette base 310 for carrying each reagent needle 320 is fixed to the transmission belt 475 via a connecting seat, thereby driving the pipette base 310 and the reagent needle 320.

[0071] In the illustrated embodiment, the first reagent area 431 and the second reagent area 432 are respectively concentrated on both sides of the lateral movement direction of the aspiration needle, that is, they are respectively arranged on the left and right sides of the reagent carrying module 420. Such an arrangement facilitates reducing the left-right dimensions of the aspiration base 310, which is beneficial for reducing weight. Furthermore, in some other embodiments, the second reagent areas 432 can be alternately arranged along the lateral movement direction of the reagent needle 320, which is beneficial for reducing the lateral movement distance of the reagent needle 320. In one embodiment, the first reagent area 431 and the second reagent area 432 can each be provided with at least two columns, and at least one column of the first reagent area 431 is provided between at least two adjacent columns of the second reagent areas 432. Specifically, a column of the first reagent area 431 and a column of the second reagent area 432 can be alternately arranged along the lateral movement direction of the reagent needle 320, which is beneficial for reducing the lateral movement distance of the reagent needle 320.

[0072] It should be noted that, in the illustrated embodiment, the aspiration base 310 for supporting each reagent needle 320 is movable in the left-right direction. In other embodiments, the aspiration base 310 may also be movable in other horizontal directions, such as forward and backward. Furthermore, the drive mechanism for implementing the reagent needle 320 may also adopt other forms, such as direct drive via a screw-nut mechanism, or driven by a cylinder, electric push rod, etc.

[0073] The chip carrier system, optical detection system 500, fluid system, and refrigeration system 400 are all connected to a control system. The control system, as a lower computer, is connected to the processing system. The control system can control the actions of the corresponding components, while the processing system, as a higher computer, can obtain detection results, process detection data, and transmit control instructions to the control system. Specifically, the processing system can be a computer module 800.

[0074] Also, please refer to Figure 1 The gene sequencing device also includes a display module 600 and a circuit module 700, which are used to display status and data and supply power to the gene sequencing device. The display module 600 can be located directly above the front of the gene sequencing device, above the chip stage 200, to facilitate human-computer interaction. The computer module 800 can be located in the upper half of the gene sequencing device, with the computer module 800 and display module 600 located on the front and rear sides of the gene sequencing device, respectively.

[0075] In one embodiment, the optical detection system 500 is located above the chip stage 200, and the display module 800 is located above the optical detection system 500 and between the two refrigeration systems 400. The layout of the optical detection system 500, display module 800, and chip stage 200 can more effectively utilize the internal space of the gene sequencing device.

[0076] To facilitate installation and maintenance of the circuit, in one embodiment, the circuit module 700 is centrally located on one side of the device frame 100 of the gene sequencing device. Specifically, the circuit module 700 may include a switching power supply 710, a circuit board 720, and a power switch. The switching power supply 710, circuit board 720, and power switch may be arranged in a vertical direction.

[0077] Since the fluid system may have the risk of leakage, in order to improve the operational safety of the gene sequencing device and take into account the convenience of maintenance, in one embodiment, please refer to Figure 2 、 48. The fluid control components of the fluid system are centrally located on another side of the device frame 100, namely, the side of the gene sequencing device facing away from the circuit module 700. These components include at least one of a fluid pressure sensor 910, a fluid control board 920, a bubble sensor 930, and a pump device 940. The fluid control components can be mounted on the chassis 110 of the device frame 100 to prevent accidental fluid leakage from affecting components above.

[0078] In one specific embodiment, mounting plates 140 are provided on both horizontal sides of the device frame 100, adjacent to the operating side. One mounting plate 140 is provided with the circuit module 700, while the other mounting plate is provided with the fluid control components. The provision of mounting plates 140 facilitates the installation of the circuit module 700 and the fluid control components, facilitating both installation and removal. Overall, through the rational arrangement of the device frame structure and internal components, the gene sequencing device fully and rationally utilizes internal space, resulting in a compact structure and convenient component removal and installation, as well as instrument operation.

[0079] It should be noted that in some other embodiments, the above-mentioned chip stage 200, circuit module 700, fluid system, optical detection system 500, etc. can also adopt other layout methods. As long as the reagent carrying module 420 is higher than the chip stage 200 in the liquid extraction state so that the liquid level in the liquid container is higher than the biochip, the generation of bubbles in the fluid system can also be reduced or eliminated.

[0080] In some other embodiments, please refer to Figures 18 to 21 In order to ensure the smooth operation of instrument components, the heat generated by the internal operation of the instrument needs to be effectively dissipated. Therefore, a heat dissipation system is also designed inside the genetic testing device.

[0081] Specifically, the genetic testing device's heat dissipation system includes a whole-machine air inlet 1010, a whole-machine air outlet 1020, and a chip stage air outlet 1030. The whole-machine air inlet 1010 is located at the lower front side of the genetic testing device housing, the whole-machine air outlet 1020 is located in the middle of the rear side of the genetic testing device housing, and the chip stage air outlet 1030 is located at the lower rear side of the device housing, used to dissipate heat from the chip stage 200. In addition, an industrial computer module air outlet 1080 is also located at the top of the genetic testing device housing to dissipate heat from upper industrial computer modules, such as computer modules and displays. After entering the whole-machine air inlet at the front of the instrument, the external airflow, driven by the instrument's internal cooling fan, cooperates with the whole-machine air outlet 1020, the chip stage air outlet 1030, and the industrial computer module air outlet 1080 to form a forward-facing, backward-exiting convection air duct, discharging internal heat from the back of the instrument.

[0082] Furthermore, because the gene sequencing device is provided with a circuit module 700 on the side, the heat dissipation system also includes a circuit module air inlet 1060 and a circuit module air outlet 1070. The circuit module air inlet 1060 is provided at the lower portion of one of the sides of the gene sequencing device, such as the left or right side, and the circuit module air outlet 1070 is provided above the circuit module air inlet 1060. Specifically, the circuit module air inlet 1060 is provided at the lower portion of the left side of the device's housing, and the circuit module air outlet 1070 is provided at the upper portion of the left side of the device's housing. A cooling fan is also provided near the circuit module air outlet 1070, forming a top-in, bottom-out heat dissipation duct to dissipate heat generated by the circuit module. Furthermore, the circuit module air inlet 1060 and the circuit module air outlet 1070 can be set diagonally. After the external air flow enters the circuit module 700 from the circuit module air inlet 1060 at the upper right corner of the left side of the instrument, the cold air passes through the inside of the left panel to dissipate heat to various components, and the hot air is discharged from the instrument to the outside through the circuit module air outlet 1070 at the lower left corner of the left panel.

[0083] Furthermore, since a TEC heat sink is installed on the back of the refrigeration box 410 of the refrigeration system 400 for heat exchange, a large amount of heat is generated during the operation of the refrigeration system 400. Therefore, the heat dissipation system is also provided with a refrigeration system air inlet 1040 and a refrigeration system air outlet 1050. The refrigeration system air inlet 1040 is provided on the rear side of the genetic testing device housing, opposite the TEC heat sink. The refrigeration system air outlet 1050 can be provided above or below the refrigeration system air outlet 1040, or can be provided at the upper and lower parts of the refrigeration system air inlet 1040, respectively, which is more conducive to heat dissipation of the refrigeration box 410. Specifically, the refrigeration system air inlet 1040 is located in the middle of the refrigeration box 410, and the refrigeration system air outlet 1050 is provided at the upper and lower parts of the refrigeration system air inlet 1040, respectively, forming a heat dissipation air duct with air inlet in the middle and air outlet at the upper and lower parts to discharge the heat generated by the refrigeration system.

[0084] The above specific examples are used to illustrate the present application, which is only used to help understand the present application and is not intended to limit the present application. For those skilled in the art of the present application, based on the concept of the present application, they can also make some simple deductions, modifications or substitutions.

Claims

1. A gene sequencing device, characterized in that: include: A chip stage, used to carry a biochip; A refrigeration system for refrigerating samples and / or sequencing reagents, the refrigeration system comprising a reagent carrying module for placing liquid containers for storing the refrigerated samples and / or sequencing reagents; a fluid system for extracting refrigerated samples and / or sequencing reagents from the refrigeration system and transporting them to the biochip on the chip stage; and an optical detection system for detecting light signals emitted by samples within the biochip; The gene sequencing device has a liquid extraction state for the fluid system to extract refrigerated samples and / or sequencing reagents from the refrigeration system. In the liquid extraction state, there is a height difference between the reagent carrying module and the chip stage. The reagent carrying module is higher than the chip stage so that the liquid level in the liquid container is higher than the biochip.

2. The gene sequencing device according to claim 1, wherein: The fluid system includes a reagent needle located above the reagent carrying module, and the reagent needle is used to extract the sample and / or sequencing reagent; The reagent carrying module is arranged to be movable in the vertical direction, and the reagent carrying module has a liquid aspiration position for inserting the reagent needle into the liquid container on its movable stroke; and / or, The refrigeration system includes a refrigeration box, the reagent carrying module is arranged in the refrigeration box, and the bottom wall of the refrigeration box is at a height of the chip table.

3. The gene sequencing device according to claim 2, wherein: The lowest position of the reagent carrying module in its movable travel is higher than the chip stage.

4. The gene sequencing device according to any one of claims 1 to 3, wherein: The height of the chip stage is no more than half the height of the main body of the gene sequencing device; and / or, At least two refrigeration systems are included, and at least two refrigeration systems are located on both sides of the chip platform in the horizontal direction.

5. The gene sequencing device according to claim 4, wherein: A display module is included, and the display module is located above the chip stage.

6. The gene sequencing device according to claim 5, wherein: The optical detection system is located above the chip stage, and the display module is located above the optical detection system.

7. The gene sequencing device according to claim 6, wherein: It also includes a computer module, which is used to control the gene sequencing device. The computer module is located in the upper half of the gene sequencing device. The computer module and the display module are respectively located on two opposite sides of the gene sequencing device.

8. The gene sequencing device according to any one of claims 1 to 3, wherein: It includes a circuit module for supplying power to the gene sequencing device, and the circuit module is centrally arranged on one side of the device frame of the gene sequencing device.

9. The gene sequencing device according to claim 8, wherein: The fluid system includes a fluid control component, which is centrally arranged on the other side of the device frame; the fluid control component includes at least one of a fluid pressure sensor, a fluid control plate, a bubble sensor, and a pump device.

10. The gene sequencing device according to claim 9, wherein: The device frame includes a chassis, and at least a portion of the fluid control components are arranged on the chassis.

11. The gene sequencing device according to any one of claims 1 to 3, wherein: It includes a device frame, which includes a frame body and a chassis. The chassis is fixed to the bottom of the frame body. The device frame has an operating side for the operator to operate. Lifting brackets are provided on both sides of the operating side in the horizontal direction of the chassis. The position of the bearing surface formed by the lifting bracket is higher than the surface of the chassis. The refrigeration system is respectively provided on the two lifting brackets, and there is a component installation space inside the lifting bracket.

12. The gene sequencing device according to claim 11, wherein: The chip stage is located between the two lifting supports in the horizontal direction; and / or, The optical detection system is located between the two refrigeration systems in the horizontal direction, and a display module is provided above the optical detection system between the two refrigeration systems.

13. The gene sequencing device according to claim 11, wherein: Mounting plates are provided on both sides of the device frame in the horizontal direction and adjacent to the operating side. A circuit module is provided on the mounting plate on one side, and a fluid control component is provided on the mounting plate on the other side.

14. The gene sequencing device according to any one of claims 1 to 2, wherein: The device further comprises a degassing module, which is arranged on the infusion tube between the liquid aspiration module and the chip carrying system, or the degassing module is arranged on the infusion tube between the refrigeration system and the chip carrying system.

15. The gene sequencing device according to claim 11, wherein: The device further comprises a waste liquid box, which is arranged at the lower part of one of the lifting supports.

16. The gene detection device according to claim 8, wherein The device also includes a whole-machine heat dissipation system, which includes a whole-machine air inlet, a whole-machine air outlet and a chip stage air outlet. The whole-machine air inlet is arranged in the middle of the front side of the device's shell, the whole-machine air outlet is arranged in the lower part of the rear side of the device's shell, and the chip stage air outlet is arranged in the lower part of the rear side of the device's shell.

17. The gene detection device according to claim 16, wherein: The heat dissipation system further comprises an industrial computer module air outlet, and the industrial computer module air outlet is arranged on the top of the housing of the device.

18. The gene detection device according to claim 16, wherein: The refrigeration system includes a refrigeration box and a TEC radiator, the TEC radiator is installed on the back of the refrigeration box, and the heat dissipation system also includes a refrigeration system air inlet and a refrigeration system air outlet, the refrigeration system air inlet is arranged opposite to the TEC radiator, and the refrigeration system air outlet is arranged above and / or below the refrigeration system air outlet.

19. The gene detection device according to claim 8, wherein The heat dissipation system further includes a circuit module air inlet and a circuit module air outlet. The circuit module air inlet is arranged at the lower portion of the one side surface, and the circuit module air outlet is arranged above the circuit module air inlet.

20. The gene detection device according to claim 19, wherein The circuit module air inlet and the circuit module air outlet are arranged diagonally, and a heat dissipation fan is arranged at the circuit module heat dissipation air outlet.

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