Gene sequencing device

Abstract

The utility model 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] The gene sequencing device can use a biochip to carry the sample to be tested, and then flow different reagents through the flow pool of the biochip. The different reagents react with the different base sequences in the genetic material to emit specific light, and then the base sequence can 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 transport samples and / or different reagents to the biochip in sequence through fluid pipelines under the action of a liquid power device (such as a pump).

[0004] However, there are usually soluble gases in liquid samples and / or reagents. When the gases precipitate and gather together, they will produce 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 the present application is that bubbles are easily generated in the fluid system of a gene sequencing device, which may affect the sequencing performance.

[0006] The present application provides a gene sequencing device, comprising:

[0007] A chip stage, used to carry a biochip;

[0008] A refrigeration system for refrigerating samples and / or sequencing reagents, wherein the refrigeration system comprises a reagent carrying module, wherein the reagent carrying module is used to place liquid containers for storing the refrigerated samples and / or sequencing reagents;

[0009] A fluid system, used for extracting refrigerated samples and / or sequencing reagents in the refrigeration system and transporting them to the biochip on the chip stage;

[0010] and an optical detection system for detecting light signals emitted by samples within the biochip;

[0011] 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.

[0012] 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 the chip platform.

[0013] 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;

[0014] 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.

[0015] In one embodiment, the reagent carrying module is at a lower position than the chip stage in its movable travel.

[0016] In one embodiment, the height of the chip stage is no more than half of the height of the main body of the gene sequencing device.

[0017] In one embodiment, at least two of the refrigeration systems are included, and at least two of the refrigeration systems are located on both sides of the chip stage in the horizontal direction.

[0018] In one embodiment, a display module is included, and the display module is located above the chip stage.

[0019] In one embodiment, the optical detection system is located above the chip stage, and the display module is located above the optical detection system.

[0020] In one embodiment, a computer module is further included, wherein the computer module is used to control the gene sequencing device, and 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.

[0021] 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.

[0022] In one embodiment, the fluid system includes a fluid control component, and the fluid control component 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.

[0023] In one embodiment, the device frame includes a chassis, and at least a portion of the fluid control component is disposed on the chassis.

[0024] In one embodiment, a gene sequencing device includes a device frame, which includes a frame body and a chassis, wherein the chassis is fixed to the bottom of the frame body, the device frame has an operating side for an operator to operate, and lifting brackets are provided on both sides of the operating side in a horizontal direction on the chassis, and the position of the bearing surface formed by the lifting brackets is higher than the surface of the chassis, and the refrigeration system is respectively provided on two of the lifting brackets, and the lifting brackets have a space for installing parts.

[0025] In one embodiment, the chip stage is located between the two lifting supports in the horizontal direction.

[0026] 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.

[0027] In one embodiment, mounting plates are provided on the sides of the device frame adjacent to the operating side in the horizontal direction, 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.

[0028] 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 carrying system.

[0029] In one embodiment, the device further comprises a degassing module, and the degassing module is disposed on the infusion tube between the refrigeration system and the chip carrying system.

[0030] In one embodiment, the device further comprises a waste liquid box, and the waste liquid box is arranged at the lower part of one of the lifting brackets.

[0031] In one embodiment, the device also includes a whole machine heat dissipation system, and the heat dissipation system includes a whole machine air inlet, a whole machine air outlet and a chip stage air outlet. The whole machine air inlet is arranged at 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.

[0032] 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.

[0033] 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.

[0034] In one embodiment, the heat dissipation system further includes a circuit module air inlet and a circuit module air outlet, wherein 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.

[0035] In one embodiment, the circuit module air inlet and the circuit module air outlet are arranged diagonally, and a cooling fan is arranged at the circuit module heat dissipation air outlet.

[0036] 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 influence of bubbles on sequencing performance, and is conducive to the liquid samples and / or sequencing reagents filling the circulation pool on the biochip, thereby ensuring the accuracy and reliability of sequencing. BRIEF DESCRIPTION OF THE DRAWINGS

[0037] Figure 1 A stereoscopic diagram of an embodiment of a gene sequencer in this application Figure 1 ;

[0038] Figure 2 A stereoscopic diagram of an embodiment of a gene sequencer in this application Figure 2 ;

[0039] Figure 3 A stereoscopic diagram of an embodiment of a gene sequencer in this application Figure 3 ;

[0040] Figure 4 A stereoscopic diagram of an embodiment of a gene sequencer in this application Figure 4 ;

[0041] Figure 5 This is a front view of an embodiment of a gene sequencer in the present application;

[0042] Figure 6 for Figure 5 A top view of

[0043] Figure 7 for Figure 5 Left view of

[0044] Figure 8 for Figure 5 Right view of;

[0045] Fig. 9 for Figure 1 Schematic diagram of the appearance of the intermediate refrigeration system;

[0046] Fig.10 for Fig. 9 Schematic diagram of the arrangement relationship between the internal components and the outer shell of the refrigeration system, with a portion of the refrigeration box body cut away;

[0047] Fig.11 for Fig.10 A three-dimensional image of the hidden shell;

[0048] Fig.12 for Fig.11 A stereogram from another perspective;

[0049] Fig.13 for Fig.11 A three-dimensional diagram of a refrigeration box with a refrigeration system hidden in it;

[0050] Fig.14 for Fig.12 A three-dimensional diagram of a refrigeration box with a refrigeration system hidden in it;

[0051] Fig.15 for Figure 1 The three-dimensional structure of the device frame Figure 1 ;

[0052] Fig.16 for Figure 1 The three-dimensional structure of the device frame Figure 2 ;

[0053] Fig.17 for Figure 1 A three-dimensional diagram of the main part of the device frame;

[0054] Figures 18 to 21 It is a heat dissipation schematic diagram of other embodiments of the gene sequencing device of the present application.

[0055] Reference numerals:

[0056] 100, device frame; 110, chassis; 120, frame body; 130, lifting bracket; 140, mounting plate; 150, waste liquid box;

[0057] 200, chip table;

[0058] 300, aspiration module; 310, aspiration base; 320, reagent needle; 330, degassing module;

[0059] 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, driving motor; 471, traverse guide rail; 472, traverse motor; 473, driving pulley; 474, driven pulley; 475, transmission belt; 480, radiator;

[0060] 500. Optical detection system;

[0061] 600, display module;

[0062] 700, circuit module; 710, switching power supply; 720, circuit board; 730, power switch;

[0063] 800, computer module;

[0064] 910. Fluid pressure sensor; 920. Fluid control board; 930. Bubble sensor; 940. Pump device.

[0065] 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

[0066] The present application is further described in detail below by specific embodiments in conjunction with the accompanying drawings. Wherein similar elements in different embodiments adopt associated similar element numbers. In the following embodiments, many detailed descriptions are intended to enable the present application to be better understood. However, those skilled in the art can easily recognize that some of the features can be omitted in different situations, or can be replaced by other elements, materials, and methods. In some cases, some operations related to the present application are not shown or described in the specification, in order to avoid the core part of the present application being overwhelmed by too much description, and for those skilled in the art, it is not necessary to describe these related operations in detail, and they can fully understand the related operations based on the description in the specification and the general technical knowledge in the art.

[0067] In addition, the features, operations or characteristics described in the specification can be combined in any appropriate manner to form various implementations. At the same time, the steps or actions in the method description can also be interchanged or adjusted in a manner that is obvious to those skilled in the art. Therefore, the various sequences in the specification and the drawings are only for the purpose of clearly describing a certain embodiment and are not meant to be a required sequence, unless otherwise specified that a certain sequence must be followed.

[0068] The serial numbers assigned to the components herein, such as "first", "second", etc., are only used to distinguish the objects described and do not have any order or technical meaning. The "connection" and "coupling" mentioned in this application, unless otherwise specified, include direct and indirect connections (couplings).

[0069] This embodiment provides a gene sequencing device.

[0070] 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.

[0071] In order to more clearly illustrate the specific implementation and technical solutions of the present application, Figure 1 The upper, lower, left, right, front and rear directions shown in the middle coordinate indication 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.

[0072] The chip carrier 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 carrier system, and the fluid interface can be connected to the fluid system, and dock with the circulation pool interface on the biochip after the biochip is loaded. Specifically, the chip carrier system may include a chip stage 200, on which a chip positioning structure and a clamping structure are provided, and 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 carrier system can adopt the existing technology, which will not be described in detail here.

[0073] In one embodiment, please refer to Figure 1 , 25. The chip carrying system is arranged in the middle of the left and right directions of the gene sequencing device, and is located in the lower middle part of the gene sequencing device. The table height of the chip table 200 does not exceed half of the height of the main body of the gene sequencing device. The chip carrying system is arranged in the lower middle part of the gene sequencing device, which is conducive to increasing the height difference between the biochip and the samples to be tested and / or sequencing reagents in the reagent carrying module 420 (to be introduced below), thereby being more conducive to avoiding the generation of bubbles in the fluid system. In addition, by reasonably designing the height of the chip carrying system, it is also convenient for the operator to take the biochip, improving the operating experience and work efficiency.

[0074] It should be noted that the setting position of the chip carrier 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 carrier 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 carrier system in the lower middle part of the gene sequencing device.

[0075] Please refer to Figures 15 to 18 In one embodiment, the device frame 100 of the chip carrier system includes a frame body 120 and a chassis 110, and the chassis 110 is fixed to the bottom of the frame body 120. The chassis 110 can be a plate-like structure that can stably support the components thereon. The device frame 100 has an operating side for the operator to operate, which is the front side in the illustrated embodiment. The chassis 110 is provided with lifting brackets 130 on both sides of the operating side in the horizontal direction (i.e., the left and right sides in the illustrated embodiment). The position of the bearing surface formed by the lifting brackets 130 is higher than the surface of the chassis. A refrigeration system is respectively provided on the two lifting brackets 130, which can conveniently make the refrigeration system have a higher layout position, which is more conducive to forming a positive pressure in the liquid circuit. In addition, the two refrigeration systems can be provided to place more reagents, which is also convenient for taking reagents. There is a component installation space in the lifting bracket 130, which not only realizes the lifting of the refrigeration system, but also realizes the full utilization of the space in the device frame 100, and the structure is compact.

[0076] Furthermore, the gene sequencing device also includes a waste liquid box, which is arranged at the lower part of the left lifting bracket 130, connected to the biochip through an infusion tube, and 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 in 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.

[0077] Furthermore, the chip stage 200 is horizontally located between the two lifting brackets 130 , which can facilitate operators to clamp / take chips. In addition, the optical detection system 500 is horizontally located between the two refrigeration systems 400 , which can also fully utilize the space in the device frame 100 .

[0078] 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 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.

[0079] 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 article access opening 411. When the reagent carrying module 420 moves to the article access opening 411 in the up-down direction, the reagent carrying module 420 can be pulled out from the access opening, thereby performing the access operation. Of course, in some other embodiments, a door body can also be provided on the refrigeration system 400, and the door body can be opened when materials need to be accessed.

[0080] The reagent carrying module 420 is used to place 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. In the case where 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 set 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 different liquid containers to be positioned at corresponding positions in the horizontal coordinate system, so that the reagent needle 320 is accurately inserted into the liquid container.

[0081] The reagent carrying module 420 is disposed in the cold storage box 410. The reagent carrying module 420 can be fixed at a fixed height in the cold storage box 410, and the height can make the liquid level in the liquid container higher than the biochip. In addition, the height of the reagent carrying module 420 in the cold storage box 410 can also be adjustable, that is, the reagent carrying module 420 can be raised and lowered in the cold storage box 410. When the gene sequencing device is in a state where the fluid system extracts the refrigerated samples and / or sequencing reagents in the cold storage system 400, there is a height difference between the reagent carrying module 420 and the chip stage 200, which can also form a positive pressure under the action of the liquid level difference in the fluid system, thereby reducing or eliminating the generation of bubbles in the fluid system.

[0082] Preferably, the bottom wall of the cold storage box 410 is higher than the chip stage 200, so that the height of the reagent carrying module 420 is guaranteed to be 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 extraction state, the lowest position of the reagent carrying module 420 in its active stroke is higher than the chip stage 200, so that it is convenient to put the sample to be tested and / or the sequencing reagent into the reagent carrying module 420 and take it out from the reagent carrying module 420 at a lower position.

[0083] In order to achieve the height position adjustment 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 lift the reagent carrying module 420. The refrigeration system 400 can be placed in the device frame 100 of the gene sequencing device as a modular device, so that the refrigeration system 400 can be independently manufactured and assembled, which is conducive to the assembly of the whole machine, and also facilitates the refrigeration performance of the reagent carrying module 420.

[0084] It should be noted that in the above-mentioned embodiment, the lifting device frame 440 of the reagent carrying module lifting device is arranged in the refrigeration box 410 of the refrigeration system 400 and is in a refrigeration environment with a relatively low temperature. In some other embodiments, the reagent carrying module 420 itself can be provided with a refrigeration component, and the reagent carrying module lifting device does not need to be in a refrigeration environment with a relatively low temperature at this time.

[0085] Please refer to Fig.10 , Fig.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 lifting drive mechanism in the horizontal direction, and the bearing seat 450 is arranged on the side of the lifting drive mechanism in the horizontal direction. The bearing seat 450 is arranged on the horizontal side of the lifting drive mechanism to facilitate full use 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.

[0086] When the article access port 411 on the front side of the refrigeration box 410 of the refrigeration system 400 is taken and placed, in order to avoid hindering the movement of the reagent bearing module 420, the bearing seat 450 is a cantilever structure, and 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 seat body 451 in the shape of a box body, and a receiving cavity for the reagent bearing module 420 to be placed is provided in the seat body 451, and the front end of the receiving cavity is provided with an inlet and outlet, and the reagent bearing module 420 can enter and exit the receiving cavity by pulling, similar to a drawer. In order to facilitate the entry and exit of the reagent bearing module 420, the inlet and outlet at the front end of the receiving cavity are provided with a guide slope arranged obliquely to form a flaring structure. The lower part of the seat body 451 is fixedly connected to the bearing arm 452, and the bearing arm 452 is a variable cross-section shape, and the bottom side is an inclined side, which is 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 by the middle part of the front and rear directions.

[0087] Please refer to Figures 10 to 13In order 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 up-down direction are arranged on both sides of the vertical guide frame 442 in the left-right direction, and the bearing seat 450 is movably assembled on the vertical guide rails 443 in the up-down direction.

[0088] By providing the bottom support plate 441, the center of gravity of the bearing seat 450 and the reagent bearing module 420 can be located above the bottom support plate 441, and the force stability of the lifting device frame 440 is better, which is conducive to preventing the reagent bearing 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.

[0089] 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, and the lifting drive device includes a screw 461 and a transmission nut (not shown in the figure), the screw 461 is connected to a drive motor 462, and the transmission nut is fixed on the bearing 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, and 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 bearing seat 450. The drive motor 462 drives the screw 461 to rotate forward and backward, so that the lifting and lowering of the bearing seat 450 can be achieved.

[0090] Considering that the drive motor 462 generates heat when working, in order to prevent the heat from affecting the temperature in the refrigeration system 400, in a specific embodiment, the drive motor 462 is fixed to the top of the refrigeration box 410 of the refrigeration system 400 through a connecting bracket. In other embodiments, when the lifting drive device adopts a screw nut mechanism, the drive motor 462 can also be set at the bottom of the refrigeration box 410 of the refrigeration system 400, or set on the left and right sides of the refrigeration box 410 of the refrigeration system 400 and achieve reversal through a reversing mechanism such as a bevel gear. In addition, in some other embodiments, the lifting drive device can also be replaced by other mechanisms, such as a cylinder, an electric push rod, etc.

[0091] The fluid system of the gene sequencing device can realize fluid delivery, for example, delivering the sample to be tested and / or the sequencing reagent to the biochip. The fluid system may 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, and the reagent needles 320 are used to extract the sample to be tested and / or the sequencing reagent in the liquid container to supply the biochip. The number of reagent needles 320 can be determined according to the type of reagent required for gene sequencing. Each reagent needle 320 is fixed on the liquid pipetting base 310 at the same time, and can correspond to each liquid container placement position on the reagent carrying module 420.

[0092] 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 lengths according to different insertion depth requirements.

[0093] 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.

[0094] In order to generate liquid driving force, the pump device can be arranged 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.

[0095] The above-mentioned pump device, rotary valve, infusion tube, suction module 300, etc. of the fluid system can all adopt structures in the prior art, and will not be described in detail here.

[0096] 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 4The 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-carrying system, and can also be arranged on the infusion tube between the refrigeration system 400 and the chip-carrying 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 the sequencing reagent pass through the degassing module 330 before entering the biochip, so as to filter out the dissolved gas in the liquid and avoid the generation of bubbles during the sequencing process, thereby improving the sequencing quality and performance.

[0097] 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, one end of which is connected to the pipetting needle and the other end is connected to the rotary valve. The degassing module 330 can also be set on an infusion tube near the rotary valve, one end of which is connected to the liquid outlet of the rotary valve and the other end is connected to the liquid inlet of the biochip.

[0098] In one embodiment, the degassing module 330 may be an independent degassing chamber component, or may be a degasser device with a degassing chamber.

[0099] In the initial state, the reagent carrying module 420 can be located at the bottom 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 sample to be tested or the sequencing reagent into the biochip, the reagent carrying module lifting device drives the reagent carrying module 420 to rise to the liquid suction position, which is the position where the reagent needle 320 can enter the liquid container to suck the sample to be tested and / or the 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 sample to be tested is attached to the inner wall of the circulation pool of the biochip, the sequencing reagent is passed into the biochip through the fluid system in sequence, and the sample to be tested reacts with various reagents passed in sequence. After each reaction, the optical detection system 500 can be used for optical detection, and finally gene sequencing is achieved.

[0100] Please refer to Figure 1 and Fig. 9 In order to ensure that a large number of reagent cartridges for storing refrigerated samples and / or sequencing reagents can be stored while avoiding the refrigeration system 400 from being too large, in one embodiment, the gene sequencing device includes two refrigeration systems 400, which are respectively arranged at a certain height on the left and right sides of the gene sequencing device, which can facilitate the removal of reagent cartridges and provide favorable conditions for the fluid system to generate positive pressure, thereby facilitating the overall performance of the gene sequencing device. In some other embodiments, according to the storage requirements of the reagents, the refrigeration system 400 can be set at only one place, or at least three places.

[0101] When the gene sequencing device is working, after the reagent carrying module 420 rises, it not only meets the liquid aspiration demand of the liquid aspiration module 300, but also can raise the height of the sample to be tested and the sequencing reagent 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 beneficial to avoid the generation of bubbles and fill the biochip.

[0102] After the gene sequencing device completes sequencing, the reagent needle 320 needs to be cleaned before the operation ends. Currently, most traditional cleaning methods are to replace the liquid container in the reagent carrying module 420, and the newly replaced liquid container contains a reagent that can clean the reagent needle 320, and then clean each reagent needle 320. However, this operation method requires manual participation, cannot achieve fully automatic cleaning, and is cumbersome to operate.

[0103] In order to solve the above problem, in one embodiment, please refer to Fig.11 , the 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, and 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 above-mentioned first reagent area 431 can be placed with sequencing reagents for realizing gene sequencing, and the second reagent area 432 can be placed with reagents for cleaning the reagent needle 320. With the above-mentioned reagent partition structure, after the gene sequencing device completes sequencing, the working position of the reagent needle 320 can be directly replaced, and it moves in the horizontal direction to a position aligned with the second reagent area 432 in the vertical direction, and the reagent needle 320 can be directly cleaned without replacing the liquid container in the reagent carrying module 420.

[0104] In a specific embodiment, please refer to Figures 11 to 14, the liquid pipetting base 310 for carrying each reagent needle 320 is movably arranged in the horizontal direction, for example, it is movably assembled to the top mounting seat 444 of the vertical guide frame 442 through the lateral guide rail 471. In order to control the movement of the liquid pipetting base 310 carrying each reagent needle 320, in one embodiment, the refrigeration system 400 also includes a lateral motor 472, which is fixed on the top of the refrigeration box 410 of the refrigeration system 400 and is arranged corresponding to the right side of the lifting bracket; at the same time, a driving pulley 473 is provided on the driving shaft connected to the lateral motor 472, and a driven pulley 474 is rotatably assembled on the left side of the lifting device frame 440, and a transmission belt 475 is wound around the driving pulley 473 and the driven pulley 474, and the liquid pipetting base 310 for carrying each reagent needle 320 is fixed on the transmission belt 475 through the connecting seat, thereby realizing the driving of the liquid pipetting base 310 and the reagent needle 320.

[0105] In the illustrated embodiment, the first reagent area 431 and the second reagent area 432 are respectively concentrated on both sides of the transverse direction of the liquid aspiration needle, that is, they are respectively arranged on the left and right sides of the reagent carrying module 420. Such an arrangement is convenient for reducing the left and right dimensions of the liquid aspiration base 310, which is conducive to reducing weight. Further, in some other embodiments, the second reagent area 432 can be alternately arranged along the transverse direction of the reagent needle 320, which is conducive to reducing the transverse distance of the reagent needle 320. In one embodiment, the first reagent area 431 and the second reagent area 432 can 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 area 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 transverse direction of the reagent needle 320, which is conducive to reducing the transverse distance of the reagent needle 320.

[0106] It should be noted that, in the illustrated embodiment, the liquid aspiration base 310 for carrying each reagent needle 320 is movably arranged along the left and right direction, and in other embodiments, the liquid aspiration base 310 may also be movable along other horizontal directions, such as front and back movements. In addition, the driving mechanism for realizing the reagent needle 320 may also be in other forms, such as directly driven by a screw nut mechanism, or driven by a cylinder, an electric push rod, etc.

[0107] The chip carrying system, optical detection system 500, fluid system and refrigeration system 400 are all connected to the control system, and the control system is connected to the processing system as a lower computer. The control system can control the actions of the corresponding components, and the processing system as a host computer can obtain the detection results, process the detection data, and transmit control instructions to the control system. Specifically, the processing system can be a computer module 800.

[0108] Also, please refer to Figure 1The gene sequencing device also includes a display module 600, a circuit module 700, etc., which are respectively used to realize status and data display and to supply power to the gene sequencing device. The display module 600 can be arranged just above the front of the gene sequencing device, above the chip stage 200, which is in line with human-computer interaction. The computer module 800 can be located in the upper half of the gene sequencing device, and the computer module 800 and the display module 600 are respectively located on the front and rear sides of the gene sequencing device.

[0109] 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 structure adopted by the optical detection system 500, the display module 800 and the chip stage 200 can make fuller use of the internal space of the gene sequencing device.

[0110] In order to facilitate installation and maintenance of the circuit, in one embodiment, the circuit module 700 is centrally arranged 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, and the switching power supply 710, the circuit board 720, and the power switch may be arranged in sequence in the up-down direction.

[0111] Since the fluid system may have a risk of leakage, in order to improve the operating safety of the gene sequencing device and take into account the convenience of maintenance, in one embodiment, please refer to Figure 2 , 4 8. The fluid control components of the fluid system are centrally arranged on another side of the device frame 100, that is, the side of the gene sequencing device facing away from the circuit module 700. The fluid control 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 arranged on the chassis 110 of the device frame 100 to prevent accidental leakage from affecting the components above.

[0112] In a specific embodiment, mounting plates 140 are provided on the sides adjacent to the operating sides on both sides of the device frame 100 in the horizontal direction, wherein the circuit module 700 is provided on the mounting plate 140 on one side, and the fluid control component is provided on the mounting plate on the other side. The installation of the mounting plate 140 can conveniently install the circuit module 700 and the fluid control component, and is convenient for disassembly and installation. Overall, by reasonably arranging the structure of the device frame and the internal components, the gene sequencing device can fully and reasonably utilize the internal space, has a compact structure, and can conveniently disassemble and install the components, as well as conveniently operate the instrument.

[0113] 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.

[0114] 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 gene sequencing device.

[0115] Specifically, the heat dissipation system of the gene sequencing device 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 arranged at the lower part of the front side of the housing of the gene sequencing device, the whole machine air outlet 1020 is arranged at the middle part of the rear side of the housing of the gene sequencing device, and the chip stage air outlet 1030 is arranged at the lower part of the rear side of the housing of the device, which is used to dissipate heat for the chip stage 200. In addition, an industrial computer module air outlet 1080 is also arranged at the top of the housing of the gene sequencing device, which is used to dissipate heat for the upper industrial computer module such as computer module, display and other components. After the external airflow enters from the whole machine air inlet in front of the instrument, under the action of the internal cooling fan of the instrument, it 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-to-backward convection air duct, and discharge the internal heat from the back of the instrument.

[0116] Furthermore, since the circuit module 700 is disposed on the side of the gene sequencing device, the heat dissipation system further includes a circuit module air inlet 1060 and a circuit module air outlet 1070. The circuit module air inlet 1060 is disposed at the lower portion of one of the sides of the gene sequencing device, such as the left side or the right side, and the circuit module air outlet 1070 is disposed at the upper portion of the circuit module air inlet 1060. Specifically, the circuit module air inlet 1060 is disposed at the lower portion of the left side of the device housing, and the circuit module air outlet 1070 is disposed at the upper portion of the left side of the device housing. At the same time, a heat dissipation fan is disposed near the circuit module air outlet 1070 to form a heat dissipation duct that enters from the top and exits from the bottom to discharge the heat generated by the circuit module. Furthermore, the circuit module air inlet 1060 and the circuit module air outlet 1070 can be arranged diagonally. After the external airflow 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 side panel to dissipate the heat of 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 side panel.

[0117] 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 will be generated during the operation of the refrigeration system 400, so 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 housing of the gene sequencing device, opposite to the TEC heat sink, and the refrigeration system air outlet 1050 can be provided on the upper or lower part of the refrigeration system air outlet 1040, or can be provided on the upper and lower parts of the refrigeration system air inlet 1040, 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 on the upper and lower parts of the refrigeration system air inlet 1040, respectively, to form a heat dissipation air duct with air inlet in the middle and air outlet in the upper and lower parts, so as to discharge the heat generated by the refrigeration system.

[0118] 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 technicians in the technical field to which the present application belongs, they can also make some simple deductions, deformations or substitutions based on the ideas of the present application.

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, wherein the refrigeration system comprises a reagent carrying module, wherein the reagent carrying module is used to place liquid containers for storing the refrigerated samples and / or sequencing reagents; A fluid system, used for extracting refrigerated samples and / or sequencing reagents in 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, characterized in that: The fluid system comprises 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 move vertically, and the reagent carrying module has a liquid suction position for inserting the reagent needle into the liquid container on its moving stroke; and / or, 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 platform.

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

4. The gene sequencing device according to any one of claims 1 to 3, characterized in that: The height of the chip stage is no more than half of 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, characterized in that: A display module is included, and the display module is located above the chip stage.

6. The gene sequencing device according to claim 5, characterized in that: 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, characterized in that: It also includes a computer module, which is used to control the gene sequencing device. The computer module is located in the upper part 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, characterized in that: It includes a circuit module for supplying power to the gene sequencing device, and the circuit module is centrally arranged on one side of a device frame of the gene sequencing device.

9. The gene sequencing device according to claim 8, characterized in that: The fluid system includes a fluid control component, and the fluid control component 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.

10. The gene sequencing device according to claim 9, characterized in that: 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, characterized in that: It includes a device frame, which includes a frame body and a chassis. The chassis is fixed at 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 the horizontal direction of 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 respectively provided on the two lifting brackets, and the lifting brackets have a space for installing parts.

12. The gene sequencing device according to claim 11, characterized in that: 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, characterized in that: Mounting plates are provided on the sides of the device frame that are adjacent to the operating side in the horizontal direction, 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.

14. The gene sequencing device according to any one of claims 1 to 2, characterized in that: The device also includes 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, characterized in that: The device also includes a waste liquid box, which is arranged at the lower part of one of the lifting brackets.

16. The gene sequencing device according to claim 8, characterized in that: 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 sequencing device according to claim 16, characterized in that: 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 sequencing device according to claim 16, characterized in that: The refrigeration system includes a refrigeration box and a TEC radiator, the TEC radiator is installed on the back of the refrigeration box, 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 sequencing device according to claim 16, characterized in that: 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 part of the one side surface, and the circuit module air outlet is arranged at the upper part of the circuit module air inlet.

20. The gene sequencing device according to claim 19, characterized in that: 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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