A gene sequencer

Abstract

The present invention discloses a gene sequencer, which belongs to the field of detection devices and includes a chip detection device, a reagent supply device, a liquid path system and a gas path system. The chip detection device is used to carry and detect a sequencing chip. The reagent supply device is used to store reagents. The liquid path system includes a confluence structure and an injection pump communicated with the confluence structure. A microchannel is arranged in the confluence structure, and the microchannel communicates the chip detection device with the reagent supply device. The gas path system is connected to both the reagent supply device and the confluence structure and is used to provide compressed air. The setting of the microchannel results in low reagent consumption, low use cost, easy operation, small volume and light weight. The setting of the injection pump can effectively reduce the reagent consumption and well guarantee the stability of the flow rate of the reagent when flowing through the detection area of the sequencing chip, having advantages such as low use cost and high detection accuracy.

Description

Technical Field

[0001] The present invention relates to the field of detection devices, and particularly to a gene sequencer. Background Art

[0002] A gene sequencer refers to an instrument used for gene sequencing. Most gene sequencers use a sequencing chip as the carrier for testing. Gene molecules / nucleic acid molecules are placed on the sequencing chip, and reagents flow over the surface of the sequencing chip, reacting chemically with the gene molecules and emitting specific light. The gene sequencer can obtain the base sequence of the gene fragment / nucleic acid fragment by detecting the color of the light.

[0003] Most existing gene sequencers use pipelines to transport liquids, resulting in large reagent consumption and high costs; moreover, the liquids are unstable during the flow process, affecting the accuracy of the detection results. Summary of the Invention

[0004] The purpose of the present invention is to provide a gene sequencer to solve the technical problems of large reagent consumption and unstable liquid flow existing in the prior art.

[0005] With the above concept, the technical solution adopted by the present invention is as follows:

[0006] A gene sequencer, comprising:

[0007] A chip detection device for carrying and detecting a sequencing chip;

[0008] A reagent supply device for storing reagents;

[0009] A liquid path system, including a confluence structure and an injection pump connected to the confluence structure. A microchannel is provided in the confluence structure, and the microchannel connects the chip detection device and the reagent supply device;

[0010] An air path system, connected to both the reagent supply device and the injection pump, for providing compressed air.

[0011] Among them, the chip detection device includes a carrying component and a detection component connected to the carrying component. The carrying component is used for positioning the sequencing chip, and the detection component is used for detecting the sequencing chip.

[0012] Among them, the carrying component includes:

[0013] A chip mounting seat having a groove, and the sequencing chip can be placed in the groove;

[0014] A hinge assembly, including a hinge base and a hinge upper cover that are hinged to each other. The hinge base is fixedly connected to the chip mounting seat;

[0015] The runner connection block is connected to the hinge upper cover, and the runner connection block connects the liquid path system and the groove.

[0016] Wherein, the chip detection device further includes a driving component, and the driving component is connected to the detection component for driving the carrying component and the detection component to move linearly synchronously.

[0017] Wherein, the reagent supply device includes a reagent mounting seat, a puncture needle assembly arranged on the reagent mounting seat, and a reagent tank assembly that can be inserted and communicated with the puncture needle assembly. A runner is arranged in the reagent mounting seat, the puncture needle assembly is communicated with the runner, and the runner is communicated with the liquid path system.

[0018] Wherein, the reagent tank assembly includes a shell, an end cover arranged at one end of the shell, and a bottle assembly arranged inside the shell and connected to the end cover. A plurality of through holes are formed in the end cover, rubber plugs are arranged in the through holes, and the puncture needle assembly includes a puncture needle that can penetrate through the rubber plug.

[0019] Wherein, the current collector structure includes:

[0020] A microchannel plate, in which microchannels are arranged, and the microchannels include a common channel and a plurality of branch channels communicated with the common channel;

[0021] Valves are arranged at the junction of the common channel and the branch channels, and one valve is arranged corresponding to each branch channel for controlling the on-off of the common channel and the branch channels.

[0022] Wherein, the common channel has a common interface, the common interface includes a cleaning liquid inlet and a total waste liquid outlet, and the plurality of branch channels include a plurality of waste liquid branch channels. One end of the waste liquid branch channel is communicated with the cleaning liquid inlet, and the other end is communicated with the total waste liquid outlet.

[0023] Wherein, the syringe pump is communicated with the cleaning liquid inlet.

[0024] Wherein, an auxiliary valve block assembly is arranged between the syringe pump and the gas path system, and the auxiliary valve block assembly includes an auxiliary valve block, and a liquid flow channel and a gas flow channel are arranged inside the auxiliary valve block.

[0025] Advantages of the present invention:

[0026] The gene sequencer proposed by the present invention has a liquid path system that connects the reagent supply device and the chip fixing device to provide a flow path for the reagent. The microchannels in the confluence structure are combined with a semiconductor chip having a micropore array, with low reagent consumption, low usage cost, easy operation, small size, and light weight. The setting of the injection pump can effectively reduce the reagent consumption while ensuring good stability of the flow rate of the reagent when it flows through the detection area of the sequencing chip, with advantages such as low usage cost and high detection accuracy. It is connected to the reagent supply device through the gas path system, and compressed air can be used to provide pressure for the flow of the reagent. In cooperation with the injection pump, the flow of the reagent is made stable. It is connected to the confluence structure through the gas path system, and compressed air can be used to clean the microchannels, which is convenient, fast, and low-cost. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 FIG. is a schematic structural diagram of the gene sequencer provided by an embodiment of the present invention;

[0028] Figure 2 is Figure 1 a schematic structural diagram after omitting the outer housing;

[0029] Figure 3 is Figure 2 a schematic structural diagram from another angle;

[0030] Figure 4 is Figure 2 a schematic exploded view;

[0031] Figure 5 FIG. is a schematic structural diagram of the chip detection device of the gene sequencer provided by an embodiment of the present invention;

[0032] Figure 6 is Figure 5 a schematic structural diagram of the drive assembly in;

[0033] Figure 7 is Figure 5 a schematic exploded view of the carrier assembly and the detection assembly in;

[0034] Figure 8 is Figure 7 a schematic exploded view of the carrier assembly in;

[0035] Figure 9 is Figure 7 a schematic structural diagram of the hinge upper cover of the carrier assembly in an open state;

[0036] Figure 10 FIG. is a schematic exploded view of the reagent supply device of the gene sequencer provided by an embodiment of the present invention;

[0037] Figure 11 is Figure 10The front view of the end cap in;

[0038] Figure 12 is Figure 10 The front view of the reagent mounting base in;

[0039] Figure 13 is Figure 10 The sectional view of the waste liquid bottle in;

[0040] Figure 14 is Figure 10 The sectional view of the reagent bottle in;

[0041] Figure 15 is Figure 10 The sectional view of the cleaning bottle in;

[0042] Figure 16 It is the schematic structural diagram when the current collector structure of the gene sequencer provided by the embodiment of the present invention is installed;

[0043] Figure 17 It is the exploded structural diagram of the current collector structure of the gene sequencer provided by the embodiment of the present invention;

[0044] Figure 18 is Figure 17 The structural diagram of the flow channel cover plate of the current collector structure in;

[0045] Figure 19 is Figure 17 The structural diagram of the flow channel plate of the current collector structure in;

[0046] Figure 20 is Figure 19 The front view of;

[0047] Figure 21 is Figure 19 The structural diagram from another angle of;

[0048] Figure 22 It is the structural diagram of the auxiliary valve block assembly of the gene sequencer provided by the embodiment of the present invention;

[0049] Figure 23 is Figure 22 The structural diagram of the auxiliary valve block in;

[0050] Figure 24 It is the working principle diagram of the gene sequencer provided by the embodiment of the present invention.

[0051] In the figure:

[0052] 10. Sequencing chip;

[0053] 11. Outer housing; 111. Heat dissipation port; 12. Display screen; 13. Installation base plate;

[0054] 2. Chip detection device; 21. Installation platform;

[0055] 22. Bearing component; 221. Chip mounting base; 222. Hinge component; 2221. Hinge base; 2222. Hinge upper cover; 223. Runner connection block;

[0056] 23. Detection component; 231. Data acquisition circuit board; 232. Data acquisition circuit board mounting plate; 233. Data acquisition circuit board cover;

[0057] 24. Driving component; 241. Motor component; 242. Pulley component; 243. Connecting plate; 244. Guide rail; 245. Slide block;

[0058] 3. Reagent supply device; 31. Reagent mounting base; 32. Puncture needle component;

[0059] 33. Reagent tank component; 331. Reagent shell; 332. End cover; 333. Waste liquid bottle; 334. Liquid guide tube; 335. Vent pipe; 336. Reagent bottle; 337. First thin film bag; 338. Cleaning bottle; 339. Second thin film bag;

[0060] 4. Confluence structure;

[0061] 41. Microchannel plate; 411. Flow channel plate; 412. Flow channel cover; 42. Valve; 43. Connection block;

[0062] 44. Cleaning liquid inlet; 45. Total waste liquid outlet; 46. Chip liquid inlet; 47. Chip liquid outlet;

[0063] 4011. Waste liquid one outlet; 4012. Waste liquid one inlet; 4021. Reagent one outlet; 4022. Reagent one inlet; 4031. Reagent two outlet; 4032. Reagent two inlet; 4041. Waste liquid two outlet; 4042. Waste liquid two inlet; 4051. Waste liquid three outlet; 4052. Waste liquid three inlet; 4061. Reagent three outlet; 4062. Reagent three inlet; 4071. Reagent four outlet; 4072. Reagent four inlet; 4081. Waste liquid four outlet; 4082. Waste liquid four inlet; 4091. Waste liquid five outlet; 4092. Waste liquid five inlet;

[0064] 5. Syringe pump; 61. Mounting plate; 62. Translational connecting rod assembly;

[0065] 71. Air pump; 72. Pressure regulating valve; 73. Air filter;

[0066] 8. Auxiliary valve block assembly; 81. Auxiliary valve block; 82. Auxiliary valve;

[0067] 801, First air inlet; 802, First air outlet; 803, Second air inlet; 804, Second air outlet; 805, First cleaning liquid inlet; 806, Second cleaning liquid inlet; 807, Liquid outlet. Detailed implementation manners

[0068] The embodiments of the present invention will be described in detail below. The examples of the embodiments are shown in the accompanying drawings, where the same or similar reference numerals denote the same or similar elements or elements having the same or similar functions throughout. The embodiments described below by referring to the accompanying drawings are exemplary and are intended to explain the present invention and should not be construed as a limitation to the present invention.

[0069] In the description of the present invention, unless otherwise clearly defined and limited, the terms "connected", "connected to", and "fixed" should be understood in a broad sense. For example, it may be a fixed connection, a detachable connection, or integrated; it may be a mechanical connection or an electrical connection; it may be directly connected or indirectly connected through an intermediate medium, and it may be the internal communication of two elements or the interaction relationship between two elements. For those of ordinary skill in the art, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.

[0070] In the present invention, unless otherwise clearly defined and limited, the first feature being "above" or "below" the second feature may include the direct contact between the first and second features, or may include the non-direct contact between the first and second features but through other features therebetween. Moreover, the first feature being "above", "above the top of", and "on the top of" the second feature includes the first feature being directly above and obliquely above the second feature, or merely indicating that the horizontal height of the first feature is higher than that of the second feature. The first feature being "below", "below the bottom of", and "under the bottom of" the second feature includes the first feature being directly below and obliquely below the second feature, or merely indicating that the horizontal height of the first feature is lower than that of the second feature.

[0071] The technical solution of the present invention will be further described below in conjunction with the accompanying drawings and through specific implementation manners.

[0072] See Figures 1 to 24 , An embodiment of the present invention provides a gene sequencer for performing gene sequencing on gene factors placed on a sequencing chip 10.

[0073] The gene sequencer includes an outer housing 11, and a chip detection device 2, a reagent supply device 3, a liquid path system, and a gas path system are arranged inside the outer housing 11. The gene sequencer further includes a display screen 12 installed on the outer housing 11. The display screen 12 can be a touch screen, having both operation and display functions, facilitating the operator to perform sequencing operations. In order to facilitate providing support, a mounting base plate 13 is provided at the bottom of the outer housing 11, and the outer housing 11 is connected to the mounting base plate 13.

[0074] The front, back, and bottom of the outer housing 11 are all provided with heat dissipation openings 111, and the back is provided with a power switch interface, a network cable interface, a USB interface, a power interface, etc. In order to achieve automatic control, a power sub-module, a data transmission and processing sub-module, a heat dissipation sub-module, and a control and drive sub-module are also provided inside the outer housing 11. The gene sequencer also has Bluetooth and WIFI functions, and can be remotely operated through a mobile terminal and the status, data, and detection results of the gene sequencer can be viewed in real time. The control principle of the electrical category will not be elaborated here, and reference can be made to the prior art.

[0075] The chip detection device 2 is used to carry and detect the sequencing chip 10, and includes a mounting platform 21, a carrying component 22 arranged on the mounting platform 21, and a detection component 23 connected to the carrying component 22. The carrying component 22 is used to position the sequencing chip 10, and the detection component 23 is used to detect the sequencing chip 10. The mounting platform 21 is arranged on the mounting base plate 13.

[0076] The carrying component 22 includes a chip mounting seat 221, a hinge component 222, and a flow channel connection block 223. A groove is formed on the chip mounting seat 221, and the sequencing chip 10 can be placed in the groove. The hinge component 222 includes a hinge base 2221 and a hinge upper cover 2222 that are hinged to each other. The hinge base 2221 is fixedly connected to the chip mounting seat 221, the flow channel connection block 223 is connected to the hinge upper cover 2222, and two flow channel through holes are formed on the flow channel connection block 223, namely a liquid inlet through hole and a liquid outlet through hole, for liquid inlet and outlet. The flow channel through holes are communicated with the groove so that the inlet liquid can contact the sequencing chip 10. The hinge upper cover 2222 can be flipped, and the flow channel connection block 223 can be flipped by a certain angle along with the hinge upper cover 2222. When the hinge upper cover 2222 is opened, the sequencing chip 10 can be placed or taken out in the groove, and a chip detection area is formed between the hinge upper cover 2222 and the groove. The flow channel connection block 223 is communicated with the hinge upper cover 2222 through a sealing ring.

[0077] The detection component 23 includes a data acquisition circuit board 231, and the carrying component 22 is installed on the data acquisition circuit board 231. One side of the data acquisition circuit board 231 is connected to the data acquisition circuit board mounting plate 232, and a data acquisition circuit board cover plate 233 is arranged on the other side of the data acquisition circuit board 231. The data acquisition circuit board cover plate 233 is connected to the data acquisition circuit board mounting plate 232. An opening is formed on the data acquisition circuit board mounting plate 232, and the carrying component 22 is arranged at the opening, which is convenient for replacing the sequencing chip 10.

[0078] The chip detection device 2 further includes a driving component 24 disposed on the mounting platform 21. The driving component 24 can drive the detection component 23 to move. Since the carrying component 22 is connected to the detection component 23, that is to say, the driving component 24 can drive the carrying component 22 and the detection component 23 to move synchronously, so that the sequencing chip 10 can move between the first position and the second position. When the sequencing chip 10 is located at the first position, the sequencing chip 10 can be tested. When the sequencing chip 10 is pushed out to the second position, the sequencing chip 10 can be replaced. After the replacement is completed, the driving component 24 pulls the sequencing chip 10 back to the first position. In order to realize the automatic movement of the sequencing chip 10, when replacing the chip, touch the relevant button, and the detection component 23 will be automatically pushed out. After the chip replacement is completed, touch the relevant button, and the detection component 23 will be automatically sent into the instrument, which is convenient to operate.

[0079] The driving component 24 includes a motor component 241 and a pulley component 242. The detection component 23 is connected to the pulley component 242. The pulley component 242 includes a conveyor belt and pulleys supported at both ends of the conveyor belt. The motor component 241 drives the pulleys to rotate, driving the conveyor belt to convey, and the detection component 23 is connected to the conveyor belt. Optionally, a connecting plate 243 is fixedly arranged on the conveyor belt, and the data acquisition circuit board mounting plate 232 of the detection component 23 is connected to the connecting plate 243.

[0080] Guide rails 244 are arranged on both sides of the conveyor belt. Sliders 245 are slidably arranged on the guide rails 244. The data acquisition circuit board mounting plate 232 is connected to the connecting plate 243 and also connected to the sliders 245. The cooperation of the guide rails 244 and the sliders 245 plays a guiding role, making the movement of the detection component 23 smoother.

[0081] When performing detection, the reagent supply device 3 needs to supply reagents to the chip detection device 2. The reagent supply device 3 is used to store reagents and includes a reagent mounting seat 31, a puncture needle component 32 disposed on the reagent mounting seat 31, and a reagent tank component 33 that can communicate with the puncture needle component 32. The reagent mounting seat 31 is disposed on the mounting base plate 13.

[0082] The display screen 12 is pivotally connected to the outer housing 11. By rotating the display screen 12, the outer housing 11 can be opened to expose the reagent mounting position. A reagent cover plate is arranged above the reagent mounting position of the reagent supply device 3. The reagent cover plate can be taken out to replace the reagent.

[0083] The reagent tank assembly 33 includes a reagent housing 331, an end cap 332, and a bottle assembly. One end of the reagent housing 331 is closed, and the other end is provided with an opening. A handle is provided at the closed end of the reagent housing 331 to facilitate installation and disassembly operations. The end cap 332 is disposed at the open end of the reagent housing 331. The reagent housing 331 is connected to the end cap 332 by bolts and sealed between them by a sealing ring, so that a sealed cavity is formed inside the reagent housing 331. The bottle assembly is located inside the cavity of the reagent housing 331 and is connected to the end cap 332. The bottle assembly includes a waste liquid bottle assembly, a reagent bottle assembly, and a cleaning bottle assembly.

[0084] The waste liquid bottle assembly is used to store waste liquid and includes a waste liquid bottle 333, a liquid guide tube 334, and a ventilation tube 335. The liquid guide tube 334 is used for the waste liquid to flow downward into the waste liquid bottle 333. The ventilation tube 335 is communicated with the outside atmosphere and is used to ensure that the pressure inside the waste liquid bottle 333 is the same as the atmosphere, so as to ensure the smooth discharge of the waste liquid. One end of the waste liquid bottle 333 is connected to the end cap 332 by a thread, and a sealing ring is used to seal between the waste liquid bottle 333 and the end cap 332.

[0085] The mouth of the waste liquid bottle 333 faces downward, and both the liquid guide tube 334 and the ventilation tube 335 extend into the bottom of the waste liquid bottle 333. The length of the ventilation tube 335 inside the waste liquid bottle 333 is greater than the length of the liquid guide tube 334 inside the waste liquid bottle 333. That is to say, the outlet of the ventilation tube 335 is higher than the outlet of the liquid guide tube 334 inside the waste liquid bottle 333. On the one hand, it enables the waste liquid to flow downward into the waste liquid bottle 333 under the action of gravity. On the other hand, it ensures that the internal space of the waste liquid bottle 333 can be fully utilized while preventing the outlet of the ventilation tube 335 from being blocked by the waste liquid.

[0086] In this embodiment, one waste liquid bottle 333 is provided, and various waste liquids flow into one waste liquid bottle 333, which is convenient for replacement. Of course, the number of waste liquid bottles 333 can also be set according to actual needs.

[0087] The reagent bottle assembly is used to store reagents and includes a reagent bottle 336 and a first thin film bag 337. Both ends of the reagent bottle 336 are provided with openings. The first thin film bag 337 is placed into the reagent bottle 336, dividing the inner cavity of the reagent bottle 336 into two isolated cavities. One cavity is used to introduce compressed air, and the other cavity is used to store reagents. When the first thin film bag 337 is squeezed by the compressed air, the reagent will flow out of the reagent bottle 336 under the action of the pressure difference. One end of the reagent bottle 336 is connected to the end cap 332 by a thread, and a sealing ring is used to seal between the reagent bottle 336 and the end cap 332.

[0088] In this embodiment, four reagent bottles 336 are provided for storing four kinds of reagents, and a first thin film bag 337 is arranged in each reagent bottle 336. Of course, the number of reagent bottles 336 can be set according to actual situations. For the convenience of distinction, the four kinds of reagents are represented by A, T, G, and C.

[0089] The cleaning bottle assembly is used for storing cleaning liquid and includes a cleaning bottle 338 and a second thin film bag 339. Both ends of the cleaning bottle 338 are provided with openings, and the second thin film bag 339 is placed into the cleaning bottle 338, dividing the inner cavity of the cleaning bottle 338 into two mutually isolated cavities. One cavity is used for introducing compressed air, and the other cavity is used for storing cleaning liquid. When the second thin film bag 339 is squeezed by the compressed air, the reagent will flow out of the cleaning bottle 338 under the action of the pressure difference. One end of the cleaning bottle 338 is connected to the end cap 332 by a thread, and a sealing ring is used for sealing between the cleaning bottle 338 and the end cap 332.

[0090] In this embodiment, two cleaning bottles 338 are provided for storing two kinds of cleaning liquids, and a second thin film bag 339 is arranged in each cleaning bottle 338. For the convenience of distinction, the two kinds of cleaning liquids are represented by W1 and W2. The sizes of the two cleaning bottles 338 can be the same or different, which is not limited herein.

[0091] A number of through holes are provided in the upper part of the end cap 332, and the bottle assembly is communicated with the through holes. These through holes enable each reagent and cleaning liquid to flow out through the end cap 332, and waste liquid, atmosphere, or compressed air can flow into the waste liquid bottle 333 or the cavity of the reagent housing 331 through the end cap 332; rubber plugs are arranged in the through holes, and the outlets or inlets of each reagent, cleaning liquid, or waste liquid, atmosphere, and compressed air on the end cap 332 are blocked by the rubber plugs.

[0092] The puncture needle assembly 32 includes a number of puncture needles. The puncture needles are installed on the reagent mounting seat 31 by threads, and a sealing ring is arranged between the puncture needles and the reagent mounting seat 31. A flow channel is arranged in the reagent mounting seat 31, and one end of the puncture needle is communicated with the flow channel. When the reagent canister assembly 33 is inserted into the puncture needle assembly 32, the puncture needle can penetrate through the rubber plug so that the other end of the puncture needle is communicated with the bottle assembly. The flow channel is communicated with the liquid path system. The flow channel is in an L shape. One end of the flow channel is connected to the puncture needle, and the other end is connected to the pipeline of the liquid path system.

[0093] It can be known that there are many pipelines arranged in the gene sequencer for the flow of gas and liquid. Only the connection relationship is described herein, and the detailed pipeline layout and quantity are not elaborated.

[0094] The liquid path system connects the chip detection device 2 and the reagent supply device 3, and is used to transport liquids such as reagents and cleaning liquids in the reagent supply device 3 to the chip detection device 2, and transport the waste gas and waste liquid generated during the detection process to the waste liquid bottle assembly of the reagent supply device 3.

[0095] The liquid path system includes a confluence structure 4 and an injection pump assembly connected to the confluence structure 4. A microchannel is provided inside the confluence structure 4, and the microchannel connects the chip detection device 2 and the reagent supply device 3. Specifically, the confluence structure 4 is connected to the flow channel through hole on the flow channel connection block 223 in the chip detection device 2 to transport the fluid to the chip detection area in the chip detection device 2. The confluence structure 4 and the flow channel connection block 223 are sealed by a sealing ring. The setting of the liquid path system has excellent anti-cross contamination ability and low system cost.

[0096] The confluence structure 4 is arranged on the mounting plate 61. Due to the need to replace the sequencing chip 10, the confluence structure 4 needs to be pushed out and retracted along with the carrier assembly 22 in the chip detection device 2. Therefore, the confluence structure 4 is rotatably connected to the mounting plate 61. The mounting plate 61 is U-shaped, the confluence structure 4 is located inside the mounting plate 61, and both ends of the confluence structure 4 are connected to the mounting plate 61 through a translational link assembly 62. When the carrier assembly 22 moves, it drives the confluence structure 4 to shift, and then makes the confluence structure 4 rotate relative to the mounting plate 61.

[0097] The injection pump assembly includes an injection pump 5 and an injection pump mounting bracket. The injection pump 5 is driven by an electric motor and is provided with a position sensor to provide accurate and stable reagent flow during gene detection. The injection pump 5 is connected to the confluence structure 4. During the operation of the injection pump 5, pressure will be generated in the pipeline and the confluence structure 4, so that the liquid can flow under the action of the pressure difference.

[0098] The confluence structure 4 includes a microchannel plate 41, a valve 42 and a connection block 43. A microchannel is provided inside the microchannel plate 41, and the microchannel includes a common channel and a plurality of branches connected to the common channel; the valve 42 is arranged at the junction of the common channel and the branch, and one valve 42 is provided corresponding to each branch to control the on-off of the common channel and the branch. The connection block 43 is used to support the microchannel plate 41, the valve 42, the microchannel plate 41 and part of the pipeline are all connected to the connection block 43, and a card slot is opened on the connection block 43, and the microchannel plate 41 is embedded in the card slot. The setting of the microchannel plate 41 omits a lot of external pipelines, has a small volume, light weight and occupies a small space. The valve 42 is used to control the on-off of the common channel and the branch, is easy to operate, makes the multiple branches independent of each other, and has excellent anti-cross contamination ability.

[0099] A branch inlet is provided for each branch, and a branch outlet is provided for each branch inlet. The valve 42 connects the branch inlet and the branch outlet. Each pair of the branch inlets and the corresponding branch outlets are arranged in pairs, and several pairs of branch inlets and branch outlets are arranged at intervals symmetrically on the microchannel plate 41, so that the lengths of all branches are the same, thereby making the control of the reagent amounts in each branch single and simple. The multiple branches include several waste liquid branches and several reagent branches.

[0100] In this embodiment, there are nine branches, namely five waste liquid branches and four reagent branches. The microchannel includes nine pairs of branch inlets and branch outlets, and there are nine valves 42 in total. For the convenience of description, the nine valves 42 are respectively represented by V2-V10, and the nine pairs of branch inlets and branch outlets are respectively the waste liquid one outlet 4011, the waste liquid one inlet 4012, the reagent one outlet 4021, the reagent one inlet 4022, the reagent two outlet 4031, the reagent two inlet 4032, the waste liquid two outlet 4041, the waste liquid two inlet 4042, the waste liquid three outlet 4051, the waste liquid three inlet 4052, the reagent three outlet 4061, the reagent three inlet 4062, the reagent four outlet 4071, the reagent four inlet 4072, the waste liquid four outlet 4081, the waste liquid four inlet 4082, the waste liquid five outlet 4091 and the waste liquid five inlet 4092.

[0101] The common flow channel has a common interface, and the common interface includes a cleaning liquid inlet 44 and a waste liquid total outlet 45. The waste liquid five inlet 4092 is communicated with the waste liquid total outlet 45. One end of the waste liquid branch is communicated with the cleaning liquid inlet 44, and the other end is communicated with the waste liquid total outlet 45. One end of the reagent branch is communicated with the reagent bottle 336, and the other end is communicated with the cleaning liquid inlet 44.

[0102] The common interface also includes a chip liquid inlet 46 and a chip liquid outlet 47. The chip liquid inlet 46 is communicated with the cleaning liquid inlet 44, and the chip liquid outlet 47 is communicated with the waste liquid total outlet 45 through one of the waste liquid branches. Specifically, the chip liquid outlet 47 is communicated with the waste liquid total outlet 45 through the waste liquid five outlet 4091 and the waste liquid five inlet 4092. In the microchannel, the flow paths of the reagents are the same, and the flow paths of the waste liquids are the same.

[0103] The microchannel plate 41 is in a T shape, and the cleaning liquid inlet 44 and the waste liquid total outlet 45 are arranged at the middle part of the microchannel plate 41. The microchannel plate 41 includes a flow channel plate 411 and a flow channel cover plate 412 that are buckled with each other. The microchannel is opened on the flow channel plate 411, and holes communicated with the microchannel are opened on the flow channel cover plate 412.

[0104] In the current collector structure 4, the waste liquid first outlet 4011 and the waste liquid first inlet 4012 are respectively connected to the NO and NC ports of the valve V9, the reagent first outlet 4021 and the reagent first inlet 4022 are respectively connected to the NC and NO ports of the valve V5, the reagent second outlet 4031 and the reagent second inlet 4032 are respectively connected to the NC and NO ports of the valve V4, the waste liquid second outlet 4041 and the waste liquid second inlet 4042 are respectively connected to the NO and NC ports of the valve V8, the waste liquid third outlet 4051 and the waste liquid third inlet 4052 are respectively connected to the NO and NC ports of the valve V7, the reagent third outlet 4061 and the reagent third inlet 4062 are respectively connected to the NC and NO ports of the valve V3, the reagent fourth outlet 4071 and the reagent fourth inlet 4072 are respectively connected to the NC and NO ports of the valve V2, the waste liquid fourth outlet 4081 and the waste liquid fourth inlet 4082 are respectively connected to the NO and NC ports of the valve V6, and the waste liquid fifth outlet 4091 and the waste liquid fifth inlet 4092 are respectively connected to the NO and NC ports of the valve V10. Among them, the NO and NC ports of the valve are the inlet and outlet of the valve 42 respectively.

[0105] The cleaning liquid inlet 44 is connected to the outlet of the injection pump 5. The chip liquid inlet 46 and the chip liquid outlet 47 are respectively connected to the liquid inlet through-hole and the liquid outlet through-hole of the flow channel connection block 223 on the chip detection device 2. The total waste liquid outlet 45 is connected to the waste liquid bottle 333 in the reagent supply device 3. The reagent first inlet 4022, the reagent second inlet 4032, the reagent third inlet 4062, and the reagent fourth inlet 4072 are respectively connected to the outlets of the four reagent bottles 336.

[0106] The gas path system is connected to both the reagent supply device 3 and the injection pump 5 to provide compressed air. On the one hand, the compressed air can squeeze the first thin film bag 337 to squeeze the reagent out of the reagent bottle 336. Similarly, the compressed air can squeeze the second thin film bag 339 to squeeze the cleaning liquid out of the cleaning liquid bottle. On the other hand, the compressed air can enter the current collector structure 4 through the injection pump 5 to flush the microchannel. Therefore, some pipelines and components of the gas path system and the liquid path system need to be shared. Both the liquid path system and the gas path system are arranged on the installation platform 21.

[0107] An auxiliary valve block assembly 8 is arranged between the gas path system and the injection pump 5. That is to say, one end of the injection pump 5 is communicated with the cleaning liquid inlet 44, and the other end of the injection pump 5 is communicated with the gas path system through the auxiliary valve block assembly 8. At the same time, the auxiliary valve block assembly 8 is communicated with the cleaning bottle assembly in the reagent supply device 3.

[0108] The auxiliary valve block assembly 8 includes an auxiliary valve block 81 and auxiliary valves 82. There are four auxiliary valves 82, which are represented by V1, V11, V12, and V13 respectively. An auxiliary flow channel is provided in the auxiliary valve block 81, and at least two interfaces are provided on the auxiliary flow channel corresponding to each auxiliary valve 82. The interfaces are represented by a, a′, b, b′, c, c′, d, d′, and d″ respectively. Among them, the interfaces a and a′ are respectively connected to the NO and NC ports of the valve V1, the interfaces b and b′ are respectively connected to the NO and NC ports of the valve V11, the interfaces c and c′ are respectively connected to the NO and NC ports of the valve V12, and the interfaces d, d′, and d″ are respectively connected to the NO, COM, and NC ports of the valve V13.

[0109] The auxiliary flow channel includes a liquid flow channel and a gas flow channel. Therefore, the auxiliary valve block 81 is provided with a first air inlet 801, a first air outlet 802, a second air inlet 803, a second air outlet 804, a first cleaning liquid inlet 805, a second cleaning liquid inlet 806, and a liquid outlet 807.

[0110] The gas path system includes an air pump assembly, a pressure regulating valve assembly, and an air filter 73. The air pump assembly includes an air pump 71 and an air pump mounting bracket. The air pump 71 is used to provide compressed air. The pressure regulating valve assembly includes a pressure regulating valve 72 and a pressure regulating valve mounting bracket. The inlet of the pressure regulating valve 72 is connected to the air outlet of the air pump 71, and the outlet of the pressure regulating valve 72 is branched through a tee and connected to the first air inlet 801 on the auxiliary valve block 81 and the air inlet of the air filter 73 respectively.

[0111] The second air outlet 804 of the auxiliary valve block 81 communicates with the atmosphere, the first air outlet 802 is connected to the compressed air inlet in the reagent tank assembly 33, the second air inlet 803 is connected to the air outlet of the air filter 73 assembly, the second cleaning liquid inlet 806 is connected to the outlet of the cleaning bottle 338 containing W2 provided in the reagent tank assembly 33, the first cleaning liquid inlet 805 is connected to the outlet of the cleaning bottle 338 containing W1 provided in the reagent tank assembly 33, and the liquid outlet 807 is connected to the inlet of the syringe pump 5.

[0112] The following is a detailed description of the usage process.

[0113] Loading of the reagent. Insert the reagent tank assembly 33 into the reagent installation position at the upper part of the outer housing 11 and press it firmly to complete the loading of the reagent. In this process, the puncture needle penetrates through the rubber stopper, so that the reagent tank assembly 33 communicates with the liquid path system. When the air pump 71 is powered on, the compressed air stabilized by the pressure regulating valve 72 enters the cavity of the bottle assembly, squeezing the first film bag 337 and the second film bag 339, so that the liquids in each reagent bottle 336 and the cleaning liquid bottle have a certain pressure. When the valve on the liquid path system is opened, the corresponding liquid can enter the liquid path system. The waste liquid generated during the working process enters the waste liquid bottle 333 through the relevant pipelines.

[0114] Place the sequencing chip 10. Touch the relevant button, and the detection component 23 and the carrier component 22 are synchronously pushed out. Open the hinge upper cover 2222, and then you can use tweezers to replace the sequencing chip 10 to be detected; touch the relevant button, and the detection component 23 and the carrier component 22 are synchronously retracted, thus completing the replacement of the sequencing chip 10.

[0115] Sequencing. Here, the injection and cleaning of reagent A are taken as examples for description, and the injection and cleaning processes of other reagents are the same as it.

[0116] First, cleaning process (before detection)

[0117] Step 11: Connect valves V1, V6, V7, V8, V9, disconnect other valves. While the injection pump 5 is reset, the cleaning liquid W1 passes through the pipeline, the injection pump 5, then enters the common flow channel through the cleaning liquid inlet 44 set on the microchannel plate 41, and is shunted into four branches through the common flow channel, flowing into the waste liquid first outlet 4011, the waste liquid second outlet 4041, the waste liquid third outlet 4051, and the waste liquid fourth outlet 4081 respectively. After passing through the corresponding valves V6, V7, V8, V9, it enters the waste liquid first inlet 4012, the waste liquid second inlet 4042, the waste liquid third inlet 4052, and the waste liquid fourth inlet 4082. After converging at the waste liquid total outlet 45, it flows into the waste liquid bottle 333 through the pipeline. After a certain delay time, close valves V1, V6, V7, V8, V9, thus realizing the cleaning of each reagent injection flow channel.

[0118] Step 12: Connect valves V1, V10, disconnect other valves. The cleaning liquid W1 passes through the pipeline, the injection pump 5, then enters the common flow channel through the cleaning liquid inlet 44 set on the microchannel plate 411, enters the chip detection area through the chip liquid inlet 46 and the liquid inlet through hole of the flow channel connection block 223, flows out through the liquid outlet through hole of the flow channel connection block 223 and then flows to the chip liquid outlet 47, and then flows to the waste liquid fifth outlet 4091. After passing through valve V10, it enters the waste liquid total outlet 45 through the waste liquid fifth inlet 4092 and then flows into the waste liquid bottle 333 through the pipeline. After a certain delay time, close valves V1, V10, thus realizing the cleaning of the chip detection flow channel.

[0119] Second, preparation process of reagent A

[0120] Step 21: Valves V1, V6, and V2 are turned on, and other valves are turned off. The cleaning liquid W1 passes through the pipeline, the injection pump 5, and then enters through the cleaning liquid inlet 44 provided on the microchannel plate 41, reaching the reagent A injection branch intersection. Reagent A passes through valve V2 and enters the reagent A injection branch from the reagent one outlet 4021. After converging with the cleaning liquid W1, it flows through the waste liquid one outlet 4011, valve V6, the waste liquid one inlet 4012, and the waste liquid total outlet 45, and then flows into the waste liquid bottle 333 through the pipeline. After a certain delay, valves V1, V6, and V2 are closed, thereby realizing the cleaning of the reagent A injection branch. During the process, control the opening time of valve V2 to ensure that the contaminated reagent A existing on the branch is excluded.

[0121] Step 22: Valve V2 is turned on, and other valves are turned off. Control the injection pump 5 to move downward (ensure sufficient suction volume). The reagent A extruded by compressed air passes through the pipeline and valve V2, then enters the reagent one outlet 4021, the common flow channel, and the cleaning liquid inlet 44 provided on the microchannel plate 41, and then enters and accumulates in the pipeline. After the syringe moves downward to complete the operation, valve V2 is turned off, valve V6 is turned on, and other valves are turned off. After a certain delay, eliminate the residual pressure in the pipeline system to realize the preparation of reagent A.

[0122] Third, Reagent Pushing Process

[0123] Step 21: Valve V10 is turned on, and other valves are closed. Control the injection pump 5 to move upward (ensure sufficient ejection volume). The reagent A accumulated in the pipeline passes through the cleaning liquid inlet 44, the common flow channel, and the chip liquid inlet 46 provided on the microchannel plate 41, and then enters the liquid inlet through hole provided in the flow channel connection block 223, and is steadily injected into the chip detection area at a certain speed, thereby realizing the injection of reagent A.

[0124] Fourth, Chip Reaction, Detection, Data Acquisition and Processing

[0125] Fifth, Cleaning Process (After Detection)

[0126] Step 51: Valves V1 and V6 are turned on, and other valves are turned off. The cleaning liquid W1 passes through the pipeline, the injection pump 5, and then enters the waste liquid one outlet 4011 through the cleaning liquid inlet 44 provided on the microchannel plate 41 and the common flow channel. Through the corresponding valve V6, it enters the reagent one inlet 4022 and flows to the waste liquid total outlet 45, and then flows into the waste liquid bottle 333 through the pipeline. After a certain delay, valves V1 and V6 are closed, thereby realizing the cleaning of the reagent A injection flow channel.

[0127] Step 52: Valves V1 and V10 are turned on, and other valves are turned off. The cleaning liquid W1 passes through the pipeline, the injection pump 5, and then enters the common flow channel through the cleaning liquid inlet 44 provided on the microchannel plate 41. Then it enters the chip detection area through the chip liquid inlet 46 and the liquid inlet through-hole of the flow channel connection block 223. After passing through the liquid outlet through-hole of the flow channel connection block 223, it flows into the chip liquid outlet 47 provided on the microchannel plate 411, flows to the waste liquid five outlet 4091, through valve V10, and then enters the waste liquid total outlet 45 through the waste liquid five inlet 4092. Then it flows into the waste liquid bottle 333 through the pipeline. After a certain delay time, valves V1 and V10 are closed, thus realizing the cleaning of the chip detection flow channel.

[0128] In addition to the above cleaning process, in some working conditions, it is also necessary to use the cleaning liquid W2 or compressed air for cleaning. Taking the cleaning of the flow channel injected with reagent A as an example, the cleaning process of injecting other reagents into the flow channel is the same as it.

[0129] Cleaning the common flow channel with compressed air includes:

[0130] Step 101: Open valves V12, V6, V7, V8, V9, and V10. The compressed air passes through the pipeline, the air filter 73, and the injection pump 5, and then enters the common flow channel through the cleaning liquid inlet 44 provided on the microchannel plate 41. It is divided into two branches. One branch passes through the waste liquid one outlet 4011, the waste liquid two outlet 4041, the waste liquid three outlet 4051, and the waste liquid four outlet 4081, and then through the corresponding valves V6, V7, V8, and V9 to the waste liquid total outlet 45 and flows into the waste liquid bottle 333; the other branch enters the chip detection area through the chip liquid inlet 46 and the liquid inlet through-hole of the flow channel connection block 223, passes through the liquid outlet through-hole of the flow channel connection block 223, the waste liquid five outlet 4091, valve V10, and the waste liquid five inlet 4092, and then flows into the waste liquid bottle 333 through the waste liquid total outlet 45. After a certain delay time, valves V12, V6, V7, V8, V9, and V10 are closed, thus realizing the purging of the common flow channel with compressed air.

[0131] Cleaning the common flow channel with the cleaning liquid W2 includes:

[0132] Step 201: Open valves V11, V6, V7, V8, V9, and V10. The cleaning liquid W2 enters through the pipeline and the injection pump 5 into the cleaning liquid inlet 44 provided on the microchannel plate 41 and then enters the common flow channel. It is divided into two branches. One branch flows through the waste liquid outlet 4011, waste liquid outlet 4041, waste liquid outlet 4051, and waste liquid outlet 4081, and then through the corresponding valves V6, V7, V8, and V9 to the waste liquid total outlet 45 and into the waste liquid bottle 333. The other branch enters the chip detection area through the chip liquid inlet 46 and the liquid inlet through hole of the flow channel connection block 223, and then through the liquid outlet through hole of the flow channel connection block 223, waste liquid outlet 4091, valve V10, and waste liquid inlet 4092, and finally through the waste liquid total outlet 45 and into the waste liquid bottle 333. After a certain delay, close valves V11, V6, V7, V8, V9, and V10, thus realizing the cleaning of the common flow channel with the cleaning liquid W2.

[0133] Step 202: Open valves V1, V6, V7, V8, V9, and V10. The cleaning liquid W1 enters through the pipeline and the injection pump 5 into the cleaning liquid inlet 44 and the common flow channel provided on the microchannel plate 41. It is divided into two branches. One branch flows through the waste liquid outlet 4011, waste liquid outlet 4041, waste liquid outlet 4051, and waste liquid outlet 4081, and then through the corresponding valves V6, V7, V8, and V9 to the waste liquid total outlet 45 and into the waste liquid bottle 333. The other branch enters the chip detection area through the chip liquid inlet 46 and the liquid inlet through hole of the flow channel connection block 223, and then through the liquid outlet through hole of the flow channel connection block 223, waste liquid outlet 4091, valve V10, and waste liquid inlet 4092, and finally through the waste liquid total outlet 45 and into the waste liquid bottle 333. After a certain delay, close valves V12, V6, V7, V8, V9, and V10, thus realizing the cleaning of the common flow channel with the cleaning liquid W1 and preventing the cleaning liquid W2 from remaining in the liquid path system.

[0134] The above steps can be repeated according to the actual situation.

[0135] Similarly, under some working conditions, when the detection is completed and the reagent is about to be consumed, it is necessary to use the cleaning liquid W2 to clean the reagent branch. Taking reagent A as an example, it includes:

[0136] Step 301: Open valves V13 and V11. Control the injection pump 5 to move downward to inhale a sufficient amount of the cleaning liquid W2, then close valve V11. Open valve V2 and control the injection pump 5 to move upward to drive the cleaning liquid W2 through the pipeline into the cleaning liquid inlet 44 provided on the microchannel plate 41, the common flow channel, the reagent outlet 4021, valve V2, and the reagent inlet 4022, and then through the pipeline into the reagent bottle A in the reagent bottle assembly. When the injection pump 5 stops pushing upward for a certain time, close valve V2, thus realizing the cleaning of the branch where reagent A is located with the cleaning liquid W2.

[0137] Step 302: Open valves V13 and V1, control the injection pump 5 to move downward. After inhaling a sufficient amount of cleaning liquid W1, close valve V1, open valve V2, control the injection pump 5 to move upward, and drive the cleaning liquid W1 to enter through the pipeline into the cleaning liquid inlet 44 provided on the microchannel plate 41, the common flow channel, the reagent one outlet 4021, valve V2, the reagent one inlet 4022, and then enter the test bottle A in the reagent bottle assembly through the pipeline; when the injection pump 5 stops pushing upward for a certain period of time, close valve V2, thereby realizing the cleaning of the branch where the reagent A is located with the cleaning liquid W1, and preventing the cleaning liquid W2 from remaining in the liquid path system.

[0138] The above steps can be repeatedly executed according to the actual situation.

[0139] Finally, relieve the pressure. When the detection is completed, it is necessary to release the compressed air inside the reagent supply device 3. Open valve V13, and the air inlet of the reagent tank assembly 33 is communicated with the atmosphere, thereby realizing the pressure relief of the reagent supply device 3.

[0140] The above embodiments only illustrate the basic principles and characteristics of the present invention. The present invention is not limited by the above embodiments. Without departing from the spirit and scope of the present invention, there are various changes and modifications to the present invention, and these changes and modifications all fall within the scope of the present invention claimed. The scope of protection of the present invention is defined by the appended claims and their equivalents.

Claims

1. A gene sequencer, characterized in that, Comprising: A chip detection device (2) for carrying and detecting a sequencing chip (10); A reagent supply device (3) for storing reagents; A liquid path system including a confluence structure (4) and an injection pump (5) communicated with the confluence structure (4), a microchannel is arranged in the confluence structure (4), and the microchannel communicates the chip detection device (2) with the reagent supply device (3); A gas path system connected to both the reagent supply device (3) and the injection pump (5) for providing compressed air; The confluence structure (4) includes: A microchannel plate (41) with a microchannel arranged inside, the microchannel includes a common channel and a plurality of branches communicated with the common channel; Valves (42) arranged at the junction of the common channel and the branches, and one valve (42) is arranged corresponding to each branch for controlling the on-off of the common channel and the branches; A connection block (43) for supporting the microchannel plate (41), the valves (42), the microchannel plate (41) and part of the pipelines are all connected to the connection block (43), a clamping groove is arranged on the connection block (43), and the microchannel plate (41) is embedded in the clamping groove; The common channel has a common interface, the common interface includes a cleaning liquid inlet (44) and a waste liquid total outlet (45), a plurality of the branches include several waste liquid branches, one end of the waste liquid branch is communicated with the cleaning liquid inlet (44), and the other end is communicated with the waste liquid total outlet (45); The microchannel plate (41) is in a T shape, the cleaning liquid inlet (44) and the waste liquid total outlet (45) are arranged at the middle part of the microchannel plate (41); the microchannel plate (41) includes a channel plate (411) and a channel cover plate (412) that are buckled with each other, the microchannel is arranged on the channel plate (411), and holes communicated with the microchannel are arranged on the channel cover plate (412).

2. The gene sequencer according to claim 1, wherein The chip detection device (2) includes a carrying component (22) and a detection component (23) connected to the carrying component (22), the carrying component (22) is used for positioning the sequencing chip (10), and the detection component (23) is used for detecting the sequencing chip (10).

3. The gene sequencer according to claim 2, wherein, The carrying component (22) includes: A chip mounting seat (221) having a groove, and the sequencing chip (10) can be placed in the groove; A hinge component (222) including a hinge base (2221) and a hinge upper cover (2222) that are hinged to each other, and the hinge base (2221) is fixedly connected to the chip mounting seat (221); A channel connection block (223) connected to the hinge upper cover (2222), and the channel connection block (223) communicates the liquid path system with the groove.

4. The gene sequencer according to claim 2, wherein The chip detection device (2) further includes a driving component (24), and the driving component (24) is connected to the detection component (23) for driving the carrying component (22) and the detection component (23) to move linearly synchronously.

5. The gene sequencer according to claim 1, characterized in that, The reagent supply device (3) includes a reagent mounting base (31), a puncture needle assembly (32) disposed on the reagent mounting base (31), and a reagent tank assembly (33) that can be inserted and communicated with the puncture needle assembly (32). A flow channel is provided in the reagent mounting base (31), the puncture needle assembly (32) is communicated with the flow channel, and the flow channel is communicated with the liquid path system.

6. The gene sequencer according to claim 5, characterized in that, The reagent tank assembly (33) includes a reagent housing (331), an end cap (332) disposed at one end of the reagent housing (331), and a bottle assembly disposed inside the reagent housing (331) and connected to the end cap (332). A plurality of through holes are formed in the end cap (332), and rubber plugs are provided in the through holes. The puncture needle assembly (32) includes a puncture needle that can pass through the rubber plug.

7. The gene sequencer according to claim 1, wherein The syringe pump (5) is communicated with the cleaning liquid inlet (44).

8. The gene sequencer according to any one of claims 1-6, characterized in that, An auxiliary valve block assembly (8) is provided between the syringe pump (5) and the gas path system. The auxiliary valve block assembly (8) includes an auxiliary valve block (81), and a liquid flow channel and a gas flow channel are provided inside the auxiliary valve block (81).

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