Device for sequencing chip surface chemical modification

Abstract

The utility model discloses a device for sequencing chip surface chemical modification, and the device comprises a first rotary valve which is used for selectively communicating a reagent; the second rotary valve is communicated with the first rotary valve and is used for conveying one reagent to the plurality of sequencing chips; a plurality of chip carrying platforms, wherein each chip carrying platform is used for carrying at least two sequencing chips; the pump is used for sucking or discharging the reagent; the first electromagnetic valve is arranged between the pump and the chip carrying table and is used for selecting the pump to be communicated with the liquid outlet end of the sequencing chip or selecting the pump to be communicated with the waste liquid barrel; the rotating disc assembly is provided with a rotating disc, the first rotating valve, the second rotating valve, the chip carrying table, the first electromagnetic valve and the pump are all arranged on the surface of the rotating disc, the chip carrying table is erected at the position close to the edge of the rotating disc, and the pump is arranged below the chip carrying table. According to the device provided by the embodiment of the invention, the chip processing efficiency is improved, and the manual operation cost and time are saved.

Description

Technical Field

[0001] This application belongs to the technical field of gene sequencing, and particularly relates to a device for chemical modification of the surface of a sequencing chip. Background Art

[0002] When a gene sequencer is performing detection, the main carrier part of the sample is the sequencing chip, and the quality of the sequencing chip itself will affect the accuracy and reliability of the sequencing results. Before sequencing, it is necessary to perform pretreatment on the sequencing chip, that is, to chemically modify the surface of the sequencing chip to enhance probe fixation, improve signal intensity and specificity, prevent non-specific adsorption, enhance surface stability, provide a multifunctional surface, optimize reaction conditions, etc. These modifications not only improve the efficiency and accuracy of sequencing, but also expand the application range of the sequencing chip, providing a more powerful tool for genomics and molecular biology research.

[0003] To chemically modify the surface of the sequencing chip, mainly the following various reagents are added during the research and development of samples and production in the laboratory: oligo, polymer, cleaning reagent, and chip preservation reagent. This process mainly relies on manual participation in the prior art to sequentially add the above reagents. However, the manual operation efficiency is low and cannot meet the demand for improving the production capacity of the sequencing chip. Therefore, there is an urgent need for a device suitable for mass production that can chemically modify the surface of the sequencing chip. Utility Model Content

[0004] This application discloses a device for chemical modification of the surface of a sequencing chip to solve the problem of low efficiency in the prior art.

[0005] This application provides a device for chemical modification of the surface of a sequencing chip, including:

[0006] A first rotary valve for selectively connecting one reagent;

[0007] A second rotary valve connected to the first rotary valve for transporting one of the reagents to a plurality of sequencing chips;

[0008] Multiple groups of chip carriers, each group of chip carriers for carrying at least four sequencing chips;

[0009] A pump for sucking or discharging reagents;

[0010] A first solenoid valve disposed between the pump and the chip carrier for selectively connecting the pump to the liquid outlet end of the sequencing chip or connecting the pump to the waste liquid bucket;

[0011] Rotating disk assembly, provided with a rotating disk, the first rotary valve, the second rotary valve, the chip stage, the first solenoid valve and the pump are all arranged on the surface of the rotating disk, the chip stage is erected at a position close to the edge of the rotating disk, and the pump is arranged below the chip stage.

[0012] Optionally, the second rotary valve is arranged on the central axis of the rotating disk.

[0013] Optionally, multiple groups of the chip stages are distributed in a regular polygon on the surface of the rotating disk, and the paths between each chip stage and the second rotary valve are equal.

[0014] Optionally, the disk assembly further includes:

[0015] Bottom plate;

[0016] Fixed shaft, fixedly connected to the bottom plate, arranged between the rotating disk and the bottom plate;

[0017] Bearing, installed on the fixed shaft;

[0018] Bearing mounting seat, surrounding the outside of the bearing, fixedly connected to the rotating disk;

[0019] Flap, fixed to the top end of the fixed shaft, used to abut against the bearing;

[0020] Caster, fixed to the bottom surface of the rotating disk through a connecting piece, used to slide on the surface of the bottom plate along with the rotating disk.

[0021] Optionally, an upper brake block is arranged on the bottom surface of the rotating disk, a lower brake block is arranged on the surface of the bottom plate, the lower brake block is arranged on the running track of the upper brake block rotating along with the rotating disk, and the lower brake block is used to limit the upper brake block.

[0022] Optionally, anti-slip pads are arranged on the surfaces of the upper brake block and the lower brake block that come into contact with each other when they touch.

[0023] Optionally, the chip stage includes: a base, a liquid path end block, and clamping components arranged on opposite sides of the base. The base is provided with a slot for placing a sequencing chip, and the flow channel of the sequencing chip is communicated with the liquid path through the liquid path end block;

[0024] The clamping component includes a hinge seat and a flap rotatably arranged on the hinge seat. A pressing member is arranged on the flap. When the flap rotates inwards to the in-place position, the pressing member tightly clamps on the surface of the chip pressing plate, and the chip pressing plate closely adheres to the surface of the sequencing chip.

[0025] Optionally, the chip stage further includes: a heating tape and a heat insulation plate disposed under the base, and the heat insulation plate is fixedly connected to the base.

[0026] Optionally, support columns are disposed on the surface of the rotating disk, and the chip stage is erected on the surface of the rotating disk through the support columns.

[0027] As can be seen from the above technical solutions, this device uses multiple identical chip stages and a reasonable layout. The rotating disk can carry at least five groups of chip stages, so at most 20 chips can be simultaneously subjected to liquid addition and modification treatment at one time, thereby improving the pre-processing efficiency of the sequencing chip and reducing the surface deviation of different sequencing chips caused by manual operation. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 It is a schematic diagram of the main structure of a device for surface chemical modification of a sequencing chip provided by an embodiment of the present application;

[0029] Figure 2 It is a schematic diagram of the structures of the first rotary valve and the second rotary valve provided by an embodiment of the present application;

[0030] Figure 3 It is a schematic diagram of the structure of a sequencing chip provided by an embodiment of the present application;

[0031] Figure 4 It is a schematic diagram of the top view structure of a device for surface chemical modification of a sequencing chip provided by an embodiment of the present application;

[0032] Figure 5 It is a schematic diagram of the structure of a rotating disk assembly provided by an embodiment of the present application;

[0033] Figure 6 It is a schematic diagram of the front view structure of a rotating disk assembly provided by an embodiment of the present application;

[0034] Figure 7 It is a schematic diagram of the structure of a rotating disk assembly from another perspective provided by an embodiment of the present application;

[0035] Figure 8 It is a schematic diagram of the structure of a chip stage provided by an embodiment of the present application;

[0036] Figure 9 It is a disassembled schematic diagram of a chip stage provided by an embodiment of the present application;

[0037] Figure 10 It is a schematic diagram of the cross-sectional view of a chip stage provided by an embodiment of the present application;

[0038] Figure 11Front view structure schematic diagram of a device for surface chemical modification of a sequencing chip provided by an embodiment of the present application;

[0039] Figure 12 Schematic diagram of the liquid path provided by an embodiment of the present application;

[0040] Figure 13 Second schematic diagram of the liquid path provided by an embodiment of the present application;

[0041] Figure 14 Third schematic diagram of the liquid path provided by an embodiment of the present application.

[0042] Reference numerals: 1 - First rotary valve; 2 - Second rotary valve; 3 - Chip stage; 4 - First solenoid valve; 5 - Pump; 6 - Rotary disc assembly; 7 - Second solenoid valve; 8 - Third solenoid valve; 11 - First liquid inlet end; 12 - First liquid outlet end; 21 - Second liquid inlet end; 22 - Second liquid outlet end; 30 - Sequencing chip; 301 - Third liquid inlet end; 302 - Third liquid outlet end; 31 - Base; 32 - Liquid path end block; 33 - Clamping assembly; 34 - Heating tape; 35 - Heat insulation plate; 36 - Fuse; 311 - Slot; 312 - Positioning plate; 313 - Partition plate; 321 - First liquid path end block; 322 - Second liquid path end block; 331 - Hinge seat; 332 - Flap; 333 - Compression member; 41 - First common port; 42 - First normally open port; 43 - First normally closed port; 61 - Rotary disc; 62 - Base plate; 63 - Fixed shaft; 64 - Bearing; 65 - Bearing mounting seat, 66 - Retaining plate; 67 - Caster; 611 - Upper brake block; 621 - Lower brake block; 612 - Support column; 71 - Second common port; 72 - Second normally open port; 73 - Second normally closed port; 81 - Third common port; 82 - Third normally open port; 83 - Third normally closed port. Detailed implementation manners

[0043] The technical solutions in the embodiments of the present application will be described clearly and completely below. Apparently, the described embodiments are only a part of the embodiments of the present application, rather than all of them. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present application without creative efforts shall fall within the protection scope of the present application.

[0044] For surface chemical modification of a sequencing chip, mainly oligo, polymer, cleaning reagent and other fluids flow through the sequencing chip in sequence through the liquid path. These reagents can undergo a series of reactions on the sequencing chip under certain temperature conditions, thereby completing the modification.

[0045] Based on this, an embodiment of the present application provides a device for surface chemical modification of a sequencing chip. Refer to Figure 1The structural schematic diagram shown, the device includes: a first rotary valve 1, a second rotary valve 2, a chip stage 3, a first solenoid valve 4, a pump 5, and a rotary disk assembly 6. The rotary disk assembly 6 is provided with a rotary disk 61 for rotation. The first rotary valve 1, the second rotary valve 2, the chip stage 3, the first solenoid valve 4, and the pump 5 are all arranged on the surface of the rotary disk 61. The chip stage 3 is mounted at a position close to the edge of the rotary disk 61, and the pump 5 is arranged below the chip stage 3.

[0046] In this device, a plurality of chip stages 3 are arranged on the surface of the rotary disk 61. Each chip stage 3 is used to carry at least two sequencing chips 30, and multiple sequencing chips can be simultaneously subjected to surface chemical modification. In this embodiment, five groups of chip stages 3 are provided. Each group of chip stages 3 is provided with two chip stages, and each chip stage is provided with a pair of chip groups. In order to carry a relatively large number of chip stages 3, the rotary disk 61 provided in the embodiment of the present application requires sufficient area, which makes the chip stages 3 closer to the inside (farther from the operator) farther away from the operator. Therefore, a rotary disk 61 with a rotation function is designed. When a chip needs to be replaced, the operator can rotate the rotary disk 61 to rotate the chip stage 3 to be replaced to a position close to the operator. When the chemical modification of a sequencing chip is completed, the replacement of this group of chips can be completed without stopping the machine, and it does not affect the progress of other groups of chips.

[0047] In order to select different reagents to communicate with different chip groups and convey specific reagents into the chips at appropriate times, the present application is provided with two rotary valves, namely a first rotary valve 1 and a second rotary valve 2. Refer to Figure 2 the structural schematic diagram shown. The first rotary valve 1 includes a plurality of first liquid inlet ends 11 and a first liquid outlet end 12. The first liquid inlet ends 11 are used to selectively communicate with one kind of reagent. The first liquid inlet ends 11 are connected with reagent needles, and the reagent needles are used to insert into a reagent kit (not shown) to suck reagents. The second rotary valve 2 includes a second liquid inlet end 21 and a plurality of second liquid outlet ends 22. The second liquid inlet end 21 is communicated with the first liquid outlet end 12. The first liquid inlet ends 11 are used to selectively communicate with one of the reagents. The reagent flows from the first liquid outlet end 12 into the second liquid inlet end 21 and then into the chip stage 3 from the second liquid outlet ends 22.

[0048] The number of the second liquid inlet ends 21 is at least equal to the number of reagent types. For example, if 5 kinds of reagents are required in this embodiment, the number of the second liquid inlet ends 21 is 5. Each second liquid inlet end 21 is communicated with one kind of reagent. When a certain reagent is needed, the first liquid inlet end 21 connected to this reagent is controlled to be communicated.

[0049] The number of the second liquid outlet ends 22 is at least equal to the number of groups of the chip platforms 3. For example, in this embodiment, there are 5 groups of chip platforms 3, so the number of the second liquid outlet ends 22 is 5. Each second liquid outlet end 22 is communicated with one group of chip platforms 3. Since the reagent flows out through the second liquid outlet ends 22 simultaneously, if the pipeline paths between each chip platform 3 and the second liquid outlet ends 22 are controlled to be equal, the reagent can be ensured to be injected into the chip platforms 3 simultaneously, so as to ensure that the chemical reagent amounts required by each platform are the same.

[0050] A plurality of sequencing chips 30 are arranged on the chip platform 3. Referring to Figure 3 the structural schematic diagram shown, the sequencing chip 30 sequentially includes a silicon layer, a sealant layer and a glass layer from bottom to top; the sealant layer is pasted on the surface of the silicon layer to form a chip flow channel on the surface of the silicon layer, and the glass layer is pasted on the side of the sealant layer away from the silicon layer to seal the chip flow channel; small holes are formed at positions corresponding to both ends of the silicon layer and the chip flow channel. The small hole near one end of the second rotary valve 2 is used as a third liquid inlet end 301, and the small hole at the other end is used as a third liquid outlet end 302. The third liquid inlet end 301 is communicated with the second liquid outlet end 22 so that the reagent can flow into the sequencing chip.

[0051] In order to provide the power for sucking the reagent and suck the reagent into the chip and into the sequencing chip, a pump 5 is arranged in the embodiment of the present application. The pump structure is located below the chip platform. There are 5 groups of chip platforms in total, and there is a pump structure below each chip platform. On the one hand, it is to reduce the length of the liquid pipeline and reduce the amount of reagent; on the other hand, it is to make reasonable use of the space and reduce the floor space of the device.

[0052] During the chip preparation process, the reagent flows through the sequencing chip at a certain flow rate. A part of the reagent participates in the reaction and stays on the chip, and the other part is sucked by the pump 5 and temporarily stored inside the pump. This part of the reagent is waste liquid. In order to discharge the waste liquid, a first solenoid valve 4 is arranged in the embodiment of the present application. The first solenoid valve 4 can be a two-position three-way solenoid valve. The first solenoid valve 4 is arranged between the pump 5 and the chip platform 3 and is used to select to communicate the pump 5 with the liquid outlet end of the sequencing chip. At this time, the pump 5 is used to suck the reagent; or, select to communicate the pump 5 with the waste liquid bucket. At this time, the pump 5 is used to discharge the reagent into the waste liquid bucket (waste).

[0053] The automation device usually has a hardware structure. The hardware structure in this embodiment is divided into two parts. One is the structure for installing the hardware board card, which is located behind the chip platform and provides control elements for liquid pipeline components such as rotary valves; the other is the power supply structure, which mainly converts alternating current into direct current to supply power to the whole device.

[0054] As can be seen from the above technical solutions, the chip surface chemical modification device provided in this embodiment mainly improves the chip processing efficiency, saves the labor operation cost and time. By designing the chip stage, rotating disk and other structures, this device realizes the placement and positioning of chips with different specifications, the chip replacement under non-stop operation, and the consistency of the liquid path systems of multiple groups of chips, improving the rate of chip surface chemical modification and the consistency of processing results.

[0055] To facilitate controlling the equal pipeline paths between the second liquid outlet end 22 and each chip stage 3, in this embodiment, the second rotary valve 2 is arranged on the central axis of the rotating disk 61.

[0056] Refer to Figure 4 In the structural schematic diagram shown, on the basis of the above settings, multiple groups of the chip stages 3 are distributed in a regular polygon on the surface of the rotating disk 61, so that the paths between each chip stage 3 and the second rotary valve 2 are equal. For example, in this embodiment, 5 groups of chip stages 3 are provided, and they are distributed in a regular pentagon on the surface of the rotating disk 61.

[0057] To ensure the liquid inlet efficiency and reduce the complexity of the liquid path, this device divides 20 chips into 5 groups, with 4 chips in each group. The liquid path reagents are also divided into 5 groups during liquid inlet to reduce the number and cost of the liquid path pumps and valves. When the number of chips for surface chemical modification at one time is less than 5 groups or it is necessary to control the chemical modification progress of different groups of chips, the second rotary valve can be used to select to supply liquid to one of the groups or delay the liquid supply, so as to realize the process differentiation of different groups of chips.

[0058] Refer to Figure 5 and Figure 6 In the structural schematic diagram shown, in this embodiment, the rotating disk structure is an important part of the chip surface chemical modification device for rotating the stage and facilitating the operator to replace the chips. The disk assembly 6 includes: a rotating disk 61, a bottom plate 62, a fixed shaft 63, a bearing 64, a bearing mounting seat 65, a retaining plate 66 and a caster 67. The fixed shaft 63 is fixedly connected to the bottom plate 62 and is arranged between the rotating disk 61 and the bottom plate 62; the bearing 64 is installed on the fixed shaft 63, and its center coincides with the centers of the fixed shaft 63 and the rotating disk 61; the bearing mounting seat 65 surrounds the outside of the bearing 64 and is fixedly connected to the rotating disk 61; the retaining plate 66 is fixed to the top of the fixed shaft 63, abuts against the top of the bearing 64, and the bottom abuts against the bearing mounting seat 65; the caster 67 is fixed to the bottom surface of the rotating disk 61 through a connecting piece and is used to slide on the bottom plate surface along with the rotating disk 61.

[0059] The rotating disk 61 is the support base plate of the chip stage 3, and the chip stage 3 is fixed above it by screws. The base plate 62 is the lowermost structure of the entire device, and 6 casters 67 are designed below it. A fixed shaft 63 is provided at the center of the rotating disk 61. This shaft is a hollow stepped shaft structure, which is the rotating shaft during rotation. It is connected to the base plate 62 below and penetrates through the rotating disk 61 above. In addition, the liquid pipeline and the hardware wire harness above the rotating disk 61 will pass through the fixed shaft 63 to reach below the rotating disk 61 and be connected to the hardware board and the corresponding liquid collection device. When the operator rotates the edge of the rotating disk 61, the rotating disk rotates by a certain angle around the fixed shaft. Bearings 64, bearing mounts 65, and retaining plates 66 are installed on the fixed shaft 63. The bearing 64 is mainly used to reduce the frictional resistance during rotation. The bearing mount 65 surrounds the bearing 64, and the retaining plate 66 is located above the bearing 64. The bearing 64, the bearing mount 65, and the retaining plate 66 work together to install the bearing and limit the axial movement of the bearing. Since the overall area of the rotating disk 61 is relatively large, if it is only supported by the rotating shaft 63, the edge part of the rotating disk 61 will warp. Therefore, casters 67 are designed at the bottom end of the rotating disk 61. These casters 67 are located below the rotating disk 61 and above the base plate 62, close to the edge of the rotating disk 61, and are used to support each structure on the rotating disk 61 and rotate by a certain angle along with the rotating disk 61. In addition, there is an observation window in the central part of the fixed shaft 63, which can be used to observe whether the wire harness is entangled and facilitate maintenance.

[0060] To prevent the liquid pipeline or the hardware wire harness from being entangled due to excessive rotation angle or unidirectional unrestricted rotation of the rotating disk 61 during rotation, a braking and limiting structure is designed on the rotating disk 61, so that the rotating disk 61 can rotate by more than 350° and less than 360°. Refer to Figure 7 the structural schematic diagram shown. An upper brake block 611 is provided on the bottom surface of the rotating disk 61, and a lower brake block 621 is provided on the surface of the base plate 62. The lower brake block 621 is arranged on the running track of the upper brake block 611 as the rotating disk 61 rotates, and the lower brake block 621 is used to limit the upper brake block 611. When the rotating disk 61 rotates to a certain angle, the upper brake block 611 and the lower brake block 621 will coincide on the running track, and at this time, the rotating disk 61 will be forced to stop.

[0061] Furthermore, anti-slip pads are provided on the surfaces where the upper brake block 611 and the lower brake block 621 come into contact when touching, so as to increase their frictional force and play a buffering role.

[0062] Refer to Figure 8 and Figure 9The structural schematic diagram shown, the chip stage 3 includes: a base 31, a liquid path end block 32, and clamping components 33 arranged on opposite sides of the base 31. The base 31 is provided with a slot 311 for placing a sequencing chip, and the flow channel of the sequencing chip is in communication with the liquid path through the liquid path end block 32; the clamping component 33 includes a hinge seat 331 and a flap 332 rotatably arranged on the hinge seat 331. One side of the flap 332 is provided with a pressing member 333. When the flap 333 rotates inwards to the in-place position, the pressing member 333 tightly clamps on the surface of the chip pressing plate, and the chip pressing plate closely adheres to the surface of the sequencing chip.

[0063] In this embodiment, the base 1 is provided with two slots 311, that is, each base 1 can be used to place two sequencing chips. The two ends of the sequencing chip are provided with flow ports, which are usually arranged at the bottom of the chip. The slot 311 is surrounded by oppositely arranged positioning plates 312 and oppositely arranged partition plates 313. When the chip is placed on the chip stage 3, the partition plates 313 and positioning plates 312 on the chip stage 3 ensure the placement tolerance of the chip, ensuring that the flow ports on the chip are aligned with the liquid inlet or outlet on the liquid path end block 32 without a large deviation. The partition plate 313 is fixed on the base 31 and can be integrally connected.

[0064] In this embodiment, the pressing member 333 is an adjusting screw. The chip stage provided in this embodiment can adapt to chips of various specifications, mainly by using different flaps 332 and adjusting screws to achieve this function. The chip flap 332 is located above the chip. Different flaps are used for chips of different specifications, and corresponding chip pressing plates are used. The chip pressing plate is specially designed for chips of different specifications. The adjusting screw is located on the flap and is fixed to the flap by threads. A wrench can be used to turn the adjusting screw to adjust the distance between it and the flap. After adjustment, the adjusting screw can be fixed by a set screw behind the flap.

[0065] When the chip is placed on the base 31, the flap 332 can be flipped to clamp on the upper end of the chip. At this time, the pre-adjusted adjusting screw presses on the upper part of the chip flap. Since the flap 332 is made of iron, it will be adsorbed by the magnet on the hinge seat 331, thereby fixing the chip on the base 31. Each flap 332 will fix two chips.

[0066] Based on the above structure, the chip stage provided in this embodiment can chemically modify sequencing chips of different specifications. A threaded adjusting rod is mainly designed, and its height after pressing can be adjusted by rotating the adjusting rod, so as to chemically modify chips of different thicknesses. In addition, it can also perform pressing functions on different chips. Since the contact between the adjusting rod and the chip diameter is a point contact, there is a risk of chip breakage. Therefore, different chip pressing plates (not labeled) are designed. On the one hand, they can distinguish different chips, and on the other hand, they can change the point contact to a surface contact to reduce the probability of chip damage.

[0067] Since chemical reagents are required for the chemical surface modification of the chip, the chip fluid inlet needs to be sealed, which is mainly achieved by the extrusion of the seal on the fluid path end block 32. The seal includes a guide shaft and a spring. The fluid path end block 32 slides on the guide shaft. The upper end of the spring abuts against the fluid path end block 32, and the lower end is fixed. When the chip is pressed by the flip cover 332, the fluid path end block will also move downward. At this time, the spring coaxial with the guide shaft and located below the fluid path end block 32 will be compressed under its action, and the seal on the fluid path end block 32 will be subjected to the combined action of the downward adsorption force of the magnet and the upward elastic force of the spring, thereby sealing the fluid inlet on the chip.

[0068] In this embodiment, the fluid inlet closest to one end of the second rotary valve 2 is the third liquid inlet end 301, and the fluid inlet closest to one end of the pump 5 is the third liquid outlet end 302.

[0069] In this application, the fluid path end blocks are of two types, namely the first fluid path end block and the second fluid path end block. The first fluid path end block is a Y-shaped flow channel provided at the third liquid inlet end, and the second fluid path end block is an I-shaped flow channel provided at the third liquid outlet end. Two fluid path end blocks 32 are provided below the inlet end bottom plate of the chip stage 3, and each fluid path end block 32 corresponds to one chip. Since the flow channel of the fluid path end block at the liquid inlet is Y-shaped, referring to Figure 10 the cross-sectional view shown, each fluid path end block at the liquid inlet can divide the reagent coming from the second liquid outlet end 22 into two parts and send them into the two flow channels of the chip to achieve the transportation of chemical reagents.

[0070] Since some chemical reagents can only react at temperatures above room temperature, the structure of the chip stage 3 is also designed with a heatable module. This module mainly consists of a heating tape 34 and a heat insulation plate 35. The heating tape 34 is located below the base 31, and there is a heating tape 34 under each chip, ensuring that the heating of each chip can be independently controlled and the temperature uniformity inside the chip. When heating is required, the heating tape 34 receives an instruction to increase the temperature and transfers the temperature to the chip through the base 31, thereby creating an environment for the chemical reagent to react. In this module, there is also a heat insulation plate 35 under each heating tape 34. On the one hand, it can isolate the influence of the temperature rise of the heating tape 34 on other components, and on the other hand, it can be pressed against the heating tape 34 by screws to ensure a tight fit between the heating tape 34 and the base 31 and ensure the temperature rise rate.

[0071] In addition, the module is also provided with a fuse 36 and a thermocouple (not shown). The fuse 36 is located below the base 31. Since every two chips share a base 31, one fuse can be used for each base 31. When the temperature heated by the heating tape 34 exceeds the limit temperature of the fuse 36, the fuse 36 will function, sending an alarm signal and disconnecting the current of the heating tape 34. The thermocouple is located inside the base 31, and there is a thermocouple under each chip. Its main function is to monitor the reaction temperature of each chip, so as to cooperate with the control to adjust the temperature of the heating tape 34 under each chip.

[0072] To ensure the service life of the magnet and prevent accidents such as scalding when an operator accidentally touches it, the chip stage is designed with a heat insulation structure, mainly by using heat insulation materials such as ABS and installing them at positions such as the base, heating tape, and screws to control the temperature brought by the heating tape on the base.

[0073] In this embodiment, the base 31 is made of a heat-conducting material and is used to conduct the heat of the heating tape to the chip.

[0074] Refer to Figure 11 As shown in the structural schematic diagram, support columns 612 are provided on the surface of the rotating disc 61, and the chip stage 3 is erected on the surface of the rotating disc 61 through the support columns 612. The area below the chip stage 3 can be used to place other devices to save space. In this embodiment, the pump 5 is fixed on the support columns 612.

[0075] The beneficial effects of this application are as follows:

[0076] 1. High efficiency. This device uses multiple identical stages and a reasonable layout, and can perform surface chemical modification of up to 20 chips simultaneously at most, improving the pre-processing efficiency of sequencing chips.

[0077] 2. Applicable to chips of various specifications. By designing the adjusting screw and chip pressing plates of different specifications, this device can be applicable to chips with different thicknesses, thus achieving the adaptation function for various types of chips and providing certain assistance for the processing of various chips.

[0078] 3. Simple operation. The operation steps of this chemical surface modification device are simple. The operator only needs to place and press the chip. The specific process is as follows: The operator independently selects the chip stage to place the chip and rotates the rotating disc to adjust the stage to a suitable position, then places the chip on the base, places the corresponding chip pressing cover above the chip, buckles down the flip covers on both sides of the chip, and then sets appropriate parameters on the computer to process the chip.

[0079] 4. Automatic processing. After the parameters are set on the computer, the built-in program of this device will automatically process the chip without the need for personnel to follow up in real time. Only the chip needs to be removed after the chip processing is completed. The automatic processing process of this device includes functions such as the selection of chemical reagents, the suction and discharge of liquids, the selection of the stage, the heating of the chip, and the monitoring of temperature.

[0080] 5. Safety protection. When processing the chip, there are potential hazards such as liquid splashing, liquid leakage, and scalding caused by human misoperation. On the one hand, this device designs shielding parts for the hardware board to prevent the influence of liquid splashing. On the other hand, heat insulation parts are designed on the heating devices to reduce the range of heat conduction and improve the safety of this device.

[0081] Figure 12 This is the liquid path schematic diagram of the liquid path system corresponding to the embodiment of this application. The reference numerals in this liquid path schematic diagram follow those in the above-mentioned device.

[0082] The liquid path system provided in this embodiment includes: a first rotary valve 1, which includes a plurality of first liquid inlet ends 11 and one first liquid outlet end 12, and the first liquid inlet ends 11 are used to selectively communicate with one kind of reagent; a second rotary valve 2, which includes one second liquid inlet end 21 and a plurality of second liquid outlet ends 22, and the second liquid inlet end 21 is communicated with the first liquid outlet end 12; a plurality of chip carriers 3, each of the chip carriers 3 is used to carry at least two sequencing chips 30, the sequencing chips 30 include a plurality of third liquid inlet ends 301 and a plurality of third liquid outlet ends 302, and the third liquid inlet ends 301 are communicated with the second liquid outlet ends 22; a first solenoid valve 4, which includes a first common port 41, a first normally open port 42 and a first normally closed port 43; a pump 5, which is arranged below the chip carrier 3, the first common port 41 is communicated with the pump 5, the first normally open port 42 is communicated with the third liquid outlet end 301, and the first normally closed port 43 is communicated with a waste bucket (waste); when the first common port 41 is communicated with the first normally open port 42, the pump 5 is used to extract the reagent and store it briefly; when the first common port 41 is communicated with the first normally closed port 43, the pump 5 is used to discharge the reagent to the waste bucket.

[0083] In order to send the reagent flowing out of the second liquid outlet end 22 of the second rotary valve 2 into each chip on the chip carrier 3, a 1-to-N joint or a plurality of consecutive three-way joints (not labeled) are arranged between the second rotary valve 2 and the chip carrier 3. In this embodiment, two sequencing chips are taken as a group, two sequencing chips are arranged on the same chip carrier 3, and two chip carriers 3 are taken as a group. Therefore, one group of chip carriers 3 corresponds to 4 sequencing chips. In this case, if a 1-to-4 joint is set, the reagent flowing out of the second liquid outlet end 22 can be divided into 4 paths; or, a three-way joint is connected to the second liquid outlet end 22. At this time, the reagent flowing out of the second liquid outlet end 22 can be divided into 2 paths, and then a three-way joint is respectively connected to the liquid outlet ends of the three-way joint, and the reagent flowing out of the second liquid outlet end 22 can be divided into 4 paths.

[0084] The reagent flowing out of the joint is divided into two by the liquid path end block 32 and then flows into the flow channels of the chip respectively. At the liquid outlet end of the sequencing chip, another liquid path end block is arranged, and this liquid path end block sends the reagent flowing out of each flow channel into the first solenoid valve. In Figure 12 In the shown liquid path schematic diagram, each group of chip carriers 3 has 4 sequencing chips, and each flow channel needs to correspond to one pump. Then, an eight-connected pump is required for each group of chip carriers 3 to form a complete liquid path system.

[0085] Based on the above liquid path schematic diagram, the embodiment of the present application further provides an improved liquid path system, such as Figure 13As shown, in this system, a second solenoid valve 7 and a tee joint are provided between the second rotary valve 2 and the chip stage 3. The second solenoid valve 7 includes a second common port 71, a second normally open port 72, and a second normally closed port 73. The second common port 71 is communicated with the second liquid outlet end 22. The second normally open port 72 and the second normally closed port 73 are respectively communicated with a tee joint, and this tee joint is used to connect half of the sequencing chips on each group of chip stages. When the second common port 71 is selected to communicate with the second normally open port 72 or the second normally closed port 73, the second liquid outlet end 22 is used to supply liquid to half of the sequencing chips on the chip stage.

[0086] Since the second solenoid valve 7 divides 8 sequencing chips into two groups, and the second solenoid valve 7 only selects 4 of the sequencing chips for liquid supply. When 4 of the sequencing chips are selected for liquid supply, the other 4 sequencing chips can suspend liquid supply. In this case, taking 4 chips as a group, two sets of four-way pumps are required to achieve a complete liquid path system.

[0087] Since when one set of four-way pumps is working, the other set of four-way pumps is in a non-working state. Further, in order to save one set of four-way pumps, the embodiment of the present application provides another improved liquid path system. As Figure 14 shown, on the basis of the foregoing sequencing system, a third solenoid valve 8 is provided between the chip stage 3 and the first solenoid valve 4. The third solenoid valve 8 includes a third common port 81, a third normally open port 82, and a third normally closed port 83. The third common port 81 is communicated with the second normally open port 82. The third normally open port 82 and the third normally closed port 83 are respectively communicated with the third liquid outlet end 302 of the corresponding half of the sequencing chips on the chip stage.

[0088] Further, the number of chip stages is five groups, each group is provided with two chip stages, each chip stage is used to carry two sequencing chips, and each sequencing chip is provided with two flow channels. In this embodiment, a total of 20 chips are provided. Therefore, at most 20 chips can be simultaneously subjected to liquid addition and modification processing at one time, thereby improving the pre-processing efficiency of the sequencing chips and reducing the surface deviation of different sequencing chips caused by manual operation.

[0089] Further, a one-to-N first liquid path end block is provided at the third liquid inlet end 301 of the chip stage 3. The first liquid path end block is used to transport the reagent flowing out from the second liquid outlet end 22 to each flow channel of the sequencing chip, and the number of N is the same as the number of flow channels.

[0090] Further, a second liquid path end block is provided at the third liquid outlet end 302 of the chip stage 3. The number of flow channels of the second liquid path end block is the same as the number of flow channels of the sequencing chip, and the second liquid path end block is an I-shaped flow channel.

[0091] The chip surface chemical modification device provided by this application can implement the principle of the above liquid path system, thereby improving the efficiency of chip surface chemical modification. By using the above device and liquid path system, multiple sequencing chips can be surface-modified simultaneously, and the automation degree of the process is high. After the modification is completed, the chips can be replaced manually.

[0092] The above are only examples of this application and are not used to limit this application. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principle of this application are included in the scope of the claims of this application pending approval.

Claims

1. A device for chemical modification of the surface of a sequencing chip, characterized in that: include: A first rotary valve, used for selecting a reagent to be connected; a second rotary valve, connected to the first rotary valve, and used to deliver one of the reagents to a plurality of sequencing chips; A plurality of groups of chip carriers, each group of the chip carriers being used to carry at least four sequencing chips; A pump, used to draw in or discharge reagents; A first solenoid valve is disposed between the pump and the chip carrier, and is used to select the pump to be connected to the liquid outlet of the sequencing chip, or to select the pump to be connected to the waste liquid bucket; The rotating disc assembly is provided with a rotating disc, the first rotating valve, the second rotating valve, the chip carrier, the first electromagnetic valve and the pump are all arranged on the surface of the rotating disc, the chip carrier is mounted near the edge of the rotating disc, and the pump is arranged below the chip carrier.

2. A device for chemical modification of the surface of a sequencing chip according to claim 1, characterized in that: The second rotary valve is disposed on the central axis of the rotary disk.

3. The device for chemical modification of the surface of a sequencing chip according to claim 2, characterized in that: A plurality of groups of the chip carriers are distributed in a regular polygonal shape on the surface of the rotating disk, and the paths between each of the chip carriers and the second rotary valve are equal.

4. The device for chemical modification of the surface of a sequencing chip according to claim 1, characterized in that: The disc assembly also includes: Base plate; A fixed shaft, fixedly connected to the bottom plate, and arranged between the rotating disc and the bottom plate; A bearing, mounted on the fixed shaft; A bearing mounting seat is arranged around the outside of the bearing and is fixedly connected to the rotating disc; A baffle, fixed to the top end of the fixed shaft and used for abutting against the bearing; The caster is fixed to the bottom surface of the rotating disc through a connecting piece and is used for sliding on the surface of the bottom plate along with the rotating disc.

5. The device for chemical modification of the surface of a sequencing chip according to claim 4, characterized in that: An upper brake block is arranged on the bottom surface of the rotating disc, and a lower brake block is arranged on the surface of the bottom plate. The lower brake block is arranged on the running track of the upper brake block rotating with the rotating disc, and the lower brake block is used to limit the upper brake block.

6. The device for chemical modification of the surface of a sequencing chip according to claim 5, characterized in that: Anti-skid pads are arranged on the surfaces of the upper brake block and the lower brake block that contact each other when they touch.

7. The device for chemical modification of the surface of a sequencing chip according to claim 1, characterized in that: The chip carrier comprises: a base, a liquid circuit end block, and a clamping assembly arranged on opposite sides of the base, the base is provided with a slot, the slot is used to place a sequencing chip, and the flow channel of the sequencing chip is connected with the liquid circuit through the liquid circuit end block; The pressing assembly includes a hinge seat and a flap rotatably arranged on the hinge seat, and a pressing piece is arranged on the flap. When the flap is rotated inwardly into place, the pressing piece is tightly pressed against the surface of the chip pressing plate, and the chip pressing plate is tightly attached to the surface of the sequencing chip.

8. The device for chemical modification of the surface of a sequencing chip according to claim 7, characterized in that: The chip carrier further includes: a heating belt and a heat insulation plate arranged below the base, and the heat insulation plate is fixedly connected to the base.

9. The device for chemical modification of the surface of a sequencing chip according to claim 1, characterized in that: The surface of the rotating disk is provided with supporting columns, and the chip carrier is mounted on the surface of the rotating disk through the supporting columns.

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