Sequencing chip liquid spreading system, liquid spreading method and sequencer

Abstract

The application provides a sequencing chip liquid laying system, comprising: a liquid laying frame configured to carry a sequencing chip to be laid with liquid and to lay liquid to the sequencing chip; and a liquid guide needle set comprising a plurality of liquid guide needles configured to inject or extract liquid to the sequencing chip through the liquid laying frame; wherein a plurality of liquid guide channels are formed on the liquid laying frame and configured to communicate with the liquid guide needles so as to inject or extract liquid to the sequencing chip. The sequencing chip liquid laying system provided by the application is beneficial to avoid liquid leakage and crystallization of the sequencing chip. The application also provides a liquid laying method using the sequencing chip liquid laying system and a sequencer.

Description

Technical Field

[0001] This application relates to a sequencing chip spreading system, a spreading method using the sequencing chip spreading system, and a sequencer. Background Technology

[0002] In gene sequencing, reagents need to be injected into the sequencing chip. Depending on the orientation of the reagent injection into the chip assembly, it can be divided into bottom injection and top injection. Bottom injection involves injecting reagents from the bottom of the chip assembly, while top injection involves injecting reagents from the top. Most current sequencing equipment uses bottom injection. However, with bottom injection, because the inlet and outlet of the chip assembly face downwards, when the sequencing chip needs to be transferred, overflow, spillage, and dripping can occur, leading to reagent crystallization. Summary of the Invention

[0003] The first aspect of this application provides a sequencing chip spreading system, comprising: A spreading frame for holding the sequencing chip to be spread with the solution and for spreading the solution onto the sequencing chip; and The liquid guide needle assembly includes multiple liquid guide needles for injecting or extracting liquid into the sequencing chip through the liquid spreading frame; The liquid-laying frame has multiple liquid-guiding channels, which are used to communicate with the liquid-guiding needle to inject or extract liquid into the sequencing chip.

[0004] The sequencing chip liquid spreading system provided in this application embodiment allows the liquid in the liquid guide needle to flow into the sequencing chip through the liquid spreading frame. It can change the liquid injection direction of the liquid guide needle, avoiding the liquid being injected directly from below the sequencing chip. This avoids phenomena such as overflow, liquid spillage, and dripping that are prone to occur during the transfer of the sequencing chip, thereby preventing reagent crystallization and contamination of the carrier device on which the sequencing chip is placed.

[0005] In one embodiment, the liquid guiding channel includes a first through hole, a second through hole, and a first flow channel groove; the first through hole and the second through hole respectively penetrate the liquid spreading frame, the first through hole is used to communicate with the liquid guiding needle, and the second through hole is used to communicate with the sequencing chip; the first flow channel groove is formed on the surface of the liquid spreading frame, so that the first through hole and the second through hole are connected.

[0006] In one embodiment, the liquid-laying frame further includes a plurality of first encapsulation sheets and a plurality of sealing gaskets, each of the first encapsulation sheets covering and sealing one of the first flow channel grooves, and each of the sealing gaskets covering one end of the first through hole away from the first flow channel groove.

[0007] In one embodiment, the liquid-laying frame is further provided with at least one waste liquid discharge channel, each of the waste liquid discharge channels being connected to one of the liquid guiding channels; the waste liquid discharge channel is used to communicate with one of the liquid guiding needles to discharge the liquid in the liquid guiding channel.

[0008] In one embodiment, the waste liquid discharge channel includes a first orifice and a second flow channel. The first orifice is formed on the liquid-laying frame and is used to communicate with one of the liquid guiding needles. The second flow channel is formed on the liquid-laying frame, such that the first orifice communicates with the liquid guiding channel. The liquid-laying frame also includes at least one second encapsulation sheet and at least one sealing gasket. Each second encapsulation sheet covers and seals one of the second flow channel channels. Each sealing gasket covers and seals the first orifice.

[0009] In one embodiment, the liquid guiding needle includes a needle tip and a liquid outlet, wherein the distance from the liquid outlet to the tip of the needle tip is less than the depth of the liquid guiding channel corresponding to the position where the second flow channel groove communicates with the liquid guiding channel.

[0010] In one embodiment, the liquid guiding needle assembly further includes a plurality of control valves, each control valve being configured corresponding to one liquid guiding needle for controlling the flow of liquid within the liquid guiding needle.

[0011] A second aspect of this application provides a liquid-spreading method for use in the above-mentioned sequencing chip liquid-spreading system, comprising: The sequencing chip is fixed on the liquid-laying frame so that each of the liquid-guiding channels is connected to the sequencing chip; The liquid guiding needle assembly is connected to the liquid spreading frame, and one liquid guiding needle is inserted into one liquid guiding channel; Liquid is injected into the liquid-filling frame through at least one of the liquid-guiding needles, and liquid or gas is discharged from the liquid-filling frame through other liquid-guiding needles.

[0012] A third aspect of this application provides a liquid-spreading method for use in the above-mentioned sequencing chip liquid-spreading system, comprising: The liquid guiding needles are inserted one by one into the liquid guiding channel and the waste liquid discharge channel, and the position of the liquid outlet of the liquid guiding needle in the liquid guiding channel is lower than the position where the second flow channel groove communicates with the liquid guiding channel; Liquid is injected into the liquid guiding channel until the waste liquid in the liquid guiding channel is discharged through the waste liquid discharge channel; Continue injecting liquid into the liquid channel so that the liquid flows into the sequencing chip.

[0013] The fourth aspect of this application provides a sequencer that includes the sequencing chip spreading system described above. Attached Figure Description

[0014] Figure 1 This is a schematic diagram of the structure of a sequencing chip spreading system in one embodiment of this application.

[0015] Figure 2 This is a partial exploded structural diagram of the sequencing chip spreading system in one embodiment of this application.

[0016] Figure 3 This is a schematic diagram of the sequencing chip structure in one embodiment of this application.

[0017] Figure 4 for Figure 3 IV-IV cross-sectional view of the sequencing chip.

[0018] Figure 5 This is a schematic diagram of the liquid-coating frame in one embodiment of this application.

[0019] Figure 6 This is an exploded structural diagram of the liquid-laying frame in one embodiment of this application.

[0020] Figure 7 for Figure 6 Sectional view VII-VII of the liquid-filled frame.

[0021] Figure 8 for Figure 6 Schematic diagram of cross section VIII-VIII of the middle liquid-filled frame.

[0022] Figure 9 This is a schematic diagram of the liquid spreading process of the sequencing chip liquid spreading system in one embodiment of this application.

[0023] Figure 10 This is a liquid inlet route diagram in one embodiment of this application.

[0024] Figure 11 This is a schematic diagram of the waste liquid discharge process of the sequencing chip spreading system in one embodiment of this application.

[0025] Figure 12 This is a flowchart of a liquid spreading method in one embodiment of this application.

[0026] Figure 13 This is a flowchart of a liquid spreading method in another embodiment of this application.

[0027] Explanation of main component symbols Sequencing chip spreading system 100 Load-bearing module 10 Positioning substrate 11 Positioning post 111 Heat sink 13 Carrier plate 20 Liquid spreading frame 30 Frame 31 First surface 311 Second surface 313 315 outer wall Positioning hole 32 Sealing gasket 33 Liquid channel 34 First through hole 341 First flow channel 342 Second through hole 343 First package chip 35 Waste liquid discharge channel 36 First slot 361 Second flow channel 362 Second package chip 37 Fixed slot 38 Inner wall 381 Fixing part 39 50 catheterization needles Fixed plate 51 Infusion needles 53, 53a, 53b, 53c Needle 531 Liquid outlet 532 Syringe 533 Control valve 55 Sequencing chip 200 Top substrate 210 220 cavity Substrate 230 Liquid inlet 231 Distance m Depth n Steps S11, S12, S13, S21, S22, S23 The following detailed description, in conjunction with the accompanying drawings, will further illustrate this application. Detailed Implementation

[0028] The technical solutions in the embodiments of this application will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of this application, and not all embodiments.

[0029] Unless otherwise defined, all technical and scientific terms used in this application have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. The terminology used in this application's specification is for the purpose of describing particular embodiments only and is not intended to be limiting of the application.

[0030] To further illustrate the technical means and effects adopted by this application in achieving its intended purpose, the following detailed description of this application is provided in conjunction with the accompanying drawings and preferred embodiments.

[0031] Please see Figure 1 The sequencing chip spreading system 100 provided in this application includes: a support module 10, a spreading frame 30, and a liquid guiding needle assembly 50. The spreading frame 30 is used to support the sequencing chip 200 to be spread and to spread liquid onto the sequencing chip 200. The support module 10 is used to support the supporting frame 300 containing the sequencing chip 200. The liquid guiding needle assembly 50 includes multiple liquid guiding needles 53 for injecting or extracting liquid into or from the sequencing chip 200 through the spreading frame 30.

[0032] Please see Figure 2 The support module 10 includes a positioning base plate 11 and a heat sink 13. The positioning base plate 11 is disposed on the heat sink 13 and is used to support and position the liquid spreading frame 30. Specifically, the positioning base plate 11 is provided with a plurality of positioning posts 111, and the liquid spreading frame 30 is provided with a plurality of positioning holes 32. Each positioning hole 32 corresponds to a positioning post 111, so that when the liquid spreading frame 30 is placed on the positioning base plate 11, each positioning post 111 passes through a positioning hole 32, thereby fixing the liquid spreading frame 30 on the positioning base plate 11.

[0033] The sequencing chip spreading system 100 also includes a carrier plate 20, which is disposed on the same side as the spreading frame 30 and is used to partially support the sequencing chip 200. Specifically, the spreading frame 30 is a square frame used to support the sequencing chip 200 from its edge. The carrier plate 20 is disposed on the support module 10, and the spreading frame 30 is placed around the carrier plate 20; that is, the carrier plate 20 can be used to assist in positioning the spreading frame 30. The carrier plate 20 is also used to support the middle position of the sequencing chip 200, thus jointly supporting the sequencing chip 200 with the spreading frame 30. The carrier plate 20 can be integrally formed with the support module 10, or it can be fixed to the support module 10 in other ways; this application does not impose any restrictions on this.

[0034] Please refer to the following: Figure 3 and Figure 4In this embodiment, the sequencing chip 200 includes an upper substrate 210 and a lower substrate 230, with a receiving cavity 220 formed between the upper substrate 210 and the lower substrate 230. The receiving cavity 220 is used to hold the sample to be sequenced. The upper substrate 210 is made of a transparent material, allowing light to pass through and illuminate the sample to be sequenced. The lower substrate 230 has multiple liquid inlet holes 231. When the sequencing chip 200 is placed on the liquid-laying frame 30, the liquid-laying frame 30 injects liquid into the sequencing chip 200 or drains liquid from the sequencing chip 200 through the liquid inlet holes 231. The sequencing chip 200 is square, and the liquid inlet holes 231 are distributed at the four corners of the sequencing chip 200. In other embodiments, the sequencing chip 200 may also have other structures, such as triangular, circular, or other shapes, which are not limited in this application.

[0035] In this embodiment, the liquid is a reagent used for biochemical reactions, such as a fluorescent reagent. The liquid is injected into the sequencing chip 200, causing it to react with the sample to be sequenced. In other embodiments, the liquid may also include a buffer solution, such as distilled water, to buffer the two reagents injected sequentially. This application does not limit the specific composition of the liquid.

[0036] Please refer to the following: Figure 5 and Figure 6 The liquid-coating frame 30 includes a frame body 31 and a plurality of sealing gaskets 33, a plurality of first encapsulation pieces 35, and at least one second encapsulation piece 37 disposed on the frame body 31. Specifically, the frame body 31 is a square frame, including opposing first surfaces 311 and second surfaces 313, and an outer wall 315 located between the first surfaces 311 and second surfaces 313 and facing outwards from the frame. The sealing gaskets 33 are disposed on the first surfaces 311, the first encapsulation pieces 35 are disposed on the second surfaces 313, and the second encapsulation pieces 37 are disposed on the outer wall 315.

[0037] A fixing groove 38 is also provided on the first surface 311 of the frame 31. The fixing groove 38 is used to fix the sequencing chip 200. A fixing part 39 is formed on the inner sidewall 381 of the fixing groove 38. The fixing part 39 protrudes towards the inside of the frame 31 and is used to clamp the sequencing chip 200 when it is placed in the fixing groove 38.

[0038] Please refer to the following: Figure 6 and Figure 7The liquid-laying frame 30 has multiple liquid-guiding channels 34, each of which is connected to a liquid-guiding needle 53 to inject or extract liquid into the sequencing chip 200. Each liquid-guiding channel 34 includes a first through-hole 341, a first flow channel 342, and a second through-hole 343. The first through-hole 341 and the second through-hole 343 respectively penetrate the liquid-laying frame 30. The first through-hole 341 is connected to the liquid-guiding needle 53, and the second through-hole 343 is connected to the sequencing chip 200. The first flow channel 342 is formed on the surface of the liquid-laying frame 30, allowing the first through-hole 341 and the second through-hole 343 to connect via the first flow channel 342.

[0039] Specifically, the first through-hole 341 penetrates the first surface 311 and the second surface 313 of the frame 31, and the second through-hole 343 penetrates the first surface 311 and the second surface 313 of the frame 31 at the position corresponding to the fixing groove 38. The end of the first through-hole 341 facing the first surface 311 is used to communicate with the liquid guiding needle 53, and the end of the second through-hole 343 facing the first surface 311 is used to communicate with the liquid inlet 231 of the sequencing chip 200. The first flow channel groove 342 is formed on the second surface 313, and the two ends of the first flow channel groove 342 are respectively connected to the end of the first through-hole 341 facing the second surface 313 and the end of the second through-hole 343 facing the second surface 313. The first encapsulation sheet 35 covers the first flow channel groove 342, and the sealing gasket 33 covers the end of the first through-hole 341 away from the first flow channel groove 342. The liquid guide needle 53 can pass through the sealing gasket 33 to communicate with the first through hole 341. Since the side of the first through hole 341 facing the first surface 311 is sealed by the sealing gasket 33 and the first flow channel 342 is covered by the first encapsulation sheet 35, the liquid can either flow into the first through hole 341 through the liquid guide needle 53, and then flow into the second through hole 343 through the first flow channel 342, and finally flow into the sequencing chip 200 from the end of the second through hole 343 facing the first surface 311; or it can flow into the second through hole 343 from the sequencing chip 200, and then flow into the first through hole 341 through the first flow channel 342, and finally flow into the liquid guide needle 53 from the first through hole 341.

[0040] In this embodiment, the sealing gasket 33 is made of an elastic material. When the liquid guiding needle 53 passes through the sealing gasket 33, the sealing gasket 33 generates an elastic force towards the liquid guiding needle 53, thereby continuing to seal the side of the first through hole 341 facing the first surface 311. When the liquid guiding needle 53 is pulled out from the liquid guiding channel 34, the elastic force generated by the sealing gasket 33 squeezes and closes the opening created when the liquid guiding needle 53 passes through the sealing gasket 33, thereby continuing to achieve the sealing effect.

[0041] Please refer to the following: Figure 6 and Figure 8The liquid-laying frame 30 is also provided with at least one waste liquid discharge channel 36, which is connected to a liquid guiding channel 34. The waste liquid discharge channel 36 is used to connect with a liquid guiding needle 53 to discharge the liquid in the liquid guiding channel 34. The waste liquid discharge channel 36 includes a first orifice 361 and a second flow channel 362. The first orifice 361 is formed on the liquid-laying frame 30 and is used to connect with a liquid guiding needle 53. The second flow channel 362 is formed on the liquid-laying frame 30, so that the first orifice 361 is connected to the liquid guiding channel 34.

[0042] Specifically, in this embodiment, a waste liquid discharge channel 36 is provided on the liquid-laying frame 30. A first groove 361 is formed on the first surface 311 of the frame 31, and a second flow channel 362 is formed on the outer side wall 315 of the frame 31. The first groove 361 and the corresponding first through hole 341 of the liquid-guiding channel 34 are arranged side-by-side. The second flow channel 362 extends from the outer side wall 315, connecting the first groove 361 and the first through hole 341. A sealing gasket 33 is disposed at one end of the first groove 361 near the first surface 311 to seal the first groove 361. A second encapsulation sheet 37 covers and seals the second flow channel 362. A liquid-guiding needle 53 passes through the sealing gasket 33 to communicate with the first groove 361, allowing liquid in the first through hole 341 to flow into the first groove 361 through the second flow channel 362, and then out of the liquid-laying frame 30 through the liquid-guiding needle 53.

[0043] Please see Figure 10 The liquid guiding needle 53 includes a needle tip 531, a liquid outlet 532, and a needle tube 533. The distance m from the liquid outlet 532 to the tip of the needle tip 531 is less than the depth n of the liquid guiding channel 34 corresponding to the position where the second flow channel groove 362 connects with the liquid guiding channel 34. Specifically, the waste liquid discharge channel 36 is used to discharge the waste liquid in the corresponding liquid guiding channel 34. During the liquid preparation process of the sequencing chip 200, different reagents are usually injected into the sequencing chip 200 in sequence. Before injecting a new reagent, water or other diluents need to be injected to drain the waste liquid in the sequencing chip 200 (such as the product after the reaction of the previously used reagent with the sample to be sequenced). In actual operation, the waste liquid in the liquid guiding channel 34 used for liquid inlet needs to be drained in advance to ensure that the liquid flowing into the sequencing chip 200 from the liquid guiding channel 34 does not contain waste liquid, thereby avoiding the problem of dead volume of waste liquid (that is, waste liquid that cannot be drained remains in the liquid guiding channel 34). By setting the distance m to be less than the depth n, the position of the outlet hole 532 of the liquid guide needle 53 after it is inserted into the liquid guide channel 34 can be lower than the connection position between the second flow channel groove 362 and the liquid guide channel 34, so that the waste liquid above the outlet hole 532 can be discharged through the second flow channel groove 362, thereby avoiding the problem of dead volume.

[0044] Please continue reading. Figure 1The liquid guiding needle assembly 50 also includes a fixing plate 51 and multiple control valves 55. The fixing plate 51 is used to fix the position of the multiple liquid guiding needles 53, and each control valve 55 is set for one liquid guiding needle 53 to control the flow of liquid in the liquid guiding needle 53.

[0045] The sequencing chip spreading system 100 provided in this embodiment will be further described below with reference to the specific spreading process.

[0046] In this embodiment, the liquid-laying frame 30 includes four liquid-guiding channels 34 and one waste liquid discharge channel 36, with the waste liquid discharge channel 36 corresponding to one of the liquid-guiding channels 34. Specifically, the liquid-guiding channel 34 corresponding to the waste liquid discharge channel 36 is used for liquid inlet, while the remaining liquid-guiding channels 34 are used for liquid outlet. That is, the liquid-guiding needle 53a corresponding to the liquid-inlet channel 34 is used to inject liquid into the liquid-laying frame 30, the liquid-guiding needle 53b corresponding to the other liquid-guiding channels 34 is used to discharge liquid from the liquid-laying frame 30, and the liquid-guiding needle 53c corresponding to the waste liquid discharge channel 36 is used to discharge waste liquid from the liquid-guiding channel 34.

[0047] Please refer to the following: Figure 1 and Figure 9 The liquid guide needle 53a of the liquid guide channel 34 corresponding to the liquid inlet passes through the sealing gasket 33 to communicate with the first through hole 341 and injects liquid into the first through hole 341. The liquid passes through the first flow channel groove 342 and the second through hole 343, thereby flowing into the sequencing chip 200 and flowing from the other end of the sequencing chip 200 into another liquid guide channel 34, and finally flowing out through the liquid guide needle 53b corresponding to the other liquid guide channel 34.

[0048] Please refer to the following: Figure 10 and Figure 11Liquid is injected into the first through hole 341 through the liquid guide needle 53a corresponding to the liquid inlet channel 34. The liquid flows into the first hole groove 361 through the second flow channel groove 362 and flows out through the liquid guide needle 53c corresponding to the waste liquid discharge channel 36, thus completing the waste liquid discharge process. By controlling the opening and closing of each control valve 55, the flow direction of the liquid flowing out of the liquid guide needle 53a corresponding to the liquid inlet channel 34 can be controlled. Specifically, by blocking the flow of liquid in the guide needle 53c corresponding to the waste liquid discharge channel 36, while allowing the flow of liquid in the guide needle 53b corresponding to other guide channels 34, the liquid flowing out of the guide needle 53a corresponding to the liquid inlet channel 34 can flow to the guide needle 53b corresponding to other guide channels 34. Similarly, by blocking the flow of liquid in all guide needles 53b corresponding to other guide channels 34, while allowing the flow of liquid in the guide needle 53c corresponding to the waste liquid discharge channel 36, the liquid flowing out of the guide needle 53a corresponding to the liquid inlet channel 34 can only flow out from the guide needle 53c corresponding to the waste liquid discharge channel 36. By controlling whether the liquid flows in multiple guide needles 53b corresponding to other guide channels 34, the flow direction of the liquid within the sequencing chip 200 can also be controlled.

[0049] The sequencing chip liquid-laying system 100 provided in this embodiment allows liquid to be injected from above into the liquid-laying frame 30 before flowing into the sequencing chip 200. This avoids direct injection of liquid from below the sequencing chip 200, thus preventing overflow, spillage, and dripping during the transfer of the sequencing chip 200. Furthermore, it prevents liquid crystallization in the sequencing chip 200 and contamination of the carrier module 10. By allowing liquid to be injected and flow out of the sequencing chip 200 through the liquid-laying frame 30, the required height difference between the inlet and outlet structures is reduced. The sealing gasket 33 also prevents residual reagents inside the sequencing chip 200 from overflowing when the liquid guide needle is reinserted after liquid transfer. By setting up a waste liquid discharge channel 36, and setting the depth n of the liquid guiding channel 34 at the position where the waste liquid discharge channel 36 connects with the liquid guiding channel 34 to be greater than the distance m from the liquid outlet hole 532 of the liquid guiding needle 53 to the tip of the needle 531, the requirements for the fit accuracy of the liquid injection position structure can be reduced, and the probabilistic leakage problem caused by the accumulation of the liquid injection position dimension chain can be solved.

[0050] This application also provides a liquid spreading method, applied to the sequencing chip liquid spreading system 100 in the above embodiments.

[0051] Please see Figure 12 One embodiment of the liquid spreading method of this application includes: Step S11: Fix the sequencing chip 200 on the liquid-laying frame 30 so that each liquid channel 34 is connected to the sequencing chip 200; Step S12: Connect the liquid guiding needle assembly 50 to the liquid spreading frame 30, and insert one liquid guiding needle 53 into one liquid guiding channel 34; Step S13: Inject liquid into the liquid-laying frame 30 through at least one liquid-guiding needle 53, and discharge the liquid or gas in the liquid-laying frame 30 through other liquid-guiding needles 53.

[0052] Specifically, step S11 involves fixing the sequencing chip 200 in the fixing groove 38 of the liquid spreading frame 30, and engaging the sequencing chip 200 with the fixing part 39, so that each liquid inlet hole 231 on the sequencing chip 200 corresponds one-to-one with the second through hole 343 of the liquid guiding channel 34 on the liquid spreading frame 30.

[0053] Step S12 specifically involves controlling the fixed plate 51 to move towards the liquid-laying frame 30, thereby driving all the liquid-guiding needles 53 to move towards the liquid-laying frame 30, and finally causing the outlet hole 532 of each liquid-guiding needle 53 to pass through the sealing gasket 33, thereby connecting with the liquid-guiding channel 34.

[0054] Step S13 specifically involves injecting liquid into the liquid-laying frame 30 through the liquid-laying needle 53a corresponding to the liquid-injection channel 34, and activating all the liquid-laying needles 53b corresponding to the other liquid-laying channels 34, so that the liquid can be spread into the sequencing chip 200. The liquid can be a reagent for staining the sample to be sequenced within the sequencing chip 200, or it can be water or other diluents; this application does not impose any restrictions on this.

[0055] In this embodiment, step S13 can be either simultaneously opening each corresponding other liquid guiding needle 53b of the other liquid guiding channel 34, or sequentially opening each corresponding other liquid guiding channel 34. This application does not limit this.

[0056] Please see Figure 13 Another embodiment of the liquid spreading method in this application includes: Step S21: Insert the liquid guiding needles 53 into the liquid guiding channel 34 and the waste liquid discharge channel 36 one by one, and make the position of the liquid outlet hole 532 of the liquid guiding needle 53 in the liquid guiding channel 34 lower than the position where the second flow channel groove 362 communicates with the liquid guiding channel 34. Step S22: Inject liquid into the liquid guiding channel 34 until the waste liquid in the liquid guiding channel 34 is discharged through the waste liquid discharge channel 36; Step S23: Continue injecting liquid into the liquid channel 34 so that the liquid flows into the sequencing chip 200.

[0057] The liquid-laying method proposed in this embodiment is applied to sequencing chip 200 where liquid has been injected at least once. By draining the waste liquid in the liquid-conducting channel 34, the liquid flowing into sequencing chip 200 can be made to include only the newly injected liquid. Specifically, in this embodiment, a new liquid-conducting needle assembly 50 can be reinserted into the liquid-laying frame 30 to inject new liquid, or the original liquid-conducting needle assembly 50 can be used, and the liquid flowing into the syringe 533 of the liquid-conducting needle assembly 50 can be replaced.

[0058] Step S22 specifically includes: closing all control valves 55 corresponding to the liquid guide needles 53b of other liquid guide channels 34, opening the control valve 55 corresponding to the liquid guide needle 53c of the waste liquid discharge channel 36, and then opening the control valve 55 corresponding to the liquid guide needle 53a, so that the liquid flows through the liquid guide channel 34 to the waste liquid discharge channel 36, thereby discharging the waste liquid above the liquid outlet hole 532 in the first through hole 341 through the waste liquid discharge channel 36. After the waste liquid is discharged, closing the control valves 55 corresponding to the liquid guide needle 53a of the liquid guide channel 34 and the liquid guide needle 53c of the waste liquid discharge channel 36.

[0059] Step S23 specifically includes: opening the control valves 55 corresponding to the liquid guide needles 53b of the other liquid guide channels 34, and opening the control valves 55 corresponding to the liquid guide needles 53a of the liquid inlet channel 34, so that liquid flows into the sequencing chip 200 through the liquid guide channels 34 and is discharged through the liquid guide needles 53b of the other liquid guide channels 34. The multiple control valves 55 corresponding to the liquid guide needles 53b of the other liquid guide channels 34 can be opened simultaneously or sequentially, and this application does not impose any restrictions on this.

[0060] The liquid-laying method provided in Embodiment 2 of this application can be used together with the liquid-laying method provided in Embodiment 1 of this application. Specifically, when liquid is injected into the sequencing chip 200 for the first time, steps S11, S12 and S13 can be executed sequentially; when liquid is injected into the sequencing chip 200 that has been injected at least once, and new reagents need to be replaced for injection, steps S11, S12, S21, S22 and S23 can be executed sequentially.

[0061] This application also provides a sequencer, including the sequencing chip bed system 100 described in the above embodiments. The sequencer may further include an image acquisition module for sequencing the bedded sequencing chip 200. The sequencer may also include a transfer device for transferring the bedded sequencing chip 200 from the sequencing chip bed system 100 to the image acquisition module. In other embodiments, the sequencing chip 200 may also be manually transferred by the user; this application does not limit this.

[0062] The sequencer provided in this application embodiment, by employing the sequencing chip liquid spreading system 100 in the above embodiment, facilitates the adjustment of the liquid injection position when injecting liquid into the sequencing chip 200, avoiding direct injection of liquid from below the sequencing chip 200, thereby avoiding phenomena such as overflow, liquid spillage, and liquid dripping that are prone to occur during the transfer of the sequencing chip 200, and further avoiding liquid crystallization in the sequencing chip 200 and contamination of the sequencer.

[0063] Those skilled in the art should recognize that the above embodiments are only used to illustrate this application and are not intended to limit this application. Any appropriate changes and variations made to the above embodiments within the essential spirit and scope of this application fall within the scope of protection claimed in this application.

Claims

1. A sequencing chip spreading system, characterized in that, include: A liquid-spreading frame for holding a sequencing chip to be coated with a liquid and for spreading the liquid onto the sequencing chip, the liquid-spreading frame including a frame body, the frame body including a first surface and a second surface opposite to the first surface, the first surface having a fixing groove; and The liquid guide needle assembly includes multiple liquid guide needles for injecting or extracting liquid into the sequencing chip through the liquid spreading frame; The liquid-laying frame has multiple liquid-guiding channels that communicate with the liquid-guiding needle to inject or extract liquid into the sequencing chip. Each liquid-guiding channel includes a first through-hole, a second through-hole, and a first flow channel. The first through-hole penetrates the first surface and the second surface, and the second through-hole penetrates the first surface and the second surface of the frame at the position corresponding to the fixing groove. One end of the first through-hole facing the first surface communicates with the liquid-guiding needle, and one end of the second through-hole facing the first surface communicates with the liquid inlet of the sequencing chip. The first flow channel is located on the second surface, and both ends of the first flow channel communicate with the ends of the first through-hole and the second through-hole facing the second surface, respectively.

2. The sequencing chip spreading system as described in claim 1, characterized in that, The liquid-laying frame also includes a plurality of first encapsulation sheets and a plurality of sealing gaskets, each of the first encapsulation sheets covering and sealing one of the first flow channel grooves, and each of the sealing gaskets covering the end of the first through hole away from the first flow channel groove.

3. The sequencing chip spreading system as described in claim 1, characterized in that, The liquid-laying frame is also provided with at least one waste liquid discharge channel, and each waste liquid discharge channel is connected to one of the liquid guiding channels; the waste liquid discharge channel is used to connect with one of the liquid guiding needles to discharge the liquid in the liquid guiding channel.

4. The sequencing chip spreading system as described in claim 3, characterized in that, The waste liquid discharge channel includes a first orifice and a second flow channel. The first orifice is formed on the liquid spreading frame and is used to communicate with one of the liquid guiding needles. The second flow channel is formed on the liquid spreading frame, so that the first orifice communicates with the liquid guiding channel. The liquid spreading frame also includes at least one second encapsulation sheet and at least one sealing gasket. Each second encapsulation sheet covers and seals one of the second flow channel channels. Each sealing gasket covers and seals the first orifice.

5. The sequencing chip spreading system as described in claim 4, characterized in that, The liquid guiding needle includes a needle tip and a liquid outlet hole. The distance from the liquid outlet hole to the tip of the needle tip is less than the depth of the liquid guiding channel corresponding to the position where the second flow channel groove communicates with the liquid guiding channel.

6. The sequencing chip spreading system as described in claim 1, characterized in that, The fluid guiding needle assembly also includes multiple control valves, each of which is configured to control the flow of liquid within the fluid guiding needle.

7. A method for spreading a solution, applied to the sequencing chip spreading system as described in any one of claims 1-6, characterized in that, include: The sequencing chip is fixed on the liquid-laying frame so that each of the liquid-guiding channels is connected to the sequencing chip; The liquid guiding needle assembly is connected to the liquid spreading frame, and one liquid guiding needle is inserted into one liquid guiding channel; Liquid is injected into the liquid-filling frame through at least one of the liquid-guiding needles, and liquid or gas is discharged from the liquid-filling frame through other liquid-guiding needles.

8. A method for spreading a solution, applied to the sequencing chip spreading system as described in claim 5, characterized in that, include: The liquid guiding needles are inserted one by one into the liquid guiding channel and the waste liquid discharge channel, and the position of the liquid outlet of the liquid guiding needle in the liquid guiding channel is lower than the position where the second flow channel groove communicates with the liquid guiding channel; Liquid is injected into the liquid guiding channel until the waste liquid in the liquid guiding channel is discharged through the waste liquid discharge channel; Continue injecting liquid into the liquid channel so that the liquid flows into the sequencing chip.

9. A sequencer, characterized in that, include: The sequencing chip spreading system as described in any one of claims 1-6.

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