Liquid spreading method

Abstract

A liquid spreading method is used for guiding fluid into a flow channel in a flow cell slide and comprises the steps that a liquid spreading device is provided, the liquid spreading device comprises a first flow channel, the first flow channel comprises a first section and a second section, the first section is communicated with a flow channel inlet, and the second section is communicated with a flow channel outlet; a power device is controlled to be started, so that the power device pushes fluid to reach the fluid inlet; the first section and the second section are controlled to be communicated, so that fluid flows from the fluid inlet to the fluid outlet; controlling the first section and the second section to be cut off; and the fluid is controlled to enter and flow through the flow channel in the flow cell slide through the first section and then flow out of the flow channel outlet through the second section. According to the invention, rapid and effective spreading of fluid is realized.

Description

[0001] This application is a divisional application with application number 202080098202.8, application date April 20, 2020, and invention name “Liquid spreading device, liquid spreading method, liquid spreading system, combined device and liquid passing device”. Technical Field

[0002] The present application relates to a liquid spreading device, a liquid spreading method, a liquid spreading system, a combined device and a liquid passing device for biological samples. Background Art

[0003] The main purpose of the liquid spreading technology on the solid surface is to spread the liquid evenly on the surface of the solid phase carrier. Commonly used in open space carriers, the corresponding technologies include: spraying, atomization deposition, coating, etc. The uniformity of the liquid spreading of the above-mentioned liquid spreading technology mainly depends on the performance or mode of action of the external spraying device, and basically does not involve the influence of the internal flow factors of the fluid. However, for the liquid spreading technology with closed space carriers, especially channel carriers with liquid inlet and outlet holes, it is difficult for external effects to reach the inside of the channel, so the fluid flow becomes the dominant factor in liquid spreading.

[0004] With the development of microfluidic technologies in recent years, the research on liquid spreading technology in channel-type carriers has gradually increased. Among them, pressure-driven flow-type liquid spreading has been widely used because of its advantages of strong controllability and easy implementation. At present, mainstream carriers often adopt channel structures with a large aspect ratio (the ratio of the long side to the short side), and have lower requirements for liquid spreading uniformity. However, carriers with a large aspect ratio generally require the signal acquisition device to have a large movement space in a certain dimension during signal acquisition, which is not conducive to the centralization and miniaturization of the signal acquisition device. In comparison, in this regard, carriers with a smaller aspect ratio have more advantages. However, for large-area carriers with a small aspect ratio, such as square carriers, there is currently a lack of effective liquid spreading methods, devices and systems.

[0005] In addition, with the rapid increase in the demand for high-throughput sequencing in the commercial sequencing field, the advantages of large-size slides in achieving high-throughput sequencing tasks have become more prominent. Designing and developing a method for spreading or passing liquid suitable for large-size slides, especially developing a method with controllable spreading uniformity, is crucial to improving the throughput, performance, and quality of sequencing and reducing sequencing costs. Therefore, the demand for effective spreading technology for large-size slides is particularly urgent. Summary of the invention

[0006] In order to solve some or all of the above problems and other potential problems in the prior art, it is necessary to propose a liquid spreading method.

[0007] The liquid spreading method of the embodiment of the present application is used to introduce fluid into a flow channel in a flow cell carrier, including: providing a liquid spreading device, the liquid spreading device including a first flow channel, the first flow channel including a first section and a second section, the first section connecting to a flow channel inlet, and the second section connecting to a flow channel outlet; controlling a power device to start so that the power device pushes the fluid to reach the fluid inlet; controlling the first section and the second section to be turned on so that the fluid flows from the fluid inlet to the fluid outlet; controlling the first section and the second section to be turned off; controlling the fluid to enter and flow through the flow channel in the flow cell carrier through the first section, and then flow out of the flow channel outlet through the second section.

[0008] The spreading method provided in the embodiment of the present application adopts a positive pressure spreading method, which significantly improves the spreading speed and reduces the possibility of bubbles appearing in the flow cell; and can be suitable for spreading the liquid of large-sized flow cell slides with a relatively small aspect ratio, and can significantly improve the replacement efficiency and spreading uniformity between reagents that enter the flow cell slides in sequence. BRIEF DESCRIPTION OF THE DRAWINGS

[0009] In order to more clearly illustrate the technical solutions of the embodiments of the present application, the drawings required for use in the embodiments of the present application will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without creative work.

[0010] Figure 1A It is a schematic diagram of the first embodiment of the flow cell carrier provided in the present application.

[0011] Figure 1B It is a schematic diagram of a second embodiment of the flow cell slide provided in the present application.

[0012] Figure 2 It is a three-dimensional schematic diagram of the first embodiment of the liquid spreading device provided in the present application.

[0013] Figure 3 yes Figure 2 An exploded view of the spreading device is shown.

[0014] Figure 4 yes Figure 2 Schematic diagram of flow channel distribution within the manifold block of the liquid spreading device shown.

[0015] Figure 5 yes Figure 4 Schematic diagram of the flow direction of fluid in the manifold block shown.

[0016] Figure 6 yes Figure 4 Schematic diagram of the flow direction of fluids in the manifold block and the flow cell slide.

[0017] Figure 7A-7C It is a schematic diagram of the process of spreading liquid in a flow cell slide in one embodiment of the present application.

[0018] Figure 8 It is a three-dimensional schematic diagram of an auxiliary cleaning tool provided in an embodiment of the present application.

[0019] Fig. 9 It is a three-dimensional schematic diagram of a cleaning device provided in an embodiment of the present application.

[0020] Fig. 10A It is a three-dimensional schematic diagram of a sealing ring provided in one embodiment of the present application.

[0021] Fig. 10B yes Fig. 10A A partial cross-sectional view of the seal ring shown.

[0022] Fig.11 It is a schematic diagram of the flow path in the manifold block in the second embodiment of the liquid spreading device provided in the present application.

[0023] Fig.12 It is a schematic diagram of the fluid flow direction in the manifold block in the third embodiment of the liquid spreading device provided in the present application.

[0024] Fig.13 It is a schematic diagram of the first embodiment of the liquid spreading system provided in the present application.

[0025] Fig.14 It is a schematic diagram of the second embodiment of the liquid spreading system provided in the present application.

[0026] The following specific implementation methods will further illustrate the present application in conjunction with the above-mentioned drawings. DETAILED DESCRIPTION

[0027] The following will be combined with the drawings in the embodiments of the present application to clearly and completely describe the technical solutions in the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, not all of the embodiments. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of this application.

[0028] It should be noted that when a component is referred to as being "fixed to" or "mounted on" another component, it may be directly on the other component or there may be a central component. When a component is considered to be "set on" another component, it may be directly set on the other component or there may be a central component at the same time. The term "and / or" as used herein includes all and any combinations of one or more of the relevant listed items.

[0029] See also Figure 1A , which is a schematic diagram of the first embodiment of the flow cell slide with a relatively small length and width in the present application. In this embodiment, the flow cell slide 1a is square and has a square flow channel 11a inside. The lower side of the flow cell slide 1a is a substrate 13a, and the upper side is a cover sheet 15a, and the cover sheet 15a is covered on the substrate 13a, and the flow channel 11a is formed between the cover sheet 15a and the substrate 13a. Openings are provided at the four corners of the substrate 13a, one of which is a flow channel inlet 111a, and the other three openings are flow channel outlets 113a, and sealing rings (not shown) are provided on the outside of the flow channel inlet 111a and the flow channel outlet 113a. A groove 115a is provided between the flow channel inlet 111a and one of the adjacent flow channel outlets 113a (hereinafter referred to as the first flow channel outlet 113a), and another groove 115a is provided between the other two flow channel outlets 113a. Both grooves 115a are provided on the side of the base 13a facing the flow channel 11a, and the two grooves 115a are used for flow rectification. One of the flow channel outlets 113a is provided at a diagonal position of the flow channel inlet 111a (hereinafter referred to as the second flow channel outlet 113a), and the other flow channel outlet 113a (hereinafter referred to as the third flow channel outlet 113a) is adjacent to the flow channel inlet 111a, and the first flow channel outlet 113a and the third flow channel outlet 113a are arranged on both sides of the line connecting the flow channel inlet 111a and the second flow channel outlet 113a.

[0030] See also Figure 1B As shown, it is a schematic diagram of the second embodiment of the flow cell slide with a relatively small length and width in the present application. In this embodiment, the flow cell slide 1b is also square, and has a square flow channel 11b inside. The lower side of the flow cell slide 1b is a substrate 13b, and the upper side is a cover sheet 15b, and the cover sheet 15b is covered on the substrate 13b, and the flow channel 11b is formed between the cover sheet 15b and the substrate 13b. Openings are provided at the four corners of the substrate 13b, one of which is a flow channel inlet 111b, and the other three openings are flow channel outlets 113b. The flow channel inlet 111b and the flow channel outlet 113b are both provided with sealing rings (not shown) on the outside. An L-shaped groove 115b for rectification is opened between the three flow channel outlets 113b. The L-shaped groove 115b first extends from one of the flow channel outlets 113b adjacent to the flow channel inlet 111b (hereinafter referred to as the first flow channel outlet 113b) to the flow channel outlet 113b located at a diagonal position of the flow channel inlet 111b (hereinafter referred to as the second flow channel outlet 113b), and then extends from the second flow channel outlet 113b to another flow channel outlet 113b adjacent to the flow channel inlet 111b (hereinafter referred to as the third flow channel outlet 113b). The second flow channel outlet 113b is located at the vertex position of the L-shaped groove 115b.

[0031] The L-shaped groove 115b is opened on one side of the base 13b facing the flow channel 11b. The first flow channel outlet 113b and the third flow channel outlet 113b are arranged on both sides of the line connecting the flow channel inlet 111b and the second flow channel outlet 113b.

[0032] See also Figure 2 and Figure 3 FIG. 2 is a schematic diagram of a first embodiment of a liquid spreading device of the present application. The liquid spreading device 2 of this embodiment can be used for Figure 1A The flow cell slide 1a and Figure 2 The flow cell slide 1b shown is spread with liquid. The liquid spreading device 2 includes a manifold block 21, a support platform 22 and a slide mounting platform 23. The slide mounting platform 23 is arranged in the middle of the support platform 22, and is used to mount the flow cell slide. In the present embodiment, the slide mounting platform 23 uses vacuum adsorption to adsorb the flow cell slide onto the slide mounting platform 23, and the outer side surface of the base of the flow cell slide is adsorbed onto the slide mounting platform 23 as a mounting and fixing surface. A gas channel 231 is provided on the slide mounting platform 23, and the gas channel 231 is connected to an external vacuum source (not shown) through a vacuum adapter 232. In the present embodiment, a temperature control module 24 is also provided on the lower side of the slide mounting platform 23, and the temperature control module 24 is used to provide a suitable temperature for the fluid in the flow cell slide mounted on the slide mounting platform 23 when necessary. A temperature measuring device 25 is also provided on one side of the temperature control module 24. The temperature measuring device 25 is used together with the temperature control module 24 to facilitate a control device (not shown) to control the temperature of the fluid in the flow cell carrier.

[0033] The manifold block 21 is disposed on the support platform 22 around the wafer mounting platform 23. In this embodiment, the manifold block 21 can be fixed on the support platform 22 by mechanical fastening methods such as screw locking, block clamping, etc., and a flow channel is disposed in the manifold block 21. Please also refer to Figure 4As shown, the flow channel includes a first flow channel 211 and a second flow channel 212. In addition, a plurality of openings connected to the internal flow channels are also provided on the manifold block 21, and the openings include a fluid inlet 213, a first fluid outlet 214, a second fluid outlet 216, and a plurality of valve connection ports 217. The manifold block 21 is connected to a plurality of valve devices 218 through the plurality of valve connection ports 217, and the valve devices 218 are controlled by the control device to connect or cut off a certain flow channel, thereby guiding the flow direction of the fluid. In this embodiment, the valve device 218 includes an inlet valve device 218a corresponding to the inlet of the flow cell carrier, an outlet valve device 218b corresponding to the outlet of the flow cell carrier, and a bypass valve device 218c arranged between the inlet valve device 218a and the outlet valve device 218b. In this embodiment, the plurality of valve devices 218 are exemplified as two-way valves, but the present application does not limit the type of the valve device 218, and the valve device 218 can be other types of valve devices, as long as the purpose required to be achieved in the present application can be achieved when applied.

[0034] Each outlet valve device 218b is arranged corresponding to a flow channel outlet of the flow cell carrier, and the outlet valve device 218b and the flow channel outlet of the flow cell carrier can be in a one-to-one correspondence. Figure 1A Taking the flow cell slide 1a as an example, there are three outlet valve devices 218b, which correspond to the three flow channel outlets 113a of the flow cell slide 1. Figure 1B Taking the spreading of the flow cell slide 1b as an example, there are three outlet valve devices 218b, which respectively correspond to the three flow channel outlets 113b of the flow cell slide 1b.

[0035] The manifold block 21 is also provided with a wafer interface 219, which is arranged corresponding to the flow channel inlet and the flow channel outlet of the flow cell wafer, and has a one-to-one correspondence with the flow channel inlet and the flow channel outlet of the flow cell wafer. Figure 1ATaking the flow cell slide 1a as an example, four slide interfaces 219 are provided on the manifold block 21, one of which corresponds to the flow channel inlet 111a of the flow cell slide 1a, and the other three slide interfaces correspond to the flow channel outlet 113a of the flow cell slide 1a. A first hole 2191 and a second hole 2192 are provided in each slide interface 219, the first hole 2191 is connected to the inlet valve device 218a or the outlet valve device 218b, and the second hole 2192 is connected to the second flow channel 212. A sealing ring 26 is installed in each slide interface 219, and a first hole 261 and a second hole 262 are provided on the sealing ring 26, the first hole 261 is connected to the first hole 2191 in the slide interface 219, and the second hole 262 is connected to the second hole 2191 in the slide interface 219. After the flow cell carrier 1 is placed on the mounting table 23, the opening on the flow cell carrier 1a is aligned one by one with the sealing ring 26, and the first hole 261 of the sealing ring 26 is connected to the flow channel inlet 111a or the flow channel outlet 113a of the flow cell carrier 1a, so that the flow channel inlet 111a of the flow cell carrier 1a is connected to the first flow channel 211 through the first hole 2191 in the carrier interface 219 and the inlet valve device 218a, and the flow channel outlet 113a of the flow cell carrier 1a is connected to the first flow channel 211 through the second hole 2192 in the carrier interface 219 and the outlet valve device 218b, so that the fluid in the first flow channel 211 can enter the flow cell carrier 1a through the inlet valve device 218a, the first holes 2191 and 261, and the flow channel inlet 111a, and the fluid in the flow cell carrier 1a can enter the first flow channel 211 through the flow channel outlet, the first holes 261 and 2191, and the outlet valve device 218b. The second hole 262 of the sealing ring 26 is connected to the second flow channel 212 through the second hole 2192 in the wafer interface 219. In this embodiment, the sealing ring 26 includes a central portion 263 and a ring body 264 sleeved on the central portion 263, and the first hole 261 is opened on the central portion 263. The edge of the ring body 264 abuts against the hole wall of the wafer interface 219, and forms a seal with the hole wall of the wafer interface 219. There is a notch on the ring body 264, and the notch is the second hole 262. The second hole 262 runs through the upper and lower sides of the ring body 264, wherein the upper side of the ring body 264 faces the outer side of the wafer interface 219, and the lower side of the ring body 264 faces the inner side of the wafer interface 219. The second hole 262 is used to guide the cleaning liquid, rectify the cleaning liquid, limit the flow, and thus discharge the residue on the sealing ring 26.

[0036] The inlet valve device 218a connects the first flow channel 211 with the first hole 261 of the sealing ring 26 installed at the inlet of the corresponding flow cell slide through the flow channel opened on the manifold block 21. Each outlet valve device 218b connects the first flow channel 211 with the first hole 261 of the sealing ring 26 installed at the outlet of the corresponding flow cell slide through the flow channel opened on the manifold block 21. In this embodiment, the bypass valve device 218c is arranged on the first flow channel 211. With the bypass valve device 218c as a reference, the first flow channel 211 includes a first section located before the bypass valve device 218c and a second section located after the bypass valve device 218c. The inlet valve device 218a is connected to the first section, and all the outlet valve devices 218b are connected to the second section. The bypass valve device 218c connects the two sections of the first flow channel 211 through the flow channels opened on the manifold block 21 to control whether the first flow channel 211 is connected or not.

[0037] In the present embodiment, one end of the first flow channel 211 is connected to the fluid inlet 213, and the other end is connected to the first fluid outlet 214, and the bypass valve device 218c is connected in the middle, and the bypass valve device 218c controls whether the first flow channel 211 is connected. When the bypass valve device 218c is turned on, the fluid flowing into the first flow channel 211 from the fluid inlet 213 can flow out of the manifold block 21 from the first fluid outlet 214. In the present embodiment, the fluid inlet 213 is a common fluid inlet, which respectively supplies reagents and cleaning fluids to enter the manifold block 21 at different time periods; the first flow channel 211 is a common flow channel, which is respectively used to flow reagents and cleaning fluids at different time periods; the second flow channel 212 is a cleaning fluid flow channel, which respectively connects the second hole 2192 of the carrier interface 219 and the second fluid outlet 216. Please also refer to Figure 5As shown, the fluid entering the first flow channel 211 from the fluid inlet 213 can enter the flow cell carrier through the inlet valve device 218a, then come out from the outlet valve device 218b, and then be discharged from the first fluid outlet 214 through the first flow channel 211 to the liquid spreading device 2, thereby achieving liquid spreading in the flow cell carrier. In the present application, the fluid circuit for supplying fluid in and out of the flow cell carrier to achieve liquid spreading of the flow cell carrier is called a "liquid spreading circuit". In the present embodiment, the first flow channel 211 constitutes a liquid spreading circuit; the fluid entering the first flow channel 211 from the fluid inlet 213 can also pass through the bypass valve device 218c, and then pass through another section of the first flow channel 211, and finally exit from the first fluid outlet 214 discharges the liquid spreading device 2, thereby eliminating excess liquid; the fluid entering the first flow channel 211 from the fluid inlet 213 can also enter the first hole 261 of the sealing ring 26 through the inlet valve device 218a, then enter the second flow channel 212 through the second hole 262, and discharge the liquid spreading device 2 from the second fluid outlet 216, thereby cleaning part of the pipeline and part of the sealing ring 26 in the manifold block 21; the fluid entering the first flow channel 211 from the fluid inlet 213 can also enter the first hole 261 of the sealing ring 26 through any outlet valve device 218b, then enter the second flow channel 212 through the second hole 262, and discharge the liquid spreading device 2 from the second fluid outlet 216. In the present application, the fluid circuit for allowing fluid to flow through to clean the manifold block and / or the related pipelines and components of the flow cell carrier is called a "cleaning circuit". In this embodiment, the first flow channel 211 and the second flow channel 212 constitute a cleaning circuit. The fluid flow directions described above can be achieved by controlling the inlet valve device 218a, the outlet valve device 218b and the bypass valve device 218c.

[0038] In actual application, the flow cell carrier is mounted on the mounting platform 23, and the inlet and outlet of the flow cell carrier are respectively pressed against the sealing ring 26 at the corresponding position, and the first hole 261 of the sealing ring 26 is aligned with the inlet or outlet of the flow cell carrier. The fluid inlet 213 of the manifold block 21 is connected to an upstream pump (such as a syringe pump, not shown) through a valve device (not shown in the figure), and the second fluid outlet 216 is connected to a downstream pump (not shown in the figure) through another valve device (not shown in the figure), and the upstream pump, the downstream pump, the inlet valve device 218a, the outlet valve device 218b and the bypass valve device can all be connected to the control device, and are started or turned on by the control device.

[0039] To be applied to Figure 1A Taking the spreading and cleaning of the flow cell slide 1a as an example, a spreading method of the present application and a cleaning method for cleaning the spreading device 2 after the spreading is completed are further explained.

[0040] Liquid laying process:

[0041] Please combine Figure 6 and 7A to 7C As shown, after the flow cell carrier 1a is installed on the mounting table 23, the inlet valve device 218a is set corresponding to the flow channel inlet 111a of the flow cell carrier 1a; the first outlet valve device 218b is set corresponding to the first flow channel outlet 113a; the second outlet valve device 218b is set corresponding to the second flow channel outlet 113a; the third outlet valve device 218b is set corresponding to the third flow channel outlet 113a. During the liquid spreading process, the upstream pump is first started, and the reagent as the fluid is pushed to the fluid inlet 213 by the upstream pump. Secondly, the inlet valve device 218a and the bypass valve device 218c are controlled to be connected, and the reagent flows through the first flow channel 211, so that the fluid inlet 213 of the manifold block 21 to the flow channel inlet 111a of the flow cell carrier 1a are filled with reagent; then the bypass valve device 218c is controlled to be closed and the first outlet valve device 218b is controlled to be connected, and the upstream pump is controlled to continue pumping liquid, and the fluid enters the flow cell carrier 1a through the inlet valve device 218a and the flow channel inlet 111a, along the groove 115a to the first flow channel outlet 113a. In this process, part of the fluid overflows the groove 115a, forming a blunt front edge in the flow channel 11a; the first The first outlet valve device 218b is closed, and the second outlet valve device 218b is turned on, and the upstream pump is controlled to continue pumping liquid, and the fluid enters the flow channel 11a through the inlet valve device 218a and the flow channel inlet 111a, and flows from the flow channel inlet 111a to the second flow channel outlet 113a; the second outlet valve device 218b is controlled to be closed, and the third outlet valve device 218b is opened, and the upstream pump is controlled to continue pumping liquid, and the fluid enters the flow channel 11a through the inlet valve device 218a and the flow channel inlet 111a, and flows from the flow channel inlet 111a to the third flow channel outlet 113a, so that the uniform liquid spreading of the entire flow channel 11a in the flow cell carrier 1a is completed. The residual liquid after the liquid spreading is completed flows out from the first fluid outlet 214. In the above steps, for fluids with lower viscosity, the pumping of the upstream pump can be completed by single-step liquid pushing, and for fluids with higher viscosity, the pumping of the upstream pump can be achieved by multi-step liquid pushing.

[0042] Cleaning process:

[0043] In order to remove residual liquid in the sealing ring 26 of each flow channel / pipeline and manifold block 21 during the liquid spreading process and avoid the influence of residual liquid on the next liquid spreading and the influence of its dissolved substances on the components of the liquid spreading device, one or more cleaning processes are performed after one or more liquid spreading.

[0044] Before cleaning, the flow cell slide is removed. During the cleaning process, firstly, the upstream pump is started, and the cleaning liquid as a fluid is pushed to the fluid inlet 213 by the upstream pump; secondly, the bypass valve device 218c is controlled to be turned on, and the cleaning liquid passes through the first flow channel 211 to the first fluid outlet 214, so that the first flow channel 211 and the downstream pipeline of the manifold block 21 are filled with the cleaning liquid; the downstream pump is started to keep the cleaning circuit in a negative pressure state so that the cleaning liquid can be discharged; the third outlet valve device 218b is controlled to be turned on, and the upstream pump is controlled to continue pumping liquid, so that the cleaning liquid is pushed out from the first hole 261 of the sealing ring 26 corresponding to the third outlet valve device 218b, falls into the second hole 262 of the sealing ring 26, and is collected by the downstream pump through the second flow channel 212 and the second fluid outlet 216; the second outlet valve device 218b is controlled to be turned on, and the upstream pump is controlled to continue pumping liquid, so that the cleaning liquid is discharged from the second outlet valve device 218b corresponding to the second outlet valve device 218b. The first hole 261 of the sealing ring 26 of the outlet valve device 218b is pushed out and falls into the second hole 262 of the sealing ring 26, and is collected by the downstream pump through the second flow channel 212 and the second fluid outlet 216; the first outlet valve device 218b is controlled to be turned on, and the upstream pump is controlled to continue pumping liquid, so that the cleaning liquid is pushed out from the first hole 261 of the sealing ring 26 of the corresponding first outlet valve device 218b, falls into the second hole 262 of the sealing ring 26, and is collected by the downstream pump through the second flow channel 212 and the second fluid outlet 216; the inlet valve device 218a is controlled to be turned on, and the upstream pump is controlled to continue pumping liquid, so that the cleaning liquid is pushed out from the first hole 261 of the sealing ring 26 of the corresponding inlet valve device 218a, falls into the second hole 262 of the sealing ring 26, and is collected by the downstream pump through the second flow channel 212 and the second fluid outlet 216. The above-mentioned cleaning method uses a pressure source located upstream of the liquid spreading device 2: the upstream pump drives the cleaning liquid with positive pressure to pass through and reach the designated pipeline and sealing ring, and then collects and discharges it through the pressure source downstream of the cleaning circuit: the downstream pump. The cleaning method can also be repeated multiple times to achieve better cleaning effect.

[0045] Then apply it to Figure 1B Taking the spreading and cleaning of the flow cell slide 1b as an example, another spreading method of the present application and another cleaning method for cleaning the spreading device 2 after the spreading is completed are described.

[0046] Liquid laying process:

[0047] After the flow cell carrier 1b is installed on the mounting table 23, the inlet valve device 218a is set corresponding to the flow channel inlet 111b of the flow cell carrier 1b; the first outlet valve device 218b is set corresponding to the first flow channel outlet 113b; the second outlet valve device 218b is set corresponding to the second flow channel outlet 113b; the third outlet valve device 218b is set corresponding to the third flow channel outlet 113b. During the liquid spreading process, the upstream pump is first started, and the reagent as the fluid is pushed to the fluid inlet 213 by the upstream pump. Secondly, the bypass valve device 218c is controlled to be turned on, and the reagent flows through the first flow channel, so that the fluid inlet 213 of the manifold block 21 to the flow channel inlet 111b of the flow cell carrier 1b is filled with reagent; then the bypass valve device 218c is controlled to be closed, and the second outlet valve device 218b is turned on, and the upstream pump is controlled to continue pumping liquid, and the reagent enters the flow cell carrier 1b through the inlet valve device 218a and the flow channel inlet 111b. The front edge of the reagent is fan-shaped, and finally guided to the second flow channel outlet 113b through the right-angle L-shaped groove 115b, so that the entire flow channel 11b in the flow cell carrier 1b is evenly spread. The residual liquid after the liquid spreading is completed flows out from the first fluid outlet 214 through the second outlet valve device 218b. In the above steps, for fluids with lower viscosity, the pumping of the upstream pump can be completed by single-step liquid pushing, and for fluids with higher viscosity, the pumping of the upstream pump can be achieved by multi-step liquid pushing.

[0048] Cleaning process:

[0049] In the cleaning method introduced this time, auxiliary cleaning tools are used to assist cleaning. Figure 8 As shown, it is a schematic diagram of the first embodiment of the auxiliary cleaning tool of the present application, in which the cleaning structure 311 of the auxiliary cleaning tool 31 of the present embodiment is pressed against the surrounding parts of the inlet and outlet of the manifold block 21 for fluid to enter and exit the flow cell carrier by the end face.

[0050] The auxiliary cleaning tool 31 includes a main body 310 and a cleaning structure 311, a positioning structure 312 and a mounting structure 313 arranged on the main body 310. The mounting structure 313 is used to install the main body 310 on the liquid spreading device 2. In the present embodiment, the mounting structure 313 is a mounting surface provided corresponding to the wafer mounting table 23. The mounting surface may be an adsorbed surface corresponding to the implementation mode in which the wafer mounting table 23 fixes the object by vacuum adsorption. The positioning structure 312 is used for positioning when the auxiliary cleaning tool 31 is clamped and installed on the liquid spreading device 2 by a robot. In the present embodiment, the positioning structure 312 has a directional orientation. The cleaning structure 311 is provided corresponding to the wafer interface 219 on the liquid spreading device 2. In this embodiment, each cleaning structure 311 is generally in the shape of a cap, including a top 3111 and a flange 3113, wherein the flange 3113 extends from the edge of the top 3111 toward the liquid spreading device 2, and the end surface of the flange 3113 presses against the surrounding parts of the inlet and outlet of the manifold block 21 for fluid to enter and exit the flow cell slide. In this embodiment, each cleaning structure 311 is fixed to the body 310 by bonding or mechanical clamping, and the body 310 is provided with a hole or a recess for accommodating the cleaning structure 311. Each cleaning structure 311 as a whole or only the flange 3113 is made of elastic material or easily deformable material, and the elastic material or easily deformable material can be rubber, silicone, foam glue, etc. A drainage structure 3115 is provided on the inner side of the top 3111 of each cleaning structure 311. The drainage structure 3115 is used to guide the fluid from the middle area of ​​the cleaning structure 311 to the edge area of ​​the cleaning structure 311. When the auxiliary cleaning tool 31 is installed on the liquid spreading device 2 to assist in the cleaning of the liquid spreading device 2, the cleaning structure 311 is correspondingly covered on the sealing ring 26 of the liquid spreading device 2. The cleaning liquid coming out of the first hole 261 of the sealing ring 26 is guided to flow to the second hole 262 through the drainage structure 3115, thereby entering the second flow channel 212 and being collected and discharged by the downstream pump. In one embodiment, the drainage structure 3115 is a drainage groove, which can be a drainage groove in the shape of a straight line, a cross, or a cross.

[0051] The cleaning process using the auxiliary cleaning tool 31 to assist in cleaning is as follows:

[0052] First, install the auxiliary cleaning tool 31 onto the liquid spreading device 2, and the cleaning structure 311 of the auxiliary cleaning tool 31 is buckled one by one around the sealing ring 26 of the liquid spreading device 2; start the upstream pump, and the cleaning liquid as a fluid is pushed to the fluid inlet 213 by the upstream pump; control the bypass valve device 218c to be turned on, and the cleaning liquid flows through the first flow channel 211 to the first fluid outlet 214, so that the first flow channel 211 and the downstream pipeline of the manifold block 21 are filled with cleaning liquid; start the downstream pump to keep the cleaning circuit in a negative pressure state so that the cleaning liquid can be discharged; control the third outlet valve device 218b to be turned on, and control the upstream pump to continue pumping liquid, so that the cleaning liquid is pushed out from the first hole 261 of the sealing ring 26 corresponding to the third outlet valve device 218b, and is guided by the corresponding cleaning structure 311 to flow to the second hole 262 of the sealing ring 26, and is collected by the downstream pump through the second flow channel 212 and the second fluid outlet 216; control the second outlet valve device 218b to be turned on, and control the upstream pump to continue pumping liquid , so that the cleaning liquid is pushed out from the first hole 261 of the sealing ring 26 corresponding to the second outlet valve device 218b, guided by the corresponding cleaning structure 311 to flow into the second hole 262 of the sealing ring 26, and collected by the downstream pump through the second flow channel 212 and the second fluid outlet 216; the first outlet valve device 218b is controlled to be turned on, and the upstream pump is controlled to continue pumping liquid, so that the cleaning liquid is pushed out from the first hole 261 of the sealing ring 26 corresponding to the first outlet valve device 218b, guided by the corresponding cleaning structure 311 to flow into the second hole 262 of the sealing ring 26, and collected by the downstream pump through the second flow channel 212 and the second fluid outlet 216; the inlet valve device 218a is controlled to be turned on, and the upstream pump is controlled to continue pumping liquid, so that the cleaning liquid is pushed out from the first hole 261 of the sealing ring 26 corresponding to the inlet valve device 218a, guided by the corresponding cleaning structure 311 to flow into the second hole 262 of the sealing ring 26, and collected by the downstream pump through the second flow channel 212 and the second fluid outlet 216.

[0053] The auxiliary cleaning tool of the present application also has a second embodiment. The auxiliary cleaning tool of the second embodiment is generally similar to the auxiliary cleaning tool 31 of the first embodiment. The main difference is that after the auxiliary cleaning tool of the second embodiment is installed on the liquid spreading device 2, there is a gap (not shown) between the cleaning structure of the auxiliary cleaning tool and the surrounding parts of the inlet and outlet of the manifold block 21 for fluid to enter and exit the flow cell carrier. The gap is used to balance the pipeline pressure between the cleaning circuit and the fluid circuit in the flow cell carrier. In this embodiment, the cleaning structure can form a male-female matching structure with the carrier interface 219 on the liquid spreading device 2. A one-way valve or a two-way solenoid valve (not shown) is provided downstream of the liquid spreading circuit, that is, downstream of the first fluid outlet 214, to reduce or prevent liquid reflux in the downstream pipeline of the liquid spreading device 2.

[0054] In this embodiment, the cleaning process assisted by the auxiliary cleaning tool is as follows:

[0055] First, start the downstream pump of the cleaning circuit to keep the cleaning circuit in a negative pressure state so that the cleaning liquid can be discharged; install the auxiliary cleaning tool on the liquid spreading device 2, and the cleaning structure of the auxiliary cleaning tool is covered one by one around the sealing ring 26 of the liquid spreading device 2; start the upstream pump, and the cleaning liquid as a fluid is pushed to the fluid inlet 213 by the upstream pump; control the bypass valve device 218c to be turned on and control the one-way pump or two-way solenoid valve downstream of the liquid spreading circuit to be turned on, so that the cleaning liquid flows through the first flow channel 211 and the first fluid outlet 214 to the downstream pipe The first flow channel and the downstream pipeline of the manifold block 21 are filled with cleaning fluid; the one-way valve or two-way solenoid valve downstream of the liquid laying circuit is controlled to be closed, and the downstream pipeline is cut off to reduce or prevent the backflow of the fluid; the third outlet valve device 218b is controlled to be turned on, and the upstream pump is controlled to continue pumping liquid, so that the cleaning fluid is pushed out from the first hole 261 of the sealing ring 26 corresponding to the third outlet valve device 218b, and is guided by the corresponding cleaning structure to flow into the second hole 262 of the sealing ring 26, and is discharged downstream through the second flow channel 212 and the second fluid outlet 216. The pump collects; the second outlet valve device 218b is controlled to be turned on, and the upstream pump is controlled to continue pumping liquid, so that the cleaning liquid is pushed out from the first hole 261 of the sealing ring 26 corresponding to the second outlet valve device 218b, and is guided by the corresponding cleaning structure to flow into the second hole 262 of the sealing ring 26, and is collected by the downstream pump through the second flow channel 212 and the second fluid outlet 216; the first outlet valve device 218b is controlled to be turned on, and the upstream pump is controlled to continue pumping liquid, so that the cleaning liquid is pushed out from the sealing ring 26 corresponding to the first outlet valve device 218b. The cleaning fluid is pushed out from the first hole 261 and guided by the corresponding cleaning structure 311 to flow into the second hole 262 of the sealing ring 26, and is collected by the downstream pump through the second flow channel 212 and the second fluid outlet 216; the inlet valve device 218a is controlled to be turned on, and the upstream pump is controlled to continue pumping liquid, so that the cleaning fluid is pushed out from the first hole 261 of the sealing ring 26 of the corresponding inlet valve device 218a, and is guided by the corresponding cleaning structure to flow into the second hole 262 of the sealing ring 26, and is collected by the downstream pump through the second flow channel 212 and the second fluid outlet 216.

[0056] See also Fig. 9Shown is a schematic diagram of a cleaning device for cleaning the flow channel inlet and the flow channel outlet of a flow cell carrier provided in one embodiment of the present application. The cleaning device 4 can be used in conjunction with the liquid spreading device 2 to clean the flow channel inlet and the flow channel outlet surrounding areas of the flow cell carrier at a fixed cleaning frequency to maintain the cleanliness of the installation and fixing surface of the flow cell carrier. The cleaning device 4 includes a manifold block 41, a support table 42 and a carrier mounting table 43. The carrier mounting table 42 is arranged in the middle position of the support table 41 and is used to install the flow cell carrier. In this embodiment, the carrier mounting table 23 uses vacuum adsorption to adsorb the flow cell carrier onto the carrier mounting table 43, and the outer side surface of the base of the flow cell carrier is adsorbed onto the carrier mounting table 23 as the installation and fixing surface. The manifold block 41 includes a plurality of blocks 410, and the plurality of blocks 410 are arranged around the carrier mounting table 23, and each block 410 is arranged corresponding to the flow channel inlet or the flow channel outlet of the flow cell carrier. The cleaning device 4 can be used for Figure 1A Taking the cleaning of the flow cell slide 1a as an example, corresponding to the flow cell slide 1a, the manifold block 41 includes four blocks 410, one of which is set corresponding to the flow channel inlet 111a of the flow cell slide 1a, and the other three blocks 410 are set corresponding to the flow outlet 113a of the flow cell slide 1a. Each block 410 is provided with a flow channel, and the flow channel includes two sections: a first section 411 and a second section 412. A slide interface 413 is also provided on each block 410 at a position facing the flow channel inlet 111a or the flow channel outlet 113a of the flow cell slide 1a, and the slide interface 413 is used to install a sealing ring 44. Please refer to Fig. 10A and Fig. 10B As shown, the sealing ring 44 is provided with a first hole 441 and a second hole 442. In this embodiment, the sealing ring 44 includes a central portion 443 as an inner ring and a ring body 444 as an outer ring. The outer side of the ring body 444 abuts against the hole wall of the wafer carrier interface 413, and forms a seal with the hole wall of the wafer carrier interface 413. The ring body 444 is separated from the central portion 443 and connected in the middle by a connecting portion 445. The connecting portion 445 separates the space between the ring body 444 and the central portion 443 into two layers, and a hole portion is provided on the connecting portion 445 to connect the upper and lower layers of space. The first hole 441 is provided on the central portion 443, and the hole portion on the connecting portion 443 is the second hole 442. The second hole 442 is used to guide the cleaning liquid, rectify the cleaning liquid, limit the flow, and thus discharge the residue on the sealing ring 26.

[0057] The bottom of the wafer interface 413 is provided with two holes: a first hole 4131 and a second hole 4132, wherein the first hole 4131 connects the first segment 411 with the first hole 441 of the sealing ring 44, and the second hole 4132 connects the second segment 412 with the second hole of the sealing ring 44, the first segment 411 connects the fluid inlet 414 provided on the manifold block 41, and the second segment 412 connects the fluid outlet 415 provided on the block 410. A connector 416 is installed on both the fluid inlet 414 and the fluid outlet, and the upstream and downstream pipelines are connected through the connector 416. Specifically, in this embodiment, the fluid inlet 414 of one of the blocks 410 serves as the fluid inlet of the manifold block 41 as a whole, and is connected to an upstream cleaning fluid source through a pipeline; the fluid outlet 415 of the other block 410 serves as the fluid outlet of the manifold block 41 as a whole, and is connected to a downstream pump of the cleaning platform 4 through a pipeline. The multiple blocks 410 are connected in series, and the fluid outlet 415 of the previous block 410 is connected to the fluid inlet 414 of the next block 410. The fluid entering from the fluid inlet 414 of the manifold block 41 passes through each block 410 in sequence and flows out from the fluid outlet 415 of the manifold block 41. When the fluid passes through the slide interface 413 of each block 410, it cleans the area around the inlet or outlet of the flow cell slide.

[0058] The specific cleaning process is as follows:

[0059] After the liquid spreading is completed or before the liquid spreading begins, the flow cell carrier is transferred and installed on the cleaning device 4, and the flow channel inlet and the flow channel outlet of the flow cell carrier are aligned with the first hole 441 of the sealing ring 44 respectively, and the sealing ring 44 and the flow cell carrier form a seal; the downstream pump is started, and the cleaning liquid as a fluid enters the fluid inlet 414 of the cleaning device 4 from the cleaning liquid fluid source, flows through the multiple blocks 410 in sequence, and fills the cleaning circuit, so that the flow channel inlet and the flow channel outlet of the flow cell carrier are infiltrated and cleaned by the cleaning liquid; the cleaning is continued for a period of time, such as 3-10s, and then the downstream valve is closed to stop cleaning.

[0060] See also Fig.11 , which is a schematic diagram of the second embodiment of the liquid spreading device in the present application. The hardware structure of the liquid spreading device 5 is substantially the same as that of the liquid spreading device 2, except that in the liquid spreading device 5, the cleaning circuit is used to clean the flow channel inlet and flow channel outlet of the flow cell slide, and the cleaning circuit and the liquid spreading circuit used for reagents to enter and exit the flow cell slide are independently arranged and not connected.

[0061] The liquid spreading device 5 includes a manifold block 51, and a first flow channel 511 and a second flow channel 512 are provided in the manifold block 51. The first flow channel 511 is used for allowing reagents to pass through to spread liquid for the flow cell slide, forming a liquid spreading circuit; the second flow channel 512 is used for allowing cleaning liquid to pass through to clean the sealing ring 52 and the flow channel inlet and the flow channel outlet around the flow cell slide, forming a cleaning circuit. The manifold block 51 is provided with a plurality of openings, and the openings include a first fluid inlet 513, a first fluid outlet 514, a second fluid inlet 515, a second fluid outlet 516, and a plurality of valve connection ports 517. Since the method of connecting the valve connection port to the valve device (not shown), and the method of using the valve device to control the flow of the fluid in the first flow channel 511 to achieve liquid spreading can refer to the above description of the liquid spreading device 2, so the description is omitted here. The first flow channel 511 is connected to the first fluid inlet 513 and the first fluid outlet 514 at the beginning and the end, and is connected to the upstream pump (not shown) through the first fluid inlet 513; the second flow channel 512 is connected to the second fluid inlet 515 and the second fluid outlet 516 at the beginning and the end, and is connected to the cleaning fluid source (not shown) through the second fluid inlet 515 and the downstream pump (not shown) through the second fluid outlet 516. The manifold block 51 is provided with a slide interface 518 corresponding to the flow channel inlet and the flow channel outlet of the flow cell slide, and the slide interface 518 is used to install the sealing ring 52. The structure of the sealing ring 52 can refer to the introduction of the sealing ring 44 above. In this embodiment, the second flow channel 512 is divided into multiple sections, and each adjacent two sections are connected through the slide interface 518. Specifically, a plurality of holes (not marked) are provided in the slide interface 518, at least one of which is connected to the first hole 521 of the sealing ring 52, and is used for guiding the fluid in the first flow channel 511 into the flow cell slide through the first hole 521, or guiding the fluid in the flow cell slide into the first flow channel 511 through the first hole 521; at least two of the holes are used to respectively connect two adjacent sections of the second flow channel 512, and are connected to the second hole 522 of the sealing ring 52, so that the fluid in the second flow channel 512 can pass through and clean the sealing ring 52 and the flow channel inlet and the flow channel outlet around the flow cell slide.

[0062] The process of using the spreading device 5 to spread the flow cell slide is as follows:

[0063] After the flow cell carrier is transferred and installed on the liquid spreading device 5, the flow channel inlet and the flow channel outlet of the flow cell carrier are aligned with the corresponding first holes 521 of the sealing ring 52, and the sealing ring 52 and the flow cell carrier form a seal; the liquid spreading begins, and the liquid spreading process can refer to the introduction of the liquid spreading process in other embodiments above, which will not be repeated here.

[0064] The cleaning process of using the liquid spreading device 5 to clean the sealing ring 52 and the flow channel inlet and the flow channel outlet of the flow cell slide is as follows:

[0065] After the liquid spreading is completed, or before the next liquid spreading begins, the downstream pump is started, and the cleaning liquid as the fluid enters the second fluid inlet 515 of the manifold block 51 from the cleaning liquid fluid source, flows through each section of the second flow channel 512 in turn, and fills the cleaning circuit, so that the sealing ring 52 and the flow channel inlet and the flow channel outlet of the flow cell carrier are infiltrated and cleaned by the cleaning liquid; the cleaning is continued for a period of time, such as 3-10 seconds, and then the downstream pump is turned off to stop cleaning.

[0066] The liquid spreading device 5 also includes a supporting platform (not shown) and a wafer mounting platform (not shown). The configuration and function of the liquid spreading device 5 can be referred to the liquid spreading device 2 and will not be described in detail here.

[0067] See also Fig.12 As shown, it is a schematic diagram of the third embodiment of the liquid spreading device in the present application. The hardware structure of the liquid spreading device 6 of this embodiment is substantially the same as that of the liquid spreading device 2, both of which include a support table, a wafer mounting table and a manifold block, wherein the arrangement and function of the support table and the wafer mounting table can refer to the liquid spreading device 2, and will not be repeated here. The difference between the liquid spreading device 6 and the liquid spreading device 2 mainly lies in the pipeline design inside the manifold block. In this embodiment, three flow channels are opened in the manifold block 61 of the liquid spreading device 6, wherein the first flow channel 611 is used for reagents to pass through to spread liquid for the flow cell wafers, forming a liquid spreading circuit, and the second flow channel 612a and the third flow channel 612b are used for cleaning liquid to pass through to clean the flow channel inlet and the flow channel outlet around the flow cell wafers, forming a cleaning circuit. The cleaning circuit and the liquid spreading circuit are independently arranged and not connected to each other.

[0068] The manifold block 61 is provided with a plurality of openings, including a first fluid inlet 613, a first fluid outlet 614, a second fluid inlet 615, a second fluid outlet 616, and a plurality of valve device connection ports 617. In this embodiment, the manner in which the valve connection port 617 is connected to the valve device 618, and the manner in which the valve device is used to control the flow of fluid in the first flow channel 611 to achieve liquid spreading can all be referred to the introduction of the liquid spreading device 2 above, and the description is omitted here. The first flow channel 611 is connected to the first fluid inlet 613 and the first fluid outlet 614 at the head and tail, and is connected to the upstream pump (not shown) and the reagent fluid source (not shown) through the first fluid inlet 613, and is connected to the downstream waste liquid storage unit (not shown) through the first fluid outlet 614; the second flow channel 612a and the third flow channel 612b are connected to the second fluid inlet 615 and the second fluid outlet 616 respectively, wherein the second fluid inlet 615 is connected to the upstream pump and the cleaning fluid source (not shown), and the second fluid outlet 616 is connected to the downstream pump (not shown) and the waste liquid storage unit (not shown). The flow channel inlet and the flow channel outlet corresponding to the flow cell carrier are provided with a carrier interface 619 on the manifold block 61, and the carrier interface 619 is used to install the sealing ring 62. The structure of the sealing ring 62 can refer to the introduction of the sealing ring 44 in the previous text. The second flow channel 612a and the third flow channel 612b are connected through the carrier interface 619. Specifically, a plurality of holes are provided in the wafer interface 619, at least one of which is connected to the first hole 621 of the sealing ring 62, and is used for guiding the fluid in the first flow channel 611 into the flow cell wafer through the first hole 621, or guiding the fluid in the flow cell wafer into the first flow channel 611 through the first hole 621; at least two of the holes are used for respectively connecting the second flow channel 612a and the third flow channel 612b, so that the cleaning fluid enters the wafer interface 619 from the second flow channel 612a, infiltrates and cleans the sealing ring 62 located in the wafer interface 619 and the surrounding areas of the flow channel inlet / flow channel outlet of the flow cell wafer, and then is discharged from the manifold block 61 from the second fluid outlet 616 through the second flow channel 612b.

[0069] The process of spreading liquid on the flow cell slide using the spreading device 6 can be referred to the above description and will not be described in detail here.

[0070] The cleaning process of using the liquid spreading device 6 to clean the sealing ring 62 and the flow channel inlet and flow channel outlet of the flow cell slide is as follows:

[0071] After the liquid spreading is completed, or before the next liquid spreading begins, start the upstream pump and the downstream pump. After the cleaning liquid as the fluid enters the second fluid inlet 615 of the manifold block 61 from the cleaning liquid fluid source, it flows through the second flow channel 612a, the wafer interface 619 and the third flow channel 612b in sequence, and fills the cleaning circuit, so that the sealing ring 52 and the flow channel inlet and the flow channel outlet of the flow pool wafer are infiltrated and cleaned by the cleaning liquid; continue cleaning for a period of time, such as 3-10s, then turn off the upstream pump and the downstream pump to stop cleaning; remove the flow pool wafer; start the downstream pump to remove the residual liquid at the sealing ring 62 through the third flow channel 612b and the second fluid outlet 616.

[0072] The present application also provides a fourth embodiment of a liquid spreading device. In the fourth embodiment, the liquid spreading device and the flow cell slide are designed as an integrated whole, and the manifold block of the liquid spreading device constitutes a cover plate of the flow cell slide. Specifically, the liquid spreading device includes a support table, a slide mounting table and a manifold block. The slide mounting table can be a certain area on the support table. In this embodiment, the slide mounting table is arranged in the central area of ​​the support table, and the substrate constituting the flow cell slide is arranged in this area. The manifold block is placed above the substrate, and a certain area on the manifold block corresponds to the substrate and is separated. In this embodiment, the substrate and the manifold block are sealed and separated. For example, a sealing fence is used to seal and separate the substrate and the manifold block, so as to form a flow channel between the substrate and the manifold block. In this embodiment, the central area of ​​the manifold block and the substrate constitute the flow cell slide, and a flow channel inlet and multiple flow channel outlets are arranged on the manifold block. A groove is also provided between the flow channel inlet and the flow channel outlet and / or between the flow channel outlets, so as to guide the spreading of the fluid in the flow channel. A wafer interface is also provided at the position corresponding to the flow channel inlet and the flow channel outlet in the manifold block. The flow channel inlet and the flow channel outlet are arranged at the bottom of the corresponding wafer interface. A sealing ring is installed in the wafer interface. The sealing ring can be set with reference to the sealing ring 26 or the sealing ring 44 in the above embodiment. A first flow channel and a second flow channel (or a third flow channel) are also provided in the manifold block. The first flow channel constitutes a liquid spreading circuit, and the second flow channel (or the second flow channel and the third flow channel) constitute a cleaning circuit. A plurality of valve devices are also provided on the outside of the manifold block to communicate with the first flow channel. The liquid spreading in the flow pool wafer is controlled by controlling the conduction and closing of the valve device. The setting of the flow channel in the manifold block, the setting of the openings on the manifold block, and the setting of the valve device can refer to the aforementioned embodiment of the present application. At least two holes are also provided in the wafer interface to connect the first flow channel and the second flow channel. The setting of the holes in the wafer interface can also refer to the aforementioned embodiment of the present application. In this embodiment, the manifold block is fixed to the support table by mechanical fastening methods such as screw locking, block clamping, etc. The manifold block fixes the substrate of the flow cell carrier tightly while fixing itself to the support table.

[0073] The liquid spreading method of the liquid spreading device using this embodiment can refer to the aforementioned introduction of this application, which will not be repeated here. The cleaning method of the pipeline and sealing ring in the liquid spreading device can also refer to the aforementioned introduction of this application, which will not be repeated here.

[0074] See also Fig.13 The figure shows a schematic diagram of the first embodiment of the liquid spreading system of the present application. The liquid spreading system 7 in the present embodiment includes a liquid spreading device 71, on which a flow cell carrier 72 can be installed or removed as needed. For example, when spreading the liquid, a flow cell carrier 72 needs to be installed on the liquid spreading device 71. When cleaning, the first case is that the flow cell carrier 72 can be retained on the liquid spreading device 71. At this time, while cleaning the pipes and sealing rings in the liquid spreading device 71, the flow channel inlet and the flow channel outlet of the flow cell carrier 72 are also cleaned; the second case is that the flow cell carrier 72 is transferred from the liquid spreading device 71. At this time, only the pipes and sealing rings in the liquid spreading device 71 are cleaned. The liquid spreading device 71 can be any of the liquid spreading devices described in the above embodiments, such as liquid spreading devices 2, 5 or 6.

[0075] A fluid source 73 is provided upstream of the liquid spreading device 71, and the fluid source 73 includes a reagent fluid source 731 and a cleaning fluid source 733, wherein the reagent fluid source 731 is used to provide reagents for the liquid spreading device 71 to spread liquid on the flow cell carrier 72, and the cleaning fluid source 733 is used to provide cleaning fluid for cleaning the internal pipelines, sealing rings and / or the flow channel inlet and flow channel outlet of the flow cell carrier 72 of the liquid spreading device 71. The reagent fluid source 731 is connected to a power device 741, and the power device 741 is used to provide power for the reagent to enter the liquid spreading device 71 and the flow cell carrier 72, and to flow in the liquid spreading device 71 and the flow cell carrier 72. The power device 741 can be a pump. A valve device 751 is provided on the fluid path between the power device 741 and the liquid spreading device 71, and the valve device 751 is used to control the opening and closing of the fluid path between the power device 741 and the liquid spreading device 71. The cleaning fluid source 733 is connected to a power device 742, which is used to provide power for the cleaning fluid to enter the liquid spreading device 71. The power device 741 may be a pump. A valve device 752 is provided between the power device 742 and the liquid spreading device 71, and the valve device 752 is used to control the connection and disconnection between the power device 742 and the liquid spreading device 71.

[0076] A waste liquid storage unit 76 is provided downstream of the liquid spreading device 71. The waste liquid storage unit 76 is used to store waste liquid flowing out of the liquid spreading device 71. A power device 743 is provided between the waste liquid storage unit 76 and the liquid spreading device 71. The power device 743 may be a pump, which is used to provide power for the waste liquid in the liquid spreading device 71 to flow into the waste liquid storage unit 76. In this embodiment, the liquid spreading system 7 is also provided with a pneumatic unit 77, which is used to provide low air pressure (such as vacuum) to the slide mounting table of the liquid spreading device 71 to adsorb the flow cell slide. In other embodiments in which the flow cell slide is mounted to the liquid spreading device 71 by mechanical fastening, the pneumatic unit 77 may be omitted. The liquid spreading system 7 is also provided with a control device 78, which may be a collection of hardware and software for controlling the power devices 741-743, valve devices 751 and 752, the pneumatic unit 77 and the valve device of the liquid spreading device 71. In one embodiment, the control device 78 can be a computer device including a processing unit, a storage unit and a computer program. The computer program is stored in the storage unit and executed by the processing unit to enable the control device 78 to control the power device 741-743, valve devices 751 and 752, the pneumatic unit 77 and the valve device of the liquid spreading device 71.

[0077] See also Fig.14 As shown, it is a schematic diagram of the second embodiment of the liquid spreading system of the present application. The liquid spreading system 8 in this embodiment can be used only to implement the liquid spreading process or only to implement the cleaning process. Therefore, compared with the liquid spreading system 7 of the first embodiment, the liquid spreading system 8 includes a functional device 81, and the functional device 81 is a liquid spreading device or a cleaning device. A flow cell carrier 82 is installed on the functional device 81. A fluid source 83 is provided upstream of the functional device 81, and the fluid source 83 can output reagents or cleaning fluids. A power device 84 and a valve device 85 are provided between the fluid source 83 and the functional device 81 in sequence. The settings downstream of the functional device 81 and other settings can refer to the liquid spreading system 7, and will not be repeated here.

[0078] The functional device 81 refers to the device being a liquid spreading device or a cleaning device, either one of the two.

[0079] The above-mentioned liquid spreading device and liquid spreading method, cleaning device and cleaning method, liquid spreading system, etc. provided in the present application can be used in some links in the field of molecular diagnosis or in vitro diagnosis that require liquid spreading and cleaning in practical applications. For example, it can be applied to nucleic acid sequencing to evenly spread nucleic acid samples or reagents on the flow cell slide, and after the liquid spreading is completed, it can be used to clean the pipeline and sealing ring of the liquid spreading device, and / or clean the flow channel inlet and flow channel outlet of the flow cell slide.

[0080] The liquid spreading device, liquid spreading method, liquid spreading system, etc. provided in the present application adopt a positive pressure liquid spreading method, which significantly improves the liquid spreading speed and reduces the possibility of bubbles appearing in the flow cell; and can be suitable for the liquid spreading of large-sized flow cell slides with relatively small aspect ratios, and can significantly improve the replacement efficiency and liquid spreading uniformity between reagents that enter the flow cell slides in sequence; at the same time, the cleaning device and cleaning method provided increase the maintainability and liquid spreading reliability of the liquid spreading device, can significantly improve the service life of the device, and reduce the failure rate of the device.

[0081] It can be understood that certain technical details or technical features of the various embodiments of the liquid spreading device and liquid spreading method, the cleaning device and cleaning method, and the liquid spreading system introduced in the present application can be referenced to or replaced with each other. For example, the sealing ring 26 of the liquid spreading device 2 in the first embodiment can be replaced by the sealing ring 44 of the cleaning device 4 introduced in another embodiment.

[0082] It can be understood that although the above-mentioned embodiment of the present application only introduces the method of setting the valve device on the outside of the manifold block, each valve device can also be set on the inside of the manifold block and only needs to be located on the corresponding fluid path.

[0083] It can be understood that although the above-mentioned embodiment of the present application only introduces the situation where the sealing ring is installed in the carrier interface and the carrier interface and the sealing ring are two independent components, in fact, the sealing ring can also be integrated with the corresponding carrier interface, or the sealing ring constitutes a part of the corresponding carrier interface.

[0084] It can be understood that although the above-mentioned embodiment introduces the manifold block of the liquid spreading device as a whole, in fact, the manifold block of the liquid spreading device can also be composed of multiple blocks. For example, the liquid spreading device can refer to the cleaning device to set the manifold block to be composed of multiple blocks, and the blocks are connected by pipelines. The inlet valve device and the outlet valve device can be set on the corresponding blocks, and the bypass valve device can be set on a certain block or can be set on the pipeline connecting the blocks.

[0085] It can be understood that although the manifold block of the cleaning device described in the above embodiment is composed of multiple blocks, the manifold block of the cleaning device can also be a whole, and the cleaning circuit runs through the manifold block, with the fluid inlet and the fluid outlet connected to the head and tail ends respectively.

[0086] It can be understood that the liquid spreading device and the cleaning device introduced in the above embodiments can essentially be collectively referred to as liquid passing devices, both of which use a manifold block equipped with a valve device and a wafer interface to implement control and drainage of the liquid, and achieve liquid spreading and / or cleaning of certain parts by setting a first hole on the wafer interface, or setting a first hole and a second hole at the same time. Specifically, a flow channel is provided in the manifold block, and a fluid inlet, a fluid outlet and a wafer interface connected to the flow channel are provided on the manifold block, the wafer interface is used to connect the flow channel in the flow cell wafer when the flow cell wafer is installed on the liquid transfer device, the wafer interface has a first hole and a second hole, the second hole in the wafer interface is connected to the flow channel through a fluid path, the first hole in the wafer interface is connected to the flow channel through a fluid path, and is used to connect the flow channel in the flow cell wafer when the flow cell wafer is installed on the liquid transfer device; wherein, the fluid entering the flow channel from the fluid inlet enters and exits the flow cell wafer through the first hole of the wafer interface, and then flows out through the fluid outlet; or, the fluid entering the flow channel from the fluid inlet enters the wafer interface through the first hole of the wafer interface, and then enters the flow channel through the second hole of the wafer interface, and flows out from the fluid outlet; or, the fluid entering the flow channel from the fluid inlet enters and exits the wafer interface through the second hole, and then flows out through the fluid outlet.

[0087] It can be understood that the liquid spreading device and the auxiliary cleaning tool introduced in the above embodiment can actually be collectively referred to as a combined device. Before cleaning certain parts, the auxiliary cleaning tool is placed on the liquid spreading device to assist in cleaning certain parts of the liquid spreading device.

[0088] Finally, it should be noted that the above embodiments are only used to illustrate the technical solution of the present application and are not intended to limit it. Although the present application has been described in detail with reference to the preferred embodiments, a person of ordinary skill in the art should understand that the technical solution of the present application may be modified or replaced by equivalents without departing from the spirit and scope of the technical solution of the present application.

Claims

1. A method for introducing a fluid into a flow channel in a flow cell slide, It is characterized in that include: A liquid spreading device is provided, the liquid spreading device comprises a first flow channel, the first flow channel comprises a first section and a second section, the first section is connected to a flow channel inlet, and the second section is connected to a flow channel outlet; Controlling the power device to start, so that the power device pushes the fluid to reach the fluid inlet; Controlling the first section and the second section to be conductive so that the fluid flows from the fluid inlet to the fluid outlet; Controlling the first section and the second section to be cut off; and The fluid is controlled to enter through the first section and flow through the flow channel in the flow cell carrier, and then flow out of the flow channel outlet through the second section.

2. The method for spreading liquid according to claim 1, It is characterized in that The liquid spreading device specifically comprises: A liquid spreading device having a manifold block is provided, wherein the first flow channel is provided in the manifold block, and a first fluid inlet, a first fluid outlet and a plurality of wafer interfaces connected to the first flow channel are provided on the manifold block, each of the wafer interfaces having a first hole, and the first hole of each wafer interface is used for docking with the flow channel inlet and one of the flow channel outlets of the flow pool wafer; an inlet valve device, a bypass valve device and a plurality of outlet valve devices are provided on the manifold block, wherein the inlet valve device, the outlet valve device and the wafer interfaces correspond one-to-one and are provided on the fluid path from the corresponding wafer interface to the first flow channel, and are used for connecting or cutting off the fluid path; the bypass valve device is provided between the first section and the second section, and is used for controlling the connection or disconnection between the first section and the second section, the inlet valve device is connected to the first section, and the outlet valve device is connected to the second section.

3. The method for spreading liquid according to claim 2, It is characterized in that The manifold block is further provided with a second flow channel, the manifold block is provided with a second fluid outlet connected to the second flow channel, each of the wafer carrier interfaces has a second hole, and the second hole of each wafer carrier interface is used to connect to the second flow channel, and the liquid spreading method further includes: When the flow channel inlet and the flow channel outlet of the flow pool carrier are not docked to the carrier interface, the fluid entering the first flow channel is controlled to enter the second hole of the carrier interface through the first hole of the corresponding carrier interface, and then flow out from the second fluid outlet through the second flow channel.

4. The method for spreading liquid according to claim 3, It is characterized in that The manifold block also has a second fluid inlet connected to the second flow channel, each of the wafer interface has at least two second holes, the second flow channel is divided into multiple sections by the wafer interface, and each two adjacent sections are connected through the second holes in the wafer interface at corresponding positions, and the method further includes: The fluid flowing in from the second fluid inlet is controlled to flow out from the second fluid outlet after passing through each of the carrier interfaces in sequence.

5. The method for spreading liquid according to claim 2, It is characterized in that The manifold block is further provided with a second flow channel and a third flow channel, the manifold block is provided with a second fluid inlet communicating with the second flow channel and a second fluid outlet communicating with the third flow channel, each of the wafer carrier interfaces has a second hole, each of the wafer carrier interfaces has at least two second holes and the two second holes are respectively connected with the second flow channel and the third flow channel, and the liquid spreading method further comprises: The fluid flowing in from the second fluid inlet is controlled to flow out from the second fluid outlet after passing through each of the carrier interfaces in sequence.

6. The method for spreading liquid according to any one of claims 2 to 5, It is characterized in that Each of the slide interface is provided with a sealing ring, each of the sealing rings is provided with a first hole connected to the first hole of the slide interface, each of the sealing rings is also provided with a second hole connected to the second hole of the slide interface, and the liquid spreading method further comprises: The control fluid enters the second hole of the wafer interface from the first hole and the second hole of the sealing ring.

7. The method for spreading liquid according to any one of claims 2 to 5, It is characterized in that The liquid spreading device further comprises a support platform and a wafer mounting platform, wherein the wafer mounting platform and the manifold block are both arranged on the support platform, and the liquid spreading method further comprises: The flow cell slide is mounted on the slide mounting table.

8. The method for spreading liquid according to claim 7, It is characterized in that Mounting the flow cell slide on the slide mounting platform specifically includes: The flow cell carrier is adsorbed onto the carrier mounting table by vacuum adsorption or low-pressure adsorption.

9. The method for spreading liquid according to any one of claims 1 to 5, It is characterized in that The spreading method is used for spreading nucleic acid samples or reagents in a flow cell slide.

10. The method for spreading liquid according to any one of claims 1 to 5, It is characterized in that The liquid spreading method uses positive pressure to push the fluid for liquid spreading and uses negative pressure to collect waste liquid.

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