Liquid spreading method

Abstract

A method for introducing fluid into a flow channel in a flow cell slide, comprising: providing a fluid delivery device, the fluid delivery device comprising a first flow channel, the first flow channel comprising a first section and a second section, the first section being in communication with a fluid inlet, the second section being in communication with a fluid outlet; controlling a power device to activate, the power device to push fluid to the fluid inlet; controlling the first section and the second section to turn on, the fluid to flow from the fluid inlet to the fluid outlet; controlling the first section and the second section to turn off; and controlling the fluid to enter the first section, to flow through the flow channel in the flow cell slide, and to exit the second section. The present application achieves fast and effective spreading of the fluid.

Description

[0001] This application is a divisional application of application number 202080098202.8, filed on April 20, 2020, entitled "Liquid spreading device, liquid spreading method, liquid spreading system and combination device and liquid passing device". Technical Field

[0002] This application relates to a liquid spreading device, liquid spreading method, liquid spreading system and combination device and liquid transfer device for biological samples. Background Technology

[0003] The main purpose of liquid spreading technology on solid surfaces is to uniformly distribute the liquid onto the surface of a solid carrier. It is commonly used for open-space carriers, and corresponding technologies include spraying, atomized deposition, and coating. The uniformity of liquid spreading in these technologies mainly depends on the performance or operation of the external spraying device, and is largely unaffected by internal fluid flow factors. However, for liquid spreading technologies on carriers with enclosed spaces, especially channel carriers with inlet and outlet holes, external forces are difficult to reach the interior of the channels; therefore, fluid flow becomes the dominant factor in liquid spreading.

[0004] With the development of microfluidic technologies in recent years, research on liquid spreading techniques in channel-type carriers has gradually increased. Among them, pressure-driven flow-based liquid spreading has been widely used due to its advantages of strong controllability and ease of implementation. Currently, mainstream slides often adopt channel structures with a large aspect ratio (ratio of the long side to the short side), which has lower requirements for liquid spreading uniformity. However, slides 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, slides with a smaller aspect ratio have more advantages in this regard. However, for large-area slides with a small aspect ratio, such as square slides, there is currently a lack of effective liquid spreading methods, devices, and systems.

[0005] Furthermore, with the rapid increase in demand for high-throughput sequencing in the commercial sequencing field, the advantages of large-size slides in achieving high-throughput sequencing tasks have become increasingly apparent. Designing and developing suitable spreading or transposition methods for large-size slides, especially methods with controllable spreading uniformity, is crucial for improving sequencing throughput, performance, quality, and reducing sequencing costs. Therefore, the need for effective spreading techniques for large-size slides is particularly urgent. Summary of the Invention

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

[0007] The liquid spreading method of this application is used to introduce fluid into a flow channel within a flow cell substrate, comprising: 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 communicating with a flow channel inlet, and the second section communicating with a flow channel outlet; controlling the activation of a power device to drive fluid to the fluid inlet; controlling the first section and the second section to be connected, so that the fluid flows from the fluid inlet to the fluid outlet; controlling the first section and the second section to be disconnected; controlling the fluid to enter through the first section and flow through the flow channel within the flow cell substrate, and then flow out through the second section and out of the flow channel outlet.

[0008] The liquid spreading method provided in this application adopts positive pressure liquid spreading, which significantly improves the liquid spreading speed and reduces the possibility of air bubbles in the flow cell; it is also applicable to liquid spreading of large-sized flow cell slides with small aspect ratios, and can significantly improve the replacement efficiency and liquid spreading uniformity between reagents entering the flow cell slides in sequence. Attached Figure Description

[0009] To more clearly illustrate the technical solutions of the embodiments of this application, the drawings used in the embodiments of this application will be briefly introduced below. Obviously, the drawings described below are only some embodiments of this application. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

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

[0011] Figure 1B This is a schematic diagram of a second embodiment of the flow cell carrier provided in this application.

[0012] Figure 2 This is a perspective view of the first embodiment of the liquid spreading device provided in this application.

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

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

[0015] Figure 5 yes Figure 4 The diagram shows the flow direction of fluid within the manifold block.

[0016] Figure 6 yes Figure 4 The diagram shows the flow direction of the fluid within the manifold block and the slide in the flow cell.

[0017] Figures 7A-7C This is a schematic diagram of the liquid spreading process in a flow cell slide according to one embodiment of this application.

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

[0019] Figure 9 This is a perspective view of a cleaning device provided in an embodiment of this application.

[0020] Figure 10A This is a three-dimensional schematic diagram of a sealing ring provided in one embodiment of this application.

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

[0022] Figure 11 This is a schematic diagram of the flow channel within the manifold block in the second embodiment of the liquid spreading device provided in this application.

[0023] Figure 12 This is a schematic diagram of the fluid flow direction within the manifold block in the third embodiment of the liquid spreading device provided in this application.

[0024] Figure 13 This is a schematic diagram of the first embodiment of the liquid spreading system provided in this application.

[0025] Figure 14 This is a schematic diagram of a second embodiment of the liquid spreading system provided in this application.

[0026] The following detailed description, in conjunction with the accompanying drawings, will further illustrate this application. Detailed Implementation

[0027] The technical solutions of 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. Based on the embodiments of this application, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of this application.

[0028] It should be noted that when a component is described as "fixed to" or "mounted to" another component, it can be directly on the other component or may be interspersed with an intermediate component. When a component is described as "set to" another component, it can be directly set on the other component or may be interspersed with an intermediate component. The term "and / or" as used herein includes all and any combination of one or more of the associated listed items.

[0029] Please see Figure 1A The diagram shown illustrates a first embodiment of the flow cell carrier with a small aspect ratio in this application. In this embodiment, the flow cell carrier 1a is square and has a square flow channel 11a inside. The lower side of the flow cell carrier 1a is a base 13a, and the upper side is a cover plate 15a. The cover plate 15a covers the base 13a, forming the flow channel 11a between the cover plate 15a and the base 13a. Openings are formed at the four corners of the base 13a, one of which is a flow channel inlet 111a, and the other three openings are flow channel outlets 113a. Sealing rings (not shown) are provided on the outer sides of both the flow channel inlet 111a and the flow channel outlets 113a. A groove 115a is formed 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). Another groove 115a is also formed between the other two flow channel outlets 113a. Both grooves 115a are formed on the side of the base 13a facing the flow channel 11a, and the two grooves 115a are used for flow rectification. One flow channel outlet 113a is located diagonally opposite 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. The first flow channel outlet 113a and the third flow channel outlet 113a are located on both sides of the line connecting the flow channel inlet 111a and the second flow channel outlet 113a.

[0030] Please see Figure 1B The diagram shown is a schematic representation of a second embodiment of the flow cell carrier with a small aspect ratio in this application. In this embodiment, the flow cell carrier 1b is also square, with a square flow channel 11b inside. The lower side of the flow cell carrier 1b is a base 13b, and the upper side is a cover plate 15b. The cover plate 15b covers the base 13b, forming the flow channel 11b between the cover plate 15b and the base 13b. Openings are formed at the four corners of the base 13b, one of which is a flow channel inlet 111b, and the other three openings are flow channel outlets 113b. A sealing ring (not shown) is provided on the outside of both the flow channel inlet 111b and the flow channel outlet 113b. An L-shaped groove 115b for flow rectification is formed between the three flow channel outlets 113b. The L-shaped groove 115b 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 diagonally opposite 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 apex of the L-shaped groove 115b.

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

[0032] Please see Figure 2 and Figure 3 The diagram shown is a schematic representation of a first embodiment of the liquid spreading device of this application. The liquid spreading device 2 of this embodiment can be used for... Figure 1A The flow cell slide 1a and shown Figure 2 The flow cell carrier 1b shown is used for liquid spreading. The liquid spreading device 2 includes a manifold block 21, a support platform 22, and a carrier mounting platform 23. The carrier mounting platform 23 is located in the middle of the support platform 22 and is used to mount the flow cell carrier. In this embodiment, the carrier mounting platform 23 uses vacuum adsorption to adsorb the flow cell carrier onto the carrier mounting platform 23, with the outer surface of the substrate of the flow cell carrier serving as the mounting surface. The carrier mounting platform 23 is provided with a gas channel 231, which is connected to an external vacuum source (not shown) via a vacuum adapter 232. In this embodiment, a temperature control module 24 is also provided on the lower side of the carrier mounting platform 23. The temperature control module 24 is used to provide a suitable temperature for the fluid in the flow cell carrier mounted on the carrier mounting platform 23 when needed. A thermometer 25 is also provided on one side of the temperature control module 24. The thermometer 25 is used in conjunction with the temperature control module 24 to facilitate a control device (not shown) to control the temperature of the fluid in the flow cell slide.

[0033] The manifold block 21 is disposed on the support platform 22 surrounding the substrate mounting stage 23. In this embodiment, the manifold block 21 can be fixed to the support platform 22 by mechanical fastening methods such as screw locking or locking with clips. The manifold block 21 has a flow channel inside. Please refer to the following document for further details. Figure 4As shown, the flow channel includes a first flow channel 211 and a second flow channel 212. Additionally, the manifold block 21 has multiple openings connecting to the internal flow channels, including a fluid inlet 213, a first fluid outlet 214, a second fluid outlet 216, and multiple valve connection ports 217. The manifold block 21 is connected to multiple valve devices 218 through these valve connection ports 217. The valve devices 218 are controlled by a control device to connect or disconnect a flow channel, thereby guiding the flow direction of the fluid. In this embodiment, the valve devices 218 include an inlet valve device 218a corresponding to the inlet of the flow tank slide, an outlet valve device 218b corresponding to the outlet of the flow tank slide, and a bypass valve device 218c disposed between the inlet valve device 218a and the outlet valve device 218b. In this embodiment, the multiple valve devices 218 are exemplified as two-way valves; however, this application does not limit the type of valve device 218. The valve device 218 can be other types of valve devices, as long as they can achieve the purpose required by this application.

[0034] Each outlet valve device 218b corresponds to a flow channel outlet of the flow cell substrate, and there can be a one-to-one correspondence between the outlet valve device 218b and the flow channel outlet of the flow cell substrate. This is applicable to... Figure 1A Taking the flow cell slide 1a as an example, there are three outlet valve devices 218b, corresponding to the three flow channel outlets 113a of the flow cell slide 1. This is for applications such as... Figure 1B Taking the liquid spreading of the flow cell carrier 1b as an example, there are three outlet valve devices 218b, which correspond to the three flow channel outlets 113b of the flow cell carrier 1b.

[0035] The manifold block 21 is also provided with a wafer carrier interface 219, which is configured to correspond one-to-one with the inlet and outlet of the flow channel of the wafer carrier in the flow cell. This is intended for use in... Figure 1ATaking the flow cell slide 1a as an example, the manifold block 21 has four slide interfaces 219. One slide interface 219 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. Each slide interface 219 has a first hole 2191 and a second hole 2192. 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. The sealing ring 26 has a first hole 261 and a second hole 262. 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 platform 23, the openings on the flow cell carrier 1a are aligned with the sealing rings 26 one by one. The first hole 261 of the sealing ring 26 connects to the flow channel inlet 111a or the flow channel outlet 113a of the flow cell carrier 1a. Thus, 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. This allows the fluid in the first flow channel 211 to 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 to 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 connects to the second flow channel 212 through the second hole 2192 in the substrate interface 219. In this embodiment, the sealing ring 26 includes a central portion 263 and an annular body 264 sleeved on the central portion 263, and the first hole 261 is formed on the central portion 263. The edge of the annular body 264 abuts against the wall of the substrate interface 219, forming a seal with the wall of the substrate interface 219. The annular body 264 has a notch, which is the second hole 262, which penetrates the upper and lower sides of the annular body 264, wherein the upper side of the annular body 264 faces the outer side of the substrate interface 219, and the lower side of the annular body 264 faces the inner side of the substrate interface 219. The second hole 262 is used to guide the cleaning fluid, rectify and limit the flow of the cleaning fluid, and thus discharge residues on the sealing ring 26.

[0036] The inlet valve device 218a connects the first flow channel 211 to the first hole 261 of the sealing ring 26 installed at the inlet of the corresponding flow tank substrate via a flow channel formed on the manifold block 21. Each outlet valve device 218b connects the first flow channel 211 to the first hole 261 of the sealing ring 26 installed at the outlet of the corresponding flow tank substrate via a flow channel formed on the manifold block 21. In this embodiment, a bypass valve device 218c is disposed on the first flow channel 211. Based on the bypass valve device 218c, the first flow channel 211 includes a first section before the bypass valve device 218c and a second section after the bypass valve device 218c. The inlet valve device 218a is connected to the first section, all outlet valve devices 218b are connected to the second section, and the bypass valve device 218c connects the two sections of the first flow channel 211 via a flow channel formed on the manifold block 21 to control whether the first flow channel 211 is connected or not.

[0037] In this embodiment, the first flow channel 211 is connected to the fluid inlet 213 at one end and to the first fluid outlet 214 at the other end, and is connected to a bypass valve device 218c in the middle, which controls whether the first flow channel 211 is open or closed. When the bypass valve device 218c is open, 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 this embodiment, the fluid inlet 213 is a common fluid inlet, which supplies reagents and cleaning solutions into the manifold block 21 at different times; the first flow channel 211 is a common flow channel, which is used to flow reagents and cleaning solutions at different times; the second flow channel 212 is a cleaning solution flow channel, which is connected to the second hole 2192 of the substrate interface 219 and the second fluid outlet 216, respectively. Please also refer to... Figure 5As shown, 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 exit through the outlet valve device 218b, and then exit the liquid spreading device 2 through the first fluid outlet 214 via the first flow channel 211. This achieves liquid spreading within the flow cell carrier. In this application, the fluid circuit used to supply fluid to the flow cell carrier to achieve liquid spreading of the flow cell carrier is called the "liquid spreading circuit". In this embodiment, the first flow channel 211 constitutes the liquid spreading circuit. Fluid entering the first flow channel 211 from the fluid inlet 213 can also pass through the bypass valve device 218c, then through another section of the first flow channel 211, and finally exit from the first fluid outlet. 214. The liquid-spreading device 2 is discharged to remove excess liquid. 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 be discharged from the liquid-spreading device 2 from the second fluid outlet 216, thereby cleaning some pipelines and some sealing rings 26 inside the manifold block 21. 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 be discharged from the liquid-spreading device 2 from the second fluid outlet 216. In this application, the fluid circuit used for supplying fluid to clean the relevant pipelines and components of the manifold block and / or flow tank carrier is called the "cleaning circuit". In this embodiment, the first flow channel 211 and the second flow channel 212 constitute the cleaning circuit. The fluid flow direction 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 practical applications, the flow cell carrier is mounted on the mounting platform 23. The inlet and outlet of the flow cell carrier are tightly pressed against the corresponding sealing rings 26, 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), and the second fluid outlet 216 is connected to a downstream pump (not shown) through another valve device (not shown). The upstream pump, downstream pump, inlet valve device 218a, outlet valve device 218b, and bypass valve device can all be connected to a control device, which is activated or turned on by the control device.

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

[0040] Liquid spreading process:

[0041] Please combine Figure 6 and Figures 7A to 7C As shown, after the flow cell carrier 1a is installed on the mounting platform 23, the inlet valve device 218a is set to correspond to the flow channel inlet 111a of the flow cell carrier 1a; the first outlet valve device 218b is set to correspond to the first flow channel outlet 113a; the second outlet valve device 218b is set to correspond to the second flow channel outlet 113a; and the third outlet valve device 218b is set to correspond to the third flow channel outlet 113a. During the liquid spreading process, the upstream pump is started first, and the reagent as 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 connected, allowing the reagent to flow through the first flow channel 211, filling the fluid inlet 213 of the manifold block 21 to the flow channel inlet 111a of the flow cell carrier 1a with reagent; then, the bypass valve device 218c is closed and the first outlet valve device 218b is connected, controlling the upstream pump 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, flowing along the groove 115a to the first flow channel outlet 113a. During this process, some fluid overflows from the groove 115a, forming a blunt, rounded leading edge in the flow channel 11a; the first... The first outlet valve device 218b is closed, and the second outlet valve device 218b is open, controlling the upstream pump to continue pumping liquid. 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 then closed, and the third outlet valve device 218b is opened, controlling the upstream pump to continue pumping liquid. 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. This completes the uniform liquid distribution throughout the entire flow channel 11a within the flow tank carrier 1a. The residual liquid after liquid distribution flows out from the first fluid outlet 214. In the above steps, for fluids with low viscosity, the upstream pump can complete the pumping in a single step; for fluids with high viscosity, the upstream pump can achieve the pumping in multiple steps.

[0042] Cleaning process:

[0043] In order to remove liquid residue from the sealing rings 26 of each flow channel / pipeline and manifold block 21 during the liquid spreading process, and to avoid the impact of residual liquid on the next liquid spreading and the impact of internal dissolved substances on the components of the liquid spreading device, one or more cleaning processes are carried out after one or more liquid spreadings.

[0044] Before cleaning, the flow cell slides are removed. During the cleaning process, firstly, the upstream pump is started, and the cleaning fluid is pushed to the fluid inlet 213. Secondly, the bypass valve device 218c is opened, and the cleaning fluid flows through the first flow channel 211 to the first fluid outlet 214, filling the downstream pipe of the first flow channel 211 and the manifold block 21 with cleaning fluid. The downstream pump is started to maintain a negative pressure state in the cleaning circuit so that the cleaning fluid can be discharged. The third outlet valve device 218b is opened, and the upstream pump continues to pump fluid, so that the cleaning fluid is pushed out from the first hole 261 of the sealing ring 26 of 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 opened, and the upstream pump continues to pump fluid, so that the cleaning fluid is discharged from the second outlet. The first outlet valve device 218b is opened, and the upstream pump continues to pump 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 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 inlet valve device 218a is opened, and the upstream pump continues to pump 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 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 above cleaning method uses an upstream pump, located upstream of the liquid spreading device 2, to drive the cleaning fluid through and to the designated pipeline and sealing ring under positive pressure. The fluid is then collected and discharged by a downstream pump, which is located downstream of the cleaning circuit. The cleaning method can be repeated multiple times to achieve better cleaning results.

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

[0046] Liquid spreading process:

[0047] After the flow cell carrier 1b is installed on the mounting platform 23, the inlet valve device 218a is set to correspond to the flow channel inlet 111b of the flow cell carrier 1b; the first outlet valve device 218b is set to correspond to the first flow channel outlet 113b; the second outlet valve device 218b is set to correspond to the second flow channel outlet 113b; and the third outlet valve device 218b is set to correspond to the third flow channel outlet 113b. During the liquid spreading process, the upstream pump is started first, and the reagent as fluid is pushed to the fluid inlet 213 by the upstream pump. Next, the bypass valve device 218c is opened, allowing the reagent to flow through the first flow channel, filling the fluid inlet 213 of the manifold block 21 to the flow channel inlet 111b of the flow cell carrier 1b with reagent. Then, the bypass valve device 218c is closed, and the second outlet valve device 218b is opened, controlling the upstream pump to continue pumping. The reagent enters the flow cell carrier 1b through the inlet valve device 218a and the flow channel inlet 111b, forming a fan-shaped leading edge. Finally, it is guided through the right-angled L-shaped groove 115b to the second flow channel outlet 113b, thus completing the uniform liquid distribution throughout the entire flow channel 11b of the flow cell carrier 1b. The residual liquid after distribution 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 upstream pump can be completed by a single-step pumping operation; for fluids with higher viscosity, the upstream pump can be completed by multiple-step pumping operations.

[0048] Cleaning process:

[0049] The cleaning method described here utilizes auxiliary cleaning tools. Please refer to [link / reference needed]. Figure 8 The diagram shown is a schematic diagram of the first embodiment of the auxiliary cleaning tool of this application. In this embodiment, the cleaning structure 311 of the auxiliary cleaning tool 31 is pressed against the surrounding parts of the inlet and outlet of the fluid inlet and outlet of the flow tank carrier on the manifold block 21 by the end face.

[0050] The auxiliary cleaning tool 31 includes a body 310 and a cleaning structure 311, a positioning structure 312, and an installation structure 313 disposed on the body 310. The installation structure 313 is used to install the body 310 onto the liquid spreading device 2. In this embodiment, the installation structure 313 is a mounting surface corresponding to the slide mounting stage 23, which is an implementation where the slide mounting stage 23 uses vacuum adsorption to fix the object. The mounting surface can be an adsorbed surface. The positioning structure 312 is used for positioning the auxiliary cleaning tool 31 on the liquid spreading device 2 when it is held and installed by a robotic arm. In this embodiment, the positioning structure 312 has a directional orientation. The cleaning structure 311 is disposed corresponding to the slide interface 219 on the liquid spreading device 2. In this embodiment, each cleaning structure 311 is generally cap-shaped, including a top 3111 and an eave 3113. The eave 3113 extends from the edge of the top 3111 toward the liquid spreading device 2, and the end face of the eave 3113 abuts and presses against the surrounding portion of the inlet and outlet of the fluid-carrying slide on the manifold block 21. In this embodiment, each cleaning structure 311 is fixed to the body 310 by adhesive or mechanical clamping. The body 310 has holes or recesses for accommodating the cleaning structure 311. Each cleaning structure 311, or only the eave 3113, is made of an elastic or easily deformable material, such as rubber, silicone, or foam adhesive. Each cleaning structure 311 has a drainage structure 3115 on its inner side at the top 3111. The drainage structure 3115 is used to guide 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 cleaning, the cleaning structure 311 is correspondingly covered on the sealing ring 26 of the liquid spreading device 2. The cleaning fluid coming out of the first hole 261 of the sealing ring 26 is guided by the drainage structure 3115 to the second hole 262, 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 channel, which can be a straight, cross-shaped, or star-shaped drainage channel.

[0051] The cleaning process using auxiliary cleaning tool 31 is as follows:

[0052] First, the auxiliary cleaning tool 31 is installed on the liquid spreading device 2, with the cleaning structure 311 of the auxiliary cleaning tool 31 correspondingly covering the sealing ring 26 of the liquid spreading device 2. The upstream pump is started, and the cleaning fluid is pushed to the fluid inlet 213 by the upstream pump. The bypass valve device 218c is opened, and the cleaning fluid flows through the first flow channel 211 to the first fluid outlet 214, filling the downstream pipe of the first flow channel 211 and the manifold block 21 with cleaning fluid. The downstream pump is started to maintain the cleaning circuit under negative pressure so that the cleaning fluid can be discharged. The third outlet valve device 218b is opened, and the upstream pump continues to pump fluid, 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, guided by the corresponding cleaning structure 311 to 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 second outlet valve device 218b is opened, and the upstream pump continues to pump fluid. The cleaning fluid 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 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 open, and the upstream pump is controlled to continue pumping fluid, so that the cleaning fluid 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 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 open, and the upstream pump is controlled to continue pumping fluid, so that the cleaning fluid 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 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 this application also has a second embodiment, which 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 fluid inlet and outlet of the flow tank carrier on the manifold block 21. This gap is used to balance the pipeline pressure between the cleaning circuit and the fluid circuit inside the flow tank carrier. In this embodiment, the cleaning structure can form a male-female mating 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 backflow in the downstream pipeline of the liquid spreading device 2.

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

[0055] First, start the downstream pump of the cleaning circuit to maintain a negative pressure state in the cleaning circuit so that the cleaning fluid can be discharged; install the auxiliary cleaning tool onto the liquid spreading device 2, with the cleaning structure of the auxiliary cleaning tool correspondingly covering the sealing ring 26 of the liquid spreading device 2; start the upstream pump, and the cleaning fluid, as a fluid, is pushed to the fluid inlet 213 by the upstream pump; control the bypass valve device 218c to open and control the one-way pump or two-way solenoid valve downstream of the liquid spreading circuit to open, so that the cleaning fluid flows through the first flow channel 211 and the first fluid outlet 214 to the downstream pipe. The system controls the flow path, filling the downstream pipe of the first flow path and manifold block 21 with cleaning fluid; it controls the one-way valve or two-way solenoid valve downstream of the fluid spreading circuit to close, cutting off the downstream pipeline to reduce or prevent fluid backflow; it controls the third outlet valve device 218b to open, controlling the upstream pump to continue pumping fluid, 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, guided by the corresponding cleaning structure to the second hole 262 of the sealing ring 26, and then passed through the second flow path 212 and the second fluid outlet 216 to the downstream... The pump collects the liquid; it controls the second outlet valve device 218b to open, controlling 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 to 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; it controls the first outlet valve device 218b to open, controlling 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 first outlet valve device 218b. The first hole 261 is pushed out and guided by the corresponding cleaning structure 311 to 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 control inlet valve device 218a is 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, guided by the corresponding cleaning structure to 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.

[0056] Please see Figure 9The diagram shows a cleaning device 4 provided in one embodiment of this application for cleaning the inlet and outlet of a flow cell slide. The cleaning device 4 can be used in conjunction with the liquid spreading device 2 to clean the area surrounding the inlet and outlet of the flow cell slide at a fixed cleaning frequency, thereby maintaining the cleanliness of the slide's mounting surface. The cleaning device 4 includes a manifold block 41, a support platform 42, and a slide mounting platform 43. The slide mounting platform 42 is located in the middle of the support platform 41 and is used to mount the flow cell slide. In this embodiment, the slide mounting platform 43 uses vacuum adsorption to adsorb the flow cell slide onto the platform 43, with the outer surface of the slide's substrate serving as the mounting surface. The manifold block 41 includes multiple segments 410 arranged around the slide mounting platform 23, each segment 410 corresponding to either the inlet or outlet of the flow cell slide. The cleaning device 4 can be used to clean the area surrounding the inlet and outlet of the flow cell slide. Figure 1A Taking the cleaning of the flow tank carrier 1a as an example, the manifold block 41, corresponding to the flow tank carrier 1a, includes four sections 410. One section 410 corresponds to the flow channel inlet 111a of the flow tank carrier 1a, and the other three sections 410 correspond to the flow outlet 113a of the flow tank carrier 1a. Each section 410 has a flow channel, which includes two segments: a first segment 411 and a second segment 412. Each section 410 also has a carrier interface 413 located directly opposite the flow channel inlet 111a or flow channel outlet 113a of the flow tank carrier 1a. The carrier interface 413 is used to install the sealing ring 44. Please refer to [link / reference]. Figure 10A and Figure 10B As shown, the sealing ring 44 has 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 an outer ring 444. The outer side of the ring 444 abuts against the hole wall of the carrier interface 413, forming a seal between them. The ring 444 and the central portion 443 are spaced apart and connected by a connecting portion 445. The connecting portion 445 divides the space between the ring 444 and the central portion 443 into upper and lower layers, and a hole on the connecting portion 445 connects the upper and lower layers. The first hole 441 is formed on the central portion 443, and the hole on the connecting portion 443 is the second hole 442. The second hole 442 is used to guide the cleaning fluid, rectify and limit its flow, and thus discharge residues on the sealing ring 26.

[0057] The substrate interface 413 has two holes at its bottom: a first hole 4131 and a second hole 4132. The first hole 4131 connects the first segment 411 to the first hole 441 of the sealing ring 44, and the second hole 4132 connects the second segment 412 to the second hole of the sealing ring 44. The first segment 411 connects to the fluid inlet 414 on the manifold block 41, and the second segment 412 connects to the fluid outlet 415 on the segment 410. Connectors 416 are installed on both the fluid inlet 414 and the fluid outlet, connecting upstream and downstream pipelines. Specifically, in this embodiment, the fluid inlet 414 of one segment 410 serves as the fluid inlet of the entire manifold block 41, connected to an upstream cleaning fluid source via a pipeline; the fluid outlet 415 of the other segment 410 serves as the fluid outlet of the entire manifold block 41, connected to the downstream pump of the cleaning platform 4 via a pipeline. Multiple sections 410 are connected in series, with the fluid outlet 415 of one section 410 connected to the fluid inlet 414 of the next section 410. Fluid entering from the fluid inlet 414 of the manifold block 41 passes through each section 410 sequentially and flows out from the fluid outlet 415 of the manifold block 41. As the fluid passes through the wafer interface 413 of each section 410, it cleans the area around the inlet or outlet of the flow cell wafer.

[0058] The specific cleaning process is as follows:

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

[0060] Please see Figure 11 The diagram shown is a schematic of a second embodiment of the liquid spreading device in this application. The liquid spreading device 5 has a largely the same hardware structure as the liquid spreading device 2, except that in the liquid spreading device 5, the cleaning circuit is used to clean the area around the inlet and outlet of the flow channel of the flow cell slide, and the cleaning circuit and the liquid spreading circuit used for reagent entry and exit from the flow cell slide are set up independently and are not connected.

[0061] The liquid spreading device 5 includes a manifold block 51, within which are a first flow channel 511 and a second flow channel 512. The first flow channel 511 is used for the passage of reagents to spread liquid for the flow cell slide, forming a liquid spreading circuit. The second flow channel 512 is used for the passage of cleaning fluid to clean the sealing ring 52 and the area around the flow channel inlet and outlet of the flow cell slide, forming a cleaning circuit. The manifold block 51 has multiple openings, including a first fluid inlet 513, a first fluid outlet 514, a second fluid inlet 515, a second fluid outlet 516, and multiple valve connection ports 517. Since the method of connecting the valve connection ports to valve devices (not shown) and the method of using valve devices to control the flow of fluid in the first flow channel 511 to achieve liquid spreading can be referred to in the previous description of the liquid spreading device 2, the description is omitted here. The first flow channel 511 is connected at both ends to the first fluid inlet 513 and the first fluid outlet 514, and is connected to the upstream pump (not shown) through the first fluid inlet 513. The second flow channel 512 is connected at both ends to the second fluid inlet 515 and the second fluid outlet 516, and is connected to the cleaning fluid source (not shown) through the second fluid inlet 515 and to the downstream pump (not shown) through the second fluid outlet 516. The manifold block 51 has a carrier interface 518 corresponding to the flow channel inlet and outlet of the flow tank carrier. The carrier interface 518 is used to install the sealing ring 52, the structure of which can be referred to the previous description of the sealing ring 44. In this embodiment, the second flow channel 512 is divided into multiple segments, and each pair of adjacent segments is connected through the carrier interface 518. Specifically, the substrate interface 518 has multiple holes (not shown), at least one of which communicates with the first hole 521 of the sealing ring 52 to guide the fluid in the first flow channel 511 into the flow cell substrate through the first hole 521, or to guide the fluid in the flow cell substrate into the first flow channel 511 through the first hole 521; at least two of the holes are used to connect two adjacent sections of the second flow channel 512 respectively, and are connected with the second hole 522 of the sealing ring 52, so that the fluid in the second flow channel 512 passes through and cleans the area around the flow channel inlet and outlet of the sealing ring 52 and the flow cell substrate.

[0062] The process of spreading liquid on the slides in the flow cell using the liquid spreading device 5 is as follows:

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

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

[0065] After the liquid coating is completed, or before the next liquid coating begins, start the downstream pump. The cleaning fluid, as the fluid, enters the second fluid inlet 515 of the manifold block 51 from the cleaning fluid fluid source, and flows through each section of the second flow channel 512 in sequence, filling the cleaning circuit. This wets and cleans the sealing ring 52 and the flow channel inlet and outlet of the flow pool carrier with the cleaning fluid. Continue cleaning for a period of time, such as 3-10 seconds, and then turn off the downstream pump to stop cleaning.

[0066] The liquid spreading device 5 also includes a support platform (not shown) and a slide mounting platform (not shown). Their arrangement and function can be referred to the liquid spreading device 2, and will not be described in detail here.

[0067] Please see Figure 12 The diagram shown is a schematic representation of the third embodiment of the liquid spreading device in this application. The liquid spreading device 6 in this embodiment has a largely the same hardware structure as the liquid spreading device 2, both including a support platform, a slide mounting platform, and a manifold block. The arrangement and function of the support platform and slide mounting platform can be referenced in the liquid spreading device 2, and will not be repeated here. The main difference between the liquid spreading device 6 and the liquid spreading device 2 lies in the internal piping design of the manifold block. In this embodiment, the manifold block 61 of the liquid spreading device 6 has three flow channels. The first flow channel 611 is used to pass reagents to spread liquid for the flow cell slides, forming a liquid spreading loop. The second flow channel 612a and the third flow channel 612b are used to pass cleaning fluid to clean the area around the flow channel inlet and outlet of the flow cell slides, forming a cleaning loop. The cleaning loop and the liquid spreading loop are independently set up and not connected.

[0068] The manifold block 61 has multiple openings, including a first fluid inlet 613, a first fluid outlet 614, a second fluid inlet 615, a second fluid outlet 616, and multiple valve device connection ports 617. In this embodiment, the method of connecting the valve connection port 617 to the valve device 618, and the method of using the valve device to control the flow of fluid in the first flow channel 611 to achieve liquid spreading, can refer to the previous description of the liquid spreading device 2, and are omitted here. The first flow channel 611 is connected to the first fluid inlet 613 and the first fluid outlet 614 at its ends, and is connected to the upstream pump (not shown) and reagent fluid source (not shown) through the first fluid inlet 613, and 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. The second fluid inlet 615 is connected to the upstream pump and cleaning fluid source (not shown), and the second fluid outlet 616 is connected to the downstream pump (not shown) and waste liquid storage unit (not shown). The manifold block 61 has a slide interface 619 corresponding to the flow channel inlet and flow channel outlet of the flow cell slide. The slide interface 619 is used to install the sealing ring 62. The structure of the sealing ring 62 can be referred to the previous description of the sealing ring 44. The second flow channel 612a and the third flow channel 612b are connected by the slide interface 619. Specifically, the substrate interface 619 has multiple holes, at least one of which communicates with the first hole 621 of the sealing ring 62, for guiding the fluid in the first flow channel 611 into the flow tank substrate through the first hole 621, or guiding the fluid in the flow tank substrate into the first flow channel 611 through the first hole 621; at least two of the holes are used to communicate with the second flow channel 612a and the third flow channel 612b respectively, so that the cleaning fluid enters the substrate interface 619 from the second flow channel 612a, wets and cleans the sealing ring 62 and the flow channel inlet / outlet of the flow tank substrate located in the substrate interface 619, and then exits the manifold block 61 through the second fluid outlet 616 via the second flow channel 612b.

[0069] The process of using the liquid spreading device 6 to spread liquid onto the slides in the flow cell can be referred to the description above, and will not be repeated here.

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

[0071] After the liquid coating is completed, or before the next liquid coating begins, start the upstream and downstream pumps. The cleaning fluid, as the fluid, enters the second fluid inlet 615 of the manifold block 61 from the cleaning fluid fluid source, and then flows sequentially through the second flow channel 612a, the substrate interface 619, and the third flow channel 612b, filling the cleaning circuit. This allows the sealing ring 52 and the area around the flow channel inlet and outlet of the flow tank substrate to be wetted and cleaned by the cleaning fluid. Continue cleaning for a period of time, such as 3-10 seconds, then turn off the upstream and downstream pumps to stop cleaning. Remove the flow tank substrate. Turn on the downstream pump to discharge the residual liquid at the sealing ring 62 through the third flow channel 612b and the second fluid outlet 616.

[0072] This application also provides a fourth embodiment of the liquid spreading device. In this fourth embodiment, the liquid spreading device and the flow cell carrier are designed as a single unit, and the manifold block of the liquid spreading device constitutes the cover of the flow cell carrier. Specifically, the liquid spreading device includes a support platform, a carrier mounting platform, and a manifold block. The carrier mounting platform can be a certain area on the support platform. In this embodiment, the carrier mounting platform is located in the central area of ​​the support platform, and the substrate constituting the flow cell carrier is set in this area. The manifold block is placed above the substrate, and a certain area on the manifold block corresponds to and is separated from the substrate. In this embodiment, the substrate and the manifold block are sealed and separated, for example, by using a sealing fence to seal and separate the two, thereby forming 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 carrier. The manifold block is provided with a flow channel inlet and multiple flow channel outlets. Grooves are also formed between the flow channel inlet and the flow channel outlet and / or between the flow channel outlets, thereby guiding the spread of fluid in the flow channel. The manifold block also includes a substrate interface at the corresponding inlet and outlet positions of the flow channel. The inlet and outlet are located at the bottom of the respective substrate interfaces. A sealing ring is installed inside the substrate interface, which can be the sealing ring 26 or sealing ring 44 described in the above embodiments. The manifold block also includes a first flow channel and a second flow channel (or a third flow channel). The first flow channel forms a liquid spreading circuit, and the second flow channel (or the second and third flow channels) forms a cleaning circuit. Multiple valve devices are also provided on the outside of the manifold block, communicating with the first flow channel. The liquid spreading in the substrate of the flow tank is controlled by controlling the opening and closing of the valve devices. The arrangement of the flow channels in the manifold block, the arrangement of the openings on the manifold block, and the arrangement of the valve devices can refer to the aforementioned embodiments of this application. The substrate interface also includes at least two holes communicating with the first and second flow channels. The arrangement of the holes in the substrate interface can also refer to the aforementioned embodiments of this application. In this embodiment, the manifold block is fixed to the support platform by mechanical fastening methods such as screw locking or clamping. While fixing itself to the support platform, the manifold block also firmly fixes the substrate of the flow cell slide.

[0073] The liquid spreading method of the liquid spreading device using this embodiment can be referred to the foregoing description of this application, and will not be repeated here. The cleaning method of the pipeline and sealing ring inside the liquid spreading device can also be referred to the foregoing description of this application, and will not be repeated here either.

[0074] Please see Figure 13 The diagram shown is a schematic representation of a first embodiment of the liquid spreading system of this application. The liquid spreading system 7 in this embodiment includes a liquid spreading device 71. A flow tank carrier 72 can be installed on or removed from the liquid spreading device 71 as needed. For example, during liquid spreading, the flow tank carrier 72 needs to be installed on the liquid spreading device 71. During cleaning, in the first case, the flow tank carrier 72 can be retained on the liquid spreading device 71. In this case, while cleaning the internal pipes and sealing rings of the liquid spreading device 71, the flow channel inlet and outlet of the flow tank carrier 72 are also cleaned. In the second case, the flow tank carrier 72 is removed from the liquid spreading device 71. In this case, only the internal pipes and sealing rings of 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. The fluid source 73 includes a reagent fluid source 731 and a cleaning fluid source 733. The reagent fluid source 731 provides reagents for the liquid spreading device 71 to spread the liquid onto the flow cell slide 72. The cleaning fluid source 733 provides cleaning fluid for cleaning the internal pipes, sealing rings, and / or the area around the inlet and outlet of the flow channel of the flow cell slide 72 of the liquid spreading device 71. The reagent fluid source 731 is connected to a power unit 741, which provides power for the reagent to enter the liquid spreading device 71 and the flow cell slide 72, and to flow within the liquid spreading device 71 and the flow cell slide 72. The power unit 741 can be a pump. A valve device 751 is provided on the fluid path between the power unit 741 and the liquid spreading device 71. The valve device 751 controls the opening and closing of the fluid path between the power unit 741 and the liquid spreading device 71. The cleaning fluid source 733 is connected to the power unit 742, which provides power for the cleaning fluid to enter the liquid spreading device 71. The power unit 742 can be a pump. A valve device 752 is provided between the power unit 742 and the liquid spreading device 71, which controls the connection and disconnection between the power unit 742 and the liquid spreading device 71.

[0076] Downstream of the liquid spreading device 71 is a waste liquid storage unit 76, which stores the waste liquid flowing out of the liquid spreading device 71. A power unit 743, which can be a pump, is installed between the waste liquid storage unit 76 and the liquid spreading device 71 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 also includes a pneumatic unit 77, which provides low-pressure (e.g., vacuum) adsorption flow cell substrates to the substrate mounting stage of the liquid spreading device 71. In other embodiments where the flow cell substrates are mounted to the liquid spreading device 71 using mechanical fastening, the pneumatic unit 77 can be omitted. The liquid spreading system 7 also includes a control device 78, which can be a combination of hardware and software for controlling the power units 741-743, valve devices 751 and 752, the pneumatic unit 77, and the valve devices of the liquid spreading device 71. In one embodiment, the control device 78 may 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 realize the control device 78's control over the power devices 741-743, valve devices 751 and 752, pneumatic unit 77, and valve devices of liquid spreading device 71.

[0077] Please see Figure 14 The diagram shown is a schematic representation of a second embodiment of the liquid spreading system of this application. In this embodiment, the liquid spreading system 8 can be used solely for implementing the liquid spreading process or solely for implementing the cleaning process. Therefore, compared to the liquid spreading system 7 of the first embodiment, the liquid spreading system 8 includes a functional device 81, which is either a liquid spreading device or a cleaning device. A flow cell carrier 82 is mounted on the functional device 81. A fluid source 83 is located upstream of the functional device 81, and the fluid source 83 can output reagents or cleaning solutions. A power device 84 and a valve device 85 are sequentially arranged between the fluid source 83 and the functional device 81. The downstream configuration and other configurations of the functional device 81 can be referenced from the liquid spreading system 7, and will not be described in detail here.

[0078] Among them, functional device 81 refers to the device being either a liquid spreading device or a cleaning device, whichever is chosen.

[0079] The liquid spreading device and method, cleaning device and method, and liquid spreading system provided in this application can be used in practical applications for steps requiring liquid spreading and cleaning in the fields of molecular diagnostics or in vitro diagnostics. For example, they can be applied to nucleic acid sequencing to uniformly spread nucleic acid samples or reagents onto a flow cell slide. After liquid spreading is completed, they can be used to clean the pipes and sealing rings of the liquid spreading device, and / or to clean the area around the inlet and outlet of the flow channel on the flow cell slide.

[0080] The liquid spreading device, method, and system provided in this application adopt a positive pressure liquid spreading method, which significantly improves the liquid spreading speed and reduces the possibility of air bubbles in the flow cell. It is also suitable for liquid spreading of large-sized flow cell slides with small aspect ratios, and can significantly improve the replacement efficiency and liquid spreading uniformity between reagents entering the flow cell slides in sequence. At the same time, the cleaning device and cleaning method provided increase the maintainability and 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 is understood that certain technical details or features of the various embodiments of the liquid spreading device and method, cleaning device and method, and liquid spreading system described above in this application can be referenced or substituted for 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 described in another embodiment.

[0082] It is understood that although the above embodiments of this application only describe 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, as long as it is located on the corresponding fluid path.

[0083] It is understood that although the above embodiments of this application only describe the case where the sealing ring is installed inside the substrate interface and the substrate interface and the sealing ring are two independent components, in reality, the sealing ring can also be integrated with the corresponding substrate interface, or the sealing ring can constitute part of the corresponding substrate interface.

[0084] It is understandable that although the manifold block of the liquid spreading device is described as a whole in the above embodiments, in reality, the manifold block of the liquid spreading device can also be composed of multiple sub-blocks. For example, the liquid spreading device can refer to the cleaning device and set the manifold block as composed of multiple sub-blocks, with the sub-blocks connected by pipes. The inlet valve device and the outlet valve device can be set on the corresponding sub-blocks, and the bypass valve device can be set on a certain sub-block or on the pipe connecting the sub-blocks.

[0085] It is understood that although the manifold block of the cleaning device described in the above embodiments is composed of multiple sections, the manifold block of the cleaning device can also be a whole, with the cleaning circuit running through the manifold block and the fluid inlet and fluid outlet connected at both ends respectively.

[0086] It is understood that the liquid spreading device and cleaning device described in the above embodiments can be collectively referred to as liquid passing devices. They both use a manifold block equipped with a valve device and a carrier interface to control and guide the liquid. By setting a first hole on the carrier interface, or setting both a first hole and a second hole at the same time, they can achieve liquid spreading and / or cleaning of certain parts. Specifically, the manifold block is provided with a flow channel, and the manifold block has a fluid inlet, a fluid outlet, and a slide interface communicating with the flow channel. The slide interface is used to connect the flow channel within the flow cell slide when the flow cell slide is installed on the liquid transfer device. The slide interface has a first hole and a second hole. The second hole in the slide interface is connected to the flow channel through a fluid path, and the first hole in the slide interface is connected to the flow channel through a fluid path and is used to connect the flow channel within the flow cell slide when the flow cell slide is installed on the liquid transfer device. Fluid entering the flow channel from the fluid inlet enters and exits the flow cell slide through the first hole of the slide interface, and then flows out through the fluid outlet; or, fluid entering the flow channel from the fluid inlet enters the slide interface through the first hole of the slide interface, then enters the flow channel through the second hole of the slide interface, and flows out through the fluid outlet; or, fluid entering the flow channel from the fluid inlet enters and exits the slide interface through the second hole, and then flows out through the fluid outlet.

[0087] It is understood that the liquid spreading device and auxiliary cleaning tool described in the above embodiments can be essentially 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 solutions of this application and are not intended to limit it. Although this application has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of this application without departing from the spirit and scope of the technical solutions of this application.

Claims

1. A method for introducing fluid into flow channels within a flow cell slide, the flow cell slide comprising a flow channel inlet and a plurality of flow channel outlets, characterized in that, include: A fluid spreading device with a manifold block is provided. The manifold block has a first flow channel, a first fluid inlet, a first fluid outlet, and multiple slide interfaces. The first flow channel includes a first section and a second section. The first section is connected to the first fluid inlet, and the second section is connected to the first fluid outlet. The manifold block is also provided with an inlet valve device, a bypass valve device, and multiple outlet valve devices. The bypass valve device is located between the first section and the second section and is used to control the connection or disconnection between the first section and the second section. The plurality of slide interfaces of the manifold block are respectively connected to the flow channel inlet and the flow channel outlet of the flow cell slide; The power unit is activated, causing it to propel the fluid to the first fluid inlet. Controlling the first and second segments to conduct fluid allows fluid to flow from the first fluid inlet to the first fluid outlet, without the fluid passing through the flow cell slide; Control the cutting of the first segment and the second segment; and The fluid is controlled to enter the inlet of the flow channel of the flow cell carrier through the first section and flow through the flow channel inside the flow cell carrier, and then flow out of the first fluid outlet through the flow channel outlet of the flow cell carrier and the second section.

2. The liquid spreading method as described in claim 1, characterized in that, Each of the slide interfaces has a first hole, which is used to connect with one of the flow channel inlet and the flow channel outlet of the flow cell slide. The inlet valve device and the outlet valve device correspond one-to-one with the slide interface and are located on the fluid path from the corresponding slide interface to the first flow channel, and are used to open or close the fluid path. The inlet valve device is connected to the first section, and the outlet valve device is connected to the second section.

3. The liquid spreading method as described in claim 2, characterized in that, The manifold block is further provided with a second flow channel, and a second fluid outlet communicating with the second flow channel is opened on the manifold block. Each slide interface has a second hole, and the second hole of each slide interface is used to communicate with the second flow channel. The liquid spreading method further includes: When the inlet and outlet of the flow channel of the flow cell substrate are not connected to the substrate interface, the fluid entering the first flow channel is controlled to enter the second hole of the substrate interface through the first hole of the corresponding substrate interface, and then flow out from the second fluid outlet through the second flow channel.

4. The liquid spreading method as described in claim 3, characterized in that, The manifold block is further provided with a second fluid inlet communicating with the second flow channel. Each of the wafer carrier interfaces has at least two second holes. The second flow channel is divided into multiple segments by the wafer carrier interface, and each pair of adjacent segments is connected through the second holes in the wafer carrier interface at corresponding positions. The method further includes: The fluid flowing in from the second fluid inlet is controlled to pass through each of the carrier interfaces in sequence and then flow out from the second fluid outlet.

5. The liquid spreading method as described in claim 2, characterized in that, The manifold block is further provided with a second flow channel and a third flow channel. A second fluid inlet communicating with the second flow channel and a second fluid outlet communicating with the third flow channel are provided on the manifold block. Each slide interface has a second hole, and each slide interface has at least two second holes, with the two second holes of each slide interface respectively communicating with the second flow channel and the third flow channel. The liquid spreading method further includes: The fluid flowing in from the second fluid inlet is controlled to pass through each of the carrier interfaces in sequence and then flow out from the second fluid outlet.

6. The liquid spreading method according to any one of claims 3 to 5, characterized in that, Each of the slide interfaces is provided with a sealing ring, each sealing ring has a first hole communicating with the first hole of the slide interface, and each sealing ring also has a second hole communicating with the second hole of the slide interface. The liquid spreading method further includes: The control fluid flows from the first hole of the sealing ring into the second hole of the sealing ring, and then into the second hole of the carrier interface.

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

8. The liquid spreading method as described in claim 7, characterized in that, Mounting the flow cell slide onto the slide mounting stage specifically includes: The flow cell slide is adsorbed onto the slide mounting stage using a low-pressure adsorption method.

9. The liquid spreading method according to any one of claims 1 to 5, characterized in that, The aforementioned liquid spreading method is used for spreading reagents within a flow cell slide.

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

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