Biological slide reaction component loading device and gene sequencing reaction equipment

Abstract

The invention discloses a biological slide reaction component loading device and gene sequencing reaction equipment, the loading device comprises a reagent source for storing reaction components, a driving mechanism and a plurality of spraying tool bits, the driving mechanism is used for pumping reaction components into the spraying tool bits through the reagent source and spraying the reaction components to the biological reaction layer through the spraying opening in a spraying mode, and the multiple spraying tool bits comprise special tool bits arranged in one-to-one correspondence with the single reaction components and multifunctional tool bits selectively communicated with at least two reaction components. The spraying distance between the multifunctional tool bit and the biological slide glass is larger than the spraying distance between the special tool bit and the biological slide glass. According to the biological slide reaction component loading device disclosed by the embodiment of the invention, the spraying distance between the multifunctional tool bit and the biological slide is greater than the spraying distance between the special tool bit and the biological slide, so that the spraying thickness of the special tool bit is smaller than that of the multifunctional tool bit, and a special reagent is saved.

Description

Technical Field

[0001] The present invention relates to the technical field of gene sequencing, and in particular to a biological slide reaction component loading device and gene sequencing reaction equipment. Background Art

[0002] Bioslides typically come in two formats: encapsulated slides with laminar flow chambers (hereafter referred to as flowcells) and open-cell slides. Due to its unique fluidic format, open sequencing significantly differs from flowcells in terms of system integration principles and operating modes. Furthermore, the more flexible fluidic system construction of open-cell slides often allows for reagent savings.

[0003] Related bioassay technologies use flowcell packaging for fluid exchange and a fluorescence microscope system (air objective) to capture fluorescent signals. The disadvantage of this method is that the flowcell consumes a lot of reagents, and most of the reagents do not participate in the reaction (less than 1% of the reagent components participate in the reaction). In recent years, open-slide detection methods have emerged, such as immersion detection methods. Due to the inherent disadvantages of high carrying capacity and large reaction reagent tank volume, immersion technology can only reduce reagent consumption to 1 / 3 of the flowcell level, and ultimately the reduction in reagent consumption is not significant. Summary of the Invention

[0004] One purpose of the present invention is to provide a biological slide reaction component loading device, in which the spraying distance between the multifunctional blade head and the biological slide is greater than the spraying distance between the dedicated blade head and the biological slide, so that the spraying thickness of the dedicated blade head can be smaller than that of the multifunctional blade head, thereby saving dedicated reagents.

[0005] Another object of the present invention is to provide a gene sequencing reaction device.

[0006] According to an embodiment of the present invention, a biological slide reaction component loading device comprises: the reaction components including sample generation components and / or sample analysis components; the biological slide comprises an open biological reaction layer; the biological reaction layer comprises biological molecules configured to chemically react with the reaction components; the loading device comprises a reagent source for storing the reaction components, a drive mechanism, and a plurality of spray heads; the drive mechanism is configured to pump the reaction components into the spray head via the reagent source and spray the reaction components onto the biological reaction layer through a spray port; the plurality of spray heads comprises a dedicated head corresponding one-to-one to a single reaction component and a multifunctional head selectively connectable to at least two reaction components; the spraying distance between the multifunctional head and the biological slide is greater than the spraying distance between the dedicated head and the biological slide.

[0007] According to the biological slide reaction component loading device of an embodiment of the present invention, the spraying distance between the multifunctional blade head and the biological slide is greater than the spraying distance between the dedicated blade head and the biological slide, so that the spraying thickness of the dedicated blade head can be smaller than that of the multifunctional blade head, thereby saving dedicated reagents.

[0008] In addition, the biological slide reaction component loading device according to the above embodiment of the present invention may also have the following additional technical features:

[0009] In some embodiments, the driving mechanism includes a driving pump, and a valve group connected between the driving pump and the reagent source and the corresponding spray tool head, the valve group includes: a first valve, the first valve corresponds to the multifunctional tool head, the first valve has a liquid outlet and multiple liquid inlets, the liquid outlet is connected to the multifunctional tool head, and the multiple liquid inlets are respectively connected to different reaction components; wherein, the driving pump corresponding to the multifunctional tool head is connected to the first valve, and is configured to drive the liquid to be selectively fed into one of the multiple liquid inlets, and drive the reaction components entering the first valve to be pumped to the multifunctional tool head.

[0010] In some embodiments, a plurality of the spraying cutter heads are arranged side by side, and the multifunctional cutter head is arranged downstream of the dedicated cutter head.

[0011] In some embodiments, an air knife is further included, which has a gas inlet, a jet outlet and a gas flow channel connecting the gas inlet and the jet outlet, the gas inlet is used to introduce gas, the jet outlet is used to clean the biological reaction layer by blowing air, and the jet outlet is inclined in the direction of gas outlet away from the spray outlet of the spray knife head.

[0012] In some embodiments, the spraying tool head includes a tool head body having a reagent inlet, a spraying port, and a reagent flow channel connecting the reagent inlet and the spraying port, wherein the reagent inlet is used to receive the reaction component.

[0013] In some embodiments, the reagent flow channel further includes a liquid guide groove, which is arranged on the other side of the flow channel body of the reagent flow channel along the width direction, and each position of the liquid guide groove along the length direction is connected to the corresponding position of the flow channel body, the height dimension of the liquid guide groove is greater than the height dimension of the flow channel body, and the liquid guide groove is connected to the reagent inlet.

[0014] In some embodiments, the cutter head body further has an exhaust port, which is connected to the liquid guide groove, and the drive pump is configured to pump an air isolation column into the cutter head body and discharge the air isolation column through the exhaust port before the multifunctional cutter head sprays different reaction components.

[0015] In some embodiments, the valve group further includes a second valve correspondingly connected to the dedicated cutter head, and the drive pump is provided in a one-to-one correspondence with the second valve and the dedicated cutter head.

[0016] In some embodiments, the height dimension of the spray port is not less than 0.01 mm and not greater than 0.1 mm, preferably, the height dimension of the spray port is 0.04 mm; or, the spray head has a reagent flow channel, and the reagent flow channel is constructed as a flat long strip flow channel, and the height dimension of the reagent flow channel is not less than 0.01 mm and not greater than 0.1 mm, preferably, the height dimension of the reagent flow channel is 0.04 mm.

[0017] The gene sequencing reaction equipment according to an embodiment of the present invention includes the aforementioned biological slide reaction component loading device. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 Schematic diagram of a biological slide reaction component loading device according to an embodiment of the present invention.

[0019] Figure 2 It is a three-dimensional schematic diagram of a spraying tool head according to an embodiment of the present invention.

[0020] Figure 3 Schematic diagram of an explosion of a spray tool head according to an embodiment of the present invention.

[0021] Figure 4 It is a schematic diagram of a spraying tool head in one direction according to an embodiment of the present invention.

[0022] Figure 5 It is a schematic diagram of a spraying tool head in another direction according to an embodiment of the present invention.

[0023] Figure 6 1 is a schematic diagram of a spraying tool head according to an embodiment of the present invention in another direction.

[0024] Figure 7 yes Figure 6 Cross-sectional view of the middle section AA.

[0025] Figure 8 yes Figure 6 Cross-sectional view of the middle section BB.

[0026] Figure 9 yes Figure 8 A partial enlarged schematic diagram of the circled area.

[0027] Figure 10 yes Figure 6 Cross-sectional view of section CC.

[0028] Figure 11Schematic diagram of a gene sequencing reaction device according to an embodiment of the present invention.

[0029] Reference numerals:

[0030] Gene sequencing reaction device 1000, loading device 100, spraying blade 10, blade body 11, reagent inlet 101, spraying port 102, reagent flow channel 103, liquid guide groove 1032, emptying port 1033, first clearance groove 1041, second clearance groove 1042, first blade body 111, second blade body 112, first splicing surface 1061, notch groove 1063, isolation groove 107, main body 1073, first branch 1074, second branch 1075, emptying connector 12, liquid inlet connector 13, switch valve 14, positioning assembly 15, positioning bolt 151, positioning pin 152, drive pump 20, dedicated blade head 10a, multi-function blade head 10b, first valve 31, liquid outlet 301, liquid inlet 302, second valve 32, air knife 40, gas inlet 401, air jet 402, gas flow channel 403, reagent source 50, biological slide 200. DETAILED DESCRIPTION

[0031] In the open slide sequencing method in the related art, there are many types of reagents and the consumption is large. To this end, the present invention provides an embodiment of a method for loading reagents on a biological slide, which can solve the problems of the related art such as the large number of reagent types, reduced reagent consumption, avoidance of contamination between reagents, prevention of evaporation during reaction, overall automated slide transfer, lane loading and local sequencing of open slides, integration of biochemical fluids and optical machines, and timing design.

[0032] The present invention designs the core functional components of an extrusion spray sequencer through a system integration method and applies them to floor-standing / desktop ultra-high-throughput sequencers.

[0033] The following describes embodiments of the present invention in detail, examples of which are shown in the accompanying drawings, wherein the same or similar reference numerals throughout represent the same or similar elements or elements having the same or similar functions. The embodiments described below with reference to the accompanying drawings are exemplary and are intended to be used to explain the present invention, and are not to be construed as limiting the present invention.

[0034] like Figure 1According to an embodiment of the present invention, the biological slide reaction component loading device 100 is used to load reaction components onto the biological slide 200, wherein the reaction components may include sample generation components and / or sample analysis components, and the reaction components may include, for example, sequencing reagents, enzymes, samples, other biological molecules and buffer solutions. The reaction components are, for example, sprayed onto the reaction site of the biofunctional layer (for example, the area where the sample is located) or immobilized within the reaction site. The reaction components can react directly or indirectly with related substances. In addition, the sample analysis components may be, for example, fluorescently labeled nucleotides. In addition, the biological slide 200 may include an open biological reaction layer, and the biological reaction layer includes biological molecules configured to chemically react with the reaction components.

[0035] The loading device 100 includes a reagent source 50 for storing reaction components, a driving mechanism, and multiple spray heads 10. The driving mechanism is used to pump the reaction components into the spray head 10 through the reagent source 50, and spray the reaction components into the biological reaction layer through the spray port 102 in a spraying manner. The multiple spray heads 10 include a dedicated head 10a and a multifunctional head 10b, wherein the dedicated head 10a is set in a one-to-one correspondence with a single reaction component, and the multifunctional head 10b can be selectively connected to at least two reaction components. The spraying distance between the multifunctional head 10b and the biological slide 200 is greater than the spraying distance between the dedicated head 10a and the biological slide 200.

[0036] According to the biological slide reaction component loading device 100 of the embodiment of the present invention, during use, the reaction components can be pumped into the spray blade head 10 via a drive mechanism. The driving force exerted by the drive pump 20 on the reaction components allows the reaction components to be sprayed out of the spray port 102. Reagents can be added to the biological slide 200 by spraying. By controlling the thickness of the liquid film, reagent consumption can be reduced, significantly reducing sequencing costs. In actual testing, the actual amount used in the present invention can reduce costs by 50% to 80% compared to reagent loading methods in related arts. Furthermore, the spray blade can be integrated into a sequencer, and its structural design can control reagent contamination, evaporation, and other factors. Furthermore, the spraying distance between the multifunctional blade head 10b and the biological slide 200 is greater than the spraying distance between the dedicated blade head 10a and the biological slide 200. This allows the dedicated blade head 10a to spray less thickly than the multifunctional blade head, thereby saving on specialized reagents.

[0037] Multiple spray heads 10 can be arranged side by side and used to sequentially spray reagents onto the biological slide 200. This allows for sequential spraying of reagents, improving the stability of the sequencing reaction. The multiple spray heads 10 can be used to spray the same reagent or different reagents. Furthermore, the multiple spray heads 10 can spray reagents simultaneously, sequentially, or randomly, improving the spraying efficiency and effectiveness of the loading device 200 and meeting different usage requirements.

[0038] like Figure 1 In some embodiments, the driving mechanism includes a driving pump 20. Multiple reagent spraying operations can be achieved through the spraying head 10 and the driving pump 20. The driving pump 20 may include multiple driving pumps 20, and the multiple driving pumps 20 may be configured to correspond to the multiple spraying heads 10.

[0039] The drive mechanism also includes a valve assembly connected between the drive pump 20, the reagent source 50, and the corresponding spray head 10, for controlling the reagent source 50 to deliver the reaction components to the spray head 10. The valve assembly includes a first valve 31, which corresponds to the multifunctional blade head 10b. The first valve 31 has a liquid outlet 301 and multiple liquid inlets 302. The liquid outlet 301 is connected to the multifunctional blade head 10b, and the multiple liquid inlets 302 are connected to different reaction components.

[0040] The drive pump 20 corresponding to the multifunctional cutting head 10b is connected to the first valve 31 and is configured to selectively drive liquid into one of the multiple liquid inlets 302 and to pump the reagents passed into the first valve 31 to the multifunctional cutting head 10b. By switching between multiple reagents through the first valve 31 and spraying them through the multifunctional cutting head 10b, the addition of the reagents can be simplified and the efficiency of the addition can be improved.

[0041] Alternatively, multiple spray heads 10 may be arranged side by side, with the multifunctional head 10b positioned downstream of the dedicated head 10a. Specifically, when loading the reaction components, the multifunctional head 10b is positioned downstream of the dedicated head 10a in the direction of travel of the biological slide 200. After the dedicated head 10a sprays the reaction components, the multifunctional head 10b is used to spray the reaction components, thereby facilitating spraying by both the dedicated and multifunctional heads 10a.

[0042] In some embodiments, the loading device 100 further includes an air knife 40 having a gas inlet 401, an air jet 402, and a gas flow channel 403. The gas inlet 401 is used to introduce gas, and the gas flow channel 403 connects the gas inlet 401 and the air jet 402. The air jet 402 is used to clean the surface of the biological slide 200 by blowing air. The air jet 402 is inclined in the direction of air outlet away from the spraying port 102 of the spraying head 10. The air knife 40 can be used to clean the surface of the biological slide 200.

[0043] like Figure 2-Figure 10 The spray blade 10 may include a blade body 11, which has a reagent inlet 101, a spray port 102, and a reagent flow channel 103. The reagent flow channel 103 connects the reagent inlet 101 and the spray port 102, and the reagent inlet 101 is used to receive the reaction components. During use of the spray blade, the reaction components are added to the blade body 11 through the reagent inlet 101, then enter the reagent flow channel 103 and flow along the reagent flow channel 103 toward the spray port 102. Since the reaction components have a certain pressure when entering the blade body 11, under the action of the pressure, the reaction components can be sprayed out from the spray port 102, thereby spraying the reaction components onto the biological slide 200, which can reduce the amount of reaction components used.

[0044] like Figure 9 In some embodiments of the present invention, the spray port 102 is configured as a strip-shaped slit, and the spray port 102 is configured as a strip-shaped slit extending along the length direction or the front-to-back direction in the accompanying drawings. The strip-shaped spray port 102 structure can increase the range of spraying at one time, thereby improving the spraying efficiency of the reaction component. In addition, setting the spray port 102 in a slit shape can improve the spraying effect and reduce the amount of reaction component used. Of course, the spray head in the present invention can also be configured as other spraying forms, for example, using a nozzle structure of other shapes in the related art to spray the reaction component.

[0045] The spray port 102 is configured in a straight, curved, or zigzag shape. The shape of the spray port 102 can be adjusted according to actual needs to meet different spraying applications. For example, a straight spray port 102 can facilitate spraying of a square biological slide 200, achieving a wide range of spraying and conveniently controlling the range and amount of spraying. For another example, a curved or zigzag shape can meet the requirements of spraying a biological slide 200 with a predetermined edge shape, or spraying a spraying area with a predetermined boundary shape, thereby effectively controlling the spraying range and further reducing the amount of reaction components.

[0046] In addition, the blade body 11 of the present invention can be configured as an elongated strip, and the spray port 102 can be configured as a strip-shaped slit extending along the length direction (refer to the front-to-back direction in the drawings) of the blade body 11. This can achieve relatively stable spraying and improve the uniformity and stability of the sprayed reaction components.

[0047] like Figure 9 The reagent flow channel 103 includes a flow channel body configured as an elongated slit, with a spray port 102 formed on one side of the flow channel body along the width direction (refer to the up-down direction in the drawings) (refer to the lower side of the flow channel body in the drawings). This maintains the pressure of the reaction components within the reagent flow channel 103, allowing the reaction components to be stably sprayed from the spray port 102. This reduces the problem of unstable spraying caused by sudden size changes and improves the spraying efficiency and effectiveness of the reaction components.

[0048] like Figure 3 In some embodiments, the reagent flow channel 103 further includes a liquid guide groove 1032. The liquid guide groove 1032 is disposed on the other side of the flow channel body along the width direction (refer to the upper side of the flow channel body in the accompanying drawings). The liquid guide groove 1032 is connected to corresponding positions of the flow channel body at various locations along the length direction (refer to the front-to-back direction in the accompanying drawings). The height dimension of the liquid guide groove 1032 (refer to the left-to-right dimension in the accompanying drawings) is greater than the height dimension of the flow channel body. The liquid guide groove 1032 is connected to the reagent inlet 101. Through the liquid guide groove 1032, the reaction components can be introduced from the reagent inlet 101 into the liquid guide groove 1032 and then passed into the flow channel body. This can provide a buffer for the flow of the reaction components to avoid turbulence during the flow of the reaction components. At the same time, the liquid guide groove 1032 can have a certain distribution function, stably distributing the reaction components to different positions of the flow channel body, achieving actual uniform spraying, improving the spraying effect, and the actual uniformity of the surface of the biological slide 200 after spraying.

[0049] In addition, in order to facilitate the spraying of the reactive components, it is sometimes necessary to evacuate the reactive components or air in the spraying cutter head 10 to facilitate the spraying of the reactive components. Therefore, in some embodiments of the present invention, the cutter head body 11 also has an emptying port 1033, and the emptying port 1033 is connected to the liquid guide groove 1032. Through the emptying port 1033, the air or reactive components in the cutter head body 11 can be evacuated to avoid contamination of the reactive components, and the spraying amount of the reactive components can be guaranteed, thereby improving the stability of the spraying. In addition, the drive pump 20 is configured to pump an air isolation column into the cutter head body 11 and discharge the air isolation column through the emptying port 1033 before the multifunctional cutter head 10b sprays different reactive components.

[0050] The reagent inlet 101 can be connected to one end of the liquid guiding groove 1032 along the length direction, and the drain port 1033 can be connected to the other end of the liquid guiding groove 1032. This can facilitate the emptying of the entire liquid guiding groove 1032 and the flow channel body, avoid contamination of the reaction components, and further improve the accuracy of the spraying amount and the accuracy of the sequencing results.

[0051] like Figure 5 and Figure 7 In some embodiments of the present invention, a first clearance groove 1041 is provided on the blade body 11, and the spray blade 10 further includes an emptying connector 12, at least a portion of which is located within the first clearance groove 1041, and the emptying connector 12 is in communication with the emptying port 1033. The emptying connector 12 can facilitate the discharge of air or waste liquid, and other conduits can be connected to the emptying connector 12 to direct waste liquid or waste gas during the emptying process to a predetermined location, thereby preventing waste gas and waste liquid from contaminating the biological slide 200 or other reagents, thereby improving the stability and efficiency of spraying. In addition, the provision of the first clearance groove 1041 to accommodate the emptying connector 12 can reduce the space occupied by the spray blade 10 and facilitate the stacking of multiple spray blades 10, thereby facilitating the spraying of multiple reaction components.

[0052] Combine Figures 8 to 10 In combination with the above-mentioned embodiment, the blade head body 11 includes an exhaust port 1033, which is connected to the reagent flow channel 103. The spraying blade head 10 also includes an on-off valve 14, which is connected to the blade head body 11 and is configured to open and close the exhaust port 1033. The on-off valve 14 can be used to control the opening and closing of the exhaust port 1033.

[0053] Specifically, during use of the spray head 10, the reaction components can be pumped into the spray head 10 from the reagent inlet 101 by a liquid pump. At this time, the exhaust port 1033 can be opened. Under the pressure provided by the liquid pump, the air and the remaining reaction components in the spray head 10 will be sent out through the spray port 102 and the exhaust port 1033. After the exhaust is completed, the switch valve 14 can be closed. At this time, the exhaust port 1033 is closed, and the reaction components will be sprayed out through the spray port 102. Of course, the above description of the emptying port 1033 is only some embodiments of the present invention, and does not limit the scope of protection of the present invention. For example, the emptying port 1033 may not be set, and the spraying head 10 may be emptied through the spraying port 102. In particular, for a spraying head 10 specifically used for spraying a single reaction component, it is only necessary to empty the air in the spraying head 10, which can be directly discharged through the spraying port 102; and for a spraying head 10 that needs to spray multiple reaction components, it is preferably provided with the emptying port 1033 to better avoid contamination of the reaction components.

[0054] In some embodiments of the present invention, the valve assembly further includes a second valve 32 connected to the dedicated cutter head 10a, and the drive pump 20 is provided in a one-to-one correspondence with the second valve 32 and the dedicated cutter head 10a. The second valve 32 can be used to control the drive pump 20 to pump the reaction component to the dedicated cutter head 10a.

[0055] In combination with the above, the driving mechanism includes a first valve 31 and multiple second valves 32, the multiple second valves 32 are respectively connected to the multiple dedicated cutter heads 10a, the first valve 31 is connected to the multi-functional cutter head 10b, and the driving pump 20 includes multiple, first valves 31 and multiple second valves 32 are respectively connected to corresponding driving pumps 20.

[0056] In some embodiments of the present invention, the height of the spray port 102 is not less than 0.01 mm and not greater than 0.1 mm. For example, the height of the spray port 102 can be 0.01 mm, 0.026 mm, 0.04 mm, 0.6 mm, or 1 mm, etc. This can avoid the spraying efficiency being affected by a too small spray port 102, and can also avoid the waste of reactive components caused by a too large spray port 102. At the same time, it can achieve stable spraying of reactive components and improve spraying uniformity. Preferably, the height of the spray port 102 is 0.04 mm.

[0057] The length direction in the present invention can be the extension direction of the spray port 102 or the blade body 11; the width direction can be the width direction of the spray port 102 or the blade body 11, or the drainage direction of the reagent flow channel 103; and the height direction can be a direction perpendicular to the length and width directions. The height dimension in the present invention refers to the dimension along the height direction. Referring to the accompanying drawings, the length direction is the front-to-back direction in the drawings, the width direction is the up-down direction in the drawings, and the height direction is the left-right direction in the drawings.

[0058] In some embodiments of the present invention, the reagent flow channel 103 is configured as a flat elongated flow channel, and the height dimension of the reagent flow channel 103 is not less than 0.01 millimeter and not more than 0.1 millimeter. Preferably, the height dimension of the reagent flow channel 103 can be 0.01 millimeter, 0.026 millimeter, 0.04 millimeter, 0.6 millimeter or 1 millimeter or the like. It is convenient to have a certain pressure on the reaction component so that the reaction component is driven to spray from the spray port 102, thereby improving the efficiency and stability of spraying. Preferably, the height dimension of the reagent flow channel 103 is 0.04 millimeter.

[0059] In some embodiments, the reagent flow channel 103 has a first plane and a second plane that are opposite each other, with a gap between the first plane and the second plane. The reagent flow channel 103 is located between the first plane and the second plane, and the spray port 102 is located between the edge of the first plane and the edge of the second plane. By cooperating with the first plane and the second plane to construct the spray port 102 and the reagent flow channel 103, the stability of the reaction component circulation within the spray tip 10 can be improved, and the spraying of the reaction component can be facilitated, thereby improving the efficiency and uniformity of the spraying.

[0060] In order to simplify the generation and assembly of the blade body 11, the blade body 11 in the present invention can be set as a split structure. The present invention mainly uses the split blade body 11 as an example for explanation, which is not a limitation of the scope of protection of the present invention. The blade body 11 in the present invention can also be set as an integrated structure. In some embodiments, the blade body 11 includes a first blade body 111 and a second blade body 112. The first blade body 111 has a first splicing surface 1061, and the second blade body 112 has a second splicing surface. The first splicing surface 1061 and the second splicing surface are spliced ​​together, and a reagent flow channel 103 is constructed between the first splicing surface 1061 and the second splicing surface. The first splicing surface 1061 and the second splicing surface are connected, and the reagent flow channel 103 is formed therebetween, which can simplify the structure of the blade body 11, improve the efficiency of assembly and production of the blade body 11, and reduce costs.

[0061] In particular, a notch groove 1063 is provided on the first splicing surface 1061, the second splicing surface covers the notch groove 1063, and a reagent flow path 103 and a spray port 102 are constructed between the notch groove 1063 and the second splicing surface. Alternatively, a groove structure may be provided on both the first splicing surface 1061 and the second splicing surface, and the groove on the first splicing surface 1061 and the groove on the second splicing surface may be used to form the reagent flow path 103 and the spray port 102. In the present invention, by providing the notch groove 1063 to form the reagent flow path 103 and the spray port 102, the structure of the cutter head body 11 can be further simplified, thereby reducing the production and processing costs of the cutter head body 11.

[0062] In combination with the aforementioned embodiment, the reagent flow channel 103 of the present invention may include a liquid guide groove 1032. Therefore, the liquid guide groove 1032 may be provided on the side of the notch groove 1063 of the present invention away from the spray port 102. The height of the liquid guide groove 1032 is greater than the height of the notch groove 1063, and the reagent inlet 101 is connected to the liquid guide groove 1032. This simplifies the structure of the liquid guide groove 1032.

[0063] In addition, since the present application adopts a split blade head body 11, an isolation groove 107 is further provided between the first blade body 111 and the second blade body 112. The isolation groove 107 is provided on the side of the reagent flow channel 103 away from the spray port 102. In this way, the reaction components can be isolated and prevented from invading the blade head body 11, thereby effectively improving the structural stability and strength of the blade head body 11 and extending the service life of the blade head body 11.

[0064] The isolation groove 107 extends along the length of the blade body 11, enhancing its isolation effectiveness. Furthermore, at least one end of the isolation groove 107 communicates with the exterior of the spray blade 10. In other words, at least one end of the isolation groove 107 defines an opening that communicates with the exterior of the spray blade 10. This further enhances the stability of the reactive component spraying. The ends of the isolation groove 107 can extend to the end surfaces of the spray blade 10, thereby forming openings at both ends of the isolation groove 107. Alternatively, a groove can be provided on the end surface of the spray blade 10, with the opening formed at the bottom of the groove.

[0065] like Figure 6 The isolation tank 107 includes a main body 1073, a first branch 1074, and a second branch 1075. The main body 1073 is located on the side of the reagent flow channel 103 away from the spray port 102. The first branch 1074 and the second branch 1075 are respectively connected to the two ends of the main body 1073 and are inclined relative to the main body 1073. The reagent flow channel 103 is located between the first branch 1074 and the second branch 1075. Therefore, the reaction components, water, or other impurities that enter the isolation tank 107 can be reversed and discharged through the first branch 1074 and the second branch 1075, reducing the possibility of contamination of the reaction components and improving the stability and anti-contamination ability of the sprayed reaction components.

[0066] In addition, the first splicing surface 1061 has a first groove portion, and the second splicing surface has a second groove portion, and the first groove portion and the second groove portion are connected to form an isolation groove 107. Through the cooperation of the first groove portion and the second groove portion, a stable isolation groove 107 can be formed, and at the same time, the isolation effect can be improved, further reducing the possibility of contaminating the reaction components, and improving the stability and anti-pollution ability of the sprayed reaction components.

[0067] Combine Figure 2 、 Figure 3 and Figure 6 The blade body 11 also includes a positioning component 15, which is connected to the first blade body 111 and the second blade body 112 respectively, and is used to fix the first blade body 111 and the second blade body 112 together. The positioning component 15 and the reagent flow channel 103 are respectively arranged on both sides of the isolation groove 107.

[0068] Combine Figure 2 and Figure 3 In some embodiments of the present invention, the blade body 11 further includes a positioning assembly 15, which includes a positioning bolt 151 and a positioning pin 152. The positioning pins 152 include at least two and are disposed through the first blade body 111 and the second blade body 112 for pre-positioning the first blade body 111 and the second blade body 112. The bolts securely connect the first blade body 111 and the second blade body 112. The positioning assembly 15 can be used to complete the assembly and positioning of the first blade body 111 and the second blade body 112. In combination with the above, the isolation groove 107 can also be used to isolate the positioning assembly 15 from the reagent flow path 103, reducing contamination of reaction components and reducing the intrusion of reaction components into the positioning assembly 15, facilitating cleaning, and improving stability. In addition, the positioning pins 152 can achieve pre-positioning of the first blade body 111 and the second blade body 112, and the bolts can achieve a stable connection between the first blade body 111 and the second blade body 112, thereby improving the structural stability of the blade body 11 and facilitating assembly.

[0069] like Figure 9 In some embodiments of the present invention, a tip-shaped convex portion is provided at one end of the blade body 11, and the spray port 102 is provided at the tip of the convex portion. This facilitates spraying of the reaction components and reduces contamination of the surface of the blade body 11 by the reaction components.

[0070] like Figure 5 The blade body 11 is provided with a second clearance groove 1042, and the spray blade 10 further includes a liquid inlet connector 13, at least a portion of which is located in the second clearance groove 1042, and the liquid inlet connector 13 is in communication with the reagent inlet 101. The second clearance groove 1042 is provided to accommodate the liquid inlet connector 13, which can reduce the space occupied by the spray blade 10 and facilitate the stacking of multiple spray blades 10, thereby facilitating the spraying of multiple reaction components. The reaction components can be easily introduced through the liquid inlet connector 13, and the liquid inlet connector 13 can be connected to a reaction component storage container, which can improve the stability and efficiency of the spraying.

[0071] like Figure 11 The present invention also provides a gene sequencing reaction device 1000, comprising the aforementioned bio-slide reaction component loading device 100. This device can reduce the consumption of reaction components, including liquid addition / replacement technology, biochemical reaction area design, and fluid timing design.

[0072] Some specific embodiments of the present invention are described below with reference to the accompanying drawings.

[0073] Combine Figures 1 to 11The loading device 100 according to an embodiment of the present invention may include a multifunctional cutting head 10b and several dedicated cutting heads 10a. This loading device 100 can solve the following core problems: multiple reagent types, high consumption of important reagents (when switching reagents), and contamination between reagents.

[0074] Among them, the multifunctional blade head 10b is used for loading multiple reaction components in biochemical processes such as loading, MDA, barcoding, etc., and is used for loading buffer on the surface of the slide in the sequencing biochemical process.

[0075] The multifunctional blade head 10b is connected to a drive pump 20 (e.g., a syringe pump) and a first valve 31 (for switching reaction components). The multifunctional blade head 10b includes an exhaust port 1033. The clearance between the multifunctional blade head 10b and the slide is greater than that between the other blade heads (the dedicated blade head 10a), allowing the thickness of the liquid film sprayed by this blade head to be greater than that of the dedicated blade head 10a. When using this multifunctional blade head 10b to load buffer in a sequencing reaction, air isolation is not required before each syringe pump aspirates liquid, and liquid is directly applied after aspiration. When using this multifunctional blade head 10b to load reaction components in a loading / MDA / Barcode reaction, an air isolation column is required before each syringe pump aspirates liquid to prevent crosstalk and contamination between reaction components. When dispensing liquid from the blade head, the exhaust port 1033 should be opened first, and the air isolation column is discharged from the exhaust port 1033 of the multifunctional blade head 10b, not from the spray port 102. After the exhaust is completed, the liquid is squeezed out of the spray port 102, spraying the reaction components onto the biological slide 200.

[0076] The dedicated blade head 10a is used for loading reaction components in sequencing reactions. Each reaction component corresponds to a dedicated blade head 10a, and usually 4 to 5 dedicated blade heads 10a are required to complete the loading of reaction components.

[0077] A dedicated blade head 10a is connected to a syringe pump and associated piping. The gap between the dedicated blade head 10a and the bioslide 200 is smaller than the gap between the multifunctional blade head 10b and the bioslide 200. As a result, the thickness of the liquid film sprayed by the dedicated blade head 10a is smaller than that of the multifunctional blade head 10b, saving the cost of reaction components. During the reaction process, the syringe pump of the dedicated blade head 10a does not draw in an air barrier when aspirating liquid. When discharging liquid, the reaction components are directly discharged from the blade head, eliminating replacement and contamination issues. During the blade head priming process, a certain amount of air is first drawn from the blade head, forming an air barrier between the reaction components and the reaction components at the rear of the syringe pump. This air barrier is present throughout the sequencing process and is not exhausted.

[0078] In addition, the loading device 200 further includes an air knife 40: the air knife 40 is arranged at the front of the entire loading device 200, and is used to clear the reaction components or other waste liquid impurities above the carrier by blowing air.

[0079] The blade arrangement of the present invention is as follows: the blade for spraying the buffer solution is placed at the front (the position that first contacts the chip during spraying). This arrangement can significantly reduce contamination.

[0080] In addition, the gene sequencing reaction equipment 1000 of the present invention also includes: a hot cover, a slide platform and a temperature rise and fall module. The hot cover and the loading device 200 are fixed above the slide platform. When the liquid needs to be changed, the slide platform is cooled down and the liquid is changed by blowing or spraying. When a reaction is required, the slide platform is moved to the bottom of the hot cover, and the slide platform is sealed with the hot cover, and then heated after sealing. After the reaction is completed, the slide platform is first cooled down to below room temperature, and then the slide platform is moved to separate the slide from the hot cover.

[0081] The slide transfer, automation and timing of the present invention are as follows: the slide is transferred from the slide platform to the optical machine for photography by a robot or a linear module; after the photography is completed, the robot or the linear module retrieves the slide and the biochemical reaction is carried out again.

[0082] The present invention significantly reduces sequencing costs by controlling the thickness of the liquid film, with an estimated reduction of 50% to 80%. The spray fluid is integrated into the sequencer, and structural design controls contamination and evaporation of reaction components. The entire system is highly scalable, allowing for the addition of multiple reaction components to the multifunctional blade head 10b. For high-value reaction components, a dedicated blade head 10a is used, reducing reaction component consumption. This method can be applied to both floor-standing and desktop fluorescence imaging-based sequencing systems.

[0083] In the description of the present invention, it should be understood that the terms "center", "longitudinal", "lateral", "length", "width", "thickness", "up", "down", "front", "back", "left", "right", "vertical", "horizontal", "top", "bottom", "inside", "outside", "clockwise", "counterclockwise", "axial", "radial", "circumferential" and the like to indicate orientations or positional relationships based on the orientations or positional relationships shown in the accompanying drawings, and are only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore should not be understood as limiting the present invention.

[0084] Furthermore, the terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of the technical features being referred to. Thus, a feature defined as "first" or "second" may explicitly or implicitly include at least one such feature. In the description of the present invention, "plurality" means at least two, such as two, three, etc., unless otherwise specifically defined.

[0085] In the present invention, unless otherwise specified or limited, the terms "installed," "connected," "connect," "fixed," etc. should be understood in a broad sense. For example, they can refer to fixed connection, detachable connection, or integration; mechanical connection, electrical connection; direct connection, or indirect connection through an intermediate medium; internal communication between two components, or interaction between two components, unless otherwise specified. Those skilled in the art will understand the specific meanings of the above terms in the present invention based on specific circumstances.

[0086] In the present invention, unless otherwise expressly specified or limited, when a first feature is "above" or "below" a second feature, it may mean that the first and second features are in direct contact, or that the first and second features are in indirect contact through an intermediary. Furthermore, when a first feature is "above," "above," or "above" a second feature, it may mean that the first feature is directly above or diagonally above the second feature, or simply means that the first feature is at a higher level than the second feature. When a first feature is "below," "below," or "below" a second feature, it may mean that the first feature is directly below or diagonally below the second feature, or simply means that the first feature is at a lower level than the second feature.

[0087] In the description of this specification, the reference terms "one embodiment", "some embodiments", "example", "specific example", or "some examples" mean that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described can be combined in any one or more embodiments or examples in a suitable manner. In addition, those skilled in the art can combine and combine different embodiments or examples described in this specification and features of different embodiments or examples without contradiction.

[0088] Although the embodiments of the present invention have been shown and described above, it will be understood that the above embodiments are illustrative and are not to be construed as limitations on the present invention. A person skilled in the art may change, modify, replace and modify the above embodiments within the scope of the present invention.

Claims

1. A device for loading reaction components on a biological slide, wherein the reaction components include a sample generation component and / or a sample analysis component, the biological slide includes an open biological reaction layer, and the biological reaction layer includes biomolecules configured to chemically react with the reaction components, characterized in that: The loading device includes a reagent source for storing the reaction components, a driving mechanism, and multiple spraying heads. The driving mechanism is used to pump the reaction components into the spraying heads through the reagent source and spray the reaction components onto the biological reaction layer through a spray port. The multiple spraying heads include a dedicated head corresponding to a single reaction component and a multifunctional head that can selectively conduct with at least two reaction components. The spraying distance between the multifunctional head and the biological slide is greater than the spraying distance between the dedicated head and the biological slide.

2. The biological slide reaction component loading device according to claim 1, characterized in that: The driving mechanism includes a driving pump and a valve group connected between the driving pump, the reagent source and the corresponding spraying tool head, and the valve group includes: a first valve, the first valve corresponding to the multifunctional cutter head, the first valve having a liquid outlet and a plurality of liquid inlets, the liquid outlet being connected to the multifunctional cutter head, and the plurality of liquid inlets being respectively connected to different reaction components; The driving pump corresponding to the multifunctional cutter head is connected to the first valve and is configured to drive the liquid to be selectively fed into one of the multiple liquid inlets, and to drive the reaction components entering the first valve to be pumped to the multifunctional cutter head.

3. The biological slide reaction component loading device according to claim 2, characterized in that: The plurality of spraying cutter heads are arranged side by side, and the multifunctional cutter head is arranged downstream of the dedicated cutter head.

4. The biological slide reaction component loading device according to claim 2, characterized in that: It also includes an air knife, which has a gas inlet, an air jet and a gas flow channel connecting the gas inlet and the air jet, the gas inlet is used to introduce gas, the air jet is used to clean the biological reaction layer by blowing air, and the air jet is inclined in the direction of gas outlet away from the spraying port of the spraying knife head.

5. The biological slide reaction component loading device according to claim 2, characterized in that: The spraying tool head includes a tool head body having a reagent inlet, a spraying port, and a reagent flow channel connecting the reagent inlet and the spraying port. The reagent inlet is used to receive the reaction component.

6. The biological slide reaction component loading device according to claim 5, characterized in that: The reagent flow channel also includes a liquid guide groove, which is arranged on one side of the flow channel body of the reagent flow channel along the width direction, and each position of the liquid guide groove along the length direction is connected to the corresponding position of the flow channel body. The height dimension of the liquid guide groove is greater than the height dimension of the flow channel body, and the liquid guide groove is connected to the reagent inlet.

7. The biological slide reaction component loading device according to claim 6, characterized in that: The cutter head body also has an emptying port, which is connected to the liquid guide groove. The driving pump is configured to pump an air isolation column into the cutter head body and discharge the air isolation column through the emptying port before the multifunctional cutter head sprays different reaction components.

8. The biological slide reaction component loading device according to claim 2, characterized in that: The valve group further includes a second valve correspondingly connected to the special cutter head, and the driving pump is provided in a one-to-one correspondence with the second valve and the special cutter head.

9. The biological slide reaction component loading device according to any one of claims 1 to 8, characterized in that: The height of the spray port is not less than 0.01 mm and not more than 0.1 mm. Preferably, the height of the spray port is 0.04 mm. Alternatively, the spray tool head has a reagent flow channel, which is constructed as a flat long strip flow channel, and the height of the reagent flow channel is not less than 0.01 mm and not more than 0.1 mm. Preferably, the height of the reagent flow channel is 0.04 mm.

10. A gene sequencing reaction device, characterized in that: The device comprises a biological slide reaction component loading device according to any one of claims 1 to 9.

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