A hybridization device

Abstract

This application discloses a hybridization device, relating to the field of biohybridization equipment. The hybridization device includes a housing, a loading stage, a heating assembly, and a liquid guiding device. The top of the housing has at least one sample loading port; the loading stage has at least one mounting groove for mounting a glass slide, located below the sample loading port; the heating assembly is mounted on the mounting groove for heating the glass slide at the mounting groove; the liquid guiding device has a through-hole extending from top to bottom, forming a connecting guide channel and a reagent cavity from top to bottom. The liquid guiding device passes through the sample loading port and is detachably connected to the housing. The bottom of the liquid guiding device abuts against the glass slide, and the guide channel accommodates a pipette tip, allowing liquid in the pipette to drip from the tip into the reagent cavity. This hybridization device, through the arrangement of the sample loading port and the liquid guiding device, ensures consistency in the liquid loading position and area size on the glass slide, thereby standardizing the position of the cell suspension and facilitating manual operation.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of biological hybridization equipment, and particularly relates to a hybridization device. BACKGROUND

[0002] Fluorescence in situ hybridization (FISH) is a method for displaying the position of nucleic acid sequence in the cell nucleus or chromosome by using non-radioactive fluorescent substances and relying on the hybridization principle of nucleic acid probes. The technology has been widely applied in the fields of cytogenetics, tumor biology, gene positioning and other molecular diagnosis. The experimental process of the technology includes sample preparation, sample hybridization pretreatment, chromosome denaturation and probe hybridization, cell nucleus or chromosome staining, fluorescence microscope examination and analysis. For FISH operation, the time and temperature of the hybridization process will directly affect the hybridization efficiency of the target DNA, and currently some special FISH instruments are used for hybridization to ensure the controllability of the temperature.

[0003] At present, the laboratory adopts manual preparation of cell sample slides, adopts drop method, and sequentially is: cell sample resuspension counting, sample dilution, using a pipette to drop a certain volume of cell suspension on a slide, and then transferring the slide to the heating plate of the hybridization instrument for baking, evaporating the water content of the liquid drop at high temperature and tightly adhering the cells on the slide. According to the process, due to the limited microscope scanning time (not more than 2 hours), the prepared cell area is controlled within 6mm, and in the conventional drop method, the liquid drop is easy to diffuse, which leads to the fact that the cell area size cannot be effectively controlled, and the cell drop positions of the slides in a batch are not the same, which is not easy to standardize the slide preparation, affects the slide quality, and the manual operation steps are many and complicated. SUMMARY

[0004] Therefore, the purpose of the present application is to overcome the deficiencies in the prior art, and the present application provides a hybridization device which can standardize the position of the cell liquid drop, effectively control the size of the liquid drop / cell area, and facilitate standardized operation.

[0005] The present application provides:

[0006] A hybridization device, comprising:

[0007] A housing, at least one sample adding hole is opened in the top of the housing;

[0008] A loading table, at least one mounting groove for mounting a slide is arranged on the loading table, and the mounting groove is located below the sample adding hole;

[0009] A heating assembly mounted on the mounting groove for heating the slide at the mounting groove;

[0010] The liquid guiding device is provided with a through hole from top to bottom, and the through hole is formed with a communicating guide channel and a reagent cavity from top to bottom. The liquid guiding device is arranged in the sample adding hole and detachably connected with the shell. The bottom of the liquid guiding device abuts against the slide glass. The guide channel is used for accommodating a gun head of a pipette, so that the liquid in the pipette is dropped into the reagent cavity from the gun head.

[0011] In addition, the hybridization device according to the present application can also have the following additional technical features:

[0012] In some embodiments of the present application, the liquid guiding device comprises:

[0013] The through hole is arranged on the body;

[0014] n protrusions, the n protrusions are arranged at intervals along the circumference of the body, and the hole wall of the sample adding hole is provided with an insertion slot for the protrusion to pass through, wherein n is an integer greater than or equal to 1.

[0015] In some embodiments of the present application, when n = 2, two protrusions are arranged on two opposite sides of the body.

[0016] In some embodiments of the present application, an exhaust channel is arranged between the guide channel and the reagent cavity. A first groove is arranged on the side wall of the guide channel. The exhaust channel is in communication with the outside air through the first groove.

[0017] In some embodiments of the present application, the cross-sectional area of the exhaust channel gradually increases from top to bottom, and the exhaust channel is tapered.

[0018] In some embodiments of the present application, a limiting ring is arranged at the connection between the exhaust channel and the guide channel. The limiting ring is used to limit the height of the gun head inserted into the reagent cavity.

[0019] In some embodiments of the present application, the liquid guiding device further comprises a sealing ring, the sealing ring is sleeved on one end of the body close to the slide glass, and a part of the sealing ring abuts against the bottom of the body.

[0020] In some embodiments of the present application, a separation sheet is arranged at the communication between the guide channel and the reagent cavity. The separation sheet is provided with a penetration area for the gun head to pass through, and the penetration area is provided with at least three cuts. When the gun head is arranged in the penetration area, the penetration area is dispersed into multiple elastic edges along the cuts. When the gun head is separated from the penetration area, the multiple elastic edges are restored to be flat and spliced along the cuts.

[0021] In some embodiments of the present application, a second groove is formed on the sidewall of the guide channel, and the second groove is arranged from top to bottom to communicate with the external air.

[0022] In some embodiments of the present application, the cross-sectional area of the guide channel gradually decreases from top to bottom, and the guide channel is tapered.

[0023] In some embodiments of the present application, the heating assembly comprises a heat-conducting block and a heating element, a through hole is formed in the bottom of the mounting groove, the top end of the heat-conducting block is inserted into the through hole and supports the glass slide, a gap is formed between the glass slide and the bottom of the mounting groove, and the heating element is arranged at the bottom of the heat-conducting block.

[0024] In some embodiments of the present application, a flange is arranged at the bottom of the heat-conducting block, and a heat insulation pad is arranged between the flange and the bottom of the mounting groove.

[0025] In some embodiments of the present application, the through hole is arranged corresponding to the position of the sample adding hole, and / or a support column is arranged on the mounting groove, and the top of the support column abuts against the glass slide.

[0026] In some embodiments of the present application, the heating assembly further comprises a temperature detection element and a controller, the temperature detection element is arranged on the heat-conducting block, and the controller is electrically connected with the temperature detection element and the heating element respectively; the temperature detection element is used to obtain the temperature value of the heat-conducting block, and the controller controls the heating power of the heating element according to the obtained temperature value.

[0027] In some embodiments of the present application, the hybridization device further comprises a heat dissipation fan, an air inlet and an air outlet are arranged on the shell, a heat dissipation air duct is formed between the air inlet and the air outlet, the heat dissipation fan is arranged on the shell and located at the air inlet or the air outlet, and the heat dissipation air duct is located below the heat-conducting block.

[0028] In some embodiments of the present application, the hybridization device further comprises a flow guide, the flow guide is located in the heat dissipation air duct, and forms a flow guide air duct with the bottom of the loading table, the cross-sectional area of the flow guide air duct in the vertical direction is smaller than that of the heat dissipation air duct in the vertical direction, and the flow guide air duct is used to guide the air entering the air inlet to below the heat-conducting block.

[0029] In some embodiments of the present application, the flow guide is a flow guide plate, the flow guide plate is bent to form a trapezoidal groove, the groove opening of the trapezoidal groove faces the bottom of the shell, and the groove bottom of the trapezoidal groove is arranged close to one side of the loading table.

[0030] In some embodiments of the present application, the shell comprises a bottom shell and a top cover, the top cover and the bottom shell form a mounting space accommodating the loading platform and the heating assembly, and the top cover and the bottom shell are detachably connected, and the sample adding hole is arranged on the top cover.

[0031] The beneficial effects of the present application are as follows compared with the prior art: the present application provides a hybridization device, at least one sample adding hole is arranged on the top of the shell, and a liquid guiding tool is fixed at the sample adding hole. In use, the pipette is used to suck the cell suspension to be tested, the gun head of the pipette is inserted into the guide channel and the reagent cavity, and then the cell suspension to be tested is dropped on the glass slide of the loading platform, so that the cell suspension is accurately dropped on the same position of each glass slide through the liquid guiding tool. Through the arrangement of the sample adding hole and the liquid guiding tool, manual liquid dropping operation is facilitated, and the consistency of the liquid adding position and the liquid adding area size on the glass slide is ensured. Meanwhile, the heating assembly is installed on the mounting groove of the transfer platform, and is used for heating the glass slide at the mounting groove, so as to realize the heating function of the glass slide. BRIEF DESCRIPTION OF DRAWINGS

[0032] In order to more clearly illustrate the technical solutions of the embodiments of the present application, the following will briefly introduce the drawings needed to be used in the embodiments. It should be understood that the following drawings only show some embodiments of the present application, and therefore should not be regarded as a limitation on the scope. For those skilled in the art, other related drawings can also be obtained without creative labor.

[0033] Figure 1 A perspective view of the hybridization device in some embodiments of the present application is shown;

[0034] Figure 2 An exploded structural view of the hybridization device in some embodiments of the present application is shown;

[0035] Figure 3 A perspective view of the hybridization device in some embodiments of the present application is shown; Figure 2 An enlarged structural view of part A in the above view is shown;

[0036] Figure 4 A perspective view of the hybridization device in some embodiments of the present application is shown;

[0037] Figure 5 A sectional view of the hybridization device in some embodiments of the present application is shown; Figure 4 An enlarged structural view of part B in the above view is shown;

[0038] Figure 6 An enlarged structural view of part C in the above view is shown; Figure 5 An enlarged structural view of part C in the above view is shown;

[0039] Figure 7 Another exploded structural view of the hybridization device in some embodiments of the present application is shown;

[0040] Figure 8 A schematic diagram of the cooperation structure between the pipette and the hybridization device in some embodiments of the present application is shown;

[0041] Figure 9 A schematic diagram of the cooperation structure between the pipette and the hybridization device in some embodiments of the present application is shown; Figure 8 A schematic diagram of the cooperation structure between the pipette and the hybridization device in some embodiments of the present application is shown;

[0042] Figure 10 A schematic diagram of the cooperation structure between the pipette and the hybridization device in some embodiments of the present application is shown; Figure 9 A schematic diagram of the cooperation structure between the pipette and the hybridization device in some embodiments of the present application is shown;

[0043] Figure 11 A schematic diagram of the cooperation structure between the pipette and the hybridization device in some embodiments of the present application is shown;

[0044] Figure 12 A schematic diagram of the cooperation structure between the pipette and the hybridization device in some embodiments of the present application is shown;

[0045] Figure 13 A schematic diagram of the cooperation structure between the pipette and the hybridization device in some embodiments of the present application is shown;

[0046] Figure 14 A schematic diagram of the cooperation structure between the pipette and the hybridization device in some embodiments of the present application is shown; Figure 13 A schematic diagram of the cooperation structure between the pipette and the hybridization device in some embodiments of the present application is shown;

[0047] Figure 15 A schematic diagram of the cooperation structure between the pipette and the hybridization device in some embodiments of the present application is shown;

[0048] Figure 16 A schematic diagram of the cooperation structure between the pipette and the hybridization device in some embodiments of the present application is shown;

[0049] Figure 17 A schematic diagram of the cooperation structure between the pipette and the hybridization device in some embodiments of the present application is shown;

[0050] Figure 18 A schematic diagram of the cooperation structure between the pipette and the hybridization device in some embodiments of the present application is shown; Figure 17 A schematic diagram of the cooperation structure between the pipette and the hybridization device in some embodiments of the present application is shown;

[0051] Figure 19 A schematic diagram of the cooperation structure between the pipette and the hybridization device in some embodiments of the present application is shown;

[0052] Figure 20 A schematic diagram of the cooperation structure between the pipette and the hybridization device in some embodiments of the present application is shown;

[0053] Figure 21 A schematic diagram of the cooperation structure between the pipette and the hybridization device in some embodiments of the present application is shown.

[0054] Main element symbol explanation:

[0055] 100 - hybridization device; 110 - housing; 111 - top cover; 1111 - sample loading hole; 1112 - slot; 112 - bottom shell; 113 - air inlet; 114 - air outlet; 115 - heat dissipation air duct; 116 - diversion air duct; 120 - loading platform; 121 - mounting groove; 1211 - through hole; 1212 - gap; 122 - support column; 123 - gap; 130 - heating assembly; 131 - heat-conducting block; 1311 - flange; 1312 - blind hole; 132 - heating element; 133 - heat insulation pad; 134 - temperature detection element; 135 - controller; 140 - liquid guiding device; 141 - body; 1411 - through hole; 14111 - guide channel; 14112 - reagent cavity; 14113 - exhaust channel; 14114 - first groove; 14115 - second groove; 1412 - limiting ring; 1413 - isolation sheet; 14131 - penetration area; 14132 - cutout; 14133 - elastic edge; 142 - protrusion; 143 - sealing ring; 150 - heat dissipation fan; 160 - flow guide; 200 - glass slide; 210 - liquid loading area; 300 - pipette; 310 - gun head. DETAILED DESCRIPTION

[0056] Embodiments of the present application are described below in detail with reference to examples thereof illustrated in the accompanying drawings, wherein like or similar elements across the various figures are denoted by like or similar reference numerals, and any reference to the application in the description is to be construed as a reference to the entire application.

[0057] In the description of the present application, it is to be understood that the terms "center", "longitudinal", "lateral", "length", "width", "thickness", "upper", "lower", "front", "back", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", "clockwise", "counterclockwise", "axial", "radial", "circumferential", and the like, indicate relative or positional relationships based on the orientation or position shown in the drawings, and are merely used to facilitate the description of the present application and simplify the description, and therefore cannot be construed as indicating or implying that the devices or elements referred to must have a particular orientation, be constructed and operated in a particular orientation, and therefore cannot be construed as limiting the present application.

[0058] In addition, the terms "first", "second", "third", etc., are used only for descriptive purposes and cannot be construed as indicating or implying relative importance or implicitly indicating the number of technical features indicated. Therefore, the features defined with "first", "second", etc. can explicitly or implicitly include one or more of the features. In the description of the present application, the meaning of "a plurality of" is two or more, unless otherwise explicitly specified.

[0059] In the present application, unless specifically defined otherwise and limited, the terms "mount", "connect", "connection", "fixed", and like terms should be interpreted broadly, for example, can be fixed connection, can also be detachable connection, or integrated; can be mechanical connection, can also be electrical connection; can be directly connected, can also be indirectly connected through an intermediate medium, can be internal communication of two elements or interaction relationship between two elements. For those skilled in the art, the specific meaning of the above terms in the present application can be understood according to the specific circumstances.

[0060] In the present application, unless specifically defined otherwise and limited, the first feature is "on" or "under" the second feature. The first and second features can be in direct contact, or the first and second features can be in indirect contact through an intermediate medium. Moreover, the first feature "above", "over" and "on" the second feature can be that the first feature is directly above or obliquely above the second feature, or only indicates that the horizontal height of the first feature is higher than that of the second feature. The first feature "below", "under" and "under" the second feature can be that the first feature is directly below or obliquely below the second feature, or only indicates that the horizontal height of the first feature is less than that of the second feature.

[0061] Embodiments

[0062] As shown in Figure 1 , Figures 5 to 7 Embodiments of the present application provide a hybridization device 100, mainly used for fluorescence in situ hybridization technology. The hybridization device 100 comprises a shell 110, a loading platform 120, a heating assembly 130 and a liquid guide 140.

[0063] The top of the shell 110 is provided with at least one sample adding hole 1111, which is used to fix the position of the liquid guide 140. The loading platform 120 is provided with at least one mounting groove 121 for mounting the glass slide 200, and the mounting groove 121 is located below the sample adding hole 1111, so that the liquid adding position on the glass slide 200 is fixed.

[0064] The heating assembly 130 is mounted on the mounting groove 121 and used to heat the glass slide 200 at the mounting groove 121.

[0065] In combination with Figure 2 , Figure 14 and Figure 18As shown, the liquid guide 140 is provided with a through hole 1411 from top to bottom, the through hole 1411 is formed with a communicating guide channel 14111 and a reagent cavity 14112 from top to bottom, the liquid guide 140 is arranged in the sample adding hole 1111 and detachably connected with the shell 110, the bottom of the liquid guide 140 abuts against the slide glass 200, the guide channel 14111 is used for accommodating the gun head 310 of the pipette 300, for guiding the gun head 310 of the pipette 300 to reach the specified position, so that the liquid in the pipette 300 is dropped from the gun head 310 into the reagent cavity 14112, and at the same time, the bottom of the liquid guide 140 abuts against the slide glass 200 and a part of the gun head 310 is in the guide channel 14111 and the reagent cavity 14112, thereby the liquid is dropped on the slide glass 200 for drying.

[0066] Referring to Figures 8 to 10 , the hybridization device 100 provided by the embodiment of the present application is provided with the sample adding hole 1111 and the liquid guide 140, in use, the cell suspension to be measured is sucked by the pipette 300, the gun head 310 of the pipette 300 is inserted into the guide channel 14111 and the reagent cavity 14112, and then the cell suspension to be measured is dropped on the slide glass 200 of the loading platform 120, so that the cell suspension is accurately dropped on the same position of each slide glass 200 through the liquid guide 140, thereby standardizing the position of the cell suspension. At the same time, the slide glass 200 can be installed on the mounting groove 121 to be baked and dried by the heating assembly 130, so that the preparation of the sample slide glass 200 and the hybridization process can be performed on one device. In addition, the setting of the reagent cavity 14112 also makes the gun head 310 naturally drop and uniformly cover the liquid adding area 210 of all the slide glasses 200, avoiding the complex cover glass installation and removal work in the prior art, facilitating manual operation and improving the hybridization efficiency.

[0067] It should be noted that the liquid guide 140 is consumable and can be replaced. The number of the mounting grooves 121 is the same as the number of the sample adding holes 1111, the mounting grooves 121 can be selected to be 6 to 36, and in the embodiment, the number of the mounting grooves 121 is 8 and the number of the sample adding holes 1111 is also 8. In addition, the specific size of the mounting groove 121 can be designed to match most of the slide glasses 200 in the related art.

[0068] As shown in Figure 11 , optionally, the mounting groove 121 is provided with an opening 1212, and the opening 1212 is arranged to facilitate the taking and placing of the slide glass 200.

[0069] As shown in Figure 12 , Figure 13 and Figure 17As shown in some embodiments of the present application, optionally, the liquid guiding device 140 comprises a body 141 and n protrusions 142. Specifically, a through hole 1411 is formed on the body 141. The n protrusions 142 are arranged at intervals along the circumference of the body 141, and the hole wall of the sample adding hole 1111 is provided with a slot 1112 for the protrusion 142 to pass through, wherein n is an integer greater than or equal to 1.

[0070] In combination with Figure 2 , Figure 3 and Figure 6 As shown in the present embodiment, the n protrusions 142 and the slots 1112 are arranged in such a way that when the body 141 is assembled into the sample adding hole 1111, the body 141 is pressed downward, at this time the protrusions 142 pass through the slots 1112 and rotate the body 141 by a preset angle, such as 30 degrees, 60 degrees or 90 degrees. The protrusions 142 abut against the inner side wall of the shell 110 to prevent the liquid guiding device 140 from sliding out of the sample adding hole 1111. In addition, when the protrusions 142 abut against the inner side wall of the shell 110, the bottom of the body 141 abuts against the glass slide 200, at this time the contact position of the body 141 with the glass slide 200 has better sealing effect, which is beneficial to the heat preservation of the reagent cavity 14112.

[0071] In addition, it should be noted that the body 141 and the protrusions 142 can be integrally formed by polypropylene material, and the main body has a funnel-shaped cylindrical structure, and the diameter of the bottom can be selected as 6mm or 10mm. Of course, in other embodiments, the body 141 and the protrusions 142 can also be made of other materials.

[0072] Further, when n=2, two protrusions 142 are arranged on two opposite sides of the body 141. The two protrusions 142 are arranged on the two sides of the body 141, and the slots 1112 are also arranged in two. In this way, when the protrusions 142 abut against the inner side wall of the shell 110, the pressure of the bottom of the body 141 on the glass slide 200 is more balanced. It should be understood that n=4, n=6, etc. can also be used, for example, when n=4, two protrusions 142 are arranged on two opposite sides of the body 141, and the other two protrusions 142 are also arranged on two opposite sides of the body 141. Of course, when n=1, the body 141 can also be fixed. In the present embodiment, n=2 is preferred. In other embodiments, n=3, 4, 5, 6, 8, etc. can also be used, which will not be illustrated one by one here.

[0073] It should be noted that in other embodiments, the liquid guiding device 140 can only comprise the body 141, which is connected to the sample adding hole 1111 by interference fit. At this time, the material of the body 141 can be selected to be a rubber material with elasticity.

[0074] As Figures 17 to 19As shown, in one embodiment of the present application, an exhaust passage 14113 is optionally provided between the guide passage 14111 and the reagent cavity 14112, and a first groove 14114 is formed in the sidewall of the guide passage 14111, and the exhaust passage 14113 is in communication with the outside air through the first groove 14114.

[0075] Further, the cross-sectional area of the exhaust passage 14113 gradually increases from top to bottom, and the exhaust passage 14113 is conical. For example, the exhaust passage 14113 is conical.

[0076] In the present embodiment, when the tip 310 of the pipette 300 reaches the designated position in the liquid guide device 140, the provision of the exhaust passage 14113 and the first groove 14114 facilitates the discharge of water vapor in the reagent cavity 14112 after the reagent cavity 14112 and the cell suspension on the slide 200 are heated. In addition, when the tip 310 is in the liquid guide device 140, the first groove 14114 also ensures that the internal and external atmospheric pressures are equal, and the tip 310 performs liquid dripping.

[0077] In addition, it should be noted that the guide passage 14111 is also conical, specifically, the guide passage 14111 is conical, which matches the tip 310 of the pipette 300. Among them, the conical guide passage 14111 is wide at the top and narrow at the bottom. The taper of the conical guide passage 14111 is the same as or slightly larger than the taper of the tip 310 of the pipette 300, and the tip of the conical guide passage 14111 is used to achieve the positioning effect by contacting the tip 310.

[0078] As shown, Figure 18 Further, a limiting ring 1412 is provided at the junction of the exhaust passage 14113 and the guide passage 14111, and the limiting ring 1412 is used to limit the height of the tip 310 extending into the reagent cavity 14112. Specifically, the limiting ring 1412 is provided at the intersection of the guide passage 14111 and the exhaust passage 14113, that is, at the place with the smallest diameter, so as to directly abut and contact the tip 310, so that the limiting ring 1412 plays a limiting role, that is, after the tip 310 contacts this position, it reaches the set height.

[0079] As shown, Figure 14 and Figure 18As shown, in some embodiments of the present application, the liquid guiding device 140 optionally further comprises a sealing ring 143 sleeved on the body 141 near one end of the slide glass 200, and a portion of the sealing ring 143 abuts against the bottom of the body 141. In this way, when the body 141 is installed at the sample adding hole 1111, the sealing ring 143 can be in direct contact with the slide glass 200, improving the sealing effect between the bottom of the body 141 and the slide glass 200. Specifically, when installing, a downward pressure is applied to cause slight deformation of the sealing ring 143, and at the same time, the body 141 is rotated so that the protrusion 142 abuts against the inner side wall of the shell 110. Due to the limitation of the protrusion 142, the sealing ring 143 cannot restore to be out of contact with the slide glass 200, thereby achieving the sealing effect.

[0080] It should be noted that in the present embodiment, the sealing ring 143 can be made of silica gel material. Of course, in other embodiments, the sealing ring 143 can also be made of other materials with elastic function.

[0081] As shown in the drawings, Figures 12 to 16 In another embodiment of the present application, the present embodiment is different from the embodiment in which the exhaust passage 14113 is arranged on the body 141. Specifically, the connecting part of the guide passage 14111 and the reagent cavity 14112 is provided with a separation sheet 1413, the separation sheet 1413 is provided with a penetration area 14131 for the gun head 310 to pass through, and the penetration area 14131 is provided with at least three cutouts 14132.

[0082] As shown in the drawings, Figure 15 and Figure 16 When the gun head 310 is arranged in the penetration area 14131, the penetration area 14131 is dispersed into multiple petal-shaped elastic edges 14133 along the cutouts 14132, and when the gun head 310 is separated from the penetration area 14131, the multiple petal-shaped elastic edges 14133 restore to be flatly spliced along the cutouts 14132.

[0083] In the present embodiment, the separation sheet 1413 is a flat sheet, the penetration area 14131 is a circular area, and the cutouts 14132 are arranged at the center of the circular area. When the center of the separation sheet 1413 is subjected to an external force, it can be deformed to be concave inwardly, and when the external force is removed, the separation sheet 1413 can restore to be flatly spliced, thereby achieving the sealing effect, which can prevent the volatilization of the liquid in the reagent cavity 14112 during heating.

[0084] In addition, by using the isolation sheet 1413, the reagent cavity 14112 realizes the function of a hybridization reaction chamber, and the hybridization efficiency can be ensured even in the case of using a small amount of probe. At the same time, the isolation sheet 1413 replaces the cover glass type reaction chamber mode in the related art, and the operation of adding probe, placing cover glass, sealing, hybridization, removing sealing glue and cover glass in the related art is simplified to adding probe and hybridization, thereby greatly improving the operation convenience of the hybridization link.

[0085] The plurality of cuts 14132 can be in the shape of a cross or a rice character. In this embodiment, the plurality of cuts 14132 are in the shape of a cross. Of course, in other embodiments, the plurality of cuts 14132 can also be in other shapes.

[0086] It should be noted that the isolation sheet 1413 is made of plastic with a certain elastic recovery shape ability, such as polycarbonate.

[0087] As shown in Figure 12 Further, a second groove 14115 is formed in the side wall of the guide channel 14111, and the second groove 14115 is arranged from top to bottom and is used for air communication with the outside. Due to the arrangement of the second groove 14115, when the gun head 310 is in the liquid guide device 140, the internal and external air pressures are the same, and the situation that the gun head 310 of the differential pressure pipettor 300 cannot drip liquid is avoided.

[0088] As shown in Figure 14 and Figure 18 In any of the above embodiments of the present application, the cross-sectional area of the guide channel 14111 gradually decreases from top to bottom, and the guide channel 14111 is conical, and the taper of the guide channel 14111 is the same as or slightly larger than the taper of the gun head 310 of the pipettor 300. In this way, the guide channel 14111 is in contact with the gun head 310 at the smallest diameter, and the height of the gun head 310 extending into the reagent cavity 14112 is positioned.

[0089] In addition, it should be noted that for the liquid guide device 140 with the exhaust channel, the positioning of the cell sample is convenient, so that the cell sample is firmly adhered to the glass slide 200 during the baking stage, and is prevented from falling off. For the liquid guide device 140 with the isolation sheet 1413, the reagent cavity 14112 forms a sealed reaction chamber when hybridization is performed after the baking stage.

[0090] In the related art, there are two kinds of hybridization devices. One is heated by contact. This device uses a bottom plate heating method, collects temperature by a PT100 platinum resistance, amplifies by an operational amplifier circuit, and heats the entire slide. The other hybridization device uses an air circulation mode for heating. When in use, the sample slide needs to be placed in a wet box, and then the wet box is placed in the hybridization device. However, whether it is iron plate heating or air heating, there is a problem of large heating range and low temperature control precision, which leads to inconsistent temperature at different positions and poor consistency of hybridization efficiency.

[0091] To solve the problem of large heating range leading to inconsistent temperature at different positions, the embodiments of the present application adopt the following method:

[0092] As shown in Figures 4 to 7 , specifically, the heating assembly 130 includes a heat-conducting block 131 and a heating element 132. The bottom of the installation groove 121 is provided with a through hole 1211, the top end of the heat-conducting block 131 is arranged in the through hole 1211 and supported on the slide 200, there is a gap 123 between the slide 200 and the bottom of the installation groove 121, and the heating element 132 is arranged at the bottom of the heat-conducting block 131. The position of the heat-conducting block 131 corresponds to the position below the reagent cavity 14112, so that the heat of the heat-conducting block 131 is directly used for the liquid adding area 210 on the slide 200, thereby achieving the effect of concentrated heating. At the same time, the gap 123 between the slide 200 and the bottom of the installation groove 121 is formed, which avoids the heat transfer to the non-liquid adding area 210 of the slide 200 due to the heat conduction of the installation groove 121, and ensures the concentrated heating of the liquid adding area 210 on the slide 200.

[0093] Further, the through hole 1211 is arranged corresponding to the position of the sample adding hole 1111. In this way, after the heating element 132 heats and transfers to the heat-conducting block 131, the heating position is accurately matched to the position corresponding to the sample adding hole 1111, that is, the heating position is accurately matched to the position corresponding to the sample adding hole 1111, so that the heating position is close to the cell dropping position on the slide 200, accurate heating is realized, heat loss caused by unnecessary area heating is reduced, heating stability is improved, and the efficiency of hybridization variation is improved.

[0094] As shown in Figure 6 , in the above-mentioned embodiments of the present application, further, the bottom of the heat-conducting block 131 is provided with a flange 1311, and a heat insulation pad 133 is arranged between the flange 1311 and the bottom of the installation groove 121. In this way, the heat-conducting block 131 avoids transferring heat to the installation groove 121, reducing heat loss, that is, the heat-conducting block 131 is isolated from other components by the heat insulation pad 133, the heat dissipation from other components is maximally reduced, and the heat is concentrated as much as possible to be conducted from the inside of the heat-conducting block 131.

[0095] In this embodiment, a support column 122 can also be provided on the mounting groove 121, with the top of the support column 122 abutting against the glass slide 200. This arrangement allows the support column 122 and the heat-conducting block 131 to jointly support the glass slide 200, preventing uneven stress on the glass slide 200 from causing tilting or breakage, thus improving the reliability of the product.

[0096] It should be noted that the heating element 132 is an electronic component used for generating heat, and can be a PI heating film (Polyimide, PI), a silicone heating film, an infrared heating tube, a semiconductor element, etc. In this embodiment, the heating element 132 uses a PI heating film. Of course, in other embodiments, the heating element 132 can also be other electronic components. The heat-conducting block 131 is made of a material with high thermal conductivity, such as copper. Of course, the heat-conducting block 131 can also be made of other materials with high thermal conductivity.

[0097] like Figure 7 and Figure 21 As shown in the above embodiments of this application, the heating assembly 130 further includes a temperature detection element 134 and a controller 135. The temperature detection element 134 is disposed on the heat-conducting block 131, and the controller 135 is electrically connected to the temperature detection element 134 and the heating element 132 respectively.

[0098] Temperature sensing element 134 is used to acquire the temperature value of heat-conducting block 131, and controller 135 controls the heating power of heating element 132 based on the acquired temperature value. In this way, the operating temperature of heating element 132 can be controlled in real time to ensure the temperature of heat-conducting block 131, thereby ensuring hybridization quality. For example, controlling the temperature range of heat-conducting block 131 from 25°C to 100°C can complete the baking and hybridization steps.

[0099] Optionally, a blind hole 1312 is formed on the heat-conducting block 131, and a temperature sensing element 134 is installed in the blind hole 1312 for real-time monitoring of the temperature change of the heat-conducting block 131.

[0100] It should be noted that the controller 135 can use control elements or processors from related technologies, and the temperature detection element 134 is a temperature sensor, which can be various types of temperature sensors such as PT1000, PT100, and DS18B20. In this embodiment, a PT1000 temperature sensor is used.

[0101] like Figure 7 and Figure 20As shown, in some embodiments of this application, optionally, the hybridization device 100 further includes a cooling fan 150, an air inlet 113 and an air outlet 114 are provided on the housing 110, a heat dissipation air duct 115 is formed between the air inlet 113 and the air outlet 114, the cooling fan 150 is disposed on the housing 110 and located at the air inlet 113 or the air outlet 114, and the heat dissipation air duct 115 is located below the heat-conducting block 131.

[0102] In this embodiment, the cooling fan 150 is configured such that when it is turned on, airflow is generated inside the cooling duct 115, thereby cooling the heat-conducting block 131 and indirectly cooling the reagent cavity 14112. This allows the temperature of the glass slide 200 to drop back to room temperature within a certain period of time.

[0103] Preferably, the cooling fan 150 is located at the air outlet 114, which makes its air cooling effect better.

[0104] like Figure 20 As shown in the above embodiments of this application, the hybridization device 100 further includes a guide member 160, which is located within the heat dissipation duct 115 and forms a diversion duct 116 with the bottom of the loading platform 120. The cross-sectional area of ​​the diversion duct 116 in the vertical direction is smaller than that of the heat dissipation duct 115 in the vertical direction, and is used to divert the air entering through the air inlet 113 to the area below the heat-conducting block 131. The arrangement of the guide member 160 makes the diversion duct 116 formed with the bottom of the loading platform 120 a narrow duct, allowing the air to concentrate and flow closely to the heat-conducting block 131. According to Bernoulli's principle, when the air flows steadily and the pressure is the same, the air velocity is greater in areas with smaller cross-sectional areas than in areas with larger cross-sectional areas. This allows the air to quickly and effectively remove the heat from the heat-conducting block 131, thereby achieving cooling.

[0105] In this embodiment, the flow guide 160 is selected as a flow guide plate, which is bent to form a trapezoidal groove. The opening of the trapezoidal groove faces the bottom of the housing 110, and the bottom of the trapezoidal groove is located on the side close to the loading platform 120. This trapezoidal groove, while functioning as the flow guide 160, has a simple structure and is easy to manufacture.

[0106] like Figure 1 and Figure 7 As shown, in any embodiment of this application, optionally, the housing 110 includes a bottom shell 112 and a top cover 111. The top cover 111 and the bottom shell 112 form an installation space for accommodating the loading platform 120 and the heating assembly 130, and the top cover 111 and the bottom shell 112 are detachably connected. The sample feeding hole 1111 is opened on the top cover 111.

[0107] In the embodiment, the structure of the top cover 111 and the bottom shell 112 facilitates the mounting and dismounting of the slide 200 when the top cover 111 is dismounted from the bottom shell 112.

[0108] The method for using the hybridization device 100 is as follows: the slide 200 is placed on the mounting groove 121 of the mounting table 120, the top cover 111 is covered, the liquid guide tool 140 is passed through the sample adding hole 1111, a downward pressure is applied to the liquid guide tool 140, and the liquid guide tool 140 is rotated by a preset angle (for example, 90 degrees), and the mounting is completed. After the mounting is completed, the sample is added by using the gun head 310 of the matched pipette 300, and then the heating assembly 130 is started to heat.

[0109] The hybridization device 100 is provided with the sample adding hole 1111, so that the liquid adding areas 210 (cell areas) of each slide 200 are in the same position, and the user only needs to insert the gun head 310 of the pipette 300 into the liquid guide tool 140 (the liquid guide tool 140 is provided with the exhaust passage 14113) to add the cell suspension sample to be tested, thereby reducing the time for confirming the drop area of the slide by the user and improving the drop efficiency. After the slide is dropped, the pipette 300 is removed, and the slide can be immediately baked.

[0110] In addition, in the prior art, after the probe is added dropwise, a cover glass with a diameter of 10 mm is needed to be covered above the probe and the sample, a reaction space is formed by the surface tension, and a substance similar to glue is used to seal the periphery of the cover glass, so that the experimental cells and reagents are in a sealed space, and the processes of DNA denaturation and probe hybridization are performed in the sealed space. Before the sample is cleaned, the sealing glue and the cover glass need to be removed; because the sealing glue is solidified to form a seal after heating, a sharp tool (for example, a scalpel or forceps) needs to be used to carefully cut the glue and then lift the cover glass. It is worth noting that because the probe is in a mucous state and has a certain viscosity, air is easily introduced when the cover glass is placed, and bubbles are formed. The places covered by the bubbles cannot be hybridized because there is no probe, which causes the unevenness of the hybridized sample area and leads to experimental failure. When the cover glass is removed, a sharp tool needs to be used, which has an operation risk for the operator. Because the probe is relatively thick, the cover glass is also removed when the cover glass is removed, which leads to experimental failure.

[0111] However, the embodiment of the present application can continue to place the prepared cell suspension sample on the hybridization device 100 after the treatment before hybridization is completed, replace the liquid guide tool 140 with the exhaust channel 14113 with the liquid guide tool 140 with the isolation sheet 1413, and then add the probe for the reaction. The isolation sheet 1413 also replaces the cover glass type reaction chamber mode in the related art, and the operation of adding the probe, placing the cover glass, sealing the piece, hybridization, removing the sealing glue and the cover glass in the related art is simplified to adding the probe and hybridization, that is, the reaction program can be adjusted according to the experimental requirements of FISH in the related art, avoiding the complex cover glass installation and removal work in the prior art, facilitating manual operation, and improving the hybridization efficiency.

[0112] Finally, it should be noted that the liquid guide tool 140 can be made into multiple disposable tools, which are replaced after each use to avoid cross contamination between samples.

[0113] In the description of the present specification, the description of the terms "one embodiment", "some embodiments", "an example", "a specific example", or "some examples" and the like means that the specific features, structures, materials or characteristics described in connection with the embodiment or example are included in at least one embodiment or example of the present application. In the present specification, the illustrative description of the above terms does not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described can be combined in any appropriate manner in any one or more embodiments or examples. In addition, different embodiments or examples described in the present specification and the features of different embodiments or examples can be combined and combined by those skilled in the art without contradiction.

[0114] Although the embodiments of the present application have been shown and described above, it can be understood that the above embodiments are exemplary and cannot be understood as limiting the present application, and those skilled in the art can make changes, modifications, replacements and variations to the above embodiments within the scope of the present application.

Claims

1. A hybridization device, characterized by The hybridization device comprises: a housing, a top of the housing being provided with at least one sample loading hole; a loading platform, provided with at least one mounting groove for mounting a slide, the mounting groove being located below the sample loading hole; a heating assembly, comprising a heat-conducting block, the heating assembly being mounted on the mounting groove for heating the slide at the mounting groove; a liquid guiding tool, comprising a body and n protrusions, the liquid guiding tool being provided with a through hole penetrating therethrough from top to bottom, the through hole being formed with a communicating guide channel and a reagent cavity from top to bottom, the through hole being provided on the body, the n protrusions being arranged along the circumference of the body, and a hole wall of the sample loading hole being provided with an insertion slot for the protrusions to penetrate, wherein n is an integer greater than or equal to 1; the liquid guiding tool penetrates the sample loading hole and is detachably connected with the housing, a bottom of the liquid guiding tool abutting against the slide, the guide channel being used for accommodating a gun head of a pipette to enable liquid in the pipette to drip from the gun head into the reagent cavity; the communicating position of the guide channel and the reagent cavity is provided with a separation sheet, the separation sheet being provided with a penetration area for the gun head to penetrate, and at least three cuts being arranged on the penetration area; the housing is provided with an air inlet and an air outlet, a heat dissipation air duct being formed between the air inlet and the air outlet, the heat dissipation air duct being located below the heat-conducting block; the hybridization device further comprises a flow guiding member, the flow guiding member being located in the heat dissipation air duct and forming a drainage air duct with a bottom of the loading platform, a cross-sectional area of the drainage air duct along a vertical direction being smaller than a cross-sectional area of the heat dissipation air duct along the vertical direction, for guiding air entering from the air inlet to below the heat-conducting block.

2. The hybridization device of claim 1, wherein When n=2, two protrusions are arranged on two opposite sides of the body.

3. The hybridization device of claim 1, wherein an exhaust channel is arranged between the guide channel and the reagent cavity, a first groove is arranged on a side wall of the guide channel, and the exhaust channel is in communication with external air through the first groove.

4. The hybridization device of claim 3, wherein a cross-sectional area of the exhaust channel gradually increases from top to bottom, and the exhaust channel is tapered.

5. The hybridization device of claim 4, wherein a limiting ring is arranged at a connecting position of the exhaust channel and the guide channel, the limiting ring being used for limiting a height of the gun head extending into the reagent cavity.

6. The hybridization device of claim 1, wherein the liquid guiding tool further comprises a sealing ring, the sealing ring being sleeved on the body close to one end of the slide, and a part of the sealing ring abutting against a bottom of the body.

7. The hybridization device of claim 1, wherein when the gun head penetrates the penetration area, the penetration area is dispersed into multiple elastic edges along the cuts, and when the gun head is separated from the penetration area, the multiple elastic edges restore to a flat splicing state along the cuts.

8. The hybridization device of claim 1, wherein a second groove is arranged on the side wall of the guide channel, the second groove being arranged from top to bottom for communication with external air.

9. The hybridization device according to any one of claims 1 to 8, characterized in that a cross-sectional area of the guide channel gradually decreases from top to bottom, and the guide channel is tapered.

10. The hybridization device according to any one of claims 1 to 8, characterized in that The heating assembly further comprises a heating element, a through hole is formed in the bottom of the mounting groove, the top end of the heat-conducting block is inserted into the through hole and supported on the glass slide, a gap is formed between the glass slide and the bottom of the mounting groove, and the heating element is arranged on the bottom of the heat-conducting block.

11. The hybridization device of claim 10, wherein The bottom of the heat-conducting block is provided with a flange, and a heat insulation pad is arranged between the flange and the bottom of the mounting groove.

12. The hybridization device of claim 10, wherein The through hole is arranged corresponding to the position of the sample adding hole, and / or a supporting column is arranged on the mounting groove, and the top of the supporting column abuts against the glass slide.

13. The hybridization device of claim 10, wherein The heating assembly further comprises a temperature detection element and a controller, the temperature detection element is arranged on the heat-conducting block, and the controller is electrically connected with the temperature detection element and the heating element; the temperature detection element is used to obtain the temperature value of the heat-conducting block, and the controller controls the heating power of the heating element according to the obtained temperature value.

14. The hybridization device of claim 1, wherein The hybridization device further comprises a heat dissipation fan, and the heat dissipation fan is arranged on the shell and located at the air inlet or the air outlet.

15. The hybridization device of claim 1, wherein The flow guide is a flow guide plate, the flow guide plate is bent to form a trapezoidal groove, the groove opening of the trapezoidal groove faces the bottom of the shell, and the groove bottom of the trapezoidal groove is arranged close to one side of the loading table.

16. The hybridization device of claim 1, wherein The shell comprises a bottom shell and a top cover, the top cover and the bottom shell form a mounting space for accommodating the loading table and the heating assembly, the top cover and the bottom shell are detachably connected, and the sample adding hole is formed in the top cover.

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