Biological sample pre-treatment apparatus

Abstract

The application discloses a biological sample pretreatment equipment and relates to the technical field of biological sample processing. The biological sample pretreatment equipment comprises a support assembly, a consumable warehouse module, a core reaction module and a liquid path module; the warehouse body of the consumable warehouse module is provided with a plurality of reagent positions for placing reagent containers and a plurality of system liquid positions for placing system liquid containers, and a reagent temperature control assembly is used for adjusting the temperature of the reaction reagent of the reagent position; the core reaction module comprises a reaction chamber and a reaction temperature control assembly, the reaction temperature control assembly is connected with the reaction chamber and is used for adjusting the sample incubation temperature of the reaction chamber; the liquid path module is communicated with the reaction chamber and is used for sucking the reagent of the reagent position and the system liquid of the system liquid position and transferring to the reaction chamber. The application provides the biological sample pretreatment equipment, can meet the large sample test demand, effectively improves the sample test efficiency, reduces the test cost, improves the stability and repeatability of the experimental results, and has small biological risk.

Description

Technical Field

[0001] This invention relates to the field of biological sample processing technology, and more particularly to a biological sample pretreatment device. Background Technology

[0002] In spatial analysis experiments, target RNA from tissues needs to be transferred from tissue slides to a capture chip using transcriptome probes for subsequent sequencing analysis to obtain spatially resolved molecular information. This process involves selecting whether to dewax the tissue slides (FF / FFPE) depending on the tissue type, followed by HE staining and scanning to preserve HE images for subsequent spatial information matching and visualization. Only after a series of complex reagent reactions can the target RNA transfer process take place. To achieve better transfer results, the reagent reaction procedures differ for different tissue types (FF / FFPE).

[0003] FF: Experimental procedure including destaining, washing, probe hybridization, washing, probe ligation, washing, and counterstaining; FFPE: Experimental procedures include decolorization, decrosslinking, cleaning, probe hybridization, cleaning, probe ligation, cleaning, and restaining.

[0004] The current experiment is conducted manually, involving various reagents (some of which require preheating), cleaning solutions, and other liquid aspiration and drainage operations. The process is lengthy (approximately 20 hours) and requires the operation of numerous pieces of equipment and the setting of different experimental conditions (37℃, 42℃, 50℃, 57℃, 95℃). Furthermore, it necessitates the repeated peeling and reapplying of membranes and sealing of the reaction chamber. The entire process is extremely complex and tedious. In addition, the varying skill levels and inconsistent experimental techniques of the operators lead to poor reproducibility of the results. The limited time and energy of the researchers prevent the simultaneous testing of multiple samples, resulting in low sample processing efficiency. Summary of the Invention

[0005] The main objective of this invention is to provide a biological sample pretreatment device that aims to improve the stability and repeatability of experimental results and increase the efficiency of biological sample pretreatment.

[0006] To achieve the above objectives, the present invention proposes a biological sample pretreatment device, comprising: Support components; A consumables compartment module is mounted on the support assembly. The consumables compartment module includes a compartment body and a reagent temperature control component. The compartment body is provided with several reagent positions for placing reagent containers and several system liquid positions for placing system liquid containers. The reagent temperature control component is located at the reagent positions and is used to adjust the temperature of the reaction reagents at the reagent positions. Several core reaction modules are mounted on the support assembly. Each core reaction module includes a reaction chamber and a reaction temperature control component. The reaction temperature control component is connected to the reaction chamber and is used to adjust the sample incubation temperature of the reaction chamber. A liquid path module is mounted on the support assembly. The liquid path module is connected to the reaction chamber and is used to draw the reagent from the reagent position and the system liquid from the system liquid position and transfer them into the reaction chamber.

[0007] Optionally, the reaction chamber includes a base, a sealing gasket, and an inlet / outlet pressure plate. The base is provided with a reaction groove for placing tissue slides. The inlet / outlet pressure plate is located at an inlet and an outlet that communicate with the liquid circuit module. The inlet / outlet pressure plate covers the groove of the reaction groove, and one end of the inlet / outlet pressure plate is hinged to the base. The other end of the inlet / outlet pressure plate is movably engaged with the base. The sealing gasket is located on the inner side of the inlet / outlet pressure plate and is used to abut against the tissue slide to form a sealed incubation space.

[0008] Optionally, the reaction temperature control component includes a first heating element, a first cooling element, a first heat sink, and an auxiliary cooling fan. The first heating element is directly or indirectly attached to the base or embedded in the base and is used to heat the base. The first cooling element is directly or indirectly attached to the base and is used to cool the base. The first heat sink is disposed on the first cooling element and is used to dissipate heat from the first cooling element. The auxiliary cooling fan is disposed on one side of the core reaction module and is used to assist in heat dissipation.

[0009] Optionally, the core reaction module further includes a shaking mechanism, the reaction chamber being mounted on the support assembly via the shaking mechanism. The shaking mechanism is used to adjust the tilt angle of the reaction chamber so that the gas in the reaction chamber is concentrated at a high position and the liquid is concentrated at a low position, and to swing the reaction chamber so that the reagents inside are in full contact with the sample.

[0010] Optionally, the shaking mechanism includes a first driving member and a crank mechanism. The input end of the crank mechanism is connected to the output end of the first driving member, and the output end of the crank mechanism is connected to a support plate. A plurality of the reaction chambers are mounted on the support plate, and both ends of the support plate are rotatably mounted on a support via a rotating shaft. The support is fixed to the support assembly.

[0011] Optionally, the core reaction module further includes a controller and an angle detection mechanism. The angle detection mechanism includes a reset plate and a position sensor. The reset plate is located on the outer end of the rotating shaft, and the position sensor is located on the support assembly and on one side of the reset plate. The position sensor is used to detect the tilt angle of the reset plate and generate an angle signal. The controller is electrically connected to the position sensor and the first drive unit respectively and is used to control the first drive unit to work according to the angle signal, so that the support plate and the reaction chamber on it can switch between a tilted position and a horizontal position.

[0012] Optionally, the consumables compartment module further includes a slide rail extending along a first direction, a slide seat slidably disposed on the slide rail, and a second driving member drivenly connected to the slide seat to drive the slide seat to move along the first direction, wherein the reagent position and the system liquid position are both disposed on the slide seat.

[0013] Optionally, the reagent temperature control component includes a second heating element, a second cooling component, and a second heat sink mounted on the second cooling component. At least one of the reagent positions is provided with the second heating element to form a cooled reagent position, and at least one of the reagent positions is provided with the second cooling component to form a cooled reagent position. The second heating element has a cooling range of RT-60℃; and / or the second cooling component has a cooling range of 4-10℃.

[0014] Optionally, the liquid circuit module includes a transfer mechanism, a needle holder, a sampling needle, a liquid aspiration pump, a liquid pipeline, and a valve group. The transfer mechanism is disposed on the support assembly, and a plurality of the sampling needles are disposed on the transfer mechanism via the needle holder. The transfer mechanism is at least used to drive the needle holder and the sampling needles thereon to move along a second direction, which is perpendicular to the first direction. The liquid outlet of the sampling needle is connected to the reaction chamber via the liquid pipeline. The liquid aspiration pump is connected to the liquid pipeline and is used to generate negative pressure to control the sampling needle to draw reagents and system liquids into the reaction chamber. The valve group is disposed on the liquid pipeline and is used to adjust the amount of reagents and system liquids used.

[0015] Optionally, the chamber is provided with a waste liquid level for placing a waste liquid collection container, the liquid pipeline is connected to the waste liquid collection container, and the liquid pipeline is provided with a drain pump for quickly transporting waste liquid into the waste liquid collection container.

[0016] In the technical solution of this invention, the biological sample pretreatment device includes a support assembly, a consumables compartment module, a core reaction module, and a liquid path module. The consumables compartment module is mounted on the support assembly and includes a compartment body and a reagent temperature control component. The compartment body has several reagent positions for placing reagent containers and several system liquid positions for placing system liquid containers. The reagent temperature control component is located at the reagent positions and is used to adjust the temperature of the reaction reagents at the reagent positions. Several core reaction modules are mounted on the support assembly. Each core reaction module includes a reaction chamber and a reaction temperature control component. The reaction temperature control component is connected to the reaction chamber and is used to adjust the sample incubation temperature of the reaction chamber. The liquid path module is mounted on the support assembly and is connected to the reaction chamber. It is used to aspirate the reagents at the reagent positions and the system liquids at the system liquid positions and transfer them into the reaction chamber. It is understood that this invention, by setting up a consumables compartment module, realizes the placement of reagent containers and system liquid containers. By setting up a reagent temperature control component, the temperature of the reaction reagent in the reagent position can be adjusted to the target temperature value, thereby preheating or precooling the reagent. This invention, by setting up a reaction chamber for incubation and a reaction temperature control component to regulate the temperature of the reaction chamber, enables the reaction chamber to form multiple incubation environments to meet different biological sample pretreatment test requirements. This invention, by setting up a liquid path module, can draw up the reagent in the reagent position and the system liquid in the system liquid position and transfer them into the reaction chamber to realize biological sample incubation. By using this biological sample pretreatment device, this invention can automatically process reagents, system liquids, etc., effectively improve the stability and repeatability of experimental results, and significantly improve the efficiency of biological sample pretreatment. Attached Figure Description

[0017] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on the structures shown in these drawings without creative effort.

[0018] Figure 1 This is a schematic diagram of the external structure of an embodiment of the biological sample pretreatment device of the present invention; Figure 2 This is a schematic diagram of the internal structure of an embodiment of the biological sample pretreatment device of the present invention; Figure 3 This is a schematic diagram of the structure of four core reaction modules at one angle in one embodiment of the biological sample pretreatment device of the present invention; Figure 4 This is a schematic diagram of the structure of four core reaction modules from another angle in one embodiment of the biological sample pretreatment device of the present invention. Figure 5This is a schematic diagram of the structure of a single core reaction module in one embodiment of the biological sample pretreatment device of the present invention; Figure 6 This is an exploded view of a single core reaction module in one embodiment of the biological sample pretreatment device of the present invention; Figure 7 This is a schematic diagram of the liquid path module in one embodiment of the biological sample pretreatment device of the present invention.

[0019] Explanation of icon numbers: 10. Support component; 20. Consumables compartment module; 30. Core reaction module; 40. Liquid circuit module; 21. Compartment body; 200. Reagent container; 300. System liquid container; 400. Waste liquid collection container; 500. Tissue slide; 31. Reaction chamber; 32. Reaction temperature control component; 311. Base; 312. Sealing gasket; 313. Inlet / outlet pressure plate; 313a. Inlet; 313b. Outlet; 321. First heating element; 322. First cooling component; 323. First radiator; 324. First driving element; 325. Crank mechanism; 326. Support; 327. Reset plate; 328. Position sensor; 329. Auxiliary cooling fan; 41. Transfer mechanism; 42. Needle holder; 43. Sampling needle; 44. Aspiration pump; 45. Liquid pipeline; 46. Valve group; 47. Drain pump.

[0020] The realization of the objective, functional features and advantages of the present invention will be further explained in conjunction with the embodiments and with reference to the accompanying drawings. Detailed Implementation

[0021] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only a part of the embodiments of the present invention, and not all of them. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0022] It should be noted that all directional indications (such as up, down, left, right, front, back, etc.) in the embodiments of the present invention are only used to explain the relative positional relationship and movement of each component in a certain specific posture (as shown in the figure). If the specific posture changes, the directional indication will also change accordingly.

[0023] In the description of this invention, it should also be noted that, unless otherwise explicitly specified and limited, the terms "installation," "connection," and "linking" should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral connection; they can refer to a mechanical connection or an electrical connection; they can refer to a direct connection or an indirect connection through an intermediate medium; and they can refer to the internal connection of two components. Those skilled in the art can understand the specific meaning of the above terms in this invention based on the specific circumstances.

[0024] Furthermore, the use of terms such as "first" and "second" in this invention is for descriptive purposes only and should not be construed as indicating or implying their relative importance or implicitly specifying the number of technical features indicated. Therefore, a feature defined with "first" or "second" may explicitly or implicitly include at least one of those features. The word "and / or" throughout the text means including three parallel solutions; for example, "A and / or B" includes solution A, solution B, or a solution that simultaneously satisfies A and B. The technical solutions of the various embodiments can be combined with each other, but this must be based on the ability of those skilled in the art to implement them. When the combination of technical solutions is contradictory or impossible to implement, it should be considered that such a combination of technical solutions does not exist and is not within the scope of protection claimed by this invention.

[0025] This invention proposes a biological sample pretreatment device.

[0026] Reference Figures 1 to 6 In one embodiment of the present invention, the biological sample pretreatment device includes a support component 10, a consumables compartment module 20, a core reaction module 30, and a liquid path module 40. The consumables compartment module 20 is disposed on the support component 10 and includes a compartment body 21 and a reagent temperature control component. The compartment body 21 has several reagent positions for placing reagent containers 200 and several system liquid positions for placing system liquid containers 300. The reagent temperature control component is disposed at the reagent positions and is used to adjust the temperature of the reaction reagents at the reagent positions. Several core reaction modules 30 are disposed on the support component 10. Each core reaction module 30 includes a reaction chamber 31 and a reaction temperature control component 32. The reaction temperature control component 32 is connected to the reaction chamber 31 and is used to adjust the sample incubation temperature of the reaction chamber 31. The liquid path module 40 is disposed on the support component 10 and is connected to the reaction chamber 31. It is used to aspirate the reagents at the reagent positions and the system liquids at the system liquid positions and transfer them into the reaction chamber 31.

[0027] In this embodiment, the support component 10 may include a base, a housing, a bracket, etc. The base is mainly used to install the consumables storage module 20, the core reaction module 30, etc. The housing can be installed on the base and cover the periphery of functional modules such as the consumables storage module 20 and the core reaction module 30 to protect these devices and devices. The bracket can be disposed inside the housing and is mainly used to support the fluid circuit module 40, etc. The specific structure of the support component 10 is not limited here.

[0028] In this embodiment, the chamber 21 can be an open-top, non-enclosed structure to facilitate the vertical insertion of the liquid path module 40 into the reagent container 200 and the system liquid container 300. Alternatively, a closed structure can be used, connecting the reagent container 200 and the system liquid container 300 via piping. Preferably, the chamber 21 can be configured with one waste liquid level, three system liquid levels, and fifteen reagent levels, wherein the waste liquid level is used to house the waste liquid collection container 400. This document does not limit the structure of the chamber 21.

[0029] It should be noted that the system fluids mainly refer to PBS, PBST, and pure water, primarily used for filling or cleaning instrument tubing. The waste level is mainly used to collect waste liquid generated from each channel. A level sensor can be installed at the bottom. When the waste liquid exceeds a certain height, there is a risk of overflow, and the system will prompt to empty the waste liquid, and testing cannot continue.

[0030] The reagent temperature control component may include heating and temperature regulation structures such as electric heating elements and / or cooling devices that can preheat and / or precool the reagent, and is not limited thereto.

[0031] To ensure the accuracy and stability of the experimental results, the reaction chamber 31 in this embodiment can adopt a sealed structure. The top or side of the sealed structure can be provided with a cover plate structure that can be opened and closed to facilitate the placement of tissue slides 500 containing biological samples.

[0032] In this embodiment, the structure of the reaction temperature control component 32 can be similar to that of the reagent temperature control component, or it can be a structure that can heat and / or cool the reaction chamber 31 so that the temperature of the reagent and sample inside reaches the target incubation conditions.

[0033] It is understood that this invention, by setting up a consumables compartment module 20, enables the placement of reagent containers 200 and system liquid containers 300. By setting up a reagent temperature control component, the temperature of the reaction reagents at the reagent position can be adjusted to the target temperature value, thereby preheating or precooling the reagents. This invention, by setting up a reaction chamber 31 for incubation and a reaction temperature control component 32 to regulate the temperature of the reaction chamber 31, enables the reaction chamber 31 to form various incubation environments, meeting different biological sample pretreatment testing requirements. This invention, by setting up a liquid path module 40, can draw reagents from the reagent position and system liquid from the system liquid position and transfer them into the reaction chamber 31 to achieve biological sample incubation. By employing this biological sample pretreatment device, this invention can automatically process reagents and system liquids, eliminating the need for manual operation, effectively improving the stability and repeatability of experimental results, and significantly improving the efficiency of biological sample pretreatment.

[0034] To further improve the stability and reproducibility of the experimental results, refer to Figures 2 to 6 In one embodiment, the reaction chamber 31 may include a base 311, a sealing gasket 312, and an inlet / outlet pressure plate 313. The base 311 is provided with a reaction groove for placing a tissue slide 500. The inlet / outlet pressure plate 313 is provided with an inlet 313a and an outlet 313b communicating with the liquid circuit module 40. The inlet / outlet pressure plate 313 covers the groove of the reaction groove, and one end of the inlet / outlet pressure plate 313 is hinged to the base 311, while the other end is movably engaged with the base 311. The sealing gasket 312 is provided on the inner side of the inlet / outlet pressure plate 313 and is used to abut against the tissue slide 500 to form a sealed incubation space. Alternatively, the sealing gasket 312 may also be provided on the tissue slide 500 and abut against it after the inlet / outlet pressure plate 313 is closed.

[0035] In this embodiment, the sealing gasket 312 is generally an irregular ring structure, but it can also be a regular ring, circle, square or polygon structure, etc. The sealing gasket 312 can be a sealing element made of flexible material such as silicone gasket, and the thickness is preferably 0.5mm, but is not limited here.

[0036] This invention provides a sealing gasket 312 on the inlet / outlet pressure plate 313. After the inlet / outlet pressure plate 313 is closed and tightened, the sealing gasket 312 abuts against the tissue slide 500 and surrounds the biological sample, forming a sealed incubation space. The inlet 313a and outlet 313b are located inside the sealing gasket 312. After the reagent enters, it can come into contact with the tissue and react, maintaining a stable environment and helping to improve the repeatability and stability of experimental results.

[0037] In one embodiment, such as Figures 2 to 6As shown, the reaction temperature control assembly 32 may include a first heating element 321, a first cooling element 322, and a first heat sink 323. The first heating element 321 is directly or indirectly attached to or embedded in the base 311 and is used to heat the base 311. The first cooling element 322 is directly or indirectly attached to the base 311 and is used to cool the base 311. The first heat sink 323 is disposed on the first cooling element 322 and is used to dissipate heat from the first cooling element 322. This arrangement allows the temperature inside the reaction chamber 31 to meet the temperature requirements of various experiments.

[0038] In this embodiment, the first heating element 321 may be a heating film, the first cooling component 322 may be a Peltier, and the first heat sink 323 may be a direct heat dissipation component mounted on the bottom of the Peltier.

[0039] In this embodiment, several auxiliary cooling fans 329 can be installed on one side of the core reaction module 30 to help regulate the temperature of the reaction chamber 31 and to dissipate heat from the various electronic components of the core reaction module 30 so that it can maintain normal operation.

[0040] It should be noted that decrosslinking is a high-temperature reaction, requiring 95°C. In this case, the heating film and Peltier can be controlled to work together. After the partial high-temperature reaction, the next low-temperature reaction needs to be carried out. At this time, the heating film can be controlled to stop working, and the Peltier can be controlled to cool down, so that the temperature in the reaction chamber 31 is controlled to the target temperature.

[0041] In one embodiment, the core reaction module 30 may further include a shaking mechanism. The reaction chamber 31 is disposed on the support assembly 10 via the shaking mechanism. The shaking mechanism is used to adjust the tilt angle of the reaction chamber 31 so that the gas in the reaction chamber 31 is concentrated at a high position and the liquid is concentrated at a low position, and to swing the reaction chamber 31 so that the reagents in it are in full contact with the sample.

[0042] Main reference Figure 4 In this embodiment, the shaking mechanism may include a first driving member 324 and a crank mechanism 325. The input end of the crank mechanism 325 is connected to the output end of the first driving member 324, and the output end of the crank mechanism 325 is connected to the support plate. A plurality of reaction chambers 31 are installed on the support plate, and the two ends of the support plate are respectively rotatably mounted on the support 326 via a rotating shaft. The support 326 is fixed on the support assembly 10.

[0043] The first driving component 324 can be a stepper motor, a cylinder, or a hydraulic cylinder, etc., and is not limited here. In addition, as a deformable method, other transmission mechanisms can be used to replace the crank mechanism 325. Any structure that can adjust the tilt angle of the reaction chamber 31 and shake it under the drive of the driving component is acceptable, and is not limited here.

[0044] In this invention, the operation of the first driving component 324 causes the crank mechanism 325 to move, controlling the tilt angle of the reaction chamber 31. This enables "liquid intake and discharge at a low position, and air intake and exhaust at a high position," effectively reducing the risk of air bubbles during liquid intake and discharge caused by "too thin a liquid surface." At the same time, the back-and-forth swing of the reaction chamber 31 can achieve full contact between the reagent and the sample tissue, thereby improving the reaction efficiency.

[0045] Based on the foregoing embodiments, further, mainly referring to Figure 4 The core reaction module 30 may further include a controller and an angle detection mechanism. The angle detection mechanism includes a reset plate 327 and a position sensor 328. The reset plate 327 is located on the outer end of the rotating shaft, and the position sensor 328 is located on the support assembly and on one side of the reset plate 327. The position sensor 328 is used to detect the tilt angle of the reset plate 327 and generate an angle signal. The controller is electrically connected to the position sensor 328 and the first drive unit 324, respectively, and is used to control the operation of the first drive unit 324 according to the angle signal, so that the support plate and the reaction chamber 31 on it can quickly switch between tilted and horizontal positions. This helps to improve the accuracy of controlling the swing of the reaction chamber 31 and ensure the repeatability and stability of the experimental structure.

[0046] In one embodiment, reference is made to Figure 1 and Figure 2 The consumables compartment module 20 may also include a slide rail extending along a first direction, a sliding seat slidably disposed on the slide rail, and a second driving component drivenly connected to the sliding seat to drive the sliding seat to move along the first direction. The reagent position and the system liquid position are both located on the sliding seat. In this way, it is convenient to pick up and put in the reagent container 200, the system liquid container 300, and the waste liquid collection container 400, etc., making the operation more efficient.

[0047] In this embodiment, the first direction can be the length or width direction of the biological sample pretreatment device, etc., and is not limited here. The entire body 21 of the consumables compartment module 20 can be driven by a drive mechanism such as a lead screw motor to realize the movement of entering and exiting the compartment.

[0048] In one embodiment, the reagent temperature control component is disposed inside the chamber 21, and may specifically include a second heating element, a second cooling component and a second heat sink mounted on the second cooling component. At least one reagent position is provided with a second heating element to form a cooled reagent position, and at least one reagent position is provided with a second cooling component to form a cooled reagent position.

[0049] In this embodiment, the cooling range of the second heating element can be set to RT-60℃. It can be an electric heating element such as a polyimide heating film, and a temperature sensor such as a PT1000 resistance thermometer can be configured to collect temperature data and feed it back to the control system in real time, so as to achieve more precise preheating temperature control of the reaction reagents.

[0050] In this embodiment, the cooling range of the second cooling component can be set to 4-10℃. It can use a Peltier semiconductor cooling device and be equipped with a turbine fan for heat dissipation to achieve efficient cooling. It is mainly used for onboard storage of reagents.

[0051] In one embodiment, please refer to Figure 2 and Figure 7 The liquid circuit module 40 may include a transfer mechanism 41, a needle holder 42, sampling needles 43, a suction pump 44, a liquid pipeline 45, and a valve assembly 46. The transfer mechanism 41 is mounted on the support assembly 10. Several sampling needles 43 are mounted on the transfer mechanism 41 via the needle holder 42. The transfer mechanism 41 is at least used to drive the needle holder 42 and the sampling needles 43 thereon to move along a second direction, which is perpendicular to the first direction. The second direction may be the height direction of the biological sample pretreatment device. The liquid outlet of the sampling needle 43 is connected to the reaction chamber 31 via the liquid pipeline 45. The suction pump 44 is connected to the liquid pipeline 45 and is used to generate negative pressure to control the sampling needle 43 to draw reagents and system liquid into the reaction chamber 31. The valve assembly 46 is mounted on the liquid pipeline 45 and is used to adjust the amount of reagents and system liquid. This configuration can further improve the efficiency of biological sample processing and further improve the stability and reproducibility of experimental results.

[0052] In this embodiment, as Figure 7 As shown, the liquid pipeline 45 is also connected to the waste liquid collection container 400, and the liquid pipeline 45 may be equipped with a drain pump 47 for quickly transporting the waste liquid to the waste liquid collection container 400.

[0053] In this embodiment, the sampling needle 43 may include several short needles for absorbing reagents and several long needles for absorbing system liquid. It is also equipped with a motor and other driving components to control the needle holder 42 to move in the Z direction (i.e., the second direction). The liquid circuit module 40 and the consumables compartment module 20 work together to realize various liquid addition and drainage operations.

[0054] In this embodiment, the valve assembly 46 may include several two-way solenoid valves, three-way solenoid valves, rotary distribution valves, etc., which can be installed at corresponding positions in the liquid pipeline 45 according to actual conditions. The liquid pipeline 45 may use Teflon tubing, etc., and is not limited here. Figure 7As shown, preferably, there are four core reaction modules 30, which can share a single liquid circuit system. All four modules use the suction function of the suction pump 44 to draw the target reagent into the reaction chamber 31. The sampling needle 43 is connected to the channel of the rotary dispensing valve via a Teflon tube. The common end of the rotary dispensing valve is connected to the downstream solenoid valve and the suction pump 44. When the target reagent needs to be drawn, the rotary dispensing valve switches to the corresponding reagent channel before the suction operation is performed. To control the tissue drying time in the reaction chamber 31, the liquid circuit module 40 can be equipped with a pre-suction pipeline to draw the target reagent from the reagent port to the inlet of the reaction chamber 31 in advance. Then, based on the number of channels participating in the reaction, the target reagent is divided into several equal portions using the air port of the solenoid valve, effectively controlling the reagent usage and cost.

[0055] In existing technology, a glass slide forms a reaction chamber using clips and a silicone pad, is sealed with a membrane, and then placed inside a PCR instrument for incubation. To change reagents, the sealing membrane must be removed, the reagent in the chamber aspirated with a pipette, new reagents added, the sealing membrane reapplied, and the incubation process repeated. The entire process is extremely cumbersome.

[0056] This invention can automatically replace reagents without frequently opening and closing the cover of the reaction chamber 31, effectively reducing the cumbersomeness of operation and significantly improving the efficiency of biological sample processing.

[0057] In addition, the biological sample pretreatment equipment is equipped with a control system, which includes a control board and a display screen and control buttons electrically connected to the control board.

[0058] Please combine Figures 1 to 7 In one application scenario, the specific experimental procedure can be as follows: ① Prepare the necessary reagents and consumables according to the experimental requirements; ② Click the start button on the display screen, and select the tissue type and the number of channels to be tested; ③ Refer to the interface prompts to load 500 units of reagents, system solutions, and tissue slides; ④ Click the start button to begin the test; ⑤ The system controls the needle holder 42 to descend, inserting the sampling needle 43 into the reagent and system liquid orifice; ⑥ The system controls the liquid path to draw the target reagent into the target reaction chamber 31 through the selected tissue type and channel, during which the shaking mechanism cooperates to tilt at various angles; ⑦ Provide the target temperature for the reaction chamber 31 according to the experimental requirements, and continue the incubation for a certain period of time; ⑧ Repeat the processes of liquid aspiration, liquid addition, liquid drainage, temperature-controlled incubation, cooling, and cleaning continuously; ⑨ After the experiment, remove 500 tissue slides, load blank slides, and proceed to the whole machine cleaning stage. After the cleaning is completed, pour out the waste liquid, remove the blank slides, and the equipment enters standby mode.

[0059] In summary, the biological sample pretreatment device of the present invention can automatically test multiple samples simultaneously. The present invention uses stable automated equipment actions to replace manual operation, which effectively improves stability and repeatability and minimizes biological risks.

[0060] The above description is merely an optional embodiment of the present invention and does not limit the patent scope of the present invention. All equivalent structural transformations made using the contents of the present invention's specification and drawings under the inventive concept of the present invention, or direct / indirect applications in other related technical fields, are included within the patent protection scope of the present invention.

Claims

1. A biological sample pretreatment device, characterized in that, include: Support components; A consumables compartment module is mounted on the support assembly. The consumables compartment module includes a compartment body and a reagent temperature control component. The compartment body is provided with several reagent positions for placing reagent containers and several system liquid positions for placing system liquid containers. The reagent temperature control component is located at the reagent positions and is used to adjust the temperature of the reaction reagents at the reagent positions. Several core reaction modules are mounted on the support assembly. Each core reaction module includes a reaction chamber and a reaction temperature control component. The reaction temperature control component is connected to the reaction chamber and is used to adjust the sample incubation temperature of the reaction chamber. A liquid path module is mounted on the support assembly. The liquid path module is connected to the reaction chamber and is used to draw the reagent from the reagent position and the system liquid from the system liquid position and transfer them into the reaction chamber.

2. The biological sample pretreatment device as described in claim 1, characterized in that, The reaction chamber includes a base, a sealing gasket, and inlet / outlet pressure plates. The base is provided with a reaction groove for placing tissue slides. The inlet / outlet pressure plates are located at the inlet and outlet of the liquid circuit module. The inlet / outlet pressure plates cover the groove of the reaction groove, and one end of the inlet / outlet pressure plates is hinged to the base. The other end of the inlet / outlet pressure plates is movably engaged with the base. The sealing gasket is located on the inner side of the inlet / outlet pressure plates and is used to abut against the tissue slides to form a sealed incubation space.

3. The biological sample pretreatment device as described in claim 2, characterized in that, The reaction temperature control component includes a first heating element, a first cooling element, a first heat sink, and an auxiliary cooling fan. The first heating element is directly or indirectly attached to the base or embedded in the base and is used to heat the base. The first cooling element is directly or indirectly attached to the base and is used to cool the base. The first heat sink is disposed on the first cooling element and is used to dissipate heat from the first cooling element. The auxiliary cooling fan is disposed on one side of the core reaction module and is used to assist in heat dissipation.

4. The biological sample pretreatment device as described in claim 1, characterized in that, The core reaction module also includes a shaking mechanism. The reaction chamber is mounted on the support assembly via the shaking mechanism. The shaking mechanism is used to adjust the tilt angle of the reaction chamber so that the gas in the reaction chamber is concentrated at a high position and the liquid is concentrated at a low position, and to swing the reaction chamber so that the reagents inside can fully contact the sample.

5. The biological sample pretreatment device as described in claim 4, characterized in that, The shaking mechanism includes a first driving member and a crank mechanism. The input end of the crank mechanism is connected to the output end of the first driving member, and the output end of the crank mechanism is connected to a support plate. A plurality of reaction chambers are installed on the support plate. Both ends of the support plate are rotatably mounted on a support via a rotating shaft. The support is fixed to the support assembly.

6. The biological sample pretreatment device as described in claim 5, characterized in that, The core reaction module also includes a controller and an angle detection mechanism. The angle detection mechanism includes a reset plate and a position sensor. The reset plate is located on the outer end of the rotating shaft. The position sensor is located on the support assembly and on one side of the reset plate. The position sensor is used to detect the tilt angle of the reset plate and generate an angle signal. The controller is electrically connected to the position sensor and the first drive component, respectively, and is used to control the first drive component to work according to the angle signal, so that the support plate and the reaction chamber on it can switch between a tilted position and a horizontal position.

7. The biological sample pretreatment device according to any one of claims 1-6, characterized in that, The consumables compartment module further includes a slide rail extending along a first direction, a slide seat slidably disposed on the slide rail, and a second driving member drivenly connected to the slide seat to drive the slide seat to move along the first direction. The reagent position and the system liquid position are both located on the slide seat.

8. The biological sample pretreatment device according to any one of claims 1-6, characterized in that, The reagent temperature control component includes a second heating element, a second cooling component, and a second heat sink mounted on the second cooling component. At least one of the reagent positions is provided with the second heating element to form a cooled reagent position, and at least one of the reagent positions is provided with the second cooling component to form a cooled reagent position. The second heating element has a cooling range of RT-60℃; and / or the second cooling component has a cooling range of 4-10℃.

9. The biological sample pretreatment device as described in claim 7, characterized in that, The liquid circuit module includes a transfer mechanism, a needle holder, a sampling needle, a liquid aspiration pump, a liquid pipeline, and a valve group. The transfer mechanism is mounted on the support assembly. A plurality of the sampling needles are mounted on the transfer mechanism via the needle holder. The transfer mechanism is at least used to drive the needle holder and the sampling needles thereon to move along a second direction, which is perpendicular to the first direction. The liquid outlet of the sampling needle is connected to the reaction chamber via the liquid pipeline. The liquid aspiration pump is connected to the liquid pipeline and is used to generate negative pressure to control the sampling needle to draw reagents and system liquids into the reaction chamber. The valve group is located on the liquid pipeline and is used to adjust the amount of reagents and system liquids used.

10. The biological sample pretreatment device as described in claim 9, characterized in that, The chamber is equipped with a waste liquid level for placing a waste liquid collection container. The liquid pipeline is connected to the waste liquid collection container, and the liquid pipeline is equipped with a drain pump for quickly transporting the waste liquid into the waste liquid collection container.

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