Fully automatic transmission electron microscope tissue and cell processing instrument

Abstract

The present application provides a fully automatic transmission electron microscope tissue and cell processing instrument, comprising a base, on which a sample basket reaction module, a well plate reaction module, a waste liquid barrel and multiple reagent storage barrels are provided. The sample basket reaction module is provided with a sample basket group. The base is also provided with a pipetting module, which is provided with a movable pipette, and the pipette is provided with a pipette. The pipette is used to transfer liquid between the sample basket reaction module, the well plate reaction module, the waste liquid barrel and the reagent storage barrel, thereby solving the problem of automated cell and tissue culture.

Description

Technical Field

[0001] The present invention relates to the field of cell and tissue culture, in particular to a full-automatic transmission electron microscope tissue and cell processing instrument. Background Art

[0002] Disease pathology diagnosis is an important means of studying the etiology and pathogenesis of diseases, as well as the changes in the body's morphological structure, function, and metabolism during the course of the disease, and even its outcome. It mainly includes tissue pathology using optical microscopy imaging technology and ultrapathology using transmission electron microscopy technology. It is of great significance for the diagnosis, treatment, and prevention of diseases. The pathological diagnosis process usually requires a series of treatments on the tissue specimens submitted for examination, such as fixation, dehydration, transparency, wax impregnation, embedding, sectioning, staining, etc. The treatment process is numerous and involves many types of processing reagents with different physical and chemical properties. Some of these reagents are highly volatile and toxic. At present, tissue pathology has a full set of instruments and equipment covering all processing links, but ultrapathology processing instruments are rarely involved.

[0003] Existing techniques mostly rely on manual labor, making the tissue processing process cumbersome and requiring the use of multiple different types and concentrations of treatment fluids. This is time-consuming, labor-intensive, difficult, and prone to errors. Some reagents are highly volatile or toxic, potentially causing some degree of harm to the operator. Summary of the Invention

[0004] The present invention provides a fully automatic transmission electron microscope tissue and cell processing instrument, which solves the problem of automatic cell and tissue culture.

[0005] To solve the above technical problems, the technical solution adopted by the present invention is: a fully automatic transmission electron microscope tissue and cell processing instrument, including a base, on which a sample basket reaction module, a well plate reaction module, a waste liquid barrel and multiple reagent storage barrels are provided, the sample basket reaction module is provided with a sample basket group, and the base is also provided with a pipette module, the pipette module is provided with a movable pipette, and the pipette is provided with a pipette, and the pipette is used to transfer liquid between the sample basket reaction module, the well plate reaction module, the waste liquid barrel and the reagent storage barrel.

[0006] In a preferred solution, an outer cover is further provided, the base is arranged inside the outer cover, an inlet door and an HMI are provided on one side of the outer cover, and an exhaust pipe communicating with the internal space is provided on the top of the outer cover.

[0007] In a preferred embodiment, the pipetting module includes a base, an X-axis linear module is provided on the base, the X-axis linear module is provided with a first movable platform, the first movable platform is provided with a Y-axis linear module, the Y-axis linear module is provided with a second movable platform, the second movable platform is provided with a Z-axis linear module, the Z-axis linear module is provided with a third movable platform, the moving directions of the first movable platform, the second movable platform and the third movable platform are perpendicular to each other, and the pipette is provided on the third movable platform.

[0008] In a preferred embodiment, the sample basket reaction module is provided with a first water bath, above which is provided an openable first upper cover, in which is provided a heat-conducting container box, in which the sample basket group is placed, and which is provided with a protrusion for a pipette to enter.

[0009] In a preferred solution, the bottom of the protrusion is inclined so that the inner bottom of the protrusion is the lowest.

[0010] In a preferred embodiment, the sample basket group includes a basket rack, the edge of the basket rack is provided with a side guard column, and the center of the basket rack is provided with a central guard column. The side guard columns and the central guard column divide the sample basket group into multiple areas, each area is provided with a stacked sample basket, and each sample basket is provided with multiple culture areas.

[0011] In a preferred embodiment, the well plate reaction module includes a base frame, a rotatable swinging platform is provided on the base frame, the swinging platform is provided with a second water bath, a culture block is provided in the second water bath, the culture block is provided with multiple culture tanks, a rotatable upper cover rotating shaft is provided on one side of the swinging platform, a second upper cover is provided above the second water bath, and one end of the second upper cover is connected to the upper cover rotating shaft.

[0012] In a preferred solution, the upper ends of the reagent storage barrel and the waste liquid barrel are provided with openable covers.

[0013] In the preferred scheme, a first linear cylinder is provided on one side of the pipette of the pipette module, the first linear cylinder is provided with a movable seat plate, and a sleeve is provided, the sleeve is connected to the seat plate, a retractable sleeve rod is provided in the sleeve, and an end of the sleeve rod extending outward is provided with a pushing cone head eccentric to the axis of the sleeve rod, a through suction hole is provided in the center of the cover body, a first turning petal and a second turning petal are provided at the suction hole, the first turning petal and the second turning petal are hinged in the middle, a shielding piece is provided at one end of the first turning petal and the second turning petal, the two shielding pieces are closed to close the suction hole, an avoidance through groove is provided on the side wall of the cover body, the other end of the first turning petal and the second turning petal passes through the avoidance through groove and is provided with a slot portion, the pushing cone head is inserted into the slot portion to open the shielding piece, and a connecting ear is provided at one end of each shielding piece away from the slot portion, a spring is connected between the two connecting ears, and a stop portion is provided at the upper end of the pushing cone head.

[0014] In the preferred solution, a guide protrusion is provided on the outer wall of one end of the sleeve rod away from the pushing cone head, a through spiral groove is provided on the side wall of the sleeve, the guide protrusion is inserted into the spiral groove, and a second linear cylinder is also provided. The cylinder rod of the second linear cylinder is connected to a transition sleeve, an annular groove is provided on the end of the transition sleeve, and a bayonet is provided on the side wall of the sleeve rod, which slides in the annular groove.

[0015] The beneficial effects of the present invention are as follows: a sample basket reaction module and a well plate reaction module are provided, which can realize the culture of tissues and monolayer adherent cells; the sample basket group is provided with multiple sample baskets, and each sample basket is provided with multiple culture areas, which can realize high-throughput batch processing of samples; equipped with an XYZ three-axis motion module, the pipette can realize free movement in three-dimensional space, and realize automated sample addition, cleaning and drainage; the reagent barrel and reaction tank adopt a closed design to prevent toxic gas volatilization and pollution; the improved scheme adopts a push cone head to trigger the cover inlet and outlet opening mechanism of the reagent barrel and waste liquid barrel in advance, thereby reducing the beat time of each sample addition and drainage, and improving overall efficiency. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] The present invention will be further described below with reference to the accompanying drawings and examples.

[0017] Figure 1 It is a schematic diagram of the present invention.

[0018] Figure 2 It is an internal schematic diagram of the present invention.

[0019] Figure 3 This is a structural diagram of the pipetting module.

[0020] Figure 4 This is the layout diagram of the base table.

[0021] Figure 5 This is the external view of the sample basket reaction module.

[0022] Figure 6 This is a diagram of the interior of the sample basket reaction module.

[0023] Figure 7 It is a schematic diagram of the present invention.

[0024] Figure 8 This is a diagram of the sample basket group structure.

[0025] Figure 9 This is the structural diagram of the well plate reaction module.

[0026] Figure 10 This is a diagram of the interior of the well plate reaction module.

[0027] Figure 11 This is a schematic diagram of a reagent barrel.

[0028] Figure 12 Schematic diagram of the sleeve rod extending.

[0029] Figure 13 Schematic diagram of the rod retraction.

[0030] Figure 14 This is the first straight line cylinder leakage state diagram.

[0031] Figure 15It is a cross-sectional view of the interior of the sleeve.

[0032] Figure 16 It is a schematic diagram of triggering the suction hole blocking mechanism.

[0033] Figure 17 This is a schematic diagram of the liquid suction hole being blocked.

[0034] Figure 18 This is a schematic diagram of the suction hole opening.

[0035] In the figure: base 1; pipetting module 2; base 201; X-axis linear module 202; first moving stage 203; Y-axis linear module 204; second moving stage 205; Z-axis linear module 206; third moving stage 207; reagent storage barrel 3; spare reagent barrel 301; cover 302; suction hole 303; avoidance through-groove 304; first flap 305; second flap 306; slot portion 307; shielding piece 308; connecting ear 309; spring 310; sample basket reaction module 4; first water bath 401; first upper cover 402; container box 403; protrusion 404; pipette 5; pipette 501; clamping device 502; spiral groove 503; guide protrusion 504; well plate reaction module 6; base frame 601; swing table 602; second upper cover 603; upper cover rotation axis 6 04; culture block 605; culture tank 606; second water bath 607; cooling and heating module 608; flip motor 609; tilt motor 610; first synchronous belt mechanism 611; second synchronous belt mechanism 612; pipette rack 7; waste liquid bucket 8; sample basket assembly 9; basket rack 901; side guard column 902; central guard column 903; sample basket 904; culture area 905; cover plate 906; pressure plate 907; through hole 908; handle 909; outer cover 10; injection door 1001; HMI 1002; exhaust duct 1003; first linear cylinder 11; seat plate 1101; sleeve 1102; sleeve rod 1103; push cone head 1104; transition sleeve 1105; second linear cylinder 1106; annular groove 1107; bayonet 1108; stopper 1109; adapter 1110. DETAILED DESCRIPTION

[0036] Example 1:

[0037] like Figure 1-18 In the invention, a fully automatic transmission electron microscope tissue and cell processing instrument includes a base 1, on which are provided a sample basket reaction module 4, a well plate reaction module 6, a waste liquid barrel 8 and multiple reagent storage barrels 3, a sample basket group 9 is provided in the sample basket reaction module 4, and a pipetting module 2 is also provided on the base 1. The pipetting module 2 is provided with a movable pipette 5, and the pipette 5 is provided with a pipette 501. The pipette 5 is used to transfer liquid between the sample basket reaction module 4, the well plate reaction module 6, the waste liquid barrel 8 and the reagent storage barrel 3.

[0038] The sample basket reaction module 4 can be used to culture conventional tissues, and the well plate reaction module 6 can be used to culture monolayer adherent cells.

[0039] The multiple reagent storage barrels 3 are arranged in a matrix, including alcohols of different concentrations and other commonly used reagents. A plurality of empty spare reagent barrels 301 are provided on the side, and new special reagents can be temporarily added according to the situation.

[0040] The pipetting module 2 is a Cartesian multi-axis moving mechanism that allows the pipette 5 to move in the X, Y, and Z directions. The pipette 5 can absorb the reagent in the reagent storage barrel 3 by connecting to negative pressure, discharge it by positive pressure, and add it to the sample basket reaction module 4 or the well plate reaction module 6, or absorb the waste liquid in the sample basket reaction module 4 and the well plate reaction module 6 and discharge it into the waste liquid barrel 8 for cleaning or recycling.

[0041] A pipette rack 7 is provided on the base 1 near the bottom of the initial position of the pipette 5. The pipette rack 7 includes a plurality of socket structures, which can hold a plurality of clean pipettes 501 for easy replacement.

[0042] In the preferred embodiment, an outer cover 10 is further provided, the base 1 is arranged inside the outer cover 10, an injection door 1001 and an HMI 1002 are provided on one side of the outer cover 10, and an exhaust pipe 1003 communicating with the internal space is provided on the top of the outer cover 10.

[0043] The side of the outer cover 10 is integrated with a control cabinet power switch and an emergency stop button, and the top of the outer cover 10 is provided with a status display light.

[0044] In the preferred embodiment, the pipetting module 2 includes a base 201, an X-axis linear module 202 is provided on the base 201, the X-axis linear module 202 is provided with a first movable platform 203, the first movable platform 203 is provided with a Y-axis linear module 204, the Y-axis linear module 204 is provided with a second movable platform 205, the second movable platform 205 is provided with a Z-axis linear module 206, the Z-axis linear module 206 is provided with a third movable platform 207, the moving directions of the first movable platform 203, the second movable platform 205 and the third movable platform 207 are perpendicular to each other, and the pipette 5 is provided on the third movable platform 207.

[0045] The X-axis linear module 202, Y-axis linear module 204, and Z-axis linear module 206 include a lead screw and slide rail mechanism. Servo motors can be used to drive the lead screws, and nuts attached to the lead screws drive the linear movement of each stage. The servo motors monitor the number of pulses emitted, thereby calculating the real-time position of each stage. Sensors can also be added to precisely control the position.

[0046] In a preferred embodiment, the sample basket reaction module 4 is provided with a first water bath 401, an openable first upper cover 402 is provided above the first water bath 401, a heat-conducting container box 403 is provided in the first water bath 401, the sample basket group 9 is placed in the container box 403, and the container box 403 is provided with a protrusion 404 for the pipette 501 to enter.

[0047] The sample basket reaction module 4 has a mounting base. Inside, near the bottom of the first water bath 401, there are cooling and heating devices to control the temperature of the liquid in the first water bath 401. The temperature is monitored by sensors. The body is equipped with thermal insulation and an external heat shield.

[0048] The side wall of the first water bath 401 is provided with three outer recesses, one of which is used to avoid the protrusion 404 , and the other two are convenient for fingers to take and place the sample basket set 9 .

[0049] In a preferred embodiment, the bottom of the raised portion 404 is inclined so that the inner bottom of the raised portion 404 is the lowest.

[0050] Due to the inclination, the bottom of the raised portion 404 is at the lowest point of the container box 403 , and the pipette 501 can completely absorb the liquid, thus reducing residual waste liquid.

[0051] In a preferred embodiment, the sample basket assembly 9 includes a basket rack 901, with side guard columns 902 provided at the edge of the basket rack 901 and a central guard column 903 provided in the center of the basket rack 901. The side guard columns 902 and the central guard column 903 divide the sample basket assembly 9 into multiple areas, each area is provided with a stacked sample basket 904, and each sample basket 904 is provided with multiple culture areas 905.

[0052] The side guard column 902 is a folded-angle body, the central guard column 903 is a cross-shaped body, the sample basket 904 is a rectangle, and the corners are clamped at the side guard column 902 and the central guard column 903. The sample basket 904 is a hollow structure, and a porous cover plate 906 is placed on the top sample basket 904.

[0053] A pressure plate 907 is also provided, and the pressure plate 907 has through holes 908 in various areas. A through hole is provided in the center of the pressure plate 907 and is sleeved on the central blocking column 903. The corners are clamped in the concave corners of the side blocking column 902. The pressure plate 907 presses the sample basket 904 to prevent the sample basket 904 from floating up. A threaded hole is provided at the upper end of the central blocking column 903 and a handle 909 is installed to facilitate picking up and placing by hand.

[0054] In the preferred embodiment, the well plate reaction module 6 includes a base frame 601, a rotatable swinging platform 602 is provided on the base frame 601, the swinging platform 602 is provided with a second water bath 607, a culture block 605 is provided in the second water bath 607, the culture block 605 is provided with multiple culture tanks 606, a rotatable upper cover rotating shaft 604 is provided on one side of the swinging platform 602, a second upper cover 603 is provided above the second water bath 607, and one end of the second upper cover 603 is connected to the upper cover rotating shaft 604.

[0055] A cooling and heating module 608 is provided at the lower end of the swing platform 602 . The cooling and heating module 608 includes a cooling plate, a heating device, etc. Liquid can be added to the second water bath 607 to conduct heat to the culture block 605 .

[0056] The base body 601 is also equipped with a tilting motor 609 and a tilting motor 610. A first synchronous belt mechanism 611 and a second synchronous belt mechanism 612 are provided at the side of the base body 601. The tilting motor 609 drives the upper cover rotation shaft 604 via the first synchronous belt mechanism 611, thereby tilting and opening the second upper cover 603. The tilting motor 610 drives the swing platform 602 via the second synchronous belt mechanism 612 to tilt a certain angle, facilitating the pipette 5 to completely aspirate waste liquid. The swing platform 602 can tilt and oscillate back and forth to achieve certain specialized culture conditions.

[0057] In a preferred embodiment, an openable cover 302 is provided on the upper ends of the reagent storage barrel 3 and the waste liquid barrel 8 .

[0058] A clamping device 502 is provided on one side of the pipette 5, and a gripping portion is provided in the center of the cover 302 for gripping by the clamping device 502. Before each aspiration of the reagent by the pipette 501, the pipetting module 2 needs to move the clamping device 502 to the top of the cover 302, move down and pick up the cover 302, then move the clamping device 502 aside, and the pipette 501 moves over and down into the reagent storage barrel 3 or waste liquid barrel 8 to complete the aspiration or discharge operation. The cover 302 is then closed to prevent the reagent or contaminating liquid from evaporating.

[0059] Since the lid needs to be opened each time the reagent is aspirated or discharged, and the position sensor needs to wait for a while to confirm the signal in place, a lot of cycle time is wasted.

[0060] In the preferred embodiment, a first linear cylinder 11 is provided on one side of the pipette 5 on the pipetting module 2. The first linear cylinder 11 is provided with a movable base plate 1101 and a sleeve 1102. The sleeve 1102 is connected to the base plate 1101. A retractable sleeve rod 1103 is provided in the sleeve 1102. One end of the sleeve rod 1103 extending outward is provided with a pushing cone head 1104 eccentric to the axis of the sleeve rod 1103. A through liquid suction hole 303 is provided in the center of the cover body 302. A first rotary flap 305 and a second rotary flap 306 are provided at the liquid suction hole 303. The first rotary flap 305 and the second rotary flap 306 are hinged in the middle. A shielding piece 308 is provided at one end of the first turning flap 305 and the second turning flap 306, and the two shielding pieces 308 are closed to close the liquid suction hole 303. An avoidance through groove 304 is provided on the side wall of the cover body 302. The other end of the first turning flap 305 and the second turning flap 306 passes through the avoidance through groove 304 and is provided with a slot portion 307. The pushing cone head 1104 is inserted into the slot portion 307 to open the shielding piece 308. A connecting ear 309 is provided at one end of each shielding piece 308 away from the slot portion 307. A spring 310 is connected between the two connecting ears 309. A stop portion 1109 is provided at the upper end of the pushing cone head 1104.

[0061] Since the reagent storage barrels 3 are densely arranged and the size of the cover 302 is limited, the pushing cone head 1104 needs to be as close to the pipette 501 as possible. However, since the root of the pipette 501 and the pipette 5 body are larger than the aspiration tip, the pushing cone head 1104 may collide with the pipette 5 and the pipette 501 when it is retracted.

[0062] In the preferred solution, a guide protrusion 504 is provided on the outer wall of one end of the sleeve rod 1103 away from the pushing cone head 1104, and a through spiral groove 503 is provided on the side wall of the sleeve 1102, and the guide protrusion 504 is inserted into the spiral groove 503. A second linear cylinder 1106 is also provided, and the cylinder rod of the second linear cylinder 1106 is connected to a transition sleeve 1105, and an annular groove 1107 is provided at the end of the transition sleeve 1105. A bayonet 1108 is provided on the side wall of the sleeve rod 1103, and the bayonet 1108 is stuck in the annular groove 1107 and slides.

[0063] The pipette 5 and the first linear cylinder 11 are both mounted on the third moving platform 207 .

[0064] The outer wall of the sleeve 1102 is provided with a connecting seat connected to the base plate 1101. Initially, the sleeve rod 1103 is in a retracted state, and the push cone head 1104 is biased away from the pipette 501. When liquid needs to be transferred, the first linear cylinder 11 is in a ventilated state, so that the sleeve 1102 is at the lower end. Then, the second linear cylinder 1106 is ventilated to drive the sleeve rod 1103 to extend. Due to the guiding effect of the spiral groove 503 on the guide protrusion 504, and the presence of the transition sleeve 1105 allowing the sleeve rod 1103 to rotate relative to the second linear cylinder 1106, the push cone head 1104 descends and rotates to approach the pipette 501, and the lowermost end of the push cone head 1104 is lower than the lowermost end of the pipette 501. At this time, the third movable platform 207 descends, and the push cone 1104 descends and inserts into the slot portion 307. The guide section at the lower end of the push cone 1104 opens the slot portion 307 so that the shielding piece 308 at the other end is also opened, exposing the suction hole 303. As the third movable platform 207 continues to descend, the pipette 501 eventually passes through the suction hole 303 unimpeded and enters the interior of the reagent storage barrel 3 or the waste liquid barrel 8. As the third movable platform 207 continues to descend to the set position, at this time, the three-position five-way electromagnetic reversing valve controlling the first linear cylinder 11 is in a neutral discharge state, the seat plate 1101 is in a state without air pressure and can move freely, the pipette 501 continues to descend, and the stopper 1109 contacts the slot portion 307 and is stopped, preventing the push cone 1104 from continuing to descend and interfering with other mechanisms.

[0065] During the whole process, the third movable platform 207 is in a continuous descending process, without any lateral movement and without the need to clamp the cover body, thus saving a lot of time and improving the efficiency of each suction and discharge, thereby greatly reducing the total cycle time.

[0066] After the pipette 501 is removed, the first linear cylinder 11 reverses the flow of air, causing the sleeve 1102 to rise. The second linear cylinder 1106 also controls the sleeve rod 1103 to retract, and the push cone 1104 is removed. Under the action of the spring 310, the two shielding plates 308 close and seal the liquid aspiration hole 303, preventing liquid from evaporating. An adapter 1110 can also be installed between the sleeve rod 1103 and the push cone 1104. The length and interface size of the adapter 1110 can be customized to facilitate the replacement of different push cones 1104.

[0067] Example 2:

[0068] A fully automatic tissue (electron microscope) sample pre-processing instrument, which consists of:

[0069] (1) Main frame - touch screen, power switch, USB port, emergency stop button, status indicator light, outer cover, electrical cabinet door, sample injection door, observation window, etc.

[0070] (2) Sample reaction module - TIP rack, sealed reagent barrel, sample basket reaction module, 6-well plate reaction module, sealed waste liquid barrel, waste TIP box, large waste liquid barrel, water cooling module, etc.;

[0071] (3) XYZ three-axis robotic arm module - robotic arm mounting frame, X-axis, Y-axis, Z-axis, pipette, electric gripper, etc.

[0072] In the present invention, the XYZ three-axis robotic arm module is used to achieve high-precision motion positioning of the X-axis, Y-axis, and Z-axis. The pipette and gripper on the motion module can achieve high-precision liquid control and object transfer in three-dimensional space.

[0073] The pipette is used in conjunction with the TIP to control the aspiration and discharge of liquids, achieving high control accuracy, multiple injections with one aspiration, and single injection with one aspiration. It can also perform actions such as reagent addition, waste liquid discharge, and liquid mixing. The software logic can support linear adjustment of reagent usage according to the number of samples, minimizing the reagent consumption per sample.

[0074] The gripper can open and close the sealed lids of the sealed reagent barrel, sample basket processing module and sealed waste liquid barrel as the XYZ three-axis robotic arm moves, ensuring that all reagents are not exposed to the outside world during the reaction process, achieving a closed reaction, reducing the volatilization of toxic gases, minimizing harm to the human body and reducing air pollution;

[0075] Up to 21 independent sealed reagent barrels are set up, each sealed reagent barrel is equipped with an independent workstation and an independently designed sealing cover. The required sealed reagent barrel is opened only when it is needed. This prevents the problem of the reagent cover linkage control in all sealed reagent barrels that requires opening all test sealed reagent barrels at the same time when using a certain reagent. This reduces the contact time between the reagent and the outside world, reduces the volatilization of toxic gases, reduces human harm and reduces air pollution. At the same time, sufficient spare sealed reagent barrels are available to support multiple process formulas;

[0076] Equipped with three sample basket processing modules and one 6-well plate sample processing module, the sample processing position can be selected according to the customer's sample type. The reaction tank of the sample basket processing module adopts temperature control and low liquid residue design to improve reaction efficiency and reduce the impact of the external environment. Three identical sample positions can meet the simultaneous processing of three groups of samples. Sample processing supports online continuous sampling, reducing the need to wait for dozens of hours after sampling before the next injection, shortening the injection cycle and improving efficiency; the 6-well plate sample processing module can realize the opening and closing of the sealing cover by rotating the synchronous belt driven by the flip drive motor, and the reaction chamber can be kept horizontal or tilted by rotating the synchronous belt driven by the tilt drive motor to meet various needs during reaction and drainage; both sample processing modules achieve temperature control through refrigeration plates and water cooling modules;

[0077] Equipped with three waste liquid barrels, waste liquid can be classified according to needs into recyclable waste liquid, heavily polluted waste liquid and general waste liquid, reducing waste liquid treatment costs. Recyclable waste liquid can be reused, reducing the cost of single test reagents;

[0078] The unique stacked sample basket design includes a sample rack, sample basket, cover, pressure plate, and handle. The four corners of the sample rack are marked with the letters ABCD, and the sample baskets have position marking grooves for precise positioning. The sample rack can accommodate up to three layers, with four sample baskets per layer. A single sample basket can hold nine samples, for a total of 108 samples. Up to 108 samples can be processed at a time, and continuous sample addition is possible, achieving a throughput of hundreds of samples.

[0079] Multiple workstations can be modularly selected according to needs, and samples can be added continuously online, with up to 108 samples loaded at a time; the amount of reagent used can be linearly adjusted according to the number of sample layers, and the amount of reagent used for 100 samples is less than 30ml; the reagents can be mixed during the reaction process to enhance the cleaning effect and reduce the reaction time; the reagent barrels and reaction tanks are designed to be sealed to prevent toxic gas volatilization and pollution; a small amount of volatile gas is connected to the external exhaust pipe through the instrument's exhaust duct to minimize pollution; multiple waste liquid barrels are designed to separately recycle and process required reagents; one-button start, automatic operation, and fully enclosed processing performance are pollution-free and environmentally friendly, and no human intervention is required for operation.

[0080] The workflow is as follows:

[0081] First, manually load the sample into the sample basket, and then place the sample basket on the sample basket rack. Cover them with covers, and then place pressure plates to press the covers to prevent them from floating up during the reaction. A maximum of 108 samples can be loaded at a time. Place the loaded sample basket into one of the sample processing modules and cover it with a sealing cover. Place the required reagents in the corresponding reagent positions and cover them with sealing covers. Fill the TIP head rack with TIP heads.

[0082] Make sure the sample, reagents, and TIP head are ready, select the corresponding sample processing module and reaction formula on the touch screen, and then click Start.

[0083] The XYZ three-axis robotic arm module automatically resets (including X-axis, Y-axis, Z-axis, pipette, and electric gripper).

[0084] The XYZ three-axis robotic arm moves, driving the pipette to the top of the first TIP head on the TIP head rack, and then the Z axis moves downward to pierce the TIP head.

[0085] The XYZ three-axis robotic arm moves, moving the pipette to the top of the buffer solution cleaning agent sealed reagent barrel. The electric gripper opens the corresponding reagent sealing cap. The XYZ three-axis robotic arm then moves, accompanied by liquid level detection, to extract the required amount of buffer solution cleaning agent. The Z axis then lifts, and the electric gripper closes the corresponding reagent sealing cap. The XYZ three-axis robotic arm moves to the top of the current round of sample processing modules. The electric gripper opens the corresponding sample processing module sealing cap. The Z axis moves to the injection and drainage holes of the current round of sample processing modules to discharge the required liquid. After repeating the above process to fill the required volume of reagent, the pipette performs aspiration and drainage actions below the liquid surface to mix the reagent, enhance the cleaning effect, and reduce reaction time. After the mixing action is completed, the electric gripper closes the corresponding sample processing module sealing cap to ensure that all sealed reagent barrels and sample reaction modules are sealed during operation.

[0086] After the reaction is completed, the waste liquid is sucked up by a pipette and transferred to a waste liquid bucket. The electric gripper opens the sealing lid of the corresponding waste liquid bucket (the lid of a large waste liquid bucket does not need to be opened). The pipette discharges the waste liquid into the waste liquid bucket, and the lid gripper closes the sealing lid of the corresponding waste liquid bucket.

[0087] The addition, reaction and waste discharge of 18 reagents, including buffer solution 1, buffer solution 2, buffer solution 3, 1% fixative, buffer solution 1, buffer solution 2, buffer solution 3, 30% dehydrating agent, 50% alcohol, 70% alcohol, 75% alcohol, 80% alcohol, 85% alcohol, 90% alcohol, 95% alcohol, 100% alcohol, permeation reagent 1, and permeation reagent 2, were carried out in sequence.

[0088] The three sample reaction modules and the six-well plate reaction module control the temperature of the entire reaction process through cooling plates and water cooling modules.

[0089] The above embodiments are merely preferred technical solutions of the present invention and should not be construed as limiting the present invention. The scope of protection of the present invention shall be the technical solutions set forth in the claims, including equivalent alternatives to the technical features of the technical solutions set forth in the claims. In other words, equivalent alternatives and improvements within this scope are also within the scope of protection of the present invention.

Claims

1. A fully automatic transmission electron microscope tissue and cell processing instrument, characterized by: The base (1) comprises a sample basket reaction module (4), a well plate reaction module (6), a waste liquid barrel (8) and a plurality of reagent storage barrels (3), the sample basket reaction module (4) is provided with a sample basket group (9), the base (1) is further provided with a liquid transfer module (2), the liquid transfer module (2) is provided with a movable pipette (5), the pipette (5) is provided with a pipette (501), and the pipette (5) is used to transfer liquid between the sample basket reaction module (4), the well plate reaction module (6), the waste liquid barrel (8) and the reagent storage barrel (3); The well plate reaction module (6) includes a base frame (601), a rotatable swinging platform (602) is provided on the base frame (601), the swinging platform (602) is provided with a second water bath (607), a culture block (605) is provided in the second water bath (607), and the culture block (605) is provided with a plurality of culture tanks (606), a rotatable upper cover rotation shaft (604) is provided on one side of the swinging platform (602), a second upper cover (603) is provided above the second water bath (607), and one end of the second upper cover (603) is connected to the upper cover rotation shaft (604); The upper ends of the reagent storage barrel (3) and the waste liquid barrel (8) are provided with openable covers (302); A first linear cylinder (11) is provided on one side of the pipette (5) on the pipetting module (2), the first linear cylinder (11) is provided with a movable base plate (1101), and is further provided with a sleeve (1102), the sleeve (1102) is connected to the base plate (1101), a retractable sleeve rod (1103) is provided in the sleeve (1102), an end of the sleeve rod (1103) extending outward is provided with a pushing cone head (1104) eccentric to the axis of the sleeve rod (1103), a through liquid suction hole (303) is provided in the center of the cover body (302), a first rotating flap (305) and a second rotating flap (306) are provided at the liquid suction hole (303), the first rotating flap (305) and the second rotating flap (306) are hinged in the middle, and the first rotating flap (305) and the second rotating flap (306) are hinged in the middle. A shielding piece (308) is provided at one end of the first flap (305) and the second flap (306), and the two shielding pieces (308) are closed to close the liquid suction hole (303). A side wall of the cover body (302) is provided with an avoidance through-groove (304). The other ends of the first flap (305) and the second flap (306) pass through the avoidance through-groove (304) and are provided with a slot portion (307). The pushing cone head (1104) is inserted into the slot portion (307) to open the shielding piece (308). A connecting ear (309) is provided at one end of each shielding piece (308) away from the slot portion (307). A spring (310) is connected between the two connecting ears (309). A stop portion (1109) is provided at the upper end of the pushing cone head (1104).

2. The fully automatic transmission electron microscope tissue and cell processing instrument according to claim 1, characterized in that: An outer cover (10) is also provided, the base (1) is provided in the outer cover (10), a sample injection door (1001) and an HMI (1002) are provided on one side of the outer cover (10), and an exhaust pipe (1003) communicating with the internal space is provided on the top of the outer cover (10).

3. The fully automatic transmission electron microscope tissue and cell processing instrument according to claim 1, characterized in that: The liquid transfer module (2) comprises a base (201), an X-axis linear module (202) is provided on the base (201), the X-axis linear module (202) is provided with a first movable platform (203), a Y-axis linear module (204) is provided on the first movable platform (203), the Y-axis linear module (204) is provided with a second movable platform (205), a Z-axis linear module (206) is provided on the second movable platform (205), the Z-axis linear module (206) is provided with a third movable platform (207), the moving directions of the first movable platform (203), the second movable platform (205) and the third movable platform (207) are perpendicular to each other, and the liquid transfer device (5) is provided on the third movable platform (207).

4. The fully automatic transmission electron microscope tissue and cell processing instrument according to claim 1, characterized in that: The sample basket reaction module (4) is provided with a first water bath (401), an openable first upper cover (402) is provided above the first water bath (401), a heat-conducting container box (403) is provided in the first water bath (401), the sample basket group (9) is placed in the container box (403), and the container box (403) is provided with a protrusion (404) for the pipette (501) to enter.

5. The fully automatic transmission electron microscope tissue and cell processing instrument according to claim 4, characterized in that: The bottom of the raised portion (404) is inclined so that the inner bottom of the raised portion (404) is the lowest.

6. The fully automatic transmission electron microscope tissue and cell processing instrument according to claim 1, characterized in that: The sample basket group (9) includes a basket frame (901), wherein the edge of the basket frame (901) is provided with a side guard column (902), and the center of the basket frame (901) is provided with a central guard column (903). The side guard columns (902) and the central guard column (903) divide the sample basket group (9) into multiple areas, each area is provided with a stacked sample basket (904), and each sample basket (904) is provided with multiple culture areas (905).

7. The fully automatic transmission electron microscope tissue and cell processing instrument according to claim 1, characterized in that: A guide protrusion (504) is provided on the outer wall of one end of the sleeve rod (1103) away from the pushing cone head (1104), a through spiral groove (503) is provided on the side wall of the sleeve (1102), the guide protrusion (504) is inserted into the spiral groove (503), and a second linear cylinder (1106) is also provided. The cylinder rod of the second linear cylinder (1106) is connected to a transition sleeve (1105), and an annular groove (1107) is provided at the end of the transition sleeve (1105). A bayonet (1108) is provided on the side wall of the sleeve rod (1103), and the bayonet (1108) is stuck in the annular groove (1107) and slides.

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