Full-automatic transmission electron microscope tissue and cell treatment instrument

Abstract

The invention provides a full-automatic transmission electron microscope tissue and cell treatment instrument, which comprises a base, a sample basket reaction module, a pore plate reaction module, a waste liquid barrel and a plurality of reagent storage barrels are arranged on the base, a sample basket group is arranged in the sample basket reaction module, a pipetting module is further arranged on the base, the pipetting module is provided with a movable pipettor, and the sample basket group is provided with a plurality of reagent storage barrels. The pipettor is provided with a pipette and is used for transferring liquid among the sample basket reaction module, the pore plate reaction module, the waste liquid barrel and the reagent storage barrel, so that the problem of automatic culture of cells and tissues is solved.

Description

Technical Field

[0001] The 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 pathological diagnosis is an important means to study the etiology and pathogenesis of the disease, as well as the changes and outcomes of the body's morphological structure, function and metabolism during the disease process. It mainly includes tissue pathology using optical microscope imaging technology and ultramicropathology using transmission electron microscope technology. It is of great significance for the diagnosis, treatment and prevention of the disease. The pathological diagnosis process usually requires a series of treatments such as fixation, dehydration, transparency, wax immersion, embedding, sectioning, staining, etc. The treatment process is numerous, involving many types of processing reagents, and the physical and chemical properties of the reagents are different. Some of the reagents are highly volatile and toxic. At present, tissue pathology has a full set of instruments and equipment covering all processing links, but ultramicropathology processing instruments are less involved.

[0003] Most existing technologies rely on manual operations. The biological tissue processing process is cumbersome and requires the use of a variety of different types and concentrations of processing fluids, which is time-consuming, labor-intensive, difficult and prone to errors. Some reagents are highly volatile or toxic, which can easily cause a certain degree of damage to the operator's body. Summary of the invention

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

[0005] In order 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 arranged, 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, a sample inlet door and an HMI are arranged on one side of the outer cover, and an exhaust duct communicating with the internal space is arranged 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 moving platform, the first moving platform is provided with a Y-axis linear module, the Y-axis linear module is provided with a second moving platform, the second moving platform is provided with a Z-axis linear module, the Z-axis linear module is provided with a third moving platform, the moving directions of the first moving platform, the second moving platform and the third moving platform are perpendicular to each other, and the pipette is arranged on the third moving platform.

[0008] In a preferred embodiment, the sample basket reaction module is provided with a first water bath, an openable first upper cover is provided above the first water bath, a heat-conducting container box is provided in the first water bath, the sample basket assembly is placed in the container box, and the container box 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 frame, the edge of the basket frame is provided with a side guard column, the center of the basket frame is provided with a central guard column, the side guard column 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 table on the base frame, the swinging table 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 table, 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 reagent storage barrel and the waste liquid barrel are provided with openable covers at their upper ends.

[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 also 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 flap and a second turning flap are provided at the suction hole, the first turning flap and the second turning flap are hinged in the middle, a shielding piece is provided at one end of the first turning flap and the second turning flap, 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 ends of the first turning flap and the second turning flap pass through the avoidance through groove and are 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 push 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 with 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, and the bayonet 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, so that the culture of tissues and monolayer adherent cells can be realized; a sample basket group is provided with a plurality of sample baskets, and each sample basket is provided with a plurality of culture areas, so that high-throughput batch processing of samples can be realized; an XYZ three-axis motion module is equipped, so that the pipette can realize free movement in three-dimensional space, and automatic sample addition, cleaning and liquid discharge are realized; a closed design is adopted for the reagent barrel and the reaction tank to prevent the volatilization and pollution of toxic gases; an improved scheme adopts a push cone head to trigger the cover inlet and outlet opening mechanism of the reagent barrel and the waste liquid barrel in advance, so as to reduce the beat time of each sample addition and liquid discharge, and improve the overall efficiency. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] The present invention will be further described below in conjunction with the accompanying drawings and embodiments.

[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 base table layout diagram.

[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 is a diagram of the sample basket group structure.

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

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

[0027] Fig.11 It is a schematic diagram of the reagent barrel.

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

[0029] Fig.13 Schematic diagram of the sleeve rod retraction.

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

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

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

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

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

[0035] In the figure: base 1; liquid transfer module 2; base 201; X-axis linear module 202; first moving platform 203; Y-axis linear module 204; second moving platform 205; Z-axis linear module 206; third moving platform 207; reagent storage barrel 3; spare reagent barrel 301; cover body 302; suction hole 303; avoidance through groove 304; first flap 305; second flap 306; slot part 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 group 9; basket rack 901; side baffle column 902; central baffle column 903; sample basket 904; culture area 905; cover plate 906; pressure plate 907; through hole 908; handle 909; outer cover 10; sample injection door 1001; HMI1002; 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] Embodiment 1: like Figure 1-18 In the invention, a fully automatic transmission electron microscope tissue and cell processing instrument is provided, comprising a base 1, on which 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 are arranged, in which a sample basket group 9 is arranged, and on the base 1 a liquid transfer module 2 is also arranged, in which a movable pipette 5 is arranged, and in which a pipette 5 is arranged, and in which a pipette 501 is arranged, and in which 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.

[0037] 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.

[0038] A plurality of 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.

[0039] The pipetting module 2 is a Cartesian multi-axis moving mechanism, which can enable the pipette 5 to move in three directions of X, Y, and Z. 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 to wait for cleaning or recycling.

[0040] A pipette rack 7 is also provided on the base 1 near the lower portion of the initial position of the pipette 5. The pipette rack 7 includes a plurality of jack structures, and a plurality of clean pipettes 501 can be placed therein for easy replacement.

[0041] 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 arranged on one side of the outer cover 10, and an exhaust duct 1003 communicating with the internal space is arranged on the top of the outer cover 10.

[0042] 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.

[0043] In a 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 moving platform 203, the first moving platform 203 is provided with a Y-axis linear module 204, the Y-axis linear module 204 is provided with a second moving platform 205, the second moving platform 205 is provided with a Z-axis linear module 206, the Z-axis linear module 206 is provided with a third moving platform 207, the moving directions of the first moving platform 203, the second moving platform 205 and the third moving platform 207 are perpendicular to each other, and the pipette 5 is arranged on the third moving platform 207.

[0044] The X-axis linear module 202, the Y-axis linear module 204 and the Z-axis linear module 206 include a lead screw and a slide rail mechanism. The lead screw can be driven by a servo motor, and the nut sleeved on the lead screw drives each mobile platform to move linearly. The servo motor can monitor the number of pulses emitted, so the real-time position of each mobile platform can be calculated, and sensors can also be installed to accurately control the position.

[0045] 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.

[0046] The sample basket reaction module 4 body is provided with a mounting base, and a cooling and heating device is provided inside near the bottom of the first water bath 401 to control the liquid temperature in the first water bath 401 and monitor the temperature through a sensor. The body is provided with heat insulation cotton and a heat insulation cover is provided on the outside.

[0047] 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 .

[0048] In a preferred solution, the bottom of the protrusion 404 is inclined so that the inner bottom of the protrusion 404 is the lowest.

[0049] Due to the inclination, the bottom of the protrusion 404 is the lowest point of the container box 403, and the pipette 501 can absorb all the liquid to reduce the residual waste liquid.

[0050] In a preferred embodiment, the sample basket group 9 includes a basket rack 901, a side guard column 902 is provided at the edge of the basket rack 901, and a central guard column 903 is provided in the center of the basket rack 901. The side guard column 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.

[0051] The side guard column 902 is an angled body, the central guard column 903 is a cross, the sample basket 904 is a rectangle, 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.

[0052] A pressing plate 907 is also provided, and the pressing plate 907 has through holes 908 in various areas. A through hole is provided in the center of the pressing 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 pressing 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.

[0053] In the preferred embodiment, the well plate reaction module 6 includes a base frame 601, and 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.

[0054] A cooling and heating module 608 is provided at the lower end of the swing table 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 .

[0055] The base frame 601 is also provided with a flip motor 609 and a tilt motor 610. The side end of the base frame 601 is provided with a first synchronous belt mechanism 611 and a second synchronous belt mechanism 612. The flip motor 609 drives the upper cover rotating shaft 604 to rotate through the first synchronous belt mechanism 611 so that the second upper cover 603 flips and opens. The tilt motor 610 drives the swing table 602 to tilt at a certain angle through the second synchronous belt mechanism 612, so that the pipette 5 can absorb the waste liquid. The swing table 602 can tilt and oscillate back and forth to complete some special culture situations.

[0056] In a preferred embodiment, an openable cover 302 is provided at the upper end of the reagent storage barrel 3 and the waste liquid barrel 8 .

[0057] A clamping device 502 can be set on one side of the pipette 5, and a gripping portion can be set in the center of the cover 302 for gripping by the clamping device 502. Before the pipette 501 absorbs the reagent each time, the pipette module 2 needs to move the clamping device 502 to the top of the cover 302, move down and clamp the cover 302, then the clamping device 502 moves aside, the pipette 501 moves over, moves down and extends into the reagent storage barrel 3 or the waste liquid barrel 8, completes the liquid absorption or liquid discharge operation, and then covers the cover 302 to prevent the reagent or the polluting liquid from volatilizing.

[0058] Since the lid needs to be opened each time the reagent is absorbed 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.

[0059] In the preferred embodiment, a first linear cylinder 11 is provided on one side of the pipette 5 on the pipetting module 2, and the first linear cylinder 11 is provided with a movable seat plate 1101 and a sleeve 1102, the sleeve 1102 is connected to the seat plate 1101, a retractable sleeve rod 1103 is provided in the sleeve 1102, and a push cone head 1104 eccentric to the axis of the sleeve rod 1103 is provided at one end of the sleeve rod 1103 extending outward, a through suction hole 303 is provided in the center of the cover body 302, and a first rotary flap 305 and a second rotary flap 306 are provided at the suction hole 303, and 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 flap 305 and the second 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 flap 305 and the second 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, and a stop portion 1109 is provided at the upper end of the pushing cone head 1104.

[0060] Since the reagent storage barrels 3 are densely arranged and the size of the cover 302 is limited, the push cone head 1104 needs to be as close to the pipette 501 as possible. However, since the root of the pipette 501 and the main body of the pipette 5 are larger than the tip of the pipette, the push cone head 1104 may collide with the pipette 5 and the pipette 501 when it is retracted.

[0061] In the preferred embodiment, a guide protrusion 504 is provided on the outer wall of one end of the sleeve rod 1103 away from the push 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.

[0062] The pipette 5 and the first linear cylinder 11 are both mounted on the third moving platform 207 .

[0063] The outer wall of the sleeve 1102 is provided with a connecting seat connected to the seat plate 1101. Initially, the sleeve rod 1103 is in a retracted state, and the push cone head 1104 is biased to the side 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, and 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 existence of the transition sleeve 1105 allows 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 moving platform 207 descends, the push cone head 1104 descends and inserts into the slot portion 307, and the guide section at the lower end of the push cone head 1104 opens the slot portion 307 so that the shielding sheet 308 at the other end is also opened, exposing the suction hole 303. As the third moving platform 207 continues to descend, the pipette 501 eventually passes through the suction hole 303 without hindrance and enters the inside of the reagent storage barrel 3 or the waste liquid barrel 8. As the third moving 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 middle leakage state, the seat plate 1101 is in a state of not being subjected to 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 head 1104 from continuing to descend and interfering with other mechanisms.

[0064] During the whole process, the third moving 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.

[0065] After the pipette 501 is pulled out, the first linear cylinder 11 is ventilated in the reverse direction to make the sleeve 1102 rise, and the second linear cylinder 1106 also controls the sleeve rod 1103 to retract, and the push cone head 1104 is pulled out. Under the action of the spring 310, the two shielding pieces 308 close and close the liquid suction hole 303 to prevent the liquid from volatilizing. An adapter 1110 can also be set between the sleeve rod 1103 and the push cone head 1104. The length and interface size of the adapter 1110 can be customized to facilitate the replacement of different push cone heads 1104.

[0066] Embodiment 2: A fully automatic tissue (electron microscope) sample pre-treatment instrument, which consists of: (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. (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.; (3) XYZ three-axis robotic arm module - robotic arm mounting frame, X-axis, Y-axis, Z-axis, pipette, electric gripper, etc.

[0067] In the present invention, the XYZ three-axis mechanical arm module is used to achieve high-precision motion positioning of the X-axis, Y-axis and Z-axis, and the pipette and clamp on the motion module can achieve high-precision liquid control and object transfer in three-dimensional space; The pipette is used with TIP to control the aspiration and discharge of liquids, which can achieve high control accuracy, multiple injections with one aspiration, one injection with one aspiration, etc., and realize reagent filling, waste liquid discharge and liquid mixing. The software logic can support linear adjustment of reagent usage according to the number of samples to minimize the reagent consumption per unit sample; The gripper can open and close the sealing covers of the sealed reagent barrel, sample basket processing module and sealed waste liquid barrel as the XYZ three-axis robotic arm moves, so that all reagents do not come into contact with the outside world during the reaction process, achieving a closed reaction, reducing the volatilization of toxic gases, reducing human harm and reducing air pollution; Set up to 21 independent sealed reagent barrels, each sealed reagent barrel is equipped with an independent workstation and an independently designed sealing cover. The required single sealed reagent barrel will be opened when needed, preventing the problem of having to open all the test sealed reagent barrels at the same time when using a certain reagent due to the linkage control of the reagent covers in all sealed reagent barrels, thereby reducing the contact time between the reagent and the outside world, reducing the volatilization of toxic gases, reducing human harm and reducing air pollution. At the same time, sufficient spare sealed reagent barrels support a variety of process formulas; Equipped with three sample basket processing modules and one 6-well plate sample processing module, the sample processing positions 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, which reduces the need to wait for dozens of hours after injection before the next injection, shortens the injection cycle, and improves efficiency; the 6-well plate sample processing module can realize the opening and closing of the sealing cover by driving the synchronous belt to rotate through the flip drive motor, and the reaction chamber can be kept horizontal or tilted by driving the synchronous belt to rotate through the tilt drive motor, meeting various needs during reaction and drainage; both sample processing modules achieve temperature control through cooling plates and water cooling modules; 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 the cost of waste liquid treatment. Recyclable waste liquid can be reused, reducing the cost of single test reagents; The unique stacked sample basket design includes a sample basket rack, sample basket, cover, pressure plate, and handle. The four corners of the sample basket rack are marked with the letters ABCD. There are position marking grooves on the sample basket to achieve precise position marking. The sample basket rack can hold up to three layers, with four sample baskets on each layer. A single sample basket can hold 9 samples, for a total of 108 samples. A maximum of 108 samples can be processed at a time, and samples can be added continuously to achieve a throughput of continuously processing hundreds of samples.

[0068] 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 barrel and reaction tank are designed to be closed to prevent toxic gas volatilization and pollution; a small amount of volatile gas is connected to the external exhaust pipe through the exhaust duct of the instrument to minimize pollution; multiple waste liquid barrels are designed to recycle and process the required reagents separately; one-button start, automatic operation, and fully enclosed processing performance are pollution-free and environmentally friendly, and no human intervention is required for operation.

[0069] The workflow is as follows: First, manually load the samples into the sample basket, and then put the sample basket on the sample basket rack, cover them with covers, and then put pressure plates on the covers to prevent them from floating up during the reaction. A maximum of 108 samples can be loaded at one time, and the loaded sample basket is placed in one of the sample processing modules and covered with a sealing cover; the required reagents are placed in the corresponding reagent positions and covered with sealing covers, and the TIP head rack is filled with TIP heads.

[0070] Make sure the samples, reagents, and TIP heads are ready, select the corresponding sample processing module and reaction recipe on the touch screen, and then click Start.

[0071] The XYZ three-axis robotic arm module automatically resets (including X-axis, Y-axis, Z-axis, pipette, and electric gripper).

[0072] 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.

[0073] The XYZ three-axis robotic arm moves to move the pipette to the top of the buffer cleaning agent sealed reagent barrel, and the electric gripper opens the corresponding reagent sealing cover. Then the XYZ three-axis robotic arm moves and detects the liquid level to extract the required amount of liquid from the buffer cleaning agent, and then the Z axis is lifted up, and the electric gripper closes the corresponding reagent sealing cover. The XYZ three-axis robotic arm moves to the top of the current round of sample processing module, and the electric gripper opens the corresponding sample processing module sealing cover. The Z axis moves to the position of the injection and drainage holes of the current round of sample processing module to discharge the required liquid. After repeating the above process to fill the required volume of reagent, the pipette performs suction and drainage actions below the liquid surface to mix the reagent, enhance the cleaning effect, and reduce the reaction time. After the mixing action is completed, the electric gripper closes the corresponding sample processing module sealing cover to ensure that all sealed reagent barrels and sample reaction modules are sealed during operation.

[0074] 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 corresponding waste liquid bucket sealing cover (the large waste liquid bucket does not need to open the cover), the pipette discharges the waste liquid into the waste liquid bucket, and the cover gripper closes the corresponding waste liquid bucket sealing cover.

[0075] 18 reagents were added, reacted and waste discharged in sequence, 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.

[0076] The three sample reaction modules and the six-well plate reaction module control the temperature of the entire reaction process through cooling sheets and water cooling modules.

[0077] The above embodiments are only preferred technical solutions of the present invention and should not be regarded as limiting the present invention. The protection scope of the present invention shall be the technical solutions recorded in the claims, including equivalent replacement solutions of the technical features in the technical solutions recorded in the claims. That is, equivalent replacement improvements within this scope are also within the protection scope of the present invention.

Claims

1. A fully automatic transmission electron microscope tissue and cell processing instrument, characterized by: The invention comprises a base (1), wherein 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) are arranged on the base (1), a sample basket group (9) is arranged in the sample basket reaction module (4), and a liquid transfer module (2) is also arranged on the base (1), wherein the liquid transfer module (2) is provided with a movable liquid transfer device (5), wherein the liquid transfer device (5) is provided with a liquid transfer tube (501), and the liquid transfer device (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).

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 arranged inside 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 arranged on the base (201), the X-axis linear module (202) is provided with a first moving platform (203), a Y-axis linear module (204) is arranged on the first moving platform (203), the Y-axis linear module (204) is provided with a second moving platform (205), a Z-axis linear module (206) is arranged on the second moving platform (205), the Z-axis linear module (206) is provided with a third moving platform (207), the moving directions of the first moving platform (203), the second moving platform (205) and the third moving platform (207) are perpendicular to each other, and the liquid transfer device (5) is arranged on the third moving 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 a pipette (501) to enter.

5. The fully automatic transmission electron microscope tissue and cell processing instrument according to claim 4 is characterized in that: The bottom of the protrusion (404) is inclined so that the inner bottom of the protrusion (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) comprises a basket frame (901), the edge of the basket frame (901) is provided with a side blocking column (902), the center of the basket frame (901) is provided with a central blocking column (903), the side blocking column (902) and the central blocking 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 is characterized in that: The well plate reaction module (6) comprises a base frame (601), a rotatable swinging platform (602) on the base frame (601), the swinging platform (602) being provided with a second water bath (607), a culture block (605) being provided in the second water bath (607), the culture block (605) being provided with a plurality of culture tanks (606), a rotatable upper cover rotating shaft (604) being provided on one side of the swinging platform (602), a second upper cover (603) being provided above the second water bath (607), and one end of the second upper cover (603) being connected to the upper cover rotating shaft (604).

8. The fully automatic transmission electron microscope tissue and cell processing instrument according to claim 7, characterized in that: An openable cover (302) is provided at the upper end of the reagent storage barrel (3) and the waste liquid barrel (8).

9. The fully automatic transmission electron microscope tissue and cell processing instrument according to claim 8, characterized in that: A first linear cylinder (11) is provided on one side of the upper pipette (5) of the liquid transfer module (2). The first linear cylinder (11) is provided with a movable seat plate (1101) and a sleeve (1102). The sleeve (1102) is connected to the seat plate (1101). A retractable sleeve rod (1103) is provided in the sleeve (1102). An outwardly extending end of the sleeve rod (1103) is provided with a push 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. The first rotating flap (305) and the second rotating flap (306) are hinged in the middle. A shielding sheet (308) is provided at one end of the first rotating flap (305) and the second rotating flap (306); the two shielding sheets (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 rotating flap (305) and the second rotating flap (306) pass through the avoidance through-groove (304) and are provided with a slot portion (307); a push cone head (1104) is inserted into the slot portion (307) to open the shielding sheet (308); a connecting ear (309) is provided at one end of each shielding sheet (308) away from the slot portion (307); a spring (310) is connected between the two connecting ears (309); and a stop portion (1109) is provided at the upper end of the push cone head (1104).

10. The fully automatic transmission electron microscope tissue and cell processing instrument according to claim 9, characterized in that: A guide protrusion (504) is provided on the outer wall of one end of the sleeve rod (1103) away from the push 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), an annular groove (1107) is provided at the end of the transition sleeve (1105), and 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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