CN111579339A - Full-automatic liquid-based cell slice-making dyeing machine and slice-making dyeing method - Google Patents

Full-automatic liquid-based cell slice-making dyeing machine and slice-making dyeing method Download PDF

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Publication number
CN111579339A
CN111579339A CN202010631638.0A CN202010631638A CN111579339A CN 111579339 A CN111579339 A CN 111579339A CN 202010631638 A CN202010631638 A CN 202010631638A CN 111579339 A CN111579339 A CN 111579339A
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CN
China
Prior art keywords
sample
needle
slice
dyeing
centrifuge
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CN202010631638.0A
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Chinese (zh)
Inventor
李必松
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Guangzhou Huayue Keju Biotechnology Co ltd
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Guangzhou Huayue Keju Biotechnology Co ltd
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Priority to CN202010631638.0A priority Critical patent/CN111579339A/en
Publication of CN111579339A publication Critical patent/CN111579339A/en
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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00Sampling; Preparing specimens for investigation
    • G01N1/28Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00Sampling; Preparing specimens for investigation
    • G01N1/28Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/30Staining; Impregnating ; Fixation; Dehydration; Multistep processes for preparing samples of tissue, cell or nucleic acid material and the like for analysis
    • G01N1/31Apparatus therefor

Abstract

The invention discloses a full-automatic liquid-based cell slice-making dyeing machine and a slice-making dyeing method. The liquid-based cell slice-making dyeing machine can realize the full automation of the liquid-based cell slice-making dyeing process, and the slice-making dyeing method is based on the slice-making dyeing machine, so that a sample needle controlled by a three-axis linkage system can be transferred into a centrifugal tube of a centrifuge after a sample and matched consumables are manually placed in a sample bottle on a sample rack; after centrifugation, the sample needle is precisely positioned by a precise positioning control mechanism, and then supernatant and centrifugal sediment in the centrifugal tube are sequentially and respectively transferred to a waste liquid tank and a slice-making dyeing plate by the sample needle; then, injecting a staining solution to the settled centrifugal precipitate on the flaking staining plate by staining to complete flaking staining; the whole process from sample loading to slice-making dyeing is completed in the whole slice-making dyeing process without manual operation, so that manpower and material resources are saved. Moreover, the liquid-based cell slice-making dyeing machine is integrated, so that the whole equipment cost is low and the space occupancy rate is small.

Description

Full-automatic liquid-based cell slice-making dyeing machine and slice-making dyeing method
Technical Field
The invention relates to the field of cell slice-making and dyeing equipment, in particular to a full-automatic liquid-based cell slice-making and dyeing machine and a slice-making and dyeing method.
Background
The sedimentation type liquid-based cell slice-making dyeing process at least needs three procedures including sample pretreatment, centrifugation and slice-making dyeing, the three procedures are sequentially and independently carried out, sample transfer work among different instruments is manually carried out, and the instruments operate after the manual transfer is finished.
The existing sedimentation type liquid-based cell flaking process is semi-automatic, the processes from sample treatment to centrifugation and from centrifugation to flaking dyeing need manual operation, the separating liquid is filled into a centrifugal tube by manual work, the centrifugal tube and a liquid-transfer injector which are filled with the separating liquid are arranged in a sample processor for pretreatment operation, then the centrifugal tube filled with the separating liquid and the sample to be tested is manually arranged in a centrifuge for completing centrifugation, the centrifugal tube is manually taken out from the centrifuge, supernatant is manually sucked away, the centrifugal tube is then oscillated on an oscillator for using centrifugal precipitation dispersion, and finally the centrifugal tube is arranged in a flaking dyeing machine for flaking dyeing. The operation is troublesome, the flow is complex, the human error is large, and time and labor are wasted; moreover, at least three instruments such as a centrifuge, a sample processor, a flaking and dyeing machine and the like are required, so that the equipment is various and complicated, the equipment cost is high, and the space occupancy rate is large.
Disclosure of Invention
The invention aims to provide a full-automatic liquid-based cell slice-making and dyeing machine aiming at the defects or shortcomings in the prior art. The liquid-based cell slice-making dyeing machine can realize full automation of a liquid-based cell slice-making dyeing process, does not need manual participation operation in the whole process from sample processing to slice-making dyeing, saves manpower and material resources, and has low equipment cost and small space occupancy rate.
The invention also aims to provide a full-automatic liquid-based cell slice-making and dyeing method based on the slice-making and dyeing machine.
The purpose of the invention is realized by the following technical scheme.
A full-automatic liquid-based cell slice-making dyeing machine comprises a sample rack, a centrifuge, a slice-making dyeing plate, a sample needle and a dyeing needle; a sample bottle is placed on the sample rack and used for containing a sample; the centrifugal machine is connected with a precise positioning control mechanism and is used for precisely positioning and controlling the rotation stop position of the centrifugal machine; a slide is placed on the sheet preparation staining plate; the sample needle and the dyeing needle can be driven by a three-axis linkage system to freely move along an X axis, a Y axis and a Z axis, and the movement of the sample needle and the movement of the dyeing needle along the Z axis are mutually independent; the sample needle and the dyeing needle are respectively connected with mutually independent plunger pumps through pipelines; the accurate positioning control mechanism, the centrifuge, the three-axis linkage system and the plunger pump are all in control connection with a circuit control system.
In a preferred embodiment, the rotating shaft of the motor of the centrifuge is lengthened and penetrates through the bottom to extend out; the accurate positioning control mechanism is arranged outside the bottom of the centrifuge motor and is in clutch transmission connection with a lengthened extension end of a rotating shaft of the centrifuge motor;
the accurate positioning control mechanism comprises a driving device, a clutch, an axial elastic coupling and a rotating speed monitoring and positioning system; one end of the axial elastic coupling member is connected to the lengthened and extended end of the rotating shaft of the centrifuge motor, one end of the clutch is connected with the other end of the axial elastic coupling member, and the output end of the driving device is in transmission connection with the other end of the clutch; the rotating speed monitoring and positioning system is used for monitoring the rotating speed of the rotating shaft of the centrifuge motor and positioning the position of the rotating shaft of the centrifuge motor, and the rotating speed monitoring and positioning system is in control connection with the driving device through the circuit control system.
In a more preferred embodiment, the rotational speed monitoring positioning system comprises a positioning sensor and a rotary code disc; the rotary coded disc is sleeved on the lengthened extending end of the rotating shaft of the centrifuge motor; the positioning sensor is arranged on the outer side of the rotary coded disc and can monitor the rotating speed of the rotary coded disc and position the rotary coded disc; the positioning sensor is connected with the driving device in a feedback control mode through the circuit control system.
In a preferred embodiment, the sample needle has at least two needle heads thereon; and at least two built-in pipelines which are respectively communicated with at least two needle heads are arranged in the sample needle; at least two built-in pipelines are respectively connected with the plunger pump corresponding to the sample needle through at least two air pipes.
In a preferred embodiment, the dyeing needle comprises several branches independent from each other; the dyeing needles which are mutually independent are connected and arranged on the three-axis linkage system through a mounting frame; and the dyeing needles which are mutually independent are respectively connected with independent plunger pumps through independent air pipes.
In a preferred embodiment, a waste liquid tank is also provided; and the bottom of the waste liquid tank is communicated with a waste liquid output pipeline.
In a preferred embodiment, the circuit control system comprises a control circuit board and a display screen connected with the control circuit board; and the control circuit board is provided with a central processing unit.
In a preferred embodiment, a suction nozzle rack and a waste collection box are also provided; a suction nozzle is arranged on the suction nozzle frame;
the suction nozzle is matched with the head of the sample needle and can be tightly sleeved on the head of the sample needle; when the sample needle transfers a sample, a centrifugate or a centrifugal sediment, the suction nozzle is sleeved on the sample needle for cooperation;
the waste collecting box is used for recovering the article materials comprising the suction nozzle; the sample needle can be arranged on a needle frame in a telescopic way along the Z axis, the needle frame is provided with an annular clamping part which is tightly matched with the head of the sample needle, and when the sample needle which is sleeved with the suction nozzle moves in a retracting way along the Z axis, the annular clamping part can prevent the suction nozzle from retracting along with the sample needle and pushing down the suction nozzle.
In a more preferred embodiment, the sample needle is connected with a motor for driving the sample needle by using an elastic coupling.
In a more preferred embodiment, a filter mesh is placed on the slide; and the filter screen sleeve can be sleeved on the sample needle for matching use and can be recovered by the waste material collecting box after being jacked by the annular clamping part.
A full-automatic liquid-based cell slice-making dyeing method is based on the full-automatic liquid-based cell slice-making dyeing machine and comprises the following steps:
s1, starting a control program of the circuit control system;
s2, the three-axis linkage system drives the sample needle to freely move along the X axis, the Y axis and the Z axis;
s3, filling the separation liquid into the centrifuge tube of the centrifuge by the sample needle;
s4, the sample needle transfers the sample in the sample bottle to a centrifuge tube of the centrifuge;
s5, starting centrifugation by the centrifuge;
s6, after the centrifugation is finished, the accurate positioning control mechanism accurately controls the positioning; driving the sample needle to suck and remove the supernatant in the centrifuge tube, transferring the centrifugal precipitate in the centrifuge tube to a slide of the slide preparation staining plate, and performing sedimentation to prepare a slide;
s7, injecting a staining solution into the slide subjected to sedimentation slide preparation by the staining needle, and staining the centrifugal precipitate on the slide;
wherein the dyeing process comprises the following steps: adding washing liquid for 1-3 times, adding buffer solution for 1-3 times, adding sujilin staining solution for 1-3 times, adding buffer solution for 1-5 times, adding washing liquid for 1-3 times, adding EAOG or EA50 staining solution for 1-3 times, and adding washing liquid for 1-3 times; before each liquid adding, the liquid in the slide is pumped out and is pumped out as clean as possible, and the times of liquid adding execution are controlled by software.
And S8, the staining needle is restored to the original position, and the liquid-based cell slice staining is completed.
Compared with the prior art, the invention has the following advantages and beneficial effects:
the liquid-based cell slice-making dyeing machine can realize the full automation of the liquid-based cell slice-making dyeing process, and in the liquid-based cell dyeing process based on the slice-making dyeing machine, after a sample and matched consumables are manually placed in a sample bottle on a sample rack, a sample needle controlled by a three-axis linkage system can fill separation liquid into a centrifugal tube, and the sample is transferred into the centrifugal tube of a centrifugal machine; after centrifugation, the sample needle is accurately positioned by an accurate positioning control mechanism, the supernatant in the centrifugal tube is transferred to a waste liquid tank, and then the centrifugal precipitate is transferred to a sheet-making dyeing plate; then, injecting a staining solution into the settled centrifugal precipitate on the flaking staining plate by a staining solution, and finishing flaking staining; the whole process from sample loading to slice-making dyeing is completed in the whole slice-making dyeing process without manual operation, so that manpower and material resources are saved.
In addition, the sample needle of the liquid-based cell slice-making dyeing machine is operated by matching a disposable suction nozzle in the transferring process of samples, centrifugate and centrifugal precipitation, so that different samples are not polluted; and is provided with a waste collecting box for matching with the recovery suction nozzle.
Moreover, the liquid-based cell slice-making dyeing machine is integrated, a centrifugal part, a sample processing part, a slice-making dyeing part, a suction nozzle placing and recovering part, waste liquid discharging and the like are integrated on the integrated equipment, and the sample needles controlled by the three-axis linkage system are connected, so that the whole equipment is low in cost and small in space occupancy rate.
Drawings
FIG. 1 is a schematic diagram of the overall structure of a fully automatic liquid-based cell slide-dyeing machine in an embodiment;
FIGS. 2a and 2b are schematic views of a partially open structure of a fully automatic liquid-based cell slide staining machine at different angles in an exemplary embodiment;
FIG. 3 is a partial schematic diagram of a fully automatic liquid-based cell slide-staining machine according to an exemplary embodiment;
FIG. 4 is a schematic view of a configuration of the centrifuge and the fine positioning control mechanism;
FIG. 5 is a schematic view of the connection structure of the fine positioning control mechanism and the motor shaft;
FIG. 6 is an exploded view of the fine positioning control mechanism;
FIG. 7 is a schematic view showing the structure of the sample needle engaged with the suction nozzle;
the attached drawings are marked as follows: 100-outer frame, 200-workbench, 101-centrifugal bin, 1011-centrifugal bin sample moving window, 102-slice dyeing bin, 1-sample frame, 2-centrifuge, 201-rotor body, 202-hanging basket, 203-centrifuge motor, 2031-motor rotating shaft, 3-precise positioning control mechanism, 301-driving device, 302-clutch, 3021-electromagnetic generating end, 3022-clutch sucking disc end, 303-axial elastic coupling, 304-rotating speed monitoring and positioning system, 3041-photoelectric sensor, 3042-rotating code disc, 305-fixing frame, 306-clutch fixing plate, 4-slice dyeing plate, 5-triaxial linkage system, 501-linear module, 502-dyeing needle mounting frame, 503-sample needle frame, 6-sample needle, 601-sample needle head, 7-dyeing needle, 8-circuit control system, 801-display screen, 802-power switch, 9-suction nozzle rack, 10-suction nozzle, 11-waste liquid tank, 12-waste collection box, 13-plunger pump, 14-liquid pump, 15-electromagnetic valve, 16-liquid inlet, 17-waste liquid outlet.
Detailed Description
The technical solutions of the present invention are further described in detail below with reference to specific examples and drawings, but the scope and implementation of the present invention are not limited thereto. In the description of the specific embodiments, it should be noted that the terms "upper", "lower", "front", "back", "left", "right", and the like refer to the orientation or position relationship shown in the drawings or the orientation or position relationship that the product of the invention is usually placed in when used, and are used for distinguishing and describing only for convenience of describing the invention and simplifying the description, but do not refer to or imply that the structures or elements that are referred to must have a specific orientation, be constructed in a specific orientation, and be operated, and therefore, cannot be construed as limiting the invention, and are not meant to indicate or imply relative importance.
Referring to fig. 1 to 2b, the full-automatic liquid-based cell slide-making and dyeing machine according to an embodiment of the present invention includes an external frame 100, side plates are disposed on left and right sides of the external frame 100, a cover plate is disposed on a top of the external frame, panels are disposed on front and rear portions of the external frame, an open type working room is disposed in a middle portion of the external frame, and a slide-making and dyeing process of the full-automatic liquid-based cell is completed in the open type working room.
A sample rack 1, a centrifuge 2 and a slice preparation dyeing plate 4 are arranged in the workshop. Wherein, having placed the sample bottle on the sample frame 1, the blank is put to the sample bottle that has the matrix arrangement setting on the sample frame 1, and each sample bottle puts the blank and has corresponding serial number, and the placing of sample bottle corresponding serial number puts the blank in the sample bottle. The centrifuge 2 comprises a centrifuge motor 203, a rotor body 201 and a hanging basket 202; the rotor body 201 is in transmission connection with a rotating shaft 2031 of the centrifuge motor 203 and can synchronously rotate along with the rotation of the rotating shaft 2031; the hanging basket 202 is arranged outside the axis of the rotor body 201 and used for loading a centrifuge tube; in the centrifugal operation, the centrifuge tube is loaded on the hanging basket 202, the centrifuge motor 203 drives the rotor body 201 to rotate, and the hanging basket 202 arranged on the rotor body 201 generates a strong centrifugal throwing movement trend. The slide is placed on the slide preparation staining plate 4, and the slide is placed on the slide preparation staining plate 4 in a matrix arrangement and has a corresponding serial number.
In an optional embodiment, a workbench 200 is arranged in the workshop, the sample rack 1 and the slide preparation and dyeing bin 102 are both arranged on the workbench 200, the bottom of one side of the workbench 200 is provided with a centrifugal bin 101, and the centrifuge 2 is arranged in the centrifugal bin 101. When the centrifuge 2 is in operation, the centrifuge chamber 101 is closed to prevent noise from propagating.
As shown in fig. 3, a centrifugal bin sample moving window 1011 is formed on the centrifugal bin 101, and a movable door capable of opening or closing the centrifugal bin sample moving window 1011 is arranged on the centrifugal bin sample moving window 1011; the sample rack 1 is specifically provided on the front and rear sides of the centrifugal chamber sample transfer window 1011. In addition, centrifuge 2 is connected with accurate positioning control mechanism 3 for accurate positioning control centrifuge 2's rotation stop position makes the centrifuging tube on the basket 202 all can reach the position that moves a kind window 101 with the centrifugation storehouse before the centrifugation application of sample or after accomplishing the centrifugation to supply application of sample or sample.
In an alternative embodiment, shown in FIG. 4, the fine positioning control mechanism 3 is located at the bottom of the centrifuge 2.
Also, referring to fig. 5, the shaft 2031 of the centrifuge motor 203 is elongated and extends through the bottom. The precise positioning control mechanism 3 is specifically arranged outside the bottom of the centrifuge motor 203, and is in clutch transmission connection with the lengthened extending end of the rotating shaft 2031. When the centrifuge 2 performs the centrifugal operation, the precise positioning control mechanism 3 and the rotating shaft 2031 are in a transmission separation state, so that the high-speed centrifugation of the centrifuge 2 is not influenced; after the centrifuge 2 finishes the centrifugal operation, the precise positioning control mechanism 3 and the rotating shaft 2031 are in a transmission closed state, and the precise positioning control mechanism 3 can drive the rotating shaft 2031 to continue to rotate, so that the cradle 202 on the rotor body 201 rotates to a position required by the automation equipment, and the automation equipment can perform subsequent automation operation.
Specifically, referring to fig. 5 and 6, the fine positioning control mechanism 3 includes a driving device 301, a clutch 302, an axial elastic coupling 303, and a rotational speed monitoring and positioning system 304. The axial elastic coupling member 303 has elasticity that extends and retracts in the axial direction, the clutch 302 can perform coaxial transmission in a working closed state and does not perform transmission in a separated state, one end of the axial elastic coupling member 303 is connected to the lengthened and extended end of the rotating shaft 3031 of the centrifuge motor 303, and one end of the clutch 302 is connected with the other end of the axial elastic coupling member 303. The output end of the driving device 301 is in transmission connection with the other end of the clutch 302; in an alternative embodiment, the transmission connection between the output of the driving device 301 and the clutch 302 includes: the output end of the driving device 301 is directly in transmission connection with the clutch 302, or the output end of the driving device 301 is in transmission connection with the clutch 302 through a transmission device. In addition, the rotation speed monitoring and positioning system 304 is used for monitoring the rotation speed of the rotating shaft 2031 and positioning the position of the rotating shaft 2031, and the rotation speed monitoring and positioning system 304 is in control connection with the driving device 301.
When the centrifuge 2 performs the centrifugal operation, the clutch 302 is in a separation state, no transmission is performed, the rotating shaft 2031 is driven by the centrifuge motor 203 to rotate, the rotating speed monitoring and positioning system 304 can monitor the rotating speed of the rotating shaft 2031 of the centrifuge motor 203, and can detect whether the centrifuge is stopped or close to a stop state after the centrifugal operation reaches the centrifugal setting time; after the centrifugation, when carrying out accurate positioning control to hanging basket 202 by accurate positioning control mechanism 3, clutch 302 work can be transmitted, this moment pass through clutch 302 and axial elastic coupling 303 transmission drive pivot 2031 by drive arrangement 301 and rotate, and it is rotatory to drive rotor body 201, and rotational speed monitoring positioning system 304 is when monitoring the rotational speed of pivot 2031 simultaneously, accessible feedback control drive arrangement 301's action is fixed a position centrifuge motor 203's pivot 2031's position, under rotational speed monitoring positioning system 304's cooperation, realize accurate location, make centrifuge hang basket 202 rotatory to the position that automation equipment needs.
In an alternative embodiment, the axially resilient coupling member 303 comprises a threaded coupling, or a coupling device with axial flexibility. The clutch 302 is an electromagnetic clutch and comprises an electromagnetic generating end 3021 and a clutch sucker end 3022; the axially resilient coupling member 303 is selectively connected to either the electromagnet generating end 3021 or the clutch cup end 3022. And the axially resilient coupling 303 is connected to the suction cup end 3022 of the clutch 302, while the electromagnetically generated end of the clutch 3022 is connected to the output of the drive means 301.
When the electromagnetic clutch does not work, a gap is kept between the upper electromagnetic generating end 3021 and the lower electromagnetic generating end 3022 and the middle locking position of the clutch sucker end 3022; when the electromagnetic clutch is powered on and works, the axial elastic coupling member 303 is stretched under the action of electromagnetic attraction when the electromagnetic clutch is powered on by utilizing the telescopic characteristic of the axial elastic coupling member 303, so that two ends of the clutch are attracted and closed through the electromagnetic attraction.
In alternative embodiments, the driving device 301 comprises a stepper motor or a servo motor.
The rotational speed monitoring and positioning system 304 includes a positioning sensor, which may include a photoelectric sensor, a proximity sensor, or an electromagnetic sensor, and a rotating encoder 3042.
In an alternative embodiment, the rotational speed monitoring and positioning system 304 includes a photoelectric sensor 3041 and a rotary encoder 3042. The rotating coded disc 3042 is sleeved on the lengthened and extended end of the rotating shaft 2031 of the centrifuge motor and can synchronously rotate along with the rotating shaft 2031; the photoelectric sensor 3041 is arranged outside the rotary encoder 3042, and the rotary encoder 3042 has an induction gap; the photoelectric sensor 3041 includes a probe in a U shape; the edge of the rotating code wheel 3042 extends into the U-shaped probe of the photoelectric sensor 3041, and when the rotating code wheel 3042 rotates, the sensing notch rotates past the U-shaped probe. The photoelectric sensor 3041 is connected to the driving device 301 by feedback control via a controller. In the process of rotating the rotating shaft 2031, each time an induction gap of the rotating code wheel 3042 passes through the U-shaped probe of the photoelectric sensor 3041, the photoelectric sensor 3041 generates a detection signal, so as to monitor the speed and position information of the induction gap, that is, the rotating speed of the rotating code wheel 3042 can be monitored and the position of the rotating code wheel 3042 can be positioned, thereby indirectly obtaining the speed and position information of the rotating shaft 2031.
In addition, optionally, the photoelectric sensor 3041 is further connected to the centrifuge motor 203 through a controller, and the centrifugal rotation speed of the rotating shaft 2031 of the centrifuge motor 203 can be feedback-controlled while the centrifugal rotation speed of the rotating shaft 2031 is monitored.
In an alternative embodiment, the driving device 301 is mounted by a fixing frame 305. The fixing frame 305 is connected to the outside of the bottom of the centrifuge motor 203, and the driving device 301 is installed on the fixing frame 305, so that the installation of the driving device 301 is stable, stable power output is maintained, and when the centrifuge has an error in balancing to generate vibration deviation, the accurate positioning control mechanism 2 can synchronously deviate along with the centrifuge motor 203, so that the centrifuge 2 and the accurate positioning control mechanism 3 maintain stable relative positions.
Optionally, the photoelectric sensor 3041 of the rotational speed monitoring and positioning system 304 is also mounted on the fixing frame 305, so that the overall precise positioning control mechanism 3 is compact in configuration and space-saving. Moreover, a clutch fixing plate 306 is further disposed on the fixing frame 305; the outer part of one end of the clutch 302 is fixedly connected with the clutch fixing plate 306, so that the stability of the clutch 302 in matching with the fixing frame 305 is ensured. In a specific alternative embodiment, the outer portion of the electromagnetic generating end 3021 of the clutch 302 is connected to the clutch mount 306.
And a sample needle 6 and a dyeing needle 7 which can freely move along an X axis, a Y axis and a Z axis are arranged above the working room. Specifically, a three-axis linkage system 5 is arranged above the workshop, the sample needle 6 and the dyeing needle 7 are respectively connected with a linear module 501 of the three-axis linkage system 5 along the X axis through a sample needle holder 503 and a dyeing needle mounting frame 502, and the sample needle 6 and the dyeing needle 7 can move along the X axis or the Y axis under the driving of the three-axis linkage system 5. The sample needle holder 503 and the dyeing needle holder 502 are respectively provided with motors for driving the sample needle 6 and the dyeing needle 7 to move up and down along the Z axis in a telescopic manner, so that the movement of the sample needle 6 and the dyeing needle 7 moving up and down along the Z axis is independent.
The side plate of the outer frame 100 has a liquid inlet 16, the liquid inlet 16 is connected to the liquid pump 14 through a liquid path, and the liquid pump 14 can supply the separation liquid and the dyeing liquid to the sample needle 6 and the dyeing needle 7, respectively. The sample needle 6 and the dyeing needle 7 are connected to plunger pumps 13 through air tubes, respectively, which are independent of each other, and the sample needle 6 and the dyeing needle 7 can perform suction or injection operations in cooperation with the plunger pumps 13. Optionally, a solenoid valve 15 for controlling the direction of the air flow is provided in the air pipe.
Specifically, the sample needle 6 has at least two needle heads 601 thereon; at least two built-in pipelines which are respectively communicated with at least two needle heads 601 are arranged in the sample needle 6 and can respectively convey separation liquid and buffer liquid; at least two built-in pipelines are respectively connected with the plunger pumps 13 corresponding to the sample needles 6 through at least two air pipes, and the suction or injection operation of the two needle heads 601 is controlled by the independent plunger pumps 13.
The dyeing needle 7 comprises a plurality of mutually independent branches; a plurality of mutually independent dyeing needles 7 are connected and arranged on the triaxial linkage system 5 through a dyeing needle mounting frame 502; the plurality of mutually independent dyeing needles 7 are respectively connected with the independent plunger pump 13 through independent air pipes, and the suction or injection operation of each dyeing needle 7 is controlled by the respective independent plunger pump 13, so that the dyeing operation of a plurality of slides can be synchronously finished by the plurality of dyeing needles 7 or the dyeing operation of a single slide can be independently finished by the single dyeing needle 7, the working efficiency of dyeing slide production is effectively improved, and the mutual operation cannot be interfered.
In addition, the centrifuge 2, the accurate positioning control mechanism 3, the three-axis linkage system 5 and the plunger pump 13 are all in control connection with the circuit control system 8. Specifically, the circuit control system 8 includes a control circuit board, and a display screen 801 connected to the control circuit board, and a power switch 802 for controlling on/off of the circuit is disposed on a side of the external frame 100. The control circuit board is provided with a central processing unit and a circuit which is in control connection with the centrifuge motor 203, the driving device 301, the three-axis linkage system 5 and the plunger pump 13.
In the preferred embodiment, a waste liquid tank 11 is also provided on the table 200. Moreover, the bottom of the waste liquid tank 11 is communicated with a waste liquid output pipeline, the waste liquid output pipeline is communicated to a waste liquid output port 17 arranged on the side edge of the outer frame 100, and the upper layer waste liquid after centrifugation can be transferred into the waste liquid tank 11 for centralized discharge, so that pollution is avoided.
In a further preferred embodiment, the sample needle 6 is automatically operated, and the scrubbing of the needle head cannot be performed at all times. Therefore, a nozzle holder 9 is further provided on the work table 200, wherein the nozzle 10 is placed on the nozzle holder 9. Specifically, the nozzle rack 9 is provided with nozzle placement spaces arranged in a matrix, each nozzle placement space is provided with a corresponding number, and the nozzles 10 are placed in the nozzle placement spaces corresponding to the numbers. The disposable suction nozzle 10 is matched with the suction or injection operation of the sample needle 6, the suction nozzle 10 is in direct contact with the sample liquid, the sample needle 6 is protected from being polluted, and therefore different samples are guaranteed from being polluted.
In a more preferred embodiment, the sample needle 6 is connected with a motor for driving the sample needle 6 by an elastic coupling, so that the sample needle 6 has a buffer function in the process of taking the suction nozzle 10, the good matching of the needle head of the sample needle 6 and the suction nozzle 10 can be ensured, liquid leakage is not easy to occur, and noise generated in the process of taking the suction nozzle 10 can be eliminated.
Referring to fig. 7, the suction nozzle 10 is fitted to the head of the sample needle 6 and can be closely fitted over the head of the sample needle 6. When the sample needle 6 transfers a sample, centrifugate or centrifugal sediment, the sample needle 6 moves above the suction nozzle rack 9 and then moves downwards along the Z axis, the head part extends into the suction nozzle 10, and the suction nozzle 10 is sleeved on the sample needle 6 and is matched with the sample needle 6 for use.
Furthermore, a waste collection box 12 is provided for recycling the supply material comprising the mouthpiece 10. Wherein, a suction nozzle dropping groove is arranged on the workbench 200, and the waste collecting box 12 is arranged at the bottom of the suction nozzle dropping groove. Further, an annular card portion which is fitted closely to the head of the sample needle 6 is provided on the sample needle holder 503. After the suction nozzle 10 and the sample needle 6 are used together, the sample needle 6 with the suction nozzle 10 is moved to the position above the nozzle drop slot, when the sample needle 6 with the suction nozzle 10 is retracted and moved along the Z-axis, the annular clamping part can prevent the suction nozzle 10 from retracting along with the sample needle 6 and ejecting the suction nozzle 10, and the suction nozzle 10 drops from the nozzle drop slot and is recovered into the waste collection box 12.
In an alternative embodiment, a filter mesh is placed over the slide. And the filter net sleeve can be sleeved on the sample needle 6 for matching use and can be recovered by the waste material collecting box 12 after being jacked by the annular clamping part on the sample needle frame 503.
Example 1
The liquid-based cell slice-making dyeing machine can fully automatically complete the slice making and Papanicolaou (or HE) dyeing of gynecological and non-gynecological samples so as to carry out cytological morphological examination.
The liquid-based cell slice-making dyeing machine provided by the embodiment of the invention is adopted for slice-making dyeing, and the specific operation flow is as follows:
(1) manually placing a centrifugal tube on a hanging basket of a centrifuge, and manually adding a cell sample into a sample bottle of a sample rack; starting a circuit switch, and operating a display screen to start a full-automatic film production and dyeing process;
(2) rotating a centrifugal tube on the centrifugal machine to a position corresponding to the sample moving window of the centrifugal bin; the three-axis linkage system drives the sample needle to be transferred to the upper part of the sample moving window of the centrifugal bin and to move downwards to extend into the centrifugal tube, and the sample separation liquid is filled into the centrifugal tube under the coordination of the plunger pump;
(3) after the sample needle is driven by the three-axis linkage system to be matched with the suction nozzle, the sample needle is transferred to the upper part of the sample rack and moves downwards to extend into a sample bottle containing a cell sample, the cell sample in the sample bottle is uniformly sucked under the coordination of the plunger pump, and then the sample is transferred into the centrifugal tube and slowly added; the three-axis linkage system drives the sample needle to a suction nozzle dropping groove to recycle the suction nozzle;
(4) closing a sample moving window of the centrifugal bin, and centrifuging by a centrifuge; after the centrifugation is finished, opening a sample moving window of the centrifugation bin, and controlling the centrifuge tube to rotate to a position corresponding to the sample moving window of the centrifugation bin by the accurate positioning control mechanism;
(5) after the sample needle is driven by the three-axis linkage system to be matched with the suction nozzle, the sample needle is transferred to a centrifugal bin sample moving window, the lower side of the suction nozzle is operated to suck under the cooperation of a plunger pump, the supernatant of the centrifugal tube is removed into a waste liquid tank, and only cell sediment is left; the three-axis linkage system drives the sample needle to a suction nozzle dropping groove to recycle the suction nozzle;
(6) after the sample needle is driven by the three-axis linkage system to be matched with the suction nozzle, the sample needle is transferred to a sample moving window of a centrifugal bin, and buffer liquid is injected into the centrifugal tube under the coordination of a plunger pump and is uniformly sucked; sucking the uniformly mixed sample liquid, and transferring the sample liquid onto a glass slide of a slide-making staining plate; naturally settling cells to the adhesive slide by gravity to finish the cell slide preparation;
(7) driving a dyeing needle by a three-axis linkage system, pumping liquid in the glass sheet and adding flushing liquid under the cooperation of a plunger pump, settling, and repeating for a plurality of times; removing liquid in the glass slide, adding a buffer solution, settling, and repeating for several times; removing liquid in the glass sheet, adding hematoxylin, settling, and repeating for several times; removing liquid in the glass slide, adding a buffer solution, settling, and repeating for several times; removing liquid in the glass sheet, adding flushing liquid, settling, and repeating for several times; removing liquid from the slide and adding eosin (EAOG, EA50), settling, and repeating for several times; removing liquid in the glass sheet, adding flushing liquid, settling, and repeating for several times;
(8) and (5) after the slide preparation and staining are finished, taking down the stained slide.
In an alternative embodiment, the slides of steps (6) - (7) are performed in a fitted filter screen. And (5) after the step (7) is finished, driving the sample needle to be matched with the filter screen sleeve by the three-axis linkage system, and transferring the sample needle to a suction nozzle falling groove for suction nozzle recovery.
In the dyeing and slide-making process, the slide-making and dyeing processes in the steps (2) to (7) are all completed in a full-automatic manner under the liquid-based cell slide-making and dyeing machine, and the full-automatic completion comprises the processes of adding separation liquid, transferring a sample to a centrifuge tube, carrying out centrifugal precipitation, sucking the supernatant of the centrifuge tube, taking a precipitate to a slide, carrying out sedimentation and slide-making, carrying out Papanicolaou (or HE) dyeing and the like.
The above embodiments are merely preferred embodiments of the present invention, and the technical solutions of the present invention are described in further detail, but the scope and implementation of the present invention are not limited thereto, and any changes, combinations, deletions, substitutions or modifications that do not depart from the spirit and principle of the present invention are included in the scope of the present invention.

Claims (10)

1. A full-automatic liquid-based cell slice-making dyeing machine is characterized by comprising a sample rack, a centrifuge, a slice-making dyeing plate, a sample needle and a dyeing needle; a sample bottle is placed on the sample rack and used for containing a sample; the centrifugal machine is connected with a precise positioning control mechanism and is used for precisely positioning and controlling the rotation stop position of the centrifugal machine; a slide is placed on the sheet preparation staining plate; the sample needle and the dyeing needle can be driven by a three-axis linkage system to freely move along an X axis, a Y axis and a Z axis, and the movement of the sample needle and the movement of the dyeing needle along the Z axis are mutually independent; the sample needle and the dyeing needle are respectively connected with mutually independent plunger pumps through pipelines; the accurate positioning control mechanism, the centrifuge, the three-axis linkage system and the plunger pump are all in control connection with a circuit control system.
2. The full-automatic liquid-based cell slice-making and dyeing machine as claimed in claim 1, wherein the motor shaft of the centrifuge is elongated and extends through the bottom; the accurate positioning control mechanism is arranged outside the bottom of the centrifuge motor and is in clutch transmission connection with a lengthened extension end of a rotating shaft of the centrifuge motor;
the accurate positioning control mechanism comprises a driving device, a clutch, an axial elastic coupling and a rotating speed monitoring and positioning system; one end of the axial elastic coupling member is connected to the lengthened and extended end of the rotating shaft of the centrifuge motor, one end of the clutch is connected with the other end of the axial elastic coupling member, and the output end of the driving device is in transmission connection with the other end of the clutch; the rotating speed monitoring and positioning system is used for monitoring the rotating speed of the rotating shaft of the centrifuge motor and positioning the position of the rotating shaft of the centrifuge motor, and the rotating speed monitoring and positioning system is in control connection with the driving device through the circuit control system.
3. The full-automatic liquid-based cell slice-making and dyeing machine as claimed in claim 2, wherein the rotation speed monitoring and positioning system comprises a positioning sensor and a rotary code disc; the rotary coded disc is sleeved on the lengthened extending end of the rotating shaft of the centrifuge motor; the positioning sensor is arranged on the outer side of the rotary coded disc and can monitor the rotating speed of the rotary coded disc and position the rotary coded disc; the positioning sensor is connected with the driving device in a feedback control mode through the circuit control system.
4. The fully automatic liquid-based cell slide-dyeing machine according to claim 1, wherein said sample needle has at least two needles thereon; and at least two built-in pipelines which are respectively communicated with at least two needle heads are arranged in the sample needle; at least two built-in pipelines are respectively connected with the plunger pump corresponding to the sample needle through at least two air pipes.
5. The full-automatic liquid-based cell slide-dyeing machine according to claim 1, wherein said dyeing needle comprises a plurality of independent pieces; a plurality of mutually independent dyeing needles are connected and arranged on the three-axis linkage system through a mounting frame; and the dyeing needles which are mutually independent are respectively connected with independent plunger pumps through independent air pipes.
6. The full-automatic liquid-based cell slice-making and dyeing machine as claimed in claim 1, wherein a waste liquid tank is further provided; and the bottom of the waste liquid tank is communicated with a waste liquid output pipeline.
7. The full-automatic liquid-based cell preparation and dyeing machine as claimed in claim 1, wherein said circuit control system comprises a control circuit board, and a display screen connected to said control circuit board; and the control circuit board is provided with a central processing unit.
8. The full-automatic liquid-based cell slice-making and dyeing machine as claimed in any one of claims 1 to 7, further comprising a suction nozzle rack and a waste collection box; a suction nozzle is arranged on the suction nozzle frame;
the suction nozzle is matched with the head of the sample needle and can be tightly sleeved on the head of the sample needle; when the sample needle transfers a sample, a centrifugate or a centrifugal sediment, the suction nozzle is sleeved on the sample needle for cooperation;
the waste collecting box is used for recovering the article materials comprising the suction nozzle; the sample needle can be arranged on a needle frame in a telescopic way along the Z axis, the needle frame is provided with an annular clamping part which is tightly matched with the head of the sample needle, and when the sample needle which is sleeved with the suction nozzle moves in a retracting way along the Z axis, the annular clamping part can prevent the suction nozzle from retracting along with the sample needle and pushing down the suction nozzle.
9. The full-automatic liquid-based cell slide-making and dyeing machine as claimed in claim 8, wherein a filter net cover is placed on said slide; and the filter screen sleeve can be sleeved on the sample needle for matching use and can be recovered by the waste material collecting box after being jacked by the annular clamping part.
10. A full-automatic liquid-based cell slice-making and dyeing method is characterized in that the full-automatic liquid-based cell slice-making and dyeing machine is based on claims 1-9, and comprises the following steps:
s1, starting a control program of the circuit control system;
s2, the three-axis linkage system drives the sample needle to freely move along the X axis, the Y axis and the Z axis;
s3, filling the separation liquid into the centrifuge tube of the centrifuge by the sample needle;
s4, the sample needle transfers the sample in the sample bottle to a centrifuge tube of the centrifuge;
s5, starting centrifugation by the centrifuge;
s6, after the centrifugation is finished, the accurate positioning control mechanism accurately controls the positioning; driving the sample needle to suck and remove the supernatant in the centrifuge tube, transferring the centrifugal precipitate in the centrifuge tube to a slide of the slide preparation staining plate, and performing sedimentation to prepare a slide;
s7, injecting a staining solution into the slide subjected to sedimentation slide preparation by the staining needle, and staining the centrifugal precipitate on the slide;
and S8, the staining needle is restored to the original position, and the liquid-based cell slice staining is completed.
CN202010631638.0A 2020-07-03 2020-07-03 Full-automatic liquid-based cell slice-making dyeing machine and slice-making dyeing method Pending CN111579339A (en)

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112179738A (en) * 2020-09-30 2021-01-05 易普森生物科技(深圳)有限公司 Novel cell pelleter
CN113624576A (en) * 2021-08-03 2021-11-09 深路医学科技(武汉)有限公司 Semi-automatic liquid-based cell pelleter
CN113684120A (en) * 2021-08-20 2021-11-23 圣湘生物科技股份有限公司 Nucleic acid detection apparatus and nucleic acid detection method
CN115839872A (en) * 2022-12-27 2023-03-24 武汉中纪生物科技有限公司 Full-automatic liquid-based cell slice-making dyeing machine

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112179738A (en) * 2020-09-30 2021-01-05 易普森生物科技(深圳)有限公司 Novel cell pelleter
CN112179738B (en) * 2020-09-30 2021-07-13 易普森生物科技(深圳)有限公司 Novel cell pelleter
CN113624576A (en) * 2021-08-03 2021-11-09 深路医学科技(武汉)有限公司 Semi-automatic liquid-based cell pelleter
CN113684120A (en) * 2021-08-20 2021-11-23 圣湘生物科技股份有限公司 Nucleic acid detection apparatus and nucleic acid detection method
CN115839872A (en) * 2022-12-27 2023-03-24 武汉中纪生物科技有限公司 Full-automatic liquid-based cell slice-making dyeing machine

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