WO2017202192A1 - Pointe polyvalente d'outil pour appareil d'induction et de culture de cellules souches et appareil d'induction et de culture de cellules souches - Google Patents

Pointe polyvalente d'outil pour appareil d'induction et de culture de cellules souches et appareil d'induction et de culture de cellules souches Download PDF

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Publication number
WO2017202192A1
WO2017202192A1 PCT/CN2017/083415 CN2017083415W WO2017202192A1 WO 2017202192 A1 WO2017202192 A1 WO 2017202192A1 CN 2017083415 W CN2017083415 W CN 2017083415W WO 2017202192 A1 WO2017202192 A1 WO 2017202192A1
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WIPO (PCT)
Prior art keywords
module
stem cell
culture apparatus
liquid
inducing culture
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/CN2017/083415
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English (en)
Chinese (zh)
Inventor
裴端卿
张骁
董建华
秦季生
卢俊
骆健忠
樊科
宋研
麦仕文
欧阳瑶
赵洪南
张凤香
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Guangzhou Institutes of Biomedicine and Health
Original Assignee
Guangzhou Institutes of Biomedicine and Health
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from CN201610368609.3A external-priority patent/CN105838583B/zh
Priority claimed from CN201610369456.4A external-priority patent/CN105817434B/zh
Priority claimed from CN201610552157.4A external-priority patent/CN105923386A/zh
Priority claimed from CN201610541183.7A external-priority patent/CN106047698A/zh
Application filed by Guangzhou Institutes of Biomedicine and Health filed Critical Guangzhou Institutes of Biomedicine and Health
Publication of WO2017202192A1 publication Critical patent/WO2017202192A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M1/00—Apparatus for enzymology or microbiology
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M3/00—Tissue, human, animal or plant cell, or virus culture apparatus

Definitions

  • the invention relates to the technical field of stem cell culture, in particular to a multifunctional head and stem cell induction culture device for stem cell induced culture equipment.
  • the invention aims to overcome the defects of the prior art, and provides a multifunctional head for a stem cell-inducing culture device with versatility, which can effectively improve the efficiency, so that the stem cell-inducing culture device adopting the multifunctional head of the structure can be fully automated, and has a very high Good promotion of use value.
  • the present invention adopts the following technical solutions:
  • the present invention provides a multi-function head for a stem cell-inducing culture apparatus, comprising the multi-function head comprising a clone acquisition module, a pipetting liquid exchange module, a culture device grasping module, a liquid level detecting module, and a driving module;
  • the cloning acquisition module comprises a cloning acquisition needle for acquiring a clone;
  • the pipetting and liquid changing module comprises a pipetting and changing needle for pipetting and changing the liquid;
  • the cloning obtaining needle is arranged side by side with the pipetting and changing needle;
  • the culture device grasping module is configured to move a cell culture device;
  • the liquid level detecting module is configured to detect a liquid surface of a cell culture medium in the cell culture device; and the driving module is configured to drive the multifunctional head movement.
  • the present invention also provides a stem cell-inducing culture apparatus comprising the above-described stem
  • the cell-inducing culture device uses a multi-function head.
  • the invention has the beneficial effects that the embodiment of the invention provides a multifunctional head for a stem cell induced culture device with versatility, which can simultaneously have a liquid exchange, a clone, a cell culture device, and a cell culture device.
  • Various functions such as the liquid level of the cell culture medium and the detection of the wind speed to control the air cleanliness.
  • the stem cell-inducing culture apparatus using the multi-function head of the structure can be fully automated. It can effectively improve efficiency and has a good promotion value.
  • the embodiment of the invention also provides a stem cell induction culture device, which can realize fully automatic intelligent operation and can effectively improve efficiency.
  • FIG. 1 is a schematic perspective view showing the structure of an automatic pallet device in a stem cell-inducing culture apparatus according to an embodiment of the present invention
  • FIG. 2 is a side view showing the structure of an automatic pallet device in a stem cell-inducing culture apparatus according to an embodiment of the present invention
  • FIG. 3 is a schematic structural view of a culture apparatus storage basket in an automatic pallet apparatus in a stem cell-inducing culture apparatus according to an embodiment of the present invention
  • FIG. 4 is a schematic structural view of a plate frame in an automatic pallet device in a stem cell-inducing culture apparatus according to an embodiment of the present invention
  • FIG. 5 is a schematic structural view of a culture instrument tray in an automatic pallet device in a stem cell-inducing culture apparatus according to an embodiment of the present invention
  • FIG. 6 is an overall view of a culture device grasping device in a stem cell-inducing culture apparatus according to an embodiment of the present invention
  • Figure 7 is a side view of a culture device grasping device in a stem cell-inducing culture apparatus according to an embodiment of the present invention.
  • Figure 8 is a bottom plan view of a culture device grasping device in a stem cell-inducing culture apparatus according to an embodiment of the present invention.
  • FIG. 9 is a schematic front view showing the structure of an automatic needle washing device in a stem cell-inducing culture apparatus according to an embodiment of the present invention.
  • Figure 10 is a schematic rear view showing the structure of an automatic needle washing device in a stem cell-inducing culture apparatus according to an embodiment of the present invention.
  • Figure 11 is a perspective view showing the structure of a multi-function head in a stem cell-inducing culture apparatus according to an embodiment of the present invention.
  • Figure 12 is a perspective view showing another perspective of a multi-function head in a stem cell-inducing culture apparatus according to an embodiment of the present invention.
  • Figure 13 is a structural diagram of a cell image acquisition device in a stem cell-inducing culture apparatus according to an embodiment of the present invention.
  • Figure 14 is a block diagram showing a control system of a cell image acquisition device in a stem cell-inducing culture apparatus according to an embodiment of the present invention
  • FIG. 15 is a flowchart of a control method of a cell image acquiring apparatus according to an embodiment of the present invention.
  • Figure 16 is a schematic view showing the structure of a pipetting and changing needle according to an embodiment of the present invention.
  • Figure 17 is a cross-sectional view taken along line A-A of Figure 16;
  • Plate rack 1 bottom plate 11, riser 12, culture device storage basket 2, handle portion 21, card position 22, iron bar 23, culture device tray 3, magnet 31, bottom support 4, self-locking type knob plunger 5, Drive module 6, slider 7;
  • first segment 4031 a first segment 4031, a second segment 4032, a third segment 4033, a hollow tip 4034, a first connecting segment 4035, a second connecting segment 4036, a third connecting segment 4037;
  • Flash 501 Flash 501, first slide 502, camera mechanism 503, second slide 504, control system 505, slider 506, scale 507, displacement detection module 508, cell culture board 509, data processing module 5051, first motion control The module 5052, the second motion control module 5053, the flash frequency control module 5054, the camera shutter control module 5055, and the displacement detecting module 5056.
  • the stem cell-inducing culture apparatus further includes a multi-function head.
  • the multifunctional head includes a clone acquisition module, a pipetting and liquid changing module, a culture device grasping module, a liquid level detecting module, and a driving module.
  • the culture device is a petri dish, a culture plate or the like which can be used for laboratory equipment for microorganism or cell culture. In an embodiment of the invention, the culture device may be a culture plate.
  • the driving module is used for driving the multi-function head movement, and the entire multi-function head can move in three dimensions of the X-axis, the Y-axis and the Z-axis.
  • the drive module can include a cylinder and a piston, and can be other structures that implement a drive function.
  • the clone acquisition module includes a clone acquisition needle 401 for acquiring a clone; the pipetting liquid exchange module includes a pipetting liquid exchange needle 403 for pipetting and liquid exchange.
  • the number of the cloning and obtaining needles 401 is the same as that of the liquid-changing needles 403, and may be one, preferably a plurality, and specifically may include four, six or eight.
  • the plurality of clone obtaining needles 401 are arranged side by side with the plurality of pipetting liquid changing needles 403, and the distance between the clone obtaining needle 401 and the pipetting liquid changing needle 403 can be determined according to the size of the cell culture apparatus, and the clone obtaining needle 401 and pipetting The liquid changing needle 403 can be moved up and down.
  • the pipetting liquid changing needle has an elongated tubular body, and the tubular body includes a first segment 4031, a second segment 4032 and a third segment 4033 which are sequentially connected.
  • the inner wall diameter of the second section 4032 is larger than the inner wall diameter of the third section 4033, and the inner wall diameter of the third section 4033 is larger than the inner wall diameter of the first section 4031.
  • one end of the tubular body is sealingly connected by a cap that is secured to the tubular body by screws.
  • the cap is fixedly coupled to the tubular body directly by four screws, the screws being evenly distributed over the cap.
  • the screw is a M1.6 screw.
  • the end of the first section 4031 has a hollow tip 4034 having an inner wall diameter that is less than the inner wall diameter of the first section 4031.
  • first segment 4031 and the second segment 4032 are connected by a first connecting segment 4035, the interior of the first connecting segment 4035 is conical; the second segment 4032 is The third segments 4033 are connected by a second connecting section 4036, and the inside of the second connecting section 4036 is conical.
  • first segment 4031 and the hollow tip 4034 are connected by a third connecting segment 4037, and the interior of the third connecting segment 4037 is conical.
  • the interior of the tubular body is provided with a coating layer having a thickness of 10 um.
  • the material of the coating layer is Teflon.
  • the outer wall of the tubular body is also provided with Teflon.
  • Teflon has good chemical stability and biological inertness, does not cause pollution and toxicity to organisms, and its ultra-low friction coefficient is conducive to the flow of liquid, no liquid, no residue and other excellent characteristics.
  • the pipetting and liquid changing module further includes a pipetting pump 408, and the pipetting pump 408 is pushed by the cylinder in the driving module to drive the pipetting and changing needle 403 to move up and down, thereby extracting and discharging the liquid.
  • the driving module may include nine cylinders for respectively driving different components in the multi-function head to move.
  • the multi-function head further includes a dispensing valve 409 for effecting the dispensing control of the outer ring punching liquid of the cloning acquisition needle 401.
  • the culture device grasping module is used to move the cell culture device, and specifically includes a gripper 404 as shown in the figure. During the operation of the multi-function head, the gripper 404 is used to grasp the cell culture device and move it to a desired position. Then put down the cell culture equipment.
  • the multi-function head also includes a visual monitoring module and a cell imaging auxiliary module.
  • the visual monitoring module is configured to track the position of the multi-function head, and monitor the situation of the stem cell-induced work surface in the culture device, and specifically includes a camera 405; the cell imaging auxiliary module may include a light source 407, and the light source 407 may be a high-speed flash. Used in conjunction with camera 405 for illumination during cell imaging.
  • the camera 405 is also used to monitor various conditions of the work surface of the stem cell-inducing culture apparatus. For example, before the gripper 404 grasps the cell culture apparatus, the position of the cell culture apparatus can be judged by the camera 405 and then grasped.
  • the detection process of the visual monitoring module is as follows: taking multiple background images without samples under different illumination conditions; removing the background image from the previous step, obtaining the approximate position information of the background, and roughly determining the position of the multi-function head; Search all the straight edge information in the approximate area of the location, find the four borders of the multi-function head from all the lines, and determine the position of the multi-function head.
  • the liquid level detecting module is used for detecting the liquid level of the cell culture medium in the cell culture device, specifically The ultrasonic sensor 402 shown in the figures is included.
  • the detection process of the liquid level detecting module is as follows: scanning the entire image, dividing each picture into small blocks of 80 pixels wide; inputting each small piece into an automatic classification algorithm, marking each piece as a background and various Cell type; count the cell type and quantity in the whole cell, calculate the liquid demand in each well according to the amount of medium required by various cells, and obtain the liquid according to the liquid demand in each well. the amount.
  • the multi-function head further includes a code scanning module.
  • the code scan module may include a code reader 406 for acquiring coded information on the cell culture device, specifically including two-dimensionally marked on the cell culture device. Code information or bar code information and so on.
  • the multi-function head further includes a wind speed detecting module, and the wind speed detecting module may include a wind speed sensor 4010 for detecting the wind speed around the cell culture apparatus, and the wind cleanliness can be further controlled by the detection and control of the wind speed.
  • the wind speed detecting module includes two wind speed sensors 4010 respectively disposed at two ends of the same side of the multi-function, which can make the wind speed detection more accurate.
  • the wind speed detecting module controls the wind speed around the cell culture apparatus to be in the range of 0.4 m/s to 0.8 m/s, and more preferably, the control wind speed is 0.5 m/s.
  • the invention relates to a stem cell-inducing culture device with a multifunctional head, which has a liquid-liquid exchange, a clone, a cell culture device, a liquid medium for detecting a cell culture medium in a cell culture device, and a wind speed control air cleanness test.
  • a stem cell-inducing culture apparatus using the multi-function head of the structure can be fully automated.
  • the stem cell-inducing culture device provided by the embodiment of the invention further comprises an automatic plate rack device for storing the culture device.
  • the automatic pallet device for storing the culture device comprises a plate holder 1; a culture device storage basket 2 connected to the plate holder 1; wherein the culture device storage basket 2 is provided with a plurality of layers of cards for placing the culture device on both sides thereof a handle 22 for lifting the culture storage basket 2; a drive module 6 for driving the movement of the automatic pallet device; and a detection module for detecting whether the culture device is placed on the card position of the culture storage basket .
  • the culture device is a petri dish, a culture plate or the like which can be used for laboratory equipment for microorganism or cell culture.
  • the culture device may be a culture dish.
  • the culture device storage basket 2 is a rectangular box structure with an open side, specifically including a first side and a second side of the left and right sides, a third side of the top, and a fourth side of the bottom. And the fifth side of the back.
  • the handle portion 21 is disposed above the third surface for convenient manual training
  • the utensil storage basket 2 is presented or put back.
  • the two sides of the culture apparatus storage basket 2 are provided with a plurality of layers of card positions for placing the culture apparatus, and the number of layers of the card position is not limited, and may be 8 layers, 10 layers or 12 layers.
  • the culture apparatus is placed on the card position 22 in the culture apparatus storage basket 2 through the culture apparatus tray 3, as shown in Fig. 5, one end of the culture apparatus tray 3 is provided with a magnet 31; and the culture apparatus storage basket 2 is opposed to the open side.
  • the iron strip 23 is provided on the surface, and the iron strip 23 in the culture apparatus storage basket 2 is engaged with the magnet 31 on the culture apparatus tray 3 to stabilize the position of the culture apparatus tray 3.
  • the two sides of the culture device storage basket 2 that is, the first side and the second side, are provided with a plurality of openings, and the openings are specifically disposed between the card position and the card position; the culture tool storage basket 2
  • the fifth side of the back opposite the open side is also provided with a plurality of openings.
  • the number of the first side and the second side opening may be one or more, preferably in accordance with the number of the card positions, that is, when the 12-layer card position is set, 12 empty openings may be opened; and the opening of the fifth side of the back side It can be set to two, which are respectively disposed on both sides of the iron bar 23. These openings are arranged to reduce the weight of the entire culture storage basket 2 on the one hand, and to facilitate the observation of the inside of the culture storage basket 2 on the other hand.
  • the pallet 1 includes a bottom plate 11 and a riser 12.
  • the bottom plate 11 is used to support the culture tool storage basket 2.
  • the bottom plate 11 may have a triangular structure and may be a triangular rib.
  • the bottom plate 11 is in contact with the culture tool storage basket 2, and the bottom tray 4 includes an automatic card holder for catching the culture device storage basket 2 so as to better secure the device storage basket 2 and the plate holder 1 in a fixed connection.
  • the bottom support 4 may be a disk bottom support. Of course, it may be provided in other shapes as long as the culture tool storage basket 2 and the plate holder 1 can be better fixed.
  • the shoe 4 includes a cylindrical boss, and the fourth surface of the bottom of the culture device storage basket 2 is provided with a cylindrical hole, and the cylindrical boss of the bottom plate 4 and the cylindrical hole of the culture storage basket 2 are precisely matched. Play a role in positioning and fixing.
  • the riser 12 is fixedly connected to the culture tool storage basket 2, and can be fixedly connected by a self-locking type knob plunger 5.
  • the vertical plate 12 of the plate frame 1 is provided with a groove through which the self-locking type knob plunger 5 passes.
  • the pallet 1 may be made of an aluminum alloy.
  • the driving module 6 is mainly used for driving the movement of the automatic pallet device, and may be a motor or the like.
  • the detecting module can be various sensors, preferably fiber optic sensors, and the fiber optic sensor is disposed in front of the rack 1 to facilitate detecting whether a culture device is placed on the card position 22, detecting the specific position of the culture device, and detecting whether the culture device is stably placed.
  • the detection module includes at least two sensors, one for detecting the culture device and one for detecting the culture device tray.
  • the automatic plate rack device for storing the culture device is disposed under the machine in the stem cell-inducing culture device, wherein the machine table is a platform outside the automatic plate rack device for storing the culture device.
  • the drive module 6 includes a motor and a drive.
  • the slider 7 on the drive is fixedly coupled to the pallet 1, the motor drives the single-axis drive to move the slider 7, and the drive module 6 drives the pallet 1 to move in the vertical direction.
  • the automatic pallet device for storing the culture equipment can automatically rise above the machine under the control of the motor.
  • the detection module in the automatic pallet device can be arranged on the machine platform, and when the pallet 1 moves, the position of the detection module is fixed.
  • the specific working process of the automatic plate rack device for storing the culture device of the present invention is: the automatic plate rack device for storing the culture device can automatically rise above the machine table under the control of the driving module 6; the detecting module detects whether each layer of the card position is The culture device, the specific position of each culture device, and whether the culture device is firmly fixed on the culture device tray; then, the data detected by the detection module is used to accurately obtain the position of the desired culture device, and then the culture device is sent to the machine. On the stage, it is convenient for the hook on the machine to automatically pull out the culture device.
  • the detection module automatically detects the vacant position on the culture device storage basket 2, and pushes the culture device back to the culture device storage basket 2 under the push of the hook on the machine table, and the magnet 31 on the culture device tray 3 will be The iron strip 23 in the culture storage basket 2 is sucked to make the culture apparatus more stable.
  • the detection module detects that the culture device has been placed, the automatic plate holder device is lowered below the machine table, saving machine space.
  • a self-locking type knob plunger 5 and a bottom bracket 4 are designed. By operating the self-locking type knob plunger 5, the culture tool storage basket 2 can also be manually taken out or put back, which facilitates the manual operation required in special cases, and the application of the device is more flexible.
  • the automatic plate rack device for storing the culture device has the advantages of simple structure, convenient access, safe and reliable automatic plate rack device for storing the culture device, fully automatic intelligent operation and large flux, which can effectively improve efficiency and has good performance. Promote the use value.
  • a stem cell-inducing culture apparatus capable of arranging an automatic plate rack device for storing a culture device under the machine in the stem cell-inducing culture device, which saves space and avoids damage and contamination of the culture device.
  • the stem cell-inducing culture device further includes a culture device grasping device for grasping the culture device 203, and the grasping device includes a clip.
  • the claw portion 2011 is composed of a connecting rod 20112 connecting two claw fingers 20111 for clamping the culture device 203;
  • the abutting portion 2012 is vertically disposed on the side of the clamping portion 201 and parallel with the claw finger 20111 for The position of the culture device 203 is restricted;
  • the control device 202 is connected to the claw portion 2011 for controlling the movement of the claw portion 2011.
  • the culture device is a petri dish, a culture plate or the like which can be used for laboratory equipment for microorganism or cell culture.
  • the culture device may be a culture plate.
  • the control device 202 has a rectangular parallelepiped shape, and two connecting ears are disposed on the lower end surface.
  • the connecting rods 20112 are fixedly connected to the connecting ears through the connecting members, the two connecting ears are disposed on the same horizontal rail, and the control device 202 controls the two connecting ears. Movement, thereby driving the link 20112 to do horizontal movement.
  • the connecting rod 20112 is connected with claws 20111 at both ends, the claw finger 20111 is vertically downward, and the bottom end of the claw finger 20111 is provided with a pallet, so that the claw finger 20111 is L-shaped, and when the culture device 203 is grasped, the pallet is just supported
  • the four corners of the culture device 203 are used to make the grasping device more stable;
  • the connecting rod 20112 can be a fixed length link or a telescopic link.
  • the connecting rod 20112 and the culture device 203 The length of any one side is the same; when the connecting rod is a retractable connecting rod, the distance between the two claw fingers 20111 can be adjusted by the telescopic rod, and can be adapted to the culture apparatus 203 of various sizes.
  • the abutting portion 2012 may be a spring piece or a baffle plate for adjusting the positional deviation of the culture device 203 during the grasping process, and preventing the culture device 203 from falling due to the positional deviation during the grasping process; the spring piece or The baffle is disposed near the claw finger 20111, the upper end is fixed to the outside of the connecting rod 20112, and the lower end is suspended.
  • the control device 202 controls the clamping portion 201 directly above the culture device 203, the control claw portion 2011 is relatively far away, and the clamping portion 201 is lowered to a position slightly lower than the bottom surface of the culture device 203, and the control claw is controlled.
  • the portion 2011 is relatively close, the abutment portion 2012 adjusts the position of the culture device 203, and when the claw finger 20111 comes into contact with the culture device 203, the control device 202 controls the clamping portion 201 to rise, and the pallet of the claw finger 20111 just supports the four corners of the culture device 203.
  • the grasping of the culture device 203 is completed.
  • the stem cell-inducing culture apparatus of the embodiment of the present invention cooperates with the gripping portion 201 by the control device 202 in the culture device grasping device, so that the gripping device is accurate and stable when the culture device 203 is grasped.
  • the stem cell-inducing culture apparatus further includes a needle automatic washing device.
  • the automatic needle washing apparatus of this embodiment includes a washing body 301 including a first washing area, a second washing area, a brushing area, a drying area, and a control area.
  • the needle automatic washing device is mainly used for washing the picking needle used in biomedical experiments. Of course, it can also be used to wash other types of needles.
  • the first cleaning zone includes a first liquid tank 302, and the first liquid tank 302 includes a first inlet hole and a first outlet hole for allowing the first cleaning liquid to flow in and out.
  • the first cleaning liquid is a buffer solution, specifically, a PBS buffer solution. It is mainly used as a buffer for picking up needles for cell picking operations.
  • the first inlet hole is located on the left side of the first liquid tank 302 shown in FIG. 9, and the first outlet hole is located at the intermediate position of the first liquid tank 302.
  • the first cleaning area further includes a second liquid tank 303, and the second liquid tank 303 includes a second inlet hole and a second outlet hole for allowing the second cleaning liquid to flow in and out.
  • the second inlet hole is located in FIG.
  • the second outlet hole is located at an intermediate position of the second liquid tank 303.
  • the second cleaning liquid is distilled water or deionized water, and is mainly used for rinsing and picking the needle.
  • the brushing area includes a groove 304 provided with a brush head, and the groove includes a third inlet hole and a third outlet hole for allowing the third cleaning liquid to flow in and out.
  • the third inlet hole is located in the groove 304 shown in FIG. On the left side, the first outlet hole, the second outlet hole, and the outlet opening of the third outlet hole are horizontally to the right.
  • the third exit hole is located at an intermediate position of the recess 304, specifically below the brush head.
  • the third cleaning liquid is an organic solvent, specifically alcohol or the like, and is mainly used for disinfecting the picking needle.
  • the picking needle is zigzag-washed or back-shaped in the groove 304 provided with the brush head. scrub.
  • the brush head is disposed in the groove 304 of the circulating alcohol, and the needle can be sterilized while brushing the residue on the needle, the brushing effect is good, and the cleaning power is stronger.
  • the brush body 301 includes a front side and a back side, wherein, as shown in FIG. 9, the first liquid tank 302, the second liquid tank 303, and the recess 304 are both disposed on the front surface of the scrubbing body 301.
  • the first liquid tank 302, the second liquid tank 303, and the recess 304 are all rounded to facilitate cleaning of the needle while avoiding the residue of waste liquid or waste.
  • the first outlet position, the second outlet position and the third outlet portion are disposed at the lowest points of the grooves of the first liquid tank 302, the second liquid tank 303 and the recess 304, which facilitates completely putting the liquid in the tank dry.
  • the water washing body 301 is further provided with a water filtering hole 307, and when the liquid in each of the first liquid tank 302, the second liquid tank 303 and the recess 304 overflows, the water is drained to the water filter. The hole 7 is discharged.
  • the drying area is used to dry the needle, and the cleaned and washed needle is dried; the drying area includes a drying zone and a draining zone.
  • the drying zone includes a drying hole 305, and the drying hole 305 can be a plurality of side by side, specifically 4, 6, or 8, etc., so as to facilitate drying of the plurality of picking needles at the same time.
  • the drying zone further includes a heating device disposed on the back surface of the brush body 1, and the heating device is configured to heat the air in the brushing device and combine the drying holes 305 to thereby dry the picked and removed needles after washing and washing.
  • the heating device is a halogen lamp.
  • the drying zone further includes an air inlet and an air outlet disposed on the back of the brush body 301, and the air inlet is a slit-shaped slit; and is used for discharging the waste liquid or waste generated during the drying process to the washing device.
  • the slit has a width of 0.2 mm and a length of 10 mm.
  • the draining area includes the air venting holes 306, and may also be a plurality of side by side, specifically 4, 6, or 8, etc., so as to facilitate the simultaneous evacuation of the plurality of picking needles. .
  • the draining zone is used to drain the needle that picks up the needle during the scrubbing process.
  • the drying hole 305 and the air venting hole 306 are respectively arranged in a four-hole side-by-side structure, or a porous side-by-side structure, which can separately clean, dry and drain different needles. Avoid cross-contamination and make the needle cleaner.
  • the control area includes a solenoid valve 308 and the like, and the solenoid valve 308 is a vacuum solenoid valve for controlling the inflow and outflow of the first cleaning liquid, the second cleaning liquid, and the third cleaning liquid.
  • the first inlet hole, the second inlet hole, the third inlet hole, and the first outlet hole, the second outlet hole, and the third outlet hole are respectively provided with an inlet switch and an outlet switch, and the electromagnetic valve 308 is used to control various places.
  • the inlet switch and the outlet switch are configured to control the inflow and outflow of the first cleaning liquid, the second cleaning liquid, and the third cleaning liquid.
  • the back surface of the brush body 301 is provided with a liquid inlet pipe 309.
  • the liquid inlet pipe 309 is a vacuum pipe, and includes a first liquid inlet pipe connected to the first inlet hole, the second inlet hole, and the third inlet hole, respectively. a second liquid inlet pipe and a third liquid inlet pipe; the back surface of the brush body 301 is further provided with a liquid discharge pipe 3010, and includes a first liquid discharge pipe respectively connected to the first outlet hole, the second outlet hole and the third outlet hole, Two outlet tubes and a third outlet tube.
  • the automatic needle washing method for the stem cell-inducing culture device of the embodiment of the present invention adopts the automatic needle washing device described above, and the method comprises the following steps: (1) moving the needle to be cleaned to the drying area to be dried; (2) drying the The needle moves to the third liquid tank and is saturated with the third cleaning Brushing the brush head of the liquid, moving the brushed needle to the drying area to dry; (3) moving the brushed and dried needle to the second liquid tank, cleaning with the second cleaning liquid, and cleaning The subsequent needle is moved to the dry area to be dried; (4) the cleaned and dried needle is moved to the first liquid tank, and the first cleaning liquid is used for soaking.
  • the picking needle to be cleaned is first moved to the air vent 306, and the residual liquid or residue on the picking needle to be cleaned is drained; then moved to the groove 4, so that the picking needle is to be cleaned Brushing on the brush head soaked with alcohol, specifically brushing in the X direction and the Y axis; then picking the brushed picking needle to the air vent 306 for pumping; picking the needle after the picking moves to the first
  • the second liquid tank 303 is rinsed with distilled water or deionized water; the picking needle after the rinsing is moved to the air vent 306 for pumping; the picked pick needle is moved to the drying hole 305 for drying; After drying, the picking needle is moved into the first liquid tank 302, so that the picking needle is immersed in the PBS buffer; after picking up the PBS buffer, the picking needle can be moved to the culture plate for cell picking.
  • the stem cell-inducing culture device and the scrubbing method with the automatic needle washing device provided by the embodiment of the present invention, several different needles can be separately cleaned at the same time, avoiding cross-contamination between different needles, and improving the cleaning efficiency and cleanness of the needle. And the entire washing process is fully mechanical and automated, easy to use and more efficient.
  • the stem cell-inducing culture apparatus further includes a cell image acquisition device and a control system 500 of the image acquisition device.
  • the technical problem to be solved by the embodiments of the present invention is how to obtain a clear cell culture image in the process of continuous power operation.
  • FIG. 13 there is shown a block diagram of a specific embodiment of a cell image acquisition device in cell culture.
  • the flash 501 is a high-speed flash, and the flash 501 is disposed on the first slide 502 through the slider 506.
  • the flash 501 is located above the cell culture plate 509 and can be moved along the first slide 502 relative to the cell culture plate 509 for the photographing process. Flash lighting in the middle.
  • Below the bottom surface (bottom surface) of the cell culture plate 509 an imaging mechanism 503 is provided, and the imaging mechanism 503 is disposed on the second slide rail 504 via a slider.
  • the first rail 502 device and the second rail 504 device are respectively coupled to a motor (not shown).
  • the control system 505 sends a signal to the motor, thereby controlling the flash 501 and the camera mechanism 503 to be along the first rail 502 and the second rail 504, respectively.
  • the cell culture plate 509 is synchronously moved at a constant speed.
  • the speed of movement of the flash 501 and the camera mechanism 503 is preset by the control system 505.
  • the flash frequency of the flash 501 is set by the control system 505 in accordance with the speed of movement of the flash 501.
  • the moving speed and the flashing frequency (1/flashing time) of the high-speed flash 501 need to satisfy the following conditions: flashing time* moving speed ⁇ motion blur distance allowed by photographing.
  • control system 505 sends a signal to the motor, and the motor control slider drives the flash 501 and the camera mechanism 502 to move at a uniform speed relative to the cell culture plate 509 along the first slide rail 502 and the second slide rail 504, respectively.
  • the control system 505 controls the shutter opening of the imaging mechanism 503, and controls the flash 501 to flash during the shutter opening of the imaging mechanism 503, thereby acquiring a cell morphology image on the cell culture plate.
  • the camera mechanism is a microscope head
  • the shutter is at most 10 milliseconds
  • the flash time is microsecond.
  • the flash device in the cell culture system further includes a storage device coupled to the camera mechanism 503 for storing the cell morphology picture.
  • the high-speed flash device in the cell culture system further includes a scale 507 and a displacement detecting module 508.
  • the scale 507 is disposed in parallel along the first rail 502 and the second rail 504, and the scale 507 It is used to calibrate the moving position of the flash 501 and the camera mechanism 503 along the slide rail.
  • the displacement detecting module 508 is configured to detect the moving distance of the flash 501 and the imaging mechanism 503 along the grating scale 507, and the displacement detecting module 508.
  • the control system 505 is further configured to receive a signal of the displacement detecting module 508, and calculate and adjust a flash frequency moving speed of the flash according to the motion signal detected by the displacement detecting module 508. Therefore, the present invention achieves the technical effect of effectively adjusting the flash frequency according to the moving speed by setting the displacement detecting module and the grating scale structure.
  • the invention controls the flash and the camera to synchronously move by the control system, and sets the flashing frequency of the flash according to the moving speed, thereby achieving the effect of effectively obtaining the cell image in the cell culture plate during the continuous motion.
  • the control system 500 includes a data processing module 5051, a first motion control module 5052, a second motion control module 5053, a flash frequency control module 5054, a camera shutter control module 5055, and a displacement detecting module 5056.
  • the specific working process is:
  • the data processing module 5051 sends a motion signal to the first motion control module 5052 and the second motion control module 5053, respectively, so that the flash module 501 and the camera mechanism 503 perform synchronous motion.
  • the data processing module 5051 is a machine controller in the cell culture system in which the cell image acquisition device is located.
  • the first motion control module 5052 controls the flash module 501 to move according to the signal of the data processing module 5051; the second motion control module 5053 controls the motion of the camera mechanism 503 according to the signal of the data processing module 5051.
  • the first motion control module 5052 and the second motion control module 5053 control the motor to drive the camera mechanism 503 and the flash module 501 to move synchronously.
  • the displacement detecting module 5056 detects the motion displacement of the flash module 501 and the imaging mechanism 503, and transmits the displacement information to the data processing module 5051. Specifically, the displacement detecting module 5056 detects the distance that the flash module 501 and the camera mechanism 503 move along the scale 507, and sends a signal to the data processing module 5051.
  • the data processing module 5051 processes the displacement information to determine whether the current moving distance reaches the position at which the shutter and the flash are turned on. If so, a shutter open signal is sent to the camera mechanism 503, and a flash turn-on signal is sent to the flash module 501.
  • the camera mechanism shutter control module 5055 controls the opening and closing of the shutter of the camera mechanism 503 according to the signal of the data processing module 5051.
  • the flash frequency control module 5054 controls the flash to turn on the flash based on the signal sent by the data processing module 51 and controls the flash time.
  • the cell image acquisition device of the culture plate is controlled by the control system to control the cell image acquisition device in the cell culture.
  • an embodiment of the present invention further provides a method for controlling a cell image acquiring device in cell culture, which specifically includes the following steps:
  • Step S1 is executed, and the data processing module separately sends the motion signal to the first motion control module and the second motion control module, so that the flash module and the camera mechanism perform synchronous motion.
  • the data processing module is a machine controller in a cell culture system in which the cell image acquisition device is located.
  • Step S2 is executed, the first motion control module controls the flash module motion according to the signal of the data processing module; and the second motion control module controls the motion of the camera mechanism according to the signal of the data processing module.
  • the first motion control module and the second motion control module control the motor to drive the camera mechanism 503 and the flash module 501 to move synchronously.
  • Step S3 is executed to detect a motion displacement of the flash module and the camera mechanism, and send displacement information to the data processing module.
  • the displacement detecting module detects a distance that the flash module and the camera mechanism move along the grating scale, and sends a signal to the number According to the processing module.
  • Step S4 the data processing module processes the displacement information to determine whether the current moving distance needs to open the position of the shutter and the flash. If not, the displacement detecting module continues to detect; if yes, the data processing module sends the shutter The signal is turned on to the camera mechanism, and a flash turn-on signal is sent to the flash module 501.
  • Step S6 is performed, the camera mechanism shutter control module controls opening and closing of the camera shutter; the flash frequency control module controls the flash to turn on the flash and controls the flash time.
  • the steps S1-S6 are cycled to complete the scanning of the entire cell culture plate, and finally the cell morphology map of the entire cell culture plate is obtained.
  • Both the first motion control module and the second motion control module are controlled by a fifth-order polynomial S-curve acceleration/deceleration motion control algorithm.
  • the acceleration curve of the fifth-order polynomial acceleration/deceleration algorithm is a Quartic curve, which is a parabola with an opening. As shown in FIG. 1 , the opening of the acceleration phase is downward, and the opening of the deceleration phase is toward Upper, the motion control curve is divided into three segments: acceleration segment t ⁇ [T0, T1], constant velocity segment t ⁇ (T1, T2), deceleration segment t ⁇ (T2, T3).
  • a mp to the maximum positive acceleration A mm is the maximum negative acceleration
  • V S is the starting speed
  • V E is the ending speed
  • V M is the uniform speed.
  • the displacement, velocity, acceleration and jerk are all flexible changes, which can not only effectively reduce the frequent switching of the machine speed and the vibration during the reversing, improve the positioning accuracy and improve the running speed. Reduce running time and ensure that biological experiments can be completed efficiently and quickly.
  • the first motion control module and the second motion control module also calculate the control output through multi-axis synchronous interpolation. Specifically:
  • the system develops and implements the 23-axis synchronous interpolation control algorithm, which divides the 23 motion axes of the whole system into multiple motion control modules according to the function module (the system has a maximum of 5);
  • each module refers to the international common CNC machine origin O as the coordinate system origin, and A fixed rectangular coordinate system consisting of X, Y, Z axes and the like, and a fixed rotating coordinate system composed of an A-axis, a B-axis, and a C-axis are established by a right-handed Cartesian rectangular coordinate system;
  • Each module adopts the same 5th polynomial S-curve acceleration/deceleration motion control algorithm to plan the displacement curve, speed curve and acceleration/deceleration curve for motion control trajectory planning. It is estimated that the actual motion curve of each module is calculated, including time, Information such as displacement, speed, acceleration and deceleration;
  • each module adopts the time division method, and the total interpolation times N Total is divided according to the interpolation period (the system is 0.5ms)
  • N Total T Total /T InterpolationTime
  • L' is the interpolation length correction amount, which is determined according to the influence of the rotation coordinate on the linear motion.
  • the calculated five module incremental interpolation values are stored in the interpolation buffer, waiting for the FPGA multi-axis synchronous interpolation completion signal to be valid.
  • the FPGA program implements the interpolation of all 23 axes to complete the "bit and" output as an external interrupt, triggering the DSP core to write the interpolation data to the FPGA for continuous smooth interpolation, thereby realizing 23-axis synchronous stable interpolation.
  • the data processing module, the motion control module, the flash frequency control module and the camera shutter control module control the flash and the camera to synchronize movement, and set the flash frequency and the shutter open time according to the motion speed, thereby achieving continuous
  • the beneficial effects of efficiently obtaining cell images in cell culture plates during exercise and by setting the displacement detecting module and the grating rule structure, the technical effect of effectively adjusting the flash frequency according to the moving speed is achieved.

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Abstract

L'invention concerne une pointe polyvalente d'outil pour un appareil d'induction et de culture de cellules souches. La pointe polyvalente d'outil comprend : un module de collecte de clones, un module de transfert et de remplacement de fluides, un module de manipulation de récipient de culture, un module de détection de niveau de fluide et un module d'entraînement. Le module de collecte de clones comprend une seringue (401) de collecte de clone pour recueillir un clone. Le module de transfert et de remplacement de fluide comprend une seringue (403) de transfert et de remplacement de fluide pour transférer et remplacer un fluide. La seringue (401) de collecte de clone et la seringue (403) de transfert et de remplacement de fluide sont disposées l'une à côté de l'autre. Le module de manipulation du récipient de culture est utilisé pour déplacer un récipient de culture cellulaire. Le module de détection de niveau de fluide est utilisé pour détecter une surface de fluide d'un milieu de culture cellulaire dans le récipient de culture cellulaire. Le module d'entraînement est utilisé pour entraîner un mouvement de la pointe polyvalente d'outil. L'invention concerne en outre un appareil d'induction et de culture de cellules souches comprenant la pointe polyvalente d'outil pour l'appareil d'induction et de culture de cellules souches.
PCT/CN2017/083415 2016-05-27 2017-05-08 Pointe polyvalente d'outil pour appareil d'induction et de culture de cellules souches et appareil d'induction et de culture de cellules souches Ceased WO2017202192A1 (fr)

Applications Claiming Priority (8)

Application Number Priority Date Filing Date Title
CN201610368609.3A CN105838583B (zh) 2016-05-27 2016-05-27 存放培养皿的自动板架装置及全自动细胞培养装置
CN201610368609.3 2016-05-27
CN201610369456.4A CN105817434B (zh) 2016-05-27 2016-05-27 一种针头自动洗刷装置及洗刷方法
CN201610369456.4 2016-05-27
CN201610552157.4 2016-07-11
CN201610552157.4A CN105923386A (zh) 2016-07-11 2016-07-11 一种培养板抓取装置
CN201610541183.7 2016-07-11
CN201610541183.7A CN106047698A (zh) 2016-07-11 2016-07-11 一种细胞培养装置用多功能头及细胞培养装置

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CN110201733A (zh) * 2018-12-29 2019-09-06 北京睿智兴科科技有限公司 一种自动排移液吸头入移液吸头盒的设备
CN110903977A (zh) * 2019-12-23 2020-03-24 深圳赛动生物自动化有限公司 基于可编程控制器的干细胞培养仓控制系统及其控制方法
CN113025482A (zh) * 2021-04-09 2021-06-25 南京艾尔普再生医学科技有限公司 一种全自动换液系统
CN114381371A (zh) * 2022-01-13 2022-04-22 山东大学齐鲁医院 一种用于乳腺癌免疫治疗的腺癌干细胞培养装置
CN114410451A (zh) * 2022-01-17 2022-04-29 罗志勇 一种肿瘤科用肿瘤细胞培养装置
CN115505527A (zh) * 2022-10-10 2022-12-23 黄小冬 一种干细胞提取快速反应装置
CN117778168A (zh) * 2023-11-27 2024-03-29 创芯国际生物科技(广州)有限公司 一种细胞培养自动化装置
CN119198506A (zh) * 2024-11-22 2024-12-27 深圳市帝迈生物技术有限公司 一种细胞参数联合分析仪

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CN110201733A (zh) * 2018-12-29 2019-09-06 北京睿智兴科科技有限公司 一种自动排移液吸头入移液吸头盒的设备
CN110903977A (zh) * 2019-12-23 2020-03-24 深圳赛动生物自动化有限公司 基于可编程控制器的干细胞培养仓控制系统及其控制方法
CN113025482A (zh) * 2021-04-09 2021-06-25 南京艾尔普再生医学科技有限公司 一种全自动换液系统
CN114381371A (zh) * 2022-01-13 2022-04-22 山东大学齐鲁医院 一种用于乳腺癌免疫治疗的腺癌干细胞培养装置
CN114381371B (zh) * 2022-01-13 2023-11-07 山东大学齐鲁医院 一种用于乳腺癌免疫治疗的腺癌干细胞培养装置
CN114410451A (zh) * 2022-01-17 2022-04-29 罗志勇 一种肿瘤科用肿瘤细胞培养装置
CN115505527A (zh) * 2022-10-10 2022-12-23 黄小冬 一种干细胞提取快速反应装置
CN117778168A (zh) * 2023-11-27 2024-03-29 创芯国际生物科技(广州)有限公司 一种细胞培养自动化装置
CN119198506A (zh) * 2024-11-22 2024-12-27 深圳市帝迈生物技术有限公司 一种细胞参数联合分析仪
CN119198506B (zh) * 2024-11-22 2025-05-16 深圳市帝迈生物技术有限公司 一种细胞参数联合分析仪

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