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CN110538679B - A robotic arm pipetting system for microfluidic sample processing equipment - Google Patents

A robotic arm pipetting system for microfluidic sample processing equipment Download PDF

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Publication number
CN110538679B
CN110538679B CN201910762342.XA CN201910762342A CN110538679B CN 110538679 B CN110538679 B CN 110538679B CN 201910762342 A CN201910762342 A CN 201910762342A CN 110538679 B CN110538679 B CN 110538679B
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CN
China
Prior art keywords
chip
mechanical arm
lifting
hole
gun head
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CN201910762342.XA
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Chinese (zh)
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CN110538679A (en
Inventor
颜菁
朱海龟
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Jiangsu Huixian Pharmaceutical Technology Co ltd
Suzhou Bofu Biomedical Ltd
Original Assignee
Kunshan Huixian Medical Technology Co ltd
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Priority to CN201910762342.XA priority Critical patent/CN110538679B/en
Publication of CN110538679A publication Critical patent/CN110538679A/en
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    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/56Labware specially adapted for transferring fluids
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L9/00Supporting devices; Holding devices

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  • Health & Medical Sciences (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)

Abstract

The invention discloses a mechanical arm pipetting system of microfluidic sample processing equipment, which is convenient for realizing automatic processing of microfluidic samples. The mechanical arm pipetting system of the microfluidic sample processing equipment comprises a mechanical arm, a lifting device and a translation device, wherein the mechanical arm is provided with a gun head used for loading a chip clamp, an air flow channel used for communicating an inner cavity of the chip clamp is formed in the gun head, the lifting device is used for driving the gun head to lift so as to load the chip clamp or enable the chip clamp to be inserted into or separated from a reagent, and the translation device is used for driving the gun head to move above the chip clamp or move above the reagent, and the mechanical arm is arranged on the translation device and connected with the lifting device.

Description

Mechanical arm pipetting system of microfluidic sample processing equipment
Technical Field
The invention belongs to the technical field of biological detection, and relates to a mechanical arm pipetting system of microfluidic sample processing equipment.
Background
Microfluidic technology is an important method of sorting analysis of cells or biomolecules, such as the capture of Circulating Tumor Cells (CTCs), which has the advantage of simple operation and low amounts of antibodies required. The microfluidic chip is a core component of microfluidic technology, has a microchannel and is attached with a specific antibody, and is used for trapping and capturing target cells or biomolecules of a sample flowing through the microfluidic chip. These captured cells or biomolecules often require a series of post-treatments for analysis, such as washing, primary or secondary antibody treatment, staining, etc. At present, most of the treatments are manually carried out, so that the operation is complex and inconvenient, the efficiency is low, and the degree of automation is low.
Disclosure of Invention
The invention aims to provide a mechanical arm pipetting system of a microfluidic sample processing device, which is convenient for realizing automatic processing of microfluidic samples.
In order to achieve the above purpose, the invention adopts the following technical scheme:
a robotic pipetting system for a microfluidic sample processing device, comprising:
the mechanical arm is provided with a gun head for loading the chip clamp, and an air flow channel for communicating the inner cavity of the chip clamp is formed in the gun head;
a lifting device for driving the gun head to lift to load or insert or separate the chip holder into or from a reagent, and
Translation means for driving the gun head to move over the chip holder or over the reagent;
the mechanical arm is arranged on the translation device and connected with the lifting device.
Preferably, the mechanical arm further comprises a shell and a lifting rod penetrating through the shell in a sliding manner along the up-down direction, and the gun head is fixedly arranged at the lower end part of the lifting rod.
More preferably, the lifting device comprises a lifting rotating shaft assembly driven to rotate by a lifting power mechanism, one or more circles of teeth are formed on the outer circumferential surface of the lifting rotating shaft assembly, the lifting rod is provided with a rack part extending along the up-down direction, and the rack part and the teeth on the lifting rotating shaft assembly are meshed with each other.
Further, the lifting rotating shaft assembly comprises a lifting rotating shaft driven to rotate by the lifting power mechanism and one or more gears rotating along with the lifting rotating shaft, polygonal holes are formed in the gears, and the lifting rotating shaft is inserted into the polygonal holes and can allow the gears to horizontally move relative to the lifting rotating shaft.
Further, the gear is fixedly arranged in the shell.
Still further, the translation device comprises an x-direction component for driving the mechanical arm to move along the left-right direction, and the mechanical arm is arranged on the x-direction component.
Specifically, the X is to the subassembly including mounting panel and along the lead screw that left and right sides orientation extends, the lead screw can set up with rotating around self axial lead in on the mounting panel, the lead screw wear to locate in the arm and with the arm passes through threaded connection, be provided with on the mounting panel along the guide part of left and right sides orientation extension, the casing of arm can set up with along left and right sides orientation sliding in on the guide part.
Specifically, the translation device further comprises a y-direction component used for driving the mechanical arm to move along the front-back direction, and the x-direction component is arranged on the y-direction component.
More preferably, the lifting rod is arranged in a hollow mode, and the upper end portion of the lifting rod is arranged at a joint used for communicating the negative pressure liquid suction device.
In one embodiment, the gun head includes a body, a first flange extending outwardly from an outer surface of a lower portion of the body, and a second flange, the first flange being located a distance above the second flange.
More preferably, the outer diameter of the first flange is smaller than the outer diameter of the second flange.
In a further preferred embodiment, the robotic pipetting system further comprises a negative pressure pipetting device for providing negative pressure for pipetting and positive pressure for pipetting the gun head.
More preferably, the negative pressure liquid suction device comprises a piston driven by a negative pressure motor to reciprocate along a straight line and a piston shell provided with a gas cavity, and the piston is inserted into the gas cavity of the piston shell.
More preferably, the negative pressure liquid suction device further comprises an air duct, one end part of the air duct is fixedly connected with the piston shell and is communicated with the air cavity, and the other end part of the air duct is fixedly connected with the mechanical arm.
In a further preferred embodiment, the robotic arm pipetting system further comprises failure detection means for detecting if the robotic arm exceeds a maximum set stroke.
More preferably, the fault detection device comprises at least one detection unit, wherein the detection unit comprises a pair of photoelectric detection switches arranged at intervals and a baffle plate moving along with the mechanical arm, and the baffle plate is arranged between the pair of photoelectric detection switches.
Further, the fault detection device further comprises a controller, the controller is electrically connected with each photoelectric detection switch, and the controller is used for controlling the mechanical arm to stop moving after any one photoelectric detection switch is triggered.
Further, the fault detection device further comprises a fault indicator lamp, the controller is electrically connected with the fault indicator lamp, and the controller is further used for controlling the fault indicator lamp to switch the light color after any one of the photoelectric detection switches is triggered.
Further, the fault detection device further comprises a sound alarm device, the controller is electrically connected with the sound alarm device, and the controller is further used for controlling the sound alarm device to send out alarm sound after any one of the photoelectric detection switches is triggered.
Compared with the prior art, the invention has the following advantages:
According to the mechanical arm pipetting system of the microfluidic sample processing equipment, the gun head can load the chip clamp and absorb and drain liquid, and the gun head is lifted and translated by combining the lifting device and the translation device, so that the microfluidic chip in the chip clamp is subjected to the treatments of capturing, fixing, antibody incubation, dyeing and the like, the series of treatments on the microfluidic sample are automatically realized, manual intervention is reduced, the automation degree is high, and the treatment efficiency is improved.
Drawings
In order to more clearly illustrate the technical solutions of the present invention, the drawings that are needed in the description of the embodiments will be briefly described below, it being obvious that the drawings in the following description are only some embodiments of the present invention, and that other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.
Fig. 1 is a schematic perspective view of a microfluidic sample processing device;
fig. 2a is a schematic view of the internal structure of a microfluidic sample processing device, wherein part of the housing is not shown;
FIG. 2b is an enlarged view of a portion of FIG. 2a at A;
Fig. 3 is a top view of a microfluidic sample processing device, wherein a portion of the housing is not shown;
Fig. 4 is a front view of a microfluidic sample processing device, wherein a portion of the housing is not shown;
FIGS. 5, 6, and 7 are schematic perspective views of a tray assembly, respectively, wherein portions of the upper plate and the baffle of FIG. 7 are not shown;
FIG. 8 is a schematic perspective view of a robotic arm;
FIG. 9 is a schematic view of a single robotic arm;
FIG. 10 is a schematic view of a single robotic arm, wherein the housing is not shown;
FIG. 11 is a partial cross-sectional view of a robotic arm, lifting device, and translation device;
fig. 12 is a cross-sectional view of a negative pressure suction device.
In the above-mentioned figures of the drawing,
1. 10, The shell, 101, the door;
2. The kit comprises a kit body, a waste liquid collecting hole, a fixing liquid hole, a buffer liquid hole, a first primary antibody hole, a second primary antibody hole, a dyeing liquid hole, a chip recycling hole and a chip recycling hole, wherein the kit body comprises a kit body, a waste liquid collecting hole, a fixing liquid hole, a buffer liquid hole, a first primary antibody hole, a second antibody hole, a dyeing liquid hole and a chip recycling hole;
3. A chip clamp; 30 parts of a body, 31 parts of a honeycomb duct, 32 parts of a cylinder body;
4. Tray device 40, mounting groove 41, bottom plate 42, upper plate 421, left and right extension part 422, front and back extension part 423, slot 424, positioning protrusion 43, baffle;
5. 50 parts of mechanical arm, a shell, 51 parts of gun head, 511 parts of first flange, 512 parts of second flange, 52 parts of lifting rod, 521 parts of rack, 53 parts of joint;
6. the negative pressure liquid suction device comprises a negative pressure motor, 611, a push plate, 62, a piston, 63, a piston shell, 631, a gas cavity, 64, a photoelectric detection switch, 65 and a baffle plate;
7. lifting device, 71, lifting rotating shaft, 72, gear, 721, square hole, 73, lifting motor;
8. The device comprises a translation device, 81, a mounting plate, 811, a guide rail, 82, an x-direction motor, 83, a lead screw, 84, a y-direction motor, 85, a synchronous belt transmission mechanism, 86, a slide rail, 87 and a slide block;
9. The device comprises a fault detection device, a first photoelectric detection switch, a first baffle plate, a second photoelectric detection switch, a second baffle plate, a third photoelectric detection switch and a fault indicator lamp, wherein the fault detection device comprises a first photoelectric detection switch, a first baffle plate, a second photoelectric detection switch, a second baffle plate, a third photoelectric detection switch and a fault indicator lamp.
Detailed Description
Preferred embodiments of the present invention will be described in detail below with reference to the attached drawings so that the advantages and features of the present invention can be more easily understood by those skilled in the art. The description of these embodiments is provided to assist understanding of the present invention, but is not intended to limit the present invention.
Fig. 1 to 11 show a microfluidic sample processing device employing the robotic pipetting system of the present embodiment. Referring to fig. 1 to 11, the mechanical arm pipetting system mainly includes a mechanical arm 5, a negative pressure pipetting device 6, a lifting device 7 and a translation device 8, where the mechanical arm 5, the negative pressure pipetting device 6 and the translation device 8 are all disposed on a frame 1 of the microfluidic sample processing apparatus, a housing 10 is covered on the periphery of the frame 1, and the above devices are covered in the housing 10. The microfluidic sample processing equipment mainly comprises a tray device 4, a mechanical arm 5, a negative pressure imbibition device 6, a lifting device 7 and a translation device 8, wherein the tray device 4 is used for accommodating a reagent and a chip clamp 3 provided with a microfluidic chip, the mechanical arm 5 is provided with a gun head 51 used for loading the chip clamp 3, an air flow channel used for communicating an inner cavity of the chip clamp 3 is formed in the gun head 51, the negative pressure imbibition device 6 is used for providing air pressure for the air flow channel of the gun head 51 and comprises negative imbibition pressure and positive pressure for draining liquid, the lifting device 7 is used for driving the gun head 51 to lift so as to load the chip clamp 3 or enable the chip clamp 3 to be inserted into or separated from the reagent, and the translation device 8 is used for driving the gun head 51 to move above the chip clamp 3 or move above the reagent. The tray device 4 is located below the mechanical arm 5, and the mechanical arm 5 is arranged on the translation device 8 and connected with the lifting device 7. Specifically, the tray device 4 is provided with one or more reagent kits 2, the reagent kits 2 are provided with chip clamps 3, and the microfluidic chip is installed in the chip clamps 3 and is fixed by the chip clamps 3. As shown in fig. 1, the housing 10 is provided with a door 101, the door 101 is slidably disposed up and down, the door 101 is disposed opposite to the tray device 4, and when the door 101 slides up, the tray device 4 is exposed, so that the reagent kit 2 can be conveniently mounted or replaced.
In this embodiment, a plurality of cartridges 2 are mounted in the tray device 4 in parallel in the left-right direction (as shown in fig. 3, four cartridges 2 can be mounted at a time in the tray device 4). Referring to fig. 5, the kit 21 includes a case 20, and the case 20 is provided with a waste liquid collection hole 21 for inserting the chip holder 3 and storing waste liquid, one or more reagent holes for storing reagents, and a chip recovery hole 28 for recovering the chip holder 3. The reagent wells specifically comprise a fixing solution well 22 for storing fixing solution, a buffer solution well 23 for storing buffer solution, a primary antibody well for storing primary antibody, a secondary antibody well 26 for storing secondary antibody and a staining solution well 27 for storing staining solution. The primary antibody holes specifically comprise a primary antibody hole 24 for storing a primary antibody and a secondary antibody hole 25 for storing a secondary antibody. The waste liquid collecting hole 21 and the chip recovering hole 28 are respectively stepped holes with the upper aperture larger than the lower aperture so as to match the shape of the chip clamp 3, thereby facilitating the insertion of the chip clamp 3. The chip recovery hole 28 is a long hole or a kidney-shaped hole, and the longitudinal direction of the chip recovery hole 28 coincides with the longitudinal direction of the case 20. In the kit 21, the reagent and the chip clamp 3 are disposable in the kit 21, can treat a plurality of steps such as pipetting, sorting, waste liquid and the like, and has small pollution risk due to internal operation. Moreover, the whole design of the kit 21, and the reagents in the reagent holes are stored separately without mixing, so that the kit is suitable for long-term storage due to different use concentrations of different steps. The reagent storage area and the reagent kit 21 are of an integral structure, so that the reagent is more stable to store and is more stable to operate. The waste liquid collecting hole 21 in the reagent kit 21 is not only the installation position of the chip clamp 3, but also the waste liquid treatment position, namely the space of the reagent kit 21 is saved, and an operator is not required to additionally prepare a container for collecting waste liquid.
The waste liquid collecting hole 21 and the chip recovering hole 28 are respectively positioned on the front end and the rear end of the box body 20, the fixing liquid hole 22, the buffer liquid hole 23 and the primary antibody hole are sequentially arranged between the waste liquid collecting hole 21 and the chip recovering hole 28, and the secondary antibody hole 26 and the dyeing liquid hole 27 are arranged between the primary antibody hole and the chip recovering hole 28 in parallel left and right. That is, the waste liquid collecting hole 21, the fixing liquid hole 22, the buffer liquid hole 23, the primary antibody hole, the secondary antibody hole 26, or the staining liquid hole 27, the chip recovering hole 28 are arranged at intervals in order along the longitudinal direction (i.e., the front-rear direction) of the cartridge 20. In this embodiment, the waste liquid collection well 21 is used for storing samples (such as blood, urine, tissue fluid, spinal fluid, etc.), reagents, etc. discharged from the microfluidic chip, the fixing fluid well 22 is used for storing fixing fluid, the buffer well 23 is used for storing PBS buffer, the first primary antibody well 24 is used for storing primary antibody A, the second primary antibody well 25 is used for storing primary antibody B, the second antibody well 26 is used for storing secondary antibody, and the staining fluid well 27 is used for storing DAPI staining fluid.
Referring to fig. 8, the chip holder 3 includes a body 30 and a flow guide 31 having a flow guide for sucking and discharging liquid, the microfluidic chip is installed in an inner cavity of the body 30, and the flow guide 31 extends downward from the body 30 and communicates with the inner cavity. The body 30 has a cylindrical body 32 formed at an upper portion thereof into which a lower end portion of the robot arm 5 is inserted. The cylindrical body 32 is hollow and communicates with the inner cavity of the body 30. The body 30 of the chip fixture 3 can store samples, the flow guide pipe 31 at the lower part can discharge waste liquid and absorb reagents, the waste liquid flowing through the microfluidic chip is guided and the reagents are absorbed so as to enable the waste liquid to flow through the microfluidic chip for incubation or cleaning, and the like, so that the microfluidic chip can conveniently capture target cells or biomolecules in the samples and conveniently absorb or discharge the reagents.
The microfluidic sample processing device has a waste liquid collection state, a chip recovery state and a pipetting state. When the microfluidic sample processing device is in the waste liquid collecting state, the chip fixture 3 is inserted into the waste liquid collecting hole 21 of the reagent kit 21, the body 30 thereof is located at the upper part of the step hole, and the flow guide tube 31 is inserted into the lower part of the step hole, as shown in the leftmost chip fixture 3 in fig. 5 to 7. When the microfluidic sample processing device is in the chip recovery state, the chip clamp 3 is inserted into the chip recovery hole 28 of the kit 21, the body 30 thereof is located at the upper part of the stepped hole, and the flow guide tube 31 is inserted into the lower part of the stepped hole, as shown in the positions of the middle two chip clamps 3 in fig. 5 to 7. When the microfluidic sample processing device is in a pipetting state, the chip clamp 3 is disengaged from the waste liquid collection hole 21, the chip clamp 3 is positioned above one of the reagent holes, and the flow guide tube 31 is inserted into the reagent hole.
Specifically, as shown in fig. 5 to 7, the tray device 4 is provided with a plurality of mounting grooves 40 arranged side by side in the left-right direction, and one reagent cartridge 2 is inserted into each mounting groove 40. In this embodiment, the tray device 4 includes a bottom plate 41 fixedly disposed on the frame 1 and an upper plate 42 fixedly disposed on the bottom plate 41, the upper plate 42 includes a left-right extending portion 421 and a plurality of front-rear extending portions 422 extending forward from the left-right extending portion 421, the plurality of front-rear extending portions 422 are juxtaposed in the left-right direction and are disposed at intervals, and the mounting grooves 40 having front sides and upper sides open are formed between any two adjacent front-rear extending portions 422, respectively. Each front and rear extension portion 422 is provided with a slot 423 extending in the front and rear direction, the slots 423 on two adjacent front and rear extension portions 422 are arranged oppositely, and the left and right side edges of the kit 2 are inserted into the corresponding two slots 423. The upper plate 42 is specifically formed by stacking an upper plate and a lower plate, and the slot 423 is formed between the upper plate and the lower plate.
The upper plate 42 is provided with a positioning mechanism for positioning the reagent cartridge 2. In this embodiment, as shown in FIG. 7, the positioning mechanism includes an upwardly extending positioning boss 424 formed on the upper plate 42, with the cartridge having a downwardly facing recess. When the kit is mounted in place, the positioning protrusions 424 are inserted into the recesses of the kit, and the kit is fixed in the mounting groove 40 by being fitted with the slots 423 on both sides, preventing the kit from shaking. In the mounting, the left and right side edges of the reagent cartridge 2 are inserted into the insertion grooves 423 on both sides, and pushed in from the front side of the mounting groove 40 until they are caught on the positioning projections 424.
Further, the tray device 4 further includes a shutter 43, and a portion of the chip recovery hole is located directly below the shutter 43. The baffle 43 is specifically and fixedly arranged on the bottom plate 41 or the rack 1, and the baffle 43 is positioned above the upper plate 42 and partially shields the chip recovery hole 28 of the lower kit, so as to prevent the chip clamp 3 from separating from the chip recovery hole 28. When the microfluidic sample processing device is in the waste liquid collection state, the chip holder 3 is slidably inserted in the chip recovery hole 28 in the front-rear direction. In recovering the microfluidic chip, the chip holder 3 is inserted downward into the chip recovery hole 28 from the front end of the chip recovery hole 28 (as in the position of the second chip holder 3 on the left in fig. 5 to 7), and then moved along the chip recovery hole 28 to the rear end thereof (as in the position of the third chip holder 3 on the left in fig. 5 to 7), and is restrained in the chip recovery hole 28 by the shutter 43, thereby detaching the chip holder 3 from the robot arm 5.
In this embodiment, the number of the mechanical arms 5 is plural, such as four as shown in fig. 8. The plurality of mechanical arms 5 are arranged in parallel along the left-right direction and respectively correspond to the plurality of reagent boxes 2 below one by one. As shown in fig. 8 to 11, each of the robot arms 5 includes a housing 50, a lift rod 52 penetrating the housing 50 so as to be movable in the up-down direction, a gun head 51 provided on the lower end of the lift rod 52, and a joint 53 provided on the upper end of the lift rod 52. The joint 53 is used for communicating the joint 53 of the negative pressure liquid absorbing device 6, the lifting rod 52 is arranged in a hollow mode, and air pressure for absorbing or draining liquid is provided for the gun head 51 through the negative pressure liquid absorbing device 6.
As shown in fig. 9, the gun head 51 includes a body 30, a first flange 511 and a second flange 512 extending outwardly from an outer surface of a lower portion of the body 30, the first flange 511 is located at a distance above the second flange 512, and an outer diameter of the first flange 511 is smaller than an outer diameter of the second flange 512. The lower end of the gun head 51 is generally in a gourd shape, and when the gun head is inserted into the barrel 32 of the chip clamp 3, the connection is firm, so that the chip clamp 3 is prevented from falling from the gun head 51.
As shown in fig. 3,4, 10 and 11, the lifting device 7 includes a lifting shaft assembly driven to rotate by a lifting power mechanism, one or more rings of teeth are formed on the outer circumferential surface of the lifting shaft assembly, the lifting rod 52 has a rack portion 521 extending in the up-down direction, and the rack portion 521 and the teeth on the lifting shaft assembly are engaged with each other. Specifically, the lifting power mechanism is specifically a lifting motor 73, the lifting shaft assembly includes a lifting shaft 71 driven to rotate by the lifting motor 73 and one or more gears 72 rotating along with the lifting shaft 71, polygonal holes are formed in the gears 72, and the lifting shaft 71 is inserted into the polygonal holes and can allow the gears 72 to move horizontally relative to the lifting shaft 71. The gear 72 is fixedly disposed within the housing 50. The number of the gears 72 corresponds to the number of the mechanical arms 5, that is, one gear 72 is fixedly arranged in the housing 50 of each mechanical arm 5. As shown in fig. 11, the polygonal hole is specifically a square hole 721, the section of the lifting shaft 71 is square, the lifting shaft 71 extends in the left-right direction and sequentially passes through the square holes 721 of the gears 72 in the plurality of mechanical arms 5, and when the lifting shaft 71 rotates, the gears 72 can be driven to rotate, and the lifting rod 52 is driven to move up and down under the cooperation of the racks and the gears. Meanwhile, when the mechanical arm 5 receives a leftward or rightward force applied by the translation device 8, the gear 72 can be allowed to slide on the lifting rotating shaft 71, so that the mechanical arm 5 can move in the left-right direction under the driving of the translation device 8.
As shown in fig. 3, fig. 4 and fig. 11, the translation device 8 includes an x-direction component for driving the mechanical arm 5 to move in the left-right direction and a y-direction component for driving the mechanical arm 5 to move in the front-back direction, wherein the mechanical arm 5 is disposed on the x-direction component, the x-direction component is disposed on the y-direction component, and the y-direction component is disposed on the frame 1. Specifically, the x-direction component includes a mounting plate 81 and a screw 83 extending in the left-right direction, the screw 83 is rotatably disposed on the mounting plate 81 around its axis, and the screw 83 is disposed in the mechanical arm 5 in a penetrating manner and is connected with the mechanical arm 5 through threads. The mounting plate 81 is fixedly provided with a guide rail 811 extending in the left-right direction, and each of the robot arms 5 is slidably provided on the guide rail 811 in the left-right direction, specifically, the housing 50 of the robot arm 5 and the guide rail 811 are slidably connected. The x-direction assembly also includes an x-direction motor 82 for driving the rotation of the lead screw 83. The screw 83 and the lifting rotating shaft 71 are arranged in parallel, the screw 83 is located above the lifting rotating shaft 71, the screw 83 penetrates through the upper portion of the mechanical arm 5, and the lifting rotating shaft 71 penetrates through the lower portion of the mechanical arm 5. The y-direction component comprises a sliding rail 86 extending along the front-back direction and a sliding block 87 slidably arranged on the sliding rail 86, the sliding rail 86 is fixedly arranged on the frame 1, and the mounting plate 81 of the x-direction component is fixedly arranged on the sliding block 87. The y-direction assembly further includes a y-direction motor 84 and a timing belt drive 85 driven by the y-direction motor 84, the timing belt drive 85 being connected to the slider 87.
As shown in fig. 2b and 12, the negative pressure suction device 6 includes a piston 62 driven by a negative pressure motor 61 to reciprocate in a straight line and a piston housing 63 provided with a gas chamber 631, the piston housing 63 is fixedly provided on a mounting plate 81, and the piston 62 is movably inserted into the gas chamber 631 of the piston housing 63. The negative pressure suction device 6 further includes an air duct (not shown in the drawings), one end of which is fixedly connected to the piston housing 63 and communicates with the air chamber 631, and the other end of which is fixedly connected to the robot arm 5. In this embodiment, the number of pistons 62, gas chambers 631 and gas ducts is plural, and corresponds to the number of robot arms 5. That is, a plurality of independent gas chambers 631 are provided in the piston housing 63, and each of the gas chambers 631 is slidably provided with a piston 62, so that when the negative pressure motor 61 drives the piston 62 to reciprocate, the gas chamber 631 and the air pressure in the gun head 51 communicating with the gas chamber 631 through the air duct are changed accordingly, thereby sucking or discharging the reagent. The negative pressure liquid suction device 6 utilizes the principle of a piston 62 to generate pressure to control the suction or discharge of liquid in a closed state, when the head is under the liquid level, the piston 62 moves backwards to generate negative pressure so as to achieve the purpose of sucking the liquid, otherwise, when the liquid exists in the gun head 51, the piston 62 moves forwards to generate positive pressure so as to discharge the liquid. The front end of the piston 62 is provided with a rubber gasket by which the tightness is increased.
The negative pressure suction device 6 further includes a piston detection mechanism for monitoring the displacement of the piston 62. In this embodiment, as shown in fig. 2b, the piston detecting mechanism includes a photoelectric detection switch 64 fixedly disposed on the piston housing 63 and a blocking piece 65 moving synchronously with the piston 62, when the piston 62 moves to a maximum set displacement, the blocking piece 65 moves to the photoelectric detection switch position 64, and the photoelectric detection switch 64 is triggered to send out a detection signal. The photoelectric detection switch 64 of the piston detection mechanism is electrically connected with the controller through a wire, the negative pressure motor 61 is electrically connected with the controller through a wire, when the photoelectric detection switch 64 is triggered to send out a detection signal, the controller receives the detection signal and sends out a control signal for stopping operation to the negative pressure motor 61, and the negative pressure motor 61 stops operation in response to the control signal, so that the piston 62 stops moving. Specifically, the negative pressure motor 61 is mounted on the piston housing 63, the motor shaft of the negative pressure motor 61 is connected with a push plate 611 and drives the push plate 611 to reciprocate along a straight line, the plurality of pistons 62 are fixedly arranged on the push plate 611, the push plate 611 drives the pistons to synchronously move, and the baffle plate 65 is fixedly arranged on the push plate 611.
The robotic pipetting system further comprises a fault detection device 9. The fault detection device 9 includes at least one detection unit including a pair of photo-detection switches arranged at intervals and a blocking piece moving along with the gun head 51, the blocking piece being arranged between the pair of photo-detection switches. The baffle is specifically a metal baffle. In this embodiment, the number of the detection units is three, and the detection units are a first detection unit, a second detection unit and a third detection unit. The first detecting unit is used for detecting the moving distance of the gun head 51 along the up-down direction, the second detecting unit is used for detecting the moving distance of the gun head 51 along the left-right direction, and the third detecting unit is used for detecting the moving distance of the gun head 51 along the front-back direction. As shown in fig. 8, the first detecting unit includes a pair of first photoelectric detecting switches 91 and a first blocking piece 92, where the pair of first photoelectric detecting switches 91 are disposed close to the mechanical arms 5, specifically fixedly disposed on the housing 50 of one of the mechanical arms 5, and disposed along the up-down direction with a first interval therebetween, the first interval is greater than the maximum set travel of the lifting rod 52 moving along the up-down direction, and the first blocking piece 92 is fixedly connected to the lifting rod 52 and located between the pair of first photoelectric detecting switches 91. As shown in fig. 3, the second detecting unit includes a pair of second photoelectric detecting switches 93 and a second blocking piece 94, where the pair of second photoelectric detecting switches 93 are disposed close to the mechanical arm 5, specifically fixedly disposed at a position of the mounting plate 81 close to the mechanical arm 5, and disposed along a left-right direction with a second interval therebetween, the second interval is greater than a maximum set travel of the mechanical arm 5 moving along the left-right direction, and the second blocking piece 94 is fixedly connected to one of the mechanical arms 5 (specifically, the housing 50 of the mechanical arm 5) and is located between the pair of second photoelectric detecting switches 93. Referring to fig. 2b and fig. 3, the third detecting unit includes a pair of third photoelectric detecting switches 95 and a third baffle (not shown in the drawing), where the pair of third photoelectric detecting switches 95 are fixedly disposed at a position of the frame 1 near the sliding block 87, specifically disposed beside the sliding rail 86, and disposed along the front-rear direction and having a third interval, where the third interval is greater than the maximum set travel of the mechanical arm 5 moving along the front-rear direction, and the third baffle is fixedly connected to the sliding block 87 and located between the pair of third photoelectric detecting switches 95.
The fault detection device 9 further comprises a controller, the controller is electrically connected with the photoelectric detection switches, and the controller is used for controlling the mechanical arm 5 to stop moving after any photoelectric detection switch is triggered. The fault detection device 9 further includes a fault indicator 96, and the controller is electrically connected to the fault indicator 96, and is further configured to control the fault indicator 96 to switch the light color after any one of the photoelectric detection switches is triggered. Specifically, the controller is electrically connected to the pair of first photoelectric detection switches 91, the pair of second photoelectric detection switches 93 and the pair of third photoelectric detection switches 95 through wires, and the controller is also electrically connected to the lift motor 73, the x-direction motor 82 and the y-direction motor 84 through wires. When the mechanical arm 5 moves up and down beyond the maximum set displacement, the first blocking piece 92 moves to a position of a certain first photoelectric detection switch 91, the first photoelectric detection switch 91 is triggered to send out a fault signal, the controller receives the fault signal and then sends out first control signals for stopping operation to the lifting motor 73, the x-direction motor 82 and the y-direction motor 84, meanwhile, the controller also sends out second control signals for switching indication colors to the fault indicator lamp 96, the lifting motor 73, the x-direction motor 82 and the y-direction motor 84 stop operation in response to the first control signals, and the color of the fault indicator lamp 96 is changed from green to red in response to the second control signals. As shown in fig. 1, the fault indicator 96 is specifically disposed on the housing 10 and includes an elongated LED lamp, where when the microfluidic sample processing device is operating normally, the color of the fault indicator 96 is displayed as green, and when the movement of the mechanical arm 5 in any direction exceeds the maximum set travel, the fault of the microfluidic sample processing device is determined, the operation of each motor is stopped, the movement of the mechanical arm 5 is stopped, and the fault indicator 96 is displayed as red. Erroneous operation of the robotic arm 5 is avoided damaging the sample and the machine itself.
The detection principle of the photoelectric detection switch adopted in the embodiment is that after the baffle plate moves to the photoelectric detection position, detection light of the photoelectric detection switch is shielded, so that the photoelectric detection switch is triggered. The photoelectric detection switch is typically an infrared detection switch, and the infrared detection switch is triggered when the baffle plate shields infrared rays emitted by the infrared detection switch.
In other embodiments, the fault detection device 9 further includes an audible alarm device, and the controller is electrically connected to the audible alarm device, and the controller is further configured to control the audible alarm device to emit a warning sound after any one of the photoelectric detection switches is triggered.
In the fault detection device 9, a small distance is reserved between the normal operation range of the mechanical arm 5 and the photoelectric detection switch, so that the probability of false triggering of the photoelectric detection switch is greatly reduced. Once the mechanical arm 5 fails, the baffle sheet reaches the position of the photoelectric detection switch, and the mechanical arm 5 immediately stops moving, so that the safety of the machine is effectively improved. The operation is simple, and the fault response is visual.
The working process of the mechanical arm pipetting system is as follows:
1. The reagent box 2 is put into the mounting groove 40 of the tray device 4, the translation device 8 drives the mechanical arm 5 to horizontally move so that each gun head 51 is positioned right above the corresponding chip clamp 3, the lifting device 7 drives the mechanical arm 5 to lift so that the lower end part of each gun head 51 is inserted into the cylinder part 32 of the corresponding chip clamp 3, the chip clamp 3 is loaded on the gun head 51, at the moment, the chip clamp 3 is initially positioned in the waste liquid collecting hole 21, a sample (such as blood, urine, tissue liquid, spinal cord liquid and the like) is stored in the upper section of the chip clamp 3, the mechanical arm can move with the whole chip clamp 3 after being inserted into the cylinder part 32, and when the mechanical arm is inserted, the negative pressure liquid absorbing device 6 provides positive pressure, the sample is pushed into the inner cavity of the chip clamp 3 to flow through the microfluidic chip for cell capturing, waste liquid flows out of the flow guide pipe 31 at the lower end of the chip clamp 3 after passing through the microfluidic chip, the waste liquid is remained in the waste liquid collecting hole 21, and waste liquid involved in the later operation is recovered into the waste liquid collecting hole 21.
2. The lifting device 7 drives the mechanical arm to move upwards to move the chip clamp 3 out of the waste liquid collecting hole 21 integrally, the y-direction motor 84 of the translation device 8 acts to enable the mechanical arm 5 to drive the chip clamp 3 to move above the fixing liquid hole 22, the lifting device 7 operates to enable the mechanical arm 5 to drive the chip clamp 3 to move downwards to insert the guide pipe 31 into the fixing liquid hole 22, the negative pressure liquid suction device 6 provides negative pressure to enable the guide pipe 31 to suck fixing liquid in the fixing liquid hole 22, the fixing liquid passes through a chip from bottom to top to fix cells captured on the chip, the y-direction motor 84 of the translation mechanism acts, the mechanical arm 5 moves back to above the waste liquid collecting hole 21, the negative pressure liquid suction device 6 provides positive pressure to discharge the fixing liquid to the waste liquid collecting hole 21, and waste liquid treatment in later steps is the same.
3. The mechanical arm 5 controls the chip fixture 3 to move to the upper part of the buffer solution hole 23, the guide pipe 31 is inserted into the buffer solution hole 23, PBS buffer solution is sucked, the chip is cleaned, the mechanical arm 5 moves back to the upper part of the waste solution collecting hole 21, and the waste solution is treated to the waste solution collecting hole 21 for 2 times.
4. The mechanical arm 5 controls the chip fixture 3 to sequentially move to the upper part of the first primary antibody hole 24, the guide pipe 31 is inserted into the first primary antibody hole 24 to suck the primary antibody A, the chip is incubated for the primary antibody A for 60 minutes, the chip is returned to the buffer solution hole 23 after the waste liquid is discharged from the waste liquid collecting hole 21, the chip is washed for 2 times, the chip is moved to the second primary antibody hole 25 to incubate the primary antibody B for 60 minutes, the chip is returned to the buffer solution hole 23 after the waste liquid is discharged from the waste liquid collecting hole 21, the chip is moved to the second primary antibody hole 26 to incubate for 60 minutes, the chip is returned to the buffer solution hole 23 after the waste liquid is discharged from the waste liquid collecting hole 21, the chip is washed for 2 times, the chip is moved to the dyeing solution hole 27, the DAPI is dyed for 5 minutes, and the chip is returned to the buffer solution hole 23 after the waste liquid is discharged from the waste liquid collecting hole 21, and the chip is washed for 2 times.
5. The translation device 8 acts to enable the mechanical arm to drive the chip clamp 3 to move to the front end of the chip recovery hole 28, the lifting device 7 acts to enable the mechanical arm 5 to drive the chip clamp 3 to move downwards to be inserted into the front end of the chip recovery hole, the y-direction motor 84 of the translation device 8 operates to enable the mechanical arm 5 to drive the chip clamp 3 to move to the rear end of the chip recovery hole in the chip recovery hole, at the moment, part of the chip clamp 3 is located under the baffle 43, the lifting device 7 acts to enable the mechanical arm 5 to move upwards, and the chip clamp 3 is blocked by the baffle 43 and is left in the chip recovery hole, so that separation of the chip clamp 3 and the gun head 51 is achieved.
The microfluidic sample processing device integrates the functions of capturing, fixing, cleaning, incubating antibodies, dyeing and the like of cells or biomolecules, automatically realizes a series of processing on microfluidic samples, reduces manual intervention, has higher degree of automation, improves processing efficiency, can synchronously operate a plurality of chip clamps 3 at the same time, facilitates parallel experiments, further improves processing efficiency, and has compact structure, reasonable layout and reduced space occupied by the device.
The above-described embodiments are provided for illustrating the technical concept and features of the present invention, and are intended to be preferred embodiments for those skilled in the art to understand the present invention and implement the same according to the present invention, not to limit the scope of the present invention. All equivalent changes or modifications made according to the principles of the present invention should be construed to be included within the scope of the present invention.

Claims (7)

1. A robotic pipetting system for microfluidic sample processing devices, comprising:
the mechanical arm is provided with a gun head for loading the chip clamp, and an air flow channel for communicating the inner cavity of the chip clamp is formed in the gun head; the mechanical arm further comprises a shell and a lifting rod which is arranged on the shell in a penetrating manner in a sliding manner along the up-down direction, and the gun head is fixedly arranged at the lower end part of the lifting rod;
A lifting device for driving the gun head to lift to load the chip fixture or to insert or separate the chip fixture from a reagent, the lifting device comprising a lifting shaft assembly driven to rotate by a lifting power mechanism, one or more rings of teeth being formed on an outer circumferential surface of the lifting shaft assembly, the lifting rod having a rack portion extending in a vertical direction, the rack portion and the teeth on the lifting shaft assembly being engaged with each other, the lifting shaft assembly comprising a lifting shaft driven to rotate by the lifting power mechanism and one or more gears rotating with the lifting shaft, the gears being provided with polygonal holes, the lifting shaft being inserted into the polygonal holes and being capable of allowing the gears to move horizontally with respect to the lifting shaft, and
Translation means for driving the gun head to move over the chip holder or over the reagent;
The mechanical arm is arranged on the translation device and connected with the lifting device so as to be positioned above a tray device; the tray device is internally provided with one or more reagent boxes, the reagent boxes comprise box bodies, the box bodies are provided with chip recovery holes for recovering the chip clamps, and the chip recovery holes are long holes or waist-shaped holes;
The mechanical arm is configured to carry the chip clamp to be slidably inserted into the chip recovery hole in a front-rear direction, when the chip clamp is recovered, the mechanical arm carries the chip clamp to be inserted into the chip recovery hole from the front end of the chip recovery hole and then drives the chip clamp to move backwards to the rear end of the chip recovery hole along the chip recovery hole, the chip clamp is limited in the chip recovery hole by the baffle, the chip clamp is separated from the gun head when the mechanical arm moves upwards, and the chip clamp and a microfluidic chip in which captured cells are fixed are held in the chip recovery hole;
The chip clamp comprises a body and a flow guide pipe, wherein the micro-fluid control device is arranged in an inner cavity of the body, and the flow guide pipe extends downwards from the body and is communicated with the inner cavity;
The cartridge body is also provided with a waste liquid collecting hole, the chip clamp is initially positioned in the waste liquid collecting hole, a sample is stored at the upper section of the chip clamp, when the gun head is inserted into the barrel body, the sample is pushed into the inner cavity and flows through the microfluidic chip to capture cells, and waste liquid flows into the waste liquid collecting hole from the guide pipe after passing through the microfluidic chip.
2. The robotic pipetting system of claim 1, wherein the gear is fixedly disposed within the housing.
3. The robotic arm pipetting system of claim 1, wherein the translation device comprises an x-direction assembly for driving the robotic arm to move in a side-to-side direction, the robotic arm being disposed on the x-direction assembly.
4. The pipetting system of claim 3, wherein the x-direction assembly comprises a mounting plate and a screw rod extending in a left-right direction, the screw rod is rotatably arranged on the mounting plate around a self axis, the screw rod is arranged in the robotic arm in a penetrating manner and is connected with the robotic arm through threads, a guide part extending in the left-right direction is arranged on the mounting plate, and a shell of the robotic arm is slidably arranged on the guide part in the left-right direction.
5. The robotic pipetting system of claim 3, wherein the translating apparatus further comprises a y-direction assembly for driving the robotic arm to move in a front-to-back direction, the x-direction assembly being disposed on the y-direction assembly.
6. The pipetting system of claim 1, wherein the lifting rod is hollow, and the upper end of the lifting rod is arranged at a joint for communicating with a negative pressure pipetting device.
7. The mechanical arm pipetting system as recited in claim 1, further comprising a negative pressure pipetting device for providing negative pressure for pipetting and positive pressure for pipetting the gun head and/or a fault detection device for detecting whether the mechanical arm exceeds a maximum set stroke.
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