WO2024021222A1 - 外泌体提取仪 - Google Patents

外泌体提取仪 Download PDF

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Publication number
WO2024021222A1
WO2024021222A1 PCT/CN2022/116580 CN2022116580W WO2024021222A1 WO 2024021222 A1 WO2024021222 A1 WO 2024021222A1 CN 2022116580 W CN2022116580 W CN 2022116580W WO 2024021222 A1 WO2024021222 A1 WO 2024021222A1
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liquid level
component
cylinder
level detection
assembly
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PCT/CN2022/116580
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English (en)
French (fr)
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徐震宇
吴钍荣
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广州兆瑞医学生物科技有限公司
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Publication of WO2024021222A1 publication Critical patent/WO2024021222A1/zh

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    • C12M33/00Means for introduction, transport, positioning, extraction, harvesting, peeling or sampling of biological material in or from the apparatus
    • C12M33/04Means for introduction, transport, positioning, extraction, harvesting, peeling or sampling of biological material in or from the apparatus by injection or suction, e.g. using pipettes, syringes, needles
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    • C12M33/00Means for introduction, transport, positioning, extraction, harvesting, peeling or sampling of biological material in or from the apparatus
    • C12M33/14Means for introduction, transport, positioning, extraction, harvesting, peeling or sampling of biological material in or from the apparatus with filters, sieves or membranes
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    • C12M41/48Automatic or computerized control
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    • C12M47/00Means for after-treatment of the produced biomass or of the fermentation or metabolic products, e.g. storage of biomass
    • C12M47/04Cell isolation or sorting
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02ATECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • This application relates to the technical field of medical devices, especially to exosome extraction instruments.
  • Exosomes are extracellular vesicles produced by cells and contain important intercellular communication mediators such as nucleic acids and proteins. The role of exosomes in immune responses has been demonstrated by a large amount of literature and recorded by clinical data. In addition, in research on exosomes and disease treatment, cardiovascular diseases, neurodegenerative diseases, early diagnosis of cancer, and even respiratory diseases such as COVID-19 are closely related to exosomes. At the same time, exosomes can be used in disease diagnosis and drug treatment carriers.
  • exosomes have far-reaching application prospects for clinical medicine and cutting-edge medical research. Since exosome extraction requires relatively professional biological and medical experimental foundations, it is not conducive to large-scale promotion of manual extraction, and there is currently no mature and stable extraction kit. In view of the important functions of exosomes in medical diagnosis and drug treatment, in order to eliminate the artificial interference of manual extraction, there is an urgent need for a mechanism that can efficiently extract exosomes to ensure that the extraction results are authentic and reliable and to avoid cross-contamination.
  • the purpose of this application is to provide an extraction instrument for accurate and efficient extraction of exosomes, especially a fully automatic extraction instrument, aiming to improve the shortcomings of the current traditional exosome extraction method with numerous steps and improve the authenticity and reliability of the extraction results. .
  • the exosome extraction instrument provided by this application includes the following technical solutions.
  • the exosome extraction instrument includes a base, and the base is provided with:
  • the liquid level detection mechanism detects the liquid level of the experimental sample and records the position
  • a multi-axis manipulator mechanism includes a first support frame and a second support frame. One end of the second support frame is slidingly connected to the first support frame.
  • a sampling device is slidably provided on the second support frame. assembly, there is an angle between the movement trajectory of the second support frame and the movement trajectory of the sampling assembly;
  • the sampling assembly includes a sampling piece
  • the sterilization and filtration mechanism includes a material displacement component, a pressure maintaining component and a sterilization component.
  • the material displacement component is slidably connected to the base.
  • the sterilization component is arranged on the material displacement component.
  • the pressurizing and maintaining component is arranged on the sliding path of the material displacement component on the base;
  • Consumables collection mechanism is used to collect experimental consumables used during the sampling process.
  • the liquid level automatic detection mechanism can detect the liquid level of the experimental sample, record its position, and then cooperate with the multi-axis manipulator mechanism to achieve accurate extraction of the experimental sample volume.
  • the multi-axis manipulator mechanism is slidingly connected to the first supporting frame through the second supporting frame.
  • the sampling component is slidingly connected to the second supporting frame to realize mobile sampling in the plane, and the sampling part moves up and down on the first driving part to realize three-dimensional sampling.
  • the consumables recycling mechanism can promptly recycle test tubes, filter membrane tubes and other experimental consumables used for automatic extraction and separation of exosomes, so as to facilitate subsequent reuse or centralized and unified processing.
  • the above institutions have implemented a fully automatic extraction process of exosomes, effectively avoiding contamination and errors caused by manual operations and ensuring the true reliability of the extraction results.
  • the automatic liquid level detection mechanism includes a liquid level detection up and down moving assembly, which includes a moving plate, a second driving member and a detector mounting plate;
  • the second driving member includes a first Motor and first screw rod, the first screw rod is arranged perpendicular to the moving plate, the first motor is connected to the first screw rod, a first lifting block is provided on the first screw rod, and the detector is installed
  • the plate is connected to the first lifting block; a detector for detecting the liquid level position of the experimental sample is installed on the detector mounting plate.
  • the first motor drives the first screw rod to rotate to drive the first lifting block to move up and down, thereby causing the detector mounting plate connected to the first lifting block to move up and down, driving the detector to move up and down to detect the experimental sample. Liquid level height is detected.
  • the automatic liquid level detection mechanism also includes a liquid level detection horizontal movement component, which includes a first mounting frame, a first driving member and a first transmission provided on the first mounting frame. component, the first driving component is connected to the first transmission component;
  • the moving plate is slidingly connected to the first mounting frame and fixedly connected to the first transmission member; the moving plate is driven by the first driving member and moves horizontally along with the transmission of the first transmission member.
  • a liquid level detection horizontal moving component is set up to detect the liquid levels of different experimental samples in the horizontal direction.
  • the automatic liquid level detection mechanism also includes a sample grabbing rotating assembly, which includes a third driving member, a third transmission member, a rotating shaft and a grabbing member; the third transmission member One end is connected to the third driving member, and the other end is connected to the rotating shaft.
  • a sample grabbing rotating assembly which includes a third driving member, a third transmission member, a rotating shaft and a grabbing member; the third transmission member One end is connected to the third driving member, and the other end is connected to the rotating shaft.
  • the grabber includes a clamping jaw and a first cylinder, the rotating shaft is connected to the first cylinder, and the clamping jaw is symmetrically arranged on both sides of the first cylinder.
  • the third driving member drives the third transmission member to drive the rotation of the rotating shaft.
  • the rotation of the rotating shaft drives the connected grabbing member to rotate.
  • the clamping jaws are driven toward or away from each other by the first cylinder, thereby realizing the holding of the holding parts.
  • the reagent tube containing the experimental sample is clamped and positioned to facilitate the accurate measurement of the liquid level of the experimental sample by the detector installed on the detector mounting plate; the clamping claws are more adapted to the outer wall of the reagent tube, making it easier to clamp stably.
  • the side surfaces of the clamping jaws that are close to each other are arranged in an arc shape.
  • the sides of the clamping jaws that are close to each other can also be set in a wavy shape, a horseshoe shape, a tapered shape, etc.
  • the clamping claws are more suitable for the outer wall of the reagent tube, which plays an anti-slip role and facilitates stable clamping.
  • a third support frame is slidably connected to the second support frame, and a clamping assembly is provided on the third support frame.
  • the clamping assembly includes a clamping member and a fourth driving member. Four driving parts drive the clamping parts to clamp the experimental equipment.
  • the material shifting assembly includes an operating platform, the operating platform is slidably connected to the base, and a plurality of positioning holes are provided on the operating platform.
  • the operating platform slidably connected to the base can move the position of the experimental sample, and the positioning holes can fix the experimental equipment.
  • the experimental equipment here is specifically a bracket and a filter membrane tube assembly.
  • the sampling assembly also includes a sixth driving member, and the sampling member moves up and down under the driving of the sixth driving member.
  • the pressure-maintaining component is disposed above one end of the operating platform, the pressure-maintaining component includes a support member, a cover plate and a seventh driving member, the seventh driving member includes an air compressor;
  • the air compressor is arranged on the support member, and the cover plate is connected to the second cylinder air compressor.
  • the cover plate moves up and down driven by the air compressor and the air compressor.
  • a plurality of pressurizing holes are provided on the cover plate, and the pressurizing holes are connected to the pressure pump through air pipes.
  • the air compressor drives the cover plate to move downward and interacts with the filter membrane containing the sample.
  • the tube is adapted, and the pressure pump generates pressure to apply pressure to the sample in the filter membrane tube through the pressure hole, thereby completing the filtration operation.
  • the disinfection component includes a disinfection reagent bottle and an extrusion piece, and the disinfection reagent bottle contains disinfection reagent;
  • the extrusion piece includes a third cylinder and an extrusion block; one end of the extrusion block is connected to The third cylinder is connected, and the other end of the extrusion block is connected with the disinfectant bottle.
  • the disinfecting reagent (such as disinfecting ethanol, etc.) contained in the disinfecting reagent bottle is driven by the third cylinder, and the extrusion block squeezes the disinfecting reagent bottle.
  • the disinfecting reagent bottle deforms and squeezes the disinfecting reagent inside. Spray out to disinfect.
  • the consumables collection mechanism includes a transmission assembly, a recovery tank and a storage cavity;
  • the recovery tank is arranged between the placing platform and the operating platform;
  • the transmission assembly includes a fifth driving member and a transmission belt.
  • the transmission belt is arranged at the bottom of the recovery tank.
  • the transmission belt communicates with the recovery tank and the storage chamber.
  • the consumables used during each sampling need to be replaced in time, enter from the recycling tank, and then be transported by the transmission mechanism to the storage chamber for recycling and storage.
  • the opening diameter of the recovery tank gradually decreases from top to bottom.
  • the recycling chute plays a guiding role, and discarded experimental consumables will not fall outside the recycling chute.
  • the high-throughput fully automatic exosome extraction instrument provided by this application has the following beneficial effects: it can extract stratified sample liquids through special reagents, filter membranes and clean container holders, by adding reagents, The steps of air pressure holding, filtration, automatic sample transfer, and disinfection to prevent cross-infection realize fully automated extraction of exosomes, which can effectively improve the efficiency of exosome extraction and the reliability of the final extraction structure.
  • Figure 1 is a schematic diagram of the internal structure of the exosome extraction instrument disclosed in the embodiment of the present application.
  • Figure 2 is a schematic structural diagram of the placement platform and experimental equipment of the exosome extraction instrument disclosed in the embodiment of the present application;
  • Figure 3 is a schematic structural diagram of the automatic liquid level detection mechanism of the exosome extraction instrument disclosed in the embodiment of the present application from a first perspective;
  • Figure 4 is a schematic structural diagram of the automatic liquid level detection mechanism of the exosome extraction instrument disclosed in the embodiment of the present application from a second perspective;
  • Figure 5 is a partial structural schematic diagram of the exosome extraction instrument disclosed in the embodiment of the present application.
  • Figure 6 is an enlarged view of point A in Figure 5;
  • FIG. 7 is a schematic structural diagram of the sampling component and the TIP head assembly and disassembly component of the exosome extraction instrument disclosed in the embodiment of the present application;
  • Figure 8 is an enlarged view of B in Figure 5;
  • Figure 9 is a schematic structural diagram of the sterilization and filtering mechanism of the exosome extraction instrument disclosed in the embodiment of the present application.
  • Figure 10 is an enlarged view of C in Figure 9;
  • Figure 11 is a schematic structural diagram of the consumable collection mechanism of the exosome extraction instrument disclosed in the embodiment of the present application.
  • Base 10. Frame; 100. Fixed plate; 101. Partition plate; 102. Support plate; 1021. Limiting plate;
  • First mounting bracket 3010. Accommodating slot
  • Second mounting bracket 303.
  • Third mounting bracket 303.
  • First support frame 402.
  • Second support frame 403.
  • Third support frame 4031. Installation plate; 4032. Connection frame;
  • TIP head assembly and disassembly parts 431.
  • Limit sliding sleeve 432. Assembly and disassembly of cylinder;
  • Material shifting component 511. Operating platform; 5111. First operating area; 5112. Second operating area; 512. Third motor;
  • Disinfection component 531. Disinfection nozzle; 532. Disinfection reagent bottle; 533. Guide seat; 534. Extrusion block; 535. Third cylinder;
  • first and second are used for descriptive purposes only and cannot be understood as indicating or implying relative importance or implicitly indicating the quantity of indicated technical features. Therefore, features defined as “first” and “second” may explicitly or implicitly include at least one of these features.
  • “plurality” means at least two, such as two, three, etc., unless otherwise expressly and specifically limited.
  • connection In this application, unless otherwise clearly stated and limited, the terms “installation”, “connection”, “connection”, “fixing” and other terms should be understood in a broad sense. For example, it can be a fixed connection or a detachable connection. , or integrated into one; it can be a mechanical connection or an electrical connection; it can be a direct connection or an indirect connection through an intermediate medium; it can be an internal connection between two elements or an interactive relationship between two elements, unless otherwise specified limitations. For those of ordinary skill in the art, the specific meanings of the above terms in this application can be understood according to specific circumstances.
  • the exosome extraction instrument includes a base 1.
  • the base 1 is provided with a placement platform 2, an automatic liquid level detection mechanism 3, a multi-axis manipulator mechanism 4, a sterilization and filtering mechanism 5 and a consumables collection mechanism. 6.
  • Experimental samples, experimental reagents and experimental equipment are placed on the placement platform 2.
  • a number of mounting holes 20 are provided on the placement platform 2 so that the above experimental equipment can be stably fixed at corresponding positions.
  • the automatic liquid level detection mechanism 3 will automatically move to the location of the sample and detect the liquid level height of the sample, and record the liquid level position.
  • the multi-axis manipulator mechanism 4 will place the bracket on the platform 2 And the filter membrane tube 241 is clamped and moved to the operating platform 511 of the sterilization and filtration mechanism 5, and then a series of operations such as transferring the sample, filtering and maintaining pressure are performed, and finally the target object is extracted.
  • a series of operations such as transferring the sample, filtering and maintaining pressure are performed, and finally the target object is extracted.
  • the target object is extracted.
  • These wastes are recycled and shipped out through the consumable collection mechanism 6; and the obtained target
  • the objects are moved to the collection tube 221 by the multi-axis manipulator mechanism 4, and the used brackets are reset and restored by the multi-axis manipulator mechanism 4.
  • the entire operation process is fully automatic without manual intervention, the extraction efficiency is high, and cross-contamination can be effectively reduced, thereby ensuring the authenticity and reliability of the extraction structure.
  • the experimental reagents are reagents required for extracting exosomes.
  • the experimental equipment includes a TIP head 231 and a TIP head holder 23, a test tube 211 and a test tube rack 21.
  • the filter tube assembly 24 includes a filter tube 241 and a filter tube holder 242, and is mainly used for filtration of exosome samples.
  • a number of corresponding mounting holes 20 are provided on the placement platform 2.
  • the shapes of the mounting holes 20 include circular and square.
  • the liquid level automatic detection mechanism 3 includes a liquid level detection horizontal movement component 31, a liquid level detection up and down movement component 32, a sample grabbing rotation component 33 and a first mounting bracket 301 for installing the liquid level detection horizontal movement component 31. , the second mounting bracket 302 for mounting the liquid level detection vertical movement component 32 and the third mounting bracket 303 for mounting the sample grabbing and rotating component 33 .
  • the liquid level detection horizontal moving component 31 drives the liquid level detection up and down moving component 32 and the sample grabbing rotating component 33 to move in the Y-axis direction consistent with the direction in which the experimental samples are arranged on the placement platform 2; the experimental samples are detected.
  • the liquid level detection up and down moving component 32 is slidingly connected to the liquid level detection horizontal component to detect the liquid levels of different experimental samples placed on the platform 2 .
  • the liquid level detection horizontal movement assembly 31 includes a base plate 311, a first driving member 312 and a first transmission member 313; the base plate 311 is connected to two first mounting brackets 301, and the first mounting bracket 301 is provided with a receiving slot 3010.
  • a driving member 312 is disposed in the receiving groove 3010 to improve stability.
  • the first driving member 312 is a motor
  • the first transmission member 313 includes a driving wheel 3131 and a driven wheel 3132, as well as a conveyor belt 3133 connecting the driving wheel 3131 and the driven wheel 3132.
  • the conveyor belt 3133 is fixedly connected to the liquid level detection up and down moving assembly 32.
  • a fixed block is provided to be fixed to the conveyor belt 3133, thereby realizing the smooth movement of the liquid level detecting up and down moving assembly 32 and maintaining the accuracy of liquid level detection. sex.
  • the liquid level detection up and down moving assembly 32 includes a moving plate 321, a second driving member 322, a detector mounting plate 323, and a lifting block 324 connecting the detector mounting plate 323 and the second driving member 322.
  • a detector (not shown in the figure) is fixedly installed on the detector mounting plate 323 .
  • the second mounting bracket 302 is disposed on the moving plate 321, and the second driving member 322 is disposed on the second mounting frame 302. Driven by the second driving member 322, the detector mounting plate 323 moves in the Z-axis direction.
  • the second driving member 322 includes a first motor 3221 and a first screw rod 3222.
  • the lifting block 324 is connected to the screw rod.
  • the first motor 3221 drives the first screw rod 3222 to rotate, thereby driving the installation of the detector on the lifting block 324.
  • the plate 323 moves up and down, thereby moving the detector.
  • the detector in the embodiment of the present application is a laser sensor. Because the liquid level of the experimental sample is stratified, the color difference between different liquid level layers is obvious; when the laser sensor passes through liquid levels of different colors, the laser sensor will be triggered to give different signals and transmit the position of the motor. to the control system, converted into position coordinates through calculation, and recorded and saved.
  • the first transmission member 313 is connected to the moving plate 321. Driven by the first driving member 312, the liquid level detection vertical moving assembly 32 moves in the Y-axis direction along with the transmission member.
  • a slide rail 3111 is provided on the base plate 311, and a slider 325 is provided between the moving plate 321 and the base plate 311.
  • the moving plate 321 is slidingly connected to the base plate 311 through the slider 325, and then moves horizontally under the transmission of the conveyor belt 3133.
  • a first origin sensor 3112 is provided on the base plate 311 to position and limit the moving plate 321 to achieve accurate detection.
  • the third mounting bracket 303 is disposed on the second mounting bracket 302 , and the sample grabbing rotation assembly 33 is disposed on the third mounting bracket 303 .
  • the sample grabbing rotating assembly 33 includes a third driving member 331 , a third transmission member 332 , a rotating shaft 333 and a grabbing member 334 .
  • the third driving member 331 is arranged on the third mounting bracket 303.
  • the rotating shaft 333 passes through the third mounting bracket 303 and is connected to the third transmission member 332, and rotates under the driving of the third driving member 331.
  • the lower end of the rotating shaft 333 A grabber 334 is provided.
  • the grabber 334 includes a clamping claw 3341 and a first cylinder 3342.
  • the clamping claw 3341 is symmetrically arranged on both sides of the first cylinder 3342.
  • the clamping claw 3341 is driven by the first cylinder 3342 to clamp the reagent tube of the experimental sample.
  • the surfaces of the clamping claws 3341 that are close to each other are set in an arc shape.
  • a second origin sensor 335 is provided on the third mounting bracket 303 , specifically disposed near the connection between the rotation axis 333 and the third mounting bracket 303 . The precise positioning of the sample grabbing rotating component 33 is achieved.
  • the third driving member 331 is a motor
  • the third transmission member 332 is a conveyor belt, a driving wheel and a driven wheel.
  • the implementation principle and connection relationship are conventional technical means and will not be described in detail here.
  • the first cylinder 3342 needs to drive the clamping claw 3341 to clamp the test tube 211 containing the experimental sample, and rotate it until the laser sensor has a signal.
  • the laser sensor completes the liquid level detection of an experimental sample
  • the third driving part 331 stops working, and the first cylinder 3342 drives the clamping jaw 3341 to loosen; the liquid level detection horizontal moving mechanism drives the sample rotation and grabbing mechanism to move, and the first shown at this time
  • the cylinder 3342 and the clamping jaw 3341 will not interfere with the test tube 211 when moving.
  • a frame 10 is provided on the base 1 to install the multi-axis manipulator mechanism 4.
  • the frame 10 includes three fixed plates 100 that are parallel to each other and perpendicular to the base 1 and connect the three fixed plates 100.
  • the partition 101 specifically, the fixed plate 100 is an L-shaped plate, and the fixed plate 100 is also provided with openings.
  • the L-shaped fixing plate 100 is arranged on the base 1 to effectively improve stability, and secondly, openings are provided to facilitate heat dissipation and observation of the working status of internal components.
  • the multi-axis manipulator mechanism 4 includes a first support frame 401 , a second support frame 402 and a third support frame 403 .
  • the first support frame 401 is disposed at the top of the fixed plate 100 (that is, the fixed plate 100 is away from the base 1 One end), one end of the first support frame 401 is slidingly connected to the second support frame 402, and the third support frame 403 is slidingly connected to the second support frame 402.
  • the first supporting frame 401 is arranged in the Y-axis direction
  • the second supporting frame 402 is arranged in the X-axis direction, and they are perpendicular to each other.
  • the second support frame 402 slides on the first support frame 401 along the Y-axis direction
  • the third support frame 403 slides on the second support frame 402 along the X-axis direction.
  • the third support frame 403 includes a mounting plate 4031 and a connection frame 4032. One end of the installation plate 4031 is slidingly connected to the second support frame 402, and the other end is connected to the connection frame 4032.
  • the third support frame 403 is provided with a clamping assembly 41 and a sampling assembly 42.
  • the clamping assembly 41 is arranged on the mounting plate 4031, and the sampling assembly 42 is arranged on the connection frame 4032, so that they are located on both sides of the second support frame 402.
  • the space layout is reasonable and the sampling and clamping steps do not affect each other.
  • the clamping assembly 41 includes a clamping member 411 and a fourth driving member 412.
  • the fourth driving member 412 is a cylinder
  • the clamping member 411 is two clamping blocks symmetrically arranged on both sides of the cylinder.
  • the cylinder drives the clamping blocks closer to or farther away from each other to realize clamping and releasing of experimental equipment.
  • the experimental equipment is mainly a filter membrane tube assembly.
  • a second motor 413 and a second screw 414 are provided.
  • One end of the second screw 414 is connected to the second motor 413, and then the second screw 414 is connected to the cylinder.
  • the second motor 413 drives the second screw rod 414 to rotate, and the rotation of the second screw rod 414 is converted into driving the cylinder to move upward or downward.
  • a positioning block (not shown in the figure) is provided on the sides of the two clamping blocks that are close to each other, so that the experimental equipment can be accurately positioned when clamping, and the stability during the clamping movement can be maintained.
  • the sampling assembly 42 includes a sixth driving member and a sampling member 421.
  • the sixth driving member is connected to the sampling member 421 and allows the sampling member 421 to move in the Z-axis direction.
  • the sampling piece 421 is a sampling column with an air hole in the middle.
  • the sampling principle of this application is negative pressure sampling. The specific setting is as follows: one end of the sampling piece 421 has an interference fit with the TIP head 231 (the diameter of the sampling piece 421 is slightly larger than the TIP head 231 diameter, so that the TIP head 231 can be clamped on the sampling piece 421).
  • the other end of the sampling piece 421 is connected to the air pump 422. By pumping air, negative pressure is generated in the sampling column to suck the sample, and the exhaust gas causes the sample to be discharged.
  • the sixth driving member is specifically a screw motor, that is, the sampling member 421 is driven by the screw motor to move in the Z-axis direction.
  • sampling component 42 also needs to move on the Z-axis.
  • the specific settings and principles are the same as those of the clamping component 41, and will not be described in detail here.
  • a TIP head assembly and disassembly assembly 43 is provided on the sampling assembly 42.
  • the TIP head assembly and disassembly assembly 43 includes a limiting sliding sleeve 431 and an assembly and disassembly cylinder 432.
  • the limiting sliding sleeve 431 is slidably sleeved on the sampling piece 421, and the limiting sliding sleeve 431 can abut with the upper edge of the TIP head 231; the assembly and disassembly cylinder 432 is fixedly connected to the connection frame 4032, and the piston rod of the assembly and disassembly cylinder 432 is connected to the discharge sliding sleeve 431. Its working principle is: after the piston rod of the assembly and disassembly cylinder 432 is extended, the limiting sliding sleeve 431 can separate and retreat the TIP head 231 from the sampling piece 421, thereby realizing the disassembly of the TIP head 231.
  • a reagent adding component 54 is set up.
  • the reagent adding component 54 includes a mounting base 541, a silicone tube 542 and a peristaltic pump. 543, the silicone tube 542 is installed on the mounting base 541; the peristaltic pump 543 is connected with the silicone tube 542, and the peristaltic pump 543 is also directly connected with the vessel loaded with reagent liquid, thereby realizing the addition of large doses of reagent liquid. .
  • the frame 10 further includes a support plate 102 , which is connected to three fixing plates 100 to form a stable support structure for supporting the sterilization and filtering mechanism 5 .
  • the sterilization and filtering mechanism 5 includes a material displacement component 51 , a pressure maintaining component 52 and a sterilization component 53 .
  • the material shifting assembly 51 includes an operating platform 511 , which is slidingly connected to the support plate 102 .
  • a driving assembly is provided on the operating platform 511 to drive the operating platform 511 to move along the Y-axis direction on the base 1 .
  • the driving component is specifically the third motor 512; the operating platform 511 is divided into a first operating area 5111 and a second operating area 5112.
  • Operation area 5112 adds reagents and performs filtration and sterilization steps.
  • the operating platform 511 is provided with positioning holes (not shown), which can firmly fix the filter membrane holder and maintain its stability.
  • a limiting plate 1021 is provided at one end of the supporting plate 102 close to the first operating area 5111.
  • the pressurizing and maintaining assembly 52 is disposed above one end of the operating platform 511, and specifically includes a support member 521, a cover plate 522, and a seventh driving member.
  • the seventh driving member includes an air compressor and a second cylinder 523.
  • the support member 521 is specifically an L-shaped support column, and both ends of the support column are fixedly connected to the base 1 and the partition 101 respectively;
  • the second cylinder 523 is provided at the upper end of the support column, and the air compressor is provided behind the second cylinder 523 ( (not shown in the figure), the cover plate 522 is arranged below the driving cylinder, and is driven by the second cylinder 523 to move up and down along the Z-axis direction.
  • the cover plate 522 is pressed down and lifted up under the drive of the second cylinder 523, and the air compressor provides air pressure.
  • the cover plate 522 is pressed down and sealed with the filter membrane tube bracket, the pressurization and pressure maintaining functions are realized.
  • the cover plate 522 is provided with a pressurizing hole 5220 that matches the test tube 211 holder.
  • the pressurizing hole 5220 is connected to the pressure pump through the air pipe, and applies pressure to the sample in the filter membrane tube 241 to allow it to pass through the filter membrane. Tube 241 thereby achieves filtration.
  • a sealing gasket 524 is provided on the side of the cover plate 522 away from the driving cylinder, in order to strengthen the sealing performance between the cover plate 522 and the filter membrane tube 241 bracket, thereby better achieving pressure maintenance.
  • the filter tube 241 holder When the experimental sample needs to be filtered, the filter tube 241 holder will be clamped by the clamping assembly 41 from the first operating area 5111 to the second operating area 5112, and then moved to directly below the cover plate 522 by the driving cylinder on the operating platform 511 , at this time, the pressure-maintaining driving cylinder drives the cover plate 522 to cover the filter membrane tube holder, and performs pressurized filtration.
  • the sterilization assembly 53 is disposed on the operating platform 511 and includes a sterilization nozzle 531, a sterilization reagent bottle 532, a guide seat 533 for fixing the sterilization reagent bottle 532, a squeeze block 534 for squeezing the reagent bottle, and a third cylinder. 535.
  • Disinfection reagent bottle 532 contains disinfectant reagent.
  • the squeezing block 534 squeezes the sterilizing reagent bottle 532 driven by the third cylinder 535, and the sterilizing liquid is sprayed from the reagent bottle through the sterilizing nozzle 531 to sterilize the cover plate 522.
  • the consumable collection mechanism 6 includes a recovery tank 61 , a transfer assembly 62 and a storage cavity 63 .
  • the recovery tank 61 is provided between the placement platform 2 and the operation platform 511, and the diameter of the slot of the recovery tank 61 gradually decreases from top to bottom to form a guide opening 610, which facilitates the collection of consumables and enables the consumables to fall steadily on the recycling platform. in slot 61.
  • the transmission assembly 62 is specifically a transmission belt assembly, including a fifth driving member 621 and a transmission belt 622.
  • the fifth driving member includes a motor and a transmission belt, as well as a driving wheel and a driven wheel.
  • the transmission belt 622 is in the fifth driving member. It rotates under the drive to realize the transmission function.
  • the connection relationship and principle of the fifth driving member 621 are conventional technical means in the industry and will not be described in detail here.
  • the conveyor belt 622 connects the recovery tank 61 and the storage cavity 63.
  • the fifth driving member 621 drives the transmission belt 622 to transport the consumables dropped in the recovery tank 61 to the storage cavity 63 for temporary storage, so that they can be taken out and discarded later.
  • a drawer 64 is provided to cover the storage cavity 63 .
  • the drawer 64 includes three side panels 641 and a bottom panel 642 .
  • a sliding guide rail is provided on the side wall of the storage cavity 63 away from the storage cavity 63.
  • the side plate 641 of the drawer 64 is slidingly connected to the sliding guide rail, so that the drawer 64 can be opened and closed at any time.
  • a handle 643 is provided on one side plate 641 of the drawer 64.
  • the beneficial effect of the location of the recovery tank 61 is that the multi-axis manipulator mechanism 4 reciprocates between the placement platform 2 and the operation platform 511 for sampling and clamping test tubes 211, filter membrane tubes 241 brackets and other consumables, and each time they are recycled Above the tank 61, that is, after the TIP head 231 is used once, it can be discarded in the recycling tank 61 on the way, which saves the moving path of the multi-axis manipulator mechanism 4, thereby improving efficiency.
  • the implementation principle of the embodiment of this application is: after starting the exosome extraction instrument, the liquid level detection mechanism will detect the liquid level of the experimental sample placed on the platform 2 and record the position; then the clamping assembly 41 will pair the filter membrane tube 241 and The filter membrane tube 241 holder is clamped and moved from the placement platform 2 to the operating platform 511; the sampling assembly 42 performs sampling. After each sampling, the used TIP head 231 will be pushed out of the assembly and dropped to the consumables.
  • the reagent adding component 54 adds the reagent into the membrane tube 241, moves it to the corresponding position through the material shifting component 51 for pressure maintenance and disinfection, and finally collects it into the collection tube 221 through the sampling component 42, and completes the entire extraction process.
  • the entire process is fully automatic, high-efficiency, and high-precision, reducing cross-contamination and effectively ensuring the accuracy and reliability of exosome extraction results.

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Abstract

本申请提供一种外泌体提取仪,涉及医疗器械的技术领域,其包括液面自动检测机构、多轴机械手机构、消毒过滤机构和用于取样过程中使用过的实验耗材收集的耗材收集机构,其中液面自动检测机构能够有效的检测样品液面高度,精准地计算样本提取和加入量,多轴机械手机构则实现样本提取以及耗材的移动自动化,消毒过滤机构则保证了提取过程中的卫生,有效防止了交叉污染。本申请实现外泌体的全自动提取,放置好样品和各种实验耗材后,启动仪器,其它过程动作全部采用全自动机械化,没有人工的参与,多样本一次提取,既提高了效率,又保证了提取过程的卫生,降低了交叉感染风险的同时保证样本提取结果的一致性。

Description

外泌体提取仪 技术领域
本申请涉及医疗器械的技术领域,尤其是涉及外泌体提取仪。
背景技术
外泌体是细胞产生的胞外小泡,内含核酸、蛋白质等重要胞间通讯介质。外泌体在免疫反应中的作用已被大量文献论证及临床数据记录。此外针对外泌体与疾病治疗的研究中,心血管病、神经衰退型疾病、癌症早期诊断乃至新冠肺炎等呼吸道疾病均与外泌体有密切关联。同时外泌体可应用于疾病诊断以及药物治疗载体。
可见外泌体对于临床医学以及前沿医疗研究有非常深远的应用前景。由于外泌体提取需要相对专业的生科医疗实验基础,不利于大规模推广手动提取,而且目前尚未有成熟的稳定提取试剂盒。鉴于外泌体可应用于医疗诊断以及药物治疗等重要作用,为排除手动提取的人为干扰,急需一种能够对外泌体进行高效提取的机构,从而确保提取结果真实可靠,避免交叉污染。
因此,在本领域中仍然需要一种能够克服外泌体提取不够精确高效的缺陷的技术。
发明内容
本申请的目的是提供一种精准高效提取外泌体的提取仪,尤其是一种全自动提取仪,旨在改善目前传统的外泌体提取方法步骤繁多的弊端,提升提取结果的真实可靠性。
本申请提供的外泌体提取仪包括以下技术方案,外泌体提取仪,包括基座,所述基座上设置有:
液面自动检测机构,所述液面检测机构对所述实验样本的液面进行检测并记录位置;
多轴机械手机构,所述多轴机械手机构包括第一支撑架和第二支撑架,所述第二支撑架的一端滑移连接于第一支撑架,所述第二支撑架上滑动设置有取样组件,所述第二支撑架的运动轨迹与取样组件的运动轨迹之间有夹角;
所述取样组件包括取样件;
消毒过滤机构,所述消毒过滤机构包括物料移位组件、加压保压组件和消毒组件,所述物料移位组件滑移连接在所述基座上,所述消毒组件设置在物料移位组件上,所述加压保压组件设置在物料移位组件在基座上的滑移路径上;
耗材收集机构,用于收集取样过程中使用过的实验耗材。
传统的外泌体提取的步骤繁多,往往包括取样、移液、过滤、消毒等;其中取样移 液的过程要求十分精细,对于实验操作要求高,手动进行提取往往精度不够,而且耗时费力;一般来说,常规的实验器材包括试剂管、试剂架、TIP头等。
通过采用上述技术方案,液面自动检测机构能够对实验样本的液面进行检测,并记录其位置,然后配合多轴机械手机构以实现实验样本量的精准提取。
多轴机械手机构通过第二支撑架与第一支撑架滑移连接,取样组件与第二支撑架滑移连接实现平面内的移动取样,而取样件在第一驱动件上下移动实现三维立体取样,实现自动取样,操作平稳,精度高;耗材回收机构能够对外泌体进行自动提取分离时所用到的试管,滤膜管等实验耗材进行及时回收,便于后续重复利用或集中统一处理。以上机构实现了外泌体的全自动提取流程,有效避免了人工操作所带来的污染以及误差,保证了提取结果的真实可靠性。
可选的,所述液面自动检测机构包括液面检测上下移动组件,所述液面检测上下移动组件包括移动板、第二驱动件以及检测器安装板;所述第二驱动件包括第一电机和第一丝杆,所述第一丝杆垂直于移动板设置,所述第一电机与第一丝杆连接,所述第一丝杆上设置有第一升降块,所述检测器安装板与第一升降块连接;所述检测器安装板上安装有用于检测实验样本的液面位置的检测器。
通过采用上述技术方案,第一电机驱动第一丝杆转动从而带动第一升降块上下移动,从而使与第一升降块连接的检测器安装板上下移动,带动检测器上下移动从而对实验样本的液面高度进行检测。
可选的,所述液面自动检测机构还包括液面检测水平移动组件,所述液面检测水平移动组件包括第一安装架以及设置在第一安装架上的第一驱动件和第一传动件,所述第一驱动件与第一传动件连接;
所述移动板与第一安装架滑动连接,且与第一传送件固定连接;所述移动板在所述第一驱动件的驱动下随着第一传动件的传动进行水平移动。
通过采用上述技术方案,设置液面检测水平移动组件实现水平方向上对不同实验样本的液面进行检测。
可选的,所述液面自动检测机构还包括样本抓取旋转组件,所述样本抓取旋转组件包括第三驱动件、第三传动件、旋转轴以及抓取件;所述第三传动件的一端与第三驱动件连接,另一端与所述旋转轴连接。
所述抓取件包括夹爪和第一气缸,所述旋转轴与第一气缸连接,所述夹爪对称设置在第一气缸的两侧。
通过采用上述技术方案,第三驱动件驱动第三传动件从而带动旋转轴旋转,旋转轴旋转带动其连接的抓取件旋转,夹爪在第一气缸的驱动下互相靠近或远离,实现对盛放实验样本的试剂管进行夹取定位,方便安装在检测器安装板上的检测器对实验样本液面的精准测量;夹爪与试剂管的外壁更加适配,方便稳定夹取。
可选的,所述夹爪相互靠近的侧面设置成弧形。
可选的,所述夹爪相互靠近的侧面还可以设置成波浪形、马蹄形、锥形等。
通过采用上述技术方案,夹爪与试剂管的外壁更加适配,起到防滑的作用,方便稳定夹取。
可选的,所述第二支撑架上还滑移连接有第三支撑架,第三支撑架上设置有夹取组件,所述夹取组件包括夹持件和第四驱动件,所述第四驱动件驱动夹持件对实验器材进行夹持。
可选的,所述物料移位组件包括操作平台,所述操作平台滑移连接于基座上,所述操作平台上设置有若干定位孔。
通过采用上述技术方案,滑移连接于基座上的操作平台能够实现对实验样本位置的移动,另外定位孔能够固定实验器材,此处的实验器材具体为支架及滤膜管组件。
可选的,取样组件还包括第六驱动件,取样件在第六驱动件的驱动下做上下往返运动。
可选的,所述加压保压组件设置在操作平台一端的上方,所述加压保压组件包括支撑件、盖板以及第七驱动件,所述第七驱动件包括以及空气压缩机;所述空气压缩机设置在支撑件上,所述盖板与第二气缸空气压缩机连接,所述盖板在空气压缩机以及空气压缩机的驱动下做上下往返运动。
可选的,所述盖板上设置有若干加压孔,所述加压孔通过气管与压力泵连通。
通过采用上述技术方案,当置于滤膜管组件内的样本在物料移位组件移到加压保压组件的正下方时,空气压缩机驱动盖板向下运动,与盛有样本的滤膜管适配,压力泵产生压力通过加压孔向滤膜管内的样本施加压力,从而完成过滤操作。
可选的,所述消毒组件包括消毒试剂瓶和挤压件,所述消毒试剂瓶内盛放有消毒试剂;所述挤压件包括第三气缸和挤压块;所述挤压块一端与第三气缸连接,所述挤压块另一端与消毒试剂瓶连接。
通过采用上述技术方案,消毒试剂瓶内盛放的消毒试剂(如消毒乙醇等),在第三气缸的驱动下,挤压块挤压消毒试剂瓶,消毒试剂瓶发生形变将内部的消毒试剂挤出喷洒,从 而进行消毒。
可选的,所述耗材收集机构包括传输组件、回收槽和存放腔;
所述回收槽设置在放置平台和操作平台之间;
所述传输组件包括第五驱动件和传输带,所述传输带设置在所述回收槽的槽底,所述传输带连通回收槽和存放腔。
通过采用上述技术方案,在每次进行取样时所使用过的耗材,需要及时更换,从回收槽进入,然后在传输机构的运输下到达存放腔进行回收存放。
可选的,所述回收槽的槽口口径从上往下逐渐减小。
通过采用上述技术方案,回收槽起到导向作用,废弃的实验耗材不会掉落在回收槽之外的地方。
综上所述,本申请提供的外泌体高通量全自动提取仪具有以下的有益效果:能够针对已经分层好的样本液体,通过专用试剂、滤膜和洁净的容器支架,经过添加试剂、气压加压保压、过滤、样本自动转移,以及防止交叉感染的消毒等步骤实现外泌体全自动化提取,能够有效的提高外泌体提取的效率以及最终提取结构的可靠性。
附图说明
图1是本申请实施例公开的外泌体提取仪的内部结构示意图;
图2是本申请实施例公开的外泌体提取仪的放置平台以及实验器材等结构示意图;
图3是本申请实施例公开的外泌体提取仪的液面自动检测机构的第一视角的结构示意图;
图4是本申请实施例公开的外泌体提取仪的液面自动检测机构的第二视角的结构示意图;
图5是本申请实施例公开的外泌体提取仪的部分结构示意图;
图6是图5中A处的放大图;
图7是本申请实施例公开的外泌体提取仪的取样组件以及TIP头装拆组件的结构示意图;
图8是图5中B处的放大图;
图9是本申请实施例公开的外泌体提取仪的消毒过滤机构的结构示意图;
图10是图9中C处的放大图;
图11是本申请实施例公开的外泌体提取仪的耗材收集机构的结构示意图。
附图标记说明:
1、基座;10、机架;100、固定板;101、隔板;102、支撑板;1021、限位板;
2、放置平台;20、安装孔;21、试管架、211、试管;22、收集管支架;221、收集管;23、TIP头支架;231、TIP头;24、滤膜管组件;241、滤膜管;242、滤膜管支架;
3、液面自动检测机构;
301、第一安装架;3010、容纳槽;302、第二安装架;303、第三安装架;
31、液面检测水平移动组件;311、基板;3111、滑轨;3112、第一原点感应器;312、第一驱动件;313、第一传动件;3131、主动轮;3132、从动轮;3133、传送带;
32、液面检测上下移动组件;321、移动板;322、第二驱动件;3221、第一电机;3222、第一丝杆;323、检测器安装板;324、升降块;325、滑块;
33、样本抓取旋转组件;331、第三驱动件;332、第三传动件;333、旋转轴;334、抓取件;3341、夹爪;3342、第一气缸;335、第二原点感应器;
4、多轴机械手机构;
401、第一支撑架;402、第二支撑架;403、第三支撑架;4031、安装板;4032、连接框;
41、夹取组件;411、夹持件;412、第四驱动件;413、第二电机;414、第二丝杆;
42、取样组件;421、取样件;422、气泵;
43、TIP头装拆件;431、限位滑套;432、装拆气缸;
5、消毒过滤机构;
51、物料移位组件;511、操作平台;5111、第一操作区;5112、第二操作区;512、第三电机;
52、加压保压组件;521、支撑件;522、盖板;5220、加压孔;523、第二气缸;524、密封垫圈;
53、消毒组件;531、消毒喷嘴;532、消毒试剂瓶;533、导向座;534、挤压块;535、第三气缸;
54、试剂添加组件;541、安装座;542、硅胶管;543、蠕动泵;
6、耗材收集机构;
61、回收槽;610、导向口;
62、传输组件;621、第五驱动件;622、传输带;
63、存放腔;
64、抽屉;641、侧板;642、底板;643、拉手。
具体实施方式
以下结合附图1-附图11,对本申请作进一步详细说明。
为方便理解本申请实施例,现对下文中所提到的方向进行解释,参照图中进行定义X、Y和Z轴的方向,以及文中所提到的上下左右等方位词均是为了更好理解本方案,不应视为 对本申请的限制。
在本申请的描述中,需要理解的是,术语“中心”、“纵向”、“横向”、“长度”、“宽度”、“厚度”、“上”、“下”、“前”、“后”、“左”、“右”、“竖直”、“水平”、“顶”、“底”、“内”、“外”、“顺时针”、“逆时针”、“轴向”、“径向”、“周向”等指示的方位或位置关系为基于附图所示的方位或位置关系,仅是为了便于描述本申请和简化描述,而不是指示或暗示所指的装置或元件必须具有特定的方位、以特定的方位构造和操作,因此不能理解为对本申请的限制。
此外,术语“第一”、“第二”仅用于描述目的,而不能理解为指示或暗示相对重要性或者隐含指明所指示的技术特征的数量。由此,限定有“第一”、“第二”的特征可以明示或者隐含地包括至少一个该特征。在本申请的描述中,“多个”的含义是至少两个,例如两个,三个等,除非另有明确具体的限定。
在本申请中,除非另有明确的规定和限定,术语“安装”、“相连”、“连接”、“固定”等术语应做广义理解,例如,可以是固定连接,也可以是可拆卸连接,或成一体;可以是机械连接,也可以是电连接;可以是直接相连,也可以通过中间媒介间接相连,可以是两个元件内部的连通或两个元件的相互作用关系,除非另有明确的限定。对于本领域的普通技术人员而言,可以根据具体情况理解上述术语在本申请中的具体含义。
实施例:参照图1和2,外泌体提取仪包括基座1,基座1上设置有放置平台2、液面自动检测机构3、多轴机械手机构4、消毒过滤机构5和耗材收集机构6。放置平台2上放置有实验样本、实验试剂以及实验器材,放置平台2上设置有若干安装孔20,使得以上实验器材能够稳定固定在相应位置上。启动外泌体提取仪后,液面自动检测机构3会自动移动到样本所在位置并进行检测样本的液面高度,并记录液面位置,接着多轴机械手机构4会将放置平台2上的支架以及滤膜管241夹取并移动到消毒过滤机构5的操作平台511上,然后进行转移样本、过滤保压等一系列的操作,最终提取目标物。在每一次进行取样时,需要进行消毒以及自动更换与样本或者试剂接触的TIP头231、丢弃使用过的滤膜管241,这些废弃物通过耗材收集机构6进行回收运出;而所得到的目标物由多轴机械手机构4移到收集管221中,所使用过的支架经多轴机械手机构4进行复位还原。整个操作流程全自动,无需人工介入,提取效率高,还能有效减少交叉污染,从而确保提取结构真实可靠。
参照图2,放置平台2上放置有若干实验器材,具体的,实验试剂为提取外泌体所需用到的试剂,实验器材包括TIP头231及TIP头支架23、试管211及试管架21、收集管支架22以及收集管221、滤膜管组件24等。滤膜管组件24包括滤膜管241以及滤膜管支架 242,主要用于外泌体样本的过滤。为加固实验试剂以及实验器材的稳定性,在放置平台2上设置有若干个相应的安装孔20,安装孔20的形状有圆形,方形。
参照图3和图4,液面自动检测机构3包括液面检测水平移动组件31、液面检测上下移动组件32、样本抓取旋转组件33和安装液面检测水平移动组件31第一安装架301、安装液面检测上下移动组件32的第二安装架302以及安装样本抓取旋转组件33的第三安装架303。
液面检测水平移动组件31带动液面检测上下移动组件32和样本抓取旋转组件33在Y轴方向移动与实验样本在放置平台2上布置的方向一致;对实验样本进行检测。
液面检测上下移动组件32与液面检测水平组件滑移连接,实现对放置平台2上的不同实验样本的液面进行检测。具体的,液面检测水平移动组件31包括基板311、第一驱动件312和第一传动件313;基板311连接两个第一安装架301,第一安装架301上设置有容纳槽3010,第一驱动件312设置在容纳槽3010内,提高稳定性。
具体的,第一驱动件312为电机,第一传动件313包括主动轮3131和从动轮3132以及连接主动轮3131和从动轮3132的传送带3133。传送带3133与液面检测上下移动组件32固定连接,具体到本申请实施例中,设有一个固定块与传送带3133固定,从而实现液面检测上下移动组件32平缓的移动,保持液面检测的准确性。
继续参照图3和图4,液面检测上下移动组件32包括移动板321、第二驱动件322和检测器安装板323以及连接检测器安装板323与第二驱动件322的升降块324,在检测器安装板323上固定安装有检测器(图中未示出)。第二安装架302设置在移动板321上,第二驱动件322设置在第二安装架302上,在第二驱动件322的驱动下,检测器安装板323在Z轴方向上移动。具体的,第二驱动件322包括第一电机3221和第一丝杆3222,升降块324与丝杆连接,第一电机3221驱动第一丝杆3222转动,从而带动升降块324上的检测器安装板323上下移动,从而带动检测器移动。本申请实施例中的检测器为激光感应器。因为实验样本液面分层,不同的液面层之间,颜色的差异明显;激光感应器在不同颜色液面经过时,激光感应器就会触发而给出不同信号,并把电机的位置传输给控制系统,经过计算换算转化为位置坐标,并记录保存下来。
第一传动件313与移动板321连接,在第一驱动件312的驱动下,使得液面检测上下移动组件32随传动件做向Y轴方向的移动。
进一步地,为减少传送带3133传动液面检测上下移动组件32的阻力,在基板311上设置有滑轨3111,并在移动板321与基板311之间设置有滑块325。移动板321通过滑块 325与基板311滑动连接,然后在传送带3133的传动下实现水平的移动。
进一步地,在基板311上设置有第一原点感应器3112,对移动板321进行定位和限位,实现精准检测。
第三安装架303设置在第二安装架302上,样本抓取旋转组件33设置在第三安装架303上。
样本抓取旋转组件33包括第三驱动件331、第三传动件332、旋转轴333和抓取件334。第三驱动件331设置在第三安装架303上,旋转轴333穿过第三安装架303与第三传动件332连接,并在第三驱动件331的驱动下发生转动,旋转轴333的下端设置有抓取件334。抓取件334包括夹爪3341和第一气缸3342,夹爪3341对称设置在第一气缸3342的两侧,夹爪3341在第一气缸3342的驱动下对实验样本的试剂管进行夹取。
进一步地,为了更加贴合试剂管的试管211壁的弧度,实现稳定夹取,将夹爪3341相互靠近的面设置成弧形。
进一步地,在第三安装架303上设置有第二原点感应器335,具体设置在靠近旋转轴333与第三安装架303连接处。实现对样本抓取旋转组件33的精准定位。
本申请实施例中的第三驱动件331为马达,第三传动件332为传送带、主动轮和从动轮,其实施原理以及连接关系为常规技术手段,此处不过多赘述。
这样在检测液面高度位置之前,需要第一气缸3342带动夹爪3341夹紧装有实验样本的试管211,旋转到激光感应器有信号,当激光感应器测完成一个实验样本的液面检测,进行下一个实验样本的液面检测,第三驱动件331停止工作,第一气缸3342带动夹爪3341松开;液面检测水平移动机构带动样本旋转抓取机构移动,这时所示的第一气缸3342和夹爪3341在移动时不会和试管211发生干涉。
参照图5,基座1上设置有机架10用以安装多轴机械手机构4,机架10包括三个互相平行且垂直设置于基座1上的固定板100以及连接三个固定板100的隔板101,具体的,固定板100为L型板,且固定板100上还设有开孔。L型的固定板100设置在基座1上能够有效的提高稳定性,其次设置开孔,利于散热以及观察内部零部件的工作状态。
参照图6,多轴机械手机构4包括第一支撑架401、第二支撑架402和第三支撑架403,第一支撑架401设置在固定板100的顶端(即固定板100远离基座1的一端),第一支撑架401的一端与第二支撑架402滑移连接,第三支撑架403与第二支撑架402滑移连接。第一支撑架401设置在Y轴方向,第二支撑架402设置在X轴方向,两者相互垂直。第二支撑架402在第一支撑架401上沿着Y轴方向上滑动,第三支撑架403在第二支撑架402 上沿着X轴方向上滑动。
第三支撑架403包括安装板4031和连接框4032,安装板4031一端与第二支撑架402滑移连接,另一端与连接框4032连接。第三支撑架403上设置有夹取组件41和取样组件42,夹取组件41设置在安装板4031上,取样组件42设置在连接框4032上,使其两者处于第二支撑架402的两侧,空间布局合理,对于取样以及夹取步骤互不影响。
夹取组件41包括夹持件411和第四驱动件412,具体的,第四驱动件412为气缸,夹持件411为两个对称设置在气缸两侧的夹持块。气缸驱动夹持块相互靠近或远离,实现对实验器材的夹取和松放。本申请实施例中,实验器材主要为滤膜管组件。
为实现夹取组件41在Z轴方向上的移动,设置有第二电机413以及第二丝杆414,第二丝杆414一端与第二电机413连接,然后第二丝杆414再与气缸连接,第二电机413驱动第二丝杆414转动,第二丝杆414的转动转化为带动气缸向上或向下移动。
进一步地,两个夹持块相互靠近的侧面上设置有定位块(图中未示出),在对实验器材夹取时能够精准定位,保持夹取移动过程中的稳定。
取样组件42包括第六驱动件和取样件421,第六驱动件与取样件421连接并使得取样件421实现Z轴方向上的移动。取样件421为一中间设有气孔的取样柱,本申请的取样原理为负压取样,具体设置为:取样件421的一端与TIP头231过盈配合(取样件421的直径略大于TIP头231的直径,这样才能将TIP头231卡接在取样件421上),取样件421的另一端与气泵422连接,通过抽气使得取样柱内产生负压从而吸取样本,排气使得样本排出。在本申请实施例中,第六驱动件具体为丝杆电机,即取样件421在丝杆电机的驱动下实现Z轴方向上的移动。
同样的,在取样过程中也需要取样组件42在Z轴上的移动,具体设置以及原理同夹取组件41一样,此处不过多赘述。
参照图7,每一次进行取样时,都需要更换与实验试剂或实验样本接触过的TIP头231,为了实现自动更换。在取样组件42上设置TIP头装拆组件43,TIP头装拆组件43包括限位滑套431以及装拆气缸432,限位滑套431滑动套设在取样件421上,并且限位滑套431能与TIP头231的上端边缘抵接;装拆气缸432固定连接在连接框4032上,并且装拆气缸432的活塞杆与卸料滑套431相连接。其工作原理为:在装拆气缸432的活塞杆伸出后,限位滑套431便能够将TIP头231从取样件421上分离并退下,从而实现TIP头231的拆卸。
参照图1和图7,在对外泌体进行提取时,还需要加入相关试剂,为实现自动添加试剂的功能,设置了试剂添加组件54试剂添加组件54包括安装座541、硅胶管542和蠕动泵 543,硅胶管542穿设在安装座541上;蠕动泵543则与硅胶管542相连通,并且蠕动泵543还直接与装载有试剂液的器皿相连通,从而来实现大剂量试剂液的添加工作。
参照图5和图8,机架10还包括支撑板102,支撑板102连接三个固定板100,形成稳定的支撑结构,用以支撑消毒过滤机构5。消毒过滤机构5包括物料移位组件51、加压保压组件52和消毒组件53。物料移位组件51包括操作平台511,操作平台511与支撑板102滑移连接,在操作平台511上设置有驱动组件驱动操作平台511在基座1上沿Y轴方向移动。在本申请实施例中,该驱动组件具体为第三电机512;操作平台511分为第一操作区5111和第二操作区5112,在第一操作区5111内完成取样操作,后转移到第二操作区5112添加试剂以及进行过滤和消毒的步骤。操作平台511上设有定位孔(未示出),能够将滤膜支架稳稳固定住,保持其稳定性。
进一步地,为限制操作平台511的过渡移动,在支撑板102的靠近第一操作区5111的一端设置有限位板1021。
操作平台511与支撑板102的滑移连接,以及其中操作平台511实现X轴方向的移动原理与上述的液面检测水平移动组件31的原理相同,此处不在赘述。
参照图8和图9,加压保压组件52设置在操作平台511一端的上方,具体包括支撑件521、盖板522以及第七驱动件,第七驱动件包括空气压缩机和第二气缸523。支撑件521具体为L型的支撑柱,支撑柱的两端分别与基座1和隔板101固定连接;第二气缸523设置在支撑柱上端,空气压缩机设置在第二气缸523的后面(图中未示出),盖板522与设置在驱动气缸下方,在第二气缸523的驱动下,沿Z轴方向上下运动。即盖板522在第二气缸523的驱动下做下压和抬起动作,空气压缩机提供空气压力,在盖板522下压与滤膜管支架密封时,实现加压与保压功能。
参照图10,盖板522上设置有与试管211支架相匹配的加压孔5220,加压孔5220通过气管与压力泵连接,通过向滤膜管241内的样本施加压力,使其通过滤膜管241从而实现过滤。
具体的,盖板522远离驱动气缸的一侧都设有密封垫圈524,这样是为了加固盖板522与滤膜管241支架的密封性,从而更好的实现加压保压。
当需要对实验样本过滤时,滤膜管241支架会被夹取组件41从第一操作区5111夹到第二操作区5112,然后被操作平台511上的驱动气缸移动至盖板522的正下方,此时加压保压的驱动气缸驱动盖板522将滤膜管支架盖住,进行加压过滤。
参照图9和图10,消毒组件53设置在操作平台511上,包括消毒喷嘴531、消毒试 剂瓶532以及固定消毒试剂瓶532的导向座533以及挤压试剂瓶的挤压块534和第三气缸535,消毒试剂瓶532中装有消毒试剂。挤压块534在第三气缸535的驱动下对消毒试剂瓶532进行挤压,消毒液从试剂瓶中喷出经消毒喷嘴531喷出对盖板522进行消毒。
参照图11,耗材收集机构6包括回收槽61、传输组件62以及存放腔63。回收槽61设置在放置平台2和操作平台511之间,且回收槽61的槽口的口径从上往下逐渐减少,形成一个导向口610,方便耗材的收集,使耗材稳稳掉落在回收槽61内。传输组件62具体为传输带组件,包括第五驱动件621和传输带622,在本申请实施例中,第五驱动件包括电机和传送带以及主动轮和从动轮,传输带622在第五驱动件的驱动下发生转动,实现传输功能。第五驱动件621的连接关系以及原理为行业内常规技术手段,此处不做过多描述。
传输带622的连通回收槽61与存放腔63,第五驱动件621驱动传输带622传动,将落在回收槽61内的耗材运输至存放腔63进行暂时存放,便于后续取出丢弃。为进一步方便对耗材的收集和存放,设置有抽屉64将存放腔63盖合。抽屉64包括三个侧板641和一个底板642。存放腔63的侧壁远离存放腔63的一侧设置有滑导轨,抽屉64的侧板641与滑导轨滑移连接,使得抽屉64能够随时打开关闭。为方便抽屉64的开闭,在抽屉64的一侧板641上设置有拉手643。
其中回收槽61的设置位置的有益效果在于,多轴机械手机构4在放置平台2以及操作平台511之间来回往复的取样以及夹取试管211、滤膜管241支架等耗材,每次会经过回收槽61上方,即在TIP头231使用一次后即可在途中将其丢弃在回收槽61内,节省了多轴机械手机构4移动路径,从而提高效率。
本申请实施例的实施原理为:启动外泌体提取仪后,液面检测机构会对放置平台2上的实验样本进行液面检测,并记录位置;然后夹取组件41对滤膜管241以及滤膜管241支架进行夹取移动,从放置平台2夹取到操作平台511上;取样组件42进行取样,每一次取样后,使用过的TIP头231会被推出组件进行推出,并落到耗材收集机构6中;试剂添加组件54向滤膜管241内添加试剂,通过物料移位组件51移到相应位置进行加压保压和消毒,最终通过取样组件42进行收集到收集管221中,完成整个提取过程。整个过程全自动,效率高,精度高,降低了交叉污染,有效的保证了外泌体提取结果的准确可靠性。
本具体实施方式的实施例均为本申请的较佳实施例,并非依此限制本申请的保护范围,其中相同的零部件用相同的附图标记表示。故:凡依本申请的结构、形状、原理所做的等效变化,均应涵盖于本申请的保护范围之内。

Claims (11)

  1. 外泌体提取仪,其特征在于,包括基座(1),所述基座(1)上设置有:
    液面自动检测机构(3),所述液面检测机构对实验样本的液面进行检测并记录位置;
    多轴机械手机构(4),所述多轴机械手机构(4)包括第一支撑架(401)和第二支撑架(402),所述第二支撑架(402)的一端滑移连接于第一支撑架(401),所述第二支撑架(402)上滑动设置有取样组件(42),所述第二支撑架(402)的运动轨迹与取样组件(42)的运动轨迹之间有夹角;
    所述取样组件(42)包括取样件(421);
    消毒过滤机构(5),所述消毒过滤机构(5)包括物料移位组件(51)、加压保压组件(52)和消毒组件(53),所述物料移位组件(51)滑移连接在所述基座(1)上,所述消毒组件(53)设置在物料移位组件(51)上,所述加压保压组件(52)设置在物料移位组件(51)滑移路径上;
    耗材收集机构(6),用于收集取样过程中使用过的实验耗材。
  2. 根据权利要求1所述的外泌体提取仪,其特征在于,所述液面自动检测机构(3)包括液面检测上下移动组件(32),所述液面检测上下移动组件(32)包括移动板(321)、第二驱动件(322)以及检测器安装板(323);所述第二驱动件(322)包括第一电机(3221)和第一丝杆(3222),所述第一丝杆(3222)垂直于移动板(321)设置,所述第一电机(3221)与第一丝杆(3222)连接,所述第一丝杆(3222)上设置有第一升降块(324),所述检测器安装板(323)与第一升降块(324)连接;所述检测器安装板(323)上安装有用于检测实验样本的液面位置的检测器。
  3. 根据权利要求2所述的外泌体提取仪,其特征在于,所述液面自动检测机构(3)还包括液面检测水平移动组件(31),所述液面检测水平移动组件(31)包括第一安装架(301)以及设置在第一安装架(301)上的第一驱动件(312)和第一传动件(313),所述第一驱动件(312)与第一传动件(313)连接;
    所述移动板(321)与第一安装架(301)滑动连接,且与第一传送件固定连接;所述移动板(321)在所述第一驱动件(312)的驱动下随着第一传动件(313)的传动进行水平移动。
  4. 根据权利要求1所述的外泌体提取仪,其特征在于,所述液面自动检测机构(3)还包括样本抓取旋转组件(33),所述样本抓取旋转组件(33)包括第三驱动件(331)、第三传动件(332)、旋转轴(333)以及抓取件(334);所述第三传动件(332)的一端与第三驱动件(331)连接,另一端与所述旋转轴(333)连接;
    所述抓取件(334)包括夹爪(3341)和第一气缸(3342),所述旋转轴(333)与第一气缸(3342)连接,所述夹爪(3341)对称设置在第一气缸(3342)的两侧。
  5. 根据权利要求1所述的外泌体提取仪,其特征在于,所述第二支撑架(402)上还滑移连接有第三支撑架(403),第三支撑架(403)上设置有夹取组件(41),所述夹取组件(41)包括夹持件 (411)和第四驱动件(412),所述第四驱动件(412)驱动夹持件(411)对实验器材进行夹持。
  6. 根据权利要求1所述的外泌体提取仪,其特征在于,所述物料移位组件(51)包括操作平台(511),所述操作平台(511)滑移连接于基座(1)上,所述操作平台(511)上设置有若干定位孔。
  7. 根据权利要求6所述的外泌体提取仪,其特征在于,所述加压保压组件(52)设置在操作平台(511)一端的上方,所述加压保压组件(52)包括支撑件(521)、盖板(522)以及第二气缸(523);所述第二气缸(523)设置在支撑件(521)上,所述盖板(522)与第二气缸(523)连接,所述盖板(522)在第二气缸(523)的驱动下做上下往返运动。
  8. 根据权利要求1所述的外泌体提取仪,其特征在于,所述消毒组件(53)包括消毒试剂瓶(532)和挤压件,所述消毒试剂瓶(532)内盛放有消毒试剂;所述挤压件包括第三气缸(535)和挤压块(534);所述挤压块(534)一端与第三气缸(535)连接,所述挤压块(534)另一端与消毒试剂瓶(532)连接。
  9. 根据权利要求1所述的外泌体提取仪,其特征在于,所述耗材收集机构(6)包括传输组件(62)、回收槽(61)和存放腔(63);
    所述回收槽(61)设置在放置平台(2)和操作平台(511)之间;
    所述传输组件(62)包括第五驱动件(621)和传输带(622),所述传输带(622)设置在所述回收槽(61)的槽底,所述传输带(622)连通回收槽(61)和存放腔(63)。
  10. 根据权利要求9所述的外泌体提取仪,其特征在于,所述回收槽(61)的槽口口径从上往下逐渐减小。
  11. 根据权利要求1所述的外泌体提取仪,其特征在于,所述取样组件(42)还包括第六驱动件,所述取样件(421)在所述第六驱动件的驱动下做上下往返运动。
PCT/CN2022/116580 2022-07-26 2022-09-01 外泌体提取仪 WO2024021222A1 (zh)

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