WO2024138818A1 - 基因处理设备 - Google Patents
基因处理设备 Download PDFInfo
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- WO2024138818A1 WO2024138818A1 PCT/CN2023/073157 CN2023073157W WO2024138818A1 WO 2024138818 A1 WO2024138818 A1 WO 2024138818A1 CN 2023073157 W CN2023073157 W CN 2023073157W WO 2024138818 A1 WO2024138818 A1 WO 2024138818A1
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- NJPPVKZQTLUDBO-UHFFFAOYSA-N novaluron Chemical compound C1=C(Cl)C(OC(F)(F)C(OC(F)(F)F)F)=CC=C1NC(=O)NC(=O)C1=C(F)C=CC=C1F NJPPVKZQTLUDBO-UHFFFAOYSA-N 0.000 claims 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M1/00—Apparatus for enzymology or microbiology
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M1/00—Apparatus for enzymology or microbiology
- C12M1/02—Apparatus for enzymology or microbiology with agitation means; with heat exchange means
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M1/00—Apparatus for enzymology or microbiology
- C12M1/34—Measuring or testing with condition measuring or sensing means, e.g. colony counters
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M1/00—Apparatus for enzymology or microbiology
- C12M1/36—Apparatus for enzymology or microbiology including condition or time responsive control, e.g. automatically controlled fermentors
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M1/00—Apparatus for enzymology or microbiology
- C12M1/36—Apparatus for enzymology or microbiology including condition or time responsive control, e.g. automatically controlled fermentors
- C12M1/38—Temperature-responsive control
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M1/00—Apparatus for enzymology or microbiology
- C12M1/40—Apparatus specially designed for the use of free, immobilised, or carrier-bound enzymes, e.g. apparatus containing a fluidised bed of immobilised enzymes
Definitions
- the first transmission member is driven to rotate forward or reversely by the first driving mechanism, so that the first slider moves upward or downward along the first guide rail.
- the piston principle is used to form negative pressure or positive pressure inside the vacuum chamber, thereby driving the suction tip on the pipette head to produce a suction and injection effect on the reagent, and the reagent is pipetted by the suction tip installed on the pipette head.
- the second driving mechanism drives the second transmission member to rotate forward or reversely, so that the push plate moves upward or downward.
- the limit plate moves downward to push the cooling cover guide rod downward, and then the cooling cover plate connected to the bottom of the cooling cover guide rod moves downward, and the heat cover installed on the heating column is unloaded by the force of the cooling cover plate.
- the second driving mechanism drives the second transmission member to rotate in the opposite direction, drives the push plate to move upward, and the push plate returns to its initial position.
- the push plate leaves the limit plate, and the cooling cover guide rod returns to its initial position under the elastic force of the second elastic member, so that the cooling cover plate is reset.
- the X-direction lead screw is made to rotate forward and reverse, driving the X-direction lead screw nut and the lead screw nut connecting seat to move back and forth, so that the X-direction motion plate moves forward and backward along the positive and reverse directions of the X-axis, thereby driving the Y-axis base plate to move forward and backward along the positive and reverse directions of the X-axis.
- the synchronous belt transmission assembly is driven to move left and right along the Y-axis direction, and the left and right movement of the synchronous belt transmission assembly drives the Z-axis motion assembly to move left and right in the Y-axis direction.
- the Z-direction driving motor to drive the Z-direction lead screw to rotate
- the Z-direction lead screw rotates, driving the Z-direction lead screw nut and the lead screw nut connecting seat to move, so that the Z-direction motion plate slides along the Z-direction slide rail, so that the Z-direction motion plate can move up and down along the Z-axis direction.
- a refrigeration component is further provided in the table assembly module, and the refrigeration component is provided at the bottom of the reagent box for cooling the reagent wells.
- FIG3 is a schematic diagram of the structure of an X-axis motion assembly provided in an embodiment of the present application.
- 1-gene processing equipment 100-frame; 200-station switching module; 210-support frame; 211-second position sensor; 220-bottom plate of the support frame; 221-through hole of the guide rod of the suction head; 222-through hole of the guide rod of the cooling cover; 230-X-axis motion assembly; 231-X-axis bottom plate; 2311-X-direction slide rail; 232-X-direction driving mechanism; 2321-X-direction transmission member; 233-X-direction connecting member; 234-X-direction motion plate; 2341-X-direction position sensing positioning plate; 240-Y-axis motion assembly; 241-Y-axis bottom plate; 2411-Y-direction slide rail; 2412-Y-direction position sensing positioning plate; 242-Y-direction driving Mechanism; 243- synchronous belt drive assembly; 2431- synchronous pulley; 2432- synchronous belt; 250- Z-axis motion assembly; 251- Z-axis bottom plate; 2511- Z-direction slide rail
- the terms “set”, “installed”, “connected” and “connected” should be understood in a broad sense.
- it can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection or an electrical connection; it can be a direct connection or an indirect connection through an intermediate medium, and it can be the internal connection of two elements.
- the premise of genetic testing is to extract high-quality and high-purity nucleic acids from biological samples. Therefore, nucleic acid extraction and purification, gene library construction, and PCR amplification have become important steps in genetic testing. According to the sequence of known nucleic acids, specific primers and probes are designed, and the designed primers are synthesized. The extracted nucleic acids are used as templates for fluorescent quantitative PCR experiments. The positive and negative nature of the template samples is judged based on the fluorescent signals. Nucleic acid extraction is a key step in genetic testing. The quality of nucleic acids obtained will directly affect the success or failure of subsequent experiments.
- gene pre-processing processes such as nucleic acid extraction and gene library construction are mainly carried out in an open experimental environment, mostly manually, or each step is completed with the help of different instruments, or the same automated instrument is used but the samples are not isolated.
- the efficiency is low and the operation requirements for technicians are high; when multiple instruments are used, samples are contaminated with each other, the process is complicated, and the requirements for technicians are high; when a single pipetting station-type automated instrument is used to transfer multiple samples, it is necessary to wait for multiple samples to arrive before working, which is not flexible enough. Therefore, the above three gene processing methods all have different problems, resulting in reduced efficiency of gene processing. Therefore, based on the above problems, the present application provides a gene processing device 1.
- a single sample can be tested as soon as it arrives, with a fast speed, and can be applied to different reagents and different gene sequencing schemes. There is no mutual contamination during the operation process, which improves the efficiency and accuracy of gene detection processing.
- a gene processing device 1 includes: a frame 100, a station switching module 200, a base support module 300, a composite function module 400, a table assembly module 500, and an environmental control module 600; the station switching module 200 is arranged in the frame 100, and a support frame 210 is arranged on the station switching module 200; the base support module 300 is arranged in the frame 100, the table assembly module 500 is arranged on the base support module 300, and a reagent kit 510 is arranged on the table assembly module 500, and a plurality of reagent kits 510 are arranged on the reagent kit 510 Functional hole 511, a temperature-controlled magnetic suction component 520 is provided in the table assembly module 500; the composite functional module 400 is arranged on the support frame 210, and the station switching module 200 is used to drive the composite functional module 400 to transfer between various functional hole positions 511; wherein, the composite functional module 400 includes: a pipetting component 410 and a hot cover heating component 420; the pipetting component 410 is
- the rack 100 may be assembled from a plurality of supporting sheet metal parts, and is used to fix and install various components in the gene processing device 1.
- the shape of the rack 100 may be designed according to various devices in the gene processing device 1, and an anti-pollution transparent observation window may be installed on the rack 100 for the operator to observe the experimental process at any time.
- the rack 100 is a rectangular parallelepiped structure, and a coordinate system is established with the height direction of the rack 100 as the Z axis, the width direction of the rack 100 is the X axis, the length direction of the rack 100 is the Y axis, and the bottom surface of the rack 100 is the XY reference plane.
- the X axis, the Y axis, and the Z axis are perpendicular to each other, and the positive direction of the X axis is defined as forward, the positive direction of the Y axis is rightward, and the positive direction of the Z axis is upward.
- the Y-axis motion assembly 240 includes: a Y-axis base plate 241, a Y-direction driving mechanism 242, and a synchronous belt transmission assembly 243.
- the Y-axis base plate 241 is connected to the X-direction motion plate 234 shown in FIG. 2 ;
- the Y-direction driving mechanism 242 is disposed on the Y-axis base plate 241 along the Y direction; and
- the synchronous belt transmission assembly is in transmission connection with the Y-direction driving mechanism 242.
- the X-direction lead screw is made to rotate forward and reverse, driving the X-direction lead screw nut and the lead screw nut connecting seat to move back and forth, so that the X-direction motion plate 234 moves forward and backward along the positive and reverse directions of the X-axis, thereby driving the Y-axis bottom plate 241 to move forward and backward along the positive and reverse directions of the X-axis.
- the forward and reverse rotation of the Y-direction driving motor is controlled to drive the synchronous belt transmission assembly 243 to move left and right along the Y-axis direction.
- the Y-direction slide rail 2411 is located at the outer end of the synchronous belt 2432, and the Z-axis base plate 251 can slide along the Y-direction slide rail 2411; the Z-direction motion plate 252 is slidably arranged on the Z-axis base plate 251. Specifically, a Z-direction slide rail 2511 is symmetrically arranged on the Z-axis base plate 251.
- the Z-direction moving plate 252 can slide along the Z-direction slide rail 2511; the support frame 210 is connected to the Z-direction moving plate 252, and the support frame 210 and the Z-direction moving plate 252 can be fixedly connected by welding.
- the Z-direction driving mechanism 253 is arranged on the support frame 210 along the Z direction, and the Z-direction driving mechanism 253 is connected to a Z-direction transmission member 2531, and the Z-direction transmission member 2531 is transmission-connected to the Z-direction connecting member 254, and the Z-direction connecting member 254 can be fixed by a fixed seat, etc.
- the method is arranged on the Z-direction motion plate 252.
- the Z-direction lead screw is connected to the output end of the Z-direction driving motor, and the Z-direction lead screw is driven to rotate by the Z-direction driving motor, and the Z-direction lead screw rotates, driving the Z-direction lead screw nut and the lead screw nut connecting seat to move, so that the Z-direction motion plate 252 slides along the Z-direction slide rail 2511, so that the Z-direction motion plate 252 can move up and down along the Z-axis direction.
- the Z-direction lead screw is made to rotate forward and reverse, thereby driving the Z-direction lead screw nut and the lead screw nut connecting seat to move back and forth, so that the Z-direction motion plate 252 moves up and down along the positive and reverse directions of the Z-axis.
- the X-direction lead screw is made to rotate forward and reverse, driving the X-direction lead screw nut and the lead screw nut connecting seat to move back and forth, so that the X-direction motion plate 234 moves forward and backward along the positive and reverse directions of the X-axis, thereby driving the Y-axis base plate 241 to move forward and backward along the positive and reverse directions of the X-axis.
- the synchronous belt transmission assembly 243 is driven to move left and right along the Y-axis direction.
- the left and right movement of the synchronous belt transmission assembly 243 drives the Z-axis motion assembly 250 to move left and right in the Y-axis direction.
- the Z-direction driving motor to drive the Z-direction lead screw to rotate
- the Z-direction lead screw rotates, driving the Z-direction lead screw nut and the lead screw nut connecting seat to move, so that the Z-direction motion plate 252 slides along the Z-direction slide rail 2511, so that the Z-direction motion plate 252 can move up and down along the Z-axis direction.
- the Z-direction lead screw By controlling the forward and reverse rotation of the Z-direction driving motor, the Z-direction lead screw can be rotated forward and reversed, thereby driving the Z-direction lead screw nut and the lead screw nut connecting seat to move back and forth, so that the Z-direction motion plate 252 moves up and down along the positive and reverse directions of the Z-axis, and finally drives the support frame 210 connected to the Z-direction motion plate 252 to move up and down, driving the composite functional module 400 on the support frame 210 to move up and down.
- a Y-direction position sensing positioning plate 2412 may be installed on the Y-axis base plate 241; in order to more accurately locate the moving position of the Z-direction motion plate 252, a Z-direction position sensing positioning plate 2512 may be installed on the Z-axis base plate 251.
- the liquid transfer assembly 410 and the hot cover heating assembly 420 are integrated on the bottom plate 220 of the support frame. This arrangement can make the components in the composite functional module 400 more compact and save space.
- the liquid transfer assembly 410 includes: a first mounting plate 411, a first driving mechanism 412, a first slider 413, a piston rod 414, a vacuum chamber 415 and a liquid transfer gun head 416.
- the first mounting plate 411 is parallel to the Z-axis direction and is arranged on the support frame 210.
- the first driving mechanism 412 is arranged on the first mounting plate 411.
- the first driving mechanism 412 is connected to a first transmission member 4121.
- the first driving mechanism 412 is connected to the first slider 413 through the first transmission member 4121.
- the first slider 413 is arranged on the first mounting plate 411.
- a first guide rail 4111 is symmetrically arranged on the first mounting plate 411.
- the first slider 413 can slide up and down along the first guide rail 4111.
- a piston rod 414 is arranged at the bottom of the first slider 413, and a vacuum chamber 415 is arranged on the bottom plate 220 of the support frame.
- the first driving mechanism 412 is used to drive the first slider 413 to rise and fall, thereby driving the piston rod 414 to move and extend into the vacuum chamber 415;
- a pipette tip 416 is connected to the vacuum chamber 415, and the pipette tip 416 extends to the bottom from the bottom plate 220 of the support frame.
- the pipette tip 416 is used to install a suction tip, and a through hole 4161 is arranged in the pipette tip 416, and the through hole 4161 is connected to the bottom of the vacuum chamber 415.
- a first position sensor 4112 may be provided on the first mounting plate 411 .
- the first driving mechanism 412 is preferably a first motor
- the first transmission member 4121 is preferably a first screw
- the first screw is fixed to the first slider 413 by a screw nut and a screw nut connecting block.
- the first driving mechanism 412 drives the first transmission member 4121 to rotate forward or reversely, so that the first slider 413 moves upward or downward along the first guide rail 4111, and the piston principle is used to form a negative pressure or a positive pressure inside the vacuum chamber 415, thereby driving the suction head on the pipette tip 416 to produce a suction and injection effect on the reagent, and the reagent is pipetted by the suction head installed on the pipette tip 416.
- an auxiliary piston rod 4141 is further provided at the bottom of the first slider 413.
- the auxiliary piston rod 4141 is used to drive the piston in the sealing area of the reagent box, and shares the same first driving mechanism 412 and the first slider 413 with the pipette tip 416.
- a hole is provided on the bottom plate 220 of the support frame for the auxiliary piston rod 4141 to pass through, and a guide bearing is provided at the hole on the bottom plate 220 of the support frame, so that an auxiliary guide force exists at the contact surface between the auxiliary piston rod 4141 and the bottom plate 220 of the support frame, thereby providing a more accurate position for the auxiliary piston rod 4141.
- the function of the auxiliary piston rod 4141 will be described in detail below.
- the pipetting assembly 410 further includes: a pipette tip ejection plate 417, a pipette tip ejection guide rod 418, and a first elastic member 419; wherein the pipette tip ejection plate 417 is movably disposed on the pipette tip 416, the pipette tip ejection guide rod 418 is disposed on the pipette tip ejection plate 417, a pipette tip ejection guide rod through hole 221 is disposed on the bottom plate 220 of the support frame, the pipette tip ejection guide rod 418 passes through the pipette tip ejection guide rod through hole 221, and extends toward the first slider 413; the first elastic member 419 is sleeved on the end of the pipette tip ejection guide rod 418 extending toward the first slider 413.
- the first elastic member 419 is
- the first driving mechanism 412 drives the first transmission member 4121 to rotate, thereby driving the first slider 413 to slide downward.
- the first slider 413 continues to move downward, pushing the tip ejection guide rod 418 to move downward, thereby causing the tip ejection guide rod 418 to push the tip ejection plate 417 to move downward, and the tip installed on the pipette tip 416 is unloaded by the force of the tip ejection plate 417.
- the first driving mechanism 412 drives the first transmission member 4121 to rotate in the opposite direction, driving the first slider 413 to slide upward, and the first slider 413 returns to the initial position.
- the first slider 413 leaves the tip ejection guide rod 418, and the tip ejection guide rod 418 returns to the initial position under the elastic force of the first elastic member 419, so that the tip ejection plate 417 is reset.
- the bottom of the column 423 is used to connect the heat cover; the cooling cover plate 424 is movably arranged on the heating column 423; the cooling cover guide rod 425 is arranged on the cooling cover plate 424, and the bottom plate 220 of the support frame is provided with a cooling cover guide rod through hole 222, and the cooling cover guide rod 425 passes through the cooling cover guide rod through hole 222 and extends to the push plate 422; the limit plate 426 is arranged on one end of the cooling cover guide rod 425 extending to the push plate 422; the second elastic member 427 is sleeved on the cooling cover guide rod 425 and is located between the bottom plate 220 of the support frame and the limit plate 426.
- the second elastic member 427 is preferably a spring.
- the heat cover is preferably a contoured heat cover, and a temperature sensor and a heating rod are arranged inside the contoured heat cover to heat up the heat cover.
- the second driving mechanism 421 is preferably a second motor, and the second transmission member 4211 is preferably a second screw, which is fixed to the push plate 422.
- the second driving mechanism 421 drives the second transmission member 4211 to rotate forward or reversely, so that the push plate 422 moves upward or downward, when the push plate 422 moves downward and approaches the limit plate 426, and continues to drag the limit plate 426 downward, the limit plate 426 moves downward to push the cooling cover guide rod 425 downward, and then the cooling cover plate 424 connected to the bottom of the cooling cover guide rod 425 moves downward, and the heat cover installed on the heating column 423 is unloaded by the force of the cooling cover plate 424.
- the second driving mechanism 421 drives the second transmission member 4211 to rotate in the opposite direction, drives the push plate 422 to move upward, and the push plate 422 returns to its initial position.
- the push plate 422 leaves the limiting plate 426, and the cooling cover guide rod 425 returns to its initial position under the elastic force of the second elastic member 427, so that the cooling cover plate 424 is reset.
- the base support module 300 includes: a base 310, a station switching support base 320, and a translation assembly 330; wherein the station switching support base 320 is disposed on the base 310 and connected to the station switching module 200. Specifically, the station switching support base 320 is connected to the bottom of the X-axis bottom plate 231 on the X-axis motion assembly 230. The translation assembly 330 is disposed on the base 310.
- the translation assembly 330 includes: a first guide rail connecting plate 331, a second guide rail connecting plate 332, and a drawer-type motion plate 333; the first guide rail connecting plate 331 is fixed on the base 310, and the second guide rail connecting plate 332 is slidably disposed on the first guide rail connecting plate 331.
- the first guide rail connecting plate 331 is provided with a first connecting plate guide rail 3311, and a slider capable of sliding on the first connecting plate guide rail 3311 is disposed at the bottom of the second guide rail connecting plate 332; the drawer-type motion plate 333 is connected to the top of the second guide rail connecting plate 332.
- a pressure rod 501 may be provided on both outer sides of the table assembly module 500, and a spring is sleeved around the pressure rod 501.
- the drawer-type motion plate 333 When the drawer-type motion plate 333 is pulled away from the edge of the rack 100, the pressure plate 311 cancels the pressure on the pressure rod 501, and under the action of the spring, the pressure rod 501 pops outward to restore the initial state, and the reagent box 510 is released from the fixed state.
- the drawer-type motion plate 333 can be pushed manually, or it can be automatically pushed by a hydraulic cylinder or a motor.
- the reagent kit 510 has a plurality of functional holes 511, which include: at least one pipette tip storage hole 5111 for storing pipette tips, at least one test tube storage hole 5112 for storing detachable tubes, at least one first reaction hole 5113 (denoted as W1), in which fragmentation and hybridization reactions can be performed, the bottom of the first reaction hole 5113 can be heated, and the top is sealed with a hot cover, and the capacity is preferably 0.2 ml, at least one second reaction hole 5114 (denoted as W2), in which nucleic acid extraction, post-fragment sorting/purification, and post-PCR purification reactions can be performed, the bottom of the second reaction hole 5114 can be magnetically attracted and heated, and the capacity is preferably 1 ml, and a plurality of reagent holes 5115 for storing a relatively large amount of reagents, such as washing liquid, preferably 4 slots.
- the reagent box 510 is also provided with a sealed box body 550, which is connected to the PCR reaction assembly 560.
- a chuck rotating assembly 570 is provided in the table assembly module 500, which is transmission-connected to the bottom of the sealed box body 550.
- the sealed box body 550 is provided for performing a sealed PCR reaction.
- the sealed box body 550 has a receiving chamber 551, a sealing chamber 553 and a reaction chamber 554; a piston chamber 552 is provided in the receiving chamber 551, a first channel 5511 communicating with the piston chamber 552 is provided on the outer circumference of the receiving chamber 551, and a second channel 5531 is provided at the bottom of the sealing chamber 553.
- the PCR reaction assembly 560 includes: a first reaction channel 561, a second reaction channel 562 and a reaction body 563, the reaction body 563 is connected through the first reaction channel 561 and the second reaction channel 562, the reaction body 563 is used for performing PCR reaction, and the second reaction channel 562 is communicated with the reaction chamber 554.
- the chuck rotating assembly 570 is transmission-connected to the bottom of the receiving chamber 551, and is used to drive the sealed box body 550 to rotate, so that the first channel 5511 is selectively communicated with the second channel 5531 or the first reaction channel 561.
- An open hole 512 and a sealing hole 513 are correspondingly provided on the upper cover of the reagent box 510, wherein the open hole 512 is connected to the reaction chamber 554, and the open hole 512 is used to realize the exchange of reagents between the PCR reaction area and the outside world, and the sealing hole 513 is connected to the sealing chamber 553, and the sealing hole 513 is used to seal the magnetic bead hole in the PCR area.
- a sealing cover 5131 is placed on the sealing hole 513, and the sealing cover 5131 has a built-in filter element, which can only pass air, but not nucleic acids, proteins and other substances, and can balance the internal air pressure and prevent internal and external pollution.
- the chuck rotating assembly 570 drives the sealed box body 550 to rotate so that the first channel 5511 is connected to the first reaction channel 561.
- the pipetting assembly 410 is moved to the upper part of the sealed box body 550, and the first driving mechanism 412 on the pipetting assembly 410 drives the first slider 413 to move downward, so that the first slider 413 drives the auxiliary piston rod 4141 to be inserted into the piston cavity 552, and then the first driving mechanism 412 drives the first slider 413 to continue to move downward.
- the table assembly module 500 is connected to the first heat dissipation duct 611 through a seal 612, and a fan can be set in the first heat dissipation duct 611. From the direction indicated by the arrow in FIG. 15 , near the bottom of the rack 100, the fan is turned on, and negative pressure is formed in the rack 100. Air enters from the rear side of the rack 100 (the direction indicated by the arrow), and passes through the heat dissipation cavity of the refrigeration component 530 in the table assembly module 500, the seal 612, the first heat dissipation duct 611, and the front side of the rack 100 (the direction indicated by the arrow), thereby forming a cooling air path.
- the gene processing equipment of the present application can reduce contamination between samples during gene detection and processing, improve detection accuracy, have a high degree of automation, reduce operational difficulty, and thus improve work efficiency.
- Step 03 Place the reagent kit 510 with the reagents placed in it into the preset position of the table assembly module 500.
- Step 12 Replace the pipette tip. This step can be replaced according to customer needs. Replacing the pipette tip can obtain a purer product, but it will increase time and consumables consumption.
- Step 123 The pipette tip 416 moves to above the new tip storage hole 5111, and the first driving mechanism 412 controls the pipette tip 416 to absorb the tip through interference force.
- Step 14 The temperature-controlled magnetic suction assembly 520 at the bottom of the second reaction well 5114 (W2) works, and after standing for a period of time, the pipette tip 416 removes all liquids except the magnetic beads from the second reaction well 5114 (W2) to the waste liquid area 5116.
- Step 16 The pipette tip 416 transfers part of the eluate from the reagent well 5115 into the second reaction well 5114 (W2).
- Step 17 The temperature-controlled magnetic suction component 520 at the bottom of the second reaction well 5114 (W2) stops working, and the pipette tip 416 blows the reagent in the second reaction well 5114 (W2) for a period of time.
- Step 18 The temperature-controlled magnetic suction component 520 at the bottom of the second reaction hole 5114 (W2) works and stands for a period of time.
- Step 19 The pipette tip 416 moves to above the tip storage hole 5111 to perform the tip withdrawal operation.
- Step 20 The heat cover heating assembly 420 moves to above the first reaction well 5113 (W1) to remove the heat cover.
- Step 21 The pipette tip 416 is moved again to above the tip storage hole 5111 to perform the tip removal operation.
- Step 23 The pipette tip 416 takes TE buffer and fragmentation reaction solution from the reagent well 5115 and adds them to the first reaction well 5113 (W1), and mixes them using the pipette tip 416.
- Step 24 The pipette tip 416 moves to above the tip storage hole 5111 and retracts the tip so that the tip returns to the tip storage hole 5111 .
- Step 26 The heating column 423 is operated to heat the heat cover, and a certain temperature is set.
- the temperature control at the bottom of the first reaction well 5113 (W1) is The magnetic attraction component 520 starts to work and heats up for a period of time (fragmentation thermal reaction process).
- Step 27 The temperature-controlled magnetic suction component 520 stops working. After a period of heat dissipation, the Z-direction driving mechanism 253 drives the heating column 423 and the heat cover to move upward, so that the first reaction hole 5113 (W1) is opened.
- Step 28 The heating column 423 stops working, and after a period of heat dissipation, the Z-direction driving mechanism 253 moves upward to open the heat cover.
- Step 30 The pipette tip 416 takes part of the linker reagent to the first reaction well 5113 (W1) and mixes.
- Step 31 The pipette tip 416 moves to above the tip storage hole 5111 to unload the tip.
- Step 33 The heating column 423 works to heat the heat cover, a certain temperature is set, and the temperature control component at the bottom of the first reaction hole 5113 (W1) starts to work and heats for a period of time.
- Step 34 Move the pipette tip 416 to above the tip storage hole 5111 and take the tip.
- Step 35 The pipette tip 416 aspirates all the reagents in the first reaction well 5113 (W1) to the second reaction well 5114 (W2).
- Step 36 The pipette tip 416 moves to above the tip storage hole 5111 to unload the tip.
- Step 37 Move the hot cover to above the hot cover hole of the reagent kit 510, unwind the hot cover, and return the hot cover to its original position.
- Step 38 The pipette tip 416 moves to above the tip storage hole 5111, and the pipette tip 416 takes the tip.
- Step 39 The pipette tip 416 transfers all the liquid in the first reaction well 5113 (W1) to the second reaction well 5114 (W2).
- Step 40 The pipette tip 416 takes a portion of the screened magnetic beads from the reagent well 5115 to the second reaction well 5114 (W2).
- Step 41 The pipette tip 416 blows the second reaction well 5114 (W2) for a period of time.
- Step 43 The pipette tip 416 takes away all reagents except the magnetic beads and temporarily stores them in the waste liquid area 5116.
- Step 44 The temperature-controlled magnetic suction assembly 520 at the bottom of the second reaction hole 5114 (W2) stops working, and the first reaction hole 5113 (W1) and the second reaction hole 5114 (W2) are “washed”.
- Step 46 The pipette tip 416 blows the liquid for a period of time.
- Step 47 The pipette tip 416 takes all reagents except the magnetic beads from the second reaction well 5114 (W2) to the waste liquid area 5116.
- Step 48 The temperature-controlled magnetic suction assembly 520 at the bottom of the second reaction hole 5114 (W2) does not work.
- Step 49 “Wash the magnetic beads” (can be repeated once).
- Step 50 The pipette tip 416 takes the eluate from the reagent well 5115 to the second reaction well 5114 (W2).
- Step 51 The temperature-controlled magnetic suction assembly 520 at the bottom of the second reaction well 5114 (W2) does not work, and the pipette tip 416 blows the reagent for a period of time.
- Step 52 The temperature-controlled magnetic suction component 520 at the bottom of the second reaction hole 5114 (W2) works and stands for a period of time.
- Step 53 Take the supernatant from the second reaction well 5114 (W2) to the open well 512.
- Step 54 After thorough mixing, add into the sealing hole 513.
- step 38 to step 55 is the DNA chain length screening process, and the PCR reaction process is entered next.
- Step 56 The auxiliary piston rod 4141 cooperates with the piston chamber 552 to move.
- Step 59 After the PCR reaction is introduced, cool to room temperature.
- Step 64 The pipette tip 416 moves to above the open hole 512 and retrieves all products into the second reaction hole 5114 (W2).
- Step 69 The pipette tip 416 blows the liquid for a period of time.
- Step 70 The temperature-controlled magnetic suction component 520 at the bottom of the second reaction hole 5114 (W2) works and stands for a period of time.
- Step 71 The pipette tip 416 takes all reagents except the magnetic beads from the second reaction well 5114 (W2) to the waste liquid area 5116.
- Step 72 Repeat the above steps 65-67 once.
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Abstract
本申请提供一种基因处理设备,属于基因检测技术领域。该基因处理设备包括:机架;基座支撑模块,设于机架内;台面组装模块,设于基座支撑模块上,台面组装模块上设有试剂盒,试剂盒上设有多个功能孔位,台面组装模块内设有温控磁吸组件;工位切换模块,设于机架内,工位切换模块上设有支撑架体;复合功能模块,设于支撑架体上,工位切换模块用于驱动复合功能模块在各个功能孔位之间进行转移;其中,复合功能模块包括:移液组件和热盖加热组件;移液组件设于支撑架体上,用于进行移液操作;热盖加热组件设于支撑架体上,用于进行热盖的加热及取卸操作。本申请能够降低基因检测处理过程中样本之间的污染,提高了检测的准确度,自动化程度较高,操作难度降低,进而提高了工作效率。
Description
相关申请的交叉引用
本申请要求于2022年12月27日提交国家知识产权局的申请号为202211685480.0、名称为“基因处理设备”的中国专利申请的优先权,其全部内容通过引用结合在本申请中。
本申请涉及基因检测的技术领域,具体而言,涉及一种基因处理设备。
随着医疗领域的快速发展,基因测序领域的不断拓展,对基因测序前的样本的处理要求越来越高,未来将向着单样本可用的、无交叉污染的、快速的、低成本的方向前进。
基因检测已成为临床分子实验中主要使用的研究手段,例如对于新型冠状病毒感染的患者确诊及疑似解除、术后重症患者感染情况分析等都需要基因检测结果的佐证。
基因检测的前提是提取到高质量和高纯度的生物样本核酸。因此,核酸提取纯化、基因文库构建、PCR扩增已成为基因检测中的重要步骤。
目前核酸提取、基因文库构建等基因前处理过程主要在开放的实验环境下,多以手动操作,或是各步骤分别借助不同仪器完成,或是使用同一台自动化的仪器但各样本之间没有进行隔离,致使生物样本易被释放到外界环境中,使得各样本之间发生污染,最终导致核酸检测的准确度降低,核酸检测的效率降低。
发明内容
本申请的目的是提供一种基因处理设备,本申请的基因处理设备能够降低基因检测处理过程中样本之间的污染,提高了检测的准确度,自动化程度较高,操作难度降低,进而提高了工作效率。
本申请的实施例是这样实现的:本申请提供一种基因处理设备,包括:
机架;基座支撑模块,设于所述机架内;台面组装模块,设于所述基座支撑模块上,所述台面组装模块上设有试剂盒,所述试剂盒上设有多个功能孔位,所述台面组装模块内设有温控磁吸组件;工位切换模块,设于所述机架内,所述工位切换模块上设有支撑架体;以及复合功能模块,设于所述支撑架体上,所述工位切换模块用于驱动所述复合功能模块在各个所述功能孔位之间进行转移;其中,所述复合功能模块包括:移液组件和热盖加热组件;所述移液组件设于所述支撑架体上,用于进行移液操作,所述热盖加热组件设于所述支撑架体上,用于进行热盖的加热及取卸操作。
在上述技术方案中,移液组件设于支撑架体上,用于进行移液操作,热盖加热组件设于支撑架体上,用于进行热盖的加热及取卸操作。移液组件和热盖加热组件一起集成在同一个支撑架体的底板上,如此设置,可以使复合功能模块中各部件之间更紧凑节约空间。
上述各个部件均集成在机架内,从而使整个基因处理过程处于较低的污染风险下,并且复合功能模块集成在支撑架体上,只需要工位切换模块调整位置,使复合功能模块能够在试剂盒上按照需要进行移动。
于一实施例中,所述移液组件包括:第一安装板,设于所述支撑架体上,所述第一安装板上设有第一导轨;第一驱动机构,设于所述第一安装板上,所述第一驱动机构上连接有第一传动件;第一滑块,设于所述第一安装板上,并能沿所述第一导轨滑动,所述第一驱动机构通过所述第一传动件与所述第一滑块传动连接;活塞杆,设于所述第一滑块底部;真空腔体,设于所述支撑架体的底板上,所述第一驱动机构用于驱动所述第一滑块升降,进而驱动所述活塞杆移动并伸入所述真空腔体内;以及移液枪头,与所述真空腔体连接,用于安装吸头,所述移液枪头内设有通孔,所述通孔与所述真空腔体底部连通。
在上述技术方案中,通过第一驱动机构驱动第一传动件正向或反向旋转,使得第一滑块沿着第一导轨向上或向下移动,利用活塞原理,使用真空腔体内部形成负压或者正压,从而带动移液枪头上的吸头对试剂产生吸注液效果,通过移液枪头上安装的吸头对试剂进行移液操作。
于一实施例中,所述移液组件还包括:退吸头板,能活动的设于所述移液枪头上:退吸头导向杆,设于所述退吸头板上,所述支撑架体的底板上设有退吸头导杆通孔,所述退吸头导向杆穿过所述退吸头导杆通孔,并伸向所述第一滑块;以及第一弹性件,套设于所述退吸头导向杆伸向所述第一滑块的端部上。
在上述技术方案中,通过第一驱动机构驱动第一传动件转动,进而带动第一滑块向下滑动,当移液枪头达到最大行程后第一滑块继续向下,推动退吸头导向杆下移,进而使退吸头导向杆推动退吸头板向下移动,通过退吸头板的作用力将安装在移液枪头上的吸头卸载。卸载完成后,第一驱动机构带动第一传动件反向转动,带动第一滑块向上滑动,第一滑块恢复到初始位置,第一滑块离开退吸头导向杆,退吸头导向杆在第一弹性件的弹性作用力下恢复初始位置,使退吸头板复位。
于一实施例中,所述热盖加热组件包括:第二驱动机构,设于所述支撑架体的底板上,所述第二驱动机构上连接有第二传动件;推板,与所述第二传动件传动连接;加热柱,设于所述支撑架体的底板底部,所述加热柱内设有加热棒;退热盖板,能活动的设于所述加热柱上;退热盖导杆,设于所述退热盖板上,所述支撑架体的底板上设有退热盖导杆通孔,所述退热盖导杆穿过所述退热盖导杆通孔,并伸向所述推板;限位板,设于所述退热盖导杆伸向所述推板的一端部上;以及第二弹性件,套设于所述退热盖导杆上,且位于所述支撑架体的底板与所述限位板之间。
在上述技术方案中,通过第二驱动机构驱动第二传动件正向或反向旋转,使得推板沿着向上或向下移动,当推板向下移动靠近限位板,并继续拖动限位板向下移动,限位板下移推动退热盖导杆向下移动,进而退热盖导杆底部连接的退热盖板向下移动,通过退热盖板的作用力将安装在加热柱上的热盖卸载。卸载完成后,第二驱动机构带动第二传动件反向转动,带动推板向上移动,推板恢复到初始位置,推板离开限位板,退热盖导杆在第二弹性件的弹性作用力下恢复初始位置,使退热盖板复位。
于一实施例中,所述工位切换模块包括:X轴运动组件、Y轴运动组件以及Z轴运动组件;所述X轴运动组件,设于所述机架内;所述Y轴运动组件,与所述X轴运动组件传动连接;所述Z轴运动组件,与所述Y轴运动组件传动连接;所述支撑架体设于所述Z轴运动组件上;所述Z轴运动组件用于驱动所述复合功能模块沿Z方向运动,所述Y轴运动组件用于驱动所述复合功能模块沿Y方向运动,所述X轴运动组件用于驱动所述复合功能模块沿X方向运动;其中,X方向、Y方向、Z方向相互垂直。
在上述技术方案中,通过X轴运动组件、Y轴运动组件和Z轴运动组件的相互协调配合,使复合功能模块进行前后、左右、上下运动,在各个功能孔位进行在之间进行转移,以实现移液组件的移液操作,以及热盖加热组件的热盖加热和取卸操作。
于一实施例中,所述X轴运动组件包括:X轴底板,设于所述机架内;X方向驱动机构,沿所述X方向设于所述X轴底板上,所述X方向驱动机构上连接有X方向传动件,所述X方向传动件传动连接X方向连接件;以及X方向运动板,滑动设于所述X轴底板上,所述X方向连接件设于所述X方向运动板上。
在上述技术方案中,在X方向驱动电机的输出端传动连接X方向丝杠,通过X方向驱动电机驱动X方向丝杠转动,X方向丝杠转动,带动X方向丝杆螺母和丝杆螺母连接座移动,以使X方向运动板沿着X方向滑轨进行滑动,从而使X方向运动板能够沿X轴方向进行前后移动。通过控制X方向驱动电机的正转和反转,进而使X方向丝杆正转和反转,从而带动X方向丝杆螺母和丝杆螺母连接座前后来回运动,从而使X方向运动板沿X轴正方向和反方向进行前后移动。
于一实施例中,所述Y轴运动组件包括:Y轴底板,与所述X方向运动板连接;Y方向驱动机构,沿所述Y方向设于所述Y轴底板上;以及同步带传动组件,与所述Y方向驱动机构传动连接。
在上述技术方案中,通过Y方向驱动电机驱动同步带轮转动,在同步带的传动作用下,带动另一个同步带轮转动。通过控制X方向驱动电机的正转和反转,进而使X方向丝杆正转和反转,带动X方向丝杆螺母和丝杆螺母连接座前后来回运动,使X方向运动板沿X轴正方向和反方向进行前后移动,从而带动Y轴底板沿X轴正方向和反方向进行前后移动,在Y轴底板进行前后移动的同时,通过控制Y方向驱动电机的正转和反转,带动同步带传动组件沿Y轴方向左右移动。
于一实施例中,所述Z轴运动组件包括:Z轴底板,与所述同步带传动组件传动连接,且所述Z轴
底板滑动连接于所述Y轴底板上;Z方向运动板,滑动设于所述Z轴底板上,所述支撑架体连接于所述Z方向运动板上;以及Z方向驱动机构,沿所述Z方向设于所述支撑架体上,所述Z方向驱动机构上连接有Z方向传动件,所述Z方向传动件传动连接Z方向连接件,所述Z方向连接件与所述Z方向运动板连接。
在上技术方案中,通过控制X方向驱动电机的正转和反转,进而使X方向丝杆正转和反转,带动X方向丝杆螺母和丝杆螺母连接座前后来回运动,使X方向运动板沿X轴正方向和反方向进行前后移动,从而带动Y轴底板沿X轴正方向和反方向进行前后移动,在Y轴底板进行前后移动的同时,通过控制Y方向驱动电机的正转和反转,带动同步带传动组件沿Y轴方向左右移动,同步带传动组件的左右移动,带动Z轴运动组件在Y轴方向进行左右移动,同时,通过控制Z方向驱动电机驱动Z方向丝杠转动,Z方向丝杠转动,带动Z方向丝杆螺母和丝杆螺母连接座移动,以使Z方向运动板沿着Z方向滑轨进行滑动,从而使Z方向运动板能够沿Z轴方向进行上下移动。通过控制Z方向驱动电机的正转和反转,进而使Z方向丝杆正转和反转,从而带动Z方向丝杆螺母和丝杆螺母连接座前后来回运动,从而使Z方向运动板沿Z轴正方向和反方向进行上下移动,最终带动Z方向运动板上连接的支撑架体进行上下移动,带动支撑架体上的复合功能模块的上下移动。
于一实施例中,所述基座支撑模块包括:基座;工位切换支撑座,设于所述基座上,且与所述工位切换模块连接;平移组件,设于所述基座上,所述平移组件包括:第一导轨连接板,设于所述基座上;第二导轨连接板,滑动设于所述第一导轨连接板上;以及抽屉式运动板,连接于所述第二导轨连接板;所述台面组装模块设于所述抽屉式运动板上,所述台面组装模块上设有试剂盒固定组件,所述基座上设有与所述试剂盒固定组件配合的压板件,用于当所述台面组装模块通过所述平移组件推入到预设位置处时,所述压板件与所述试剂盒固定组件配合将所述试剂盒固定。
在上技术方案中,通过手动或电气驱动的方式,推动抽屉式运动板333,使试剂盒固定在基座支撑模块上。
于一实施例中,所述基因处理设备还包括:环境控制模块,所述环境控制模块包括:第一环境控制组件,设于所述机架内,用于将所述台面组装模块以及所述机架连通;以及第二环境控制组件,设于所述机架内,用于将PCR反应组件、所述工位切换支撑座以及所述机架连通。
在上述技术方案中,通过环境控制模块调整机架内的环境状况,使其形成一个适用于开放式结构的试剂盒工作的环境,以避免样品间的污染。
于一实施例中,所述试剂盒上还设有密封盒体,所述密封盒体与所述PCR反应组件连接;所述台面组装模块内还设有:卡盘旋转组件,与所述密封盒体底部传动连接。
在上述技术方案中,设置密封盒体的原因是为了进行密封PCR反应。
于一实施例中,所述密封盒体具有容纳腔、密封腔和反应腔;所述容纳腔内设有活塞腔,所述容纳腔外周面上开设有与所述活塞腔连通的第一通道,所述密封腔底部开设有第二通道;所述PCR反应组件包括:第一反应通道、第二反应通道以及反应本体,所述反应本体通过所述第一反应通道、所述第二反应通道连接,所述第二反应通道与所述反应腔连通;所述卡盘旋转组件与所述容纳腔底部传动连接,用于驱动所述密封盒体转动,以使所述第一通道择一地与所述第二通道或所述第一反应通道连通。
在上述技术方案中,卡盘旋转组件驱动密封盒体转动,以使第一通道与第一反应通道连通时,如前所述,通过控制工位切换模块,使移液组件移动到位于密封盒体上部,移液组件上的第一驱动机构驱动第一滑块向下移动,使第一滑块带动辅助活塞杆***到活塞腔内,再通过第一驱动机构驱动第一滑块继续向下移动,根据空气置换原理将从试剂孔内的吸取的试剂推入活塞腔内,进而使活塞腔内的试剂通过第一反应通道推入到反应本体内,完成PCR反应。
于一实施例中,所述功能孔位包括:至少一个吸头存放孔、至少一个试管存放孔、至少一个第一反应孔、至少一个第二反应孔以及多个试剂孔。
在上述技术方案中,多个功能孔位的种类、数量和排布的设置可以根据需要进行设计。
于一实施例中,所述温控磁吸组件,设于所述试剂盒底部,用于对所述第一反应孔和/或第二反应孔进行控温和吸磁。
在上述技术方案中,通过丝杆电机模组驱动导热块到达第一反应孔和/或第二反应孔底部,对第一反应孔和/或第二反应孔底部进行加热,同时,环形磁钢可对第一反应孔和/或第二反应孔内的磁珠进行磁吸。
于一实施例中,所述台面组装模块内还设有制冷组件,所述制冷组件设于所述试剂盒底部,用于对所述试剂孔进行制冷。
在上述技术方案中,制冷片通过电流形成上下两面的温差,上冷下热时,下侧散热器与风扇工作,从而加快制冷。
为了更清楚地说明本申请实施例的技术方案,下面将对实施例中所需要使用的附图作简单地介绍,应当理解,以下附图仅示出了本申请的某些实施例,因此不应被看作是对范围的限定,对于本领域普通技术人员来讲,在不付出创造性劳动的前提下,还可以根据这些附图获得其他相关的附图。
图1为本申请一实施例提供的基因处理设备的结构示意图;
图2为本申请一实施例提供的工位切换模块的结构示意图;
图3为本申请一实施例提供的X轴运动组件的结构示意图;
图4为本申请一实施例提供的Y轴运动组件的结构示意图;
图5为本申请一实施例提供的Z轴运动组件的结构示意图;
图6为本申请一实施例提供的复合功能模块的结构示意图;
图7为本申请一实施例提供的移液组件的结构示意图;
图8为本申请一实施例提供的热盖加热组件的结构示意图;
图9为本申请一实施例提供的基座支撑模块的结构示意图;
图10为本申请一实施例提供的平移组件的结构示意图;
图11为本申请一实施例提供的台面组装模块与平移组件的连接关系示意图;
图12为本申请一实施例提供的台面组装模块的结构示意图;
图13为本申请一实施例提供的密封盒体的剖视图;
图14为本申请一实施例提供的卡盘旋转组件的结构示意图;
图15为本申请一实施例提供的温控磁吸组件的结构示意图;
图16为本申请一实施例提供的基因处理设备的正视图;
图17为本申请一实施例提供的基因处理设备的后视图。
图标:
1-基因处理设备;100-机架;200-工位切换模块;210-支撑架体;211-第二位置传感器;220-支撑架体的底板;221-退吸头导杆通孔;222-退热盖导杆通孔;230-X轴运动组件;231-X轴底板;2311-X方向滑轨;232-X方向驱动机构;2321-X方向传动件;233-X方向连接件;234-X方向运动板;2341-X方向位置感应定位片;240-Y轴运动组件;241-Y轴底板;2411-Y方向滑轨;2412-Y方向位置感应定位片;242-Y方向驱动机构;243-同步带传动组件;2431-同步带轮;2432-同步带;250-Z轴运动组件;251-Z轴底板;2511-Z方向滑轨;2512-Z方向位置感应定位片;252-Z方向运动板;253-Z方向驱动机构;2531-Z方向传动件;254-Z方向连接件;300-基座支撑模块;310-基座;311-压板件;320-工位切换支撑座;330-平移组件;331-第一导轨连接板;3311-第一连接板导轨;332-第二导轨连接板;333-抽屉式运动板;400-复合功能模块;410-移液组件;411-第一安装板;4111-第一导轨;4112-第一位置传感器;412-第一驱动机构;4121-第一传动件;413-第一滑块;414-活塞杆;4141-辅助活塞杆;415-真空腔体;416-移液枪头;4161-通孔;417-退吸头板;418-退吸头导向杆;419-第一弹性件;420-热盖加热组件;421-第二驱动机构;4211-第二传动件;422-推板;4221-定位片;423-加热柱;424-退热盖板;425-退热盖导杆;426-限位板;427-第二弹性件;500-台面组装模块;501-压杆;510-试剂盒;511-功能孔位;5111-吸头存放孔;5112-试管存放孔;5113-第一反应孔;5114-第二反应孔;5115-试剂孔;5116-废液区;512-开放孔;513-密封孔;5131-密封盖;520-温控磁吸组件;521-丝杆电机模组;522-电机底板;523-电机连接块;5231-环形磁钢;524-隔热底块;525-导热块;526-加热片;527-温控磁吸定位片;528-温控磁吸传感器;530-
制冷组件;540-试剂盒固定组件;550-密封盒体;551-容纳腔;5511-第一通道;552-活塞腔;553-密封腔;5531-第二通道;554-反应腔;560-PCR反应组件;561-第一反应通道;562-第二反应通道;563-反应本体;570-卡盘旋转组件;571-步进电机;572-支撑底盘;573-垫高块;574-旋转卡片;575-卡盘旋转传感器;576-卡盘旋转定位片;600-环境控制模块;610-第一环境控制组件;611-第一散热风道;612-密封件;620-第二环境控制组件;621-第二散热风道。
术语“第一”、“第二”、“第三”等仅用于区分描述,并不表示排列序号,也不能理解为指示或暗示相对重要性。
此外,术语“水平”、“竖直”、“悬垂”等术语并不表示要求部件绝对水平或悬垂,而是可以稍微倾斜。如“水平”仅仅是指其方向相对“竖直”而言更加水平,并不是表示该结构一定要完全水平,而是可以稍微倾斜。
在本申请的描述中,需要说明的是,术语“内”、“外”、“左”、“右”、“上”、“下”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,或者是该申请产品使用时惯常摆放的方位或位置关系,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。
在本申请的描述中,除非另有明确的规定和限定,术语“设置”、“安装”、“相连”、“连接”应做广义理解,例如,可以是固定连接,也可以是可拆卸连接,或一体地连接;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。
基因检测的前提是提取到高质量和高纯度的生物样本核酸。因此,核酸提取纯化、基因文库构建、PCR扩增已成为基因检测中的重要步骤。根据已知核酸的序列,进行特异性的引物和探针设计,并将设计好的引物进行合成,以提取的核酸为模板进行荧光定量PCR实验,根据荧光信号来判断模板样本的阴阳性,核酸提取是基因检测处理的关键一步,获得核酸质量将直接影响后续实验的成败。
目前核酸提取、基因文库构建等基因前处理过程主要在开放的实验环境下,多以手动操作、或是各步骤分别借助不同仪器完成,或是使用同一台自动化的仪器但各样本之间没有进行隔离。当以手动操作完成整个核酸提取过程时,效率低,对于技术人员的操作要求高;以多台仪器进行工作时,样本间互相污染,过程复杂,且对技术人员的要求较高;单台移液站式自动化仪器进行多个样本间的转移时,需要等待多个样本到达才能工作,不够灵活。因此,上述三种基因处理方式都存在不同的问题,致使基因处理的效率降低。因此,根据上述问题,本申请提供一种基因处理设备1,使用该基因处理设备1过程中,单个样本随到随检,速度快,可适用不同试剂、不同基因测序方案,操作过程无互相污染,提高了基因检测处理的效率和准确性。
下面将结合附图对本申请的技术方案进行描述。
请参照图1,一种基因处理设备1,包括:机架100、工位切换模块200、基座支撑模块300、复合功能模块400、台面组装模块500以及环境控制模块600;工位切换模200设于机架100内,工位切换模块200上设有支撑架体210;基座支撑模块300设于机架100内,台面组装模块500设于基座支撑模块300上,台面组装模块500上设有试剂盒510,试剂盒510上设有多个功能孔位511,台面组装模块500内设有温控磁吸组件520;复合功能模块400设于支撑架体210上,工位切换模块200用于驱动复合功能模块400在各个功能孔位511之间进行转移;其中,复合功能模块400包括:移液组件410和热盖加热组件420;移液组件410设于支撑架体210上,用于进行移液操作,热盖加热组件420设于支撑架体210上,用于进行热盖的加热及取卸操作。
机架100可以是由多个支撑钣金件组装而成,用于固定安装基因处理设备1中的各个部件。机架100的形状可以根据基因处理设备1中的各个设备进行设计,机架100上可安装有防污染透明观察窗,供操作人员随时观察实验过程。
本实施例中,机架100为长方体结构,以机架100的高度方向作为Z轴建立坐标系,则机架100的宽度方向为X轴,机架100的长度方向为Y轴,机架100的底面为X-Y基准平面。其中,X轴、Y轴、Z轴相互垂直,定义X轴的正方向为向前,Y轴的正方向为向右,Z轴的正方向为向上。
请参照图2,工位切换模块200的实现方式可以有多种,本实施例中,工位切换模块200包括:X轴运动组件230、Y轴运动组件240以及Z轴运动组件250。X轴运动组件230与Y轴运动组件240传动连接;Z轴运动组件250与Y轴运动组件传动连接;支撑架体210设于Z轴运动组件250上;Z轴运动组件250用于驱动复合功能模块400沿Z方向运动,Y轴运动组件240用于驱动复合功能模块400沿Y方向运动,X轴运动组件230用于驱动复合功能模块400沿X方向运动。通过X轴运动组件230、Y轴运动组件240和Z轴运动组件250的相互协调配合,使复合功能模块400进行前后、左右、上下运动,在各个功能孔位511进行在之间进行转移,以实现移液组件410的移液操作,以及热盖加热组件420的热盖加热和取卸操作。
请参照图3,X轴运动组件230包括:X轴底板231、X方向驱动机构232、X方向传动件2321、X方向连接件233、X方向运动板234。其中,X轴底板231可通过螺栓连接或焊接等方式固定安装在机架100的宽度方向上,X方向驱动机构232沿X方向固定设置在X轴底板231上,X方向驱动机构232上连接X方向传动件2321,X方向传动件2321传动连接X方向连接件233,X方向运动板234滑动设于X轴底板231上,具体地,在X轴底板231沿X方向对称设置X方向滑轨2311,X方向运动板234可沿着X方向滑轨2311进行滑动;X方向连接件233可通过固定座等方式设于X方向运动板234上。
于一实施例中,为了精确定位X方向运动板234的移动位置,可在X方向运动板234上安装X方向位置感应定位片2341。
本实施例中,X方向驱动机构232优选为X方向驱动电机,X方向传动件2321优为X方向丝杠,X方向连接件233优选为X方向丝杆螺母和丝杆螺母连接座,在X方向丝杆的另一端部可通过轴承座与轴承安装固定在X轴底板231上。示例性的,在X方向驱动电机的输出端传动连接X方向丝杠,通过X方向驱动电机驱动X方向丝杠转动,X方向丝杠转动,带动X方向丝杆螺母和丝杆螺母连接座移动,以使X方向运动板234沿着X方向滑轨2311进行滑动,从而使X方向运动板234能够沿X轴方向进行前后移动。通过控制X方向驱动电机的正转和反转,进而使X方向丝杆正转和反转,从而带动X方向丝杆螺母和丝杆螺母连接座前后来回运动,从而使X方向运动板234沿X轴正方向和反方向进行前后移动。
请参照图4,Y轴运动组件240包括:Y轴底板241、Y方向驱动机构242、同步带传动组件243。其中,Y轴底板241与图2中所示的X方向运动板234连接;Y方向驱动机构242沿Y方向设于Y轴底板241上;同步带传动组件与Y方向驱动机构242传动连接。
具体地,同步带传动组件243包括两个同步带轮2431和一个同步带2432,两个同步带轮2431均安装在Y轴底板241上,其中一个同步带轮2431与Y方向驱动机构242连接。
本实施例中,Y方向驱动机构242优选为Y方向驱动电机。示例性的,在Y方向驱动电机的输出端与其中一个同步带轮2431连接,通过Y方向驱动电机驱动同步带轮2431转动,在同步带2432的传动作用下,带动另一个同步带轮2431转动。通过控制X方向驱动电机的正转和反转,进而使X方向丝杆正转和反转,带动X方向丝杆螺母和丝杆螺母连接座前后来回运动,使X方向运动板234沿X轴正方向和反方向进行前后移动,从而带动Y轴底板241沿X轴正方向和反方向进行前后移动,在Y轴底板241进行前后移动的同时,通过控制Y方向驱动电机的正转和反转,带动同步带传动组件243沿Y轴方向左右移动。
请参照图4和图5,Z轴运动组件250包括:Z轴底板251、Z方向运动板252、Z方向驱动机构253、Z方向连接件254。其中,Z轴底板251与同步带传动组件243传动连接,且Z轴底板251滑动连接于Y轴底板241上,具体地,在Y轴底板241上对称设有Y方向滑轨2411,Y方向滑轨2411位于同步带2432外端,Z轴底板251可沿着Y方向滑轨2411进行滑动;Z方向运动板252滑动设于Z轴底板251上,具体地,在Z轴底板251上对称设有Z方向滑轨2511,Z方向运动板252可沿着Z方向滑轨2511进行滑动;支撑架体210连接于Z方向运动板252上,支撑架体210与Z方向运动板252可通过焊接方式进行固定连接,Z方向驱动机构253沿Z方向设于支撑架体210上,Z方向驱动机构253上连接有Z方向传动件2531,Z方向传动件2531传动连接Z方向连接件254,Z方向连接件254可通过固定座等
方式设于Z方向运动板252上。
本实施例中,Z方向驱动机构253优选为Z方向驱动电机,Z方向传动件2531优为Z方向丝杠,Z方向连接件254优选为Z方向丝杆螺母和丝杆螺母连接座。示例性的,在Z方向驱动电机的输出端传动连接Z方向丝杠,通过Z方向驱动电机驱动Z方向丝杠转动,Z方向丝杠转动,带动Z方向丝杆螺母和丝杆螺母连接座移动,以使Z方向运动板252沿着Z方向滑轨2511进行滑动,从而使Z方向运动板252能够沿Z轴方向进行上下移动。通过控制Z方向驱动电机的正转和反转,进而使Z方向丝杆正转和反转,从而带动Z方向丝杆螺母和丝杆螺母连接座前后来回运动,从而使Z方向运动板252沿Z轴正方向和反方向进行上下移动。
如前所述,通过控制X方向驱动电机的正转和反转,进而使X方向丝杆正转和反转,带动X方向丝杆螺母和丝杆螺母连接座前后来回运动,使X方向运动板234沿X轴正方向和反方向进行前后移动,从而带动Y轴底板241沿X轴正方向和反方向进行前后移动,在Y轴底板241进行前后移动的同时,通过控制Y方向驱动电机的正转和反转,带动同步带传动组件243沿Y轴方向左右移动,同步带传动组件243的左右移动,带动Z轴运动组件250在Y轴方向进行左右移动,同时,通过控制Z方向驱动电机驱动Z方向丝杠转动,Z方向丝杠转动,带动Z方向丝杆螺母和丝杆螺母连接座移动,以使Z方向运动板252沿着Z方向滑轨2511进行滑动,从而使Z方向运动板252能够沿Z轴方向进行上下移动。通过控制Z方向驱动电机的正转和反转,进而使Z方向丝杆正转和反转,从而带动Z方向丝杆螺母和丝杆螺母连接座前后来回运动,从而使Z方向运动板252沿Z轴正方向和反方向进行上下移动,最终带动Z方向运动板252上连接的支撑架体210进行上下移动,带动支撑架体210上的复合功能模块400的上下移动。
于一实施例中,为了更精确地定位Z轴底板251的移动位置,可在Y轴底板241上安装Y方向位置感应定位片2412;为了更精确地定位Z方向运动板252的移动位置,可在Z轴底板251上安装Z方向位置感应定位片2512。
请参照图6,移液组件410和热盖加热组件420集成设于支撑架体的底板220上,如此设置,可以使复合功能模块400中各部件之间更紧凑节约空间。
请参照图7,移液组件410包括:第一安装板411、第一驱动机构412、第一滑块413、活塞杆414、真空腔体415以及移液枪头416。其中,第一安装板411与Z轴方向平行,设置在支撑架体210上,第一驱动机构412设于第一安装板411上,第一驱动机构412上连接有第一传动件4121,第一驱动机构412通过第一传动件4121与第一滑块413传动连接,第一滑块413设于第一安装板411上,具体地,在第一安装板411上对称设有第一导轨4111,第一滑块413能够沿第一导轨4111进行上下滑动,在第一滑块413底部设置活塞杆414,在支撑架体的底板220上设置真空腔体415,第一驱动机构412用于驱动第一滑块413升降,进而驱动活塞杆414移动并伸入真空腔体415内;移液枪头416与真空腔体415连接,移液枪头416由支撑架体的底板220伸向底部,移液枪头416用于安装吸头,移液枪头416内设有通孔4161,通孔4161与真空腔体415底部连通。
于一实施例中,为了更精确的获取第一滑块413的移动位置,在第一安装板411上可设有第一位置传感器4112。
本实施例中,第一驱动机构412优选第一电机,第一传动件4121优选第一丝杆,第一丝杆与第一滑块413之间通过丝杆螺母与丝杆螺母连接块固定。示例性的,通过第一驱动机构412驱动第一传动件4121正向或反向旋转,使得第一滑块413沿着第一导轨4111向上或向下移动,利用活塞原理,使用真空腔体415内部形成负压或者正压,从而带动移液枪头416上的吸头对试剂产生吸注液效果,通过移液枪头416上安装的吸头对试剂进行移液操作。
于一实施例中,在第一滑块413底部还设有辅助活塞杆4141,该辅助活塞杆4141用于试剂盒上密封区域的活塞驱动,与移液枪头416公用同一个第一驱动机构412和第一滑块413,在支撑架体的底板220上设有供辅助活塞杆4141穿过的孔,在支撑架体的底板220上的孔处设置了导向轴承,功使辅助活塞杆4141与支撑架体的底板220接触面处存在一个辅助导向力,从而为辅助活塞杆4141提供更精准的位置。辅助活塞杆4141的作用将在下文详细描述。
由于在移液操作过程中,需要不停的更换吸头,放置交叉感染,请继续参照图7,移液组件410还包括:退吸头板417、退吸头导向杆418以及第一弹性件419;其中,退吸头板417能活动的设于移液枪头416上,退吸头导向杆418设于退吸头板417上,支撑架体的底板220上设有退吸头导杆通孔221,退吸头导向杆418穿过退吸头导杆通孔221,并伸向第一滑块413;第一弹性件419套设于退吸头导向杆418伸向第一滑块413的端部上。第一弹性件419优选弹簧。
本实施例中,通过第一驱动机构412驱动第一传动件4121转动,进而带动第一滑块413向下滑动,当移液枪头416达到最大行程后第一滑块413继续向下,推动退吸头导向杆418下移,进而使退吸头导向杆418推动退吸头板417向下移动,通过退吸头板417的作用力将安装在移液枪头416上的吸头卸载。卸载完成后,第一驱动机构412带动第一传动件4121反向转动,带动第一滑块413向上滑动,第一滑块413恢复到初始位置,第一滑块413离开退吸头导向杆418,退吸头导向杆418在第一弹性件419的弹性作用力下恢复初始位置,使退吸头板417复位。
请参照图8,热盖加热组件420包括:第二驱动机构421、推板422、加热柱423、退热盖板424、退热盖导杆425、限位板426、第二弹性件427;其中,第二驱动机构421设于支撑架体的底板220上,第二驱动机构421上连接有第二传动件4211;推板422与第二传动件4211传动连接;加热柱423设于支撑架体的底板220底部,加热柱423内设有加热棒,加热柱423底部用于连接热盖;退热盖板424能活动的设于加热柱423上;退热盖导杆425设于退热盖板424上,支撑架体的底板220上设有退热盖导杆通孔222,退热盖导杆425穿过退热盖导杆通孔222,并伸向推板422;限位板426设于退热盖导杆425伸向推板422的一端部上;第二弹性件427套设于退热盖导杆425上,且位于支撑架体的底板220与限位板426之间。第二弹性件427优选弹簧。热盖优选为仿形热盖,仿形热盖内设温度传感器和加热棒,可使热盖升温。
于一实施例中,为了更精确的获取推板422的移动位置,在推板422顶部可设有定位片4221,在支撑架体210的对应位置上设有检测定位片4221的第二位置传感器211。
本实施例中,第二驱动机构421优选第二电机,第二传动件4211优选第二丝杆,第二丝杆与推板422固定。示例性的,通过第二驱动机构421驱动第二传动件4211正向或反向旋转,使得推板422沿着向上或向下移动,当推板422向下移动靠近限位板426,并继续拖动限位板426向下移动,限位板426下移推动退热盖导杆425向下移动,进而退热盖导杆425底部连接的退热盖板424向下移动,通过退热盖板424的作用力将安装在加热柱423上的热盖卸载。卸载完成后,第二驱动机构421带动第二传动件4211反向转动,带动推板422向上移动,推板422恢复到初始位置,推板422离开限位板426,退热盖导杆425在第二弹性件427的弹性作用力下恢复初始位置,使退热盖板424复位。
请参照图2-图8,通过X轴运动组件230、Y轴运动组件240、Z轴运动组件250的协调配合,调整复合功能模块400在多个功能孔位511之间进行转移,并到达指定位置,使移液组件410能够完成装载、移液、混合、退吸头等操作,使热盖加热组件420能够完成热盖加热和取卸操作,进一步提高了复合功能模块400的自动化程度。
请参照图9,基座支撑模块300包括:基座310、工位切换支撑座320、平移组件330;其中,工位切换支撑座320设于基座310上,且与工位切换模块200连接。具体地,工位切换支撑座320与X轴运动组件230上的X轴底板231底部连接。平移组件330设于基座310上。
请参照图10,平移组件330包括:第一导轨连接板331、第二导轨连接板332、抽屉式运动板333;第一导轨连接板331固定在基座310上,第二导轨连接板332滑动设于第一导轨连接板331上。具体地,第一导轨连接板331上设有第一连接板导轨3311,第二导轨连接板332底部设置能够在第一连接板导轨3311上滑动的滑块;抽屉式运动板333连接于第二导轨连接板332顶部。
请参照图11,台面组装模块500设于抽屉式运动板333上。台面组装模块500上设有试剂盒固定组件540,基座310上设有与试剂盒固定组件540配合的压板件311,压板件311用于当台面组装模块500通过平移组件330推入到预设位置处时,压板件311与试剂盒固定组件540配合将试剂盒510固定。
于一实施例中,在台面组装模块500的两外侧面上可设置压杆501,压杆501周向套设弹簧,当抽屉式运动板333被推入到预设位置(示例性的,推入到位于最顶端靠近机架100边缘位置处),位于基
座310上的压板件311对压杆501施加压力,将压杆501向试剂盒510方向(向内)推动,压杆501卡柱试剂盒510上的台阶处,从而使试剂盒510固定。当向远离机架100边缘位置拉动抽屉式运动板333时,压板件311取消对压杆501的压力,在弹簧作用下,压杆501向外弹出恢复初始状态,试剂盒510被解除固定状态。本实施例中,可以通过手动推动抽屉式运动板333,也可以通过液压缸或电机自动推动抽屉式运动板333。
请参照图12,试剂盒510上有多个功能孔位511,功能孔位511包括:至少一个吸头存放孔5111,用于存放吸头,至少一个试管存放孔5112,用于存放可拆卸的管体,至少一个第一反应孔5113(记为W1),第一反应孔5113内可进行片段化、杂交反应,第一反应孔5113底部可进行加热,顶部用热盖密封,容量优选0.2ml,至少一个第二反应孔5114(记为W2),第二反应孔5114内可进行核酸提取、片段后分选/纯化、以及PCR后的纯化反应,第二反应孔5114底部可进行磁吸和加热,容量优选为1ml,多个试剂孔5115,用于存放较大量的试剂,如洗涤液,优选4个槽。除此之外,试剂盒510上还可以设置废液区5116,用于放置基因处理后的各种产物,利于回收处理。其中第一框体内为常温区,常温区内的试剂孔5115不用进行温控,第二框体内为制冷区,制冷区内的试剂孔5115需要进行制冷操作。多个功能孔位511的种类、数量和排布的设置可以根据需要进行设计。
请参照图13,试剂盒510上还设有密封盒体550,密封盒体550与PCR反应组件560连接,台面组装模块500内设有卡盘旋转组件570,卡盘旋转组件570与密封盒体550底部传动连接。设置密封盒体550的原因是为了进行密封PCR反应。
于一实施例中,请参照图13,密封盒体550具有容纳腔551、密封腔553和反应腔554;容纳腔551内设有活塞腔552,容纳腔551外周面上开设有与活塞腔552连通的第一通道5511,密封腔553底部开设有第二通道5531。PCR反应组件560包括:第一反应通道561、第二反应通道562以及反应本体563,反应本体563通过第一反应通道561、第二反应通道562连接,反应本体563内用于进行PCR反应,第二反应通道562与反应腔554连通。卡盘旋转组件570与容纳腔551底部传动连接,用于驱动密封盒体550转动,以使第一通道5511择一地与第二通道5531或第一反应通道561连通。
在试剂盒510的上盖上对应开设有开放孔512和密封孔513,其中开放孔512与反应腔554连通,开放孔512是实现PCR反应区与外界交换试剂交换的,密封孔513与密封腔553连通,密封孔513是实现对PCR区内磁珠孔进行密封的。于一实施例中,密封孔513上置密封盖5131,密封盖5131内置滤芯,滤芯仅可通过空气,不可通过核酸、蛋白质等物质,可平衡内部气压,放置内部和外部污染。
本实施例中,卡盘旋转组件570驱动密封盒体550转动,以使第一通道5511与第一反应通道561连通时,如前所述,通过控制工位切换模块200,使移液组件410移动到位于密封盒体550上部,移液组件410上的第一驱动机构412驱动第一滑块413向下移动,使第一滑块413带动辅助活塞杆4141***到活塞腔552内,再通过第一驱动机构412驱动第一滑块413继续向下移动,根据空气置换原理将从试剂孔5115内的吸取的试剂推入活塞腔552内,进而使活塞腔552内的试剂通过第一反应通道561推入到反应本体563内,完成PCR反应。
请参照图14,卡盘旋转组件570包括步进电机571、支撑底盘572、垫高块573、旋转卡片574、卡盘旋转传感器575以及卡盘旋转定位片576,其中,步进电机571优选为带减速比步进电机,步进电机571的输出端连接支撑底盘572,垫高块573设置在支撑底盘572上,垫高块573用于支撑密封盒体550底部,在支撑底盘572中部设置旋转卡片574,旋转卡片574用于与密封盒体550上的容纳腔551底部连接。本实施例中,通过步进电机571驱动旋转卡片574的转动,从而带动容纳腔551转动,使密封盒体550转动,从而使第一通道5511择一地与第二通道5531或第一反应通道561连通。
请参照图15,台面组装模块500内设有温控磁吸组件520,温控磁吸组件520设于试剂盒510底部,用于对第一反应孔5113和/或第二反应孔5114进行控温和吸磁。具体地,温控磁吸组件520包括:丝杆电机模组521、电机底板522、电机连接块523、环形磁钢5231、隔热底块524、导热块525、加热片526、温控磁吸定位片527以及温控磁吸传感器528。丝杆电机模组521和电机底板522均设置在台面组装模块500底部,丝杆电机模组521与电机连接块523传动连接,电机连接块523顶部固定环形磁钢5231,在环形磁钢5231四周通过隔热底块524支撑,隔热底块524设置在电机底板522上,在隔热底块524
上设置有加热片526,加热片526优选陶瓷加热片,温控磁吸定位片527设置在电机连接块523上,温控磁吸传感器528设置在电机底板522上。本实施例中,通过丝杆电机模组521驱动导热块525到达第一反应孔5113和第二反应孔5114底部,对第一反应孔5113和第二反应孔5114底部进行加热,或者选择性的仅对第一反应孔5113底部进行加热或仅对第二反应孔5114底部进行加热,同时,环形磁钢5231可对第一反应孔5113和第二反应孔5114内的磁珠进行磁吸,或者选择性的仅对第一反应孔5113内的磁珠进行磁吸或者仅对第二反应孔5114内的磁珠进行磁吸。
于一实施例中,台面组装模块500内还设有制冷组件530,制冷组件530设于试剂盒510底部,用于对试剂孔5115进行制冷。请参照图12,制冷组件530用于对图11中的第二框体内的试剂孔5115进行制冷。制冷组件530的结构属于现有技术中的常见结构,在此不再赘述,其原理是制冷片通过电流形成上下两面的温差,上冷下热时,下侧散热器与风扇工作,从而加快制冷。
请参照图16和图17所示,基因处理设备1还包括:环境控制模块600,环境控制模块600包括:第一环境控制组件610和第二环境控制组件620;其中,第一环境控制组件610用于将台面组装模块500以及机架100连通。
示例性的,请参照图16,台面组装模块500与第一散热风道611之间通过密封件612连接,在第一散热风道611内可以设置风扇,从图15中的箭头所示方向,在机架100靠近底部位置,打开风扇,机架100内形成负压,由机架100的后侧(箭头指入的方向)进风,依次经过台面组装模块500内制冷组件530的散热腔、密封件612、第一散热风道611、机架100的前侧(箭头指出的方向),从而形成一条制冷风路。在机架100靠近顶部位置,机架100后侧(箭头指入的方向)靠近顶部位置设置HEPA(High efficiency particulate air Filter,高效空气过滤器),在机架100的前侧(箭头指出的方向),形成一条新风风路。
第二环境控制组件620用于将PCR反应组件560、工位切换支撑座320以及机架100连通。示例性的,请参照图17,从图17中的箭头所示方向,基座支撑模块300的基座310底部为进风口,制冷组件530的散热腔内设置风扇,打开风扇,机架100内形成负压,风经过制冷组件530的散热腔,以及经过PCR反应组件560,并经过第二散热风道621以及机架100的前侧,形成另一条制冷风路。
于一实施例中,在机架100内部可设置紫外灯,用于杀菌以防污染。机架100上需设有多个通风口,机架100上除通风口以外全部封闭设置,在各个通风口上可设置过滤间,用于过来废气以防止外界污染和对外界污染。
本实施例通过环境控制模块600调整机架100内的环境状况,使其形成一个适用于开放式结构的试剂盒510工作的环境,以避免样品间的污染。
本申请中,在机架100内可内置电气柜,包括:供电单元、人机交互界面、通信单元、处理器和控制单元。供电单元可以是外接电源或者蓄电池。人机交互界面可以为显示屏、键盘、触摸屏、按键、旋钮、音响和led灯等计算机输入、输出设备,用于输入指令和读取信息,从而实现人机交互、信息的互通。通信单元可以是收发器,控制单元可以是微控制器(Microcontroller Unit,简称:MCU)。电气柜作为主控模块,通过人机交互界面来接收指令和数据并将该指令、数据传递给处理器,且可以通过人机交互界面传递消息来提示操作人员。主控模块通过处理器处理人机交互界面和通信单元反馈的信息,并通过控制单元控制工位切换模块200、复合功能模块400、温控磁吸组件520、卡盘旋转组件570、环境控制模块600。
本申请的基因处理设备能够降低基因检测处理过程中样本之间的污染,提高了检测的准确度,自动化程度较高,操作难度降低,进而提高了工作效率。
请参照图1-图17,下面为本申请基因处理设备1的使用方法,包括如下步骤:
步骤01:首先按照预先设计配置好液体,将所有试剂预封装后,送至客户;或客户自己通过手动或其他手段加入该多种试剂。
步骤02:客户收到后在第二反应孔5114(W2)加入样本与蛋白酶K,在试剂孔5115内加入捕获磁珠,并将密封盖盖在试剂孔5115上。
步骤03:将放置好试剂的试剂盒510放入台面组装模块500的预设位置。
步骤04:手动推动平移组件330上的抽屉式运动板333,使将试剂盒510进行固定。
其中,步骤01-04为准备过程,下面进入核酸提取过程。
步骤05:X轴运动组件230、Y轴运动组件240、Z轴运动组件250配合运动,使移液枪头416移动到位于试剂盒510中吸头存放孔5111的上方位置处。
步骤06:Z轴运动组件250驱动移液组件410向下运动,移液枪头416取出存放于吸头存放孔5111的吸头,并复位。
步骤07:X轴运动组件230、Y轴运动组件240、Z轴运动组件250配合运动,使移液枪头416位于试剂孔5115的上方,Z方向驱动机构253驱动移液枪头416向下运动使吸头进入试剂孔5115。其中,后续不再说明特意说明X轴运动组件230、Y轴运动组件240、Z轴运动组件250的运动。
步骤08:控制移液枪头416从试剂孔5115取部分纯化磁珠至第二反应孔5114(W2)。
步骤09:控制移液枪头416吹打液体,第二反应孔5114(W2)底部的温控磁吸组件520工作,开始进行细胞裂解DNA过程。
步骤10:经过预设时间后,温控磁吸组件520停止加热,第二反应孔5114(W2)底部温控磁吸组件520工作,静置一段时间。
步骤11:移液枪头416移走第二反应孔5114(W2)内除磁珠外所有液体。
步骤12:更换吸头,该步骤中可根据客户需求是否进行更换,更换吸头可获得更纯净的产物,但会增加时间和耗材消耗。
步骤121:移液枪头416移动到吸头存放孔5111上方;
步骤122:第一驱动机构412控制第一滑块413继续向下,推动退吸头导向杆418下移,进而使退吸头导向杆418推动退吸头板417向下移动,通过退吸头板417的作用力将安装在移液枪头416上的吸头卸载,将吸头退落至原孔位;
步骤123:移液枪头416移动至新的吸头存放孔5111上方,第一驱动机构412控制移液枪头416通过过盈力吸取吸头。
步骤13:移液枪头416从试剂孔5115取部分洗涤液至第二反应孔5114(W2),第二反应孔5114(W2)底部温控磁吸组件520停止工作,移液枪头416吹打第二反应孔5114(W2)内试剂一段时间。
步骤14:第二反应孔5114(W2)底部温控磁吸组件520工作,静置一段时间,移液枪头416移走第二反应孔5114(W2)除磁珠外所有液体至废液区5116。
步骤15:步骤11-步骤13的过程可重复一次或多次,使洗涤更充分。其中,后续步骤11-步骤13的过程为使用“洗涤磁珠”一词代替。
步骤16:移液枪头416从试剂孔5115移取部分洗脱液进入第二反应孔5114(W2)。
步骤17:第二反应孔5114(W2)孔底部的温控磁吸组件520停止工作,移液枪头416吹打第二反应孔5114(W2)内试剂一段时间。
步骤18:第二反应孔5114(W2)底部温控磁吸组件520工作,静置一段时间。
步骤19:移液枪头416移动至吸头存放孔5111上方,进行退吸头操作。
步骤20:热盖加热组件420移动到第一反应孔5113(W1)上方,进行取热盖。
步骤21:移液枪头416重新移动到吸头存放孔5111上方,进行取吸头操作。
步骤22:移液枪头416重移走除磁珠外所有液体,一半至第一反应孔5113(W1)一半至产物区(试管存放孔5112内放置的试管)留样。
其中,步骤05-步骤22为核酸提取过程,下面进入片段化过程。
步骤23:移液枪头416分别从试剂孔5115取TE buffer、片段化反应液加入至第一反应孔5113(W1),并使用移液枪头416混合。
步骤24:移液枪头416移动至吸头存放孔5111上方,退吸头,使吸头退回至吸头存放孔5111内。
步骤25:X轴运动组件230、Y轴运动组件240、Z轴运动组件250配合移动,使移液枪头416移动到第一反应孔5113(W1)上方,Z方向驱动机构253驱动加热柱423向下运动。
步骤26:加热柱423工作对热盖进行加热,设定一定的温度,第一反应孔5113(W1)底部的温控
磁吸组件520开始工作,加热一段时间(片段化热反应过程)。
步骤27:温控磁吸组件520停止工作,散热一段时间后,Z方向驱动机构253驱动加热柱423和热盖上移,使得第一反应孔5113(W1)打开。
步骤28:加热柱423停止工作,散热一段时间后,Z方向驱动机构253上移,将热盖打开。
步骤29:移液枪头416移动至吸头存放孔5111上方,取吸头。
步骤30:移液枪头416取部分加接头试剂至第一反应孔5113(W1),并混合。
步骤31:移液枪头416移动至吸头存放孔5111上方,卸吸头。
步骤32:X轴运动组件230、Y轴运动组件240、Z轴运动组件250配合移动,使加热柱423移动到第一反应孔5113(W1)上方,Z方向驱动机构253向下运动,使加热柱423将热盖压出第一反应孔5113(W1)。
步骤33:加热柱423工作对热盖进行加热,设定一定温度,第一反应孔5113(W1)底部温控部件开始工作,加热一段时间。
步骤34:移液枪头416移动至吸头存放孔5111上方,取吸头。
步骤35:移液枪头416将第一反应孔5113(W1)内的试剂全部吸取至第二反应孔5114(W2)。
步骤36:移液枪头416移动至吸头存放孔5111上方,卸吸头。
步骤37:热盖移动至试剂盒510热盖孔上方,退热盖,热盖退回至原位置。
其中,步骤23-步骤37为片段化过程,下面进入DNA链长筛选过程。
步骤38:移液枪头416移动至吸头存放孔5111上方,移液枪头416进行取吸头。
步骤39:移液枪头416将第一反应孔5113(W1)内所有液体转移至第二反应孔5114(W2)。
步骤40:移液枪头416从试剂孔5115取部分筛选磁珠至第二反应孔5114(W2)。
步骤41:移液枪头416吹打第二反应孔5114(W2)一段时间。
步骤42:第二反应孔5114(W2)底部的温控磁吸组件520工作,静置一段时间。
步骤43:移液枪头416取走除磁珠外所有试剂至废液区5116暂存。
步骤44:第二反应孔5114(W2)底部的温控磁吸组件520停止工作,对第一反应孔5113(W1)和第二反应孔5114(W2)进行“洗孔”。
步骤45:移液枪头416将洗涤液取回至第一反应孔5113(W1)。
步骤46:移液枪头416吹打液体一段时间。
步骤47:移液枪头416取第二反应孔5114(W2)除磁珠外所有试剂至废液区5116。
步骤48:第二反应孔5114(W2)底部的温控磁吸组件520不工作。
步骤49:“洗涤磁珠”(可重复一次)。
步骤50:移液枪头416从试剂孔5115取洗脱液至第二反应孔5114(W2)。
步骤51:第二反应孔5114(W2)底部的温控磁吸组件520不工作,移液枪头416吹打试剂一段时间。
步骤52:第二反应孔5114(W2)底部的温控磁吸组件520工作,静置一段时间。
步骤53:取第二反应孔5114(W2)上清液至开放孔512。
步骤54:充分混合后,加入到密封孔513。
步骤55:对第二反应孔5114(W2)进行“洗孔”。
其中,步骤38-步骤55为DNA链长筛选过程,下面进入PCR反应过程。
步骤56:辅助活塞杆4141配合活塞腔552运动。
步骤57:将试剂从密封孔513转移至PCR反应组件560。
步骤58:PCR反应组件560的反应本体563内进行PCR扩增热循环反应。
其中,步骤56-步骤58为PCR反应过程。
步骤59:PCR反应介绍后,冷却至常温。
步骤60:辅助活塞杆4141合活塞腔552运动。
步骤61:将试剂从反应本体563内转移至封闭的密封孔513(预装筛选磁珠)。
步骤62:辅助活塞杆4141合活塞腔552运动。
步骤63:将产物转移至开放孔512。
步骤64:移液枪头416移动至开放孔512上方,将所有产物取回至第二反应孔5114(W2)内。
步骤65:静置一段时间后,第二反应孔5114(W2)底部温控磁吸组件520工作,并静置一段时间。
步骤66:移液枪头416取走除磁珠外所有试剂至废液区5116。
步骤67:洗涤磁珠。
步骤68:移液枪头416从试剂孔5115内取洗涤液至第二反应孔5114(W2)。
步骤69:移液枪头416吹打液体一段时间。
步骤70:第二反应孔5114(W2)底部温控磁吸组件520工作,静置一段时间。
步骤71:移液枪头416取第二反应孔5114(W2)除磁珠外所有试剂至废液区5116。
步骤72:重复上述65-67步骤一次。
步骤73:移液枪头416从试剂孔5115取洗脱液至第二反应孔5114(W2)。
步骤74:第二反应孔5114(W2)底部温控磁吸组件520不工作,静置一段时间。
步骤75:第二反应孔5114(W2)底部温控磁吸组件520工作,静置一段时间。
步骤76:移液枪头416取第二反应孔5114(W2)上清液至产物区(试管存放孔5112内放置的试管)。
需要说明的是,在不冲突的情况下,本申请中的实施例中的特征可以相互结合。
以上仅为本申请的优选实施例而已,并不用于限制本申请,对于本领域的技术人员来说,本申请可以有各种更改和变化。凡在本申请的精神和原则之内,所作的任何修改、等同替换、改进等,均应包含在本申请的保护范围之内。
Claims (15)
- 一种基因处理设备,其特征在于,包括:机架;基座支撑模块,设于所述机架内;台面组装模块,设于所述基座支撑模块上,所述台面组装模块上设有试剂盒,所述试剂盒上设有多个功能孔位,所述台面组装模块内设有温控磁吸组件;工位切换模块,设于所述机架内,所述工位切换模块上设有支撑架体;以及复合功能模块,设于所述支撑架体上,所述工位切换模块用于驱动所述复合功能模块在各个所述功能孔位之间进行转移;其中,所述复合功能模块包括:移液组件和热盖加热组件;所述移液组件设于所述支撑架体上,用于进行移液操作;所述热盖加热组件设于所述支撑架体上,用于进行热盖的加热及取卸操作。
- 根据权利要求1所述的基因处理设备,其特征在于,所述移液组件包括:第一安装板,设于所述支撑架体上,所述第一安装板上设有第一导轨;第一驱动机构,设于所述第一安装板上,所述第一驱动机构上连接有第一传动件;第一滑块,设于所述第一安装板上,并能沿所述第一导轨滑动,所述第一驱动机构通过所述第一传动件与所述第一滑块传动连接;活塞杆,设于所述第一滑块底部;真空腔体,设于所述支撑架体的底板上,所述第一驱动机构用于驱动所述第一滑块升降,进而驱动所述活塞杆移动并伸入所述真空腔体内;以及移液枪头,与所述真空腔体连接,用于安装吸头,所述移液枪头内设有通孔,所述通孔与所述真空腔体底部连通。
- 根据权利要求2所述的基因处理设备,其特征在于,所述移液组件还包括:退吸头板,能活动的设于所述移液枪头上:退吸头导向杆,设于所述退吸头板上,所述支撑架体的底板上设有退吸头导杆通孔,所述退吸头导向杆穿过所述退吸头导杆通孔,并伸向所述第一滑块;以及第一弹性件,套设于所述退吸头导向杆伸向所述第一滑块的端部上。
- 根据权利要求1所述的基因处理设备,其特征在于,所述热盖加热组件包括:第二驱动机构,设于所述支撑架体的底板上,所述第二驱动机构上连接有第二传动件;推板,与所述第二传动件传动连接;加热柱,设于所述支撑架体的底板底部,所述加热柱内设有加热棒;退热盖板,能活动的设于所述加热柱上;退热盖导杆,设于所述退热盖板上,所述支撑架体的底板上设有退热盖导杆通孔,所述退热盖导杆穿过所述退热盖导杆通孔,并伸向所述推板;限位板,设于所述退热盖导杆伸向所述推板的一端部上;以及第二弹性件,套设于所述退热盖导杆上,且位于所述支撑架体的底板与所述限位板之间。
- 根据权利要求1至4任一项所述的基因处理设备,其特征在于,所述工位切换模块包括:X轴运动组件、Y轴运动组件以及Z轴运动组件;所述X轴运动组件,设于所述机架内;所述Y轴运动组件,与所述X轴运动组件传动连接;所述Z轴运动组件,与所述Y轴运动组件传动连接;所述支撑架体设于所述Z轴运动组件上;所述Z轴运动组件用于驱动所述复合功能模块沿Z方向运动,所述Y轴运动组件用于驱动所述复合功能模块沿Y方向运动,所述X轴运动组件用于驱动所述复合功能模块沿X方向运动;其中,X方向、Y方向、Z方向相互垂直。
- 根据权利要求5所述的基因处理设备,其特征在于,所述X轴运动组件包括:X轴底板,设于所述机架内;X方向驱动机构,沿所述X方向设于所述X轴底板上,所述X方向驱动机构上连接有X方向传动件,所述X方向传动件传动连接X方向连接件;以及X方向运动板,滑动设于所述X轴底板上,所述X方向连接件设于所述X方向运动板上。
- 根据权利要求6所述的基因处理设备,其特征在于,所述Y轴运动组件包括:Y轴底板,与所述X方向运动板连接;Y方向驱动机构,沿所述Y方向设于所述Y轴底板上;以及同步带传动组件,与所述Y方向驱动机构传动连接。
- 根据权利要求7所述的基因处理设备,其特征在于,所述Z轴运动组件包括:Z轴底板,与所述同步带传动组件传动连接,且所述Z轴底板滑动连接于所述Y轴底板上;Z方向运动板,滑动设于所述Z轴底板上,所述支撑架体连接于所述Z方向运动板上;以及Z方向驱动机构,沿所述Z方向设于所述支撑架体上,所述Z方向驱动机构上连接有Z方向传动件,所述Z方向传动件传动连接Z方向连接件,所述Z方向连接件与所述Z方向运动板连接。
- 根据权利要求1所述的基因处理设备,其特征在于,所述基座支撑模块包括:基座;工位切换支撑座,设于所述基座上,且与所述工位切换模块连接;平移组件,设于所述基座上,所述平移组件包括:第一导轨连接板,设于所述基座上;第二导轨连接板,滑动设于所述第一导轨连接板上;以及抽屉式运动板,连接于所述第二导轨连接板;所述台面组装模块设于所述抽屉式运动板上,所述台面组装模块上设有试剂盒固定组件,所述基座上设有与所述试剂盒固定组件配合的压板件,用于当所述台面组装模块通过所述平移组件推入到预设位置处时,所述压板件与所述试剂盒固定组件配合将所述试剂盒固定。
- 根据权利要求9所述的基因处理设备,其特征在于,所述基因处理设备还包括:环境控制模块,所述环境控制模块包括:第一环境控制组件,设于所述机架内,用于将所述台面组装模块以及所述机架连通;以及第二环境控制组件,设于所述机架内,用于将PCR反应组件、所述工位切换支撑座以及所述机架连通。
- 根据权利要求10所述的基因处理设备,其特征在于,所述试剂盒上还设有密封盒体,所述密封盒体与所述PCR反应组件连接;所述台面组装模块内还设有:卡盘旋转组件,与所述密封盒体底部传动连接。
- 根据权利要求11所述的基因处理设备,其特征在于,所述密封盒体具有容纳腔、密封腔和反应腔;所述容纳腔内设有活塞腔,所述容纳腔外周面上开设有与所述活塞腔连通的第一通道,所述密封腔底部开设有第二通道;所述PCR反应组件包括:第一反应通道、第二反应通道以及反应本体,所述反应本体通过所述第一反应通道、所述第二反应通道连接,所述第二反应通道与所述反应腔连通;所述卡盘旋转组件与所述容纳腔底部传动连接,用于驱动所述密封盒体转动,以使所述第一通道择一地与所述第二通道或所述第一反应通道连通。
- 根据权利要求10所述的基因处理设备,其特征在于,所述功能孔位包括:至少一个吸头存放孔、至少一个试管存放孔、至少一个第一反应孔、至少一个第二反应孔以及多个试剂孔。
- 根据权利要求13所述的基因处理设备,其特征在于,所述温控磁吸组件,设于所述试剂盒底部,用于对所述第一反应孔和/或第二反应孔进行控温和吸磁。
- 根据权利要求13所述的基因处理设备,其特征在于,所述台面组装模块内还设有制冷组件,所述制冷组件设于所述试剂盒底部,用于对所述试剂孔进行制冷。
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CN108624493A (zh) * | 2018-08-01 | 2018-10-09 | 德诺杰亿(北京)生物科技有限公司 | 一体化dna分析仪 |
CN114134032A (zh) * | 2021-12-02 | 2022-03-04 | 杭州奥盛仪器有限公司 | 基因测序前处理装置 |
CN114164094A (zh) * | 2021-11-04 | 2022-03-11 | 杭州奥盛仪器有限公司 | 一种全自动ngs文库构建***的pcr高效率扩增装置 |
CN216473243U (zh) * | 2021-12-02 | 2022-05-10 | 杭州奥盛仪器有限公司 | 一种带荧光检测模块的自动化样本制备*** |
CN114752491A (zh) * | 2022-03-25 | 2022-07-15 | 杭州奥盛仪器有限公司 | 一种基因提取模块及基因检测设备 |
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CN108624493A (zh) * | 2018-08-01 | 2018-10-09 | 德诺杰亿(北京)生物科技有限公司 | 一体化dna分析仪 |
CN114164094A (zh) * | 2021-11-04 | 2022-03-11 | 杭州奥盛仪器有限公司 | 一种全自动ngs文库构建***的pcr高效率扩增装置 |
CN114134032A (zh) * | 2021-12-02 | 2022-03-04 | 杭州奥盛仪器有限公司 | 基因测序前处理装置 |
CN216473243U (zh) * | 2021-12-02 | 2022-05-10 | 杭州奥盛仪器有限公司 | 一种带荧光检测模块的自动化样本制备*** |
CN114752491A (zh) * | 2022-03-25 | 2022-07-15 | 杭州奥盛仪器有限公司 | 一种基因提取模块及基因检测设备 |
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