WO2024098557A1 - 基因检测处理设备及方法 - Google Patents
基因检测处理设备及方法 Download PDFInfo
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- WO2024098557A1 WO2024098557A1 PCT/CN2023/073142 CN2023073142W WO2024098557A1 WO 2024098557 A1 WO2024098557 A1 WO 2024098557A1 CN 2023073142 W CN2023073142 W CN 2023073142W WO 2024098557 A1 WO2024098557 A1 WO 2024098557A1
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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
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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
- C12M1/26—Inoculator or sampler
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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
- C12M1/34—Measuring or testing with condition measuring or sensing means, e.g. colony counters
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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
- C12M1/36—Apparatus for enzymology or microbiology including condition or time responsive control, e.g. automatically controlled fermentors
- C12M1/38—Temperature-responsive control
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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
- C12M1/42—Apparatus for the treatment of microorganisms or enzymes with electrical or wave energy, e.g. magnetism, sonic waves
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- Y—GENERAL 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
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Definitions
- the present application relates to the technical field of gene detection, and in particular, to a gene detection processing device and method.
- Genetic testing has become the main research method used in clinical molecular experiments.
- the premise of genetic testing is to extract high-quality and high-purity nucleic acids from biological samples.
- the magnetic rod-type magnetic bead uptake extraction technology based on the magnetic bead method is usually used, which uses the characteristics of nanomagnetic beads specifically binding and detaching from nucleic acid molecules under different environments to achieve the purpose of purifying nucleic acids from samples.
- the extraction steps are generally divided into lysis, binding, several washes and elution.
- Nucleic acid extraction can be done from a variety of samples, including blood, body fluids, tissue sections, and environmental samples.
- concentration of nucleic acid in samples varies, and low-concentration samples are the most difficult to extract. They are often used in free nucleic acid extraction scenarios, such as body fluid extraction (sputum, urine, fecal processing fluid, etc.) for early cancer screening and nucleic acid extraction from amniotic fluid, plasma, and other samples for prenatal screening. Since the target nucleic acid content in these samples is low, a large amount of sample volume is often required for nucleic acid extraction.
- the nucleic acid and magnetic beads need to be fully mixed to improve the efficiency of nucleic acid extraction; as the binding system continues to increase, whether the magnetic beads that have bound to nucleic acid molecules in the liquid can be fully captured after the binding is completed is also a key factor affecting the efficiency of nucleic acid extraction.
- an extremely low elution volume is often required to increase the concentration of the nucleic acid elution product.
- nucleic acid extraction equipment For nucleic acid extraction of large binding systems, existing nucleic acid extraction equipment usually uses independent pipettes for sample transfer and washing during nucleic acid sample elution and magnetic absorption treatment, and then uses independent magnetic sleeve lifting devices for magnetic absorption and demagnetization treatment. This makes the overall structure of the nucleic acid extraction equipment larger and more complex, occupies a large space, and has a low degree of automation, thereby reducing the efficiency of nucleic acid extraction.
- the purpose of this application is to provide a gene detection processing device that integrates a pipetting module and a magnetic absorption module, saves space, makes the structure more compact, and improves the automation of the gene detection processing device.
- the integration of the pipetting module and the magnetic absorption module enables the gene detection processing device to simultaneously process large and small volume reagents, and can meet more application scenarios.
- the present application provides a genetic testing and processing device, comprising: a base; a reagent kit carrier, which is arranged on the base, and a plurality of functional holes are provided on the reagent kit carrier; a station adjustment module, which is arranged on the base; a composite function module, which is connected to the station adjustment module, and the station adjustment module is used to drive the composite function module to transfer between each of the functional holes; wherein the composite function module comprises: a top plate, which is connected to the station adjustment module; a bottom plate, which is connected to the station adjustment module; a pipetting module, which is connected to the top plate and the bottom plate, and is used for pipetting operations and reagent mixing operations; a magnetic absorption module, which is arranged opposite to the pipetting module, and is used for magnetic bead adsorption operations.
- the top plate and the bottom plate are both connected to the station adjustment module
- the liquid transfer module is connected to the top plate and the bottom plate
- the magnetic absorption module is connected to the top plate and the bottom plate
- the magnetic absorption module is arranged opposite to the liquid transfer module.
- the station adjustment module is used to drive the composite functional module to transfer between various functional wells, so that the liquid transfer module performs liquid transfer and reagent mixing operations, and the magnetic absorption module performs magnetic bead adsorption operations.
- the pipetting module and the magnetic absorption module share the same top plate and bottom plate. This configuration integrates the pipetting module and the magnetic absorption module together, which not only saves space, makes the structure more compact, reduces the difficulty of operation, but also improves the degree of automation of the gene detection processing equipment.
- the magnetic attraction module includes: a magnetic rod frame guide rod, connecting the top plate and the bottom plate; a magnetic rod bracket, sleeved on the magnetic rod frame guide rod and located between the top plate and the bottom plate, and a plurality of first through holes are provided on the bottom plate; a plurality of magnetic rods, one end of which is connected to the magnetic rod bracket and the other end passes through the first through hole; a magnetic sleeve mounting portion, which is provided on the bottom plate and is used to mount the magnetic rod sleeve; And a magnetic rod driving component is arranged on the top plate, and the output end of the magnetic rod driving component is drivingly connected with the magnetic rod support, so as to drive the magnetic rod support to move up and down.
- the magnetic rod driving member drives the magnetic rod bracket to descend, thereby driving multiple magnetic rods to move downward.
- the magnetic rod driving member drives the magnetic rod bracket to descend until the top of the magnetic rod passes through the magnetic sleeve mounting portion until the top of the magnetic rod fits with the tip of the magnetic rod sleeve
- the magnetic rod sleeve is inserted into the magnetic sleeve mounting portion and firmly clamped on the magnetic sleeve mounting portion, thereby realizing the loading of the magnetic rod sleeve.
- the above structure can improve the degree of automation of the magnetic rod sleeve installation.
- the magnetic absorption module also includes: a demagnetization rod sleeve plate, movably arranged on the magnetic sleeve mounting portion; a demagnetization rod sleeve elastic guide rod, arranged on the demagnetization rod sleeve plate, a demagnetization rod sleeve elastic guide rod through hole is provided on the bottom plate, the demagnetization rod sleeve elastic guide rod passes through the demagnetization rod sleeve elastic guide rod through hole and extends toward the magnetic bar bracket.
- the magnetic rod support is driven downward by the magnetic rod driving member, and the magnetic rod support pushes the elastic guide rod of the demagnetization rod sleeve downward, thereby causing the elastic guide rod of the demagnetization rod sleeve to push the demagnetization rod sleeve plate downward, and the magnetic rod sleeve installed on the magnetic sleeve mounting portion is unloaded by the force of the demagnetization rod sleeve plate.
- the magnetic rod reset switch is triggered, the magnetic rod driving member stops automatically, the magnetic rod support returns to the initial position, the magnetic rod support leaves the elastic guide rod of the demagnetization rod sleeve, and the elastic guide rod of the demagnetization rod sleeve returns to the initial position under the elastic force, so that the demagnetization rod sleeve plate is reset.
- the magnetic rod, the first through hole, and the magnetic sleeve mounting portion are all coaxially arranged and correspond one to one.
- the number of magnetic bars is consistent with the number of piston rods.
- the pipetting module includes: a piston rod rack guide rod connecting the top plate and the bottom plate, and a plurality of second through holes are provided on the bottom plate; a piston bracket, which is sleeved on the piston rod rack guide rod and is located between the top plate and the bottom plate; a plurality of piston cylinders, which are provided in the second through holes, and the piston cylinders have a accommodating cavity; a plurality of piston rods, one end of which is connected to the piston bracket and the other end of which can be extended into the piston cylinder; a tip mounting part, which is provided on the bottom plate and is used to mount a tip, and a vent is provided in the tip mounting part, and the vent is connected to the bottom of the piston cylinder; and a pipetting drive component, which is provided on the top plate, and the output end of the pipetting drive component is transmission-connected to the piston bracket for driving the piston bracket to lift and lower.
- the piston bracket is driven down by the pipetting drive, thereby driving multiple piston rods to move downward, and multiple piston rods are correspondingly inserted into the accommodating chamber in the piston cylinder located on the bottom plate.
- the pipetting drive continues to drive the piston bracket down, the top of the piston rod contacts the bottom of the piston cylinder.
- the height of the pipetting module is adjusted by controlling the vertical lifting module, so that the tip mounting part gradually approaches the tip at the tip hole position under the driving force of the pipetting drive, and then the piston bracket is driven down by the pipetting drive.
- the tip Under the action of the pipetting drive, the tip is installed on the tip mounting part and firmly clamped on the tip mounting part, completing the loading of the tip.
- the above structure can improve the degree of automation of tip installation.
- the pipetting module further includes: a tip ejection plate, movably disposed on the tip mounting portion; a tip ejection elastic guide rod, disposed on the tip ejection plate, a tip ejection elastic guide rod through hole being provided on the bottom plate, the tip ejection elastic guide rod passing through the tip ejection elastic guide rod through hole and extending toward the piston bracket.
- the pipetting drive is controlled to work, and the pipetting drive drives the piston bracket to descend.
- the bottom of the piston bracket touches the elastic guide rod of the suction head ejection, and under the driving force of the pipetting drive, the piston bracket pushes the elastic guide rod of the suction head ejection downward, so that the elastic guide rod of the suction head ejection pushes the suction head ejection plate to move downward, so that the suction head installed on the suction head mounting part is unloaded and dropped off through the suction head ejection plate.
- a first sealing ring is provided on the contact surface between the tip mounting portion and the tip ejection plate; a second sealing ring is also provided on the tip mounting portion; and a third sealing ring is provided on the contact surface between the piston cylinder and the second through hole.
- a first sealing ring is provided at the contact surface between the tip mounting portion and the tip ejection plate, which can further enhance the sealing and stability of the contact between the tip mounting portion and the tip ejection plate.
- a second sealing ring is also provided on the tip mounting portion to prevent the tip mounting portion from leaking samples and causing contamination during the pipetting operation after the tip is installed.
- a third sealing ring is provided on the contact surface between the piston cylinder and the second through hole to prevent the piston cylinder from moving in the second through hole when the pipetting drive drives the piston bracket to rise and fall, thereby further enhancing the sealing and stability of the contact between the piston cylinder and the second through hole.
- the piston rod, the piston cylinder, the second through hole, and the suction head mounting portion are all coaxially arranged and correspond one to one.
- the number of piston rods is consistent with the number of piston cylinders.
- the composite functional module further includes: a film puncturing module, the film puncturing module includes: a plurality of puncture needles connected to the piston bracket, the pipetting drive drives the piston bracket to move up and down so that the puncture needles perform film puncturing operations.
- a membrane piercing module is also provided on the pipetting module.
- the sealing film is pierced by controlling the membrane piercing module.
- the workstation adjustment module includes: a horizontal movement module, which is arranged on the base; a vertical lifting module, which is arranged on the horizontal movement module; and the composite function module is arranged on the vertical lifting module.
- the horizontal moving module is used to adjust the moving position of the composite functional module in the horizontal direction
- the vertical lifting module is used to adjust the position of the composite functional module in the vertical height direction.
- the composite functional module can be moved above the reagent cartridge carrier as needed and moved to the location of the designated functional well position, so as to perform the corresponding operations such as pipetting, mixing and magnetic absorption in the nucleic acid extraction process.
- the horizontal movement module includes: a horizontal slide rail, which is arranged on the base; a horizontal slider assembly, which is movably arranged on the horizontal slide rail; a horizontal mounting base, which is arranged on the horizontal slider assembly; a first transmission member, which is arranged on the base, and the horizontal slider assembly is sleeved on the first transmission member; and a horizontal driving member, which is connected to the first transmission member and is used to drive the horizontal slider assembly to move horizontally.
- the horizontal driving member is in transmission connection with the first transmission member, and is used to drive the first transmission member to rotate, thereby driving the horizontal slider assembly to move on the first transmission member, so that the horizontal slider assembly can move horizontally on the horizontal slide rail.
- the vertical lifting module includes: a lifting mounting base, which is arranged on the horizontal mounting base; a vertical slide rail, which is arranged on the lifting mounting base; a vertical slider assembly, which is movably arranged on the vertical slide rail; a lifting mounting plate, which is arranged on the vertical slider assembly, and the top plate and the bottom plate are both arranged on the lifting mounting plate; a second transmission member, which is arranged on the lifting mounting base, and the vertical slider assembly is sleeved on the second transmission member; and a vertical driving member, which is connected to the second transmission member and is used to drive the vertical slider assembly to drive the lifting mounting plate to lift and lower.
- the vertical driving member is connected to the second transmission member for driving the second transmission member to rotate, thereby driving the vertical slider assembly to move on the second transmission member, so that the vertical slider assembly can be lifted and lowered on the vertical slide rail, thereby driving the lifting mounting plate to lift and lower, and then driving the pipetting module and the magnetic absorption module arranged on the lifting mounting plate to move in the vertical direction.
- the functional holes include: reagent holes for placing extraction reagents, the reagent holes include first capacity reagent holes and second capacity reagent holes; elution tube holes for placing eluents; reagent tube holes for placing reagents; sample tube holes for placing samples; magnetic rod sleeve holes for placing magnetic rod sleeves; and pipette tip holes for placing pipette tips.
- the multiple functional holes on the reagent kit carrier can be divided into: reagent holes, elution tube holes, reagent tube holes, sample tube holes, magnetic rod sleeve holes, and pipette tip holes.
- the reagent holes are used to place extraction reagents (including binding solution, magnetic beads, and various washing solutions) as a generation container for extracting nucleic acid samples
- the elution tube holes are used to place eluents
- the reagent tube holes are used to place related reagents (reagents can be automatically added during the experiment)
- the sample tube holes are used to place samples (such as lysed serum samples)
- the magnetic rod sleeve holes are used to place magnetic rod sleeves for magnetic bead adsorption
- the pipette tip holes are used to place pipette tips, and the tip of the pipette tip is open, and samples or reagents can be sucked in and injected through the opening at the tip of the pipette tip, thereby achieving sample mixing and pipetting.
- the genetic testing and processing equipment also includes: a temperature control module, which is arranged on the base and located under the reagent kit carrier, and is used to adjust the temperature;
- the temperature control module includes: a reagent area temperature control unit, which is arranged on the base and located at the bottom of the reagent kit carrier, and is used to control the temperature of the reagent in the reagent hole; and a reaction area temperature control unit, which is arranged on the base and located at the bottom of the reagent kit carrier, and is used to control the temperature of the reagent in the elution tube hole.
- the temperature control module is arranged below the reagent kit carrier and is used to perform temperature control reactions in the lysis and elution steps.
- the reagent area temperature control unit includes: a first processing block, arranged on the base, located at the bottom of the reagent hole; a first refrigeration block, arranged at the bottom of the first processing block; a first insulation block, connected to the first refrigeration block; and a first radiator, arranged at the bottom of the first refrigeration block.
- the first processing block is arranged at the bottom of the first volume reagent well, and can be adapted to various types of support different structures.
- the first processing block is set in a groove shape, which fits the first reagent well of the combination system.
- the first reagent well of the first volume can be heated or cooled according to the experimental needs. When the first reagent well is cooled, the reagent after cleavage and heating can quickly reach the required temperature range, thereby accelerating the reaction process. Because the next step of cleavage and combination needs to react at room temperature.
- the reaction zone temperature control unit includes: a second heating block, arranged on the base, located at the bottom of the elution tube hole; a second insulation block, arranged on the second heating block; and a second radiator, arranged at the bottom of the second heating block.
- the reaction zone temperature control unit can control the temperature of the reagents in the elution tube holes, so as to reach a suitable temperature range during the experiment.
- the present application provides a gene detection and processing method, using the gene detection and processing equipment as described in any of the aforementioned embodiments, including the following steps: driving the composite function module to the corresponding functional hole position through the work station adjustment module; performing pipetting and mixing operations through the pipetting module, and performing magnetic absorption operations through the magnetic absorption module to achieve gene extraction and detection processing.
- the horizontal moving module is used to adjust the horizontal moving position of the composite functional module
- the vertical lifting module is used to adjust the vertical height position of the composite functional module, so that the composite functional module can move above the reagent cartridge carrier as needed and move to the position of the designated functional well, thereby performing the corresponding operations such as pipetting, mixing and magnetic absorption in the nucleic acid extraction process.
- the pipetting and mixing operations performed by the pipetting module include: performing a tip loading operation by the pipetting module; transferring the reagent to be detected between the plurality of functional wells by the pipetting module; and driving the pipetting module to move in a preset direction by the station adjustment module, so that the pipetting module can fully mix the reagent to be detected.
- the horizontal moving module drives the pipetting module to move left and right
- the vertical lifting module drives the pipetting module to move up and down.
- the magnetic absorption operation performed by the magnetic absorption module includes: performing a magnetic rod sleeve loading operation by the magnetic absorption module; driving the magnetic absorption module to move to the corresponding functional hole position containing magnetic beads by the work position adjustment module, and driving the magnetic absorption module to move in a preset direction so that the magnetic absorption module performs a magnetic absorption operation; driving the magnetic absorption module to perform a demagnetization operation by the work position adjustment module.
- the magnetic absorption module is driven to move left and right by the horizontal moving module, and the magnetic absorption module is driven to move up and down by the vertical lifting module, which can meet the requirement of sufficient adsorption of magnetic beads.
- FIG1 is a schematic diagram of the structure of a gene detection and processing device provided in one embodiment of the present application.
- FIG2 is a schematic diagram of the structure of a horizontal movement module provided in an embodiment of the present application.
- FIG3 is a schematic structural diagram of a vertical movement module provided in an embodiment of the present application.
- FIG4 is a schematic diagram of the structure of a reagent kit carrier provided in one embodiment of the present application.
- FIG5 is a schematic diagram of the structure of a pipetting module provided in one embodiment of the present application.
- FIG6 is a cross-sectional view of a pipetting module provided in one embodiment of the present application.
- FIG7 is an enlarged schematic diagram of point A in FIG5;
- FIG8 is a schematic diagram of a pipette tip withdrawal state in a pipetting module provided in an embodiment of the present application.
- FIG9 is a schematic structural diagram of a film piercing module provided in one embodiment of the present application.
- FIG10 is a schematic structural diagram of a magnetic attraction module provided in an embodiment of the present application.
- FIG11 is a cross-sectional view of a magnetic attraction module provided in one embodiment of the present application.
- FIG12 is a schematic diagram of a demagnetizing rod sleeve in a magnetic absorption module provided in an embodiment of the present application.
- FIG13 is a schematic diagram of the structure of a temperature control module provided in an embodiment of the present application.
- FIG14 is an enlarged schematic diagram of point B in FIG13;
- FIG15 is a schematic diagram of the structure of a first processing block provided in an embodiment of the present application.
- FIG16 is a schematic diagram of a process flow of a gene detection processing method provided in an embodiment of the present application.
- FIG17 is a schematic diagram of the structure of a magnetic frame provided in one embodiment of the present application.
- FIG. 18 is a cross-sectional view of a magnetic frame providing a magnetic attraction according to an embodiment of the present application.
- 1-gene detection and processing equipment 100-base; 200-station adjustment module; 210-horizontal movement module; 211-horizontal slide rail; 212-horizontal slider assembly; 213-horizontal mounting base; 214-first transmission member; 215-horizontal drive member; 2151-first motor; 220-vertical lifting module; 221-lifting mounting base; 222-vertical slide rail; 223-vertical slider assembly; 224-lifting mounting plate; 225-second transmission member; 226-vertical drive member; 2261-second motor; 300-test kit carrier; 31 0-functional hole position; 311-reagent hole position; 3111-first volume reagent hole position; 3112-second volume reagent hole position; 312-elution tube hole position; 313-reagent tube hole position; 314-sample tube hole position; 315-magnetic rod sleeve hole position; 3151-magnetic rod sleeve; 316-pipette tip hole position; 3161-pipette tip; 31611-pipe
- horizontal does not mean that the components are required to be absolutely horizontal or overhanging, but can be slightly tilted.
- “horizontal” only means that its direction is more horizontal than “vertical”, and does not mean that the structure must be completely horizontal, but can be slightly tilted.
- 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.
- Genetic testing is a relatively accurate medical testing technology, which is mainly used in the fields of disease detection, material analysis, biomedicine, etc. By extracting nucleic acids from the peripheral venous blood, tissues and other body fluids of the subject, and analyzing the DNA or RNA molecules in the cells of the subject through testing equipment, the genetic information of the subject can be understood, and then the cause of the disease or the risk of disease can be determined.
- the premise of genetic testing is to extract high-quality and high-concentration nucleic acid samples.
- a larger amount of sample is required for extraction.
- high-concentration nucleic acids are extracted from a larger amount of sample.
- the extraction process involves nucleic acid lysis, full binding, several washes, and more complete elution from the magnetic beads.
- the nucleic acid extraction equipment or instrument is not only required to achieve efficient mixing and sufficient elution of nucleic acid samples, but also required to have the function of extracting and processing large-volume nucleic acid samples.
- FIG. 1 is a structural diagram of a gene detection processing device 1 provided in an embodiment of the present application.
- the gene detection processing device 1 includes: a base 100, a station adjustment module 200, a reagent kit carrier 300, and a composite function module 400.
- the reagent kit carrier 300 is arranged on the base 100, and a plurality of functional holes 310 are provided on the reagent kit carrier 300; the station adjustment module 200 is arranged on the base 100; and the composite function module 400 is connected to the station adjustment module 200.
- the composite function module 400 includes: a top plate 410, a bottom plate 420, a pipetting module 430 and a magnetic absorption module 440, the top plate 410 and the bottom plate 420 are both connected to the station adjustment module 200, the pipetting module 430 connects the top plate 410 and the bottom plate 420, the magnetic absorption module 440 connects the top plate 410 and the bottom plate 420, and the magnetic absorption module 440 is arranged opposite to the pipetting module 430.
- Station adjustment module 200 It is used to drive the composite function module 400 to transfer between various functional wells 310, so that the pipetting module 430 performs pipetting operations and reagent mixing operations, and the magnetic absorption module 440 performs magnetic bead absorption operations.
- the pipetting module 430 and the magnetic attraction module 440 share the same top plate 410 and bottom plate 420.
- This configuration integrates the pipetting module 430 and the magnetic attraction module 440 together, which not only saves space, makes the structure more compact, reduces the difficulty of operation, but also improves the degree of automation of the gene detection and processing equipment 1.
- the station adjustment module 200 includes: a horizontal moving module 210 and a vertical lifting module 220.
- the horizontal moving module 210 is arranged on the base 100
- the vertical lifting module 220 is arranged on the horizontal moving module 210
- the composite function module 400 is arranged on the vertical lifting module 220.
- the horizontal moving module 210 is used to adjust the horizontal movement position of the composite function module 400
- the vertical lifting module 220 is used to adjust the position of the composite function module 400 in the vertical height direction.
- the composite function module 400 can move above the reagent box carrier 300 as needed, and move to the position of the designated functional hole 310, so as to perform the corresponding operations such as pipetting, mixing and magnetic absorption in the nucleic acid extraction process.
- FIG. 2 is a schematic diagram of the structure of a horizontal moving module 210 provided in an embodiment of the present application.
- the horizontal moving module 210 includes: a horizontal slide rail 211, a horizontal slider assembly 212, a horizontal mounting base 213, a first transmission member 214, and a horizontal driving member 215.
- the horizontal slide rail 211 is arranged on the base 100; the horizontal slider assembly 212 is movably arranged on the horizontal slide rail 211; the horizontal mounting base 213 is arranged on the horizontal slider assembly 212; the first transmission member 214 is arranged on the base 100, the horizontal slider assembly 212 is sleeved on the first transmission member 214, and the horizontal driving member 215 is connected to the first transmission member 214 for driving the first transmission member 214 to rotate, thereby driving the horizontal slider assembly 212 to move on the first transmission member 214, so that the horizontal slider assembly 212 can move horizontally on the horizontal slide rail 211.
- the horizontal driving member 215 is a first motor 2151.
- the first transmission member 214 is a lead screw, and the output end of the first motor 2151 is connected to the lead screw in a transmission manner.
- the horizontal driving member 215 may also be a hydraulic motor or the like.
- FIG3 is a schematic diagram of the structure of a vertical moving module 220 provided in an embodiment of the present application.
- the vertical lifting module 220 includes: a lifting installation base 221 , a vertical slide rail 222 , a vertical slider assembly 223 , a lifting installation plate 224 , a second transmission member 225 and a vertical driving member 226 .
- the lifting and lowering mounting base 221 is arranged on the horizontal mounting base 213; the vertical slide rail 222 is arranged on the lifting and lowering mounting base 221; the vertical slider assembly 223 is movably arranged on the vertical slide rail 222; the lifting and lowering mounting plate 224 is arranged on the vertical slider assembly 223, and the top plate 410 and the bottom plate 420 are both arranged on the lifting and lowering mounting plate 224; the second transmission member 225 is arranged on the lifting and lowering mounting base 221, and the vertical slider assembly 223 is sleeved on the second transmission member 225, and the vertical driving member 226 is connected to the second transmission member 225 for driving the second transmission member 225 to rotate, thereby driving the vertical slider assembly 223 to move on the second transmission member 225, so that the vertical slider assembly 223 is lifted and lowered on the vertical slide rail 222, thereby driving the lifting and lowering mounting plate 224 to lift and lower, and then can drive the pipetting module 430 and the magnetic absorption module 440 arranged on the lifting
- the transmission mode of the vertical driving member 226 and the second transmission member 225 can be consistent with the transmission mode of the horizontal driving member 215 and the first transmission member 214.
- the vertical driving member 226 is a second motor 2261
- the second transmission member 225 is a lead screw
- the output end of the second motor 2261 is connected to the lead screw.
- the vertical driving member 226 can also be a hydraulic motor, etc.
- FIG 4 is a schematic diagram of the structure of the reagent kit carrier 300 provided in an embodiment of the present application.
- the reagent kit carrier 300 adopts a split design, which is mainly used to place the reagents, sample tubes, reagent tubes, magnetic rod sleeves 3151 and pipette tips 3161 required for the experiment.
- the multiple functional holes 310 on the reagent kit carrier 300 can be divided into: reagent hole 311, elution tube hole 312, reagent tube hole 313, sample tube hole 314, magnetic rod sleeve hole 315, and pipette tip hole 316.
- the reagent hole 311 is used to place the extraction reagent (including binding solution, magnetic beads, and various washing solutions) as a generation container for extracting nucleic acid samples
- the elution tube hole 312 is used to place the elution solution
- the reagent tube hole 313 is used to place the relevant reagents (reagents can be automatically added during the experiment)
- the sample tube hole 314 is used to place the sample (for example, a lysed serum sample)
- the magnetic rod sleeve hole 315 is used to place the magnetic rod sleeve 3151 for magnetic bead adsorption
- the pipette tip hole 316 is used to place the pipette tip 3161, the tip of the pipette tip 3161 is open, and the sample or reagent can be sucked in and injected through the opening at the tip of the pipette tip 3161, thereby achieving sample mixing and pipetting.
- the reagent wells 311 are selected to be 5-wells, 7-wells or 8-wells. Based on the capacity of the nucleic acid sample, the reagent wells 311 can be divided into first-capacity reagent wells 3111 and second-capacity reagent wells 3112. Taking the 5-well reagent wells 311 as an example, one of the wells is the first-capacity reagent well 3111, which supports a maximum binding system of 7 ml, and the remaining 4 wells are all second-capacity reagent wells 3112, which can support small-volume binding systems, such as 1 ml or 2 ml.
- one of the wells is the first-capacity reagent well 3111, which supports a maximum binding system of 15 ml Binding system
- the remaining 4 holes are all second capacity reagent holes 3112, supporting small volume binding system.
- the 8-hole reagent hole position 311 one of the holes is the first capacity reagent hole position 3111, and the first capacity reagent hole position 3111 supports a maximum binding system of 2.5ml, and the remaining 4 holes are all second capacity reagent holes 3112, which can support small volume binding system.
- the reagent hole position 311 selects 5 holes, wherein the first capacity reagent hole position 3111 is marked as hole No. 1, and the other 4 second capacity reagent holes 3112 adjacent to the first capacity reagent hole position 3111 are marked as hole No. 2, hole No. 3, hole No. 4, and hole No. 5 from right to left.
- the pipetting module 430 includes: a piston rod frame guide rod 431, a piston bracket 432, a plurality of piston cylinders 433, a plurality of piston rods 435, a pipette head mounting portion 436, and a pipetting drive 437.
- the piston rod frame guide rod 431 connects the top plate 410 and the bottom plate 420
- the piston bracket 432 is sleeved on the piston rod frame guide rod 431 and is located between the top plate 410 and the bottom plate 420, and the piston bracket 432 can slide up and down along the piston rod frame guide rod 431.
- a plurality of second through holes 423 are provided on the bottom plate 420, and the piston cylinder 433 is provided in the second through hole 423, and each piston cylinder 433 has a accommodating chamber 434; one end of the piston rod 435 is connected to the piston bracket 432, and the other end can extend into the accommodating chamber 434 of the piston cylinder 433; the tip mounting portion 436 is provided on the bottom plate 420, and is used to install the tip 3161, and the tip mounting portion 436 is provided with a vent hole 4361, and the vent hole 4361 is connected to the bottom of the piston cylinder 433; the pipetting drive component 437 is provided on the top plate 410, and the output end of the pipetting drive component 437 is transmission-connected to the piston bracket 432, and is used to drive the piston bracket 432 to rise and fall.
- the liquid transfer drive 437 is a third motor 4371, and the output end of the third motor 4371 can be connected to the piston support 432 through a transmission assembly.
- the output end of the third motor 4371 can be connected to a lead screw, and the rotational motion of the motor is converted into a linear motion through the lead screw, and then the piston support 432 is driven to rise and fall by controlling the forward and reverse rotation of the third motor 4371.
- the liquid transfer drive 437 can also be a cylinder, and the output end of the cylinder is directly connected to the piston support 432, and the piston support 432 is driven to rise and fall through the telescopic movement of the cylinder.
- a pipetting reset switch 411 may be provided on the top plate 410 , and when the pipetting reset switch 411 is triggered, the pipetting drive 437 may automatically stop, even if the piston support 432 returns to the initial position.
- the piston rod frame guide rod 431 is set to 4, which is used to support the connection between the top plate 410 and the bottom plate 420.
- the piston cylinder 433, the piston rod 435, the second through hole 423 and the tip mounting portion 436 are all coaxially arranged and correspond one to one.
- the piston rod 435 is set to 24, so the number of the piston cylinder 433, the second through hole 423 and the tip mounting portion 436 is also set to 24. It should be noted that the number of the piston cylinder 433, the piston rod 435 and the tip mounting portion 436 can be set according to the actual needs of nucleic acid extraction, and no specific limitation is made here. In this way, when the pipetting drive 437 drives the 24 piston rods 435 to enter the piston cylinder 433 relatively centered.
- the pipetting module 430 further includes: a head ejection plate 438 and a head ejection elastic guide rod 439.
- the head ejection plate 438 is movably disposed on the head mounting portion 436.
- the head ejection elastic guide rod 439 is disposed on the head ejection plate 438.
- the bottom plate 420 is provided with a head ejection elastic guide rod through hole 424.
- the head ejection elastic guide rod 439 passes through the head ejection elastic guide rod through hole 424 and extends toward the piston bracket 432.
- the piston bracket 432 is driven downward by the pipetting driving member 437, and the piston bracket 432 pushes the head ejection elastic guide rod 439 downward, thereby causing the head ejection elastic guide rod 439 to push the head ejection plate 438 downward, and the head 3161 mounted on the head mounting portion 436 is unloaded by the force of the head ejection plate 438.
- the pipetting reset switch 411 is triggered, the pipetting drive 437 stops automatically, the piston bracket 432 returns to the initial position, the piston bracket 432 leaves the suction head ejection elastic guide rod 439, and the suction head ejection elastic guide rod 439 returns to the initial position under the elastic force, so that the suction head ejection plate 438 is reset.
- a first sealing ring 450 is provided at the contact surface between the tip mounting portion 436 and the tip ejection plate 438, which can further enhance the sealing and stability of the contact between the tip mounting portion 436 and the tip ejection plate 438.
- a second sealing ring 460 is also provided on the tip mounting portion 436 to prevent the tip mounting portion 436 from leaking a sample and causing contamination during the pipetting operation after the tip 3161 is installed.
- a third sealing ring 470 is provided on the contact surface between the piston cylinder 433 and the second through hole 423 to prevent the piston cylinder 433 from moving in the second through hole 423 when the pipetting drive 437 drives the piston bracket 432 to move up and down, thereby further enhancing the sealing and stability of the contact between the piston cylinder 433 and the second through hole 423.
- the pipetting module 430 can be adjusted to reach the specified position, so that the pipetting module 430 can complete operations such as loading, pipetting, mixing, and withdrawing the pipette tip 3161, further improving the degree of automation of the pipette module 430.
- a film is usually placed on the surface of the functional wells 310 on the reagent kit carrier 300 to prevent the consumables of the functional wells 310 on the reagent kit carrier 300 from being contaminated.
- the film on the functional wells 310 is torn off manually, which can easily cause contamination of the nucleic acid sample. Therefore, in order to minimize contamination during the experiment, the gene detection processing device 1 of the present application is used in the pipetting process.
- the module 430 is also provided with a film piercing module 480. Through the joint regulation of the horizontal moving module 210 and the vertical lifting module 220, after the film piercing module 480 reaches the designated position, the sealing film is pierced by controlling the film piercing module 480.
- the film piercing module 480 may be disposed on the rear side of the pipetting module 430 and away from the magnetic absorption module 440.
- the film piercing module 480 includes: a plurality of piercing needles 481, and the piercing needles 481 are connected to the piston bracket 432.
- the piston bracket 432 is driven to rise and fall by the pipetting drive 437, and the piercing needles 481 are driven to rise and fall, so that the piercing needles 481 pierce the sealing film and perform the film piercing operation.
- the number of the piercing needles 481 corresponds to the number of the piston cylinder 433, the second through hole 423 and the tip mounting portion 436, and is also set to 24.
- the magnetic attraction module 440 includes: a magnetic rod frame guide rod 441, a magnetic rod bracket 442, a plurality of magnetic rods 443, a magnetic sleeve mounting portion 444, and a magnetic rod driving member 445.
- the magnetic rod frame guide rod 441 connects the top plate 410 and the bottom plate 420
- the magnetic rod bracket 442 is sleeved on the magnetic rod frame guide rod 441 and is located between the top plate 410 and the bottom plate 420
- the magnetic rod bracket 442 can slide up and down along the magnetic rod frame guide rod 441
- the bottom plate 420 is provided with a plurality of first through holes 421, and one end of a plurality of magnetic rods 443 is connected to the magnetic rod bracket 442, and the other end can pass through the first through hole 421.
- a magnetic sleeve mounting portion 444 for mounting the magnetic rod sleeve 3151 is provided on the bottom plate 420.
- the magnetic sleeve mounting portion 444 is designed as a hollow structure to allow the magnetic rod 443 to pass through.
- a magnetic rod driving component 445 is provided on the top plate 410. The output end of the magnetic rod driving component 445 is transmission-connected to the magnetic rod bracket 442 for driving the magnetic rod bracket 442 to move up and down.
- the transmission principle of the magnetic rod driver 445 can be consistent with the transmission principle of the aforementioned liquid transfer driver 437, and the magnetic rod driver 445 is a fourth motor 4451, and the output end of the fourth motor 4451 can be connected to the magnetic rod support 442 through a transmission assembly.
- the output end of the fourth motor 4451 can be connected to a lead screw, and the rotational motion of the motor is converted into a linear motion through the lead screw, and then the forward and reverse rotation of the fourth motor 4451 is controlled to drive the magnetic rod support 442 to rise and fall.
- the magnetic rod driver 445 can also be a cylinder, and the output end of the cylinder is directly connected to the magnetic rod support 442, and the magnetic rod support 442 is driven to rise and fall through the telescopic movement of the cylinder.
- liquid transfer driver 437 and the magnetic rod driver 445 are disposed on the same top plate 410 , but the liquid transfer driver 437 and the magnetic rod driver 445 do not interfere with each other and are independently controlled.
- a magnetic rod reset switch 412 may be provided on the top plate 410 .
- the magnetic rod driving member 445 may automatically stop, that is, the magnetic rod support 442 may be restored to the initial position.
- the magnetic rod support 442 and the magnetic rod support guide rod 441 in the magnetic absorption module 440 can be consistent with the structure of the piston support 432 and the piston rod support guide rod 431 in the pipetting module 430. Therefore, the magnetic rod support guide rod 441 can also be set to 4, which is used to support the connection between the top plate 410 and the bottom plate 420.
- the magnetic rod 443, the first through hole 421, and the magnetic sleeve mounting portion 444 are all coaxially arranged and correspond one to one.
- the number of magnetic rods 443 is consistent with the number of piston rods 435, and the magnetic rods 443 are also set to 24.
- the number of magnetic rods 443, the first through hole 421, and the magnetic sleeve mounting portion 444 is also set to 24. It should be noted that the number of magnetic rods 443, the first through hole 421, and the magnetic sleeve mounting portion 444 can be set according to the actual needs of nucleic acid extraction, and no specific limitation is made here. With such arrangement, when the magnetic rod driving member 445 drives the 24 magnetic rods 443 , they can enter the magnetic sleeve mounting portion 444 and the magnetic rod sleeve 3151 relatively centrally.
- the magnetizing module 440 further includes: a demagnetizing rod sleeve plate 446 and a demagnetizing rod sleeve elastic guide rod 447.
- the demagnetizing rod sleeve plate 446 is movably disposed on the magnetic sleeve mounting portion 444, and the demagnetizing rod sleeve elastic guide rod 447 is disposed on the demagnetizing rod sleeve plate 446.
- a demagnetizing rod sleeve elastic guide rod through hole 422 is further disposed on the bottom plate 420, and the demagnetizing rod sleeve elastic guide rod 447 passes through the demagnetizing rod sleeve elastic guide rod through hole 422 and extends toward the magnetic rod bracket 442.
- the principle of the demagnetizing rod sleeve 3151 of the magnetic absorption module 440 is consistent with the principle of the demagnetizing head 3161 of the pipetting module 430.
- the magnetic rod driving member 445 drives the magnetic rod bracket 442 to move downward, and the magnetic rod bracket 442 pushes the demagnetizing rod sleeve elastic guide rod 447 downward, thereby causing the demagnetizing rod sleeve elastic guide rod 447 to push the demagnetizing rod sleeve plate 446 downward, and the magnetic rod sleeve 3151 installed on the magnetic sleeve mounting portion 444 is unloaded by the force of the demagnetizing rod sleeve plate 446.
- the magnetic rod reset switch 412 is triggered, the magnetic rod driving member 445 stops automatically, the magnetic rod bracket 442 returns to the initial position, the magnetic rod bracket 442 leaves the demagnetizing rod sleeve elastic guide rod 447, and the demagnetizing rod sleeve elastic guide rod 447 returns to the initial position under the elastic force, so that the demagnetizing rod sleeve plate 446 is reset.
- the temperature control module 500 is arranged on the base 100 and is located below the reagent kit carrier 300, and is used to adjust the temperature in the lysis and elution steps.
- the temperature control module 500 includes: a reagent area temperature control unit 510 and a reaction area temperature control unit 520. Among them, the reagent area temperature control unit 510 is used to control the temperature of the reagent in the reagent well 311; the reaction area temperature control unit 520 is used to control the temperature of the reagent in the elution tube well 312.
- the reagent zone temperature control unit 510 includes: a first processing block 511, a first cooling block 512, a first heat insulating block 513, and a first heat sink 514.
- the first processing block 511 is located at the bottom of the reagent well 311; the first cooling block 512 is located at the bottom of the first processing block 511; bottom; a first insulation block 513 is connected to the first refrigeration block 512; a first radiator 514 is provided at the bottom of the first refrigeration block 512 for heat dissipation.
- the first processing block 511 is disposed at the bottom of the first volume reagent well 3111, and can be adapted to various types of first volume reagent wells 3111 supporting different binding systems.
- the first processing block 511 is configured in a groove shape, and fits with the first volume reagent well 3111.
- the first volume reagent well 3111 can be heated or cooled according to experimental needs. When the first volume reagent well 3111 is cooled, the reagent after cracking and heating can quickly reach the required temperature range, thereby accelerating the reaction process.
- the reaction zone temperature control unit 520 includes: a second heating block 521, a second heat insulating block 522, and a second heat sink 523.
- the second heating block 521 is located at the bottom of the elution tube hole 312; the second heat insulating block 522 is disposed on the second heating block 521; and the second heat sink 523 is disposed at the bottom of the second heating block 521 for heat dissipation.
- Figure 16 is a flow chart of a gene detection and processing method provided in an embodiment of the present application.
- the method uses the gene detection and processing device 1 as described in any of the above embodiments, and includes the following steps:
- Step S110 driving the composite function module 400 to the corresponding function hole position 310 through the station adjustment module 200 .
- the No. 1 hole of the corresponding reagent wells 311 on the reagent cartridge carrier 300 is the first volume reagent well 3111, in which the binding solution is pre-packaged; the No. 2 hole is the second volume reagent well 3112, in which the magnetic beads are installed; the No. 3 hole is the second volume reagent well 3112, in which the washing solution 1 is installed; the No. 4 hole is the second volume reagent well 3112, in which the washing solution 2 is installed; the No. 5 hole is the second volume reagent well 3112, in which the washing solution 3 is installed.
- the lysed serum sample is pre-added in the sample tube well 314.
- the elution solution is pre-placed in the elution tube well 312.
- the horizontal position of the film piercing module 480 can be adjusted by controlling the horizontal moving module 210, and the height position of the film piercing module 480 can be adjusted by controlling the vertical lifting module 220, so as to complete the film piercing operation.
- the horizontal driving member 215 drives the first transmission member 214 to rotate, driving the horizontal slider assembly 212 to move on the first transmission member 214, so that the horizontal slider assembly 212 can move horizontally on the horizontal slide rail 211, and adjust the piercing needle 481 on the film piercing module 480 to reach the reagent hole 311.
- the vertical driving member 226 drives the second transmission member 225 to rotate, thereby driving the vertical slider assembly 223 to move on the second transmission member 225, so that the vertical slider assembly 223 descends on the vertical slide rail 222, thereby driving the lifting installation plate 224 to descend, and then driving the film piercing module 480 connected to the lifting installation plate 224 to descend, so that the piercing needle 481 extends into the reagent hole 311, pierces the sealing film on the reagent hole 311, and completes the film piercing operation.
- This process can complete the film piercing operation of 24 reagent holes 311 at one time.
- Step S120 Performing pipetting and mixing operations through the pipetting module 430 and performing magnetic attraction operations through the magnetic attraction module 440 to achieve gene extraction and detection processing.
- step S120 the pipetting module 430 performs pipetting and mixing operations, which specifically include steps S121 to S123 .
- Step S121 performing a loading operation of the pipette tip 3161 through the pipetting module 430 .
- the pipetting module 430 performs a loading operation on the pipette tip 3161.
- the specific loading steps are as follows: the pipetting drive 437 drives the piston bracket 432 to descend, thereby driving the multiple piston rods 435 to move downward, and the multiple piston rods 435 are correspondingly inserted into the accommodating cavity 434 in the piston cylinder 433 located on the bottom plate 420.
- the pipetting drive 437 continues to drive the piston bracket 432 to descend, the top of the piston rod 435 contacts the bottom of the piston cylinder 433. Under the joint regulation of the horizontal moving module 210 and the vertical lifting module 220, the pipetting is completed.
- the height of the pipetting module 430 is adjusted by controlling the vertical lifting module 220, so that the tip mounting portion 436 gradually approaches the tip 3161 at the tip hole 316 under the driving force of the pipetting drive 437, and then the piston bracket 432 is driven down by the pipetting drive 437.
- the tip 3161 is loaded onto the tip mounting portion 436 and firmly clamped on the tip mounting portion 436, completing the loading of the tip 3161.
- 24 tips 3161 can be loaded at one time, which improves efficiency.
- the pipetting drive 437 can be automatically stopped by triggering the pipetting reset switch 411, and the piston bracket 432 returns to the initial position.
- Step S122 transferring the reagent to be detected between the multiple functional wells 310 through the pipetting module 430 .
- the sample addition operation needs to be performed.
- the specific steps are as follows: by controlling the horizontal moving module 210, the pipetting module 430 is driven to move in the horizontal direction, so that the pipette tip 3161 on the pipetting module 430 moves to the top of the sample tube hole 314, and then the pipette module 430 is driven down by controlling the vertical lifting module 220, and the bottom of the pipette tip 3161 is inserted into the sample tube hole 314, and the piston bracket 432 is driven to rise by controlling the pipetting drive 437, so that the multiple piston rods 435 connected to the piston bracket 432 are pulled upward from the piston cylinder 433, and the serum sample that has been lysed in the sample tube hole 314 is extracted into the pipette tip 3161 through the pipette tip through hole 31611 in the pipette tip 3161 by using the same principle as the syringe.
- the vertical lifting module 220 is controlled to drive the pipetting module 430 to rise, so that the suction tip 3161 on the pipetting module 430 leaves the sample tube hole 314, and then the horizontal moving module 210 is controlled to drive the pipetting module 430 to move to the first volume reagent hole 3111 (i.e., hole 1) in the reagent hole 311, and the piston bracket 432 is driven to descend by controlling the pipetting drive 437, thereby driving the multiple piston rods 435 connected to the piston bracket 432 to advance to the bottom of the piston cylinder 433, so that the lysed serum sample in the suction tip 3161 is injected into the first volume reagent hole 3111 (i.e., hole 1), completing the sample transfer.
- this step can complete the transfer of 24 samples at one time, greatly improving the sample processing efficiency.
- Step S123 The station adjustment module 200 drives the pipetting module 430 to move in a preset direction, so that the pipetting module 430 can fully mix the reagent to be detected.
- step S122 the pipette tip 3161 on the pipetting module 430 is kept at the first volume reagent hole position 3111 (i.e., hole No. 1) and does not move.
- the first processing block 511 in the reagent area temperature control unit 510 is controlled to cool the first volume reagent hole position 3111 (i.e., hole No. 1) of hole No. 1 to cool down hole No. 1 to room temperature.
- the horizontal moving module 210 is controlled to move back and forth in the horizontal direction, thereby driving the suction head 3161 on the pipetting module 430 to move back and forth in the first reagent well position 3111 (i.e., well 1).
- the piston bracket 432 is driven to rise by controlling the pipetting drive 437, so that the multiple piston rods 435 connected to the piston bracket 432 are pulled upward from the piston cylinder 433, and the serum sample in the first reagent well position 3111 (i.e., well 1) is extracted into the suction head 3161.
- the vertical lifting module 220 is controlled to move in the vertical direction, thereby driving the suction head 3161 on the pipetting module 430 to move upward, so that the suction head 3161 leaves the first volume reagent hole 3111 (i.e., hole 1), and then the vertical lifting module 220 is controlled to move downward in the vertical direction, thereby driving the suction head 3161 on the pipetting module 430 to move downward, so that the suction head 3161 enters the first volume reagent hole 3111 (i.e., hole 1) again, and then the piston bracket 432 is driven to descend by controlling the pipetting drive 437, driving the multiple piston rods 435 connected to the piston bracket 432 to advance to the bottom of the piston cylinder 433, so that the lysed serum sample in the suction head 3161 is injected into the first volume reagent hole 3111 (i.e., hole 1) again, thereby completing one sample throughput.
- 24 samples can be fully mixed at one time. Repeat the above operation several times.
- the pipetting module 430 drives the suction head 3161 to move horizontally left and right while moving vertically up and down.
- the pipetting module 430 cooperates with the suction head 3161 to repeatedly pump and discharge the serum sample, so as to achieve the purpose of fully mixing the serum sample and the binding liquid.
- the above-mentioned blowing and mixing process can last for 15 minutes to allow the serum sample to be fully mixed with the binding liquid in the first volume reagent hole 3111 (i.e., hole No. 1).
- the pipetting reset switch 411 can be triggered, and the pipetting drive 437 can automatically stop, so that the piston bracket 432 returns to the initial position.
- the horizontal movement control mode of the horizontal moving module 210 and the vertical movement control mode of the vertical lifting module 220 have been described in detail in the previous step S110, and will not be repeated here.
- the volume of the first volume reagent well 3111 i.e., well No. 1
- the amplitude of the horizontal reciprocating movement of the horizontal moving module 210 and the amplitude of the vertical reciprocating movement of the vertical lifting module 220 should not be too large, otherwise it is easy for the suction head 3161 to touch the hole wall of the first volume reagent well 3111 (i.e., well No. 1) during the mixing operation, resulting in sample contamination and reduced detection accuracy.
- the software control program can be designed in advance to accurately control the movement amplitude, action time and other parameters of the horizontal moving module 210 and the vertical lifting module 220, and the above-mentioned software control method can refer to the relevant control method in the prior art, which will not be repeated here.
- the pipette tip 3161 needs to be replaced.
- the used pipette tip 3161 is unloaded, which specifically includes the following steps: by controlling the horizontal moving module 210, the pipette module 430 is driven to move in the horizontal direction, so that the pipette tip 3161 on the pipette module 430 moves to the position of withdrawing the pipette tip 3161, and then by controlling the pipette drive 437 to work, the pipette drive 437 drives the piston bracket 432 to descend.
- the bottom of the piston bracket 432 touches the elastic guide rod 439 of the pipette tip, and under the driving force of the pipette drive 437, the piston bracket 432 pushes the elastic guide rod 439 of the pipette tip downward, thereby causing the elastic guide rod 439 of the pipette tip to be withdrawn.
- the suction head ejection plate 438 is pushed downward, so that the suction head 3161 installed on the suction head mounting portion 436 is unloaded and removed through the suction head ejection plate 438 .
- a waste liquid or waste material recovery box may be installed at the position where the suction head 3161 is removed in this step, and the used suction head 3161 after unloading may fall into the waste liquid or waste material recovery box.
- a new suction tip 3161 is reloaded and the magnetic beads are transferred.
- the specific steps of loading the suction tip 3161 can refer to the description of step S121 and will not be repeated here.
- the transfer of magnetic beads is performed by the pipetting module 430 in the same manner as step S122.
- the specific steps are as follows: by controlling the horizontal moving module 210, the pipetting module 430 is driven to move in the horizontal direction, so that the suction head 3161 on the pipetting module 430 moves to the second volume reagent hole 3112 (i.e., hole 2), and then the pipetting module 430 is driven down by controlling the vertical lifting module 220, and the bottom of the suction head 3161 is inserted into the second volume reagent hole 3112 (i.e., hole 2), and the piston bracket 432 is driven to rise by controlling the pipetting drive 437, so that the multiple piston rods 435 connected to the piston bracket 432 are pulled upward from the piston cylinder 433, and the magnetic bead reagent in the second volume reagent hole 3112 (i.e., hole 2) is extracted into the suction head 3161.
- the vertical lifting module 220 is controlled to drive the pipetting module 430 to rise, so that the pipette tip 3161 on the pipetting module 430 leaves the second volume reagent hole 3112 (i.e., hole No. 2), and then the horizontal moving module 210 is controlled to drive the pipetting module 430 to move to the first volume reagent hole 3111 (i.e., hole No.
- step S120 the magnetic attraction module 440 performs a magnetic attraction operation, which specifically includes steps S124 to S126 .
- Step S124 performing a loading operation of the magnetic rod sleeve 3151 through the magnetic attraction module 440 .
- step S124 Before performing step S124, it is also necessary to unload the used suction head 3161 and reload the magnetic rod sleeve 3151.
- the loading operation steps of the magnetic rod sleeve 3151 are the same as the loading operation steps of the suction head 3161.
- the specific loading steps are as follows: by controlling the horizontal moving module 210, the magnetic absorption module 440 is driven to move in the horizontal direction, so that the magnetic absorption module 440 moves to the top of the magnetic rod sleeve hole 315, and the magnetic rod driving member 445 drives the magnetic rod bracket 442 to descend, thereby driving multiple magnetic rods 443 to move downward, when the magnetic rod driving member 445 drives the magnetic rod bracket 442 to descend until the top of the magnetic rod 443 passes through the magnetic sleeve mounting portion 444 until the top of the magnetic rod 443 fits with the tip of the magnetic rod sleeve 3151, the magnetic rod sleeve 3151 is installed on the magnetic sleeve mounting portion 444 and firmly clamped on the magnetic sleeve mounting portion 444, thereby completing the loading of the magnetic rod sleeve 3151.
- 24 magnetic rod sleeves 3151 can be loaded at one time.
- Step S125 The station adjustment module 200 drives the magnetic attraction module 440 to move to the corresponding functional hole 310 equipped with magnetic beads, and drives the magnetic attraction module 440 to move in a preset direction, so that the magnetic attraction module 440 performs a magnetic attraction operation.
- step S123 magnetic beads remain in the first volume reagent hole 3111 (i.e., hole No. 1).
- the magnetic absorption module 440 is driven to move to the first volume reagent hole 3111 (i.e., hole No. 1) in the reagent hole 311, and by controlling the magnetic rod driving member 445, the magnetic rod bracket 442 is driven to descend, thereby driving the multiple magnetic rods 443 to move downward, so that the magnetic rod sleeve 3151 installed on the magnetic sleeve mounting part 444 extends into the first volume reagent hole 3111 (i.e., hole No. 1).
- the horizontal moving module 210 is controlled to move left and right in the horizontal direction, driving the magnetic rod sleeve 3151 on the magnetic absorption module 440 to move back and forth in the first volume reagent hole 3111 (i.e., hole No. 1), and then the vertical lifting module 220 is controlled to move back and forth in the vertical direction, driving the magnetic rod sleeve 3151 and the magnetic rod 443 on the magnetic absorption module 440 to move back and forth up and down at the same time, so that the magnetic beads in the first volume reagent hole 3111 (i.e., hole No. 1) are fully and completely adsorbed on the magnetic rod sleeve 3151.
- the magnetic rod driving member 445 drives the magnetic rod 443 to be inserted into the magnetic rod sleeve 3151 and remains motionless, otherwise the magnetic beads will fall off the magnetic rod sleeve 3151.
- the role of binding is to make the magnetic beads specifically bind to the nucleic acid molecules.
- This process often requires the use of an effective mixing method. Therefore, the magnetic rod sleeve 3151 is driven by the magnetic absorption module 440 to move horizontally left and right and vertically up and down, so that the magnetic beads can be fully adsorbed on the magnetic rod sleeve 3151, so that the magnetic beads and the nucleic acid molecules are specifically bound and fully contacted.
- the amplitude of the horizontal reciprocating movement of the horizontal moving module 210 and the amplitude of the vertical reciprocating movement of the vertical lifting module 220 in the vertical direction should not be too large.
- Step S126 driving the magnetic attraction module 440 to perform a demagnetization operation through the station adjustment module 200.
- the adsorbed magnetic beads need to be released by the magnetic absorption module 440, i.e., the demagnetization operation.
- the specific steps of the demagnetization operation are as follows: by controlling the vertical lifting module 220, the magnetic absorption module 440 is driven to rise, so that the magnetic rod sleeve 3151 leaves the first volume reagent hole 3111 (i.e., hole 1). At this time, by controlling the horizontal movement module 210 to translate in the horizontal direction, the magnetic absorption module 440 Together with the magnetic rod sleeve 3151, it is translated to above the second capacity reagent hole 3112 (i.e., hole No.
- the vertical lifting module 220 is controlled to drive the magnetic absorption module 440 to descend, so that the magnetic rod sleeve 3151 extends into the second capacity reagent hole 3112 (i.e., hole No. 3).
- the magnetic rod bracket 442 is driven to rise by the magnetic rod driving member 445, thereby driving multiple magnetic rods 443 to move upward, so that the magnetic rod 443 rises and slowly separates from the magnetic rod sleeve 3151. Due to the disappearance of the magnetic absorption effect, the magnetic beads attached to the magnetic rod sleeve 3151 are released into the washing solution 1 in the second capacity reagent hole 3112 (i.e., hole No. 3).
- the magnetic rod cover 3151 on the magnetic absorption module 440 is driven to move back and forth up and down, so that the magnetic rod cover 3151 that slowly removes the magnetic rod 443 slowly oscillates up and down in the washing solution 1 for several times, and the magnetic beads on the surface of the magnetic rod cover 3151 are fully released into the washing solution 1 in the second volume reagent hole 3112 (i.e., hole No. 3).
- the vertical lifting module 220 is controlled again to drive the magnetic rod cover 3151 on the magnetic absorption module 440 to leave the second volume reagent hole 3112 (i.e., hole No. 3), thereby completing the demagnetization operation.
- the magnetic rod sleeve 3151 needs to be unloaded.
- the specific unloading steps are as follows: by controlling the horizontal moving module 210, the magnetic absorption module 440 is driven to move in the horizontal direction, so that the magnetic rod sleeve 3151 on the magnetic absorption module 440 moves to the position where the magnetic rod sleeve 3151 is removed, and then by controlling the magnetic rod driving member 445 to work, the magnetic rod driving member 445 drives the magnetic rod bracket 442 to descend.
- the bottom of the magnetic rod bracket 442 touches the elastic guide rod 447 of the demagnetization rod sleeve, and under the driving force of the magnetic rod driving member 445, the magnetic rod bracket 442 pushes the elastic guide rod 447 of the demagnetization rod sleeve downward, thereby causing the elastic guide rod 447 of the demagnetization rod sleeve to push the demagnetization rod sleeve plate 446 downward, so that the magnetic rod sleeve 3151 installed on the magnetic sleeve mounting portion 444 is unloaded and removed by the force of the demagnetization rod sleeve plate 446.
- the position where the magnetic rod cover 3151 is removed in this step can be the same as the position where the suction head 3161 is removed, that is, the used magnetic rod cover 3151 and the used suction head 3161 after unloading can be thrown into the waste liquid or waste material recycling box together.
- the pipetting module 430 needs to reload the pipette tip 3161 on the pipette tip mounting portion 436, and then perform the washing operation.
- the washing operation is performed by the pipetting module 430, and the specific steps are as follows: through the joint regulation of the horizontal moving module 210 and the vertical lifting module 220, the pipette tip 3161 on the pipetting module 430 is driven to move to the second volume reagent hole 3112 (i.e., hole No. 3), and the washing solution 1 in the second volume reagent hole 3112 (i.e., hole No.
- step S123 is blown and mixed for 1 minute in the same manner as step S123, and fully washed.
- the combination of the magnetic rod sleeve 3151 and the magnetic rod 443 can also be used during the washing process, but before that, the magnetic rod sleeve 3151 needs to be reloaded on the magnetic sleeve mounting portion 444.
- the washing process is consistent with the method of magnetic attraction and demagnetization in steps S125 and S126, and will not be repeated here.
- the first magnetic absorption operation needs to be performed.
- the magnetic frame 600 is disposed on the base 100, and a magnet is disposed at one end of the magnetic frame 600, and the other end is connected to the magnetic driving member 610.
- the magnetic driving member 610 may be a cylinder.
- the pipette tip 3161 on the pipetting module 430 is driven to move to the second volume reagent hole 3112 (i.e., hole No. 4), and the washing solution 2 in the second volume reagent hole 3112 (i.e., hole No. 4) is blown and mixed for 1 minute in the same manner as step S123 to fully wash.
- the combination of the magnetic rod sleeve 3151 and the magnetic rod 443 can also be used during the secondary washing process, which will not be repeated here.
- a second magnetic absorption operation is required.
- the aforementioned magnetic absorption method of the magnetic stand 600 can be used to absorb the magnetic beads in the second volume reagent well 3112 (i.e., well No. 4) to the inner wall of the suction head 3161 through the magnet until all the magnetic beads are captured.
- this magnetic absorption operation can also use the magnetic absorption method of the combination of the magnetic rod sleeve 3151 and the magnetic rod 443 described above.
- the suction head 3161 on the pipetting module 430 is driven to move to the second volume reagent well 3112 (i.e., well No. 5) through the joint regulation of the horizontal moving module 210 and the vertical lifting module 220.
- the washing solution 3 in the second volume reagent well 3112 i.e., well No. 5 is blown and mixed for 1 minute in the same manner as step S123 to fully wash.
- the combination of the magnetic rod sleeve 3151 and the magnetic rod 443 can also be used in the three washing processes, which will not be repeated here.
- the third magnetic absorption operation is required. This can be done by using the aforementioned magnetic absorption method of the magnetic rack 600, where the magnetic beads in the second volume reagent well 3112 (i.e., well No. 5) are absorbed onto the inner wall of the suction head 3161 by the magnet on the magnetic rack 600 until all the beads are absorbed. The magnetic beads are all captured.
- this magnetic attraction operation can also adopt the magnetic attraction method of the combination of the magnetic rod sleeve 3151 and the magnetic rod 443 described above.
- the particles bound to the magnetic beads and nucleic acids are cleaned to remove some impurities captured by the magnetic beads while capturing nucleic acids, such as proteins, salts, etc.
- the suction head 3161 can be used for washing and mixing operations as needed, and the suction head 3161 can be used in conjunction with the magnetic rack 600 to perform magnetic absorption operations; or a combination of a magnetic rod sleeve 3151 and a magnetic rod 443 can be used for washing, mixing or magnetic absorption operations, and this application does not make specific restrictions on this.
- the suction tip 3161 After several washes, an elution operation is required. Before the elution operation, the suction tip 3161 also needs to be replaced. After loading a new suction tip 3161, the elution operation is performed.
- the specific elution steps are as follows: by controlling the horizontal moving module 210 and the vertical lifting module 220, as well as the liquid transfer drive 437, the suction tip 3161 is driven to transfer the magnetic beads after magnetic absorption in the second volume reagent hole 3112 (i.e., hole No.
- the magnetic drive 610 drives the magnetic rack 600 away from the position of the suction tip 3161, and by controlling the vertical lifting module 220, the suction tip 3161 on the liquid transfer module 430 is driven to extend into the elution tube hole 312, and then the mixing is performed for 6 minutes according to the method of step S123.
- the pipetting drive 437 drives the piston bracket 432 to rise, the multiple piston rods 435 connected to the piston bracket 432 are pulled upward from the piston cylinder 433, and the eluate in the elution tube hole 312 is extracted into the suction head 3161.
- the magnetic drive 610 drives the magnetic frame 600 to approach the position of the suction head 3161 and starts to attract magnets. After the magnets are fully attracted, the pipetting drive 437 is used to inject the eluate in the suction head 3161 back into the elution tube hole 312.
- the suction head 3161 with the magnetic beads adsorbed thereon is moved to the position of the second volume reagent well 3112 (i.e., well No. 3), and then the mixture is mixed by blowing for a few seconds in accordance with the method of step S123, and the magnetic frame 600 is driven away from the position of the suction head 3161 by the magnetic driving member 610, so that the magnetic beads on the suction head 3161 are released into the washing waste liquid of the second volume reagent well 3112 (i.e., well No. 3).
- the gene detection processing device 1 in the present application integrates the pipetting module 430 and the magnetic absorption module 440, which saves space, makes the structure more compact, and improves the degree of automation of the gene detection processing device 1. Secondly, the integration of the pipetting module 430 and the magnetic absorption module 440 enables the gene detection processing device 1 to simultaneously process large and small volume reagents, solving the pain point that the industry often needs to use a large sample volume, but needs to obtain a small volume elution sample. The use of the gene detection processing device 1 of the present application can achieve efficient mixing of large-volume binding systems and can meet more application scenarios.
- the horizontal moving module 210 drives the pipetting module 430 to move left and right
- the vertical lifting module 220 drives the pipetting module 430 and the magnetic absorption module 440 to move up and down.
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Abstract
本申请公开了一种基因检测处理设备,该基因检测处理设备包括:基座;试剂盒载架,设于基座上,试剂盒载架上设有多个功能孔位;工位调节模块,设于基座上;复合功能模块,与工位调节模块连接,工位调节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:顶板,与工位调节模块连接;底板,与工位调节模块连接;移液模块,连接顶板和底板,用于进行移液操作和试剂混合操作;吸磁模块,与移液模块相对设置,用于进行磁珠吸附操作。本申请还公开了使用该基因检测处理设备进行基因检测处理的方法。本申请中的基因检测处理设备将移液模块和吸磁模块集成在一起,节省了空间,使结构更加紧凑。该基因检测处理设备具备同时处理大体积和小体积试剂的功能,能够满足更多的应用场景。
Description
相关申请的交叉引用
本申请要求于2022年11月10日提交国家知识产权局的申请号为202211405808.9、名称为“基因检测处理设备及方法”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,涉及一种基因检测处理设备及方法。
基因检测已成为临床分子实验中主要使用的研究手段。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。核酸提取场景中,通常使用的是基于磁珠法的磁棒式磁珠上吸法提取技术,利用纳米磁珠在不同的环境下与核酸分子特异性结合与脱离的特性来实现核酸从样本中提纯的目的。提取的步骤一般分为裂解、结合、数次洗涤和洗脱。
核酸提取的样本对象有很多,有血液类、体液、组织切片、环境样本等,且样本含有的核酸浓度有高有低,其中低浓度样本的提取最为困难,常见于游离核酸提取场景,比如肿瘤早筛中的体液提取(痰液、尿液、粪便处理液等)和产前早筛中的羊水、血浆等样本的核酸提取。由于这类样本中目标核酸含量低,往往需要投入较多的样本量进行核酸提取。
在核酸提取的结合步骤下,当样本量较多时(有时高达15ml),需要使核酸与磁珠充分混合,才能提高核酸提取的效率;随着结合体系的不断增加,结合完成后能否充分捕获液体中的已经结合了核酸分子的磁珠颗粒也是影响核酸提取效率的关键因素。此外,由于核酸含量低,为了满足检测灵敏度要求,往往需要极低的洗脱体积来提高核酸洗脱产物的浓度。对于小体积的洗脱液,现有技术如磁套升降/左右/自旋混合法都因为耗材太粗,液体太少,导致混合时磁珠与液体接触不充分,洗脱不完全,加之移液器混合因为其吸头较细,只能够满足很小体积混合需求。
对于大的结合体系的核酸提取,现有的核酸提取设备在进行核酸样本洗脱和吸磁处理时,通常分别使用独立的移液器进行样本转移和洗涤处理,再通过独立的磁套升降装置进行吸磁和脱磁处理,这样使得核酸提取设备的整体结构较大较复杂,空间占用大,自动化程度低,从而导致核酸提取的效率降低。
发明内容
本申请的目的是提供一种基因检测处理设备,将移液模块和吸磁模块集成在一起,节省了空间,使结构更加紧凑,提高了基因检测处理设备的自动化程度。移液模块和吸磁模块的集成使基因检测处理设备具备同时处理大体积和小体积试剂的功能,能够满足更多的应用场景。
本申请的实施例是这样实现的:第一方面,本申请提供一种基因检测处理设备,包括:基座;试剂盒载架,设于所述基座上,所述试剂盒载架上设有多个功能孔位;工位调节模块,设于所述基座上;复合功能模块,与所述工位调节模块连接,所述工位调节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:顶板,与所述工位调节模块连接;底板,与所述工位调节模块连接;移液模块,连接所述顶板和所述底板,用于进行移液操作和试剂混合操作;吸磁模块,与所述移液模块相对设置,用于进行磁珠吸附操作。
在上述技术方案中,顶板和底板均与工位调节模块连接,移液模块连接顶板和底板,吸磁模块连接顶板和底板,并且吸磁模块与移液模块相对设置。工位调节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,以使移液模块进行移液操作和试剂混合操作,吸磁模块进行磁珠吸附操作。
移液模块和吸磁模块共用同一个顶板和底板,这样设置,使移液模块和吸磁模块集成在一起,不仅节省空间,使结构更紧凑,降低了操作难度,提高基因检测处理设备的自动化程度。
于一实施例中,所述吸磁模块包括:磁棒架导杆,连接所述顶板和所述底板;磁棒支架,套设于所述磁棒架导杆上,且位于所述顶板和所述底板之间,所述底板上设有若干个第一通孔;若干个磁棒,一端与所述磁棒支架连接,另一端穿过所述第一通孔;磁套安装部,设于所述底板上,用于安装磁棒套;
以及磁棒驱动件,设于所述顶板上,所述磁棒驱动件的输出端与所述磁棒支架传动连接,用于驱动所述磁棒支架进行升降。
在上述技术方案中,通过磁棒驱动件驱动磁棒支架下降,从而带动多个磁棒向下移动,当磁棒驱动件驱动磁棒支架下降到使磁棒顶端穿过磁套安装部直至磁棒顶端与磁棒套尖端贴合,将磁棒套装入到磁套安装部上并稳稳卡紧在磁套安装部上,实现磁棒套的装载。采用上述结构,可提高磁棒套安装的自动化程度。
于一实施例中,所述吸磁模块还包括:退磁棒套板,活动设于所述磁套安装部上;退磁棒套弹性导杆,设于所述退磁棒套板上,所述底板上设有退磁棒套弹性导杆通孔,所述退磁棒套弹性导杆穿过所述退磁棒套弹性导杆通孔,并伸向所述磁棒支架。
在上述技术方案中,通过磁棒驱动件驱动磁棒支架向下移动,磁棒支架向下推动退磁棒套弹性导杆下移,进而使退磁棒套弹性导杆推动退磁棒套板向下移动,通过退磁棒套板的作用力将安装在磁套安装部上的磁棒套卸载。卸载完成后,触发磁棒复位开关,磁棒驱动件自动停止,磁棒支架恢复到初始位置,磁棒支架离开退磁棒套弹性导杆,退磁棒套弹性导杆在弹性作用力下恢复初始位置,使退磁棒套板复位。
于一实施例中,所述磁棒、所述第一通孔、所述磁套安装部均同轴设置,且一一对应。
在上述技术方案中,磁棒个数与活塞杆个数保持一致,如此设置,当磁棒驱动件驱动磁棒可以相对居中的进入磁套安装部以及磁棒套中。
于一实施例中,所述移液模块包括:活塞杆架导杆,连接所述顶板和所述底板,所述底板上设有若干个第二通孔;活塞支架,套设于所述活塞杆架导杆上,且位于所述顶板和所述底板之间;若干个活塞筒,设于所述第二通孔内,所述活塞筒具有容纳腔;若干个活塞杆,一端与所述活塞支架连接,另一端能伸入所述活塞筒内;吸头安装部,设于所述底板上,用于安装吸头,所述吸头安装部内设有通气孔,所述通气孔与所述活塞筒底部连通;以及移液驱动件,设于所述顶板上,所述移液驱动件的输出端与所述活塞支架传动连接,用于驱动所述活塞支架进行升降。
在上述技术方案中,通过移液驱动件驱动活塞支架下降,从而带动多个活塞杆向下移动,并使多个活塞杆对应插入到位于底板上的活塞筒内的容纳腔中,当移液驱动件继续驱动活塞支架下降,使活塞杆顶端接触到活塞筒的底部,在水平移动模块和垂直升降模块的共同调节作用下,移液模块到达试剂盒载架上的吸头孔位处后,通过控制垂直升降模块调整移液模块的高度,使吸头安装部在移液驱动件的驱动力作用下逐渐向吸头孔位处的吸头靠近,再通过移液驱动件驱动活塞支架下降,在移液驱动件的作用力下,使吸头装入到吸头安装部上并稳稳卡紧在吸头安装部上,完成吸头的装载。采用上述结构,可提高吸头安装的自动化程度。
于一实施例中,所述移液模块还包括:退吸头板,活动设于所述吸头安装部上;退吸头弹性导向杆,设于所述退吸头板上,所述底板上设有退吸头弹性导向杆通孔,所述退吸头弹性导向杆穿过所述退吸头弹性导向杆通孔,并伸向所述活塞支架。
在上述技术方案中,通过控制移液驱动件工作,移液驱动件驱动活塞支架下降,在活塞支架下降的过程中,活塞支架底部触碰到退吸头弹性导向杆,并在移液驱动件的驱动作用力下,活塞支架将退吸头弹性导向杆向下推压,进而使退吸头弹性导向杆推动退吸头板下移,从而通过退吸头板将安装在吸头安装部上的吸头卸载脱落。
于一实施例中,所述吸头安装部与所述退吸头板的接触表面设有第一密封圈;所述吸头安装部上还设有第二密封圈;所述活塞筒与所述第二通孔的接触表面设有第三密封圈。
在上述技术方案中,在吸头安装部与退吸头板的接触表面处设有第一密封圈,可以进一步增强吸头安装部与退吸头板接触处的密封性和稳定性。在吸头安装部上还设有第二密封圈,防止吸头安装部在安装吸头后,进行移液操作过程中发生样本泄漏导致污染的问题。在活塞筒与第二通孔的接触表面设有第三密封圈,防止移液驱动件驱动活塞支架进行升降时,活塞筒在第二通孔内发生移动,进而可进一步增强活塞筒与第二通孔的接触处的密封性和稳定性。
于一实施例中,所述活塞杆、所述活塞筒、所述第二通孔、所述吸头安装部均同轴设置,且一一对应。
在上述技术方案中,活塞杆个数与活塞筒个数保持一致,如此设置,当移液驱动件驱动活塞杆可以相对居中的进入活塞筒中。
于一实施例中,所述复合功能模块还包括:刺膜模块,所述刺膜模块包括:若干个刺针,与所述活塞支架连接,所述移液驱动件驱动所述活塞支架进行升降,以使所述刺针进行刺膜操作。
在上述技术方案中,为了尽可能地减少实验过程中的污染,本申请的基因检测处理设备中,在移液模块上还设置了刺膜模块。通过水平移动模块和垂直升降模块的共同调节作用,使刺膜模块到达指定位置后,通过控制刺膜模块刺破封膜。
于一实施例中,所述工位调节模块包括:水平移动模块,设于所述基座上;垂直升降模块,设于所述水平移动模块上;所述复合功能模块设于所述垂直升降模块上。
在上述技术方案中,水平移动模块用于调节复合功能模块在水平方位的移动位置,垂直升降模块用于调节复合功能模块在竖直高度方向的位置。本实施例中,通过水平移动模块和垂直升降模块的共同调节作用,使复合功能模块能够根据需要在试剂盒载架上方移动,并移动到指定的功能孔位所在位置处,从而执行对应的核酸提取过程中的移液、混合吸磁等操作。
于一实施例中,所述水平移动模块包括:水平滑轨,设于所述基座上;水平滑块组件,可移动地设于所述水平滑轨上;水平安装底座,设于所述水平滑块组件上;第一传动件,设于所述基座上,所述水平滑块组件套设于所述第一传动件上;以及水平驱动件,与所述第一传动件连接,用于驱动所述水平滑块组件进行水平方向移动。
在上述技术方案中,水平驱动件与第一传动件传动连接,用于驱动第一传动件转动,进而带动水平滑块组件在第一传动件上移动,从而使水平滑块组件可在水平滑轨上进行水平方向的移动。
于一实施例中,所述垂直升降模块包括:升降安装底座,设于所述水平安装底座上;垂直滑轨,设于所述升降安装底座上;垂直滑块组件,可移动地设于所述垂直滑轨上;升降安装板,设于所述垂直滑块组件上,所述顶板和所述底板均设于所述升降安装板上;第二传动件,设于所述升降安装底座上,所述垂直滑块组件套设于所述第二传动件上;以及垂直驱动件,与所述第二传动件连接,用于驱动所述垂直滑块组件带动所述升降安装板进行升降。
在上述技术方案中,垂直驱动件与第二传动件传动连接,用于驱动第二传动件转动,进而带动垂直滑块组件在第二传动件移动,从而使垂直滑块组件在垂直滑轨上升降,从而带动升降安装板进行升降,进而可以带动升降安装板上设置的移液模块和吸磁模块进行竖直方向上的移动。
于一实施例中,所述功能孔位包括:试剂孔位,用于放置提取试剂,所述试剂孔位包括第一容量试剂孔位和第二容量试剂孔位;洗脱管孔位,用于放置洗脱液;试剂管孔位,用于放置试剂;样本管孔位,用于放置样本;磁棒套孔位,用于放置磁棒套;以及吸头孔位,用于放置吸头。
在上述技术方案中,根据不同的功能及作用,试剂盒载架上多个功能孔位可以划分为:试剂孔位、洗脱管孔位、试剂管孔位、样本管孔位、磁棒套孔位、吸头孔位。其中,试剂孔位用于放置提取试剂(包括结合液、磁珠、多种洗涤液),作为提取核酸样本的发生容器,洗脱管孔位用于放置洗脱液,试剂管孔位用于放置相关试剂(在实验过程中可自动添加试剂),样本管孔位用于放置样本(例如已裂解的血清样本);磁棒套孔位用于放置磁棒套,用于磁珠吸附;吸头孔位用于放置吸头,吸头的尖端开口,样本或试剂可以通过吸头尖端的开口吸入和注出,从而实现样本的混合和移液。
于一实施例中,所述基因检测处理设备还包括:温控模块,设于所述基座上,且位于所述试剂盒载架下,用于调节温度;所述温控模块包括:试剂区控温单元,设于所述基座上,位于所述试剂盒载架底部,用于对所述试剂孔位内的试剂进行控温;以及反应区控温单元,设于所述基座上,位于所述试剂盒载架底部,用于对所述洗脱管孔位内的试剂进行控温。
在上述技术方案中,温控模块设于试剂盒载架下方,用于对裂解和洗脱步骤进行温控反应。
于一实施例中,所述试剂区控温单元包括:第一处理块,设于所述基座上,位于所述试剂孔位内底部;第一制冷块,设于所述第一处理块底部;第一隔热块,与所述第一制冷块连接;以及第一散热器,设于所述第一制冷块底部。
在上述技术方案中,第一处理块设于第一容量试剂孔位底部,并且可以适配多种类型的支持不同结
合体系的第一容量试剂孔位,第一处理块设为凹槽形,与第一容量试剂孔位贴合,可以根据实验需要对第一容量试剂孔位进行加热或制冷处理。当对第一容量试剂孔位进行制冷处理时,可使裂解加热后的试剂迅速达到所需温度范围,从而加快反应过程。因为裂解的下一步结合需要在室温下进行反应。
于一实施例中,所述反应区控温单元包括:第二加热块,设于所述基座上,位于所述洗脱管孔位内底部;第二隔热块,设于所述第二加热块上;第二散热器,设于所述第二加热块底部。
在上述技术方案中,反应区温控单元可以对洗脱管孔位内的试剂进行温度控制,从而使实验过程中达到符合的温度范围。
第二方面,本申请提供一种基因检测处理方法,使用如前述实施例任一项所述的基因检测处理设备,包括以下步骤:通过所述工位调节模块驱动所述复合功能模块到达对应的所述功能孔位处;通过所述移液模块进行移液以及混合操作,并通过所述吸磁模块进行吸磁操作,以实现基因提取和检测处理。
在上述技术方案中,通过水平移动模块调节复合功能模块在水平方位的移动位置,垂直升降模块调节复合功能模块在竖直高度方向的位置。使复合功能模块能够根据需要在试剂盒载架上方移动,并移动到指定的功能孔位所在位置处,从而执行对应的核酸提取过程中的移液、混合吸磁等操作。
于一实施例中,所述通过所述移液模块进行移液以及混合操作,包括:通过所述移液模块进行吸头装载操作;通过所述移液模块将待检测试剂在多个所述功能孔位之间进行转移;通过所述工位调节模块驱动所述移液模块按照预设方向移动,以使所述移液模块对待检测试剂进行充分混合。
在上述技术方案中,通过水平移动模块驱动移液模块左右移动,通过垂直升降模块驱动移液模块上下移动,通过控制吸头反复吞吐的样本的这种吹打混合的样本处理方法,能够满足样本的充分混合均匀的要求。
于一实施例中,所述通过所述吸磁模块进行吸磁操作,包括:通过所述吸磁模块进行磁棒套装载操作;通过所述工位调节模块驱动所述吸磁模块移动到对应的装有磁珠的所述功能孔位处,并驱动所述吸磁模块按照预设方向移动,以使吸磁模块进行吸磁操作;通过所述工位调节模块驱动所述吸磁模块进行脱磁操作。
在上述技术方案中,通过水平移动模块驱动吸磁模块左右移动,通过垂直升降模块驱动吸磁模块上下移动,能够满足磁珠充分吸附的要求。
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检测处理设备的结构示意图;
图2为本申请一实施例提供的水平移动模块的结构示意图;
图3为本申请一实施例提供的垂直移动模块的结构示意图;
图4为本申请一实施例提供的试剂盒载架的结构示意图;
图5为本申请一实施例提供的移液模块的结构示意图;
图6为本申请一实施例提供的移液模块的剖视图;
图7为图5中A处放大示意图;
图8为本申请一实施例提供的移液模块中退吸头状态示意图;
图9为本申请一实施例提供的刺膜模块的结构示意图;
图10为本申请一实施例提供的吸磁模块的结构示意图;
图11为本申请一实施例提供的吸磁模块的剖视图;
图12为本申请一实施例提供的吸磁模块中退磁棒套示意图;
图13为本申请一实施例提供的温控模块的结构示意图;
图14为图13中B处放大示意图;
图15为本申请一实施例提供的第一处理块的结构示意图;
图16为本申请一实施例提供的基因检测处理方法的流程示意图;
图17为本申请一实施例提供的磁力架的结构示意图;
图18为本申请一实施例提供的磁力架吸磁的剖视图。
图标:
1-基因检测处理设备;100-基座;200-工位调节模块;210-水平移动模块;211-水平滑轨;212-水平滑块组件;213-水平安装底座;214-第一传动件;215-水平驱动件;2151-第一电机;220-垂直升降模块;221-升降安装底座;222-垂直滑轨;223-垂直滑块组件;224-升降安装板;225-第二传动件;226-垂直驱动件;2261-第二电机;300-试剂盒载架;310-功能孔位;311-试剂孔位;3111-第一容量试剂孔位;3112-第二容量试剂孔位;312-洗脱管孔位;313-试剂管孔位;314-样本管孔位;315-磁棒套孔位;3151-磁棒套;316-吸头孔位;3161-吸头;31611-吸头通孔;400-复合功能模块;410-顶板;411-移液复位开关;412-磁棒复位开关;420-底板;421-第一通孔;422-退磁棒套弹性导杆通孔;423-第二通孔;424-退吸头弹性导向杆通孔;430-移液模块;431-活塞杆架导杆;432-活塞支架;433-活塞筒;434-容纳腔;435-活塞杆;436-吸头安装部;4361-通气孔;437-移液驱动件;4371-第三电机;438-退吸头板;439-退吸头弹性导向杆;440-吸磁模块;441-磁棒架导杆;442-磁棒支架;443-磁棒;444-磁套安装部;445-磁棒驱动件;4451-第四电机;446-退磁棒套板;447-退磁棒套弹性导杆;450-第一密封圈;460-第二密封圈;470-第三密封圈;480-刺膜模块;481-刺针;500-温控模块;510-试剂区控温单元;511-第一处理块;512-第一制冷块;513-第一隔热块;514-第一散热器;520-反应区控温单元;521-第二加热块;522-第二隔热块;523-第二散热器;600-磁力架;610-磁力驱动件。
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。
基因检测是一种较为精准的医学检测技术,主要应用于疾病检测、物质分析、生物医药等领域。通过提取被检测者外周静脉血、组织以及其他体液中的核酸,通过检测设备对被检测者细胞中的DNA分子或者RNA分子信息进行分析,从而了解被检测者的基因信息,进而确定病因或患病风险。
基因检测的前提是提取到高质量和高浓度的核酸样本。核酸提取的样本对象很多,对于浓度较低的一些目标核酸样本,需要投入较多的样本量进行提取,再基于磁珠上吸法提取技术,从较多的样本量中提取出高浓度的核酸。提取的过程涉及到核酸裂解、充分结合、数次洗涤以及从磁珠上更充分地洗脱。
因此,在进行核酸提取实验时,不仅要求核酸提取设备或仪器能够实现核酸样本的高效混合以及充分洗脱,同时还需要核酸提取设备或仪器能够具备提取和处理大体积核酸样本的功能。
下面将结合附图对本申请的技术方案进行清楚、完整地描述。
请参照图1,其为本申请一实施例提供的基因检测处理设备1的结构示意图。基因检测处理设备1包括:基座100、工位调节模块200、试剂盒载架300、复合功能模块400。试剂盒载架300设于基座100上,试剂盒载架300上设有多个功能孔位310;工位调节模块200设于基座100上;复合功能模块400与工位调节模块200连接。其中,复合功能模块400包括:顶板410、底板420、移液模块430和吸磁模块440,顶板410和底板420均与工位调节模块200连接,移液模块430连接顶板410和底板420,吸磁模块440连接顶板410和底板420,并且吸磁模块440与移液模块430相对设置。工位调节模块200
用于驱动复合功能模块400在各个功能孔位310之间进行转移,以使移液模块430进行移液操作和试剂混合操作,吸磁模块440进行磁珠吸附操作。
本实施例中,移液模块430和吸磁模块440共用同一个顶板410和底板420,这样设置,使移液模块430和吸磁模块440集成在一起,不仅节省空间,使结构更紧凑,降低了操作难度,提高基因检测处理设备1的自动化程度。
于一实施例中,工位调节模块200包括:水平移动模块210和垂直升降模块220。水平移动模块210设于基座100上,垂直升降模块220设于水平移动模块210上,复合功能模块400则设于垂直升降模块220上。水平移动模块210用于调节复合功能模块400在水平方位的移动位置,垂直升降模块220用于调节复合功能模块400在竖直高度方向的位置。本实施例中,通过水平移动模块210和垂直升降模块220的共同调节作用,使复合功能模块400能够根据需要在试剂盒载架300上方移动,并移动到指定的功能孔位310所在位置处,从而执行对应的核酸提取过程中的移液、混合吸磁等操作。
请参照图2,其为本申请一实施例提供的水平移动模块210的结构示意图。水平移动模块210包括:水平滑轨211、水平滑块组件212、水平安装底座213、第一传动件214以及水平驱动件215。水平滑轨211设于基座100上;水平滑块组件212可移动地设于水平滑轨211上;水平安装底座213设于水平滑块组件212上;第一传动件214设于基座100上,水平滑块组件212套设于第一传动件214上,水平驱动件215与第一传动件214传动连接,用于驱动第一传动件214转动,进而带动水平滑块组件212在第一传动件214上移动,从而使水平滑块组件212可在水平滑轨211上进行水平方向的移动。
示例性的,水平驱动件215为第一电机2151。第一传动件214为丝杠,第一电机2151的输出端与丝杠传动连接。在其他实施例中,水平驱动件215也可以为液压马达等。
请参照图3,其为本申请一实施例提供的垂直移动模块220的结构示意图。垂直升降模块220包括:升降安装底座221、垂直滑轨222、垂直滑块组件223、升降安装板224、第二传动件225以及垂直驱动件226。升降安装底座221设于水平安装底座213上;垂直滑轨222设于升降安装底座221上;垂直滑块组件223可移动地设于垂直滑轨222上;升降安装板224设于垂直滑块组件223上,顶板410和底板420均设于升降安装板224上;第二传动件225设于升降安装底座221上,垂直滑块组件223套设于第二传动件225上,垂直驱动件226与第二传动件225传动连接,用于驱动第二传动件225转动,进而带动垂直滑块组件223在第二传动件225移动,从而使垂直滑块组件223在垂直滑轨222上升降,从而带动升降安装板224进行升降,进而可以带动升降安装板224上设置的移液模块430和吸磁模块440进行竖直方向上的移动。
示例性的,垂直驱动件226与第二传动件225的传动方式可以与水平驱动件215与第一传动件214的传动方式一致。垂直驱动件226为第二电机2261,第二传动件225为丝杠,第二电机2261的输出端与丝杠传动连接。在其他实施例中,垂直驱动件226也可以为液压马达等。
请参照图4,其为本申请一实施例提供的试剂盒载架300的结构示意图。试剂盒载架300采用分体式设计,主要用于放置实验所需的试剂、样本管、试剂管、磁棒套3151和吸头3161。根据不同的功能及作用,试剂盒载架300上多个功能孔位310可以划分为:试剂孔位311、洗脱管孔位312、试剂管孔位313、样本管孔位314、磁棒套孔位315、吸头孔位316。其中,试剂孔位311用于放置提取试剂(包括结合液、磁珠、多种洗涤液),作为提取核酸样本的发生容器,洗脱管孔位312用于放置洗脱液,试剂管孔位313用于放置相关试剂(在实验过程中可自动添加试剂),样本管孔位314用于放置样本(例如已裂解的血清样本);磁棒套孔位315用于放置磁棒套3151,用于磁珠吸附;吸头孔位316用于放置吸头3161,吸头3161的尖端开口,样本或试剂可以通过吸头3161尖端的开口吸入和注出,从而实现样本的混合和移液。
可选地,根据实验需求,试剂孔位311选为5孔、7孔或8孔。再根据核酸样本量的容量大小,试剂孔位311又可以划分为第一容量试剂孔位3111和第二容量试剂孔位3112。以5孔的试剂孔位311为例,其中1个孔位为第一容量试剂孔位3111,该第一容量试剂孔位3111支持最大7ml的结合体系,剩余的4个孔位均为第二容量试剂孔位3112,可以支持小体积结合体系,如1ml或2ml等。以7孔的试剂孔位311为例,其中1个孔位为第一容量试剂孔位3111,该第一容量试剂孔位3111支持最大15ml
的结合体系,剩余的4个孔位均为第二容量试剂孔位3112,支持小体积结合体系。或者,以8孔的试剂孔位311为例,其中1个孔位为第一容量试剂孔位3111,该第一容量试剂孔位3111支持最大2.5ml的结合体系,剩余的4个孔位均为第二容量试剂孔位3112,可以支持小体积结合体系。如图4所示,本实施例中,试剂孔位311选择5孔,其中第一容量试剂孔位3111标记为1号孔,相邻于第一容量试剂孔位3111的其他4个第二容量试剂孔位3112,从右往左依次标记为2号孔、3号孔、4号孔、5号孔。
请参照图5和图6,移液模块430包括:活塞杆架导杆431、活塞支架432、若干个活塞筒433、若干个活塞杆435、吸头安装部436以及移液驱动件437。其中,活塞杆架导杆431连接顶板410和底板420,活塞支架432套设于活塞杆架导杆431上,且位于顶板410和底板420之间,活塞支架432能够沿着活塞杆架导杆431上下滑动。底板420上设有若干个第二通孔423,活塞筒433设于第二通孔423内,每个活塞筒433均具有容纳腔434;活塞杆435一端与活塞支架432连接,另一端能伸入活塞筒433的容纳腔434内;吸头安装部436设于底板420上,用于安装吸头3161,吸头安装部436内设有通气孔4361,通气孔4361与活塞筒433底部连通;移液驱动件437设于顶板410上,移液驱动件437的输出端与活塞支架432传动连接,用于驱动活塞支架432进行升降。
示例性地,移液驱动件437为第三电机4371,第三电机4371的输出端可以通过传动组件与活塞支架432传动连接。例如,第三电机4371的输出端可以连接丝杠,通过丝杠将电机的旋转运动转换为直线运动,进而通过控制第三电机4371的正转和反转,驱动活塞支架432进行升降。在其他的实施例中,移液驱动件437也可以为气缸,气缸的输出端直接与活塞支架432连接,通过气缸的伸缩运动驱动活塞支架432进行升降。
于一实施例中,在顶板410上可设有移液复位开关411,触发该移液复位开关411时移液驱动件437可以自动停止,即使活塞支架432恢复到初始位置。
于一实施例中,活塞杆架导杆431设为4个,用于支撑连接顶板410和底板420。活塞筒433、活塞杆435、第二通孔423以及吸头安装部436均同轴设置,且一一对应。活塞杆435设为24个,因此,活塞筒433、第二通孔423以及吸头安装部436的数量对应也设为24个。需要说明的是,活塞筒433、活塞杆435以及吸头安装部436的设置数量可以根据实际核酸提取的需要进行设置,在此不做具体限定。如此设置,当移液驱动件437驱动24个活塞杆435可以相对居中的进入活塞筒433中。
请参照图8,移液模块430还包括:退吸头板438、退吸头弹性导向杆439,退吸头板438活动设于吸头安装部436上;退吸头弹性导向杆439设于退吸头板438上,底板420上设有退吸头弹性导向杆通孔424,退吸头弹性导向杆439穿过退吸头弹性导向杆通孔424,并伸向活塞支架432。本实施例中,通过移液驱动件437驱动活塞支架432向下移动,活塞支架432向下推动退吸头弹性导向杆439下移,进而使退吸头弹性导向杆439推动退吸头板438向下移动,通过退吸头板438的作用力将安装在吸头安装部436上的吸头3161卸载。卸载完成后,触发移液复位开关411,移液驱动件437自动停止,活塞支架432恢复到初始位置,活塞支架432离开退吸头弹性导向杆439,退吸头弹性导向杆439在弹性作用力下恢复初始位置,使退吸头板438复位。
于一实施例中,请参照图7,在吸头安装部436与退吸头板438的接触表面处设有第一密封圈450,可以进一步增强吸头安装部436与退吸头板438接触处的密封性和稳定性。在吸头安装部436上还设有第二密封圈460,防止吸头安装部436在安装吸头3161后,进行移液操作过程中发生样本泄漏导致污染的问题。在活塞筒433与第二通孔423的接触表面设有第三密封圈470,防止移液驱动件437驱动活塞支架432进行升降时,活塞筒433在第二通孔423内发生移动,进而可进一步增强活塞筒433与第二通孔423的接触处的密封性和稳定性。
本实施例中,通过水平移动模块210和垂直升降模块220的共同调节作用,可以调整移液模块430到达指定位置,使移液模块430能够完成吸头3161装载、移液、混合、退吸头3161等操作,进一步提高了移液模块430的自动化程度。
在核酸提取过程中,通常会在试剂盒载架300上的功能孔位310表面封膜,可防止试剂盒载架300上的功能孔位310耗材被污染。在实验过程中,通过人工将功能孔位310上的封膜撕去,很容易造成核酸样本的污染。因此,为了尽可能地减少实验过程中的污染,本申请的基因检测处理设备1中,在移液
模块430上还设置了刺膜模块480。通过水平移动模块210和垂直升降模块220的共同调节作用,使刺膜模块480到达指定位置后,通过控制刺膜模块480刺破封膜。
于一实施例中,请参照图9,刺膜模块480可设置在移液模块430的后侧,且远离吸磁模块440。刺膜模块480包括:若干个刺针481,刺针481与活塞支架432连接。当试剂盒载架300上的功能孔位310上预封膜时,通过移液驱动件437驱动活塞支架432进行升降的同时,驱动刺针481进行升降,以使刺针481刺破封膜,进行刺膜操作。本实施例中,刺针481的个数与活塞筒433、第二通孔423以及吸头安装部436的数量对应一致,也设为24个。
请参照图10、图11,吸磁模块440包括:磁棒架导杆441、磁棒支架442、若干个磁棒443、磁套安装部444、磁棒驱动件445。其中,磁棒架导杆441连接顶板410和底板420,磁棒支架442套设于磁棒架导杆441上,且位于顶板410和底板420之间,磁棒支架442能够沿着磁棒架导杆441上下滑动,底板420上设有若干个第一通孔421,若干个磁棒443一端与磁棒支架442连接,另一端能穿过第一通孔421。在底板420上设置有用于安装磁棒套3151的磁套安装部444,磁套安装部444被设计为中空结构,允许磁棒443通过,在顶板410上设有磁棒驱动件445,磁棒驱动件445的输出端与磁棒支架442传动连接,用于驱动磁棒支架442进行升降。
示例性地,磁棒驱动件445的传动原理可与前述移液驱动件437的传动原理一致,磁棒驱动件445为第四电机4451,第四电机4451的输出端可以通过传动组件与磁棒支架442传动连接。例如,第四电机4451的输出端可以连接丝杠,通过丝杠将电机的旋转运动转换为直线运动,进而通过控制第四电机4451的正转和反转,驱动磁棒支架442进行升降。在其他的实施例中,磁棒驱动件445也可以为气缸,气缸的输出端直接与磁棒支架442连接,通过气缸的伸缩运动驱动磁棒支架442进行升降。
本实施例中,移液驱动件437与磁棒驱动件445共同设置在同一个顶板410上,但移液驱动件437与磁棒驱动件445之间互不干涉影响,独立控制。
于一实施例中,在顶板410上可设有磁棒复位开关412,触发该磁棒复位开关412时磁棒驱动件445可以自动停止,即使磁棒支架442恢复到初始位置。
可选地,吸磁模块440中磁棒支架442、磁棒架导杆441可与移液模块430中活塞支架432、活塞杆架导杆431的结构保持一致,因此,磁棒架导杆441也可设为4个,用于支撑连接顶板410和底板420。磁棒443、第一通孔421、磁套安装部444均同轴设置,且一一对应。磁棒443个数与活塞杆435个数保持一致,磁棒443也设为24个,因此,磁棒443、第一通孔421、磁套安装部444的数量对应也设为24个。需要说明的是,磁棒443、第一通孔421、磁套安装部444的设置数量可以根据实际核酸提取的需要进行设置,在此不做具体限定。如此设置,当磁棒驱动件445驱动24个磁棒443可以相对居中的进入磁套安装部444以及磁棒套3151中。
请参照图12,吸磁模块440还包括:退磁棒套板446、退磁棒套弹性导杆447。退磁棒套板446活动设于磁套安装部444上,退磁棒套弹性导杆447设于退磁棒套板446上,在底板420上还设有退磁棒套弹性导杆通孔422,退磁棒套弹性导杆447穿过退磁棒套弹性导杆通孔422,并伸向磁棒支架442。
本实施例中,吸磁模块440退磁棒套3151的原理与移液模块430退吸头3161的原理一致,通过磁棒驱动件445驱动磁棒支架442向下移动,磁棒支架442向下推动退磁棒套弹性导杆447下移,进而使退磁棒套弹性导杆447推动退磁棒套板446向下移动,通过退磁棒套板446的作用力将安装在磁套安装部444上的磁棒套3151卸载。卸载完成后,触发磁棒复位开关412,磁棒驱动件445自动停止,磁棒支架442恢复到初始位置,磁棒支架442离开退磁棒套弹性导杆447,退磁棒套弹性导杆447在弹性作用力下恢复初始位置,使退磁棒套板446复位。
请参照图13,其为本申请一实施例提供的温控模块500的结构示意图。温控模块500设于基座100上,且位于试剂盒载架300下方,用于裂解和洗脱步骤中调节温度。温控模块500包括:试剂区控温单元510和反应区控温单元520。其中,试剂区控温单元510用于对试剂孔位311内的试剂进行控温;反应区控温单元520用于对洗脱管孔位312内的试剂进行控温。
请参照图14,试剂区控温单元510包括:第一处理块511、第一制冷块512、第一隔热块513、第一散热器514。其中,第一处理块511位于试剂孔位311内底部;第一制冷块512设于第一处理块511
底部;第一隔热块513与第一制冷块512连接;第一散热器514设于第一制冷块512底部,用于散热。
于一实施例中,请参照图15,第一处理块511设于第一容量试剂孔位3111底部,并且可以适配多种类型的支持不同结合体系的第一容量试剂孔位3111,第一处理块511设为凹槽形,与第一容量试剂孔位3111贴合,可以根据实验需要对第一容量试剂孔位3111进行加热或制冷处理。当对第一容量试剂孔位3111进行制冷处理时,可使裂解加热后的试剂迅速达到所需温度范围,从而加快反应过程。
请参照图14,反应区控温单元520包括:第二加热块521、第二隔热块522和第二散热器523。其中,第二加热块521位于洗脱管孔位312内底部;第二隔热块522设于第二加热块521上;第二散热器523设于第二加热块521底部,用于散热。
请参照图16,其为本申请一实施例提供的基因检测处理方法的流程示意图。该方法使用如前述实施例任一项所述的基因检测处理设备1,包括以下步骤:
步骤S110:通过工位调节模块200驱动复合功能模块400到达对应的功能孔位310处。
在本步骤开始前,请参照图4,试剂盒载架300上对应的试剂孔位311的1号孔为第一容量试剂孔位3111,其内预封装有结合液;2号孔为第二容量试剂孔位3112,其内装有磁珠;3号孔为第二容量试剂孔位3112,其内装有洗涤液1;4号孔为第二容量试剂孔位3112,其内装有洗涤液2;5号孔为第二容量试剂孔位3112,其内装有洗涤液3。样本管孔位314内预先加入已裂解的血清样本。洗脱管孔位312内预先放置洗脱液。
如果试剂盒载架300的功能孔位310上预封膜,可通过控制水平移动模块210来调整刺膜模块480的水平位置,通过控制垂直升降模块220来调整刺膜模块480的高度位置,从而完成刺膜操作。具体地,通过水平驱动件215驱动第一传动件214转动,带动水平滑块组件212在第一传动件214上移动,从而使水平滑块组件212可在水平滑轨211上进行水平方向的移动,调整刺膜模块480上的刺针481到达试剂孔位311处。再通过控制垂直驱动件226工作,垂直驱动件226驱动第二传动件225转动,进而带动垂直滑块组件223在第二传动件225移动,从而使垂直滑块组件223在垂直滑轨222上下降,从而带动升降安装板224进行下降,进而带动连接在升降安装板224上的刺膜模块480下降,使刺针481伸入试剂孔位311内,刺破试剂孔位311上的封膜,完成刺膜操作。该过程一次性可以完成24个试剂孔位311的刺膜操作。
若需要对其他功能孔位310,例如洗脱管孔位312、试剂管孔位313、样本管孔位314、磁棒套孔位315、吸头孔位316表面的封膜进行刺膜操作时,可采用上述相同的方法,在此不再赘述。
需要说明的是,如果试剂盒载架300的功能孔位310上未预封膜,则可以忽略上述刺膜步骤。
步骤S120:通过移液模块430进行移液以及混合操作,并通过吸磁模块440进行吸磁操作,以实现基因提取和检测处理。
当刺膜操作完成后,需要先通过移液模块430完成吸头3161的装载,再通过吸头3161进行移液操作和样本的混合操作。
于一实施例中,步骤S120中通过移液模块430进行移液以及混合操作,具体包括步骤S121-步骤S123。
步骤S121:通过移液模块430进行吸头3161装载操作。
移液模块430进行吸头3161装载操作,具体装载步骤如下:通过移液驱动件437驱动活塞支架432下降,从而带动多个活塞杆435向下移动,并使多个活塞杆435对应插入到位于底板420上的活塞筒433内的容纳腔434中,当移液驱动件437继续驱动活塞支架432下降,使活塞杆435顶端接触到活塞筒433的底部,在水平移动模块210和垂直升降模块220的共同调节作用下,移液模块430到达试剂盒载架300上的吸头孔位316处后,通过控制垂直升降模块220调整移液模块430的高度,使吸头安装部436在移液驱动件437的驱动力作用下逐渐向吸头孔位316处的吸头3161靠近,再通过移液驱动件437驱动活塞支架432下降,在移液驱动件437的作用力下,使吸头3161装入到吸头安装部436上并稳稳卡紧在吸头安装部436上,完成吸头3161的装载。该步骤中一次性可以完成24个吸头3161的装载,提高了效率。本步骤完成后,可通过触发移液复位开关411使移液驱动件437自动停止,活塞支架432恢复到初始位置。
步骤S122:通过移液模块430将待检测试剂在多个功能孔位310之间进行转移。
吸头3161装载完成后,需要进行加样操作。具体步骤如下:通过控制水平移动模块210,带动移液模块430在水平方向上移动,使移液模块430上的吸头3161移动到达样本管孔位314上方,再通过控制垂直升降模块220带动移液模块430下降,并使吸头3161底部插入到样本管孔位314内,通过控制移液驱动件437驱动活塞支架432上升,从而带到与活塞支架432连接的多个活塞杆435从活塞筒433内向上抽出,利用和注射器相同的原理,将样本管孔位314内裂解好的血清样本通过吸头3161内的吸头通孔31611,抽取到吸头3161内。当吸头3161内吸入血清样本后,此时,控制垂直升降模块220带动移液模块430上升,使移液模块430上的吸头3161离开样本管孔位314,再通过控制水平移动模块210带动移液模块430移动到试剂孔位311中的第一容量试剂孔位3111(即1号孔)处,通过控制移液驱动件437驱动活塞支架432下降,进而带动与活塞支架432连接的多个活塞杆435向活塞筒433底部推进,从而将吸头3161内的裂解好的血清样本注入到第一容量试剂孔位3111(即1号孔)内,完成样本的加样转移。如前所述,该步骤一次性可以完成24个样本的加样转移,大幅提高了样本处理效率。
步骤S123:通过工位调节模块200驱动移液模块430按照预设方向移动,以使移液模块430对待检测试剂进行充分混合。
在步骤S122结束后,保持移液模块430上的吸头3161位于第一容量试剂孔位3111(即1号孔)的位置不动,先控制试剂区控温单元510内的第一处理块511对1号孔的第一容量试剂孔位3111(即1号孔)进行制冷降温,使1号孔降至室温。
当1号孔的第一容量试剂孔位3111(即1号孔)内降至室温并稳定后,通过控制水平移动模块210在水平方向上往复移动,从而带动移液模块430上的吸头3161在第一容量试剂孔位3111(即1号孔)内左右来回移动。同时,再通过控制移液驱动件437驱动活塞支架432上升,带到与活塞支架432连接的多个活塞杆435从活塞筒433内向上抽出,将第一容量试剂孔位3111(即1号孔)内的血清样本抽取到吸头3161内。当完成一次吸取后,通过控制垂直升降模块220在竖直方向上移动,进而带动移液模块430上的吸头3161向上移动,使吸头3161离开第一容量试剂孔位3111(即1号孔),再通过控制垂直升降模块220在竖直方向下移动,进而带动移液模块430上的吸头3161向下移动,使吸头3161再次进入第一容量试剂孔位3111(即1号孔)内,再通过控制移液驱动件437驱动活塞支架432下降,带动与活塞支架432连接的多个活塞杆435向活塞筒433底部推进,从而将吸头3161内的裂解好的血清样本再次注入到第一容量试剂孔位3111(即1号孔)内,由此完成一次样本的吞吐。同样,该步骤中一次性可以处理24个样本的充分混合。重复上述操作数次。
本步骤中,移液模块430带动吸头3161一边左右横向移动,一边竖直上下移动,同时移液模块430配合吸头3161对血清样本进行反复吞吐,从而可以达到血清样本与结合液充分混合的目的。上述的吹打混合过程可以持续15分钟,以使血清样本与第一容量试剂孔位3111(即1号孔)内的结合液完成充分混合。本步骤结束后,可通过触发移液复位开关411,移液驱动件437自动停止,使活塞支架432恢复到初始位置。
本步骤中,水平移动模块210在水平方向的移动控制方式和垂直升降模块220在竖直方向的移动控制方式在前文步骤S110中已经详细描述,在此不再赘述。但需要说明的是,由于第一容量试剂孔位3111(即1号孔)体积并不大,因此,水平移动模块210在水平方向上往复移动的幅度和垂直升降模块220在竖直方向往复移动的幅度都不可过大,否则容易使吸头3161在进行混合的操作过程中触碰到第一容量试剂孔位3111(即1号孔)的孔壁,导致样本的污染和检测的精度降低问题。因此,实验前,可以预先设计好软件控制程序,从而精确控制水平移动模块210和垂直升降模块220的移动幅度、动作时间等参数,而上述软件控制方法可以参照现有技术中的相关控制方法,在此也不再赘述。
完成样本加样转移后,需要重新更换吸头3161。首先,卸载使用过的吸头3161,具体包括如下步骤:通过控制水平移动模块210,带动移液模块430在水平方向上移动,使移液模块430上的吸头3161移动到达退去吸头3161位置处,再通过控制移液驱动件437工作,移液驱动件437驱动活塞支架432下降,在活塞支架432下降的过程中,活塞支架432底部触碰到退吸头弹性导向杆439,并在移液驱动件437的驱动作用力下,活塞支架432将退吸头弹性导向杆439向下推压,进而使退吸头弹性导向杆439
推动退吸头板438下移,从而通过退吸头板438将安装在吸头安装部436上的吸头3161卸载脱落。
可选地,本步骤中的退去吸头3161位置可以安装废液或废材回收箱,卸载后的使用过的吸头3161可以掉落到废液或废材回收箱处。
卸载吸头3161完成后,重新装载新的吸头3161并进行磁珠的转移,吸头3161装载的具体步骤可参照步骤S121的描述,在此不再赘述。
按照和步骤S122相同的方法,通过移液模块430进行磁珠的转移。具体步骤如下:通过控制水平移动模块210,带动移液模块430在水平方向上移动,使移液模块430上的吸头3161移动到达第二容量试剂孔位3112(即2号孔)上方,再通过控制垂直升降模块220带动移液模块430下降,并使吸头3161底部插入到第二容量试剂孔位3112(即2号孔)内,通过控制移液驱动件437驱动活塞支架432上升,从而带到与活塞支架432连接的多个活塞杆435从活塞筒433内向上抽出,将第二容量试剂孔位3112(即2号孔)内的磁珠试剂抽取到吸头3161内。当吸头3161内吸取了磁珠试剂后,此时,控制垂直升降模块220带动移液模块430上升,使移液模块430上的吸头3161离开第二容量试剂孔位3112(即2号孔),再通过控制水平移动模块210带动移液模块430移动到试剂孔位311中的第一容量试剂孔位3111(即1号孔)处,通过控制移液驱动件437驱动活塞支架432下降,进而带动与活塞支架432连接的多个活塞杆435向活塞筒433底部推进,从而将吸头3161内的磁珠试剂注入到第一容量试剂孔位3111(即1号孔)内,完成磁珠的转移。
于一实施例中,步骤S120中通过所述吸磁模块440进行吸磁操作,具体包括步骤S124-步骤S126。
步骤S124:通过吸磁模块440进行磁棒套3151装载操作。
在进行步骤S124之前,同样需要卸载使用过的吸头3161,再重新装载磁棒套3151。磁棒套3151的装载操作步骤与吸头3161的装载操作步骤原理相同。具体的装载步骤如下:通过控制水平移动模块210,带动吸磁模块440在水平方向上移动,使吸磁模块440移动到达磁棒套孔位315上方,通过磁棒驱动件445驱动磁棒支架442下降,从而带动多个磁棒443向下移动,当磁棒驱动件445驱动磁棒支架442下降到使磁棒443顶端穿过磁套安装部444直至磁棒443顶端与磁棒套3151尖端贴合,将磁棒套3151装入到磁套安装部444上并稳稳卡紧在磁套安装部444上,由此完成磁棒套3151的装载。同理,该步骤中一次性可以完成24个磁棒套3151的装载。
步骤S125:通过工位调节模块200驱动吸磁模块440移动到对应的装有磁珠的功能孔位310处,并驱动吸磁模块440按照预设方向移动,以使吸磁模块440进行吸磁操作。
经过步骤S123后,第一容量试剂孔位3111(即1号孔)内留有磁珠,此时,通过控制水平移动模块210,带动吸磁模块440移动到试剂孔位311中的第一容量试剂孔位3111(即1号孔)处,通过控制磁棒驱动件445,驱动磁棒支架442下降,进而带动多个磁棒443向下移动,使安装在磁套安装部444上的磁棒套3151伸入到第一容量试剂孔位3111(即1号孔)。按照与步骤S123中相同的方式,控制水平移动模块210在水平方向上左右移动,带动吸磁模块440上的磁棒套3151在第一容量试剂孔位3111(即1号孔)内左右来回移动,再通过控制垂直升降模块220在竖直方往复移动,带动吸磁模块440上的磁棒套3151和磁棒443同时上下往复移动,使第一容量试剂孔位3111(即1号孔)内的磁珠充分完全吸附到磁棒套3151上。需要说明的是,此过程中,磁棒驱动件445驱动磁棒443插入到磁棒套3151后就保持不动,否则磁珠将会从磁棒套3151上脱落。
本步骤中,结合的作用是使磁珠与核酸分子特异性结合,这个过程往往需要采用有效的混合方式,因此,通过吸磁模块440带动磁棒套3151一边左右横向移动,一边竖直上下移动,从而可以使磁珠充分吸附到磁棒套3151上,使磁珠与核酸分子特异性结合充分接触。
如前所述,水平移动模块210在水平方向上往复移动的幅度和垂直升降模块220在竖直方向上下往复移动的幅度都不可过大。
步骤S126:通过工位调节模块200驱动吸磁模块440进行脱磁操作。
在步骤S125中完成磁珠吸附后,需要通过吸磁模块440将吸附的磁珠进行释放,即脱磁操作。脱磁操作具体步骤如下:通过控制垂直升降模块220,带动吸磁模块440上升,使磁棒套3151离开第一容量试剂孔位3111(即1号孔),此时,通过控制水平移动模块210在水平方向上平移,使吸磁模块440
连同磁棒套3151平移到第二容量试剂孔位3112(即3号孔)上方,再通过控制垂直升降模块220,带动吸磁模块440下降,使磁棒套3151伸入第二容量试剂孔位3112(即3号孔)内,此时,通过磁棒驱动件445驱动磁棒支架442上升,从而带动多个磁棒443向上移动,使磁棒443上升并缓慢脱离磁棒套3151,由于吸磁效果的消失,使附着在磁棒套3151上的磁珠释放至第二容量试剂孔位3112(即3号孔)内的洗涤液1中。再通过控制垂直升降模块220,带动吸磁模块440上的磁棒套3151上下往复移动,从而使慢慢脱去磁棒443的磁棒套3151在洗涤液1中缓慢上下震荡若干次,将磁棒套3151表面的磁珠充分释放到第二容量试剂孔位3112(即3号孔)内的洗涤液1中,当磁棒套3151上的磁珠都释放完毕后,再通过控制垂直升降模块220,带动吸磁模块440上的磁棒套3151离开第二容量试剂孔位3112(即3号孔),由此完成脱磁操作。
完成脱磁操作后,需要卸载磁棒套3151。具体卸载步骤如下:通过控制水平移动模块210,带动吸磁模块440在水平方向上移动,使吸磁模块440上的磁棒套3151移动到达退去磁棒套3151位置处,再通过控制磁棒驱动件445工作,磁棒驱动件445驱动磁棒支架442下降,在磁棒支架442下降的过程中,磁棒支架442底部触碰到退磁棒套弹性导杆447,并在磁棒驱动件445的驱动作用力下,磁棒支架442将退磁棒套弹性导杆447向下推压,进而使退磁棒套弹性导杆447推动退磁棒套板446下移,从而通过退磁棒套板446的作用力将安装在磁套安装部444上的磁棒套3151卸载脱落。
可选地,本步骤中的退去磁棒套3151位置可以与退去吸头3161位置为同一位置,即卸载后的使用过的磁棒套3151与使用过的吸头3161可以一起丢落到废液或废材回收箱处。
磁棒套3151卸载后,移液模块430需要在吸头安装部436上重新装载吸头3161,再进行洗涤操作,吸头3161的具体步骤请参照步骤S121中关于的描述。通过移液模块430进行洗涤操作,具体步骤如下:通过水平移动模块210和垂直升降模块220的共同调节作用,带动移液模块430上的吸头3161移动至第二容量试剂孔位3112(即3号孔)中,按照与步骤S123相同的方式对第二容量试剂孔位3112(即3号孔)内的洗涤液1进行吹打混合1分钟,充分洗涤。可选地,洗涤过程中也可以使用磁棒套3151加磁棒443的组合方式进行,但在此之前需要在磁套安装部444上重新装载磁棒套3151。洗涤过程与步骤S125、步骤S126中吸磁脱磁的方法一致,在此不再赘述。
经过第一次洗涤后,需进行第一次吸磁操作。吸磁方式也有两种,一种是前文所述的采用磁棒套3151和磁棒443组合的吸磁方式。另一种则是采用吸头3161进行吸磁,如果是采用吸头3161吸磁的方式,则需要借助磁力架600。
于一实施例中,请参照图17和图18,磁力架600设于基座100上,磁力架600的一端部设有磁铁,另一端连接磁力驱动件610。磁力驱动件610可以是气缸。当移液模块430上的吸头3161位于第二容量试剂孔位3112(即3号孔)内,通过磁力驱动件610驱动磁力架600移动到吸头3161所在位置处,使磁力架600上的磁铁贴近吸头3161底部,通过磁铁将第二容量试剂孔位3112(即3号孔)内的磁珠吸附到吸头3161内侧壁上,直至所有磁珠均被捕获。
接着,再进行第二次洗涤操作。通过水平移动模块210和垂直升降模块220的共同调节作用,带动移液模块430上的吸头3161移动至第二容量试剂孔位3112(即4号孔)中,按照步骤S123相同的方式对第二容量试剂孔位3112(即4号孔)内的洗涤液2进行吹打混合1分钟,充分洗涤。可选地,二次洗涤过程中也可以使用磁棒套3151加磁棒443的组合方式进行,在此也不再赘述。
经过第二次洗涤后,需进行第二次吸磁操作。可采用前述关于磁力架600吸磁的方式,通过磁铁将第二容量试剂孔位3112(即4号孔)内的磁珠吸附到吸头3161内侧壁上,直至所有磁珠均被捕获。可选地,本次吸磁操作也可以采用前文所述的磁棒套3151加磁棒443的组合方式的吸磁方式。
然后,再进行第三次洗涤操作,如前所述,通过水平移动模块210和垂直升降模块220的共同调节作用,带动移液模块430上的吸头3161移动至第二容量试剂孔位3112(即5号孔)中,按照步骤S123相同的方式对第二容量试剂孔位3112(即5号孔)内的洗涤液3进行吹打混合1分钟,充分洗涤。可选地,三次洗涤过程中也可以使用磁棒套3151加磁棒443的组合方式进行,在此也不再赘述。
经过三次洗涤后,需进行第三次吸磁操作。可采用前述关于磁力架600吸磁的方式进行,通过磁力架600上的磁铁将第二容量试剂孔位3112(即5号孔)内的磁珠吸附到吸头3161内侧壁上,直至所有
磁珠均被捕获。可选地,本次吸磁操作也可以采用前文所述的磁棒套3151和磁棒443组合的吸磁方式。
经过数次洗涤后,将磁珠与核酸结合的颗粒进行清洗,可以洗去磁珠捕获核酸的同时捕获的一些杂质,如蛋白、盐等。
需要说明的是,上述数次洗涤过程中,可根据需要采用吸头3161进行洗涤、混合操作,以及吸头3161配合磁力架600进行吸磁操作;或可以采用磁棒套3151加磁棒443的组合方式进行洗涤、混合或吸磁操作,本申请中对此不作具体限制。
经过数次洗涤后,需要进行洗脱操作。在洗脱操作前,同样需要重新更换吸头3161,装载新的吸头3161后,进行洗脱操作,具体洗脱步骤如下:通过控制水平移动模块210和垂直升降模块220,以及移液驱动件437,驱动吸头3161将在第二容量试剂孔位3112(即5号孔)内吸磁后的磁珠转移至洗脱管孔位312内,通过磁力驱动件610驱动磁力架600远离吸头3161所在位置,通过控制垂直升降模块220带动移液模块430上的吸头3161伸入到洗脱管孔位312内,再按照步骤S123的方式进行吹打混合6分钟。当移液驱动件437驱动活塞支架432上升,带到与活塞支架432连接的多个活塞杆435从活塞筒433内向上抽出,将洗脱管孔位312内的洗脱液抽取到吸头3161内,此时,通过磁力驱动件610驱动磁力架600靠近吸头3161所在位置,开始吸磁,待充分吸磁后再通过移液驱动件437的作用,将吸头3161内的洗脱液注回洗脱管孔位312内。
再通过水平移动模块210和垂直移动模块220的共同调节作用,使吸附有磁珠的吸头3161移动到第二容量试剂孔位3112(即3号孔)位置处,再按照步骤S123的方式吹打混合数秒,通过磁力驱动件610驱动磁力架600远离吸头3161所在位置,从而使吸头3161上的磁珠释放至第二容量试剂孔位3112(即3号孔)的洗涤废液中。最后,再按照前述退吸头3161和退磁棒套3151的方式将使用过的吸头3161和磁棒套3151丢至废液或废材回收箱处,至此完成全部核酸提取和处理工作。
本申请中的基因检测处理设备1将移液模块430和吸磁模块440集成在一起,节省了空间,使结构更加紧凑,提高了基因检测处理设备1的自动化程度。其次,移液模块430和吸磁模块440的集成使基因检测处理设备1具备同时处理大体积和小体积试剂的功能,解决了行业中往往需要使用大样本量,但又需要得到小体积洗脱样本的痛点。采用本申请的基因检测处理设备1可以实现大体积结合体系的高效混合,能够满足更多的应用场景。
此外,本申请的基因检测处理方法中,通过水平移动模块210驱动移液模块430左右移动,通过垂直升降模块220驱动移液模块430和吸磁模块440上下移动,通过控制吸头3161反复吞吐的样本的这种吹打混合的样本处理方法,能够满足样本的充分混合均匀的要求。采用本申请的方法,可以大幅度提高基因检测处理的效率。
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 (19)
- 一种基因检测处理设备,其特征在于,包括:基座;试剂盒载架,设于所述基座上,所述试剂盒载架上设有多个功能孔位;工位调节模块,设于所述基座上;复合功能模块,与所述工位调节模块连接,所述工位调节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:顶板,与所述工位调节模块连接;底板,与所述工位调节模块连接;移液模块,连接所述顶板和所述底板,用于进行移液操作和试剂混合操作;吸磁模块,与所述移液模块相对设置,用于进行磁珠吸附操作。
- 根据权利要求1所述的基因检测处理设备,其特征在于,所述吸磁模块包括:磁棒架导杆,连接所述顶板和所述底板;磁棒支架,套设于所述磁棒架导杆上,且位于所述顶板和所述底板之间,所述底板上设有若干个第一通孔;若干个磁棒,一端与所述磁棒支架连接,另一端穿过所述第一通孔;磁套安装部,设于所述底板上,用于安装磁棒套;以及磁棒驱动件,设于所述顶板上,所述磁棒驱动件的输出端与所述磁棒支架传动连接,用于驱动所述磁棒支架进行升降。
- 根据权利要求2所述的基因检测处理设备,其特征在于,所述吸磁模块还包括:退磁棒套板,活动设于所述磁套安装部上;退磁棒套弹性导杆,设于所述退磁棒套板上,所述底板上设有退磁棒套弹性导杆通孔,所述退磁棒套弹性导杆穿过所述退磁棒套弹性导杆通孔,并伸向所述磁棒支架。
- 根据权利要求2所述的基因检测处理设备,其特征在于,所述磁棒、所述第一通孔、所述磁套安装部均同轴设置,且一一对应。
- 根据权利要求1所述的基因检测处理设备,其特征在于,所述移液模块包括:活塞杆架导杆,连接所述顶板和所述底板,所述底板上设有若干个第二通孔;活塞支架,套设于所述活塞杆架导杆上,且位于所述顶板和所述底板之间;若干个活塞筒,设于所述第二通孔内,所述活塞筒具有容纳腔;若干个活塞杆,一端与所述活塞支架连接,另一端能伸入所述活塞筒内;吸头安装部,设于所述底板上,用于安装吸头,所述吸头安装部内设有通气孔,所述通气孔与所述活塞筒底部连通;以及移液驱动件,设于所述顶板上,所述移液驱动件的输出端与所述活塞支架传动连接,用于驱动所述活塞支架进行升降。
- 根据权利要求5所述的基因检测处理设备,其特征在于,所述移液模块还包括:退吸头板,活动设于所述吸头安装部上;退吸头弹性导向杆,设于所述退吸头板上,所述底板上设有退吸头弹性导向杆通孔,所述退吸头弹性导向杆穿过所述退吸头弹性导向杆通孔,并伸向所述活塞支架。
- 根据权利要求6所述的基因检测处理设备,其特征在于,所述吸头安装部与所述退吸头板的接触表面设有第一密封圈;所述吸头安装部上还设有第二密封圈;所述活塞筒与所述第二通孔的接触表面设有第三密封圈。
- 根据权利要求5所述的基因检测处理设备,其特征在于,所述活塞杆、所述活塞筒、所述第二通孔、所述吸头安装部均同轴设置,且一一对应。
- 根据权利要求5所述的基因检测处理设备,其特征在于,所述复合功能模块还包括:刺膜模块,所述刺膜模块包括:若干个刺针,与所述活塞支架连接,所述移液驱动件驱动所述活塞支架进行升降,以使所述刺针进行刺膜操作。
- 根据权利要求1至9任一项所述的基因检测处理设备,其特征在于,所述工位调节模块包括:水平移动模块,设于所述基座上;垂直升降模块,设于所述水平移动模块上;所述复合功能模块设于所述垂直升降模块上。
- 根据权利要求10所述的基因检测处理设备,其特征在于,所述水平移动模块包括:水平滑轨,设于所述基座上;水平滑块组件,可移动地设于所述水平滑轨上;水平安装底座,设于所述水平滑块组件上;第一传动件,设于所述基座上,所述水平滑块组件套设于所述第一传动件上;以及水平驱动件,与所述传动件连接,用于驱动所述水平滑块组件进行水平方向移动。
- 根据权利要求11所述的基因检测处理设备,其特征在于,所述垂直升降模块包括:升降安装底座,设于所述水平安装底座上;垂直滑轨,设于所述升降安装底座上;垂直滑块组件,可移动地设于所述垂直滑轨上;升降安装板,设于所述垂直滑块组件上,所述顶板和所述底板均设于所述升降安装板上;第二传动件,设于所述升降安装底座上,所述垂直滑块组件套设于所述第二传动件上;以及垂直驱动件,与所述第二传动件连接,用于驱动所述垂直滑块组件带动所述升降安装板进行升降。
- 根据权利要求1所述的基因检测处理设备,其特征在于,所述功能孔位包括:试剂孔位,用于放置提取试剂,所述试剂孔位包括第一容量试剂孔位和第二容量试剂孔位;洗脱管孔位,用于放置洗脱液;试剂管孔位,用于放置试剂;样本管孔位,用于放置样本;磁棒套孔位,用于放置磁棒套;以及吸头孔位,用于放置吸头。
- 根据权利要求13所述的基因检测处理设备,其特征在于,所述基因检测处理设备还包括:温控模块,设于所述基座上,且位于所述试剂盒载架下,用于调节温度;所述温控模块包括:试剂区控温单元,设于所述基座上,位于所述试剂盒载架底部,用于对所述试剂孔位内的试剂进行控温;以及反应区控温单元,设于所述基座上,位于所述试剂盒载架底部,用于对所述洗脱管孔位内的试剂进行控温。
- 根据权利要求14所述的基因检测处理设备,其特征在于,所述试剂区控温单元包括:第一处理块,设于所述基座上,位于所述试剂孔位内底部;第一制冷块,设于所述第一处理块底部;第一隔热块,与所述第一制冷块连接;以及第一散热器,设于所述第一制冷块底部。
- 根据权利要求14所述的基因检测处理设备,其特征在于,所述反应区控温单元包括:第二加热块,设于所述基座上,位于所述洗脱管孔位内底部;第二隔热块,设于所述第二加热块上;第二散热器,设于所述第二加热块底部。
- 一种基因检测处理方法,其特征在于,使用如权利要求1至16任一项所述的基因检测处理设备,包括以下步骤:通过所述工位调节模块驱动所述复合功能模块到达对应的所述功能孔位处;通过所述移液模块进行移液以及混合操作,并通过所述吸磁模块进行吸磁操作,以实现基因提取和检测处理。
- 根据权利要求17所述的基因检测处理方法,其特征在于,所述通过所述移液模块进行移液以及混合操作,包括:通过所述移液模块进行吸头装载操作;通过所述移液模块将待检测试剂在多个所述功能孔位之间进行转移;通过所述工位调节模块驱动所述移液模块按照预设方向移动,以使所述移液模块对待检测试剂进行充分混合。
- 根据权利要求17所述的基因检测处理方法,其特征在于,所述通过所述吸磁模块进行吸磁操作,包括:通过所述吸磁模块进行磁棒套装载操作;通过所述工位调节模块驱动所述吸磁模块移动到对应的装有磁珠的所述功能孔位处,并驱动所述吸磁模块按照预设方向移动,以使吸磁模块进行吸磁操作;通过所述工位调节模块驱动所述吸磁模块进行脱磁操作。
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