WO2015062552A1 - 一种核酸提取仪 - Google Patents

一种核酸提取仪 Download PDF

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Publication number
WO2015062552A1
WO2015062552A1 PCT/CN2014/090131 CN2014090131W WO2015062552A1 WO 2015062552 A1 WO2015062552 A1 WO 2015062552A1 CN 2014090131 W CN2014090131 W CN 2014090131W WO 2015062552 A1 WO2015062552 A1 WO 2015062552A1
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WO
WIPO (PCT)
Prior art keywords
motor
nucleic acid
base
console
heating
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PCT/CN2014/090131
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English (en)
French (fr)
Inventor
王中平
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利多(香港)有限公司
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Publication of WO2015062552A1 publication Critical patent/WO2015062552A1/zh

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    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/10Processes for the isolation, preparation or purification of DNA or RNA
    • C12N15/1003Extracting or separating nucleic acids from biological samples, e.g. pure separation or isolation methods; Conditions, buffers or apparatuses therefor
    • C12N15/1006Extracting or separating nucleic acids from biological samples, e.g. pure separation or isolation methods; Conditions, buffers or apparatuses therefor by means of a solid support carrier, e.g. particles, polymers
    • C12N15/1013Extracting or separating nucleic acids from biological samples, e.g. pure separation or isolation methods; Conditions, buffers or apparatuses therefor by means of a solid support carrier, e.g. particles, polymers by using magnetic beads
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS 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
    • C12M47/00Means for after-treatment of the produced biomass or of the fermentation or metabolic products, e.g. storage of biomass
    • C12M47/06Hydrolysis; Cell lysis; Extraction of intracellular or cell wall material
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/00584Control arrangements for automatic analysers
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/0099Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor comprising robots or similar manipulators
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N2035/00178Special arrangements of analysers
    • G01N2035/00306Housings, cabinets, control panels (details)
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N2035/00465Separating and mixing arrangements
    • G01N2035/00534Mixing by a special element, e.g. stirrer
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N2035/1027General features of the devices
    • G01N2035/1048General features of the devices using the transfer device for another function
    • G01N2035/1053General features of the devices using the transfer device for another function for separating part of the liquid, e.g. filters, extraction phase
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/0098Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor involving analyte bound to insoluble magnetic carrier, e.g. using magnetic separation

Definitions

  • the present invention relates to a nucleic acid extractor.
  • nucleic acid molecules are the main research object, and the separation and linearization of nucleic acids is the basic technology of nucleic acid research.
  • Nucleic acid is the basic unit representing the genetic characteristics of living organisms.
  • Nucleic acid detection is an advanced biological test at the molecular level. It is more sensitive, specific, and windowless than traditional morphological, cytological, and immunological tests. Significant advantages such as the period.
  • Nucleic acid detection includes qualitative PCR, molecular hybridization, real-time fluorescent quantitative PCR and other technologies.
  • the primary key of these nucleic acid detection technologies is to complete the extraction of nucleic acids from biological samples. Therefore, the efficient and accurate extraction of nucleic acid templates has become the premise of subsequent nucleic acid detection.
  • domestic nucleic acid extraction mainly adopts the traditional manual preparation method, which is not only inefficient, high in cost, but also has poor repeatability and stability.
  • An object of the present invention is to provide a nucleic acid extractor comprising: a base, an outer casing connected to the base, an instrument body located inside the outer casing and mounted to the base; and the instrument body including the base a moving console and a first motor group, a second motor group, and a third motor group respectively fixed to the base, wherein the first motor group is configured to drive the console substantially parallel to a plane in which the base is located In-plane motion, the second motor group and the third motor group are fixed to the base and are immovable relative to the base, the console including A clamp for automatically fixing a deep well plate and a heating device for heating the deep well plate.
  • the axis of the first motor group is substantially parallel to the plane in which the base is located, and the axes of the second motor group and the third motor group are substantially perpendicular to the plane in which the base is located.
  • the first motor group includes: a motor fixed on the base and capable of generating relative displacement with respect to the base, a ball screw connected by a coaxial line of the connector to the shaft of the motor, and a slide connected to the ball screw A block and a guide rail that guides the slider.
  • the second and third motor groups are fixed to the slider of the first motor group by the motor bracket, and reciprocated along the axial direction of the motor of the first motor group under the driving of the first motor group, the motor bracket includes The first panel and the second panel are substantially perpendicular to each other, the first panel is for fixing the second and third motor groups, and the second panel is fixed to the slider on the first motor group.
  • the third motor group includes an encoder for controlling the operation of the motor, the encoder including a component that monitors the operating condition of the motor of the third motor group and a component that issues a correction command to the motor.
  • the third motor unit is fixed with an optical sensor arm on the outer side of the slider, and an optocoupler sensor is disposed at the initial position and the maximum stroke position of the slider in the third motor group, and the optocoupler sensor passes the induction The position of the light sensing arm to monitor the position of the slider.
  • the heating device comprises a plurality of rows of movable heating plates disposed on the operation table of the nucleic acid extractor, each row of heating plates comprising a plurality of heating hole walls closely matching the shape of the bottom of the heated deep hole plate,
  • the heating plate is made of a heat conductive material, and has a heating member inside, a heat insulating member is disposed on the outer circumference thereof, and a plurality of independent compression springs are disposed under the heating plate, and the compression spring abuts against the heating plate.
  • a heat sink is disposed under the console, the heat sink including a cross flow fan hidden under the console.
  • the instrument body further includes a power pack and at least one set of power management components for controlling power energy output, the power management component including at least one printed circuit board, a plurality of capacitors and resistors, and at least one power conditioner and the snug A heat sink for a power conditioner, the power conditioner including a heat-generating electronic component for converting a transient overload voltage or an overload current that may be generated during operation of the nucleic acid extractor into thermal energy.
  • the power management component including at least one printed circuit board, a plurality of capacitors and resistors, and at least one power conditioner and the snug A heat sink for a power conditioner, the power conditioner including a heat-generating electronic component for converting a transient overload voltage or an overload current that may be generated during operation of the nucleic acid extractor into thermal energy.
  • the clamp comprises a motor located under the base, a support portion located inside the console, a plurality of clamp arms and a micro switch, wherein the motor includes a cam, and when the motor is started, the cam pushes the support portion up and down Moving, the support portion further pushes the clamp arm to rotate, and the clamp arm clamps or releases the outer wall of the deep hole plate, the micro switch includes a tilted spring piece and a push button switch, when the deep hole plate is placed at a predetermined position of the operation table When the bottom of the deep hole plate pushes the spring piece compression button switch, the micro switch is turned on to start the motor work.
  • the invention has the beneficial effects that since the present invention fixes the second motor group that needs to output power and the third motor group that needs to output high frequency vibration on the base, the operation table that does not need to be moved at a high speed is designed to be relative to The susceptor moves to solve the problem of the instability caused by designing the third motor group that needs to output high frequency vibration into a movable type in the prior art. Therefore, the nucleic acid extractor of the present invention has high nucleic acid extraction efficiency, high operational precision, and good stability. The extraction efficiency is 2-4 times higher than that of the prior art, and the extracted concentration is 2-4 times higher than that of the prior art, and therefore, it can be used for hypersensitivity detection.
  • the present invention adopts a movable heating device, and a plurality of springs are arranged under the heating plate.
  • the deep hole plate When the deep hole plate is placed on the heating plate, the bottom of the deep hole plate is pressed downward to press the heating plate, so that the two are formed. Very good Fit. Therefore, each well is uniformly heated, the temperature difference is small, and the speed and degree of cracking of the sample in each well are more uniform than in the prior art.
  • the magnetic rod sleeve is made of a hydrophobic material, and therefore, its magnetic absorption and demagnetization and mechanical agitation are high and uniform.
  • the present invention uses a stepping motor with higher frequency than the prior art and a ball screw with higher precision as a transmission system.
  • the movement precision of the magnetic rod sleeve and the magnetic rod is higher than that of the prior art, and the magnetic rod
  • the mechanical stirring efficiency of the sleeve is higher, the magnetic rod is controlled accurately, does not touch the wall, and does not touch the magnetic beads.
  • the magnetic bead recovery rate is very high, reaching over 98%.
  • Ultra-quiet after using the ball screw, the overall noise generated by the instrument is less than 60dB, even lower than 53dB, and the prior art is greater than 80dB.
  • the power regulator included in the nucleic acid extractor is used to convert the instantaneous overload voltage or overload current which may be generated during the operation of the nucleic acid extractor into heat energy to avoid burning the power conditioner due to excessive temperature.
  • the invention provides an encoder on the motor group, and the encoder sends a correction command according to the running condition of the step electrode, and timely corrects the stroke of the stepping motor according to each pulse, thereby avoiding the motor out of step in advance.
  • the occurrence of the vibration of the motor-driven magnetic rod sleeve is improved.
  • Figure 1 is a schematic illustration of a nucleic acid extractor of the present invention
  • Figure 2 is a schematic view of Figure 1 after removing the outer casing and the base;
  • Figure 3 is a schematic view of another perspective of Figure 2;
  • Figure 4 is a schematic view of the nucleic acid extracting apparatus of the present invention after removing the inner and outer casings;
  • Figure 5 is a schematic view of another perspective of Figure 4.
  • Figure 6 is a schematic view of Figure 5 after removing parts
  • Figure 7 is a schematic view of Figure 6 after removing parts
  • Figure 8 is a schematic view similar to Figure 4, showing the nucleic acid extractor of the present invention in an initial state
  • FIG. 9 is similar to FIG. 8 and is a schematic view of the nucleic acid extracting device of the present invention after being inserted into a magnetic sleeve;
  • Figure 10 is similar to Figure 9 and is a schematic view of the nucleic acid extracting apparatus of the present invention after placing a deep-well plate;
  • Figure 11 is a view similar to Figure 10, showing the magnetic rod of the nucleic acid extractor of the present invention after entering the deep well plate;
  • Figure 12 is a plan view showing the magnetic rod sleeve and the magnetic rod of the nucleic acid extracting apparatus of the present invention in a first position after entering the deep hole plate;
  • Figure 13 is similar to Figure 12, but the first motor group drives the second and third motor groups to move to the second position;
  • Figure 14 is a schematic view showing the magnetic rod sleeve and the magnetic rod of the nucleic acid extracting apparatus of the present invention after adsorbing magnetic beads and nucleic acids;
  • Figure 15 is a plan view showing the movement of the magnetic rod sleeve and the magnetic rod of the nucleic acid extracting instrument of the present invention.
  • Figure 16 is a plan view similar to Figure 13, but with both the magnetic rod sleeve and the magnetic rod entering the second position of the deep orifice plate;
  • Figure 17 is a plan view of the console
  • Figure 17A is a partial enlarged view of the marked portion of Figure 17;
  • Figure 18 is a plan view showing another angle of the console
  • Figure 18A is a partial enlarged view of the marked portion of Figure 18;
  • Figure 19 is a plan view similar to Figure 18, the switch is in a triggered state
  • Figure 19A is a partial enlarged view of the marked portion in Figure 19;
  • Figure 20-23 is a schematic view of the operation of the fixture
  • Figure 24 is an enlarged schematic view of the power control component
  • Figure 24A is a partial enlarged view of Figure 24;
  • Figure 25 is an enlarged schematic view of the first motor unit
  • Figure 26 is an enlarged schematic view of a third motor unit
  • Figure 27 is a schematic view of the nucleic acid extracting apparatus of the present invention after removing parts
  • Figure 27A is a partial enlarged view of Figure 27;
  • Figure 28 is a schematic view showing the bottom plate and the operation table of the nucleic acid extracting instrument of the present invention.
  • Figure 28A is a partial enlarged view of Figure 28;
  • Figure 29 is a schematic view of Figure 28 after removing the operation panel
  • Figure 30 is a schematic view of the bottom plate viewed from the bottom;
  • Figure 31 is a schematic view of the principle of the present invention.
  • Figure 32 is a schematic illustration of the door of the nucleic acid extractor of the present invention.
  • Figure 32A is a partial enlarged view of Figure 32;
  • Figure 33 is a partially enlarged schematic view showing the door of the nucleic acid extracting apparatus of the present invention.
  • Figure 33A is a partial enlarged view of Figure 33;
  • Figure 34 is a schematic view showing the operation of the nucleic acid extracting apparatus of the present invention.
  • Figure 35 is a schematic illustration of the nucleic acid extractor of the present invention clamping a deep well plate and heating the deep well plate.
  • the nucleic acid extractor 1 of the present invention comprises a base 10 at the bottom, an outer casing 20 above the base, an instrument body 30 located inside the outer casing and fixed to the base 10.
  • the susceptor 10 is made of a material with a relatively high specific gravity and low cost (such as cast iron, steel, or filled with concrete), so that the pedestal has a large mass, thereby effectively preventing the nucleic acid extractor from occurring during operation. Vibration and displacement.
  • the outer casing 20 is preferably made of a stainless steel plate of 0.1-2.0 mm thick by cold rolling and cold cutting. In other solutions, the outer casing 20 can also be made of a plastic material and manufactured by an injection molding process to reduce costs.
  • a plurality of ribs or ribs which are parallel or criss-crossing each other may be designed on the outer casing 20 to increase the strength of the outer casing.
  • the outer casing 20 can also be subjected to painting, computer printing, computer engraving, etching or electroplating to make the outer casing have a better appearance.
  • the outer casing 20 is provided with an instrument panel 22 and a door 24 which can be opened and closed a plurality of times.
  • the instrument panel 22 can be designed with a display screen and a plurality of operation keys to facilitate the operation of the operator.
  • the instrument panel 22 is designed with a touch liquid crystal display, so that the operator can directly touch the liquid crystal display to operate.
  • the instrument body 30 includes a bottom plate 32 fixed to the base 10, an inner casing 34, a gantry 36, a console 38, a power pack 40, a main control unit 42, and a first motor unit 44, The second motor group 46 and the third motor group 48.
  • the bottom plate 32 provides at least one plane for supporting the aforementioned components.
  • the bottom plate 32 is between 1.0 and 10.0 in thickness.
  • the millimeter steel plate should have moderate rigidity and can maintain at least one surface in a flat shape, which is not prone to bending, twisting and local lifting.
  • the bottom plate 32 can also be made by a hard plastic injection molding process, or a hard wood or bamboo material can be produced by a woodworking process.
  • the bottom plate 32 can also serve as the base 10 when the bottom plate 32 has sufficient thickness, rigidity, and mass.
  • the inner casing 34, the gantry 36, the console 38, the power pack 40 and the first motor unit 44 are respectively fixed to the bottom plate 32.
  • the main control unit 42 is placed on the back of the power pack 40 (shown in Figure 3). As shown in FIGS.
  • the first motor unit 44 is fixed to the upper surface of the bottom plate 32, and its longitudinal direction or axis is parallel to the upper surface of the bottom plate; the second motor group 46 and the third motor group 48 are first. It is fixed to the motor bracket 50 and then mounted to the first motor unit 44 by the motor bracket 50.
  • the second motor group 46 and the third motor group 48 are arranged adjacent to each other in parallel with their axes parallel to each other and perpendicular to the upper surface of the bottom plate 32, respectively.
  • the gantry 36 is provided with a guide rail or a slide rail 43.
  • the motor bracket 50 is provided with a slider 51 corresponding to the guide rail 43, and the slider 51 is defined to slide within the guide rail 43.
  • the gantry 36 includes at least one beam 37 and two vertical beams 39 and 41 for supporting the girders 37.
  • the guide rails 43 are designed on the beam 37, and the vertical beams 39 and 41 are respectively fixed to the bottom plate 32 or the upper surface of the base 10.
  • the console 38 includes a flat, generally rectangular parallelepiped operation panel 52 adjacent the front side of the nucleic acid extractor 1.
  • the operation panel 52 should have appropriate Rigidity and strength, not easily deformed.
  • the operation panel 52 may be fabricated by a cold working process from a stainless steel plate or by an injection molding process of a hard plastic.
  • the operation panel 52 includes a platform table substantially parallel to the upper surface of the bottom plate 32, and the operation of extracting nucleic acid is basically performed on the platform.
  • the platform includes two longitudinal sides that are substantially parallel to the front side of the nucleic acid extractor 1.
  • the first motor unit 44 is mounted at the rear of the console 38 (i.e., at a position further away from the front of the nucleic acid extractor than the console 38, see Figs. 6 and 7).
  • the longitudinal or axial direction of the first motor unit 44 is substantially parallel to the longitudinal sides of the console 38.
  • Power pack 40 includes an elementary component (not labeled) that converts a 220 volt or 110 volt universal voltage into a voltage suitable for driving various electronic components within the nucleic acid extractor of the present invention and at least one set of power management components 54. To save space, the power management component 54 is secured above the power pack 40 (as shown in Figures 4 and 5). Referring to FIG. 24 and FIG. 24A, the power management component 54 includes at least one printed circuit board 56, a plurality of electronic components such as capacitors and resistors, and at least one power conditioner 58 and heat sink 60. The heat sink 60 abuts the power conditioner 58.
  • the power conditioner 58 includes heat-generating electronic components for consuming the instantaneous overload voltage or overload current that may be generated during operation of the nucleic acid extractor into thermal energy.
  • the heat sink 60 is used to conduct the heat generated by the power conditioner 58 in time to cool the power conditioner 58 to avoid burning the power conditioner 58 due to excessive temperature.
  • the motor bracket 50 includes a first panel 62 and a second panel 64 that are substantially perpendicular to each other, wherein the second panel 62 is fixed with a second motor unit 46 and a third motor. Group 48, second panel 64 is secured to first motor set 44.
  • the motor bracket 50 can be made by a cold working process of a steel plate or by an injection molding process of a hard plastic.
  • the motor bracket 50 is generally in the shape of a capital letter "L" as a whole.
  • at least one weir or rib 66 is provided at the angle between the first panel 62 and the second panel 64 at a substantially 90 degree angle. As shown in FIGS.
  • the first motor unit 44 includes a motor 68 that is fixed to the upper surface of the bottom plate 32 and that does not have a relative displacement with respect to the bottom plate 32, and is coaxially connected to the shaft of the motor 68 by the connector 70.
  • the shaft of the motor 68 drives the ball screw 72 to rotate along its axis through the connector.
  • the axis rotation of the ball screw 72 drives the slider 74 to reciprocate along the axis of the ball screw.
  • the slider 74 drives the motor bracket 50 when the slider 74 reciprocates along the axis of the ball screw 72.
  • the second and third motor units 46, 48 reciprocate between positions "A" and "B” in a plane parallel to the bottom plate 32 and the longitudinal direction of the console 38 (as shown in Fig. 25).
  • the nucleic acid extractor of the present invention includes a magnetic rod holder 78 fixedly coupled to the slider of the second motor unit 46 and a magnetic rod holder 80 fixedly coupled to the slider of the third motor unit 48.
  • the magnetic bar holder 78 is provided with a plurality of rows of magnetic bars 82 downwardly, each row having a plurality of magnetic bars (preferably 4 x 8 magnetic bars).
  • the magnetic rod holder 80 is provided with a number of channels 84 corresponding to the number of magnetic rod rows (e.g., four). Each of the channels 84 can be inserted into a magnetic rod sleeve.
  • the nucleic acid extractor 1 of the present invention is sequentially operated in accordance with the following steps.
  • the sample is placed - a deep well plate (also called a 96-well plate) 88 after the sample is placed is placed at a designated position of the console 38, and then the magnetic rod sleeve 86 is fixed to the magnet holder 80.
  • Channel 84 the first step, the sample is placed - a deep well plate (also called a 96-well plate) 88 after the sample is placed is placed at a designated position of the console 38, and then the magnetic rod sleeve 86 is fixed to the magnet holder 80.
  • Channel 84 also called a 96-well plate
  • the second step, cracking starts the third motor unit 48, causing the magnetic rod sleeve 80 to drive the magnetic rod sleeve 86 down until the magnetic rod sleeve 86 enters the hole of the designated row of the deep hole plate 88, and then the third motor unit 48 drives the magnetic rod sleeve 80 and the magnetic rod sleeve 86 together for a predetermined time at a frequency selected from (2-100) HZ (preferably 2, 4, 8, 16, 21, 30, 50, 80, 100 Hz), magnetic
  • the end of the rod sleeve 86 remote from the rod sleeve 80 is twisted in the hole of the deep orifice plate 88 with a mixture of the sample, the lysate and the magnetic beads (which have been previously placed in the holes of the deep well plate) so that the sample is in the sample.
  • the nucleic acid is separated from the sample (ie, the nucleic acid is cleaved) and adsorbed onto the magnetic beads.
  • the third step, adsorption - the second motor unit 46 starts and drives the magnetic rod holder 78 down until the magnetic rod 82 enters the designated position of the magnetic rod sleeve 86, and is allowed to stand for a predetermined time, so that all the magnetic beads are separated from the sample.
  • the nucleic acid is adsorbed together on the outer surface of the magnetic rod sleeve 86, and then the magnetic rod holder 78 and the magnetic rod sleeve 86 are moved upward together to cause the magnetic rod sleeve 86 and the magnetic rod 82 to enter the washing holes of the designated row of the deep well plate 88 together. Wash to remove impurities.
  • the elution-magnetic bar holder 78 and the magnetic rod sleeve 86 are brought into the elution hole from the washing hole, and the nucleic acid is released from the magnetic beads by the eluent.
  • the magnetic beads are recovered - the magnetic beads adsorbed on the outer surface of the magnetic rod sleeve 86 are transferred from the elution holes into the magnetic bead recovery holes, and the magnetic rods 82 are separated from the magnetic rod sleeve 86.
  • the magnetic detachment - the magnetic rod sleeve 86 vibrates in the magnetic bead recovery hole, so that the magnetic beads are all detached from the outer surface of the magnetic rod sleeve 86.
  • Step 7 clean up - remove the magnetic rod sleeve 86, remove the deep well plate, and return the instrument to the starting position. Among them, in the cleavage and elution steps, it is necessary to heat the sample mixture in the deep well plate to a preset temperature range.
  • the first, second and third motor groups 44, 46, 48 have substantially the same structure, and both adopt precise stepping stepping motors and ball screws.
  • the repeatability of the stepping motor used in the present invention i.e., the displacement error produced by each cycle
  • the first motor unit 44 functions to drive the second and third motor groups 46, 48 to move between the first position and the second position in accordance with a predetermined program.
  • the second motor unit 46 functions to drive the magnetic bar frame 78 up and down.
  • the function of the third motor unit 48 is to drive the magnetic rod sleeve 80 up and down and to vibrate.
  • the present invention provides an encoder 90 on the third motor unit 48.
  • the encoder 90 includes components for monitoring the operation of the stepper motor and components for issuing correction commands to the stepper motor.
  • the encoder issues a correction command to correct the output of the stepper motor according to each pulse.
  • the stroke thus avoids the occurrence of motor out-of-step in advance, and improves the accuracy of the vibration of the third motor unit 48 driving the magnetic rod sleeve 80.
  • the technical solution adopted by the present invention is to fix a light sensing arm 92 on the outer side of the slider 74 of each motor group, and to provide an optocoupler sensor 93 in the initial position and the maximum stroke position of the sliding 74. .
  • the optocoupler sensor 93 senses the sense of light The position of the slider 74 is monitored by the position of the arm 92.
  • the first motor unit 44 can accurately control the cracking of the second and third motor groups (i.e., the magnetic rod holder 80 and the magnetic rod holder 78) corresponding to the deep orifice plate 88.
  • the position of the magnetic beads is washed, eluted, and recovered; the second and third motor groups can accurately control the lowest and highest positions of the magnetic rod holder 80 and the magnetic rod holder 78.
  • each row of heater plates 94 includes a plurality of heating orifice walls 96 that closely conform to the shape of the bottom of the deep orifice plate 88.
  • the heating plate 94 is preferably made of a metal material, and has a heating member (not shown) such as a resistance wire inserted therein, and a heat insulating member (not labeled) is provided on the outer periphery thereof.
  • a plurality of mutually independent compression springs 98 are disposed under the heating plate 94 to urge all of the heating hole walls 96 of the heating plate 94 to more evenly adhere to the bottom of the deep hole plate 88, thereby making the heat of the respective holes more uniform. This will greatly improve the cleavage and elution efficiency of the samples in each well on the deep well plate 88, thereby greatly reducing the error in nucleic acid extraction efficiency in each well.
  • the console 38 includes at least one set of clamps for automatically grasping and loosening the deep orifice plate 88 placed on the console 38.
  • the jig includes a motor 100 located below the bottom plate 32 (i.e., the back of the console 38) (the number of motors corresponds to the number of deep-hole plates), a support portion 104 located inside the console 38, a plurality of clamp arms 106, and micro Switch 108.
  • the clamp arm 106 includes a shaft 105. The up and down movement of the support portion pushes the clamp arm to rotate about the shaft, and the clamp arm 107 clamps or loosens the deep orifice plate.
  • Motor 100 includes a cam 102.
  • the cam 102 pushes the support portion 104 up and down.
  • the support portion 104 further urges the clamp arm 106 to rotate clockwise or counterclockwise in accordance with the principle of leverage, and the clamp arm 106 clamps or releases the outer wall of the deep orifice plate 88.
  • a torsion spring (not numbered) is disposed on the clamp arm 106.
  • the microswitch 108 is located near one end of the console 38.
  • the microswitch 108 includes a spring leaf 110 and a push button switch 112.
  • Fig. 18A is a state in which the micro switch is in a closed state
  • Fig. 19A is a state in which the micro switch is in an on state.
  • the support portion 104 further urges the clamp arm 106 to rotate in accordance with the principle of the lever, so that the clamp arm 106 grips the outer wall of the deep orifice plate 88, thereby precisely fixing the position of the deep orifice plate 88 on the console 38.
  • the operator issues an instruction to release the deep well plate 88 through the instrument panel 22.
  • the motor 100 drives the cam 102 to operate, and the support portion 104 moves downward under the action of the spring and its own gravity.
  • the clamp arm 106 Under the action of the torsion spring, the clamp arm 106 is reversed, returning to the state in which the deep hole plate 88 is released, and no clamping force is applied to the deep hole plate. Thus, the operator can easily remove the deep well plate 88 from the console 38.
  • the console 38 is provided at its end adjacent the instrument panel 22 with a cross flow fan 114 for dissipating heat outside the instrument.
  • the cross flow fan 114 is hidden below the operation panel 52 of the console 38.
  • the air outlet of the cross flow fan 114 is located at the bottom of the nucleic acid extractor of the present invention.
  • the instrument body 30 of the nucleic acid extractor of the present invention is substantially The base 10 and the outer casing 20 are closed, and only the cross-flow fan 114 is provided with an air outlet at the bottom of the base 10.
  • the nucleic acid extractor of the present invention is further provided with an inner casing 34 and an operation panel 52.
  • the inner casing 34 and the operating panel 52 substantially confine the deep orifice plate 88 to a relatively enclosed space. The above structural design is very beneficial to prevent the external environment from affecting the cleaning inside the instrument.
  • the door 24 of the nucleic acid extractor 1 of the present invention includes a door handle 116 and a door shaft 118.
  • the outer casing 20 is provided with a permanent magnet magnet block (not shown) at a position corresponding to the door handle 116.
  • the permanent magnet magnet block sucks the door handle 116, thereby keeping the door 24 closed.
  • the door shaft 118 includes a door inner shaft 120 fixed to the base 10 and a door bushing 122 fixed to the bottom two ends of the door.
  • the two ends of the door center shaft 120 are respectively incorporated into the door bushing 122, and a door shaft torsion spring 124 is provided at the joint of the door center shaft 120 and the door bushing 122.
  • the door shaft torsion spring 124 maintains a certain damping coefficient for the combination between the door center shaft 120 and the door bushing 122, thereby increasing the hand feeling when the door 24 is opened and closed, which increases the operator's pleasure.
  • Figure 34 illustrates the working principle and steps of the nucleic acid extractor of the present invention.
  • Step 1 Add a sample (such as whole blood) to the deep well plate.
  • Step 2 Heat and lyse the sample under the on-board vibration of the magnetic rod sleeve.
  • the third step the magnetic rod enters the magnetic rod sleeve and adsorbs the magnetic beads and the nucleic acid.
  • the fourth step washing off the impurities under the action of the washing liquid.
  • Step 5 The nucleic acid is eluted from the magnetic rod sleeve under the action of the eluent.
  • Step 6 Recycle the magnetic beads.
  • Step 7 The magnetic rod is removed from the magnetic rod sleeve, and under the mechanical vibration of the magnetic rod sleeve, the magnetic beads are detached from the magnetic rod sleeve and fall into the magnetic bead recovery hole.
  • Figure 35 is a schematic view of Figure 34 showing the immobilized deep well plate and the sample of the nucleic acid extractor of the present invention.
  • a part A of the present patent application (including the patent application specification and the claims) is fixed to another part B or a similar description means that a part A is directly or indirectly fixed to another part B, including One component A and the other component B are fixedly coupled to each other in contact with each other, and a component A and another component B are not in contact with each other, but are fixedly connected by a third component.
  • a part A is directly or indirectly fixed to another part B, including One component A and the other component B are fixedly coupled to each other in contact with each other, and a component A and another component B are not in contact with each other, but are fixedly connected by a third component.

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Abstract

本发明的目的在于提供一种核酸提取仪,包括:基座、与基座相连的外机壳、位于外机壳的内部并且被安装到基座的仪器主体。仪器主体包括相对于基座可移动的操作台和被分别固定到基座的第一电机组、第二电机组以及第三电机组。其中,第一电机组用于驱动所述操作台在与基座所在的平面大致平行的平面内运动,第二电机组和第三电机组被固定到基座,并且相对于基座不可移动。所述操作台包括用于自动固定深孔板的夹具和对深孔板进行加热的加热装置。本发明所述核酸提取仪的核酸提取效率高、运行精度高、稳定性好。

Description

一种核酸提取仪 技术领域
本发明涉及一种核酸提取仪。
背景技术
在基因工程和蛋白质工程技术研究领域,核酸分子是主要研究对象,而核酸的分离和线性化是核酸研究的基本技术。核酸是代表生命体遗传特征的基本单元,核酸检测是在分子水平上进行先进的生物检测,相比传统的形态学检测、细胞学检测、免疫学检测等更具灵敏性、特异性、无窗口期等显著优点。核酸检测包括定性PCR、分子杂交,实时荧光定量PCR等技术,这些核酸检测技术的首要关键是要完成对生物样本的核酸进行提取,因此有效、准确地提取核酸模板成为了后续核酸检测的前提。目前,国内核酸提取主要采用传统的手工制备方法,不仅效率低下,成本高,而且重复性和稳定性都不好。
发明内容
本发明的目的在于提供一种核酸提取仪,包括:基座、与基座相连的外机壳、位于外机壳的内部并且被安装到基座的仪器主体;仪器主体包括相对于基座可移动的操作台和被分别固定到基座的第一电机组、第二电机组以及第三电机组,其中,第一电机组用于驱动所述操作台在与基座所在的平面大致平行的平面内运动,第二电机组和第三电机组被固定到基座,并且相对于基座不可移动,所述操作台包括 用于自动固定深孔板的夹具和对深孔板进行加热的加热装置。
进一步地,第一电机组的轴线与基座所在的平面大致平行,第二电机组和第三电机组的轴线与基座所在的平面大致垂直。
进一步地,第一电机组包括:固定在基座上的相对于基座不能产生相对位移的电机、藉由连接器与电机的轴同轴线连接的滚珠丝杆、连接至滚珠丝杆的滑块和对滑块起导向作用的导轨。
进一步地,第二、第三电机组籍由电机支架固定至第一电机组的滑块,在第一电机组的驱动下沿第一电机组之电机的轴线方向往复运动,所述电机支架包括大致相互垂直的第一面板和第二面板,第一面板用于固定第二、第三电机组,第二面板被固定至第一电机组上的滑块。
进一步地,第三电机组包括用于控制其电机运转的编码器,所述编码器包括监测第三电机组之电机运行状况的元器件和向该电机发出修正指令的元器件。
进一步地,第三电机组在其滑块的外侧边固定一个光感应臂,而在滑块位于第三电机组的初始位置和最大行程位置处各设置一个光耦传感器,光耦传感器通过感应光感应臂的位置来监控滑块的位置。
进一步地,所述加热装置包括设置在核酸提取仪之操作台上的若干排活动的加热板,每一排加热板包括与被加热的深孔板之底部形状密切吻合的若干个加热孔壁,加热板采用导热材料,其内部贯穿有加热部件,其外周设置有隔热部件,在加热板的下面设置有若干个相互独立的压缩弹簧,压缩弹簧抵靠在加热板的下方。
进一步地,还包括位于操作台下方的散热装置,所述散热装置包括被隐藏在操作台下方的横流风机。
进一步地,仪器主体还包括电源组和至少一组用于控制电源能量输出的电源管理组件,所述电源管理组件包括至少一块印刷电路板、若干电容和电阻,以及至少一个电源调节器和紧贴电源调节器的散热器,所述电源调节器包括用于把在核酸提取仪运行过程中可能产生的瞬时过载电压或者过载电流转换成热能而消耗掉的发热电子元器件。
进一步地,所述夹具包括位于基座下方的电机、位于操作台内部的支撑部、若干个夹臂和微动开关,其中,电机包括一个凸轮,在电机启动时,凸轮推动支撑部上、下移动,支撑部进一步推动夹臂转动,夹臂夹紧或者释放深孔板的外壁,所述微动开关包括一个倾斜的弹簧片和一个按钮开关,当深孔板被放置到操作台的预定位置时,深孔板的底部推动弹簧片压缩按钮开关,从而开启微动开关,启动电机工作。
本发明有益效果是:由于本发明将需要输出动力的第二电机组和需要输出高频率振动的第三电机组固定在基座上,而将不需要做高速移动的操作台设计成可相对于基座移动,从而解决了现有技术中把需要输出高频率振动的第三电机组设计成活动式所导致的不稳定性的问题。因此,本发明的核酸提取仪的核酸提取效率高、运行精度高、稳定性好。提取效率比现有技术高2-4倍,提取出来的浓度比现有技术高2-4倍,因此,可以用于做超敏检测。原因是,本发明采用活动的加热装置,在加热板的下方设置若干个弹簧,当深孔板放置到加热板上后,深孔板的底部向下挤压加热板,因此二者之间形成很好 的贴合度。因此,各个孔受热均匀,温度差异小,各个孔内的样本被裂解的速度和程度比现有技术更加均一。另外,磁棒套采用疏水性材料制作,因此,其吸磁和脱磁和机械搅拌效率高,并且均匀。再者,本发明采用比现有技术更高频率的步进电机和精度更高的滚珠丝杆做为传动系统,因此,磁棒套和磁棒的运动精度比现有技术更高,磁棒套的机械搅拌效率更高,磁棒控制精准,不碰壁,不沾磁珠。磁珠回收率非常高,达98%以上。超静音,采用滚珠丝杆后,仪器产生的整体噪音低于60dB,甚至低于53dB,现有技术大于80dB。核酸提取仪所包括的电源调节器用于把在核酸提取仪运行过程中可能产生的瞬时过载电压或者过载电流转换成热能而消耗掉,以避免因温度过高而烧毁电源调节器。本发明在电机组上设置了一个编码器,该编码器会根据步进电极的运行情况,发出一个修正指令,及时修正步进电机按照每个脉冲所输出的行程,从而提前避免了电机失步的发生,提高了电机组驱动磁棒套架振动的精度。
附图说明
图1是本发明核酸提取仪的示意图;
图2是图1移除外机壳和底座后的示意图;
图3是图2之另一视角的示意图;
图4是本发明核酸提取仪去掉内、外机壳后的示意图;
图5是图4的另一视角的示意图;
图6是图5移除部分部件后的示意图;
图7是图6移除部分部件后的示意图;
图8与图4相似,是本发明核酸提取仪处于初始状态时的示意图;
图9与图8相似,是本发明核酸提取仪插入磁套后的示意图;
图10与图9相似,是本发明核酸提取仪放置深孔板后的示意图;
图11与图10相似,是本发明核酸提取仪的磁棒套进入深孔板后的示意图;
图12是本发明核酸提取仪的磁棒套和磁棒均进入深孔板后在第一位置时的平面示意图;
图13与图12相似,但第一电机组驱动第二、第三电机组移动到第二位置时的平面示意图;
图14是本发明核酸提取仪的磁棒套和磁棒吸附磁珠和核酸后的示意图;
图15是本发明核酸提取仪的磁棒套和磁棒运动过程中的平面示意图;
图16与图13相似,但磁棒套和磁棒均进入深孔板的第二位置时的平面示意图;
图17是操作台的平面示意图;
图17A是图17中标示部位的局部放大视图;
图18是操作台的另一角度的平面示意图;
图18A是图18中标示部位的局部放大视图;
图19是与图18相似的平面示意图,开关处于触发状态;
图19A是图19中标示部位的局部放大视图;
图20-23是夹具工作示意图;
图24是电源控件部件的放大示意图;
图24A是图24的局部放大图;
图25是第一电机组的放大示意图;
图26是第三电机组的放大示意图;
图27是本发明核酸提取仪移除部分部件后的示意图;
图27A是图27的局部放大示意图;
图28是本发明核酸提取仪之底板和操作台的示意图;
图28A是图28的局部放大示意图;
图29是图28移除操作面板后的示意图;
图30是从下向上看底板的示意图;
图31是本发明的原理示意图;
图32是本发明核酸提取仪之门的示意图;
图32A是图32之局部放大示意图;
图33是本发明核酸提取仪之门的局部放大示意图;
图33A是图33之局部放大示意图;
图34是本发明核酸提取仪的操作流程示意图;
图35是本发明核酸提取仪夹紧深孔板和对深孔板进行加热的示意图。
具体实施方式
下面结合具体附图对本发明进行详细的说明。这些具体的实施例 仅仅是在不违背本发明精神下的有限列举,并不排除本领域的一般技术人员把现有技术和本发明结合而产生的其他具体的实施方案。
如图1所示,本发明核酸提取仪1包括位于底部的基座10、位于基座之上的外机壳20、位于外机壳的内部并且固定到基座10的仪器主体30。基座10选用比重较重、成本低廉的材料制作(如铸铁、钢材,或者钢板内填充混泥土等),以使基座具有较大的质量,从而可有效防止核酸提取仪在运行过程中发生振动和位移。外机壳20优先选用0.1-2.0毫米厚的不锈钢板经冷轧和冷切割等工艺加工制作。在其它的方案中,外机壳20也可以选用塑料材料,采用注塑成型工艺制作,以便降低成本。在外机壳20上还可以设计若干条相互平行或者纵横交错的筋或者肋,以提高外机壳的强度。优选地,根据选用的材料不同,对外机壳20还可以进行喷漆、电脑喷绘、电脑雕刻、蚀刻或电镀等工艺处理,以使外机壳具有更佳的外观。外机壳20在面对操作者的那一面,即核酸提取仪1的正面,设计有仪表面板22和可以多次开启和关闭的门24。其中,仪表面板22上可以设计有显示屏和若干个操作键,方便操作者进行操作。优选地,仪表面板22上设计有触摸液晶显示屏,从而方便操作者可以直接触摸液晶显示屏进行操作。
如图2-6所示,仪器主体30包括固定到前述基座10的底板32、内机壳34、龙门架36、操作台38、电源组40、主控装置42和第一电机组44、第二电机组46以及第三电机组48。底板32提供至少一个用于支撑前述组件的平面。优选地,底板32是厚度介于1.0-10.0 毫米的钢板,它应当具备适度的刚性并且能够保持至少一个面成一个平面的形状,不容易发生弯曲、扭曲和局部翘起等。为节约成本,在满足上述要求的条件下,底板32也可以由硬质塑料经注塑成型工艺制作,或者选用硬质木材、竹材经木工加工工艺制作。在一个实施例中,当底板32具有足够的厚度、刚性和质量时,底板32也可以充当基座10。其中,在一个较佳的实施例中,内机壳34、龙门架36、操作台38、电源组40和第一电机组44分别被固定到所述底板32上。为了节约空间,主控装置42被安置在电源组40的背面(如图3所示)。如图6和图7所示,第一电机组44被固定在底板32的上表面上,并且其纵长方向或者轴线与底板的上表面平行;第二电机组46和第三电机组48先被固定至电机支架50上,然后再藉由电机支架50安装到第一电机组44上。第二电机组46和第三电机组48相邻并行排列,其轴线相互平行,并且分别与底板32的上表面垂直。龙门架36上设计有一个导轨或者滑道43,电机支架50对应该导轨43处设计一个滑块51,滑块51被限定在导轨43内滑动。如此设计既可以提高电机支架50在运动中的稳定性,又可以提高本发明核酸提取仪在运输和搬动过程中对电机支架50的保护作用。在一种实施方式中,龙门架36包括至少一根横梁37和两根用于支撑栋梁37的竖梁39和41。其中所述导轨43就被设计在横梁37上,竖梁39和41则分别被固定至底板32或者基座10的上表面。
如图4所示,操作台38包括一个邻近核酸提取仪1之正面的偏平的、大致呈长方体形的操作面板52。操作面板52应当具有适当的 刚性和强度,不容易变形。操作面板52可以由不锈钢板经冷加工工艺制作,或者由硬质塑料经注塑成型工艺制作。操作面板52包括一个与底板32之上表面大致平行的平台台,提取核酸的操作基本上都是在此平台上完成的。该平台包括二条与核酸提取仪1之正面大致平行的纵长边。在门24处于开启状态时,操作者可以双手或者单手从门24进入,在操作台38上进行提取核酸的操作。在操作台38的后方(即比操作台38更远离核酸提取仪正面的位置,请参阅图6和图7),安装有第一电机组44。第一电机组44的纵长或者轴线方向与操作台38的纵长边大致平行。
电源组40包括将220伏特或者110伏特的通用电压转换成适合驱动本发明核酸提取仪内部各种电子元器件之电压的元器组件(未标号)和至少一组电源管理组件54。为节省空间,电源管理组件54被固定在电源组40的上方(如图4和图5所示)。请参阅图24和图24A,电源管理组件54包括至少一块印刷电路板56、若干电容、电阻等电子元器件,以及至少一个电源调节器58和散热器60。散热器60紧贴电源调节器58。电源调节器58包括发热电子元器件,用于把在核酸提取仪运行过程中可能产生的瞬时过载电压或者过载电流转换成热能而消耗掉。散热器60则用于把电源调节器58产生的热能及时导走,从而给电源调节器58降温,以避免因温度过高而烧毁电源调节器58。
如图6所示,电机支架50包括大致相互垂直的第一面板62和第二面板64,其中,第一面板62上固定有第二电机组46和第三电机 组48,第二面板64被固定至第一电机组44。电机支架50可以由钢板经冷加工工艺制作,也可以由硬质塑料经注塑成型工艺制作。电机支架50整体上大致呈大写字母“L”形。为提高电机支架50的强度,并且节省用料和降低重量,在第一面板62和第二面板64大致呈90度角的那个夹角设置至少一条筯或者肋66。如图6和图25所示,第一电机组44包括固定在底板32之上表面并且相对于底板32不能产生相对位移的电机68、藉由连接器70与电机68的轴同轴线连接的滚珠丝杆72、连接至滚珠丝杆72的滑块74和对滑块74起导向作用的导轨76。当第一电机组44工作时,电机68的轴通过连接器带动滚珠丝杆72沿其轴线转动。滚珠丝杆72的轴线转动驱动滑块74沿滚珠丝杆的轴线做往复移动。因为电机支架50的第二面板64是被固定至第一电机组44上的滑块74的,所以,当滑块74沿滚珠丝杆72的轴线做往复移动时,滑块74驱动电机支架50和第二、三电机组46、48在平行于底板32的平面和操作台38的纵长方向在位置“A”和“B”之间做往复移动(如图25所示)。
如图8所示,本发明核酸提取仪包括固定连接至第二电机组46之滑块的磁棒架78和固定连接至第三电机组48之滑块的磁棒套架80。磁棒架78向下设有若干排磁棒82,每排有若干根磁棒(优选为4X8根磁棒)。磁棒套架80向下设有与磁棒排数对应数量(如四个)的槽道84。每个槽道84可以插入一个磁棒套。
图8-16示意了本发明核酸提取仪1的运行过程。在起始位置时,磁棒架78与磁棒套架80是相互分开的,并且与操作台38相隔足够 大的距离。本发明核酸提取仪1按照下列步骤依次运行。第一步,加样――把加入样本后的深孔板(又叫96孔板)88放入到操作台38的指定位置处,然后,把磁棒套86固定到磁棒套架80的槽道84。第二步,裂解――启动第三电机组48,使磁棒套架80带动磁棒套86下行,直到磁棒套86进入深孔板88之指定排的孔内,然后,第三电机组48带动磁棒套架80和磁棒套86一起按选自于(2-100)HZ(优选2、4、8、16、21、30、50、80、100HZ)的频率振动预定时间,磁棒套86之远离磁棒套架80的那一端在深孔板88的孔内绞拌样本、裂解液和磁珠(已被预先放置在深孔板的孔内)的混合物,使样本中的核酸从样本中分离出来(即核酸被裂解),并且被吸附到磁珠上。第三步,吸附――第二电机组46启动并带动磁棒架78下行,直到磁棒82进入磁棒套86的指定位置,静置预定时间,使全部磁珠连同从样本里裂解出来的核酸一起被吸附在磁棒套86的外表面,然后,磁棒架78和磁棒套86一起上行再使磁棒套86和磁棒82一起进入深孔板88之指定排的洗涤孔内进行洗涤,以除去杂质。第四步,洗脱――磁棒架78和磁棒套86一起由洗涤孔进入到洗脱孔内,在洗脱液的作用下,核酸从磁珠中释放出来。第五步,回收磁珠――将吸附在磁棒套86之外表面的磁珠由洗脱孔转移至磁珠回收孔内,磁棒82离开磁棒套86。第六步,弃磁――磁棒套86在磁珠回收孔内振动,使磁珠全部从磁棒套86的外表面脱落。第七步,清理――卸下磁棒套86,移走深孔板,仪器回到起始位置。其中,在裂解、洗脱步骤,需要将深孔板内的样本混合液加热到预先设定的温度范围。
如图7、图25和图26所示,第一、二、三电机组44,46,48的结构大致相同,均采用精确走位的步进电机和滚珠丝杆。本发明所采用的步进电机的重复精度(即每一个循环所产生的位移误差)小于0.02毫米。如前所述,第一电机组44的作用是用于按照预先设定的程序驱动第二、三电机组46、48在第一位置和第二位置之间移动。第二电机组46的作用是用于驱动磁棒架78上下移动的。第三电机组48的作用是用于驱动磁棒套架80上下移动和振动。由于第三电机组48要驱动磁棒套架80高频率地振动,振动频率越高,磁棒套架本身的质量产生的惯性对第三电机组48的冲量越大,干扰越大。因此,电机失步(在一个脉冲下,步进电机输出的位移误差超出发设计值的情况称之为电机失步)的发生概率也越大。为了避免电机失步,本发明在第三电机组48上设置了一个编码器90。编码器90包括监测步进电机运行状况的元器件和向步进电机发出修正指令的元器件。当步进电机接收一个脉冲后产生的行程与预先设计的值的误差大于预先设定的值(如1.25微米)时,编码器发出一个修正指令,及时修正步进电机按照每个脉冲所输出的行程,从而提前避免了电机失步的发生,提高了第三电机组48驱动磁棒套架80振动的精度。
除了电机组的运行精度以外,影响磁棒套架80和磁棒架78运动精度的因素还包括磁棒套架80和磁棒架78的初始定位精度和最大行程的位置精度。为此,本发明采取的技术方案是:在每个电机组之滑块74的外侧边固定一个光感应臂92,而在滑快74的初始位置和最大行程位置各设置一个光耦传感器93。光耦传感器93藉由感应光感 应臂92的位置来监控滑块74的位置。因此,本发明在采用光耦传感器93后,第一电机组44可以准确地控制第二和第三电机组(也就是磁棒套架80和磁棒架78)对应于深孔板88的裂解、洗涤、洗脱和回收磁珠的位置;第二、三电机组可以准确地控制磁棒套架80和磁棒架78的最低和最高位置。
如图17和图17A所示,在操作台38上设置有若干排活动的加热板94。每一排加热板94包括与深孔板88之底部形状密切吻合的若干个加热孔壁96。加热板94优选金属材料,其内部贯穿有电阻丝等加热部件(未标号),其外周设置有隔热部件(未标号)。在加热板94的下面设置有若干个相互独立的压缩弹簧98,促使加热板94的所有加热孔壁96更加均匀地贴附深孔板88的底部,从而使各个孔的受热更加的均匀。这将大大地提高深孔板88上各个孔内样本的裂解和洗脱效率的一致性,从而大大减小了各个孔内核酸提取效率的误差。
如图23、27、27A和30所示,操作台38包括至少一套用于自动抓紧和松开放置到操作台38上之深孔板88的夹具。该夹具包括位于底板32之下方(即操作台38的背面)的电机100(电机的数量与深孔板的数量对应)、位于操作台38之内部的支撑部104、若干个夹臂106和微动开关108。所述的夹臂106包括一个轴105,支撑部的上下移动推动夹臂绕该轴转动,夹臂的夹头107夹紧或松开深孔板。电机100包括一个凸轮102。在电机100启动时,凸轮102推动支撑部104上、下移动。支撑部104进一步推动夹臂106按照杠杆原理进行顺时针或逆时针转动,夹臂106夹紧或者释放深孔板88的外壁。在 夹臂106上设置有扭簧(未标号),当操作台38没有放置深孔板88时,扭簧使夹臂保持松开状态,以减少把深孔板88放置到操作台38的阻碍。
如图18、18A、19、19A、20、21、22、23、28和28A所示,微动开关108位于操作台38的一端附近。微动开关108包括一个弹簧片110和一个按钮开关112。图18A是微动开关处于关闭的状态,图19A是微动开关处于开启的状态。当深孔板88被放置到操作台38的预定位置时,深孔板88的侧壁推动弹簧片110压缩按钮开关112,从而开启微动开关108,启动电机100工作。电机100带动凸轮102推动支撑部104向上移动。支撑部104进一步推动夹臂106按照杠杆原理转动,使夹臂106夹紧深孔板88的外壁,从而精确固定深孔板88在操作台38上的位置。当提取核酸的全程结束以后需要从操作台38取下深孔板88时,操作者通过仪表面板22发出释放深孔板88的指令。电机100带动凸轮102运转,在弹簧和自身重力的作用下,支撑部104下移。在扭簧的作用下,夹臂106反转,回复到释放深孔板88的状态,并且不对深孔板施加夹持力。因而,操作者可以轻易地从操作台38上移走深孔板88。
如图28、29和30所示,操作台38在其靠近仪表面板22的那一端设置有用于向仪器外散发热量的横流风机114。所述横流风机114被隐藏在操作台38之操作面板52的下方。横流风机114的出风口位于本发明核酸提取仪的底部。
如图1、2和3所示,本发明核酸提取仪的仪器主体30基本上被 基座10和外机壳20所封闭,而仅在基座10的底部为横流风机114设置了出风口。本发明核酸提取仪还进一步设置有内机壳34和操作面板52。内机壳34和操作面板52基本上把深孔板88限制在一个相对封闭的空间内。上述结构设计既非常利于防止外部环境影响仪器内部的清洁。
如图32、32A和33、33A所示,本发明核酸提取仪1的门24包括门拉手116和门轴118。其中,外机壳20在对应于门拉手116的位置处设置有永磁磁块(未图示),当门关闭时,永磁磁块吸住门拉手116,从而使门24保持闭合状态。门轴118包括固定在固定至基座10的门中轴120和固定至门的底部二端的门轴套122。门中轴120的二端分别被组入到门轴套122内,并且在门中轴120与门轴套122结合处设置有门轴扭簧124。门轴扭簧124使门中轴120与门轴套122之间的结合保持有一定的阻尼系数,从而增加开启和关闭门24时的手感,增加了操作者的愉悦感。
图34示意了本发明核酸提取仪的工作原理和步骤。第一步:向深孔板内加入样本(如全血)。第二步:加热并且在磁棒套的机载振动下裂解样本。第三步:磁棒进入磁棒套内并且吸附磁珠和核酸。第四步:在洗涤液的作用下洗涤掉杂质。第五步:在洗脱液的作用下把核酸从磁棒套上洗脱下来。第六步:回收磁珠。第七步:把磁棒移出磁棒套,在磁棒套的机械振动作用下,磁珠从磁棒套脱落,掉入到磁珠回收孔内。
图35示意了图34示意了本发明核酸提取仪固定深孔板和对样本 进行加热的步骤。第一步:放置深孔板。第二步:触发微动开关。第三步:CPU信号响应。第四步:电机启动。第五步:支撑部上移。第六步:夹臂夹紧。第七步:加热板与深孔板紧密贴合。
本专利申请(包括专利申请说明书和权利要求书)所记载的某部件A被固定至另一部件B或者相类似的描述是指,某部件A被直接或者间接地固定至另一部件B,包括某部件A与另一部件B相互接触地固定连接在一起和某部件A与另一部件B不相互接触、而是通过第三部件固定地连接在一起二种情况。广义地说,只要某部件A与另一部件B不能相对运动,均属于本专利申请所记载的某部件A被固定至另一部件B的范围。
本专利申请所披露的内容仅仅是对本发明创造之具体实施方式的有限记载,任何根据本专利申请所披露的内容而进行的不需要做出创造性劳动的有限改进均属于本发明创造的范畴。

Claims (10)

  1. 一种核酸提取仪,包括:基座、与基座相连的外机壳、位于外机壳的内部并且被安装到基座的仪器主体;其特征在于,仪器主体包括相对于基座可移动的操作台和被分别固定到基座之上表面的第一电机组、第二电机组以及第三电机组,其中,第一电机组用于驱动所述操作台在与基座的上表面平行的平面内运动,第二电机组和第三电机组被固定到基座,并且相对于基座不可移动,所述操作台包括用于自动固定深孔板的夹具和对深孔板进行加热的加热装置。
  2. 根据权利要求1所述的核酸提取仪,其特征在于:第一电机组的轴线与基座的上表面平行,第二电机组和第三电机组的轴线与基座的上表面垂直。
  3. 根据权利要求1所述的核酸提取仪,其特征在于:第一电机组包括:固定在基座上的相对于基座不能产生相对位移的电机、藉由连接器与电机的轴同轴线连接的滚珠丝杆、连接至滚珠丝杆的滑块和对滑块起导向作用的导轨。
  4. 根据权利要求3所述的核酸提取仪,其特征在于:第二、第三电机组籍由电机支架固定至第一电机组的滑块,在第一电机组的驱动下沿第一电机组之电机的轴线方向往复运动,所述电机支架包括相互垂直的第一面板和第二面板,第一面板用于固定第二、第三电机组,第二面板被固定至第一电机组上的滑块。
  5. 根据权利要求1-4之一所述的核酸提取仪,其特征在于:第三电机组包括用于控制其电机运转的编码器,所述编码器包括监测第三电机组之电机运行状况的元器件和向该电机发出修正指令的元器件。
  6. 根据权利要求5所述的核酸提取仪,其特征在于:第三电机组在其滑块的外侧边固定一个光感应臂,而在滑块位于第三电机组的初始位置和最大行程位置处各设置一个光耦传感器,光耦传感器通过感应光感应臂的位置来监控滑块的位置。
  7. 根据权利要求6所述的核酸提取仪,其特征在于:所述加热装置包括设置在核酸提取仪之操作台上的若干排活动的加热板,每一排加热板包括与被加热的深孔板之底部形状密切吻合的若干个加热孔壁,加热板采用导热材料,其内部贯穿有加热部件,其外周设置有隔热部件,在加热板的下面设置有若干个相互独立的压缩弹簧,压缩弹簧抵靠在加热板的下方。
  8. 根据权利要求7所述的核酸提取仪,其特征在于:还包括位于操作台下方的散热装置,所述散热装置包括被隐藏在操作台下方的横流风机。
  9. 根据权利要求1-4之任一者所述的核酸提取仪,其特征在于:仪器主体还包括电源组和至少一组用于控制电源能量输出的电源管理组件,所述电源管理组件包括至少一块印刷电路板、若干电容和电阻,以及至少一个电源调节器和紧贴电源调节器的散热器,所述电源调节器包括用于把在核酸提取仪运行过程中可能产生的瞬时过载电压或者过载电流转换成热能而把能量消耗掉的发热电子元器件。
  10. 根据权利要求1-4之任一者所述的核酸提取仪,其特征在于:所述夹具包括位于基座下方的电机、位于操作台内部的支撑部、若干个夹臂和微动开关,其中,电机包括一个凸轮,在电机启动时,凸轮 推动支撑部上、下移动,支撑部进一步推动夹臂转动,夹臂夹紧或者释放深孔板的外壁,所述微动开关包括一个倾斜的弹簧片和一个按钮开关,当深孔板被放置到操作台的预定位置时,深孔板的底部推动弹簧片压缩按钮开关,从而开启微动开关,启动电机工作。
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