CN110361527B - Magnetic bead cleaning and separating device and chemiluminescence immunoassay analyzer - Google Patents
Magnetic bead cleaning and separating device and chemiluminescence immunoassay analyzer Download PDFInfo
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- CN110361527B CN110361527B CN201810252678.7A CN201810252678A CN110361527B CN 110361527 B CN110361527 B CN 110361527B CN 201810252678 A CN201810252678 A CN 201810252678A CN 110361527 B CN110361527 B CN 110361527B
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- 239000011324 bead Substances 0.000 title claims abstract description 196
- 238000004140 cleaning Methods 0.000 title claims abstract description 115
- 238000003018 immunoassay Methods 0.000 title claims abstract description 14
- 238000012546 transfer Methods 0.000 claims abstract description 165
- 238000006243 chemical reaction Methods 0.000 claims abstract description 159
- 239000007788 liquid Substances 0.000 claims abstract description 150
- 238000002347 injection Methods 0.000 claims abstract description 82
- 239000007924 injection Substances 0.000 claims abstract description 82
- 238000001179 sorption measurement Methods 0.000 claims description 66
- 230000002776 aggregation Effects 0.000 claims description 49
- 238000004220 aggregation Methods 0.000 claims description 49
- 239000000758 substrate Substances 0.000 claims description 37
- 238000005406 washing Methods 0.000 claims description 32
- 238000000926 separation method Methods 0.000 claims description 11
- 238000004458 analytical method Methods 0.000 claims description 7
- 230000000149 penetrating effect Effects 0.000 claims description 7
- 238000007599 discharging Methods 0.000 claims description 4
- 230000000694 effects Effects 0.000 abstract description 19
- 230000001965 increasing effect Effects 0.000 abstract description 9
- 238000000034 method Methods 0.000 description 14
- 230000008569 process Effects 0.000 description 12
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- 230000009471 action Effects 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
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- 238000011534 incubation Methods 0.000 description 1
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- 238000004020 luminiscence type Methods 0.000 description 1
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/02—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
- G01N35/04—Details of the conveyor system
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
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- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/02—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
- G01N35/025—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations having a carousel or turntable for reaction cells or cuvettes
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- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
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- G01N35/04—Details of the conveyor system
- G01N2035/0401—Sample carriers, cuvettes or reaction vessels
- G01N2035/0437—Cleaning cuvettes or reaction vessels
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
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- G01N35/02—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
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Abstract
The invention provides a magnetic bead cleaning and separating device which comprises a base, a transfer disc, a liquid injection and drainage assembly and a plurality of magnetic pieces. The transfer disc movably arranged on the base transfers the reaction cups to corresponding operation positions on the base in sequence. The magnetic pieces are arranged on two side surfaces of the transfer path of the reaction cup, an arrangement included angle is formed between a connecting line of each magnetic piece passing through the end parts of the two magnetic poles and the vertical line, and the arrangement included angles comprise a first included angle and a second included angle which are different. The invention also provides a chemiluminescent immunoassay analyzer comprising the magnetic bead cleaning and separating device. In the magnetic bead cleaning and separating device and the chemiluminescent immunoassay analyzer, the magnetic parts arranged at different sides form a pulling effect on the magnetic beads in the reaction cup, and the magnetic parts with different included angles are arranged to attract the magnetic beads in different directions, so that the magnetic beads in the reaction cup are sufficiently and rapidly scattered. The magnetic pieces with different included angles can be arranged to gather the magnetic beads in different directions, so that the gathering speed of the magnetic beads is increased.
Description
Technical Field
The invention relates to the technical field of medical device cleaning, in particular to a magnetic bead cleaning and separating device and a chemiluminescent immunoassay analyzer.
Background
Chemiluminescent immunoassay is a novel ultramicro analysis technology established by combining luminescent analysis and immune reaction. The technology utilizes a chemical or bioluminescent system as an indicator system for an antigen-antibody reaction, thereby quantitatively detecting an antigen or antibody. This method combines high sensitivity of luminescence analysis with high specificity of antigen-antibody reaction. Magnetic bead washing separation is an important preparatory step for chemiluminescent immunoassay. During the process of cleaning and separating the magnetic beads, the aggregated magnetic beads need to be scattered to increase the cleaning effect of the magnetic beads. Traditional magnetic bead washs separator and breaks up the structure through mechanical type and realizes breaking up of magnetic bead, and not only the structure is complicated, bulky, manufacturing cost is high, and exists and breaks up the risk that the effect is poor because of structural failure causes, for example shakes the pollution that splashes that produces, breaks up the in-process friction and causes scrape the flower and then influence the result measurement, or breaks up carrying pollution etc. that the device brought. In recent years, scattering and aggregation in the process of cleaning and separating magnetic beads are realized by using magnet arrangement in a small number of magnetic bead cleaning and separating devices. However, in a magnetic bead cleaning and separating device for scattering and gathering magnetic beads by using magnet arrangement, the stress of the magnetic beads is single, the scattering and gathering speed of the magnetic beads is low, and the loss rate of the magnetic beads is high.
Disclosure of Invention
Accordingly, it is necessary to provide a magnetic bead washing and separating apparatus and a chemiluminescent immunoassay analyzer having a low magnetic bead loss rate, in order to solve the problem of high magnetic bead loss rate in the conventional magnetic bead washing and separating apparatus.
A magnetic bead washing and separating device, comprising:
the base is provided with a plurality of operation positions;
the transfer disc is movably arranged on the base, a plurality of bearing positions for bearing the reaction cups are arranged on the transfer disc, and the transfer disc sequentially transfers the reaction cups to the corresponding operation positions;
the liquid injection and drainage assembly is arranged on the corresponding operation position and is used for injecting and draining liquid into the reaction cup;
the magnetic pieces are arranged on two side surfaces of the transfer path of the reaction cup, and each magnetic piece corresponds to one operation position independently;
each magnetic piece passes through a connecting line of two magnetic pole ends to form an arrangement included angle with a vertical line, and the arrangement included angles comprise a first included angle and a second included angle, and the first included angle is different from the second included angle.
In one embodiment, the plurality of magnetic pieces comprises a plurality of first magnetic pieces and a plurality of second magnetic pieces, and the first magnetic pieces and the second magnetic pieces are respectively arranged on two side surfaces of the transfer path of the reaction cup; the arrangement included angle formed by the connecting line of the two magnetic pole ends and the vertical line of the first magnetic piece is a first included angle, and the arrangement included angle formed by the connecting line of the two magnetic pole ends and the vertical line of the second magnetic piece is a second included angle.
In one embodiment, the transfer disc is provided with a rotating shaft, the rotating shaft is rotatably arranged on the base, and the transfer disc sequentially transfers the reaction cups to the corresponding operation positions by rotating around the rotating shaft; the extending direction of the rotating shaft is parallel to the vertical line, and the connecting line of the first magnetic piece passing through the two magnetic pole ends is intersected with the straight line where the extending direction of the rotating shaft is located.
In one embodiment, the line of the first magnetic piece passing through the two magnetic pole ends is perpendicular to the vertical line, and the line of the second magnetic piece passing through the two magnetic pole ends is parallel to the vertical line.
In one embodiment, the first magnetic members are disposed on the inner side of the transfer path of the reaction cup, and the second magnetic members are disposed on the outer side of the transfer path of the reaction cup.
In one embodiment, one pole end of the second magnetic member is proximate to the cleaning region of the cuvette and the other pole end of the second magnetic member is distal to the cuvette.
In one embodiment, one pole end of the first magnetic member is proximate to the cleaning region of the cuvette and the other pole end of the first magnetic member is distal to the cuvette.
In one embodiment, the operation position comprises a plurality of liquid injection levels and a plurality of liquid discharge levels which are alternately arranged, and the liquid injection and discharge assembly comprises a plurality of liquid injection needles and a plurality of liquid discharge needles; the liquid injection needles are in one-to-one correspondence with the liquid injection levels, and the liquid discharge needles are in one-to-one correspondence with the liquid discharge levels; the first magnetic piece and the second magnetic piece are arranged between each liquid injection level and the corresponding liquid discharge level.
In one embodiment, a plurality of first magnetic pieces and a plurality of second magnetic pieces are adjacently arranged between each liquid injection level and the corresponding liquid discharge level.
In one embodiment, an included angle between the magnetic pole directions of two adjacent first magnetic pieces is an obtuse angle; the magnetic pole directions of two adjacent second magnetic pieces are opposite.
In one embodiment, the operation positions comprise a first-order filling level, two first-order adsorption positions, a first-order aggregation position, a first-order discharge level, a second-order filling level, two second-order adsorption positions, a second-order aggregation position and a second-order discharge level which are sequentially arranged; the two first-order adsorption positions and the two second-order adsorption positions are respectively provided with one first magnetic piece along one side surface of the transfer path; the first-order aggregation position, the first-order liquid level, the second-order aggregation position and the second-order liquid level are respectively provided with one second magnetic piece along the other side face of the transfer path.
In one embodiment, the first magnetic pieces are disposed at the inner side of the transfer path of the reaction cup, and the connecting lines of the two first-order adsorption positions and the two second-order adsorption positions, through which the first magnetic pieces pass through the two magnetic pole ends, are distributed along the radial direction of the transfer disc; the second magnetic piece is arranged on the outer side of the transfer path of the reaction cup, and the connecting lines of the second magnetic piece penetrating through the end parts of the two magnetic poles are parallel to the vertical lines.
In one embodiment, the two first magnetic pieces corresponding to the two first-order adsorption positions have different magnetic poles facing the rotating shaft, and the two first magnetic pieces corresponding to the two second-order adsorption positions have different magnetic poles facing the rotating shaft; the magnetic pole directions of the two second magnetic pieces corresponding to the first-order aggregation position and the first-order liquid discharge position are opposite, and the magnetic pole directions of the two second magnetic pieces corresponding to the second-order aggregation position and the second-order liquid discharge position are opposite.
In one embodiment, the operation position further includes a third-order injection liquid level, three third-order adsorption positions, a third-order aggregation position and a third-order liquid discharge position, where the third-order injection liquid level, the three third-order adsorption positions, the third-order aggregation position and the third-order liquid discharge position are sequentially disposed downstream of the second-order liquid discharge level along a transfer path of the reaction cup; the three third-order adsorption positions are respectively provided with one first magnetic piece along one side surface of the transfer path; the third-order aggregation position and the other side face of the third-order liquid discharge position along the transfer path are respectively provided with a second magnetic piece.
In one embodiment, the first magnetic pieces are arranged at the inner side of the transfer path of the reaction cup, and the connecting lines of the first magnetic pieces corresponding to the three third-order adsorption positions passing through the two magnetic pole ends are distributed along the radial direction of the transfer disc; the second magnetic piece is arranged on the outer side of the transfer path of the reaction cup, and the connecting lines of the second magnetic piece penetrating through the end parts of the two magnetic poles are parallel to the vertical lines.
In one embodiment, the magnetic poles of the first magnetic parts corresponding to the adjacent third-order adsorption positions towards the rotating shaft are different; and the magnetic pole directions of the two second magnetic parts corresponding to the third-order aggregation position and the third-order liquid discharge position are opposite.
In one embodiment, the operation position further comprises a substrate injection position and a picking and placing position, wherein the substrate injection position and the picking and placing position are sequentially arranged between the third-order liquid level and the first-order liquid level; a substrate injection port is arranged on the substrate injection position, the substrate injection port is connected with a substrate injection assembly, and the substrate injection assembly injects the substrate into a reaction cup at the substrate injection position; the taking and placing position is used for taking out or placing in the reaction cup.
A chemiluminescent immunoassay analyzer comprising an analytical device and the magnetic bead cleaning and separation device according to any one of the above schemes; the analysis device is used for analyzing the magnetic beads cleaned by the magnetic bead cleaning and separating device.
Above-mentioned magnetic bead washs separator and chemiluminescence immunoassay appearance, with a plurality of magnetic parts setting at the both sides face of the transfer route of transfer dish, form the effect to drawing to the magnetic bead in the reaction cup in the transportation process to the magnetic part that two magnetic pole tip lines are different with vertical fastener angle can attract the magnetic bead in different directions, fully, quick break up the magnetic bead in the reaction cup under the condition that does not increase magnetic bead washs separator structure complexity and manufacturing cost. The magnetic pieces with different connecting lines of the two magnetic pole ends and vertical wire clamping angles can be used for gathering the magnetic beads in different directions, so that the gathering speed of the magnetic beads is increased, and the loss rate of the magnetic beads is lower under the same operation time.
Drawings
FIG. 1 is a schematic side view of a magnetic bead cleaning and separating apparatus according to an embodiment of the present invention;
FIG. 2 is a partial schematic view of the internal structure of FIG. 1;
FIG. 3 is a schematic side view of a part of a magnetic bead cleaning and separating apparatus according to an embodiment of the present invention;
FIG. 4 is a schematic front view of a part of a magnetic bead cleaning and separating apparatus according to an embodiment of the present invention;
FIG. 5 is a schematic diagram illustrating an auxiliary description of defining an included angle of arrangement according to an embodiment of the present invention;
FIG. 6 is a schematic diagram illustrating the definition of the included angle between the magnetic poles of the magnetic member according to an embodiment of the present invention;
FIG. 7 is a schematic diagram illustrating a process of completing a second-order bead cleaning and separating by using the bead cleaning and separating device according to an embodiment of the present invention;
FIG. 8 is a schematic diagram illustrating a third-order bead cleaning and separating process performed by the bead cleaning and separating apparatus according to an embodiment of the present invention;
FIG. 9 is a schematic top view showing the distribution of the first magnetic member and the second magnetic member after the transfer path of FIG. 8 is unfolded into a straight line;
FIG. 10 is a schematic view showing the horizontal distribution of the first magnetic member and the second magnetic member after the transfer path of FIG. 8 is unfolded into a straight line;
fig. 11 is a schematic diagram showing the distribution of the first magnetic member and the second magnetic member along the extending direction of the transfer path after the transfer path in fig. 8 is unfolded into a straight line.
Wherein:
10-magnetic bead cleaning and separating device
100-base
110-transfer tank
120-mounting groove
130-floor
140-cover plate
141-pick-and-place opening
142-substrate injection port
200-transfer plate
300-liquid filling and draining assembly
301-a first-order liquid injection needle; 302-a first-order drainage needle; 303-second-order liquid injection needle; 304-second order drainage needle; 305-third-order liquid injection needle; 306-third-order liquid discharge needle; 307-liquid injection base; 308-lifting structure; 309-washing the swab;
400-magnetic member
410-first magnetic member
420-second magnetic coupling
500-magnetic shield
600-operating position
601-first order filling level; 602-first order adsorption sites; 603-first order aggregation bits; 604—first order level; 605-second order filling level; 606-second order adsorption sites; 607-second order aggregation bits; 608-second order drainage level; 609-third order filling level; 610-third order adsorption sites; 611-third order aggregation bits; 612-third order drainage level; 613-taking and placing; 614-substrate injection site;
700-reaction cup
800-gear
900-code disc
Detailed Description
In order to make the objects, technical schemes and advantages of the present invention more clear, the following embodiments are used to further describe a magnetic bead cleaning and separating device and a chemiluminescent immunoassay analyzer according to the present invention in detail with reference to the accompanying drawings.
It will be understood that when an element is referred to as being "fixed to" another element, it can be directly on the other element or intervening elements may also be present. When an element is referred to as being "connected" to another element, it can be directly connected to the other element or intervening elements may also be present. In contrast, when an element is referred to as being "directly on" another element, there are no intervening elements present. The terms "vertical," "horizontal," "left," "right," and the like are used herein for illustrative purposes only. The various objects in the drawings of the embodiments are drawn to scale for ease of illustration and not to scale for actual components.
As shown in fig. 1-5, the present invention provides a magnetic bead washing and separating apparatus 10 for washing incubation-bound magnetic beads and separating the magnetic beads from free interfering substances. The magnetic bead washing and separating device 10 comprises a base 100, a transfer plate 200, a liquid injection and drainage assembly 300 and a plurality of magnetic pieces 400. The base 100 is a supporting structure of the whole magnetic bead cleaning and separating device 10, and a plurality of operation positions are arranged on the base 100. The magnetic bead washing and separating apparatus 10 performs corresponding operations, such as injecting a washing liquid, discharging a washing liquid, adsorbing magnetic beads, etc., on the reaction cup 700 containing the magnetic beads and the washing liquid at a specific operation position. The transfer tray 200 is movably disposed on the base 100, and a plurality of carrying positions for carrying the reaction cups 700 are disposed on the transfer tray 200, and the transfer tray 200 sequentially transfers the reaction cups 700 to corresponding operation positions. The liquid filling and draining assembly 300 is installed on the corresponding operation position, and the liquid filling and draining assembly 300 is used for filling and draining liquid into the reaction cup 700. The plurality of magnetic pieces 400 are arranged on two side surfaces of the transfer path of the reaction cup 700, each magnetic piece 400 corresponds to one operation position independently, the magnetic pieces 400 have adsorption effect on the magnetic beads in the reaction cup 700 on the corresponding operation positions, and the magnetic beads in the reaction cup 700 move to one side close to the magnetic beads and gather under the adsorption effect of the magnetic pieces 400.
In the process of cleaning and separating magnetic beads, the scattering and reagglomeration of the magnetic beads are particularly important. The arrangement position and angle of the magnetic pieces 400 directly influence the scattering and aggregation efficiency of the magnetic beads in the cleaning and separating process, and further directly influence the effect and efficiency of the magnetic bead cleaning and separating device 10 in cleaning and separating the magnetic beads. In the magnetic bead cleaning and separating device 10 provided by the invention, an arrangement included angle is formed between a connecting line of each magnetic piece 400 passing through two magnetic pole ends and a vertical line, and the arrangement included angles comprise a first included angle alpha and a second included angle gamma, and the first included angle alpha and the second included angle gamma are different. It should be noted that, the two poles of the magnetic member 400 refer to the N-level and the S-level, and as shown in fig. 5, the connection line passing through the ends of the two poles refers to a broken line passing through the center of the end faces of the two poles of the magnetic member 400. The vertical line is a vertical line in space, and is a vertical solid line in fig. 5. The included angles are included angles alpha and gamma formed between the connecting line of the magnetic piece 400 passing through the two magnetic pole ends and the vertical line.
When the transfer disc 200 drives the reaction cup 700 to pass through the position where the magnetic pieces 400 are arranged on the transfer path, the magnetic pieces 400 positioned at two sides of the transfer path adsorb the magnetic beads in the reaction cup 700 to one side close to the magnetic pieces 400 respectively. Thus, when the reaction cup 700 moves along the transfer path, the internal magnetic member 400 moves back and forth in the horizontal plane, and the magnetic member 400 has a pull-up effect on the magnetic beads in the reaction cup 700, so that the magnetic beads are fully contacted with the cleaning solution in the reaction cup 700 to ensure that the interfering substances attached to the magnetic beads are separated from the magnetic beads. When the angle between the line passing through the two pole ends of the magnetic member 400 and the vertical line changes, one pole end of the magnetic member 400 is still kept close to the reaction cup 700. In this way, the magnetic beads in the reaction cup 700 are collected to a position near the end of the magnetic pole on the magnetic member 400. The magnetic pieces 400 with different included angles are arranged to attract the magnetic beads in different directions, so that the motion dimension of the magnetic beads in the cleaning liquid in the reaction cup 700 is increased, the magnetic beads in the reaction cup 700 are sufficiently and rapidly scattered, the cleaning and separating effects of the magnetic beads are finally increased, and the cleaning and separating time of the magnetic beads is shortened. The magnetic pieces 400 with different included angles can also gather magnetic beads in different directions, so that the gathering speed of the magnetic beads is increased, and the loss rate of the magnetic beads is lower under the same operation time.
In the magnetic bead cleaning and separating device 10 provided by the invention, the arrangement included angles of the plurality of magnetic pieces 400 can be different from each other, or the arrangement included angles of the partial magnetic pieces 400 can be the same. The arrangement angle of the magnetic member 400 may be changed randomly or regularly. The present invention is not limited to a specific number of angles of placement between the plurality of magnetic members 400. In an embodiment of the invention, the plurality of magnetic elements 400 includes a plurality of first magnetic elements 410 and a plurality of second magnetic elements 420, and the first magnetic elements 410 and the second magnetic elements 420 are respectively disposed on two sides of the transfer path of the reaction cup 700. The arrangement angle between the connecting line of the first magnetic piece 410 passing through the two magnetic pole ends and the vertical line is a first angle alpha, and the arrangement angle between the connecting line of the second magnetic piece 420 passing through the two magnetic pole ends and the vertical line is a second angle gamma. The first magnetic member 410 and the second magnetic member 420 disposed at opposite sides of the transfer path can pull the magnetic beads in a horizontal plane during the transfer of the cuvette 700. The arrangement included angles of the plurality of first magnetic pieces 410 are the first included angles, and the arrangement included angles of the plurality of second magnetic pieces 420 are the second included angles, so that the magnetic beads in the reaction cup 700 can be repeatedly scattered and gathered in the set direction, the scattering degree and the gathering effect of the magnetic beads in the reaction cup 700 are enhanced, the cleaning and separating effect of the magnetic beads is finally increased, and the cleaning and separating time of the magnetic beads is shortened. In other embodiments of the present invention, the arrangement angles between the plurality of magnetic members 400 arranged on the same side of the transfer path are not exactly the same.
In the magnetic bead washing and separating apparatus 10 provided by the present invention, the transfer path of the cuvette 700 may be linear, circular, elliptical, or any other realizable form. The invention is not limited to a particular form of transport path. In an embodiment of the present invention, as shown in fig. 1, 3 and 4, the transfer path of the reaction cup 700 is circular, and the transfer plate 200 has a rotating shaft, which is rotatably mounted on the base 100 through a bearing, and the transfer plate 200 sequentially transfers the reaction cup 700 to the corresponding operation position by rotating around the rotating shaft. The base 100 is also a revolving structure, and a plurality of operation positions are also distributed along the transport direction on the base 100, and a plurality of magnetic members 400 are respectively disposed on the inner side or the outer side of the corresponding operation positions along the transport path. The circular distribution transfer path and the base 100 and the transfer disc 200 of the rotary structure greatly reduce the volume of the magnetic bead cleaning and separating device 10, reduce the structural complexity of the magnetic bead cleaning and separating device 10, and can also carry out assembly line type magnetic bead cleaning and separating, thereby greatly improving the utilization efficiency of the magnetic bead cleaning and separating device 10, increasing the testing speed and simultaneously ensuring the cleaning and separating effect of the magnetic beads.
As one way of realisation, as shown in fig. 6, the larger circles represent the transfer paths of the cuvette 700, and the smaller diameter circles on the transfer paths represent one operation site 600, respectively. The extension direction of the rotation shaft is parallel to the vertical line, and the rotation shaft of the transfer tray 200 is disposed at the center position of the transfer path. The line of the first magnetic element 410 passing through the two magnetic pole ends intersects with the straight line where the extending direction of the rotating shaft is located, that is, the line of the first magnetic element 410 passing through the two magnetic poles is coplanar with the straight line where the extending direction of the rotating shaft is located. Further, the line of the first magnetic element 410 passing through the two magnetic pole ends is perpendicular to the vertical line, i.e. the first angle α is 90 °, and the line of the second magnetic element 420 passing through the two magnetic pole ends is parallel to the vertical line, i.e. the second angle γ is 0 °. The connection line of the first magnetic element 410 passing through the two magnetic poles and the connection line of the second magnetic element 420 passing through the two magnetic poles are coplanar with the rotation axis of the transfer disc 200, that is, the arrangement included angles of the magnetic element 400 and the vertical line are all included angles in the plane of the rotation axis center line. The first magnetic pieces 410 can gather magnetic beads in the horizontal direction, the second magnetic pieces 420 can gather magnetic beads in the vertical direction, the first magnetic pieces 410 and the second magnetic pieces 420 distributed on different sides of the reaction cup 700 are matched together to pull the magnetic beads in the horizontal plane, so that the magnetic beads are fully contacted with the cleaning liquid, quick scattering and gathering of the magnetic beads are realized, and the loss rate of the magnetic beads in the cleaning and separating process is reduced. The first magnetic member 410, which passes through the connecting line of the two magnetic pole ends and is perpendicular to the vertical line, is actually horizontally disposed, hereinafter referred to as a horizontally disposed first magnetic member 410, and the second magnetic member 420, which passes through the connecting line of the two magnetic pole ends and is parallel to the vertical line, is actually vertically disposed, hereinafter referred to as a vertically disposed second magnetic member 420.
As another implementation manner, the arrangement manner of the first magnetic element 410 and the second magnetic element 420 may be reversed, that is, the line of the first magnetic element 410 passing through the two magnetic pole ends is parallel to the vertical line, and the line of the second magnetic element 420 passing through the two magnetic pole ends is perpendicular to the vertical line. The two realizable modes can achieve the same effect, and the present invention is not limited to the specific arrangement of the first magnetic element 410 and the second magnetic element 420, as long as the purpose of sufficiently scattering, oppositely pulling and collecting the magnetic beads in different directions can be achieved.
Further, as shown in fig. 4 and 6, the plurality of first magnetic members 410 are disposed inside the transfer path of the cuvette 700, and the plurality of second magnetic members 420 are disposed outside the transfer path of the cuvette 700. The second magnetic member 420 disposed vertically extends in a vertical direction, and the first magnetic member 410 disposed horizontally extends in a radial direction of the transfer tray 200. The first magnetic member 410 extending along the radial direction of the transfer tray 200 is disposed at the inner side of the transfer path, the first magnetic member 410 is accommodated in the space below the transfer tray 200, and the second magnetic member 420 is disposed at the outer side of the transfer path, so that the radial dimension of the magnetic bead cleaning and separating device 10 is further reduced. In other embodiments of the present invention, the first magnetic member 410 disposed horizontally may be disposed outside the transfer path of the cuvette 700, and the second magnetic member 420 disposed vertically may be disposed inside the transfer path of the cuvette 700.
To increase the attraction of the magnetic member 400 to the magnetic beads within the reaction cup 700, in one embodiment of the present invention, one pole end of the second magnetic member 420 is near the cleaning region of the reaction cup 700 and the other pole end of the second magnetic member 420 is far from the reaction cup 700. The magnetic induction lines of the magnetic pole ends are denser, so that the magnetic pole ends have stronger attraction force on the magnetic beads. Further, one pole end of the first magnetic member 410 is close to the cleaning region of the reaction cup 700, and the other pole end of the first magnetic member 410 is far from the reaction cup 700. The first magnetic element 410 and the second magnetic element 420 can both form stronger adsorption force on the magnetic beads in the reaction cup 700 on the corresponding operation position 600, and even if the magnetic beads are on one side far away from the first magnetic element 410 or the second magnetic element 420, the first magnetic element 410 or the second magnetic element 420 can still attract the magnetic beads in the shortest time, so that the scattering effect and the aggregation effect of the magnetic beads in the reaction cup 700 can be enhanced simultaneously.
In this embodiment, the cleaning area of the reaction cup 700 is an area of the reaction cup 700 containing the cleaning solution, and is generally located near the bottom of the reaction cup 700. Optionally, the cleaning area of the reaction cup 700 is an area that starts from the bottom of the reaction cup 700 and occupies one eighth of the total length of the reaction cup 700; or the cleaning area of the reaction cup 700 is an area which is from the bottom of the reaction cup 700 and has a length which is one fourth of the total length of the reaction cup 700; or the cleaning area of the reaction cup 700 is an area which is started from the bottom of the reaction cup 700 and the length of which is one third of the total length of the reaction cup 700; or the cleaning area of the reaction cup 700 is an area which is started from the bottom of the reaction cup 700 and the length of which is one half of the total length of the reaction cup 700; alternatively, the cleaning area of the cuvette 700 may be an area which is a certain distance from the bottom of the cuvette 700 and which has a certain length which is a certain proportion of the total length of the cuvette 700. As another definition, the cleaning area of the cuvette 700 may be a portion below the liquid surface of the cleaning liquid. The specific position of the cleaning area is not limited in this embodiment, as long as the magnetic member 400 can form a strong attractive force to the magnetic beads.
The magnetic bead cleaning and separating device 10 provided by the invention can be used for cleaning and separating first-order magnetic beads and multi-order magnetic beads, and is not limited to the specific application of the magnetic bead cleaning and separating. In one embodiment of the present invention, as shown in fig. 6-11, the magnetic bead washing and separation device 10 can perform multi-stage magnetic bead washing and separation. Correspondingly, the operation position 600 comprises a plurality of liquid injection levels and a plurality of liquid discharge levels which are alternately arranged, and the liquid injection and discharge assembly 300 comprises a plurality of liquid injection needles matched with the liquid paths and a plurality of liquid discharge needles matched with the gas paths. The liquid injection needles are in one-to-one correspondence with the liquid injection levels, and the liquid discharge needles are in one-to-one correspondence with the liquid discharge levels. A first magnetic element 410 and a second magnetic element 420 are disposed between each priming level and the corresponding discharge level.
When the transfer disc 200 transfers the reaction cup 700 to a specific liquid filling level, the reaction cup 700 stays at the liquid filling level for a set time, and meanwhile, the corresponding liquid filling needle fills the cleaning liquid into the reaction cup 700. After the liquid injection needle finishes the liquid injection, the transfer disc 200 drives the reaction cup 700 to pass through the positions where the first magnetic piece 410 and the second magnetic piece 420 are arranged on the transfer path and stay at the positions where the first magnetic piece 410 or the second magnetic piece 420 are arranged for a set time, so that the first magnetic piece 410 and the second magnetic piece 420 attract the magnetic beads in the reaction cup 700, and finally, the magnetic beads are quickly scattered and quickly gathered in the horizontal direction and the vertical direction. When the transfer disc 200 transfers the reaction cup 700 to a specific liquid discharge level, the magnetic beads are gathered under the adsorption of the magnetic piece 400, and the corresponding liquid discharge needle discharges the cleaning liquid in the reaction cup 700. Then the transfer disc 200 drives the reaction cup 700 to move to the next filling level, and the process is circulated until the reaction cup 700 moves to the last draining level to finish the process of cleaning and separating the magnetic beads. The multistage magnetic bead cleaning and separating is not only beneficial to enhancing the cleaning effect of the magnetic beads, but also can realize the pipelined cleaning of the magnetic beads, and improves the cleaning efficiency of the magnetic beads.
Further, a plurality of first magnetic members 410 and a plurality of second magnetic members 420 are disposed between each liquid filling level and the corresponding liquid discharging level. The plurality of first magnetic pieces 410 and the plurality of second magnetic pieces 420 are adjacently arranged, the adsorption directions of the adjacent first magnetic pieces 410 or second magnetic pieces 420 to the magnetic beads in the reaction cup 700 are the same, and the aggregation effect of the magnetic beads in the reaction cup 700 in the horizontal or vertical direction is enhanced. Meanwhile, the first magnetic piece 410 and the second magnetic piece 420 which are arranged at opposite sides of the transfer path and have vertical included angles can still ensure that the magnetic beads are oppositely pulled in the horizontal direction and the vertical direction to be fully scattered, so that the magnetic beads are fully contacted with the cleaning liquid. Alternatively, the number of the first magnetic members 410 or the second magnetic members 420 that are adjacently arranged may be two, or three, or may be other numbers that are arranged according to the actual working conditions. The present invention is not limited to a specific number of the first magnetic members 410 or the second magnetic members 420 adjacently disposed, as long as the aggregation effect of the magnetic beads in the reaction cup 700 in the horizontal or vertical direction can be enhanced.
Further, as shown in fig. 6, the included angle β between the magnetic pole directions of two adjacent first magnetic members 410 is an obtuse angle. The magnetic poles of the adjacent two second magnetic pieces 420 are opposite in direction. In the present embodiment, the magnetic pole direction of the magnetic element 400 is a vector, and the magnetic pole direction of the magnetic element 400 specifically refers to a vector pointing to the center of the S-stage end of the magnetic element 400 with the center of the N-stage end of the magnetic element 400 as the starting point. As shown in fig. 6, the included angle β of the magnetic pole directions between the two first magnetic members 410 disposed inside the transfer path is an obtuse angle. Since the transfer path is circular, the distribution position of the first magnetic member 410 rotates along with the transfer path. As one possible way, the poles of the first magnetic members 410 disposed on the same side and adjacent to each other are opposite to each other near one end of the transfer path. Further, the first magnetic members 410 are all arranged along the radial direction of the transfer disc 200, that is, the connection line of the first magnetic members 410 passing through the two magnetic pole ends extends along the radial direction of the transfer disc 200. The magnetic poles of the first magnetic pieces 410 arranged on the same side and adjacent to each other are opposite at one end, close to the rotating shaft of the transfer disc 200, so that an included angle beta between the magnetic pole directions of the two adjacent first magnetic pieces 410 is an obtuse angle.
The second magnetic members 420 are vertically arranged, and the magnetic poles of the upper ends of the adjacent second magnetic members 420 are opposite. The included angle between the magnetic pole directions of the two adjacent first magnetic pieces 410 is an obtuse angle, and the magnetic pole directions of the two adjacent second magnetic pieces 420 are opposite, and the dissimilar magnetic poles between the two adjacent first magnetic pieces 410 or second magnetic pieces 420 are close to each other, so that the magnetic field intensity of the magnetic pole end parts of the first magnetic pieces 410 or the second magnetic pieces 420 can be further increased, the attraction force of the first magnetic pieces 410 or the second magnetic pieces 420 on the magnetic beads is further enhanced, the rapid scattering and rapid gathering of the magnetic beads in the horizontal direction and the vertical direction are ensured, and the cleaning and separating efficiency of the magnetic bead cleaning device provided by the invention on the magnetic beads is improved.
In one embodiment of the present invention, as shown in fig. 1 and 7, the magnetic bead washing and separating apparatus 10 can perform the second-order magnetic bead washing and separating. Specifically, the operation station 600 includes a first-order filling level 601, two first-order adsorption stations 602, a first-order aggregation station 603, a first-order liquid discharge station 604, a second-order filling level 605, two second-order adsorption stations 606, a second-order aggregation station 607, and a second-order liquid discharge station 608, which are sequentially arranged. The black dots in fig. 7 represent aggregated magnetic beads, the larger diameter circles represent the transfer path of the cuvette 700, and the cuvette 700 is transferred counterclockwise along the transfer path to the corresponding handling station 600. The operation bits 600 are sequentially disposed on the base 100 in a counterclockwise direction. The edge of the transfer disc 200 is provided with bearing positions with the same number as the operation positions 600, and the intervals among the bearing positions are the same as the intervals among the operation positions 600, so that each bearing position still corresponds to one operation position 600 after rotating by a set angle. Correspondingly, the liquid injection and drainage assembly 300 comprises a first-order liquid injection needle 301, a first-order liquid drainage needle 302, a second-order liquid injection needle 303 and a second-order liquid drainage needle 304. The first-order injection needle 301, the first-order drain needle 302, the second-order injection needle 303, and the second-order drain needle 304 are provided corresponding to the first-order injection level 601, the first-order drain level 604, the second-order injection level 605, and the second-order drain level 608, respectively.
Further, two first-order adsorption sites 602 and two second-order adsorption sites 606 are respectively provided with a first magnetic element 410 along the inner side of the transfer path. The connection lines of the two first-order adsorption sites 602 and the two second-order adsorption sites 606, respectively corresponding to the first magnetic members 410 passing through the two magnetic pole ends, are distributed along the radial direction of the transfer disc 200. The two first magnetic pieces 410 corresponding to the two first-order adsorption positions 602 have different magnetic poles facing the rotating shaft, and the two first magnetic pieces 410 corresponding to the two second-order adsorption positions 606 have different magnetic poles facing the rotating shaft. The first-order aggregation site 603, the first-order drainage site 604, the second-order aggregation site 607 and the second-order drainage site 608 are respectively provided with a second magnetic piece 420 along the outer side of the transfer path, and the connecting lines of the second magnetic piece 420 penetrating through the two magnetic pole ends are parallel to the vertical line. The magnetic pole directions of the two second magnetic pieces 420 corresponding to the first-order aggregation position 603 and the first-order liquid discharge position 604 are opposite, and the magnetic pole directions of the two second magnetic pieces 420 corresponding to the second-order aggregation position 607 and the second-order liquid discharge position 608 are opposite.
Specifically, in this embodiment, as shown in fig. 7, along the transferring direction of the reaction cup 700, the magnetic poles of the first magnetic pieces 410 inside the two adjacent first-order adsorption positions 602 near the rotating shaft of the transfer tray 200 are respectively S-stage and N-stage, the upward magnetic pole of the second magnetic piece 420 outside the first-order collection position 603 is S-stage, the upward magnetic pole of the second magnetic piece 420 outside the first-order liquid discharge position 604 is N-stage, the magnetic poles of the first magnetic pieces 410 inside the two adjacent second-order adsorption positions 606 near the rotating shaft of the transfer tray 200 are respectively S-stage and N-stage, the upward magnetic pole of the second magnetic piece 420 outside the second-order collection position 607 is S-stage, and the upward magnetic pole of the second magnetic piece 420 outside the second-order liquid discharge position 608 is N-stage.
When the transfer plate 200 transfers the reaction cup 700 containing the magnetic beads to the first-order filling level 601, the first-order filling needle 301 fills a certain amount of cleaning solution into the reaction cup 700. After the first-order injection needle 301 finishes injecting liquid, the transfer disc 200 drives the reaction cup 700 to sequentially pass through two adjacent first-order adsorption positions 602, and the reaction cup 700 stays at the two adjacent first-order adsorption positions 602 for a set time. When the cuvette 700 is at the first-order adsorption position 602, the magnetic beads are collected inside the cuvette 700 along the transfer direction under the attraction of the first magnetic member 410. When the reaction cup 700 is at the second first-order adsorption position 602, the magnetic beads are further collected inside the reaction cup 700 along the transferring direction under the attraction of the first magnetic piece 410. Then, the transfer disc 200 drives the reaction cup 700 to move to the first-order aggregation position 603 and stay for a set time, the magnetic beads rapidly move to the outer side of the reaction cup 700 along the transfer path under the attraction of the second magnetic piece 420, and meanwhile, the magnetic beads aggregate towards the bottom of the reaction cup 700 under the attraction of the magnetic pole end of the second magnetic piece 420. The movement of the magnetic beads within the cuvette 700 has components in the horizontal and vertical directions as the cuvette 700 is transported to the first order aggregation site 603. Then, the transfer disc 200 drives the reaction cup 700 to move to the first-order liquid discharge position 604, and the magnetic beads outside the reaction cup 700 are further gathered towards the bottom of the reaction cup 700 under the attraction of the second magnetic piece 420. The first-order liquid discharge needle 302 discharges the cleaning liquid in the reaction cup 700 to complete the first-order cleaning and separation of the magnetic beads. Transfer plate 200 continues to move reaction cup 700 to second order fill level 605.
When the transfer plate 200 transfers the reaction cup 700 containing the magnetic beads to the second-order filling level 605, the second-order filling needle 303 fills a certain amount of cleaning liquid into the reaction cup 700. After the second-order injection needle 303 finishes injecting liquid, the transfer disc 200 drives the reaction cup 700 to sequentially pass through two adjacent second-order adsorption positions 606, and the reaction cup 700 stays at the two adjacent second-order adsorption positions 606 for a set time. When the reaction cup 700 is at the first second-order adsorption position 606, the magnetic beads are collected inside the reaction cup 700 along the transferring direction under the attraction of the first magnetic piece 410. When the reaction cup 700 is at the second-order adsorption position 606, the magnetic beads are further collected inside the reaction cup 700 along the transfer direction under the attraction of the first magnetic piece 410. Then, the transfer disc 200 drives the reaction cup 700 to move to the second-order aggregation position 607 and stay for a set time, the magnetic beads rapidly move to the outer side of the reaction cup 700 along the transfer path under the attraction of the second magnetic piece 420, and meanwhile, the magnetic beads aggregate towards the bottom of the reaction cup 700 under the attraction of the magnetic pole end of the second magnetic piece 420. The movement of the magnetic beads within the cuvette 700 has components in both the horizontal and vertical directions as the cuvette 700 is transported to the second order aggregation site 607. Then, the transfer disc 200 drives the reaction cup 700 to move to the second level 608, and the magnetic beads outside the reaction cup 700 are further gathered towards the bottom of the reaction cup 700 under the attraction of the second magnetic piece 420. The second-order liquid discharge needle 304 discharges the cleaning liquid in the reaction cup 700 to complete the second-order cleaning and separation of the magnetic beads.
In an embodiment of the present invention, the magnetic bead cleaning and separating device 10 can complete the cleaning and separating of the third-order magnetic beads, and the operation position 600 further includes a third-order filling level 609, three third-order adsorption positions 610, a third-order aggregation position 611 and a third-order liquid discharge position 612 as shown in fig. 1 and fig. 8-11 based on the above embodiment. The third-order filling level 609, the three third-order adsorption levels 610, the third-order aggregation levels 611, and the third-order drain level 612 are sequentially disposed downstream of the second-order drain level 608 along the transfer path of the reaction cup 700. The black dots in fig. 8 represent aggregated magnetic beads, the larger diameter circles represent the transfer path of the cuvette 700, and the cuvette 700 is transferred counterclockwise along the transfer path to the corresponding handling station 600. The operation bits 600 are sequentially disposed on the base 100 in a counterclockwise direction. The edge of the transfer disc 200 is provided with bearing positions with the same number as the operation positions 600, and the intervals among the bearing positions are the same as the intervals among the operation positions 600, so that each bearing position still corresponds to one operation position 600 after rotating by a set angle. Correspondingly, the liquid injection and drainage assembly 300 further comprises a third-order liquid injection needle 305 and a third-order liquid drainage needle 306 on the basis of the above embodiment. The third-stage filling needle 305 and the third-stage draining needle 306 are provided corresponding to the third-stage filling level 609 and the third-stage draining level 612, respectively.
Further, on the basis of the above embodiment, the inner sides of the three third-order adsorption positions 610 along the transfer path are respectively provided with a first magnetic member 410, the connecting lines of the first magnetic members 410 corresponding to the three third-order adsorption positions 610 passing through the two magnetic pole ends are all distributed along the radial direction of the transfer disc 200, and the magnetic poles of the first magnetic members 410 corresponding to the adjacent third-order adsorption positions 610 facing the rotating shaft are different. The third-order aggregation position 611 and the third-order liquid discharge position 612 are respectively provided with a second magnetic piece 420 along the outer side of the transfer path, the connecting lines of the second magnetic piece 420 penetrating through the two magnetic pole ends are parallel to the vertical line, and the magnetic pole directions of the two second magnetic pieces 420 respectively corresponding to the third-order aggregation position 611 and the third-order liquid discharge position 612 are opposite.
Specifically, based on the above embodiment, along the transferring direction of the reaction cup 700, the magnetic poles of the first magnetic pieces 410 at the inner sides of the adjacent three third-order adsorption positions 610 near the rotating shaft of the transfer disc 200 are respectively S-level, N-level and S-level, the upward magnetic pole of the second magnetic piece 420 at the outer side of the third-order aggregation position 611 is N-level, and the upward magnetic pole of the second magnetic piece 420 at the outer side of the third-order liquid level 612 is S-level.
After the second-order cleaning and separating process of the magnetic beads is completed, the transfer disc 200 rotates to transfer the reaction cup 700 containing the magnetic beads to the third-order filling level 609, and the third-order filling needle 305 fills quantitative cleaning liquid into the reaction cup 700. After the third-order injection needle 305 finishes injecting liquid, the transfer disc 200 drives the reaction cup 700 to sequentially pass through three adjacent third-order adsorption positions 610, and the reaction cup 700 stays at the three adjacent third-order adsorption positions 610 for a set time. When the reaction cup 700 is at the first third-order adsorption position 610, the magnetic beads are collected inside the reaction cup 700 along the transfer direction under the attraction of the first magnetic piece 410. When the reaction cup 700 is at the second third-order adsorption position 610 and the third-order adsorption position 610, the magnetic beads are further collected inside the reaction cup 700 along the transfer direction under the attraction of the first magnetic member 410. Then, the transfer disc 200 drives the reaction cup 700 to move to the third-order aggregation position 611 and stay for a set time, the magnetic beads rapidly move to the outer side of the reaction cup 700 along the transfer path under the attraction of the second magnetic piece 420, and meanwhile, the magnetic beads aggregate towards the bottom of the reaction cup 700 under the attraction of the magnetic pole end of the second magnetic piece 420. The movement of the magnetic beads within the cuvette 700 has components in the horizontal and vertical directions as the cuvette 700 is transported to the third-order aggregation site 611. Then, the transfer disc 200 drives the reaction cup 700 to move to the third-order liquid level 612, and the magnetic beads outside the reaction cup 700 are further gathered towards the bottom of the reaction cup 700 under the attraction of the second magnetic piece 420. The third-order liquid discharge needle 306 discharges the cleaning liquid in the reaction cup 700 to finish the third-order cleaning and separation of the magnetic beads.
As a way of realizing the above embodiment, as shown in fig. 1 to 4, the base 100 has a hollow cavity, and the transfer disc 200 is rotatably disposed in the hollow cavity of the base 100. The inner wall of the hollow cavity of the base 100 is also provided with a transfer groove 110 extending along the rotation direction of the transfer disc 200, and the transfer disc 200 drives the reaction cup 700 to move in the transfer groove 110. The transfer disc 200 is rotatably arranged in the hollow cavity of the base 100, so that the magnetic bead cleaning and separating device 10 provided by the invention has a compact structure, and the volume of the magnetic bead cleaning and separating device 10 provided by the invention is further reduced. The reaction cup 700 is transported in the transport groove 110, so that the reaction cup 700 is prevented from being damaged due to contact with other elements during movement. As one possible way, the inner wall of the hollow cavity of the base 100 has a flange extending along the rotation direction of the transfer plate 200, and the flange is bent to form the transfer groove 110. As another implementation manner, the inner wall of the hollow cavity of the base 100 is directly provided with the transfer groove 110.
As shown in fig. 1 and 2, a plurality of mounting grooves 120 are further formed in the base 100, the mounting grooves 120 are used for mounting the magnetic pieces 400, the mounting grooves 120 are disposed on two sides of the transfer groove 110 along the transfer direction, and the distribution positions of the mounting grooves 120 in the base 100 are in one-to-one correspondence with the distribution positions of the first magnetic pieces 410 and the second magnetic pieces 420 on two sides of the transfer path. The mounting groove 120 opens toward the bottom of the base 100, allowing the magnetic member 400 to be mounted and dismounted from the bottom of the base 100. The magnetic member 400 is put into or taken out from the bottom of the base 100 along the extending direction of the reaction cup 700, which is beneficial to reducing the distance between the magnetic member 400 and the transferring path of the reaction cup 700, further reducing the distance between the magnetic member 400 and the outer wall of the reaction cup 700, and increasing the aggregation effect of the magnetic beads. Optionally, the base 100 includes a bottom plate 130, and the bottom plate 130 is disposed at the bottom of the base 100 to compress the magnetic member 400 in the mounting groove 120. As shown in fig. 3 and 4, the magnetic bead washing and separating apparatus 10 further includes a gear 800 and a code wheel 900. The gear 800 is disposed at the lower portion of the base 100 and is in transmission connection with the rotating shaft of the transfer disc 200, and the gear 800 is driven by an additional power member to further drive the transfer disc 200 to rotate. The code wheel 900 is fixedly provided at a lower end portion of the gear 800 and rotates in synchronization with the gear 800 to facilitate rotation control of the gear 800. As an achievable way, the external motor drives the gear 800 to rotate through the belt, and the code teeth on the code wheel 900 are matched with the optocoupler to drive the transfer disc 200 to rotate step by step, so that the reaction cup 700 is positioned at the operation position 600.
Further, the base 100 further includes a cover plate 140, and the cover plate 140 is disposed on top of the base 100. The liquid injection and drainage assembly 300 further comprises three liquid injection bases 307, a lifting structure 308 and three cleaning swabs 309, wherein the three liquid injection bases 307 are respectively and fixedly arranged on the upper portion of the cover plate 140, the positions of the three liquid injection bases 307 are respectively in one-to-one correspondence with the first-order liquid injection level 601, the second-order liquid injection level 605 and the third-order liquid injection level 609, and the first-order liquid injection needle 301, the second-order liquid injection needle 303 and the third-order liquid injection needle 305 are respectively arranged on the corresponding liquid injection bases 307 in a penetrating mode. The lifting structure 308 is mounted on the side of the cover plate 140 remote from the transfer plate 200. The first-stage liquid discharge needle 302, the second-stage liquid discharge needle 304 and the third-stage liquid discharge needle 306 are respectively installed on the lifting structure 308, and are lifted or lowered under the driving of the lifting structure 308 to complete the process of discharging the cleaning liquid. In this embodiment, the lifting structure 308 is lifted by a motor and a screw slider. Three cleaning swabs 309 are respectively installed at the upper portion of the cover plate 140, and the positions of the three cleaning swabs 309 are respectively in one-to-one correspondence with the first-order drain 604, the second-order drain 608, and the third-order drain 612. The cleaning swab 309 has a cleaning through hole, and the cleaning swab 309 is used for cleaning the corresponding drain needle. The drain needle passes through the cleaning aperture in the cleaning swab 309 during the ascent or descent. The cover plate 140 is also provided with through holes respectively corresponding to the three liquid injection bases 307 and the three cleaning swabs 309, so that the liquid injection needle can inject cleaning liquid into the reaction cup 700 or the liquid discharge needle can descend to discharge the cleaning liquid in the reaction cup 700. The cover plate 140 is used for realizing the supporting function of various elements, so that the magnetic bead cleaning and separating device 10 provided by the invention has compact and simplified structure, and the volume of the magnetic bead cleaning and separating device 10 provided by the invention is further reduced.
Further, the magnetic bead washing and separating apparatus 10 further includes a magnetic shield 500, and the magnetic shield 500 is provided at an outer edge of the magnetic member 400. The magnetic shielding cover 500 can limit the magnetic action of the magnetic piece 400 in the magnetic bead cleaning and separating device 10, avoid the magnetic piece 400 from interfering with electromagnetic magnetic elements near the magnetic bead cleaning and separating device 10, further allow corresponding magnetic elements to be arranged near the magnetic bead cleaning and separating device 10, increase the space utilization rate of the magnetic bead cleaning and separating device 10, and further reduce the overall size of the chemiluminescent immunoassay analyzer. Alternatively, the magnetic element 120 in the magnetic separation assembly 100 may be a permanent magnet or an electromagnet. As one implementation, the magnetic element 400 is a permanent magnet and the magnetic element 400 includes a rubidium magnet.
In one embodiment of the invention, the manipulation stage 600 further comprises a pick-and-place stage 613 and a substrate injection stage 614. The substrate injection position 614 and the picking and placing position 613 are sequentially disposed between the third-order liquid level 612 and the first-order liquid level 601, that is, the picking and placing position 613 is disposed upstream of the first-order liquid level 601 along the transfer direction, and is used for placing the reaction cup 700 into the transfer tray 200 or taking out the reaction cup 700 from the transfer tray 200. The substrate injection site 614 is disposed downstream of the third-order liquid discharge site 612 in the transport direction for adding a luminescent substrate (enzymatic chemiluminescence) or an oxidizing agent (direct chemiluminescence) to the cuvette 700. Correspondingly, the cover plate 140 is provided with a pick-and-place port 141 and a substrate injection port 142. The reaction cup 700 is placed into the transfer disc 200 from the taking and placing port 141, and the transfer disc 200 rotates anticlockwise by one operation position 600 after a fixed interval time, so that the reaction cup 700 sequentially reaches a first-order filling liquid level 601, two first-order adsorption positions 602, a first-order aggregation position 603, a first-order liquid discharge position 604, a second-order filling liquid level 605, two second-order adsorption positions 606, a second-order aggregation position 607, a second-order liquid discharge position 608, a third-order filling liquid level 609, three third-order adsorption positions 610, a third-order aggregation position 611 and a third-order liquid discharge position 612 to realize the third-order cleaning separation of magnetic beads. The transfer plate 200 continues to rotate and the cuvette 700 moves to the substrate injection site 614. The cuvette 700 is injected with a luminescent substrate (enzymatic chemiluminescence) or an oxidizing agent (direct chemiluminescence) at the substrate injection site 614 of the substrate injection port 142, and finally the cuvette 700 is taken out after being transferred back to the pick-and-place site 613 corresponding to the pick-and-place port 141. As one implementation, the substrate injection port 142 is coupled to a substrate injection assembly that injects a substrate into the reaction cup 700 at the substrate injection site 614. Specifically, the substrate injection assembly includes a dosing pump in communication with the substrate, through which the substrate is injected into the reaction cup 700 at the substrate injection site 614.
The invention also provides a chemiluminescent immunoassay analyzer comprising an analysis device and the magnetic bead cleaning and separating device 10 according to any one of the above schemes. The analysis device is used for analyzing the magnetic beads washed by the magnetic bead washing and separating device 10.
The technical features of the above-described embodiments may be arbitrarily combined, and all possible combinations of the technical features in the above-described embodiments are not described for brevity of description, however, as long as there is no contradiction between the combinations of the technical features, they should be considered as the scope of the description.
The foregoing examples illustrate only a few embodiments of the invention and are described in detail herein without thereby limiting the scope of the invention. It should be noted that it will be apparent to those skilled in the art that several variations and modifications can be made without departing from the spirit of the invention, which are all within the scope of the invention. Accordingly, the scope of protection of the present invention is to be determined by the appended claims.
Claims (18)
1. A magnetic bead cleaning and separating device, comprising:
the base is provided with a plurality of operation positions;
The transfer disc is movably arranged on the base, a plurality of bearing positions for bearing the reaction cups are arranged on the transfer disc, the reaction cups are sequentially transferred to the corresponding operation positions by the transfer disc, the transfer disc is provided with a rotating shaft, and the extending direction of the rotating shaft is parallel to the vertical line;
the liquid injection and drainage assembly is arranged on the corresponding operation position and is used for injecting and draining liquid into the reaction cup;
the magnetic pieces are arranged on two side surfaces of the transfer path of the reaction cup, and each magnetic piece corresponds to one operation position independently;
each magnetic piece passes through a connecting line of two magnetic pole ends to form an arrangement included angle with a vertical line, a plurality of arrangement included angles comprise a first included angle and a second included angle, the first included angle is different from the second included angle, the plurality of magnetic pieces comprise a first magnetic piece and a second magnetic piece, and the first magnetic piece and the second magnetic piece are respectively arranged on two side surfaces of a transfer path of the reaction cup; the arrangement included angle formed between the connecting line of the first magnetic part passing through the two magnetic pole end parts and the vertical line is a first included angle, and the arrangement included angle formed between the connecting line of the second magnetic part passing through the two magnetic pole end parts and the vertical line is a second included angle.
2. The magnetic bead washing and separation device according to claim 1 wherein the plurality of magnetic members comprises a plurality of first magnetic members and a plurality of second magnetic members.
3. The magnetic bead cleaning and separating device according to claim 2, wherein the rotating shaft is rotatably arranged on the base, and the transferring disc sequentially transfers the reaction cups to the corresponding operation positions by rotating around the rotating shaft; the connecting line of the first magnetic piece passing through the two magnetic pole ends is intersected with the straight line where the extending direction of the rotating shaft is located.
4. A magnetic bead washing and separating device according to claim 3 wherein the line of the first magnetic member passing through the two pole ends is perpendicular to the vertical line and the line of the second magnetic member passing through the two pole ends is parallel to the vertical line.
5. The magnetic bead washing and separating apparatus of claim 3, wherein the plurality of first magnetic members are disposed inside the transfer path of the cuvette, and the plurality of second magnetic members are disposed outside the transfer path of the cuvette.
6. The magnetic bead washing and separating device according to claim 2, wherein one magnetic pole end of the second magnetic member is close to the washing area of the reaction cup, and the other magnetic pole end of the second magnetic member is far from the reaction cup.
7. The magnetic bead washing and separating device according to claim 2, wherein one magnetic pole end of the first magnetic member is close to the washing area of the reaction cup, and the other magnetic pole end of the first magnetic member is far from the reaction cup.
8. The magnetic bead washing and separation device according to any one of claims 4 to 7 wherein the operating site comprises a plurality of filling levels and a plurality of draining levels alternately arranged, the filling and draining assembly comprising a plurality of filling needles and a plurality of draining needles; the liquid injection needles are in one-to-one correspondence with the liquid injection levels, and the liquid discharge needles are in one-to-one correspondence with the liquid discharge levels; the first magnetic piece and the second magnetic piece are arranged between each liquid injection level and the corresponding liquid discharge level.
9. The magnetic bead washing and separating device according to claim 8, wherein a plurality of the first magnetic members and a plurality of the second magnetic members are adjacently disposed between each of the liquid filling level and the corresponding liquid discharging level.
10. The magnetic bead cleaning and separating device according to claim 9, wherein an included angle between the magnetic pole directions of two adjacent first magnetic members is an obtuse angle; the magnetic pole directions of two adjacent second magnetic pieces are opposite.
11. The magnetic bead washing and separating device according to any one of claims 3 to 7, wherein the operation positions include a first-order filling level, two first-order adsorption positions, a first-order aggregation position, a first-order discharge level, a second-order filling level, two second-order adsorption positions, a second-order aggregation position, and a second-order discharge level, which are sequentially arranged; the two first-order adsorption positions and the two second-order adsorption positions are respectively provided with one first magnetic piece along one side surface of the transfer path; the first-order aggregation position, the first-order liquid level, the second-order aggregation position and the second-order liquid level are respectively provided with one second magnetic piece along the other side face of the transfer path.
12. The magnetic bead cleaning and separating device according to claim 11, wherein the first magnetic member is disposed at an inner side of a transfer path of the reaction cup, and connecting lines of the first magnetic member passing through two magnetic pole ends corresponding to the two first-order adsorption positions and the two second-order adsorption positions respectively are distributed along a radial direction of the transfer disc; the second magnetic piece is arranged on the outer side of the transfer path of the reaction cup, and the connecting lines of the second magnetic piece penetrating through the end parts of the two magnetic poles are parallel to the vertical lines.
13. The magnetic bead cleaning and separating device according to claim 12, wherein the two first magnetic pieces corresponding to the two first-order adsorption positions have different magnetic poles facing the rotating shaft, and the two first magnetic pieces corresponding to the two second-order adsorption positions have different magnetic poles facing the rotating shaft; the magnetic pole directions of the two second magnetic pieces corresponding to the first-order aggregation position and the first-order liquid discharge position are opposite, and the magnetic pole directions of the two second magnetic pieces corresponding to the second-order aggregation position and the second-order liquid discharge position are opposite.
14. The magnetic bead cleaning and separating device according to claim 11, wherein the operation position further comprises a third-order filling level, three third-order adsorption positions, a third-order aggregation position and a third-order liquid discharge position, and the third-order filling level, the three third-order adsorption positions, the third-order aggregation position and the third-order liquid discharge position are sequentially arranged at the downstream of the second-order liquid discharge level along a transfer path of the reaction cup; the three third-order adsorption positions are respectively provided with one first magnetic piece along one side surface of the transfer path; the third-order aggregation position and the other side face of the third-order liquid discharge position along the transfer path are respectively provided with a second magnetic piece.
15. The magnetic bead cleaning and separating device according to claim 14, wherein the first magnetic members are disposed at the inner side of the transfer path of the reaction cup, and the connecting lines of the three third-order adsorption positions, through which the first magnetic members pass through the two magnetic pole ends, are distributed along the radial direction of the transfer disc; the second magnetic piece is arranged on the outer side of the transfer path of the reaction cup, and the connecting lines of the second magnetic piece penetrating through the end parts of the two magnetic poles are parallel to the vertical lines.
16. The magnetic bead washing and separating device according to claim 15, wherein the magnetic poles of the first magnetic members corresponding to the adjacent third-order adsorption positions are different toward the rotating shaft; and the magnetic pole directions of the two second magnetic parts corresponding to the third-order aggregation position and the third-order liquid discharge position are opposite.
17. The magnetic bead washing and separating device according to claim 14, wherein the operation position further comprises a substrate injection position and a pick-and-place position, the substrate injection position and the pick-and-place position being sequentially disposed between the third-order liquid level and the first-order liquid level; a substrate injection port is arranged on the substrate injection position, the substrate injection port is connected with a substrate injection assembly, and the substrate injection assembly injects the substrate into a reaction cup at the substrate injection position; the taking and placing position is used for taking out or placing in the reaction cup.
18. A chemiluminescent immunoassay analyzer comprising an analytical device and the magnetic bead cleaning and separation device of any one of claims 1-17; the analysis device is used for analyzing the magnetic beads cleaned by the magnetic bead cleaning and separating device.
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CN203816777U (en) * | 2014-03-19 | 2014-09-10 | 东南大学 | Magnetic separation device |
CN204255840U (en) * | 2014-12-16 | 2015-04-08 | 合肥运涛光电科技有限公司 | A kind of luminous tester reaction cup and corresponding washing separator structure thereof |
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JP6472973B2 (en) * | 2014-10-24 | 2019-02-20 | 日本電子株式会社 | Automatic analyzer and separation cleaning method |
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CN203816777U (en) * | 2014-03-19 | 2014-09-10 | 东南大学 | Magnetic separation device |
CN204255840U (en) * | 2014-12-16 | 2015-04-08 | 合肥运涛光电科技有限公司 | A kind of luminous tester reaction cup and corresponding washing separator structure thereof |
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