CN101319976B - Micro-pore plate type electromagnetic separator - Google Patents

Micro-pore plate type electromagnetic separator Download PDF

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CN101319976B
CN101319976B CN2008101161325A CN200810116132A CN101319976B CN 101319976 B CN101319976 B CN 101319976B CN 2008101161325 A CN2008101161325 A CN 2008101161325A CN 200810116132 A CN200810116132 A CN 200810116132A CN 101319976 B CN101319976 B CN 101319976B
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micro
type electromagnetic
electromagnet
magnetic core
plate type
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CN101319976A (en
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林金明
李智勇
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Tsinghua University
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Tsinghua University
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Abstract

A millipore plate electromagnetic separator includes a salver; an electric magnet array consisting of a plurality of small electric magnets is arranged on the salver; each small electric magnet includes a magnetic core and a loop sheathed outside the magnetic core; the two ends of the loop are connected with powers; the upper surface of the electric magnet array is provided with a cover plate; a hole corresponding to the magnetic core is arranged on the cover plate; a pair of clamping springs are arranged in the two corresponding frames of the salver; a millipore plate is arranged at the top part of the cover plate and is clamped on the lower surface of the two clamping springs; the centers of 4 to 6 neighboring millipores on the millipore plate are corresponding to one small electric magnet. The millipore plate electromagnetic separator has the advantages of simple structure, low cost, fast separating speed and high efficiency; can realize single or uniformed control on each small electric magnet, is flexibly operated, is conveniently combined with an automatic plate washing device to realize the automatization of separation and can play the important roles on the aspects like clinical laboratory, environment detection, bioanalysis, drug screening, etc.

Description

A kind of micro-pore plate type electromagnetic separator
Technical field
The present invention relates to a kind of magnetic separator, particularly about a kind of micro-pore plate type electromagnetic separator that uses the magnetic particle to carry out immunoassay as separation agent.
Background technology
After being suggested the 1950's, obtain great advance from immunoassay since half a century, be widely used in environment now, clinical, in food and the technical analysis.Be accompanied by the development of immunoassay, the separation method of immunoassay is also constantly weeded out the old and bring forth the new.Immunoassay can be divided into homogeneous immunoassay and heterogeneous immunoassay, and all phase disengagement method comprises immunoprecipitation analysis method (containing the precipitation method and coacervation) and liposome dissolving analytic approach.All phase disengagement method does not need to separate with excess reagent in analytic process, but very little owing to existing many formidable problems to cause it to use proportion in the practical application, heterogeneous analytic approach is the main flow of present immunoassay always.A critical process of heterogeneous analysis is exactly to detect and the separating of excessive labelled reagent, separation method commonly used has liquid phase adsorption method (promptly to utilize anion exchange resins, absorption testing samples such as glucose covering activated charcoal make it to separate), liquid-phase precipitation method (promptly adopts ammonium sulfate, polyglycol etc. get off the determinand coagulative precipitation), the solid phase adsorption method is (promptly with glass fibre membrane, plastic bead, the plastic microporous plate, nylon wire, plastics small test tubes etc. separate determinand as solid phase carrier) and solid phase precipitation method (promptly utilize magnetic granule etc. it is captured determinand make it from matrix, to separate).In the last few years, magnetic particle separation technology is because its specific surface area is big, it is fast to catch analytic target, simple operation and other advantages has obtained extensive studies and application in immunoassay, and board-like magnetic particle method with the high flux of microwell plate reactor and magnetic particulate vector fast, low consumption combines, and has solved in the tubular process variation problem that the difference because of pipe causes simultaneously, thereby has had a bigger research prospect.Simultaneously, corresponding with it various magnetic separators also arise at the historic moment.
At present, the magnetic separator of public use has following several:
1, tubular type magnetic separation technique: the Beijing Bei Ai Kang Biotechnology Co., Ltd public use the tubular type magnetic separator, this is the most frequently used in the market a kind of separation vessel.This separation vessel comprises a magnetic sheet and a pipe support, can put into a plurality of reaction tubes on the pipe support, in each reaction tube bottom, a corresponding circular small magnet is arranged.After in immunological assay reagents adds pipe, test tube is put on the pipe support, magnetic bead is deposited to the bottom in hole under the action of a magnetic field, will manage then and separation vessel together back-off to clean filter paper, lay equal stress on bottom kowtowing several under, remove supernatant.This method is applicable to the pipe reaction system that volume is bigger, and needs manually-operated to separate, wash.
2, patent No. ZL03265041.8 discloses a kind of magnetic resolution device that is applicable in the orifice-plate type magnetic immuno analytical technology, and its structure comprises that parallel placement, big plane stack and clamp the yoke and the fixed frame of magnetic sheet.This device well combines magnetic particle separation and microwell plate analysis, but it is inhomogeneous also to exist the suffered magnetic field intensity in each hole simultaneously, and quality is heavier, is difficult to realize deficiencies such as robotization, needs further perfect.
3, patent No. ZL200520103142.7 discloses a kind of ELISA Plate dedicated magnetic separation vessel, comprise a skeleton that has groove, the small magnetic fourth array of arranging on the groove, a micropore of the corresponding microwell plate of each magnetic fourth, cover with a cover plate on the groove, the ELISA Plate chucking device also is equipped with in the skeleton both sides.This patent has well solved magnetic field inequality in the last patent, and the deficiency of quality heaviness, but still be applicable to manual operations is difficult to realize the robotization that separates.
Summary of the invention
At the problems referred to above, it is little to the purpose of this invention is to provide a kind of volume, in light weight, and magnetic field is stressed evenly is convenient to realize automatic separation, is applicable to the micro-pore plate type electromagnetic separator in the micro-pore plate type magnetic immunoassay.
For achieving the above object, the present invention takes following technical scheme: a kind of micro-pore plate type electromagnetic separator, it is characterized in that: it comprises a pallet, described pallet is provided with the electromagnet array of being made up of a plurality of little electromagnet, each described little electromagnet comprises a magnetic core and is enclosed within the coil of described magnetic core outside, the two ends of described coil connect power supply, on described electromagnet array, be provided with a cover plate, the hole corresponding with each described magnetic core is set on the described cover plate, be provided with a pair of jump ring in the frame two of described pallet two correspondences, one microwell plate is arranged on the top of described cover plate, and be fastened on described two jump rings below, the corresponding described little electromagnet in 4~6 adjacent micropore centers on the described microwell plate.
The magnetic core of described little electromagnet is fixedly connected on the described pallet by screw thread.
Adjacent micropore on the described microwell plate of described little electromagnet is 4.
The magnetic core of described little electromagnet exceeds described cover plate or equal with described cover plate.
Each described little electromagnet connects described power supply by a switch respectively.
A kind of board-like Chemiluminescence Apparatus that micro-pore plate type electromagnetic separator of the present invention has been installed.
A kind of microplate reader that micro-pore plate type electromagnetic separator of the present invention is installed.
The present invention is owing to take above technical scheme, it has the following advantages: 1, because the present invention adopts that magnetic-particle the method on the chamber wall of microwell plate of being adsorbed on is realized detecting and the separating of excessive labelled reagent, so simple structure of the present invention, with low cost, velocity of separation is fast, efficient is high, is convenient to and washes the panel assembly coupling automatically and realize the robotization separate.2, because the array of the electromagnet among the present invention is to be formed by a plurality of little electromagnet combinations, each little electromagnet twines the multiturn coil of conductive wire by a magnetic core and outside and constitutes, therefore can realize independent or unified control by to coil electricity whether control to each small magnet.3, owing to can the position relation of the magnetic core of cover plate and small magnet be provided with among the present invention, so wherein any of the flat microwell plate that all fuses between all having at the bottom of certain slit microwell plate and each hole between can making it to be applicable at the bottom of each hole.4, because the electromagnet array among the present invention is to be formed by a plurality of little electromagnet combinations, therefore also can make the present invention be applicable to the microwell plate of multiple model, also can in the tubular type instrument, adopt identical thinking simultaneously by the quantity of the medium and small electromagnet of transform array.5, because electromagnetic separator volume of the present invention is less, microwell plate pallet sizableness with common microplate reader or board-like Chemiluminescence Apparatus inside, therefore can replace the support holder structure of two kinds of instrument internal with it, simultaneously at supporting integrated magnetic separator power supply and the control circuit of powering on of instrument internal, and wash the plate system automatically, realize the robotization of immunoassay.The present invention is skillfully constructed, and flexible operation is convenient to realize robotization, and is applied widely, can be in clinical examination, and environment measuring, bioanalysis, aspects such as drug screening play a significant role.
Description of drawings
Fig. 1 is structure of the present invention and use principle synoptic diagram
Fig. 2 is an electromagnet array synoptic diagram of the present invention
Fig. 3 is that the position of the micropore in medium and small electromagnet of the present invention and the microwell plate concerns synoptic diagram
Fig. 4 is the present invention's magnetic particle state of living in the microwell plate when separating
Fig. 5 is that the magnetic core of the medium and small electromagnet of the present invention exceeds the cover plate synoptic diagram
Fig. 6 is the equal synoptic diagram with cover plate of the magnetic core of the medium and small electromagnet of the present invention
Fig. 7 is the tripping device of magnetic particle in the microwell plate
Fig. 8 is that electromagnetic separator of the present invention combines synoptic diagram with board-like Chemiluminescence Apparatus
Embodiment
Below in conjunction with drawings and Examples, the present invention is described in detail.
As shown in Figure 1 and Figure 2, the present invention includes pallet 1, pallet 1 is provided with one group of electromagnet array of being made up of a plurality of little electromagnet 2, and each little electromagnet 2 comprises a magnetic core 3 and the coil 4 by the winding of multiturn lead that is enclosed within magnetic core 3 outsides, and the two ends of coil 4 connect power supply.On the electromagnet array, be provided with a cover plate 5, on cover plate 5, have the hole that allows each little magnetic core 3 correspondence, in the frame 6 of 1 liang of correspondence of pallet, be provided with a pair of jump ring 7.Be provided with a microwell plate 8 at the top of cover plate 5, the dual-side of microwell plate 8 be fastened on two jump rings 7 below.
In the foregoing description, the quantity of little electromagnet 2 is decided according to the model of microwell plate 8, can be around each little electromagnet 2 round four (as shown in Figure 3) or six micropores 9, when inserting an immunological assay reagents container in the micropore 9 at microwell plate, the magnetisable material in the immunological assay reagents just can accumulate near on the chamber wall around the little electromagnet 2 (as shown in Figure 4).
In the foregoing description, the magnetic core 3 of little electromagnet 2 can be fixed on the pallet 1 by screw thread, also can adopt alternate manner to be fixed on the pallet 1.The magnetic core 3 of the little electromagnet 1 of the present invention can exceed cover plate 5 certain distances (as shown in Figure 5), also can with cover plate 5 equal (as shown in Figure 6).
Following the present invention is an example with the micro-pore plate type electromagnetic separator that is applicable to 96 hole ELISA Plate or tissue culturing plate, and the specific embodiment of the present invention is described:
8, one aluminium alloy pallets 1 of 96 hole microwell plates that present embodiment adopts Yingke Xinchuang (Ximen) Sci. ﹠ Tech. Co., Ltd. to produce are provided with 24 little electromagnet 2, make per four micropores in the microwell plate center on a little electromagnet 2.The magnetic core 3 of little electromagnet 2 uses silicon steel material, the diameter of magnetic core 3 is 3.5cm for 0.4cm length, with plastic barrel parcel magnetic core 3 conduct insulation, twines copper wire in the outside of plastic barrel in magnetic core 3 outsides, form an independently little electromagnet 2, the diameter of little electromagnet 2 is 1.3cm.A thin aluminium alloy is covered on the electromagnet array as cover plate 5, have the identical hole of magnetic core 3 quantity with little electromagnet 2 on the cover plate 5, the magnetic core 3 of little electromagnet 2 is passed hole on the cover plate 5, and exceed about 0.5cm.The pallet 1 of present embodiment, cover plate 5 also can adopt other nonmagnetic substance to make.Little electromagnet 2 adopts 30 volts of DC power supply, and each little electromagnet 2 connects power supply by a switch respectively, thereby realizes the independent control or the interlock control of each little electromagnet 2.
When the present invention uses, in each micropore of microwell plate 8, put into the container that magnetic resolution reagent and immunoreagent are housed respectively, treat that two kinds of reagent fully react completely after, microwell plate 8 is put on the cover plate 5, and fixing with jump ring 7.Then with 2 energisings of little electromagnet, the time of energising back 30s~1min, can realize detecting and the separating of excessive labelled reagent.
When cleaning microwell plate 8, can adopt manual method, paste container bottom with liquid-transfering gun and liquid in the hole is being siphoned away away from a side of magnetic particle 10.As shown in Figure 7, cleaning microwell plate 8 also can adopt washes panel assembly automatically, adopt when washing panel assembly automatically, need the drawing liquid head 11 of washing the plate machine in the prior art is adjusted to the position that faces container center in the microwell plate 8, utilize stepper motor 12 driving drawing liquid heads 11 to move downward reagent is taken away, and the magnetic-particle 10 in the reagent still can be stayed on the chamber wall to the bottom of container.Liquid feeding head 13 injects cleaning fluid in the container under the effect of air pump 14 subsequently, cleans.If repeatedly wash plate then should be noted that the interval of washing the plate time, to guarantee to add the stand-by period that has behind the cleaning fluid about 1min at every turn.In order to ensure that little electromagnet 2 can be drawn onto magnetic particle 10 on the chamber wall of microwell plate 8 fully, prevent that magnetic particle 10 from losing, in washing the plate operating process, little electromagnet 2 is in "on" position all the time.When operating once more, little electromagnet 2 outages add reaction reagent once more in container, and magnetic particle 10 can be distributed in the reagent again again and react.
As shown in Figure 8, the present invention can also be integrated in board-like Chemiluminescence Apparatus or the inner alternative original microwell plate pallet of microplate reader uses, like this can be so that combine the realization full-automatic operation with automatic washer, concrete integrated approach in instrument internal is as follows: with section's beautiful KPS-KM template formula chemical illumination immunity analysis instrument is example, its pallet 15 is to link to each other with slide rail 17 by a reguline metal stilt 16, reguline metal stilt 16 lower ends and slide rail 17 are chimeric, can slide freely, the upper end is connected with pallet 15 by screw 18.When using electromagnetic separator of the present invention, only need metal support 16 and pallet 15 are separated, and pallet 1 of the present invention is fixed on the metal support 16 by screw 18, promptly finish the present invention's integrated on board-like Chemiluminescence Apparatus.

Claims (11)

1. micro-pore plate type electromagnetic separator, it is characterized in that: it comprises a pallet, described pallet is provided with the electromagnet array of being made up of a plurality of little electromagnet, each described little electromagnet comprises a magnetic core and is enclosed within the coil of described magnetic core outside, the two ends of described coil connect power supply, on described electromagnet array, be provided with a cover plate, the hole corresponding with each described magnetic core is set on the described cover plate, be provided with a pair of jump ring in the frame of described pallet two correspondences, one microwell plate is arranged on the top of described cover plate, and be fastened on described two jump rings below, the corresponding described little electromagnet in 4~6 adjacent micropore centers on the described microwell plate.
2. a kind of micro-pore plate type electromagnetic separator as claimed in claim 1 is characterized in that: the magnetic core of described little electromagnet is fixedly connected on the described pallet by screw thread.
3. a kind of micro-pore plate type electromagnetic separator as claimed in claim 1 is characterized in that: the adjacent micropore on the described microwell plate of described little electromagnet is 4.
4. a kind of micro-pore plate type electromagnetic separator as claimed in claim 2 is characterized in that: the adjacent micropore on the described microwell plate of described little electromagnet is 4.
5. as claim 1 or 2 or 3 or 4 described a kind of micro-pore plate type electromagnetic separators, it is characterized in that: the magnetic core of described little electromagnet exceeds described cover plate.
6. as claim 1 or 2 or 3 or 4 described a kind of micro-pore plate type electromagnetic separators, it is characterized in that: the magnetic core of described little electromagnet is equal with described cover plate.
7. as claim 1 or 2 or 3 or 4 described a kind of micro-pore plate type electromagnetic separators, it is characterized in that: each described little electromagnet connects described power supply by a switch respectively.
8. a kind of micro-pore plate type electromagnetic separator as claimed in claim 5 is characterized in that: each described little electromagnet connects described power supply by a switch respectively.
9. a kind of micro-pore plate type electromagnetic separator as claimed in claim 6 is characterized in that: each described little electromagnet connects described power supply by a switch respectively.
10. board-like Chemiluminescence Apparatus of having installed as the described micro-pore plate type electromagnetic separator of claim 1~9.
11. microplate reader of having installed as the described micro-pore plate type electromagnetic separator of claim 1~9.
CN2008101161325A 2008-07-03 2008-07-03 Micro-pore plate type electromagnetic separator Active CN101319976B (en)

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CN103920585B (en) * 2014-04-10 2016-02-10 东南大学 The full-automatic magnetic fluid tripping device of a kind of high flux
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CN2819220Y (en) * 2005-07-29 2006-09-20 中国科学院理化技术研究所 Magnetic separator of enzyme target board

Patent Citations (2)

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Publication number Priority date Publication date Assignee Title
US5779907A (en) * 1996-12-06 1998-07-14 Systems Research Laboratories, Inc. Magnetic microplate separator
CN2819220Y (en) * 2005-07-29 2006-09-20 中国科学院理化技术研究所 Magnetic separator of enzyme target board

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