CN103846156B - Magnetic separation unit and magnetic separation device - Google Patents

Magnetic separation unit and magnetic separation device Download PDF

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Publication number
CN103846156B
CN103846156B CN201210548265.6A CN201210548265A CN103846156B CN 103846156 B CN103846156 B CN 103846156B CN 201210548265 A CN201210548265 A CN 201210548265A CN 103846156 B CN103846156 B CN 103846156B
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magnetic
magneto separate
separation device
separate unit
those
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CN103846156A (en
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唐敏注
黄玉婷
陈立国
林忆珊
黄祥鸣
林欣荣
徐伟成
王孝荣
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Industrial Technology Research Institute ITRI
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Abstract

The invention discloses a magnetic separation unit and a magnetic separation device. The magnetic separation unit includes: the magnetic strips are arranged closely, and a plurality of continuous and mutually parallel first fluid flow channels are defined among the magnetic strips.

Description

Magneto separate unit and magnetic separation device
Technical field
The present invention relates to bio-chemistry separation devices, and more particularly to the magnetic suitable for detaching the magnetisable material in biochemical samples Separative element and magnetic separation device.
Background technology
In biochemistry, used many technologies at present with efficiently separate one kind in compound cells suspension or A kind of cell.And the ability for the certain specific cells for representing specified disease kenel is detached from clinical blood sample for disease It diagnoses particularly useful.
Technology can successfully use magnetic devices to repel or attract labeled cell at present, mixed for pick or separation Close object in through micron-scale (>1 micron) cell of magnetic or magnetized particles label.The thin of valuable information can be provided for separation For born of the same parents, the cell that can be intended to detection go out from pick in compound liquid mixture after magnetization (be known as positive selection, or Key player on a team).Alternatively, can will also cause specific program change non-detection cell after magnetization by magnetic devices with by it It separates and (is known as Solid phase, or negative choosing).
However, the separative efficiency of magnetic cell depends on magnetic mark magnetic force suffered in detaching magnetic field, therefore it is intended to carry High separation rate must improve magnetic field and magnetic field gradient.However whether permanet magnet or electromagnet, usual magnetic field are terraced with magnetic field Degree leave magnetic material i.e. with distance decline quickly.Therefore, the one of preferably a kind of Magneto separate unit and its application is just needed Kind magnetic separation device, to promote the separative efficiency of magnetisable material.
Invention content
Include several by what is be disposed proximate in view of this, the object of the present invention is to provide a kind of Magneto separate unit Several fluid courses that magnetic bar is constituted, thus the highfield ladder of external magnetic field can be extended through these magnetic bars In degree to fluid course therebetween, and for improving Magnetic Isolation efficiency.In addition, present invention provides apply above-mentioned Magneto separate A kind of magnetic separation device of unit.
In order to achieve the above object, the present invention proposes a kind of Magneto separate unit, including:
Multiple magnetism bars, be closely arranged, and defines continuous and is mutually parallel between those magnetic bars Multiple first fluid runners.
According to another embodiment, the present invention proposes a kind of magnetic separation device, including:
One external magnetic field unit;One container component is set in the external magnetic field unit, has a central axis direction, one Fluid inlet and a fluid outlet;And Magneto separate unit as the aforementioned, it is set within the container component, wherein those are magnetic The central axis direction of bar with those first fluid runners along the container component extends or along the center of the container component Axis direction extends and reverses, and wherein the container component includes non-magnetic material, and the external magnetic field unit provides an external magnetic field At the container component and the Magneto separate unit.
For above-mentioned purpose of the invention and feature can be clearer and more comprehensible, a preferred embodiment cited below particularly, and coordinate institute Attached attached drawing, is described in detail below:
Description of the drawings
Fig. 1 is a stereogram, it is shown that a kind of Magneto separate unit of an embodiment according to the present invention;
Fig. 2 is a top view, it is shown that a kind of the upper of Magneto separate unit of an embodiment according to the present invention regards situation;
Fig. 3 a are a stereogram, it is shown that a kind of Magneto separate unit of another embodiment according to the present invention;
Fig. 3 b are side view diagram, it is shown that a kind of Magneto separate unit of another embodiment according to the present invention;
Fig. 3 c are a stereogram, it is shown that a kind of Magneto separate unit of another embodiment according to the present invention;
Fig. 4-Fig. 5 is a series of schematic diagrames, it is shown that such as one amplification situation in Fig. 2;
Fig. 6 is a schematic diagram, it is shown that a kind of magnetic separation device of an embodiment according to the present invention;And
Fig. 7 is a sectional view, it is shown that the section of Magneto separate unit as shown in FIG. 6.
Main element symbol description
100,200 ~ Magneto separate unit;
102 ~ magnetism bar;
104,106 ~ fluid course;
One of 110 ~ Magneto separate unit;
300 ~ container component;
302 ~ opening;
304 ~ opening;
400~external magnetic field unit;
402~external magnetic field;
500 ~ central axis direction;
600 ~ magnetic separation device.
Specific implementation mode
Please refer to Fig. 1, it is shown that a stereogram of a kind of Magneto separate unit 100 of an embodiment according to the present invention.
As shown in Figure 1, Magneto separate unit 100 includes several magnetic bars 102, and these magnetic bars 102 are tight It is arranged adjacently and arranges, and then defines several streams for detaching magnetic biochemical substances between these magnetic bars 102 Body runner 104.In one embodiment, these magnetic bars 102 include for pure iron, magnetic stainless steel or the metal for having magnetic permeability The magnetic materials such as soft magnetism (magneticmaterials), and the soft magnetic metal for having magnetic permeability is, for example, iron, silicon steel, ferronickel, cobalt Iron, stainless steel, soft magnetic ferrite or combinations thereof.As shown in Figure 1, these magnetic bars 102 extend along its longitudinally, and flow Body runner 104 is then the linear type runner extended along the longitudinally of magnetic bar 102.These fluid courses 104 are phase Mutually parallel continuous flow path.
The powder of magnetic material first first can be shaped to strip idiosome by the making of magnetic bar 102, for example, by using molding (molding) or molding (die-casting) etc. modes followed by arrangement, be sintered these strip idiosomes to be formed such as Fig. 1 Shown in Magneto separate unit 100.Alternatively, these magnetic bars 102 also can directly use the magnetic material of several strip structures, Closely arrangement be arranged these strip structures, also can by such as ultrasonic welding (ultrasonic welding) mode by this A little strip structures are fixed together, and then form Magneto separate unit 100 as shown in Figure 1.
Please refer to Fig. 2, it is shown that regard situation on the one of the Magneto separate unit 100 of one embodiment of foundation.As shown in Fig. 2, according to The design requirement of the magnetic separation device correlated, magnetic bar 102 can regard situation with the upper of substantial circular.Though however, So the magnetic bar 102 used in this Magneto separate unit 100 is the upper bar regarding situation of substantial circular, in other realities It applies in example, magnetic bar 102 used in Magneto separate unit 100 may be used with such as polygonal upper other regarding situation The bar of shape, rather than limit with situation shown in Fig. 2 the shape of magnetic bar 102 used in Magneto separate unit 100.
Please refer to Fig. 3 a- Fig. 3 c, it is shown that a kind of solid of Magneto separate unit 200 of multiple embodiments according to the present invention Figure and side view.Based on simplification, only describe herein at the difference between two embodiments, and similar elements are represented with identical label.
As shown in the stereogram of Fig. 3 a, several magnetic bars 102 in Magneto separate unit 200 are in being closely arranged it Afterwards, from top to bottom an angle is reversed according to a such as anticlockwise direction and arranged, and then form Magneto separate unit 200. Therefore, because these magnetic bars 102, by torsion, the fluid course 104 between these magnetic bars 102 is just The non-linear runner gradually reversed downwards along the longitudinally of magnetic bar 102.Here, these fluid courses 104 are still For the continuous flow path being substantially parallel to each other.
In addition, as shown in Figure 3b, it is shown that a section view of a kind of Magneto separate unit 200 of another embodiment according to the present invention Figure.In the present embodiment, several magnetic bars 102 in Magneto separate unit 200 are after being closely arranged, from top to bottom according to An angle is reversed according to a such as anticlockwise direction and is arranged, and then forms Magneto separate unit 200.Here, the present embodiment Shown in magnetic bar 102 by torsion and windup-degree be more than magnetic bar 102 in Fig. 3 a, it is magnetic to be located at these Fluid course 104 between bar 102 be just the longitudinally along magnetic bar 102 and gradually reverse downwards such as spiral shell Revolve the non-linear runner of shape.Here, these fluid courses 104 are still the continuous flow path being substantially parallel to each other.
Furthermore as shown in Figure 3c, it is shown that the one of a kind of Magneto separate unit 200 of another embodiment is three-dimensional according to the present invention Figure, for explaining several magnetic bars 102 after arrangement by the situation of torsion.For purposes of simplicity, in figure 3 c only Depict the implementation situation of three magnetic bars 102 of the arranged and torsion in Magneto separate unit 200.In the present embodiment In, this three magnetic bars 102 from top to bottom reverse one after being closely arranged according to a such as anticlockwise direction Angle and arrange, and then form Magneto separate unit 200.Here, passing through for magnetic bar 102 shown in the present embodiment is turned round Turn and windup-degree is also greater than magnetic bar 102 in Fig. 3 a, the fluid course being located between these magnetic bars 102 104 be just along the longitudinally of these magnetic bars 102 and gradually reverse downwards such as spiral one non-linear runner.
Fig. 4 is a top view, it is shown that in one embodiment such as one 110 amplification situation in Fig. 2.Here, in Fig. 4 Several magnetic bars 102 can regard situation with the upper of substantial circular, and it substantially closely sets according to triangle manner The fluid channel 104 set and arranged, therefore defined between these magnetic bars 102, it is thus a little magnetic respectively One of several curved surfaces of bar 102 surrounds and defines.In an externally-applied magnetic field (not shown), these magnetic strips The magnetic line of force of externally-applied magnetic field can be guided the several songs for these magnetic bars 102 that most fluid channel 104 is exposed by object 102 In place of one surface in face, for the magnetic field gradient at lifting fluid channel 104, and therefore improves and flow through fluid channel 104 Sample fluid (not shown) in the magnetic force that is received of magnetisable material (not shown), thus promote the separation effect of magnetisable material Rate.
Please refer to Fig. 5, it is shown that in another embodiment such as one 110 amplification situation in Fig. 2.Here, in Fig. 5 Several magnetism bars 102 can be with being closely arranged and arrange depending on situation and substantially according to quadrangle mode on substantial circular Row, therefore the fluid channel 104 defined between these magnetic strips shape objects 102.Fluid course 104 shown in Fig. 5 Also there is the raising for being identical to the fluid course 104 shown in Fig. 4 to flow through in the sample fluid (not shown) of fluid channel 104 Magnetic force that magnetisable material (not shown) is received and thus promoted magnetisable material separative efficiency identical effect.
In other embodiments, magnetic bar 102 shown in Fig. 4-Fig. 5 can have the substantially polygon such as quadrangle On be closely arranged and arrange depending on situation and substantially respectively in accordance with triangle or quadrangle mode, therefore in these magnetic strips Difference is defined between shape object 102, and thus one of several planes of magnetic bars 102 surrounds a bit and definition forms one Fluid channel 104.
Please refer to Fig. 6, it is shown that a kind of magnetic separation device 600 of an embodiment according to the present invention.Here, such as Fig. 6 Shown, magnetic separation device 600 includes an external magnetic field unit 400, a container component 300 and is set to container component 300 An interior Magneto separate unit (being, for example, Magneto separate unit 100 or 200 above-mentioned).As shown, container component 300 has one to open Mouthfuls 302, to be used as a sample fluid entrance and an opening 304 as sample fluid outlet to be used.Here, holding Device element 300 includes polymethyl methacrylate (PMMA), acryl, polypropylene (PP), polyethylene (PE), polyvinyl chloride (PVC), the non-magnetic material of Teflon (Teflon), plastic cement, bakelite, nonmagnetic metal or ceramics.And container component 300 is opened Mouth 302 is then less than or equal to an overall dimensions of Magneto separate unit 100/200 with the size of opening 304.
As shown in fig. 6, container component 300 is schematically shown as a cylindrical hollow shell, there is a central axis direction 500. In the present embodiment, this 500 aligned in general of central axis direction is in the opening 302 and opening 304 of container component 300.Therefore, when in appearance When in device element 300 using Magneto separate unit 100 as shown in Figure 1, the Magneto separate unit that is set within container component 300 Central axis direction 500 of several magnetic bars 102 with several fluid courses 104 therebetween along container component 300 in 100 prolongs It stretches.And in other embodiments, the opening 302 of container component 300 can then have this central axis direction of misalignment to set with opening 304 Other implementation forms set.
In another embodiment, when in container component 300 using the Magneto separate unit 200 as shown in Fig. 3 a- Fig. 3 c, The several magnetic bars 102 and several fluid courses therebetween being set in the Magneto separate unit 200 within container component 300 104 along container component 300 central axis direction 500 extend and reverse.
In other embodiments, container component 300 can then change according to the shape of used Magneto separate unit 200, Therefore it can be the hollow housing of the other shapes with such as polygon, rather than be limited with situation shown in Fig. 6.
It is broken through as shown in fig. 6, the external magnetic field unit 400 in magnetic separation device 600 provides an external magnetic field 402 Container component 300 and Magneto separate unit 100/200, to provide Magnetic Isolation effect.This external magnetic field units 400 can be permanent magnetic Stone is generated or is generated by electromagnet.In one embodiment, external magnetic field unit 400 is formed by permanet magnet, and material is for example For neodymium iron boron (NdFeB), SmCo (SmCo), samarium iron nitrogen (SnFeN), alnico (AlNiCo), ferrite (ferrite) or its group It closes.In other embodiments, external magnetic field unit 400 is formed by electromagnet, and external magnetic field 402 is then by galvanization in electromagnet And it generates.
Fig. 7 is a sectional view, it is shown that 600 inner pressurd vessel element 300 of magnetic separation device and Magneto separate list as shown in FIG. 6 One section of member.As shown in fig. 7, using Magneto separate unit 100 and 200 as Figure 1-Figure 2 in container component 300 When, it is set to the several magnetic bars 102 and container of outermost in the Magneto separate unit 100/200 within container component 300 A fluid course 106 has then been defined between element 300 more respectively.In one embodiment, this fluid course 106 is by several magnetism The surface of bar 102 and a part for the inner surface of container component 300 surround.Fluid course 106 is exposed thus Magnetic bar 102 surface the magnetic line of force of externally-applied magnetic field can guide to most fluid channel 106 be exposed these are magnetic One place of several curved surfaces of bar 102, to improve the magnetic field gradient at fluid channel 106, thus can be improved and flow through The magnetic force that magnetisable material (not shown) in the sample fluid (not shown) of fluid channel 106 is received, and thus promoted magnetic The separative efficiency of substance.
An embodiment according to the present invention, using magnetic separation device 600 as Figure 6-Figure 7 for detaching biochemical samples A kind of operating method of interior magnetisable material.
First, a magnetic separation device is provided, magnetic separation device 600 for example, shown in fig. 6.Then, provide including The biochemical sample solution of the one of magnetisable material, above-mentioned magnetisable material are, for example, magnetic biochemical substances or the biochemistry through magnetisable material label Substance.Then, biochemical samples solution is made to flow through the container member in magnetic separation device 600 from the opening 302 of container component 300 Fluid channel 104 in part 300 and 106 and magnetic separation device 600 is left from the opening of container component 300 304, for inhaling Draw or repel its interior magnetisable material and be allowed on the tube wall for being attached to adjacent fluid channel 104 and 106, is for example, adjacent to fluid On one surface of the magnetic bar 102 in channel 104 and 106.Then, remove or close 600 institutes in magnetic separation device The external magnetic field 402 of offer is for example removed by removing container component 300 with Magneto separate unit 100/200 in this step outer The external magnetic field 402 that portion's magnetic field units 400 are provided, or close the electricity of the electromagnet included by external magnetic field unit 400 It flows and its external magnetic field provided is provided.Finally, a buffer solution is provided, and makes opening 302 of the buffer solution from container component 300 Place flows through fluid channel 104 in the container component 300 in magnetic separation device 600 and 106 and from the opening of container component 300 Magnetic separation device 600 is left at 304, is remained on the magnetic bar 102 in adjacent fluid channel 104 and 106 with elution Magnetisable material.
In one embodiment, the biochemical samples that can be passed through in magnetic separation device 600 are, for example, blood sample, pachyemia Sample, tissue sample, tissue fluid sample, cell sample, cell culture fluid sample, microbiological specimens, protein example, Amino acid Sample, nucleotide sample etc., and the magnetisable material for including in it is, for example, cell, microorganism, protein, Amino acid, nucleotide Deng magnetic biochemical substances or the biochemical substances marked through magnetisable material.And the magnetisable material of possible application be, for example, containing iron, cobalt, The particle of the metals such as nickel or its oxide, and the buffer solution that may be used is, for example, trishydroxymethylaminomethane (Tris- Buffer saline, TBS) buffer solution, phosphate buffer (phosphate buffer saline, PBS), normal saline solution (normal saline), with the isotonic solution of tissue fluid and other can Protein requirement/Amino acid/nucleotide equimolecular live The solution of property.
Embodiment:
Embodiment (1)
Using magnetic separation device 600 as shown in FIG. 6, using as schemed in the container component 300 of acryl material Magneto separate unit 200 shown in 3a- Fig. 3 c.In the present embodiment, Magneto separate unit 200 includes 125 SUS430 stainless steels The magnetic bar 102 of material is arranged to be formed with torsion, and the size of magnetic bar 120 is diameter 0.5mm.Through measuring, position The size of fluid course 104 between magnetic bar 102 is about 150 ~ 190 microns, and positioned at magnetic bar 102 and appearance The size of fluid course 106 between device element 300 is about then 60 ~ 100 microns.Then a biochemical samples is made to flow through container component Fluid course 104 and 106 in 300, wherein biochemical samples are to contain Fe3O4Aqueous solution, Fe3O4Particle size is 10nm- 15nm.Biochemical samples collect flushing liquor (wash) when flowing through separation magnetic field, after removing or closing external magnetic field, are eluted with buffer solution Fluid channel collects elutriant (elution).Flushing liquor and its contained Fe amount of elutriant, measurement such as table one are measured respectively It is shown, separation rate 90.7%.
One separation rate measurement of table:
Contain content in flushing liquor 13.8μg
Content in elutriant 134.0μg
Separation rate 90.7%
Embodiment (2)
Using magnetic separation device 600 as shown in FIG. 6, using as schemed in the container component 300 of acryl material Magneto separate unit 200 shown in 3a- Fig. 3 c.In the present embodiment, Magneto separate unit 200 includes 154 SUS430 stainless steels The magnetic bar 102 of material it is arranged with reverse, the size of magnetic bar 120 is diameter 0.5mm.Through measuring, position The size of fluid course 104 between magnetic bar 102 is about 120 microns, and positioned at magnetic bar 102 and container member The size of fluid course 106 between part 300 is about then 60 ~ 100 microns.Then a biochemical samples is made to flow through container component 300 Interior fluid course 104 and 106, wherein biochemical samples are to contain Fe3O4Aqueous solution, Fe3O4Particle size is 30nm.It is raw Change when sample flows through separation magnetic field and collects flushing liquor (wash), it is logical with buffer solution eluting fluid after removing or closing external magnetic field Elutriant (elution) is collected in road.Flushing liquor and its contained Fe amount of elutriant are measured respectively, measurement is as shown in Table 1, point It is 98.4% from rate.
Two separation rate measurement of table:
Contain content in flushing liquor 2.6μg
Content in elutriant 162.0μg
Separation rate 98.4%
Although the above all embodiment has been combined to disclose the present invention, it is not limited to the present invention, it is any ripe This operator is known, without departing from the spirit and scope of the present invention, when can change and retouch, therefore protection scope of the present invention It should be subject to what the appended claims were defined.

Claims (10)

1. a kind of Magneto separate unit, including:
Multiple magnetism bars, are closely arranged, and define continuous between those magnetic bars and are mutually parallel multiple First fluid runner, wherein those magnetic bars extend and reverse along a direction with those first fluid runners.
2. a kind of magnetic separation device, including:
External magnetic field unit;
Container component is set in the external magnetic field unit, has central axis direction, fluid inlet and fluid outlet;And
Magneto separate unit as described in claim 1, is set within the container component, wherein those magnetic bars and those First fluid runner extends and reverses along a central shaft of the container component, and wherein the container component includes non-magnetic material, and The external magnetic field unit provides an external magnetic field at the container component and the Magneto separate unit.
3. the magnetic separation device described in Magneto separate unit as described in claim 1 or claim 2, wherein those magnetic strips Shape object includes the soft magnetic metal or soft magnetic ferrite for having magnetic permeability.
4. the magnetic separation device described in Magneto separate unit as described in claim 1 or claim 2, wherein those are first-class Body runner is spiral flow channel.
5. the magnetic separation device described in Magneto separate unit as described in claim 1 or claim 2, wherein being seen from upper regard It, those magnetic bars are round or polygon.
6. the magnetic separation device described in Magneto separate unit as described in claim 1 or claim 2, wherein those are first-class Body runner is surrounded by several curved surfaces or plane.
7. magnetic separation device as claimed in claim 2, the wherein non-magnetic material include polymethyl methacrylate, pressure gram Power, polypropylene, polyethylene, polyvinyl chloride, Teflon, plastic cement, bakelite, nonmagnetic metal or ceramics.
8. magnetic separation device as claimed in claim 2, the wherein size of the fluid inlet and the size of the fluid outlet are small In or equal to the Magneto separate unit size.
9. magnetic separation device as claimed in claim 2 wherein more defines between those magnetic bars and the container component Go out a second fluid runner.
10. magnetic separation device as claimed in claim 2, wherein the external magnetic field unit include permanet magnet or electromagnet.
CN201210548265.6A 2012-11-28 2012-12-17 Magnetic separation unit and magnetic separation device Active CN103846156B (en)

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CN105973682B (en) * 2016-04-26 2019-02-22 武汉格蓝丽富科技有限公司 Sample separator and separation method, biochip and its application method
US11946038B1 (en) 2020-05-29 2024-04-02 10X Genomics, Inc. Methods and systems including flow and magnetic modules

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FR2544223B1 (en) * 1983-04-14 1988-07-01 Uk I Inzh Vo SOLID PARTICLE SEPARATOR FROM FLUIDS USING A MAGNETIC FIELD
US5385707A (en) * 1988-12-28 1995-01-31 Stefan Miltenyi Metal matrices for use in high gradient magnetic separation of biological materials and method for coating the same
US5055190A (en) * 1989-04-13 1991-10-08 Combustion Engineering, Inc. High volume permanent magnet filter
CN2160655Y (en) * 1993-04-16 1994-04-06 陈镜明 Ionic water magnetic field separator
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