WO2014082752A1 - Dispositif pour la séparation de microparticules magnétiques ou magnétisables d'une suspension au moyen d'une séparation magnétique à gradient élevé - Google Patents

Dispositif pour la séparation de microparticules magnétiques ou magnétisables d'une suspension au moyen d'une séparation magnétique à gradient élevé Download PDF

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Publication number
WO2014082752A1
WO2014082752A1 PCT/EP2013/003618 EP2013003618W WO2014082752A1 WO 2014082752 A1 WO2014082752 A1 WO 2014082752A1 EP 2013003618 W EP2013003618 W EP 2013003618W WO 2014082752 A1 WO2014082752 A1 WO 2014082752A1
Authority
WO
WIPO (PCT)
Prior art keywords
surface elements
optical
suspension
deposition chamber
flow
Prior art date
Application number
PCT/EP2013/003618
Other languages
German (de)
English (en)
Inventor
Percy Kampeis
Daniel FEIND
Michael LIEBLANG
Original Assignee
Hochschule Trier
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Hochschule Trier filed Critical Hochschule Trier
Priority to EP13814428.2A priority Critical patent/EP2925453B1/fr
Publication of WO2014082752A1 publication Critical patent/WO2014082752A1/fr

Links

Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B03—SEPARATION OF SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS; MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C—MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C1/00—Magnetic separation
    • B03C1/02—Magnetic separation acting directly on the substance being separated
    • B03C1/025—High gradient magnetic separators
    • B03C1/031—Component parts; Auxiliary operations
    • B03C1/033—Component parts; Auxiliary operations characterised by the magnetic circuit
    • B03C1/034—Component parts; Auxiliary operations characterised by the magnetic circuit characterised by the matrix elements
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B03—SEPARATION OF SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS; MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C—MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C1/00—Magnetic separation
    • B03C1/02—Magnetic separation acting directly on the substance being separated
    • B03C1/28—Magnetic plugs and dipsticks
    • B03C1/282—Magnetic plugs and dipsticks with associated accumulation indicator, e.g. Hall sensor
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B03—SEPARATION OF SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS; MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C—MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C1/00—Magnetic separation
    • B03C1/02—Magnetic separation acting directly on the substance being separated
    • B03C1/28—Magnetic plugs and dipsticks
    • B03C1/286—Magnetic plugs and dipsticks disposed at the inner circumference of a recipient, e.g. magnetic drain bolt
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B03—SEPARATION OF SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS; MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C—MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C2201/00—Details of magnetic or electrostatic separation
    • B03C2201/18—Magnetic separation whereby the particles are suspended in a liquid
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B03—SEPARATION OF SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS; MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C—MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C2201/00—Details of magnetic or electrostatic separation
    • B03C2201/26—Details of magnetic or electrostatic separation for use in medical applications
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B03—SEPARATION OF SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS; MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C—MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C2201/00—Details of magnetic or electrostatic separation
    • B03C2201/32—Checking the quality of the result or the well-functioning of the device

Definitions

  • the present invention relates to a device for separating magnetic or magnetizable microparticles from a suspension by means of high-gradient magnetic separation according to the preamble of patent claim 1.
  • the suspension can again be passed through the deposition matrix and the target substance now dissolved in the desorption buffer can be discharged.
  • the microparticles are recovered at the same time for further use. During the separation process, the loading of the deposition matrix increases
  • Microparticles too.
  • agglomeration forms accumulation areas which increasingly constrict the freely permeable volume of the deposition matrix.
  • increased flow velocities within the deposition matrix with increased drag force effect occur, while at the same time the magnetic restraining forces decrease with increasing size of the attachment regions.
  • microparticles detach from the deposition matrix and are lost to the residual suspension, resulting in loss
  • Microparticles and target substance is connected.
  • a ferromagnetic catching structure for immobilizing microscopic particles in a liquid, such as biological substances, is described in DE 697 29 101 T2.
  • the construction consists of a chamber, which in an outer
  • Magnetic field is arranged and receives the loaded with particles of liquid.
  • a magnetic or magnetizable grid is attached, which generates an internal gradient by distortion of the magnetic field. Since the too
  • the object of the invention is to develop existing devices for separating magnetic or magnetizable particles from a suspension by means of high-gradient magnetic separation such that already in advance of the Detachment of microparticles from the attachment areas, ie a filter breakthrough, influence on the separation process can be taken.
  • the basic idea of the invention is to detect the loading state of the deposition matrix with microparticles in the deposition chamber and, based thereon, to make a prediction about the probability of detachment of microparticles from the deposition matrix. A risk assessment is therefore already in advance of a possible
  • Microp made with the advantage of being able to take timely countermeasures. It is the merit of the invention to have implemented this idea for the first time and with reasonable effort, with the help of an optical measuring device, the flow spaces are monitored for the suspension. Once the flow area is narrowed beyond a critical extent due to the size of the microparticle accumulations
  • Countermeasures are initiated, such as throttling or stopping the flow rate in the inlet and / or an increase in the magnetic field strength.
  • the surface elements Preferably arranged plane-parallel to each other in the deposition chamber, which allows a high packing density of the surface elements.
  • a distance between the surface elements of a maximum of 5 mm, preferably between 0.5 mm and 2 mm has been found to be particularly useful.
  • Another advantage is an arrangement of the surface elements parallel to the flow direction in order to prevent a vortex formation of the flow, which would otherwise favor a detachment of the microparticles.
  • Surface elements arranged parallel to the optical visual axes prove advantageous with respect to optimum detection of the flow spaces between the surface elements over their entire length in the detection direction.
  • the magnetic field is directed perpendicular to the surface elements.
  • the pole shoes forming the magnetic field can in this way be arranged close to the surface elements and in close proximity to one another, which results in a very strong magnetization of the surface elements, with the result of an extremely high separating effect.
  • the surface elements have a multiplicity of openings in their plane of extent.
  • the effect is used that the magnetic field strength along the edges forming the openings is particularly high, which further improves the separation effect.
  • the openings preferably have a rectangular shape and can be formed as openings in a metal sheet or of a grid structure with crossing wires.
  • the separator may have a structurally simple and robust construction, with a continuous channel-shaped deposition chamber for receiving the deposition matrix and passage of the suspension.
  • the optical measuring device whose optical axes penetrate the Abscheidhunt, while stationary on the device in the immediate vicinity of the separator, wherein optical windows in the housing wall of the separator in the region of the optical axes, the image capture in the interior of the deposition chamber
  • a reliable sterile sealing of the deposition chamber is facilitated by the arrangement of the optical measuring device outside the sterile boundary and, moreover, prevents the optical measuring device from being damaged during the steam sterilization of the deposition chamber.
  • the optical sight axes of the optical measuring device are substantially parallel to the surface elements and transversely to
  • This measure initially has the advantage that the optical measuring device and the inlet and outlet at a spatial distance from each other can be arranged so that sufficient space is available. Another advantage results from the pronounced longitudinal extension direction of the surface elements parallel to the flow direction.
  • the measuring path of the optical measuring device therefore extends over the shorter dimension of the surface elements, which allows a more accurate measurement result.
  • this does not exclude that under certain circumstances it may also be advantageous to arrange the optical sight axes parallel to the flow direction, for example if the arrangement of optical viewing windows on the sides of the deposition chamber is not possible, or both perpendicular and parallel to the flow direction by means of a additional optical measuring device is to be worked to the brightest possible illumination of the
  • measuring device To arrange measuring device opposite.
  • the optical detection of the clear distance of the surface elements takes place in the backlight, so that a particularly high-contrast recording is possible, which allows an accurate evaluation.
  • the measurement accuracy can be further increased by the use of diffused light.
  • FIG. 1 is a schematic oblique view of a separator according to the invention
  • FIG. 3 shows a longitudinal section through the separator shown in FIG.
  • FIG. 4 shows a cross section through the separator shown in FIG.
  • FIG. 5 is a side view of the separator shown in Figure 2
  • 6 is a plan view of the separator shown in Figure 5
  • Fig. 7 is an oblique view of a further embodiment of an inventive
  • FIG 8 shows a longitudinal section through an alternative embodiment of an inlet or outlet of a separator according to the invention.
  • Figure 1 corresponds to a schematic functional representation of the invention.
  • a separation chamber 1 indicated by dashed lines can be seen, in which a deposition matrix 2 having a plurality of magnetic or magnetizable surface elements 3 is arranged.
  • the surface elements 3 lie with a lateral distance parallel to the plane side by side and have a plurality of openings 4 over their entire surface.
  • On the deposition matrix 2 acts
  • the separation matrix 2 is traversed from top to bottom by a suspension whose flow direction 5 is represented by arrows.
  • Flow space 6 are monitored by an optical measuring device 7.
  • the optical sight axes 8 of the optical measuring device 7 extend parallel to the surface elements 3 and perpendicular to the flow direction 5.
  • An illumination system 9 is the optical
  • the illumination system 9 generates in this way backlight for the optical measuring device. 7
  • the activated during the separation magnetic field 23 causes a magnetization of
  • FIG. 1 A first concrete implementation of the principle explained in FIG. 1 is the subject matter of FIGS. 2 to 6. There, a separator 12 is shown, through which a suspension 5 loaded with microparticles is flowed through individually or in series or in parallel.
  • the separator 12 has a liquid-tight rectangular housing 3, which is formed by two mirror-image-shaped side walls 14 and 15, which lie with their flat, facing inner sides 16 to each other.
  • the inner sides 16 each have an outgoing from its surface extending over the entire length continuous
  • each of the view channels 21 and 22 is a respective the deposition chamber 1 gas and
  • optical window 24 form-fitting, which is flush with the inside of the deposition chamber 1.
  • a circulating sterile liquid and gas seal 25 between optical window 24 and sight channel 21, 22 ensures that no suspension from the deposition chamber 1 to the outside.
  • the optical windows 24 may be made of quartz glass, e.g. B. Suprasil.
  • the seal 25 is for this purpose preferably made of a heat-resistant elastomer, for example of an EPDM.
  • FIGS. 2 to 5 show an inlet 26 with a connecting piece 27 for a hose line, not shown, to which a funnel-shaped widening 28 adjoins.
  • Flow-conducting internals in the expansion 28 ensure that the concentrated in the connecting piece 27 incoming suspension stream 5 evenly over the Flow cross section of the deposition chamber 1 fanning and the flow spaces 6 flows through.
  • a drain 26, which is designed in accordance with the inlet 26, is arranged with connecting piece 27 and widening 28.
  • the deposition chamber 1 is thus bounded laterally by the side parts 14 and 15 and the optical windows 24 (in particular FIG. 4) and in the direction of flow 5 by the inlet 26 and outlet 30 (in particular FIGS. 2 and 3).
  • the deposition chamber 1 serves to receive a magnetizable deposition matrix 2, which is formed by a plurality of magnetizable surface elements 3.
  • the surface elements 3 are arranged plane-parallel to the inside of the side walls 14 and 15 and plane-parallel and at a lateral distance from each other. By the lateral distances between the individual
  • the surface elements 3 are held together at two opposite edges by holding elements, not shown, so that the deposition matrix 2 can be removed from the deposition chamber 1 for their replacement as a whole, for example as a filter package.
  • Each surface element 3 has a plurality of openings 4, which in the present
  • Embodiment rectangular shape may also be formed circular or slot-shaped.
  • the openings may also result from a grid structure of the surface elements 3.
  • the web width between the openings 4 is
  • FIGS. 5 and 6 also show the device for generating the magnetic field 23.
  • the pole pieces 32 and 33 of a permanent magnet or electromagnet, which receive the separator 12 in a form-fitting manner, can be seen.
  • the side walls 14, 15 lie flat against the pole pieces 32 and 33. The field lines of the generated in this way
  • Magnetic field 23 are perpendicular to the surface elements 3 of the deposition matrix. 2
  • the optical measuring device 7 comprises a camera, which has the flow cross-section in the
  • Flow chambers 6 recorded continuously or in predetermined time intervals.
  • the optical measuring device 7 outside of the separator 12 of the end face 20 is opposite arranged, wherein the optical sight axes 8 of the measuring device 7 through the viewing channels 21, 22, the flow spaces 6 and the optical windows 24 extend.
  • the illumination system 9 which is arranged at the level of the optical viewing axes 8 and light 10 in the direction of
  • the light source can consist of several discrete LEDs or a luminescent film.
  • a light diffuser for example a light diffusion foil, between the optical window 24 and the illumination system 9, or to form the optical window 24 as a diffuser.
  • FIG. 7 shows an alternative embodiment of a separator 12 'according to the invention, wherein the same reference numbers are used for identical or functionally identical features as far as this facilitates the understanding of the invention.
  • the flow direction of the suspension is again denoted by 5 and the optical sight axes by 8.
  • the separator 12 has a plate-shaped base body 34, into which a channel forming the deposition chamber 1, centrally encircled by a bottom 35 and two sides 36, is milled in the middle.
  • a slot-like opening 37 is introduced into the sides 36 of the channel, which serves for receiving the optical window 24 already described in FIGS. 1 to 6.
  • the sides 36 of the deposition chamber 1 at their in the flow direction 5 front and rear ends respectively grooves 38 which extend over the entire height of the sides 36 and perpendicular to the bottom 35.
  • the upper side of the base body 34 has a planar offset for the positive reception of a merely by Dashed line indicated cover 39, which is tensioned by means not shown releasable fastening means against the base body 34.
  • Holding elements 41 result in a stable unit, which can be removed easily and quickly as a whole when changing the surface elements 3 of the deposition chamber 1. By a groove 38 corresponding cross section of the holding elements 41, this can be easily and quickly as a whole when changing the surface elements 3 of the deposition chamber 1.
  • the deposition matrix can be inserted axially into the deposition chamber in this embodiment.
  • This embodiment is characterized by a particularly high stability and tightness.
  • the housing of the separator is formed as a disposable part, for example in the form of a
  • FIG. 8 shows a longitudinal section through an alternative embodiment of an inlet 26 'and optionally also a drain 30' in a plane-parallel plane to the
  • the inlet 26 ' has a first longitudinal section 42' in the flow direction 5 'over whose length L A the expansion 28' is completed and a subsequent cylindrical longitudinal section 43 of length L z with rectangular cross section.
  • the aspect ratio of longitudinal section 43 to longitudinal section 42 is preferably greater than 0.15 and most preferably in a range of 0.25 to 0.3.
  • the widening 28 ' has a continuous course in the direction of flow 5 without kinks and edges and likewise passes continuously into the cylindrical longitudinal section 43.
  • the angle ⁇ of the widening 28 ' is at most 15 degrees and most preferably in a range between 8 degrees and 12 degrees.
  • this geometry of the inlet 26 'with the reverse flow direction 5 is also applied to the drain 30.

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  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)

Abstract

L'invention concerne un dispositif pour la séparation de microparticules magnétiques ou magnétisables d'une suspension (5) au moyen d'une séparation magnétique à gradient élevé, Le dispositif présente un séparateur (12), dont le boîtier (13) entoure une chambre de séparation (1) qui peut être traversée par une suspension (5) dans un sens d'écoulement (5') prédéterminé. Une matrice de séparation (2) magnétique ou magnétisable est disposée dans la chambre de séparation (1) et comprend plusieurs éléments plats (3) écartés latéralement les uns des autres qui forment ainsi des espaces d'écoulement (6) pour la suspension (5). La suspension (5) est transportée via une alimentation (26) et une évacuation (30) dans et hors des espaces d'écoulement (6). Pour détecter l'état de charge de la matrice de séparation (2) par des microparticules dans la chambre de séparation (1) et pouvoir prédire, sur cette base, la probabilité d'un détachement des microparticules de la matrice de séparation (2), selon l'invention, un dispositif de mesure optique (7) et un système d'éclairage (9) sont utilisés. Pour déterminer la grandeur de l'écartement entre les éléments plats (3), les axes visuels optiques (8) du dispositif de mesure optique (7) s'étendent dans les espaces d'écoulement (6) et le système d'éclairage (9) présente au moins une source de lumière dont la lumière (10) peut être émise dans les espaces d'écoulement (6).
PCT/EP2013/003618 2012-11-30 2013-11-30 Dispositif pour la séparation de microparticules magnétiques ou magnétisables d'une suspension au moyen d'une séparation magnétique à gradient élevé WO2014082752A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP13814428.2A EP2925453B1 (fr) 2012-11-30 2013-11-30 Dispositif pour la séparation de microparticules magnétiques ou magnétisables d'une suspension au moyen d'une séparation magnétique à gradient élevé

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102012023382.5 2012-11-30
DE102012023382.5A DE102012023382A1 (de) 2012-11-30 2012-11-30 Vorrichtung zum Abscheiden magnetischer oder magnetisierbarer Mikropartikel aus einer Suspension mittelsHochgradienten-Magnetseparation

Publications (1)

Publication Number Publication Date
WO2014082752A1 true WO2014082752A1 (fr) 2014-06-05

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PCT/EP2013/003618 WO2014082752A1 (fr) 2012-11-30 2013-11-30 Dispositif pour la séparation de microparticules magnétiques ou magnétisables d'une suspension au moyen d'une séparation magnétique à gradient élevé

Country Status (3)

Country Link
EP (1) EP2925453B1 (fr)
DE (1) DE102012023382A1 (fr)
WO (1) WO2014082752A1 (fr)

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3806340A1 (de) * 1984-12-05 1989-09-07 Akad Wissenschaften Ddr Matrix fuer magnetscheider
US5053344A (en) * 1987-08-04 1991-10-01 Cleveland Clinic Foundation Magnetic field separation and analysis system
US5188239A (en) * 1991-06-17 1993-02-23 Industrial Magnetics, Inc. Tramp metal separation device
WO1994011078A1 (fr) * 1992-11-16 1994-05-26 Immunivest Corporation Immobilisation et manipulation magnetiques d'entites biologiques
WO2001075183A2 (fr) * 2000-03-31 2001-10-11 Worcester Polytechnic Institute Systems for detecting and measuring inclusions
DE69729101T2 (de) 1996-06-07 2005-05-12 Immunivest Corp., Wilmington Magnetische trennung mit hilfe von externen und internen gradienten
DE102004034541B3 (de) * 2004-07-16 2006-02-02 Forschungszentrum Karlsruhe Gmbh Hochgradienten-Magnetabscheider
DE102005034327B3 (de) 2005-07-22 2006-11-30 Forschungszentrum Karlsruhe Gmbh Vorrichtung zur Affinitätsseparation mittels magnetischer Partikel

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5055190A (en) * 1989-04-13 1991-10-08 Combustion Engineering, Inc. High volume permanent magnet filter

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3806340A1 (de) * 1984-12-05 1989-09-07 Akad Wissenschaften Ddr Matrix fuer magnetscheider
US5053344A (en) * 1987-08-04 1991-10-01 Cleveland Clinic Foundation Magnetic field separation and analysis system
US5188239A (en) * 1991-06-17 1993-02-23 Industrial Magnetics, Inc. Tramp metal separation device
WO1994011078A1 (fr) * 1992-11-16 1994-05-26 Immunivest Corporation Immobilisation et manipulation magnetiques d'entites biologiques
DE69729101T2 (de) 1996-06-07 2005-05-12 Immunivest Corp., Wilmington Magnetische trennung mit hilfe von externen und internen gradienten
WO2001075183A2 (fr) * 2000-03-31 2001-10-11 Worcester Polytechnic Institute Systems for detecting and measuring inclusions
DE102004034541B3 (de) * 2004-07-16 2006-02-02 Forschungszentrum Karlsruhe Gmbh Hochgradienten-Magnetabscheider
DE102005034327B3 (de) 2005-07-22 2006-11-30 Forschungszentrum Karlsruhe Gmbh Vorrichtung zur Affinitätsseparation mittels magnetischer Partikel

Also Published As

Publication number Publication date
EP2925453B1 (fr) 2021-11-17
DE102012023382A1 (de) 2014-06-18
EP2925453A1 (fr) 2015-10-07

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