EP1954396B1 - Separateur magnetique et procede - Google Patents

Separateur magnetique et procede Download PDF

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Publication number
EP1954396B1
EP1954396B1 EP06832055.5A EP06832055A EP1954396B1 EP 1954396 B1 EP1954396 B1 EP 1954396B1 EP 06832055 A EP06832055 A EP 06832055A EP 1954396 B1 EP1954396 B1 EP 1954396B1
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EP
European Patent Office
Prior art keywords
magnet
tubing
unit
magnets
fluid
Prior art date
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Active
Application number
EP06832055.5A
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German (de)
English (en)
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EP1954396A2 (fr
Inventor
Hilde Almaasbak
Christer The Imego Institute JOHANSSON
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Life Technologies AS
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Life Technologies AS
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Priority claimed from GB0524684A external-priority patent/GB0524684D0/en
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Publication of EP1954396A2 publication Critical patent/EP1954396A2/fr
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    • 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
    • B03C1/288—Magnetic plugs and dipsticks disposed at the outer circumference of a recipient
    • 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

Definitions

  • separating components of a solution by using magnetisable particles are disclosed. Separation of targets in a solution which comprises targets and non-targets can be performed using magnetisable particles coated with a ligand which binds to the targets, the target-particle complexes then being magnetically separated from the remaining components of the solution by applying a magnetic field with a gradient.
  • Targets can include viruses, prokaryotic cells, or eukaryotic cells.
  • Magnetisable particles are well known. These particles may be used for all affinity separation processes where the targets and non-targets are similar in molecular weight so that techniques such as centrifugation cannot be used. Instead, the targets and non-targets are separated by making use of their different affinity properties.
  • the targets and non-targets can be separated by identifying a ligand such as an antigen, antibody, protein, polysaccharide, etc. which binds to the targets but not to the non-targets.
  • the magnetisable particles are coated with this ligand and added to the sample solution. The solution is then incubated for a period so that as many as possible of the magnetisable particles attach, via the ligand, to the targets.
  • a magnetic field with a gradient is then applied to the solution to attract and thereby trap the magnetisable particles with the targets attached while the remainder of the solution with the non-targets is removed.
  • the size of the magnetisable particles and the coating applied to them may be varied depending on the application. Typically, the particles may be about 1-10 microns in diameter. In most applications, the magnetisable particles are supplied in a quantity several times the number of targets so that virtually all targets are bound by at least one magnetisable particle.
  • WO 90/14891 describes a separation device comprising a rack for tubes, with a magnet placed adjacent to each tube slot such that the tubes intersect the fields of force from the magnet.
  • the magnet attracts the magnetisable particles (and the targets to which they are bound) to the side of the tube. The remaining non-targets can then be removed by a pipette.
  • the liquid containing the target may be stored within a flexible container or an aseptic bag such as a disposable blood bag.
  • an aseptic bag such as a disposable blood bag.
  • the bag is usually laid flat on top of a planar magnet or set of magnets after incubation.
  • the magnetisable particles (with the targets attached) are drawn down towards the magnet.
  • the remaining liquid conatining the non-targets can then be evacuated through an outlet tube attached to the bag, while the magnetisable particles and targets are held in place on the bag wall by the magnet.
  • U.S. Patent No. 4,910,148 , WO 90/04019 and WO 91/11716 are all examples of such machines designed for use with cell suspensions.
  • U.S. Patent No. 6,143,577 describes an apparatus for separating magnetic particles in a fluid for a biological analysis.
  • a flexible tube is coiled into a spiral under a set of magnets that have radially arranged orientations.
  • a flexible tube is guided over a stack of magnets that have orientations that are perpendicular to the axis of the stack.
  • Separation can be performed either positively or negatively.
  • positive separation processes the magnetisable particles attach to the targets which are to be retained so that these desired targets are retained by the magnet.
  • negative separation processes the magnetisable particles attach to the non-targets which are to be removed so that these non-targets are retained by the magnet, while the desired targets are withdrawn from the system.
  • positive separation processes the desired targets which are retained are still attached to the magnetisable particles, so the magnetisable particles may need to be cleaned from the targets before further analysis.
  • negative separation processes the desired targets are withdrawn from the system and are therefore free from magnetisable particles and are ready for further analysis if desired.
  • U.S. Patent No. 4,710,472 describes a magnetic separator system where a tube through which the sample flows is held between two magnets or where a magnet is held next to the tube.
  • a tube through which the sample flows is held between two magnets or where a magnet is held next to the tube.
  • the process and the machines for carrying out the cell isolation process must meet certain requirements set by the relevant authorities, such as the Food and Drug Administration (FDA) in the United States.
  • FDA Food and Drug Administration
  • One such requirement is that the number of magnetisable particles which the system fails to capture must be below a certain threshold.
  • the FDA requirement for medical applications is that there must be less than 100 magnetisable particles per 3 million cells infused into a human subject.
  • WO 90/04019 and WO 91/11716 a similar arrangement is described wherein the cell concentrate is mixed with the magnetisable particles in a first disposable container which is placed in the primary separation chamber with the primary planar magnet.
  • the first container is connected via a tube to a second disposable container which is placed in the secondary separation chamber with the secondary planar magnet.
  • the purified cell concentrate is obtained from the outlet of the second container, while the separated cells attached to the paramagnetic particles are held along the sides of the first and second containers adjacent to the first and second magnets.
  • the primary magnetic separation unit tends to have a magnet which has a relatively large field reach, capable of attracting magnetisable particles from the whole width of the first bag.
  • the secondary magnetic separation unit tends to have a magnet which has a smaller field reach, but provides a correspondingly stronger attractive force for retaining the particles.
  • the width of the second bag is restricted so that the magnetisable particles are within the field reach of the second magnet.
  • a disadvantage of these systems is that the systems require the use of additional disposable containers or bags. For each system run on a two magnet system, at least two bags are used, plus the tubing required to feed the first container, transfer fluid from the first to the second container and extract fluid from the second container. As these bags and tubes must all be sterile and aseptically connected, this represents a significant expense to the end user. These bags must often be the proprietor's own brand bags to fit their particular machine and so may be relatively expensive.
  • planar magnet assemblies are bulky and heavy, especially when the secondary separation unit is provided with an additional pressing means for restricting the width of the bag. These systems are also complicated and time consuming to set up.
  • the invention provides a magnetic separator unit according to claim 1 for the selective separation of magnetisable particles from a fluid mixture, the magnetic separator unit comprising: a magnet unit for attracting the magnetisable particles, the magnet unit being in the form of a mandrel and comprising a plurality of magnets orientated parallel to the axis of the mandrel and angularly spaced around the mandrel around which, in use, a tubing for fluid flow is wound, so as to enable the magnet unit to attract the magnetisable particles in the fluid.
  • Such a magnetic separation unit provides a much more straightforward and easy to use set up.
  • An outlet tubing of a reservoir or sample bag containing the sample to be separated is wound around the mandrel. There is therefore no need for further unnecessary usage of disposable bags. It is also much less expensive for the end user as any standard tubing may be used.
  • the tubing wound round the magnet is downstream of the sample reservoir and is preferably directly connected to it. The tubing may easily be removed from the magnet after the separation process.
  • a magnetic separation unit may thus be used by taking a reservoir or sample bag which contains the sample with targets and non-targets to be separated and connecting an outlet tubing to it.
  • the outlet tubing can then be wound around the magnet unit of the invention as described above and the sample is passed through the tubing, next to the magnet unit, and therefore through the magnetic field of the magnet unit so that the magnetisable particles within the sample are attracted to the magnet unit and held within the tubing.
  • a peristaltic pump may be used to pump the sample through the tubing.
  • a waste chamber may be attached to the other end of the tubing to collect the non-targets (or in the case of negative separation where the non-targets are bound to the magnetisable particles, the "waste" chamber collects the targets).
  • the amount of tubing placed around or adjacent to the magnet unit can be varied according to the requirements for removal of the magnetisable particles.
  • the more tubing that is placed adjacent to the magnet unit the greater the surface area there is for magnetisable particle capture.
  • This system also has the advantage that a large surface area for capture is provided, while at the same time providing a long flow path for the fluid. Keeping the magnetisable particles in close proximity to the magnet unit over a long flow path leaves much less chance of the particles escaping from the magnetic field, i.e. a much higher capture rate.
  • the magnet unit comprises a plurality of magnets orientated parallel to the axis of the mandrel and angularly spaced around the mandrel. These magnets may be arranged around an inner cylindrical mild steel core in order to increase the magnetic field in the region of the tubing .
  • the magnet unit may comprise a plurality of magnets attached together in a row. Preferably the magnets are orientated anti-parallel as this provides a stronger magnetic field for capture of the magnetisable particles.
  • a non-magnetic material may be placed between the plurality of magnets.
  • a non-magnetic housing (for instance non-magnetic stainless steel) is provided to cover the magnets. Winding the tubing around the surface of the magnet unit gives a long flow path (with respect to the dimensions of the magnet) along which the magnetisable particles must pass and where there are magnetic fields with gradients that yield magnetic forces on the particles and hold the particles to the magnet areas.
  • the magnets are permanent magnets and more preferably they are neodymium iron boron magnets.
  • the mandrel may be generally cylindrical. Such a cylinder may be of any cross sectional shape, such as square or hexagonal, but it is preferably circular. Sharp corners may undesirably cause the tubing to kink when it is wound around the magnet unit.
  • the magnet unit comprises several magnets attached together in a row thus forming an elongate cylindrical magnet.
  • Preferably non-magnetic material is provided between these magnets.
  • the advantage of an elongate cylindrical magnet unit is that a larger surface area can be provided for a relatively low volume/bulk of magnet. A long flow path and a high capture rate may be achieved easily with such an arrangement.
  • the magnet unit is provided with at least one holder for holding the tubing adjacent to the magnet.
  • a holder helps to keep the tubing neatly arranged and in close proximity to the magnet.
  • the holder comprises a tubing clip at each end of the magnet. The tubing is wound around the magnet and then held tight by the clips at each end so that the tubing is held in close proximity to the magnet substantially throughout its length.
  • the at least one holder is arranged to hold the tubing at a plurality of regions along its length. More preferably the holder is arranged to clamp the tubing at a plurality of regions along its length.
  • the holder may hold or clamp each coil of the tubing as it is wound around the magnet unit.
  • the holder can be released after use so as to allow the tubing to be easily removed from the magnet unit.
  • the tubing clamp is magnetisable and attaches magnetically to the magnet unit. Making use of the magnetic properties of the separator is particularly useful as it negates the need for further attachment means such as bands or screws. It also allows greater flexibility in positioning the clamp on the magnet unit.
  • the clamp may be formed from a strip of magnetic or magnetisable material such as magnetic tape or magnetisable metallic tape placed over the tubing after the system has been set up.
  • the attractive force on the clamp from the magnet can be enough to squash the tubing which hinders the fluid flow therethrough. Therefore, preferably the tubing clamp comprises at least one steel clamp for magnetically attaching to the magnet and a non-magnetic retaining portion attached to the clamp for holding the tubing around or adjacent to the magnet.
  • the clamp is attached directly to the magnet and the retaining portion extending from the clamp holds the tubing around or adjacent to the magnet.
  • the retaining portion may be positioned a set distance from the magnet in order to accommodate the tubing.
  • the retaining portion may have an adjustable height so as to accommodate a range of tube diameters.
  • the retaining portion has a layer of light pressure material, e.g. soft rubber facing the magnet so as to accommodate a range of diameters and provide light pressure to the tubing to keep it in close contact with the magnet unit.
  • the magnet is typically quite strong.
  • the magnet may have a magnetic field strength of about 0.2 T to about 0.4 T, more preferably 0.25 T to about 0.35 T.
  • the clamp can be difficult to remove if it is not provided with a means of gaining purchase on it. Therefore, preferably the tubing clamp is provided with a grip which provides leverage for removing the clamp from the secondary magnet.
  • the magnet may comprise a permanent magnet. In some situations it is advantageous to be able to switch the magnetic field on or off so as to attract or release the magnetisable particles from its field. Alternatively therefore the magnet may be an electromagnet. The strength and structure of the magnet may vary a great deal and may be chosen according to the particular applications of the system.
  • the invention provides a system according to claim 15 for the selective separation of magnetisable particles from a fluid mixture, the system comprising: a primary magnetic separator comprising a primary magnet for attracting the magnetisable particles; and a secondary magnetic separator according to claim 1.
  • the fluid can generally be any type of fluid.
  • Examples of fluid include blood, serum, and urine.
  • the invention also provides a method according to claim 16 for removal of a target from a fluid, the method comprising: contacting the fluid with at least one magnetisable particle that binds said particle; attracting the magnetisable particle to a magnet being in the form of a mandrel around which a tubing for fluid flow is wound, so as to enable the magnet to attract the magnetisable particle in the fluid, wherein the magnet comprises a plurality of magnets orientated parallel to the axis of the mandrel and angularly spaced around the mandrel; and separating from the magnetisable particle from the fluid, wherein the target is removed from the fluid.
  • a primary magnetic separator unit is used for the initial separation of the magnetisable particles from the fluid mixture.
  • This stage may typically still use a disposable blood bag on a planar magnet as in the known systems, but other separation systems would be equally viable.
  • the outlet tubing instead of connecting the outlet tubing from the primary magnetic separator to a second disposable blood bag on a second planar magnet, the outlet tubing itself may be wound around the secondary magnet. There is therefore no need for further unnecessary usage of disposable bags. It is also much less expensive for the end user as any standard tubing may be used. After use, the tubing can simply be removed from the magnet.
  • the outlet tubing wound around the secondary magnet is directly connected to the primary separator unit, in particular for example, to the flexible bag of the primary separator unit.
  • the system or separator unit comprises the outlet tubing.
  • the internal diameter of the tubing is preferably chosen so that the magnet still provides a field strength at the outer edge of the tubing sufficient to attract and capture the magnetisable particles.
  • the choice of diameter also depends on the composition and/or viscosity of the sample.
  • the tubing is about 0.2 to 1 cm, most preferably about 0.5 cm in diameter.
  • the invention also provides a system comprising a separator unit as described above, the system further comprising a reservoir upstream of the separator unit for supplying fluid mixture thereto.
  • a fluid is obtained which is substantially free of targets when positive separation is used or substantially free of non-targets when negative separation is used.
  • the invention as described above is suitable for many applications. For example it may be used for the isolation of target cells from e.g. blood bags. Alternatively, the system may be used for separating parasites, bacteria or viruses from water samples. Also the system may be used for separating contaminating microbes and/or viruses from an incubated food sample in broth.
  • the magnetisable particles are preferably paramagnetic and more preferably superparamagnetic.
  • Figure 1 shows a system 1 with a first disposable bag 2 laid flat on a primary planar magnet 3.
  • the outlet of the first disposable bag 2 is connected to an outlet tube 4 which is in turn connected to the inlet of a second disposable bag 5.
  • the second disposable bag is laid flat on a secondary planar magnet 6.
  • the outlet of the second disposable bag 5 is connected to a second outlet tube 7 which leads to a storage container or further processing or analysis equipment via its downstream outlet 17.
  • the system of Figure 1 can be used as follows.
  • the cell suspension which is to be separated is fed into the first disposable bag 2 through an inlet 8 (shown sealed shut in the figures).
  • the magnetisable particles can either be fed in at the same time as the cell suspension or they can be contained in a frangible container inside the bag which is broken just before incubation starts.
  • the cell suspension and the magnetisable particles are incubated for a period of time in order to maximise the number of magnetisable particles which bind to the target cells.
  • the first disposable bag 2 is placed on the primary magnet 3 so that the magnetisable particles are drawn towards the side of the bag closest to the magnet 3.
  • the remains of the cell suspension are then directed (often pumped) through the tubing 4 attached to the outlet of bag 2 and into the second disposable bag 5 which is already laid out on top of secondary planar magnet 6.
  • any magnetisable particles which escaped or bypassed the primary magnet 3 are caught by the secondary magnet 6 before the remains of the cell suspension leave the system via outlet 17 formed at the downstream end of second outlet tube 7 which may lead to a storage container or to further processing or analysis equipment.
  • the system is arranged so that the number of magnetisable particles which do not get trapped by either the primary or the secondary magnets, i.e. the number remaining in the suspension at outlet 17 is below the required level, e.g. below a regulatory requirement level.
  • FIG 2 shows a first embodiment of the invention.
  • the system 10 comprises a first disposable bag 2 connected to an outlet tube 4 (which is typically around 0.5 cm in internal diameter). However instead of connecting the outlet tube 4 to a second disposable bag, the outlet tube 4 is removably wound directly around the cylindrical magnet 9 thus bringing the magnetisable particles close to the magnet over a long flow path.
  • the system outlet 17 is formed at the downstream end of outlet tube 4. It can immediately be seen that this system is considerably improved over the system of Figure 1 as it uses a single disposable bag and a single length of tubing rather than two disposable bags and two lengths of tubing required by the system described in Figure 1 . After the separation process, the tubing 4 can easily be removed (unwound) from the magnet 9 for further processing or disposal.
  • FIG 3 shows a second embodiment of the invention.
  • the system 10 comprises a first disposable bag 2, planar magnet 3, inlet tube 8 and outlet tube 4 as described above in relation to the system of Figure 1 .
  • the outlet tube 4 is wound directly around the cylindrical secondary magnet 9 thus bringing the magnetisable particles close to the secondary magnet over a long flow path.
  • the system outlet 17 is formed at the downstream end of outlet tube 4. It can immediately be seen that this system is a considerable improvement to that of Figure 1 as it uses a single disposable bag and a single length of tubing rather than two disposable bags and two lengths of tubing required by the Figure 1 system. After the separation process, the tubing 4 can easily be removed (unwound) from the magnet 9 for further processing or disposal.
  • Figure 4 shows an example not forming part of the invention.
  • the primary magnetic separation unit is the same as described in relation to Figure 2 .
  • the secondary magnet is an elongate cylindrical magnet 30.
  • the elongate cylindrical magnet 30 is formed from a number of magnets 31, separated from each other by non-magnetic material 32.
  • the magnetic orientations (shown by arrow 33) of the magnets 31 are aligned so that the magnetic fields of neighbouring magnets are anti-parallel.
  • FIG. 5 shows a side view of a third embodiment of the invention which also uses a generally cylindrical magnet 9 as in the first embodiment.
  • the magnet 9 is provided with top and bottom plates 41, 42 on the ends of the cylinder.
  • Each plate 41, 42 is provided with a tube clip 43 for securing the tubing 4 (not shown) around the magnet 9 during use.
  • the spool shape formed by the top and bottom plates 41, 42 and the magnet 9, acts in the same way as, for example, a cotton reel to prevent the tubing 4 from slipping off the end of the cylindrical magnet 9.
  • the tubing 4 can easily be unclipped and removed for further processing or disposal after the separation process.
  • FIG. 6 shows an end view of the third embodiment of the invention.
  • the cross section of the magnet 9 can be seen here.
  • the secondary magnet 9 has a soft magnetic steel inner core 50 in order to increase the magnetic field in the region of the tubing.
  • the outer surface of the magnet 9 is a thin shell 51 of a non-magnetic material such as non-magnetic stainless steel.
  • twelve neodymium iron boron permanent magnets 52 are arranged, equally spaced around the periphery of the core 50. These magnets are arranged with their axes parallel to the axis of the cylinder, but with their magnetisation directions orientated anti-parallel to each other. That is, each magnet has its magnetisation orientation anti-parallel with that of its neighbours.
  • the top plate 41 is provided with a clamp 43 for holding the tubing 4 in place at the top and base plate 42 is also provided with a clamp 43 for holding the tubing 4 in place at the bottom.
  • This structure could also be used for the magnets 31 in the elongate cylindrical magnet 30 used in the example not forming part of the invention.
  • the embodiments described above may be used as a separation system in their own right or they may be used as a secondary separation unit downstream of a primary magnetic separation unit.
  • the primary magnetic separation unit may be a disposable bag placed on a planar magnet as in the known systems, however it will be understood that any alternative primary magnetic separation arrangement may be used instead.
  • FIG. 7 shows a magnetic holder 60 which can be used with any of the embodiments of the invention for holding the outlet tubing 4 neatly against the magnet 9, 30.
  • the holder 60 is shown here in use against a cylindrical magnet 9.
  • the holder 60 comprises two magnetisable attachment portions 61 which magnetically attach the holder to the magnet 9. These attachment portions 61 may be small iron or steel bars.
  • the attachment portions 61 are encased within a plastics retaining portion 62 which is spaced from the magnet 9 by an amount equal to approximately the diameter of the tubing 4.
  • the holder 60 is placed over the coils of tubing so that the retaining portion 62 holds them firmly against the magnet 9.
  • the coils are held between the two attachment portions 61 and may be supported by the lower attachment portion 61.
  • FIG 8 shows another embodiment of a holder 70 which can be used with any of the embodiments of the invention.
  • the holder 70 comprises two attachment portions (small magnetisable steel or iron bars) 71 to fix the holder 70 to the magnet 9, 30.
  • the attachment portions 71 are attached to a plastics (or other non-magnetic material) base 72 which holds the tubing 4 against the magnet 9, 30.
  • a layer of soft rubber 73 (or an equivalent material) to apply light pressure on the tubing 4 to keep it in close contact with the surface of the magnet 9, 30.
  • a grip 74 is also provided on the outside of the base 72 to aid removal of the holder 70 from the magnet 9, 30 by providing a handle where the user can get purchase on the holder 70. After the separation process, the holder 60 or 70 can be removed so that the tubing 4 can easily be removed from the magnet 9, 30 for further processing or disposal.
  • Figure 9 shows a preferred separator unit.
  • the fluid pole 90 runs along side the detachable primary magnet 91, which can rotate 180° to allow for optimization of the capture process, reducing trapping of unwanted bioparticles.
  • the primary magnet is directly above the secondary magnet 92, which catches and retains residual magnetic beads that might escape initial magnetic capture from the primary magnet..
  • the unit in Figure 9 is particularly suited for use with sterile blood bags and tubing systems for medium to large-scale cell separation. In preferred embodiment the unit permits scalable fluid volumes of 50 to 330 ml in static separations and >10 L in continuous flow separations following T cell expansion protocols.
  • the unit in Figure 9 has been used to positively isolate bead-bound cells for subsequent stimulation/expansion of T cells and for removal of the beads following the expansion. Additionally, the unit has been used to deplete unwanted cell types by discarding the magnetic captured bead-bound cells, e.g. depletion of monocytes after phagocytosis.

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Claims (17)

  1. Unité de séparateur magnétique destinée à la séparation sélective de particules magnétisables à partir d'un mélange fluide, l'unité de séparateur magnétique comprenant : une unité à aimants (9) sous la forme d'un mandrin ; et un tube (4) ; dans laquelle :
    l'unité à aimants (9) comprend une pluralité d'aimants (52) orientés parallèlement à l'axe du mandrin ; caractérisée en ce que
    le tube (4) est enroulé autour de l'unité à aimants (9) de manière à permettre à l'unité à aimants (9) d'attirer les particules magnétisables du mélange de fluide sur une longue trajectoire d'écoulement.
  2. Unité de séparateur selon la revendication 1, dans laquelle la pluralité d'aimants (52) est disposée autour d'un coeur d'acier doux cylindrique intérieur (50).
  3. Unité de séparateur selon la revendication 2, dans laquelle une coque en acier inoxydable extérieure (51) est prévue pour couvrir la pluralité d'aimants (52).
  4. Unité de séparateur selon la revendication 1, dans laquelle la pluralité d'aimants (52) sont disposés de sorte que l'orientation magnétique de chaque aimant (52) est anti-parallèle à celle de ses aimants voisins (52).
  5. Unité de séparateur selon la revendication 2, 3 ou 4, dans laquelle du matériau non magnétique (32) se trouve entre la pluralité d'aimants (52).
  6. Unité de séparateur selon l'une quelconque des revendications 1 à 5, dans laquelle la pluralité d'aimants (52) comprend des aimants permanents, les aimants permanents étant de préférence des aimants au néodyme fer bore.
  7. Unité de séparateur selon la revendication 1, dans laquelle la pluralité d'aimants (52) comprend des électroaimants.
  8. Unité de séparateur selon l'une quelconque des revendications précédentes, comprenant en outre au moins un support (43, 60, 70) permettant de maintenir le tube (4) proche de l'unité à aimants (9).
  9. Unité de séparateur selon la revendication 8, dans laquelle le ou les supports (43, 60, 70) sont disposés pour maintenir le tube (4) en une pluralité de régions le long de sa longueur, et de préférence dans laquelle le ou les supports (43, 60, 70) comprennent une pince disposée pour venir en prise avec le tube (4) en une pluralité de régions le long de sa longueur.
  10. Unité de séparateur selon la revendication 8 ou 9, dans laquelle le support (43, 60, 70) est magnétiquement attaché à l'unité à aimants (9).
  11. Unité de séparateur selon la revendication 8, 9 ou 10, dans laquelle le support (43, 60, 70) comporte une région non magnétique de retenue permettant de venir en prise avec le tube (4).
  12. Unité de séparateur selon l'une quelconque des revendications 8 à 11, dans laquelle le support (43, 60, 70) est séparable de l'unité à aimants (9) et de préférence, dans laquelle le support (43, 60, 70) est doté d'une poignée (74) qui donne un bras de levier permettant de retirer le support (43, 60, 70) de l'unité à aimants (9).
  13. Unité de séparateur selon l'une quelconque des revendications précédentes, comprenant en outre un réservoir (2) en amont de l'unité séparatrice afin d'y introduire un mélange de fluides.
  14. Unité de séparateur selon la revendication 1, dans laquelle le mélange de fluides est du sang, du sérum ou de l'urine.
  15. Système (10) destiné à la séparation sélective de particules magnétisables à partir d'un mélange de fluides, le système comprenant :
    un séparateur à aimant primaire (3, 91) comprenant un aimant primaire permettant d'attirer les particules magnétisables ; et
    un séparateur à aimant secondaire (92) comprenant une unité de séparateur magnétique selon la revendication 1, dans lequel le tube (4) est disposé pour l'écoulement de fluide en aval du séparateur à aimant primaire (3, 91).
  16. Procédé d'élimination d'une cible d'un fluide, le procédé comprenant :
    l'utilisation d'un fluide dont on suspecte qu'il contient la cible ;
    la mise en contact du fluide avec au moins une particule magnétisable qui se lie à la cible ;
    l'attraction de la particule magnétisable à un aimant (9) qui a la forme d'un mandrin autour duquel est enroulé un tube (4) d'écoulement de fluide, de manière à permettre à l'aimant (9) d'attirer la particule magnétisable dans le fluide sur une longue trajectoire d'écoulement, l'aimant (9) comprenant une pluralité d'aimants (52) orientés parallèlement à l'axe du mandrin et espacés angulairement autour du mandrin ;
    la séparation de la particule magnétisable provenant du fluide, la cible étant éliminée du fluide.
  17. Procédé selon la revendication 16, dans lequel le fluide est du sang, du sérum ou de l'urine.
EP06832055.5A 2005-12-02 2006-12-02 Separateur magnetique et procede Active EP1954396B1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US74197505P 2005-12-02 2005-12-02
GB0524684A GB0524684D0 (en) 2005-12-02 2005-12-02 Magnetic separator
PCT/IB2006/054564 WO2007063529A2 (fr) 2005-12-02 2006-12-02 Separateur magnetique

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EP1954396A2 EP1954396A2 (fr) 2008-08-13
EP1954396B1 true EP1954396B1 (fr) 2018-06-06

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Publication number Priority date Publication date Assignee Title
US20190001343A1 (en) * 2015-12-31 2019-01-03 Siemens Healthcare Diagnostics Inc. Apparatus and methods for processing magnetic particles

Family Cites Families (4)

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Publication number Priority date Publication date Assignee Title
DE3522365A1 (de) * 1985-06-22 1987-01-02 Bayer Ag Trenngeraet fuer magnetische partikel aus fluessiger phase
JP3607320B2 (ja) * 1994-09-02 2005-01-05 株式会社日立製作所 微粒子を用いた分析における固相の回収方法及び装置
FR2748569B1 (fr) * 1996-05-07 1998-08-07 Biocom Sa Procede et installation de separation de particules magnetiques dans un fluide pour l'analyse biologique, et application dudit procede
EP1331035A1 (fr) * 2002-01-23 2003-07-30 F. Hoffmann-La Roche AG Appareil pour retenir des particules magnétiques dans une cellule traversée d'un fluide

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Also Published As

Publication number Publication date
WO2007063529A2 (fr) 2007-06-07
JP2009528914A (ja) 2009-08-13
WO2007063529A3 (fr) 2007-08-16
EP1954396A2 (fr) 2008-08-13

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