WO2014082752A1

WO2014082752A1 - Device for separating magnetic or magnetizable microparticles from a suspension by means of high gradient magnetic separation

Info

Publication number: WO2014082752A1
Application number: PCT/EP2013/003618
Authority: WO
Inventors: Percy Kampeis; Daniel FEIND; Michael LIEBLANG
Original assignee: Hochschule Trier
Priority date: 2012-11-30
Filing date: 2013-11-30
Publication date: 2014-06-05
Also published as: EP2925453A1; EP2925453B1; DE102012023382A1

Abstract

The invention relates to a device for separating magnetic or magnetizable microparticles from a suspension (5) by means of high gradient magnetic separation. For this purpose, the device has a separator (12), the housing (13) of which encloses a separation chamber (1) through which a suspension (5) can be made to flow in a predetermined flow direction (5'). A magnetic or magnetizable separating matrix (2), comprising a plurality of surface elements (3) with a clear lateral distance between one another which thus form flow spaces (6) for the suspension (5), is arranged in the separation chamber (1). The suspension (5) is guided into and out of the flow spaces (6) via an inlet (26) and an outlet (30). In order to detect the loading state of the separation matrix (2) with microparticles in the separation chamber (1) and, on the basis thereof, to be able to predict the probability of detachment of microparticles from the separation matrix (2), the invention provides for usage of an optical measuring device (7) and a lighting system (9), wherein the optical view axes (8) of the optical measuring device (7) run in the flow spaces (6) in order to determine the size of the clear spacing between the surface elements (3), and the lighting system (9) has at least one light source, the light (10) of which can be emitted into the flow spaces (6).

Description

"Device for separating magnetic or magnetizable microparticles from a suspension by means of high-gradient magnetic separation."

Description:

Technical area:

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.

State of the art:

Such devices are associated with the selective separation of

suspended or dissolved substances (target substances) in a suspension or solution. Preferred field of application is the processing of biotechnological

Products in which the target substance is to be selectively separated selectively from a product stream obtained in the course of a biotechnological production process with high proportions of solid constituents, nutrient salts, buffer substances and / or a large number of by-products.

The application of the high-gradient magnetic separation in combination with magnetic or magnetizable microparticles for selective separation is already known from DE 10 2005 034 327 A1, where the addition of magnetic or magnetizable microparticles (microsorbents, magnetic beads) to a solution / suspension is described. The microparticles, due to a particular packaging such. functionalization of the surface has a particularly high affinity for the target substance, so that when the microparticles are added to the suspension / solution, the target substance is bound to the surface of the microparticles via affinity adsorption (selective binding).

The separation of the microparticles loaded with the target substance occurs in the course of

Flow through a magnetic field magnetized or magnetic deposition matrix within a separator. By adhering and agglomerating the magnetic or magnetized microparticles to the deposition matrix, they are retained so that the residual suspension can be removed without microparticles. The desorption of the target substance from the microparticle surface takes place in a desorption buffer, with which the microparticles are rinsed out of the separator and simultaneously resuspended. The resulting

CONFIRMATION COPY After completion of the desorption, 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. In this case, agglomeration forms accumulation areas which increasingly constrict the freely permeable volume of the deposition matrix. As a result, 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. As a result, microparticles detach from the deposition matrix and are lost to the residual suspension, resulting in loss

Microparticles and target substance is connected.

In this connection, it is already known to determine the concentration of the microparticles in the outlet of the separator in order to monitor the effectiveness of the separation process. However, this can prevent the detachment of microparticles during the

Separation process can not be prevented, since with the detection of microparticles in the expiration of the detachment process has already begun. 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. On a transparent chamber wall, a magnetic or magnetizable grid is attached, which generates an internal gradient by distortion of the magnetic field. Since the too

are magnetically labeled, they accumulate along the grid lines, whereby it is achieved by suitable dimensioning of the grid, that the particles in the surface of the grid in only one layer, so not superimposed, arrange. This makes it possible to individually detect the individually juxtaposed particles using a laser scanning the grid lines and thus to analyze both quantitatively and qualitatively.

Presentation of the invention:

Against this background, 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.

This object is achieved by a device having the features of patent claim 1.

Advantageous embodiments will be apparent from the dependent claims.

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

Micropartikelablösung 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. By minimizing the number of microparticles in the residual suspension in this manner, an unusually high degree of microparticle precipitation from the suspension is achieved so that both the target substances and the microparticles are almost completely recovered from the suspension. An inventive device is therefore characterized by an exceptionally high efficiency.

The deposition matrix is according to a preferred embodiment of

Invention formed by surface elements in the deposition chamber. These are

Preferably arranged plane-parallel to each other in the deposition chamber, which allows a high packing density of the surface elements. In this context, 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. In a further development of the invention, 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.

According to a preferred embodiment of the invention, the surface elements have a multiplicity of openings in their plane of extent. As a result, the effect is used that the magnetic field strength along the edges forming the openings is particularly high, which further improves the separation effect. In order to produce the highest possible density of effective edges on the surface elements, 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 optical monitoring of the flow spaces within the deposition chamber is advantageously carried out from outside the separator, while the selective deposition takes place in a closed volume within the deposition chamber. Thus, 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 Abscheidkammer, 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

enable. The achieved mechanical decoupling of optical measuring device and separator allows on the one hand, that the separator regardless of the optical

Measuring device taken from the device and can be used again, which facilitates the handling and operation of a device according to the invention quite significantly. On the other hand, 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.

In a preferred embodiment of the invention, the optical sight axes of the optical measuring device are substantially parallel to the surface elements and transversely to

Flow direction of the suspension. 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. However, 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

To get deposition chamber.

It proves to be particularly advantageous, the illumination system of the optical

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.

Brief Description of the Drawings: The invention will now be described with reference to a drawing illustrated in the drawings

Embodiment explained in more detail, wherein further features and advantages of the invention will become apparent.

It shows

1 is a schematic oblique view of a separator according to the invention,

2 shows a longitudinal section through a separator according to the invention

along the line II - II shown in FIG. 3,

3 shows a longitudinal section through the separator shown in FIG

along the line III - III shown in FIG. 4,

4 shows a cross section through the separator shown in FIG

along the line IV - IV shown in FIG. 3,

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

Separators and,

8 shows a longitudinal section through an alternative embodiment of an inlet or outlet of a separator according to the invention.

Ways to carry out the invention and commercial usability:

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

Magnetic field perpendicular to the surface of the surface elements 3, which is symbolized especially in Figures 2 and 4 with the arrows 23.

The separation matrix 2 is traversed from top to bottom by a suspension whose flow direction 5 is represented by arrows. The free space between the

Surface elements 3 each form a gap-shaped flow space. 6

The contour and thus the available flow cross-section of a

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

Arranged measuring device 7 opposite and emits light 10 parallel to the

Sight axes 8 in the flow space 6, so also parallel to the surface elements 3 and perpendicular to the flow direction 5. 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

Deposition matrix 2. The forces of attraction acting on the magnetic or magnetized microparticles as a result lead to accumulations 11 of microparticles in the

Edge region of the openings 4 in the surface elements 3, where the magnetic field strength is greatest. The accumulations 11 grow with increasing loading of the deposition matrix 2 not only in the plane of the surface elements 3, but also along the magnetic field lines perpendicular to it. Above all, the spatial growth perpendicular to the surface of the surface elements 3 leads to a narrowing of the flow cross-section of the flow spaces 6, with the disadvantages described above, as soon as a certain extent is reached. Of the

The basic idea of the invention is now to monitor the change in the flow cross-section caused by three-dimensional agglomeration with the aid of the optical measuring device 7 and, even before the detachment of microparticles is to be feared, the operator of a device according to the invention via the current loading of the deposition matrix 2 and possibly required Backwashing or change the deposition matrix 2 to inform. 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

Recess 17, which after joining the side walls 14 and 15, an upwardly and downwardly open, channel-shaped deposition chamber 1 result (see especially Fig. 4).

In an analogous manner are formed in the inner sides 16 of the side walls 14 and 15 recesses 18 and 19 which extend from the end faces 20 of the housing 13 to the deposition chamber 1 and in this way aligned sight channels 21 and 22 form. In each of the view channels 21 and 22 is a respective the deposition chamber 1 gas and

inserted liquid-tight closing 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. For in-situ steam sterilization, 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.

Furthermore, 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. At the opposite end of the separation chamber 1, 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

Surface elements 3 are provided parallel adjacent flow spaces 6 for the suspension 5.

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, but may also be formed circular or slot-shaped. Alternatively, the openings may also result from a grid structure of the surface elements 3. The web width between the openings 4 is

preferably at most 2 mm.

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. In this case, 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

From Figure 6, the arrangement of the optical measuring device 7 and the

Illumination system 9 within the device according to the invention can be seen. 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. For this purpose, 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.

On the opposite side of the separator 12 can be seen the illumination system 9, which is arranged at the level of the optical viewing axes 8 and light 10 in the direction of

Measuring device 7 through the viewing channels 22 and 21, the flow chambers 6 and the optical window 24 emits. The light source can consist of several discrete LEDs or a luminescent film. In order to emit as diffused light 10 as possible into the flow spaces, it is possible to arrange 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.

In order to monitor the state of the deposition matrix 2, images of the flow spaces 6 in the direction of the illumination system 9, that is, in the backlight, are taken with the camera in the optical sight axes 8 of the optical measuring device 7 continuously or at predetermined time intervals. The calculated light-dark values are in one

Data processing unit evaluated by means of an image processing software, which determines the clear distance between the attachment regions 11 transversely to the flow direction of the suspension 5 and compared with a critical minimum distance. When falling below the critical minimum distance, a warning message is given to the operator of the device and / or throttled or stopped the supply of the separator 12 with suspension 5. In this way, detachment of the microparticles from the deposition matrix 2 is prevented in good time. 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. In each case 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. Furthermore, 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. In order to be able to seal the deposition chamber 1 tightly, 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.

In the deposition chamber 1, one again sees a magnetizable deposition matrix 2, as already described essentially already in FIGS. 1 to 6. The

Surface elements 3 of the deposition matrix 2 thus extend in plane-parallel congruent position flat between the two sides 36 with parallel alignment with respect to the flow direction 5 and the optical sight axes 8. From the longitudinal sides of the surface elements 3 are in the plane of the surface elements 3 and in extension of the transverse sides of the Surface elements 3 pin-shaped pin 40 forth. The thus arranged in rows pins 40 each bind a rod-shaped perpendicular to the plane of the

Surface element 3 extending retaining element 41, so that surface elements 3 and

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

Positive locking in the grooves 38 are attached.

Another - not graphically illustrated - embodiment of a separator according to the invention provides for the monolithic formation of a plate-shaped body, in the formation of a deposition chamber, a continuous circumferentially closed channel is milled, which is crossed in the transverse direction by a likewise continuous circumferentially closed viewing channel. 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.

Also not shown in the drawing is an embodiment of the invention in which the housing of the separator is formed as a disposable part, for example in the form of a

Injection molding made of plastic. This embodiment has the advantage that a sterilization of the separator can be omitted before each use.

Finally, 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

Area elements 3. Since the suspension should be guided through the deposition chamber 1 with as little turbulence as possible in order to prevent unwanted detachment of microparticles, the idea of the invention embodied in FIG. 8 is to maximize the suspension flow

turbulence free of the narrow flow cross-section of the supply line with the diameter Di on the flow cross-section with the larger cross-sectional dimension D ₂ of Expanding deposition chamber 1. Since, for this purpose, the suspension flow should be as free as possible from turbulence as soon as it enters the separation chamber 1, 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. In order to prevent detachment of vortices on the inner circumference of the widening longitudinal section 42, the angle α of the widening 28 'is at most 15 degrees and most preferably in a range between 8 degrees and 12 degrees.

Preferably, this geometry of the inlet 26 'with the reverse flow direction 5 is also applied to the drain 30.

Claims

Device for separating magnetic or magnetizable microparticles from a suspension (5) by means of high-gradient magnetic separation,

- With a separator (12) whose housing (13) encloses a separation chamber (1) through which the suspension (5) can flow in a predetermined flow direction (5 '),

with a magnetic or magnetizable deposition matrix (2) which comprises a plurality of surface elements (3) which are arranged in the clear lateral distance and which are arranged in the deposition chamber (1) to form flow spaces (6) for the suspension (5),

- With an inlet (26) and a drain (30) through which the suspension (5) is guided into and out of the flow spaces (6), and

- With a device for generating a magnetic field (23), in which the separator (12) is arranged, characterized by an optical measuring device (7) and an illumination system (9), wherein for determining the size of the clear distance between the surface elements ( 3) extend the optical sight axes (8) of the optical measuring device (7) in the flow spaces (6) and the

Lighting system (9) has at least one light source, the light (10) in the flow spaces (6) is emitted.

Apparatus according to claim 1, characterized in that the surface elements (3) are arranged plane-parallel to each other and parallel to the flow direction (5) and / or the optical viewing axes (8).

Apparatus according to claim 2, characterized in that the lateral spacing of the surface elements (3) is at most 5 mm, preferably between 0.5 mm and 2 mm.

Apparatus according to claim 1 or 3, characterized in that the magnetic field (23) is directed perpendicular to the plane of the surface elements (3).

Device according to one of claims 1 to 4, characterized in that the surface elements (3) have a plurality of openings (4), preferably each having a rectangular outline.

6. Device according to one of claims 1 to 5, characterized in that the surface elements (3) are formed by a metal sheet or a metal grid.

7. Device according to one of claims 1 to 6, characterized in that the

Surface elements (3) via holding elements (41) connected to each other and fixed in their relative position to the deposition chamber (1).

8. The device according to claim 7, characterized in that surface elements (3) and holding elements (41) form a stable unit, which as a whole the

Separating chamber (1) can be removed.

9. Device according to one of claims 1 to 8, characterized in that the

optical sight axes (8) of the optical measuring device (7) perpendicular or parallel to the flow direction (5).

10. Device according to one of claims 1 to 9, characterized in that the

Housing (13) has at least a first optical window (24) and the optical measuring device (7) outside the measuring chamber (1) is arranged and the optical viewing axes (8) through the optical window (24) in the deposition chamber (1) ,

11. Device according to one of claims 1 to 10, characterized in that the housing (3) has at least a second optical window (24) and the

Lighting system (9) outside the deposition chamber (1) is arranged and the light (10) through the second optical window (24) in the deposition chamber (1) is emitted.

12. The device according to claim 10 or 11, characterized in that the first

and / or second optical window (24) are designed for in-situ steam sterilization temperature resistant.

13. Device according to one of claims 1 to 12, characterized in that the light source of the illumination system (9) for generating back light of the optical measuring device (7) is arranged opposite one another.

14. Device according to one of claims 1 to 13, characterized in that in the flow spaces (6) emitted light (10) is diffused light.

15. Device according to one of claims 1 to 14, characterized in that the housing (13) of the separator (12) consists of two side parts, whose mutually facing side (14, 15) form the deposition chamber (1).

16. Device according to one of claims 1 to 14, characterized in that the housing of the separator is monolithic, with a through opening for forming a deposition chamber.

17. Device according to one of the claims 1 to 16, characterized in that the inlet (26) in the flow direction (5) on the flow cross section of the deposition chamber (1) widening expansion (28 ') has, preferably has a steady course.

18. The apparatus according to claim 17, characterized in that at the widening (28 ') forming longitudinal portion (42) is followed by a cylindrical longitudinal portion (43) with the cross-sectional dimensions of the deposition chamber (1).

19. The apparatus according to claim 18, characterized in that the length ratio of the cylindrical longitudinal portion (43) to be weitendem longitudinal portion (42) is at least 0.15, preferably in a range between 0.25 and 0.3.

20. Device according to one of claims 17 to 19, characterized in that the angle α of the expansion (28 ') is a maximum of 15 degrees, preferably between 8 degrees and 12 degrees.