TW201420192A - Magnetic separation unit and magnetic separation device - Google Patents

Abstract

A magnetic separation unit includes a plurality of closely adjacent magnetic strips, such that a plurality of continuous first fluid channels is defined between the magnetic strips, wherein the first fluid channels are continuous and parallel to each other.

Description

Magnetic separation unit and magnetic separation device

The present invention relates to a biochemical separation device, and more particularly to a magnetic separation unit and a magnetic separation device suitable for separating magnetic substances in a biochemical sample.

In the field of biochemistry, many techniques have been employed to efficiently separate one or a class of cells in a composite cell suspension. The ability to isolate certain cells representing a particular disease pattern from clinical blood samples is particularly useful for the diagnosis of disease.

Current techniques have succeeded in employing magnetic devices to repel or attract labeled cells by which to select or separate cells labeled with micron-sized (> 1 micron) magnetic or magnetized particles in the mixture. For isolation of cells that provide valuable information, the cells to be detected can be magnetized and selected from a mixture of complex liquids (referred to as positive selection, or positive selection). Alternatively, non-detecting cells that cause a particular program change may be magnetized to be separated by a magnetic device (referred to as negative selection, or negative selection).

However, the separation efficiency of magnetic cells depends on the magnetic force that the magnetic label is subjected to in the separation magnetic field, and therefore it is necessary to increase the magnetic field and the magnetic field gradient in order to increase the separation rate. However, whether it is a permanent magnet or an electromagnet, usually the magnetic field and magnetic field gradients drop rapidly with distance as they leave the magnetic material. Therefore, there is a need for a magnetic separation unit and a magnetic separation device thereof which are preferably used to improve the separation efficiency of the magnetic substance.

In view of the above, the present invention provides a magnetic separation unit comprising a plurality of fluid flow paths formed by a plurality of magnetic strips disposed in close proximity, thereby allowing a magnetic field to extend a high magnetic field of an external magnetic field. The gradient is in the fluid flow path therebetween and thereby improves the magnetic separation efficiency. Further, the present invention also provides a magnetic separation device to which the above magnetic separation unit is applied.

According to an embodiment, the present invention provides a magnetic separation unit comprising:

A plurality of magnetic strips are disposed in close proximity to define a plurality of first fluid flow paths that are continuous and parallel to each other between the magnetic strips.

According to another embodiment, the present invention provides a magnetic separation device comprising:

An external magnetic field unit; a container element disposed in the external magnetic field unit, having a central axis direction, a fluid inlet and a fluid outlet; and a magnetic separation unit as described above disposed within the container element, wherein the a magnetic strip extending from the central axis of the container element or extending along the central axis of the container element and twisted, wherein the container element comprises a non-magnetic material and the external magnetic field The unit provides an external magnetic field at the container element and the magnetic separation unit.

In order to make the above objects and features of the present invention more comprehensible, the following detailed description of the preferred embodiments and the accompanying drawings are as follows:

Referring to FIG. 1, a perspective view of a magnetic separation unit 100 in accordance with an embodiment of the present invention is shown.

As shown in FIG. 1, the magnetic separation unit 100 includes a plurality of magnetic strips 102, and the magnetic strips 102 are disposed and arranged in close proximity, and are defined between the magnetic strips 102. Separating a plurality of fluid flow channels 104 of the magnetic biochemical material. In one embodiment, the magnetic strips 102 comprise magnetic materials such as pure iron, magnetic stainless steel or magnetic soft magnetic materials, and magnetic soft magnetic materials such as iron, tantalum steel and nickel iron. , cobalt iron, stainless steel, soft ferrite or a combination thereof. As shown in FIG. 1, the magnetic strips 102 extend in the longitudinal direction thereof, and the fluid flow path 104 is a linear flow path extending in the longitudinal direction of the magnetic strips 102. The fluid flow paths 104 are continuous flow paths that are parallel to each other.

The magnetic strip 102 can be formed by first forming a powder of a magnetic material into a strip-shaped embryo body, for example, by molding or die-casting, followed by arranging and sintering the strip-shaped embryos. The body is formed into a magnetic separation unit 100 as shown in Fig. 1. Alternatively, the magnetic strips 102 may directly adopt a plurality of strip-shaped magnetic materials, and arrange and arrange the strip-like structures in close proximity, or may be strip-shaped by means of ultrasonic welding. The structures are fixed together to form a magnetic separation unit 100 as shown in Fig. 1.

Referring to Figure 2, there is shown a top view of a magnetic separation unit 100 in accordance with an embodiment. As shown in FIG. 2, the magnetic strip 102 can have a generally circular top view depending on the design requirements of the magnetic separation device to which it is applied. However, although the magnetic strips 102 used in the magnetic separation unit 100 are generally circular, as in the case of the strip, in other embodiments, The magnetic strip 102 used in the magnetic separation unit 100 can use a strip having other shapes such as a polygonal top view, instead of defining the magnetic property used by the magnetic separation unit 100 in the case shown in FIG. The shape of the strip 102.

Referring to Figures 3a-3c, there are shown perspective and side views of a magnetic separation unit 200 in accordance with various embodiments of the present invention. Based on the simplification, only the differences between the two embodiments will be described herein, and the same reference numerals will be used to refer to the same elements.

As shown in the perspective view of FIG. 3a, after the magnetic strips 102 in the magnetic separation unit 200 are disposed in the immediate vicinity, they are aligned from top to bottom in an angle such as counterclockwise, thereby forming a magnetic Separation unit 200. Therefore, since the magnetic strips 102 are twisted, the fluid flow path 104 between the magnetic strips 102 is nonlinearly tapered downward along the longitudinal direction of the magnetic strips 102. Flow path. Here, the fluid flow paths 104 are still continuous flow paths that are substantially parallel to each other.

Further, as shown in Fig. 3b, a cross-sectional view of a magnetic separation unit 200 in accordance with still another embodiment of the present invention is shown. In the present embodiment, after the magnetic strips 102 in the magnetic separation unit 200 are disposed in the immediate vicinity, they are aligned from top to bottom in an angle such as counterclockwise, thereby forming the magnetic separation unit 200. . Here, the magnetic strips 102 shown in this embodiment are twisted and twisted more than the magnetic strips 102 in FIG. 3a, and the fluid flow path 104 between the magnetic strips 102 is A spiral-like nonlinear flow path that is gradually twisted downward along the longitudinal direction of the magnetic strip 102. Here, the fluid flow paths 104 are still Continuous flow paths that are generally parallel to each other.

Further, as shown in Fig. 3c, a perspective view of a magnetic separation unit 200 according to still another embodiment of the present invention is shown, thereby illustrating the case where a plurality of magnetic strips 102 are twisted after being aligned. For the sake of simplicity, only the implementation of the three magnetic strips 102 aligned and twisted within the magnetic separation unit 200 is illustrated in Figure 3c. In the present embodiment, after the three magnetic strips 102 are disposed in close proximity, they are aligned from top to bottom in an angle such as counterclockwise, thereby forming the magnetic separation unit 200. Here, the magnetic strips 102 shown in this embodiment are twisted and twisted more than the magnetic strips 102 in FIG. 3a, and one of the fluid strips 104 between the magnetic strips 102. It is a non-linear flow path such as a spiral which is gradually twisted downward along the longitudinal direction of the magnetic strips 102.

Figure 4 is a top view showing an enlarged view of a portion 110 as in Figure 2 in an embodiment. Here, the plurality of magnetic strips 102 in FIG. 4 may have a substantially circular top view, and are disposed and aligned in a substantially triangular manner, so that between the magnetic strips 102 A fluid channel 104 is defined which is defined by a portion of the plurality of curved surfaces of the magnetic strips 102, respectively. In an applied magnetic field (not shown), the magnetic strips 102 can direct the magnetic lines of force of the applied magnetic field to the surface of one of the curved surfaces of the magnetic strips 102 exposed by the fluid passages 104. Thereby, the magnetic field gradient at the fluid passage 104 is increased, and thus the magnetic force received by the magnetic substance (not shown) in the sample fluid (not shown) flowing through the fluid passage 104 is increased, thereby lifting the magnetic substance Separation efficiency.

Referring to Figure 5, an enlarged view of a portion 110 as in Figure 2 is shown in another embodiment. Here, the plurality of magnetic strips 102 in FIG. 5 may have a substantially circular top view and are disposed and arranged in close proximity generally in a quadrilateral manner, and thus are defined between the magnetic strips 102. One of the fluid passages 104. The fluid flow path 104 shown in Fig. 5 also has magnetic material (not shown) in the sample fluid (not shown) which is enhanced by the fluid flow path 104 as shown in Fig. 4 to flow through the fluid channel 104. The magnetic force accepted and the same effect of improving the separation efficiency of the magnetic substance.

In other embodiments, the magnetic strips 102 shown in FIGS. 4-5 may have a general polygonal shape such as a quadrilateral and are arranged and arranged substantially in a triangular or quadrilateral manner, respectively. A fluid channel 104 is defined between the magnetic strips 102 and defined by one of the plurality of planes of the magnetic strips 102, respectively.

Referring to Figure 6, a magnetic separation device 600 in accordance with an embodiment of the present invention is shown. Here, as shown in FIG. 6, the magnetic separation device 600 includes an external magnetic field unit 400, a container member 300, and a magnetic separation unit (for example, the aforementioned magnetic separation unit 100 or 200) disposed in the container member 300. . As shown, the container member 300 has an opening 302 for use as a sample fluid inlet and an opening 304 for use as a sample fluid outlet. Here, the container element 300 comprises polymethyl methacrylate (PMMA), acrylic, polypropylene (PP), polyethylene (PE), polyvinyl chloride (PVC), Teflon, plastic, electricity. Non-magnetic material of wood, non-magnetic metal or ceramic. The opening 302 and the opening 304 of the container member 300 The size is less than or equal to the overall size of one of the magnetic separation units 100/200.

As shown in FIG. 6, the container member 300 is illustrated as a cylindrical hollow housing having a central axis direction 500. In the present embodiment, the central axis direction 500 is generally aligned with the opening 302 and the opening 304 of the container member 300. Therefore, when the magnetic separation unit 100 as shown in FIG. 1 is employed in the container member 300, the plurality of magnetic strips 102 disposed in the magnetic separation unit 100 within the container member 300 and the plurality of fluid flows therebetween The track 104 extends along the central axis direction 500 of the container element 300. In other embodiments, the opening 302 and the opening 304 of the container member 300 may have other embodiments that are not aligned with the central axis.

In another embodiment, when the magnetic separation unit 200 as shown in FIG. 3 is used in the container member 300, the plurality of magnetic strips 102 disposed in the magnetic separation unit 200 disposed within the container member 300 are interposed therebetween. The plurality of fluid flow passages 104 extend and twist in a central axis direction 500 of the container member 300.

In other embodiments, the container element 300 may vary according to the shape of the magnetic separation unit 200 used, and thus may be a hollow housing having other shapes such as a polygon, instead of the case shown in FIG. .

As shown in Fig. 6, the external magnetic field unit 400 in the magnetic separation device 600 provides an external magnetic field 402 that penetrates the container member 300 and the magnetic separation unit 100/200 to provide a magnetic separation effect. The external magnetic field unit 400 can be produced by a permanent magnet or by an electromagnet. In one embodiment, the external magnetic field unit 400 is formed of a permanent magnet, and the material thereof is, for example, neodymium iron boron (NdFeB), samarium cobalt (SmCo), neodymium iron nitrogen (SnFeN), aluminum nickel cobalt (AlNiCo), ferrite. (ferrite) or a combination thereof. In other embodiments, the external magnetic field unit 400 is formed by an electromagnet, and external magnetic field 402 is generated by an electric current flowing through the electromagnet.

Figure 7 is a cross-sectional view showing a cross-sectional view of the magnetic element separation unit 600 and the magnetic separation unit of the magnetic separation device 600 as shown in Figure 6. As shown in Fig. 7, when the magnetic separation units 100 and 200 as shown in Figs. 1-2 are used in the container member 300, the outermost plurality of magnetic separation units 100/200 disposed in the container member 300 are provided. A fluid flow path 106 is defined between the magnetic strip 102 and the container element 300, respectively. In one embodiment, the fluid flow path 106 is formed by a portion of the surface of the plurality of magnetic strips 102 and a portion of the inner surface of the container member 300. To this end, the surface of the magnetic strip 102 exposed by the fluid flow path 106 can guide the magnetic field lines of the applied magnetic field to a portion of the curved surfaces of the magnetic strips 102 exposed by the fluid passage 106. The magnetic field gradient at the fluid passage 106 is increased, thereby increasing the magnetic force received by the magnetic material (not shown) in the sample fluid (not shown) flowing through the fluid passage 106, thereby enhancing the separation of the magnetic material thereby effectiveness.

According to an embodiment of the present invention, a magnetic separation device 600 as shown in Figures 6-7 is used for separating a magnetic substance in a biochemical sample.

First, a magnetic separation device, such as the magnetic separation device 600 shown in Fig. 6, is provided. Next, a biochemical sample solution including one of magnetic substances such as a magnetic biochemical substance or a biochemical substance marked with a magnetic substance is provided. Next, the biochemical sample solution is passed from the opening 302 of the container member 300 through the container member 300 in the magnetic separation device 600. The fluid passages 104 and 106 exit the magnetic separation device 600 from the opening 304 of the container member 300, thereby attracting or repeling the magnetic material therein and attaching it to the wall of the adjacent fluid passages 104 and 106, for example, adjacent to the fluid passage. On the surface of one of the magnetic strips 102 of 104 and 106. Next, the external magnetic field 402 provided by the magnetic separation device 600 is removed or closed. In this step, the external magnetic field 402 provided by the external magnetic field unit 400 is removed, for example, by removing the container member 300 and the magnetic separation unit 100/200. Alternatively, the current of the electromagnet included in the external magnetic field unit 400 is turned off to turn off the external magnetic field provided by the external magnetic field unit 400. Finally, a buffer is provided and the buffer flows from the opening 302 of the container member 300 through the fluid passages 104 and 106 in the container member 300 in the magnetic separation device 600 and exits the magnetic separation device from the opening 304 of the container member 300. 600 to elute the magnetic material remaining on the magnetic strips 102 adjacent to the fluid passages 104 and 106.

In one embodiment, biochemical samples that can be passed through the magnetic separation device 600 are, for example, blood samples, blood concentrated samples, tissue samples, tissue fluid samples, cell samples, cell culture fluid samples, microbial samples, protein samples, amino acids. A sample, a nucleotide sample, or the like, and the magnetic substance included therein is, for example, a magnetic biochemical substance such as a cell, a microorganism, a protein, an amino acid, or a nucleotide, or a biochemical substance labeled with a magnetic substance. The magnetic substance that may be used is, for example, a particle containing a metal such as iron, cobalt, nickel or an oxide thereof, and a buffer which may be used, for example, a Tris-buffer saline (TBS) buffer or a phosphate. Phosphate buffer saline (PBS), normal saline, isotonic solution with tissue fluid, and other molecular activities that maintain protein/amino acid/nucleotide Solution.

Example: Example (1)

Using the magnetic separation device 600 as shown in Fig. 6, a magnetic separation unit 200 as shown in Fig. 3 is used in the container member 300 of the acrylic material. In the present embodiment, the magnetic separation unit 200 includes a magnetic strip 102 of SUS430 stainless steel material comprising 125 strips arranged and twisted, and the magnetic strip 120 has a diameter of 0.5 mm. The size of the fluid flow path 104 between the magnetic strips 102 is about 150 to 190 microns, and the size of the fluid flow path 106 between the magnetic strips 102 and the container element 300 is about 60. ~100 microns. A biochemical sample is then passed through fluid channels 104 and 106 in container element 300, wherein the biochemical sample is an aqueous solution containing Fe ₃ O ₄ having a Fe ₃ O ₄ particle size of 10 nm to 15 nm. The biochemical sample is collected by a separate magnetic field to collect the washing liquid. After removing or closing the external magnetic field, the fluid channel is eluted with a buffer to collect an elution. The amount of Fe contained in the rinse liquid and the eluent was measured separately, and the measurement results are shown in Table 1, and the separation rate was 90.7%.

Example (2)

Using the magnetic separation device 600 as shown in Fig. 6, a magnetic separation unit 200 as shown in Fig. 3 is used in the container member 300 of the acrylic material. In the present embodiment, the magnetic separation unit 200 includes magnetic strips 102 of SUS430 stainless steel material including 154 sheets, and the magnetic strips 120 have a diameter of 0.5 mm. The size of the fluid flow path 104 between the magnetic strips 102 is about 120 microns, and the size of the fluid flow path 106 between the magnetic strips 102 and the container element 300 is about 60-100. Micron. A biochemical sample is then passed through fluid channels 104 and 106 in container element 300, wherein the biochemical sample is an aqueous solution containing Fe ₃ O ₄ having a Fe ₃ O ₄ particle size of 30 nm. The biochemical sample is collected by a separate magnetic field to collect the washing liquid. After removing or closing the external magnetic field, the fluid channel is eluted with a buffer to collect an elution. The amount of Fe contained in the rinse liquid and the eluent was measured separately, and the measurement results are shown in Table 1, and the separation rate was 98.4%.

Although the present invention has been disclosed in the above embodiments, it is not intended to limit the present invention, and the present invention can be modified and retouched without departing from the spirit and scope of the present invention. The scope of protection is subject to the definition of the scope of the patent application attached.

100,200‧‧‧magnetic separation unit

102‧‧‧Magnetic strips

104, 106‧‧‧ fluid flow channels

110‧‧‧Part of the magnetic separation unit

300‧‧‧ container components

302‧‧‧ openings

304‧‧‧ openings

400‧‧‧External magnetic field unit

402‧‧‧External magnetic field

500‧‧‧Center axis direction

600‧‧‧Magnetic separation device

1 is a perspective view showing a magnetic separation unit according to an embodiment of the present invention; and FIG. 2 is a top view showing a top view of a magnetic separation unit according to an embodiment of the present invention; Figure 3 is a perspective view showing a magnetic separation unit according to another embodiment of the present invention; Figure 3b is a side view showing a magnetic separation unit according to still another embodiment of the present invention; and Figure 3c is a perspective view, A magnetic separation unit according to another embodiment of the present invention is shown; FIGS. 4-5 are a series of schematic views showing an enlarged view of a portion as shown in FIG. 2; and FIG. 6 is a schematic view showing the basis A magnetic separating device according to an embodiment of the invention; and Fig. 7 is a cross-sectional view showing a cross-sectional view of the magnetic separating unit as shown in Fig. 6.

100‧‧‧Magnetic separation unit

102‧‧‧Magnetic strips

104‧‧‧ fluid flow path

Claims (10)

A magnetic separation unit comprising: a plurality of magnetic strips disposed in close proximity to define a plurality of first fluid flow paths that are continuous and parallel to each other between the magnetic strips. A magnetic separation device comprising: an external magnetic field unit; a container element disposed in the external magnetic field unit, having a central axis direction, a fluid inlet and a fluid outlet; and the magnetic body according to claim 1 a separating unit disposed in the container member, wherein the magnetic strips and the first fluid flow channels extend in the central axis direction of the container member or extend along the central axis direction of the container member and are twisted Wherein the container element comprises a non-magnetic material and the external magnetic field unit provides an external magnetic field at the container element and the magnetic separation unit. The magnetic separation unit of claim 1, wherein the magnetic strip comprises pure iron, magnetic stainless steel or a magnetic soft magnetic or soft ferrite having magnetic permeability. The magnetic separation unit of claim 1, wherein the first fluid flow path is a linear flow path or a spiral flow path. The magnetic separation unit of claim 1, or the magnetic separation device of item 2, wherein the magnetic strips are circular or polygonal as viewed from above. The magnetic separation unit of claim 1, or the magnetic separation device of item 2, wherein the first fluid flow paths are composed of a plurality of songs Surrounded by faces or planes. The magnetic separation device of claim 2, wherein the non-magnetic material comprises polymethyl methacrylate, acrylic, polypropylene, polyethylene, polyvinyl chloride, Teflon, plastic, bakelite, non- Magnetic metal or ceramic. The magnetic separation device of claim 2, wherein the size of the first opening and the size of the second opening are less than or equal to the size of the magnetic separation unit. The magnetic separation device of claim 2, wherein a second fluid flow path is further defined between the magnetic strips and the container element. The magnetic separation device of claim 2, wherein the external magnetic field unit comprises a permanent magnet or an electromagnet.