JP2006226798A - Filter for removing blood cell - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a filter for separating and removing blood cells on a sensor, a blood collection tube or the like, in a system for sucking a small amount of blood, utilizing the phenomenon of capillarity. <P>SOLUTION: A blood cell separation filter in a system for capturing the corpuscle, when the blood passes is used. A particle of a glass bead or the like whose surface is coated with a polymer having positive charge, such as polylysine, is used as a material of the filter. Since the surface of erythrocyte is charged negatively, the erythrocyte will be captured onto the particle surface by attraction to the positive charge carried by the polymer. Especially, by utilizing particles having a diameter larger than that of the erythrocyte, quick blood cell separation becomes possible, without causing clogging. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

The present invention relates to a blood cell removal filter used in a micro device such as a chemical sensor that handles blood as a sample.

Japanese Patent Laid-Open No. 2000-171461 discloses a blood cell separation filter that is installed inside a capillary tube and separates blood cells of blood that goes up the inside of the tube. In this method, a positive charge is imparted to the inner wall of an ultrafine (inner diameter 50 μm) glass tube, and when blood rises in the tube, blood cells are adsorbed on the inner wall and separated. However, this method has a restriction that, in principle, a capillary tube with an extremely small diameter must be used. Further, in this patent, as a method of giving a positive charge to the inside of the tube, first, the inner wall of the tube is positively charged with a silane coupling agent, and an anion exchange material and a cation exchange material are alternately laminated thereon. This method is limited.
Japanese Patent Laid-Open No. 7-5173 Japanese Patent Laid-Open No. 7-27680 JP 7-504747 JP-A-8-104643 JP-A-8-208492 JP-A-9-56813 JP 2000-171461 A Japanese Patent Application Laid-Open No. 2001-116749 JP 2001-183363 A JP 2003-194806 A

As described above, the conventional method of separating blood cells using the capillary phenomenon has problems such as depending on the inner diameter of the glass tube used and requiring a complicated surface treatment process.

The present invention has been made to solve the above-described problem, and an object of the present invention is to provide a filter that quickly and efficiently captures red blood cells and allows components other than red blood cells to pass when blood passes through the tube. And

As a result of intensive studies, the present inventors have solved the above problems. That is, in order to solve the above-mentioned problem, a blood collection tube is installed inside a tube, and in the process of blood passing through the tube, blood cells are selectively captured among the blood components, and a non-blood cell is placed above the tube. Provided is a blood cell removal filter that allows only components to reach. Specifically, a filter in which a glass bead such as polylysine or the like having a water-soluble polymer having a positive charge adsorbed on the surface thereof is packed in a tube such as a glass tube can be used. More preferably, it is desirable that the diameter of the glass beads is sufficiently larger than that of red blood cells. That is, the diameter of a human erythrocyte is about 7 μm, but the glass bead size is preferably 50 to 100 μm. If the glass beads are smaller than the size of red blood cells, blood cells can be separated without using a polymer, but it takes a long time. On the other hand, when the diameter is large, suction by capillary action is quickly performed. However, when the polymer is not adsorbed, blood cell separation is not performed even if the suction is quick. It is considered that by charging the glass bead surface with a positive charge, it can interact with blood cells having a negative charge on the surface and can be separated. However, the introduction of amino groups on the glass bead surface using a silane coupling agent is not effective, and the effect is great when a water-soluble polymer such as polylysine is adsorbed on the glass beads. The reason for this is thought to be that polylysine is adsorbed to glass beads in part, while the other part protrudes deep into the solution, and there are an overwhelmingly many sites that can capture red blood cells. Although polymers such as polylysine are water-soluble, they are strongly adsorbed on the glass surface and are not easily peeled off by washing or the like. For this reason, it is used, for example, as an adhesive layer between the container and the cells during cell culture. Such a property also includes the advantage that the filter manufacturing process according to the present invention is simplified.
Moreover, a well-known thing may be sufficient as a porous fixing material for fixing this blood cell capture | acquisition material in the predetermined position in a pipe | tube.

Moreover, the microdevice using the blood cell removal filter of this invention is also provided. Specifically, a chemical sensor or the like that targets plasma in blood can be used.

As described above, according to the present invention, it is possible to quickly capture and separate red blood cells in a blood sample by providing a red blood cell separation filter in the blood collection tube.

FIG. 1 is a conceptual diagram showing the basic structure of an erythrocyte removal filter of the present invention. In this figure, a blood cell capturing agent for capturing blood cells and a porous fixing material for holding the blood cell capturing material in the tube are incorporated in a blood collection tube for sucking a blood sample.

The blood cell capturing material uses glass beads coated with polylysine on the surface (FIG. 2). Especially when this glass bead is sufficiently larger than the diameter of human erythrocytes, which is sufficiently larger than 7 μm, and having a diameter of 20 to 100 μm, erythrocytes can rapidly pass blood without causing clogging due to adsorption to the beads. .

A method for producing glass beads whose surface is coated with polylysine, which is an example of a blood cell capturing agent, will be described. First, glass beads (diameter 50 μm) are washed with a 5% dilute nitric acid solution, and further washed with pure water and dried. Then, it is immersed for 20 minutes in a 0.1% polylysine (molecular weight 300,000 or more) solution. This is further washed with pure water and dried. Here, although a polymer such as polylysine is water-soluble, it is adsorbed on the surface only by contacting with glass or the like, and is not easily peeled off from the bead surface even by washing with pure water.
Furthermore, regarding the method of creating a filter to be incorporated into a blood collection tube, basically, a porous fixing material is first packed at the lower end of the blood collection tube, and glass beads coated with polylysine on the surface from the upper end of this blood collection tube are placed in the tube densely. Further, it is produced by sealing the upper end with a porous fixing material. However, depending on the application purpose of this filter, after the glass beads are packed in the tube, an electrode or a small sensor is inserted from the upper end of the blood collection tube, and then the upper end is sealed with a porous material.

FIG. 3 is a diagram showing blood separation results when a blood collection tube formed with an erythrocyte filter prepared according to the above embodiment is brought into contact with a blood sample. As shown in the figure, when the erythrocyte filter is used, the blood sample is clearly divided into a lower red part (blood cell adsorption layer) and an upper transparent part (non-blood cell adsorption layer) in the middle of the filter. It was confirmed that blood cells were not included in the transparent part. In addition, the reason why the blood sample is sucked in the red blood cell filter is that the blood cell capturing material itself mainly made of glass beads has pores and therefore has a suction force by capillary action, and the material, shape and inner diameter of the blood collection tube It can be captured quickly and efficiently.

The schematic diagram of the blood collection tube which included the blood cell separation filter. The schematic diagram which showed the mode of the red blood cell capture | acquisition by the polylysine coat glass bead which is a blood cell capture | acquisition material. The schematic diagram which showed the mode of the blood cell separation by the blood collection tube which included the blood cell separation filter.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Blood collection tube 2 Blood cell capture | acquisition material 3 Porous fixing material 4 Glass bead 5 Polylysine 6 Red blood cell 7 Blood 8 Blood cell adsorption layer 9 Non-blood cell layer

Claims (8)

  In the blood collection tube, a blood cell removal filter that is installed inside the tube and selectively captures blood cells among the blood components in the process of blood passing through the tube, and only the non-blood cell components reach the upper part of the tube. . 2. The blood removal filter according to claim 1, wherein the surface of the one that selectively captures blood is positively charged. The blood cell removal filter according to claim 1 or 2, comprising a blood cell capturing material for selectively capturing blood cells and a porous fixing material for fixing the blood cell capturing material at a predetermined position in the tube. 4. The blood cell removal filter according to claim 3, wherein the blood cell capturing material is a particulate material. The blood cell removal filter according to claim 3 or 4, wherein the blood cell capturing material is a material having a positive charge on the surface. 6. The blood cell removing filter according to claim 5, wherein the blood cell trapping material is a material having a positively charged polymer formed on the surface thereof.   7. The blood cell removal filter according to claim 4, wherein the particle size of the particulate blood cell trapping material is larger than 7 μm which is the particle size of red blood cells.   A microdevice using the blood cell removal filter according to claim 1.

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