JPH0975076A - Filter device for selecting and removing monocyte and/or macrophage derived from monocyte - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a filter device filled with a porous filter having a specific average pore cross section in a vessel having an inlet and an outlet and selectively removing monocyte and macrophage in a cell-floating solution, and useful for marrow transplantation and blood transfusion, etc. SOLUTION: This filter device is useful for transplantation of a peripheral vascular cell, marrow transplantation, blood transfusion and removing of monocyte from blood of a patient having inflammatory disease, etc., with a very simple operation. Monocyte and/or macrophage derived from monocyte in a cell-floating solution can selectively be removed by winding a sheet of non-woven cloth, etc., made of polyethylene terephthalate, etc., having 10-20μm average fiber diameter in a hollow cylindrical shape having 1.8cm thickness of a filter part to obtain a porous filter having 100-500μm<2> average pore cross section, filling the resultant filters in a hollow vessel having an inlet and an outlet of a liquid at both ends at a bulk density of 0.05-0.5g/cm<3> and fixing the filters by providing a mesh-type supporter at the most inner peripheral part and the most outer peripheral part.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention is for selectively removing only monocytes and / or monocyte-derived macrophages from a blood cell suspension containing monocytes such as blood and / or monocyte-derived macrophages. Regarding the device.

[0002]

2. Description of the Related Art In recent years, cell separation technology using a monoclonal antibody has been developed and widely used in the fields of immunology, cell biology and hematology. That is, using a cell separation technique, only target cells are separated and collected from a cell suspension such as blood,
After performing various operations such as activation and proliferation, operations such as infusion into patients have come to be performed. An example of this is selective collection of hematopoietic stem cells and / or hematopoietic progenitor cells in autologous bone marrow transplantation. Autologous bone marrow transplantation reinjects hematopoietic stem cells collected from bone marrow fluid, etc., which had been collected from the patient and cryopreserved, for fatal hematopoietic disorders due to bone marrow depletion, which is a side effect of a large amount of anticancer agents and / or radiation therapy. This is a treatment method to avoid. However, cancer cells may be infiltrated into the bone marrow of a cancer patient, and the cancer may recur by reinfusion. In the case of so-called allogeneic bone marrow transplantation or allogeneic peripheral blood transplantation in which bone marrow or peripheral blood of another person is transplanted, graft-versus-host disease (GVH
In order to prevent serious side effects such as D), it has become an important issue to transplant only hematopoietic stem cells free from other components.

Currently known instruments for selective collection of hematopoietic stem cells and the like include antibody-bound flasks, magnetic beads, avidin-biotin column and the like (Hemato).
poietic Stem Cell, Alpha M
ed Press, 1994, 186-187). However, these do not have a sufficient recovery rate of hematopoietic stem cells / or hematopoietic progenitor cells. As a cause for this, it has been pointed out that monocytes are mixed in a suspension such as blood. As this monocyte removal method,
A method using an antibody against CD14, which is a monocyte antigen, and magnetic beads has been proposed, but the cost is high and the operation is complicated because the antibody is used. Further, recently, so-called leukopheresis, which leads blood out of patients with autoimmune diseases and inflammatory diseases to the outside of the body to remove leukocytes, and then returns the blood to the patients again, has become popular.
At present, all components of white blood cells are removed at a high rate, but the white blood cell components to be removed include beneficial immune cells such as T cells in lymphocytes, and particularly in inflammatory diseases. It is known that monocyte-derived macrophages migrate to the site of inflammation and exacerbate the condition, and it is also desired to remove monocytes preferentially and selectively.
However, until now, a technique for capturing leukocytes from a hemocyte suspension by using a filter made of a fiber or a porous material whose pore diameter has been specified by utilizing the difference in cell diameter and adhesion of leukocytes from the hemocyte suspension. Although it is already known that two types of filters with different pore diameters are used in stages to selectively separate lymphocytes from white blood cells, only monocytes can be selected in a single treatment. A filter device for selectively capturing and removing is not yet known.

[0004]

SUMMARY OF THE INVENTION The present invention is directed to monocytes and / or
Another object of the present invention is to provide a filter device excellent in operability for selectively removing only monocytes and / or macrophages from a blood cell suspension containing monocyte-derived macrophages. White blood cells are roughly classified into monocytes, granulocytes, and lymphocytes, and monocytes are known as a cell component having the largest average diameter, that is, an average diameter of about 9 to 12 μm. However, the average diameter of granulocytes is about 7-9
μm, and the difference between lymphocytes is about 5 to 8 μm, which is insignificant, and in some cases the size may be reversed depending on the individual cell, so the principle of sieving monocytes from other leukocyte components is the only principle. Therefore, it is impossible to accurately separate it from other white blood cell components. As a result of diligent studies by the present inventors, the use of a specific porous body having a pore in which the cross-sectional area of the pore portion through which the cell component passes is slightly larger than the cross-sectional area of the monocyte is surprisingly It was found that only macrophages derived from / or monocytes were captured, and granulocytes and lymphocytes passed through pores, leading to completion of the present invention. The present invention provides a porous filter mean pore cross-sectional area is 100μm ² ~500μm ^2, in a container having an inlet and an outlet of the liquid 0.0
Characterized by being filled with bulk density of ^{5g / cm 3 ~0.5g / cm 3} , a macrophage selective removal filter apparatus of the monocyte-derived and / or monocyte cell suspension fluid.

The cell suspension referred to in the present invention means a liquid containing at least monocytes and / or monocyte-derived macrophages. Specific examples include bone marrow fluid, cord blood or peripheral blood, G-
Peripheral blood administered with hematopoietic factors such as CSF and GM-CSF,
Examples include whole blood, a mononuclear cell suspension obtained by centrifuging these, or buffy coat. The porous filter referred to in the present invention has a biological effect such as phagocytosis, adhesion, electrostaticity, hydrophobicity or the like in contact with a cell suspension containing monocytes and / or monocyte-derived macrophages. A member that preferentially captures or removes monocytes and / or monocyte-derived macrophages partially or substantially entirely by chemical interaction. Examples of the porous filter used in the present invention include those made of fibrous materials such as non-woven fabric, woven fabric and cotton fabric, and those made of porous materials such as sponge, gel and porous membrane. Among them, a nonwoven fabric having a large specific surface area and having a large number of pores or a sponge-like porous body is preferably used. As the material, any material can be used as long as it is water-insoluble. However, preferable examples from the viewpoint of moldability, stability during sterilization, and safety are polyesters such as polyethylene terephthalate and polybutylene terephthalate, nylon 6, nylon 6, Synthetic polymer compounds such as polyamides such as nylon 6,6, polystyrene and its derivatives, polyvinyl formal, polysulfone, polyurethane, polyvinyl acetal, and polycarbonate, and homopolymers, copolymers, and block copolymers of monomers of these compounds. Examples thereof include coalesced products and blends of the above-mentioned polymer compounds and alloyed products, blends of regenerated fibers such as cellulose and / or derivatives thereof and the above-mentioned synthetic polymer compounds, and alloyed products. .

The average pore cross-sectional area of the porous filter according to the present invention means that when the filter is cut in the direction perpendicular to the blood flow direction, the individual pores dispersed on the cut surface are circles or ellipses. It is regarded as an arithmetic mean value of the areas obtained for them. If the shape of the pores cannot be regarded as a circle or an ellipse, for example, if the pores approximate a polygon surrounded by linear fibers, the length of the narrowest and widest pores The area is calculated using the value obtained by arithmetically averaging as the pore diameter of the pore. The average pore cross-sectional area is 0.5 mm from the surface of the porous filter to the thickness direction of the filter.
The cut surface at an arbitrary depth within the range is photographed with a scanning electron microscope, and 100 or more are randomly measured except for the pores whose diameter or major axis is less than 1 μm dispersed in the photographed surface by visual observation. Ask for. As the simplest and most easy measurement method in which errors due to the skill of the measurer do not occur, the pores on the arbitrary cut surface are photographed using an electron microscope, and the pores and pore walls are subjected to image analysis processing by a known computer. Preferable is a method of clarifying the fine pores by giving a contrast of color tone to the fine portions and arithmetically averaging the areas of the individual fine pores.
The average pore cross-sectional area of the porous filter of the present invention determined by the above measuring method is 100 μm ^{2 to} 500 μm.
^2, preferably 100μm ² ~400μm ^2.

Microscopically, the porous filter used in the present invention is composed of pores slightly larger than monocytes, which are cells to be captured. Surprisingly, however, only monocytes and / or monocyte-derived macrophages are selectively captured, and other lymphocytes and granulocytes are substantially not captured. That is, since monocytes and / or monocyte-derived macrophages are smaller than the size of the pores, considering the principle of conventional sieving, there is little chance of coming into contact with the pore wall and remaining trapped there, and it is extremely high. However, as a result of examination by the present inventors, the pores having a large cross-sectional area having the features of the present invention show that monocytes and / or macrophages derived from monocytes have their phagocytosis. By the action, they identified the filter wall as a foreign substance and found that it had a size suitable for being adsorbed there. If the average pore cross-sectional area of the porous filter is less than 100 μm ² , cell components other than monocytes may be captured. Further, when the average pore cross-sectional area exceeds 500 μm ² , the frequency of contact between the monocytes and the filter wall is reduced, so that the phagocytosis of the monocytes is no longer sufficiently exerted, and the monocyte capture rate is significantly reduced. I will end up.

It is also preferable to impart hydrophilicity to the surface of the porous filter used in the present invention. By imparting hydrophilicity, it works effectively in preventing non-specific adsorption of other cells existing in the treated cell suspension. When making the surface hydrophilic, it is also preferable to introduce a hydroxyl group for the purpose of suppressing adsorption of proteins in cell suspensions such as blood. Further, it is preferable to introduce a cationic group in order to suppress non-specific adsorption because an electrostatic action can be expected. The term "cationic group" as used herein includes amines and amine derivatives and includes tertiary and quaternary amino groups. To impart hydrophilicity to the surface of the porous filter, various functional groups are covalently bonded,
It may be bonded to the surface by ionic bond, hydrophobic bond or the like. As a bonding method, any method such as radiation grafting or coating may be used. Examples of the functional group introduced for imparting hydrophilicity include a polyethylene glycol chain having a repeating unit of 2 to 100, a hydroxyl group, an amide group, an ether group, an ester group and the like. Examples of the monomer having a polyethylene glycol chain that imparts hydrophilicity include a terminal methoxymethacrylate, a terminal methoxyacrylate, and a monomer having a polyethyleneglycol chain having 2 to 15 repeating units having one or more polymerizable functional groups at the terminals. Be done. Examples of the monomer having a hydroxyl group that imparts hydrophilicity include 2-hydroxyethyl methacrylate, 1-hydroxyethyl methacrylate, 2-hydroxyethyl acrylate, 1-hydroxyethyl acrylate, 1,2-dihydroxyethyl methacrylate, and 2,2. -Dihydroxyethyl methacrylate, vinyl alcohol, vinyl acetate and the like can be mentioned.
Examples of the monomer having another substituent that imparts hydrophilicity include, but are not limited to, acrylamide and vinylpyrrolidone. The porous filter used in the present invention is preferably made of a fiber by a melt spinning method, a flash spinning method, or the like, and if necessary, is compressed or heat-shrinked into a produced fiber medium, and any liquid is used. Secondary processing such as treatment by the above is applied to control the pore size defined in the present invention. Further, those made of a porous material include a foaming decomposition method such as a known atmospheric pressure or pressure foaming method, extrusion foaming method, injection foaming method, solvent vaporization method, gas mixing method, chemical reaction method, elution method, It is produced by a sintering method or the like, and thereafter, as in the case of the above-mentioned fiber, secondary processing is performed as necessary to control the pore size defined in the present invention.

When a fibrous filter such as a non-woven fabric is used, the fiber diameter contributes to the pore diameter and the pore distribution, so that it is important to show the effective average fiber diameter. The average fiber diameter of the present invention is obtained by photographing the surface of a fibrous filter with a scanning electron microscope and visually measuring 100 or more randomly distributed yarn diameters on the photographed surface. The fiber diameter of the filter effective in mechanical strength and monosite capturing performance is 10 μm or more and 20 μm, more preferably 12 μm or more and 18 μm or less, and further preferably 13 μm.
It is not less than m and not more than 17 μm. If the average fiber diameter is less than 10 μm, it is smaller than the diameters of other white blood cells, so that nonspecific adsorption is increased and the selectivity is decreased, which is not preferable. On the other hand, if it exceeds 20 μm, the contact frequency of monocide is lowered and the removal efficiency is lowered, which is not preferable.

In the present invention, the porous filter is used in an arbitrary container having an inlet and an outlet for cell suspension, and the amount of 0.05 to
It is filled with a bulk density of 0.5 g / cm ³ . 0.05 g /
If it is less than ³ cm ³ , it is difficult to stably secure sufficiently large pores, and it is difficult to realize a filter device having physically stable strength. Further, it is difficult to realize pores satisfying the requirements of the present invention with a porous filter having a weight of more than 0.5 g / cm ³ . Preferred packing density is 0.1 g / cm
^{3 to} 0.4 g / cm ³ , more preferably 0.15 g / c
m ³ is a ~0.3m ^3. The size of the container is appropriately set in consideration of the amount of cell suspension to be treated, the treatment speed, and the like. or,
The shape of the container and the method of filling the porous filter are not particularly limited, but from the viewpoint of efficiency, the area of the surface (front) surface of the porous filter with which the cell suspension introduced from the inlet can come into contact ( Hereinafter, it is preferable that the container volume be small while at the same time ensuring a large filter surface area).
Also, considering the capture rate of monocytes, it is not preferable that the thickness of the porous filter is too thin. However, in order to continuously supply the cell suspension liquid and continuously capture the monocytes with high efficiency, an excessively large filter thickness also causes an increase in pressure loss and causes a decrease in processing speed, which is preferable. Absent. The thickness of the filter depends on its shape, but is in a practical range of 0.1 mm to 50 mm, preferably 0.1 mm.
mm~40mm C., also from a practical range Considering the ease and general processing cell suspension volume of production well 0.5cm ² ~300cm ^2, miniaturization and operability of the filter surface area 0 .5cm ² ~250cm ^2, more preferably 0.5cm ² ~200cm ^2.

The simplest device structure of the device of the present invention is, for example, as shown in FIG. 1 of JP-A-62-243561, an inlet of a cell suspension liquid at both ends of a cylindrical container,
An outlet nozzle is provided, and a macaroni-shaped, that is, a cylindrical porous filter having a hollow core is loaded into the outlet nozzle, and a cell suspension is supplied from the outer peripheral surface side of the porous filter to the inner peripheral surface side of the treated cells. There is a form in which the floating liquid is collected and discharged out of the container through an outlet nozzle. In this case, the porous filter may be a macaroni-shaped product obtained by winding a thin non-woven fabric sheet in multiple layers, or may be a macaroni-shaped product filled or molded with fibers or a porous body.
Alternatively, in order to increase the specific surface area, it is also preferable that the sheet-shaped filter is processed into fine pleats and then wound in multiple layers. If the amount of treated cell suspension is small, for example,
As shown in FIG. 2 of JP-A-59-48173, an inlet and an outlet of a cell suspension are provided at positions facing each other through a filter filled in a disc-shaped container with a sheet-shaped filter interposed therebetween. The device structure described above is also preferably used. In the case of a disk-shaped device, it is preferable that the inside thickness (Dcm) of the container including the filter is smaller than the front surface area (Scm ² ) of the filter, and the S / D ratio is 1
0-500 cm is preferable. Further, the shape of the disk is preferably a circular shape, a polygonal shape, or the like, but a shape that tapers in a cone shape toward the liquid outlet may be used.

In the monocyte and / or macrophage selective removal filter device of the present invention, another filter having a coarser mesh than the porous filter may be laminated on the upstream portion of the porous filter. Alternatively, the porous filter itself may have a structure in which the average pore cross-sectional area is substantially continuously or stepwise reduced. Such a structure in which the average pore cross-sectional area continuously or gradually decreases can be formed by laminating a plurality of filters having different average pore cross-sectional areas, or the average pore cross-sectional area can be continuously reduced in advance. It may be molded so as to Specifically, the average pore cross-sectional area on the inlet side is 250 to 500 μm ² and that on the outlet side is 100
A porous filter having a particle size of 300 μm ² is preferably used. Further, in the monocyte and / or macrophage selective removal filter device of the present invention, depending on the cell suspension to be treated, in order to prevent clogging of the porous filter upstream of the porous filter due to microaggregates, etc. A prefilter having a cross-sectional area of 500 to 5000 μm ² can also be provided. The monocyte and / or macrophage selective removal filter device of the present invention has been sterilized by any known method such as heat sterilization such as autoclave, ethylene oxide gas sterilization, γ-ray sterilization, radiation sterilization such as electron beam sterilization, and ultraviolet sterilization. It will be put to practical use later.

[0013]

The present invention will be described in detail below with reference to specific examples.

Example 1 Nonwoven fabric made of polyethylene terephthalate (average fiber diameter 12 μm, average fine 1 cross-sectional area 265 μm
^2. Bulk density of 0.2 g / cm ³ ) A sheet is wound into a hollow cylinder so that the thickness of the filter portion is 1.8 cm, and 2.0 cmφ × 15 having a liquid inlet and outlet at both ends.
cm into a hollow container. A mesh-shaped support was provided at the innermost and outermost portions of the filter to fix the filter portion. The mononuclear cell suspension separated and collected by a centrifuge and a specific gravity centrifugation method was diluted with calcium ion- and magnesium ion-free HBSS and adjusted to 1.0 × 10 ⁸ cells / 20 ml. This mononuclear cell suspension was used as a sample. 20 ml of this mononuclear cell suspension was sent to the inlet side of the filter device using a peristaltic pump at a flow rate of 5 ml / min, and the treated liquid was recovered from the outlet of the device. The number of monocytes before and after introduction into the device was measured by a known flow cytometry method using anti-CD14 antibody as a label. At this time, the monocyte removal rate was 98.1%. The removal rate of other cells at this time was 30% for CD3 positive cells and 50% for CD34 positive cells.

[0014]

Comparative Example 1 Nonwoven fabric made of polyethylene terephthalate (average fiber diameter 42 μm, average pore cross-sectional area 620 μm
^{2. A} sheet having a bulk density of 0.2 g / cm ³ ) was assembled in the same filter device as in Example 1. 20 ml of the liquid to be treated mononuclear cell suspension similar to that in Example 1 was sent to the inlet side of the filter device using a peristaltic pump at a flow rate of 5 ml / min, and the treated liquid was recovered from the outlet of the device. The number of monocytes before and after introduction into the device was measured by a known flow cytometry method using anti-CD14 antibody as a label. The monocyte removal rate at this time was 23.2%. The removal rate of other cells at this time was 10% for CD3 positive cells and 5% for CD34 positive cells.
Met.

[0015]

Example 2 Nonwoven fabric made of polyethylene terephthalate (average fiber diameter 19 μm, average pore cross-sectional area 326 μm
² , bulk density 0.2 g / cm ³ ) A sheet is wound into a hollow cylinder so that the thickness of the filter portion is 1.8 cm, and 2.0 cmφ × 5c having a liquid inlet and outlet at both ends.
m hollow container. A mesh-shaped support was provided at the innermost and outermost portions of the filter to fix the filter portion. The mononuclear cell suspension separated and collected by a centrifuge and a specific gravity centrifugation method was diluted with calcium ion- and magnesium ion-free HBSS to obtain 1.5 × 10 ⁸ cells /
Adjusted to 20 ml. This mononuclear cell suspension was used as a sample. 20 ml of this mononuclear cell suspension was sent to the inlet side of the filter device using a peristaltic pump at a flow rate of 5 ml / min, and the treated liquid was recovered from the outlet of the device. The number of monocytes before and after introduction into the device was measured by a known flow cytometry method using anti-CD14 antibody as a label. At this time, the monocyte removal rate was 89.2%. At this time, the removal rate of other cells was 20% for CD3 positive cells and 20% for CD34 positive cells.

[0016]

Example 3 Nonwoven fabric made of polyethylene terephthalate (average fiber diameter 12 μm, average pore cross-sectional area 265 μm
² , a sheet having a bulk density of 0.1 g / cm ³ ) is wound into a hollow cylindrical shape so that the thickness of the filter portion is 3.3 cm, and another non-woven fabric made of polyethylene terephthalate is provided on the outside thereof (average fiber diameter 19 μm, average pores). Cross-sectional area 326 μm
² , bulk density 0.1 g / cm ³ ) A filter material obtained by winding a sheet so that the filter portion thickness becomes 3.0 cm, and has a liquid inlet and outlet at both ends of 6.5 cmφ ×
A 15 cm cylindrical container was filled. A mesh-shaped support was provided at the innermost and outermost portions of the filter to fix the filter portion. 2000 ml of bovine blood to which ACD-A solution was added at a ratio of 8: 1 was used to flow 5 m with a peristaltic pump.
The solution was sent to the inlet side of the filter device at 1 / min, and the treated liquid was recovered from the outlet of the device. White blood cell recovery rate is 70%
Met. The leukocyte fraction at this time was stained by the known May-Giemsa cell staining method to identify 100 cells, and the recovery rate of each cell was determined from the cell ratio before and after the filter device column and the recovery rate of leukocytes. The monocyte removal rate at this time is 7
It was 5.1%. The removal rate of other cells was 25% for lymphocytes and 35% for granulocytes.

[0017]

Comparative Example 2 Nonwoven fabric made of polyethylene terephthalate (average fiber diameter 2.3 μm, average pore cross-sectional area 1.8 μm
m ² and bulk density 0.1 g / cm ³ ) A sheet was wound into a hollow cylindrical shape so that the thickness of the filter portion was 3.3 cm, and another non-woven fabric (average fiber diameter 19 μm, average fineness) made of polyethylene terephthalate was wound on the outside thereof. Hole cross-sectional area 326μ
m ² and bulk density 0.1 g / cm ³ ) A filter material obtained by winding a sheet so that the thickness of the filter portion becomes 3.0 cm, and has a liquid inlet and an outlet at both ends of 6.5 cmφ ×
A 15 cm cylindrical container was filled. A mesh-shaped support was provided at the innermost and outermost portions of the filter to fix the filter portion. The same liquid to be treated as in Example 3 was sent to the inlet side of the filter device using a peristaltic pump at a flow rate of 5 ml / min, and the treated liquid was recovered from the outlet of the device. Leukocyte recovery rate is 10%, monocyte removal rate is 95.1%
Met. In addition, the recovery rate of other cells was 83%
% And granulocytes 95%.

[0018]

Example 4 Nonwoven fabric made of polyethylene terephthalate (average fiber diameter 15 μm, average pore cross-sectional area 350 μm
^2. Bulk density of 0.1 g / cm ³ ) The sheet was filled in a 4.5 cm × 4.5 cm rectangular flat container having a liquid inlet and an outlet at opposite positions so that the thickness of the filter portion was 1.5 cm. Bovine blood 2 to which ACD-A solution was added at a ratio of 8: 1
0 ml was sent to the inlet side of the filter device using a peristaltic pump at a flow rate of 5 ml / min, and the treated liquid was recovered from the outlet of the device. The recovery rate of white blood cells was 70%.
The leukocyte fraction at this time was stained by the known May-Giemsa cell staining method to identify 100 cells, and the recovery rate of each cell was determined from the cell ratio before and after the filter device column and the recovery rate of leukocytes. At this time, the monocyte removal rate was 77.1%. The removal rate of other cells was 21% for lymphocytes,
It was 41% of granulocytes.

[0019]

Comparative Example 3 Nonwoven fabric made of polyethylene terephthalate (average fiber diameter 40 μm, average pore cross-sectional area 3162 μ
A filter device similar to that in Example 4 was produced using a sheet having m ² and bulk density of 0.1 g / cm ³ ). 20 ml of bovine blood to which the ACD-A solution was added at a ratio of 8: 1 was sent to the inlet side of the filter device using a peristaltic pump at a flow rate of 5 ml / min, and the treated solution was recovered from the outlet of the device. The recovery rate of white blood cells was 95%. The white blood cell fraction at this time is
The cells were stained by a known May-Giemsa cell staining method, 100 cells were identified, and the recovery rate of each cell was determined from the cell ratio before and after the filter device column and the recovery rate of leukocytes. The monocyte removal rate at this time was 5%. The recovery rate of other cells was 90% for lymphocytes and 96% for granulocytes.

[0020]

INDUSTRIAL APPLICABILITY The filter device for selective removal of monocytes and / or macrophages of the present invention is for removing monocytes at the time of peripheral blood stem cell transplantation, for removing monocytes at the time of bone marrow transplantation, for blood transfusion and from blood of patients with inflammatory diseases. It is suitable for removal of monocytes and the like, and monocytes are preferentially removed by an extremely simple operation of simply passing the treated cell suspension through the device.

Claims (2)

[Claims] 1. The average pore cross-sectional area is 100 μm ^{2 to} 500.
A porous filter having a diameter of μm ² is added to a container having an inlet and an outlet for liquid in an amount of 0.05 g / cm ^{3 to} 0.5 g / cm ^3.
A device for selective removal of monocytes in a cell suspension and / or macrophage-derived macrophages in a cell suspension, the device being filled with the bulk density of 1. 2. The porous filter has an average fiber diameter of 10 μm.
The filter device for selective removal of monocytes and / or monocyte-derived macrophages in a cell suspension according to claim 1, which is composed of a non-woven fabric of about 20 μm.