KR20170127241A - Body fluid tumor cell collecting filter and body fluid tumor cell collecting device having the same - Google Patents

Abstract

According to an embodiment of the present invention, provided is a body fluid tumor cell collecting filter. Multiple rectangular fine pores formed in a matrix shape are disposed on a filter body made of a metal. When the thickness of the filter body is t, the widthwise direction length of the fine pores is a, the lengthwise direction length of the fine pores is b, the distance between the fine pores adjacent along the widthwise direction of the filter is l, and the distance between the fine pores adjacent along the lengthwise direction of the filter is m, a ratio a/b of the a and the b is 0.8 to 1.2, a ratio l/m of the l and the m is 0.8 to 1.2, and a ratio t/x (here, x is a or b) of the t and the a or of the t and the b is 0.5 to 1.8. Moreover, provided is a body fluid tumor cell collecting device including a filter having a multilayer structure in accordance with the size and the number of shape fine pores.

Description

FIELD OF THE INVENTION [0001] The present invention relates to a device for collecting a body fluid tumor cell,

The present invention relates to a body fluid tumor cell collecting filter and a body fluid tumor cell collecting apparatus having the same, and more particularly, to a body fluid tumor cell collecting apparatus capable of being applied to an automated bodily fluid tumor cell separating apparatus, The present invention relates to a cell harvesting filter and a cell harvesting device, which are capable of inhibiting damage or deformation of body fluid tumor cells.

Gene analysis, cancer diagnosis, etc., various methods of examining or examining cells using cells have been developed. For such cell-based testing or screening, techniques are needed to capture live cells from human or animal blood.

As an example of cell collection, there is a method of using body fluid tumor cells to diagnose cancer.

Although histologic examination is performed for the clinical confirmation of the current status of cancer patients, it is difficult to repeatedly perform such a histological examination due to time, cost, and condition of the patient, and may cause infection or bleeding due to side effects There are disadvantages. To solve this problem, a technique for collecting body fluid tumor cells from body fluid of cancer patients has been developed.

Body fluids are liquids in the body such as blood lymphatic fluid and tissue fluid. They transport nutrients and oxygen to tissue cells by moving inside the body, carry and remove waste products, and have functions such as eradication of pathogens and temperature control.

Especially in the body fluids, punctured ascites and peritoneal fluid are used for diagnosis and prevention of cancer.

In normal people, the abdominal cavity contains about 50 mL of liquid called effluent. In cancer patients, excess fluid can accumulate in the abdominal cavity in addition to the normal volume, which is called ascites.

In the ascites, we can find a primary mesenchymal tumor or metastatic cancer, a tumor that occurs in the mesothelium and the connective tissue that supports it. Ascites Tumor Cells (ATCs) are a primary tumor tissue, a small number of tumor cells that move away from primary carcinoma and circulate in the blood and are known to be a key factor of metastatic cancer. According to statistics, about 90% of cancer patients are known to die from metastatic cancer.

The peritoneal fluid is a liquid acting as a lubricant in the abdominal cavity present in small quantities between the peritoneal layers. The peritoneal fluid generated from mesothelial cells reduces the impact of organ movement during the digestion process and protects the outside of the organs.

Depending on the type of effluent, the diagnosis of specific diseases and conditions varies, and further tests for cancer diagnosis vary according to the type of effluent.

However, it is known that multiple tumor cells, as well as tumor cells in the peritoneal fluid, are present in a small proportion in the ascitic ascites. Therefore, for the detection of tumor cells in the body, a cell collection method having a high recovery rate as well as being safe and simple is required.

As a method for collecting tumor cells in the body, there are a method using a microfluidic device in which a capture antibody is bound to a resin surface such as a magnetic particle or a columnar structure on which an anti-EpCAM (epithelial cell adhesion molecule) antibody is immobilized, A method of using a filter using the difference in size of hemocyte cells is known.

As a method of using a filter, there is a method of using a parylene membrane filter for filtering cells from a fluid. The membrane filter is mounted within the chamber and has a plurality of pores that are formed to prevent passage of target cells. However, in this technique, there is a problem that it is difficult to collect and collect the cancer cells filtered through the membrane filter from the chamber. In addition, there is a high possibility that the cells injected into the chamber by the syringe are damaged.

As a filter for cell collection, there is a method of installing a plurality of filter patches in a central square hole of a microfiltration apparatus. The filter patches consist of a membrane having a plurality of pores for filtration of cells. However, this method is also difficult to collect and collect the cells that have been filtered in the filter patch of the microfiltration device from the central square hole, and there is a high possibility that the target cells are damaged.

Therefore, there is a demand for a simple and economical structure of a cell trapping filter that prevents damage or deformation of the cells while having a high recovery rate for the target cells and does not affect the activity.

Disclosure of Invention Technical Problem [8] The present invention provides a body fluid tumor cell collection filter capable of inhibiting cell damage, deformation, . Another object of the present invention is to provide a simple and economical bacterium tumor cell multi-layer filter and a bacterium tumor cell collection apparatus applicable to an automated cell separation apparatus.

It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory and are not intended to limit the invention to the precise form disclosed. There will be.

According to an aspect of the present invention, there is provided a body fluid tumor cell collection filter, comprising: a plurality of rectangular pores arranged in a matrix form in a filter body made of metal, A length of the pores in the longitudinal direction is b, a distance between adjacent pores along the transverse direction of the filter is l, and a distance between adjacent pores along the longitudinal direction of the filter is m, Wherein the ratio a / b of a and b is 0.8 to 1.2, the ratio l / m of 1 to m is 0.8 to 1.2, the ratio of t and a or the ratio t / x of t and b, a or b) is 0.5 to 1.8.

In the embodiment of the present invention, the ratio a / l of a and l is 0.9 to 1.6, and the ratio b / m of b and m may be 0.9 to 1.6.

In an embodiment of the present invention, the a or b may have a size of 40 to 70% with respect to the diameter of the target cell.

In an embodiment of the present invention, the filter body may be made of nickel or a nickel alloy.

According to another aspect of the present invention, there is provided a cell collection device comprising: a tube having a hollow portion capable of flowing fluid therein; and a cell collection filter provided on the lower side of the tube, And a cell harvesting apparatus.

In an embodiment of the present invention, the body fluid tumor cell collecting filter disposed on the upstream side is disposed downstream from the upstream side in the flow direction of the fluid, and includes a plurality of body fluid tumor cell collecting filters, And a storage layer for temporarily storing the fluid is provided between the filters. The present invention also provides a cell harvesting apparatus having a multi-layer structure.

Another embodiment of the present invention is characterized in that the number of the shape pores of the humor tumor cell collection filter disposed on the upstream side is smaller than the number of the shape pores of the humorous tumor cell collection filter disposed on the downstream side, to provide.

According to the embodiment of the present invention, it is possible to provide a simple and economical structure of a bacterium tumor cell collection filter having a high recovery rate for a target cell and preventing damage or deformation of the cell and not affecting activity, and a bacterium tumor cell collection device Can be provided.

In particular, damage to the target cell can be prevented by optimizing the pore (hole) or thickness formed in the humoral tumor cell collection filter.

A plurality of bacterium tumor cell collection filters arranged sequentially from the upstream side to the downstream side in the flow direction of the fluid, and the bacterium tumor cell collection filter disposed on the upstream side is larger than the filter disposed on the downstream side It is possible to increase the recovery rate of target cells by providing the shape pores.

It should be understood that the effects of the present invention are not limited to the above effects and include all effects that can be deduced from the detailed description of the present invention or the configuration of the invention described in the claims.

1 is a plan view showing a schematic configuration of a cell separation device.
2 is an exploded view showing a cell trapping apparatus according to an embodiment of the present invention.
3 is a side sectional view of the cell collection device of FIG.
4 is a perspective view showing a schematic configuration of a cell collection filter of the cell collection device of FIG.
FIG. 5 is a partial cross-sectional view illustrating a target cell collection process. FIG.
FIG. 6 is a cutaway perspective view showing a part of the cell trapping filter of FIG. 4; FIG.
FIG. 7 is a photograph showing the biomarker of multiple tumor cells recovered in body fluids. FIG.
8 is a graph comparing the recovery rates of multiple tumor cells in body fluids using a cell collection device.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Hereinafter, the present invention will be described with reference to the accompanying drawings. The present invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. In order to clearly illustrate the present invention, parts not related to the description are omitted, and similar parts are denoted by like reference characters throughout the specification.

Throughout the specification, when a part is referred to as being "connected" (connected, connected, coupled) with another part, it is not only the case where it is "directly connected" "Is included. Also, when an element is referred to as "comprising ", it means that it can include other elements, not excluding other elements unless specifically stated otherwise.

The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. The singular expressions include plural expressions unless the context clearly dictates otherwise. In this specification, the terms "comprises" or "having" and the like refer to the presence of stated features, integers, steps, operations, elements, components, or combinations thereof, But do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, or combinations thereof.

Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings.

1 is a plan view showing a schematic configuration of a cell separation device.

As shown, the cell separation device 1 includes a pipetting module 10 and a working module 20, and the pipetting module 10 is connected to the working module 20 along the rails 30, (Moving in the left and right direction in the drawing) and performs a cell separation / collection process.

The pipetting module 10 may include a plurality of pipette workbenches 11 and a driving unit 12 for vertically and horizontally moving the pipette workbench 11 relative to the pipetting module body.

The working module 20 includes a sample tube storage section 21, a first pipette rack 22, a process section 23, a dish / chip cartridge section 24, A rack 25, and a collection tube storage section 26. [ In the present specification, one of the first pipette rack 22 and the second pipette rack 25, or both, is collectively referred to as a pipette rack.

In the process section 23, a buffer solution storage tube and a process tube for solution mixing / extraction / separation are disposed.

A plurality of pipettes of different sizes may be stored in the first and second pipette racks 22 and 25 and a collection box for collecting used pipettes may be provided together or separately.

As described above, the cell separation device 1 includes various components for the cell separation / collection / recovery process. One of the most important processes using the cell separation device 1 is to centrifuge the blood or to mix the buffer solution And then filtering the target cells from the mixed sample. To this end, the cell collection device 100 having the cell collection filter 200 (see FIG. 2) is placed on a dish, and a buffer solution or the like is put into the cell collection device to perform filtering by the flow pressure of the fluid.

Buffer liquids discharged into the dish can be collected in a separate place. Also, the cell collecting apparatus 100 may be subjected to a filtering operation while being placed on a dish already having a buffer solution. The buffer solution may be introduced into the cell collection device 100 a plurality of times, and the buffer solution introduced into the cell collection device 100 may be supplied from the buffer solution storage tube or may be supplied from the buffer solution in the dish have.

As described above, the cell separation device 1 is a device for separating and collecting target cells from blood, and includes a cell collection device 100 provided with a cell collection filter 200. Here, the cell collection device 100 may be represented by a cell collection chip, or simply a chip.

Hereinafter, the configuration of the cell collection device or the cell collection filter will be described in detail.

2 is a side sectional view of the cell trapping apparatus of FIG. 2, and FIG. 4 is a schematic cross-sectional view of a cell trapping filter of the cell trapping apparatus of FIG. 2 according to an embodiment of the present invention. Fig.

2, the cell trapping apparatus 100 may include a first tube 110 on the upper side and a second tube 120 on the lower side, A collection filter 200 may be provided.

Referring to FIG. 3, the first tube 110 may have a first tube body 111 and a protruding engaging portion 112 provided below the first tube body 111. The second tube 120 may have a second tube body 121 and a protrusion 122 protruding inward from the lower side of the second tube body 121. And the cell collection filter 200 may be fixedly coupled to the lower side of the protrusion 122. The cell collection filter 200 may be fixedly coupled to the upper side of the protrusion 122 as shown in FIG.

The cell trapping apparatus 100 may include a tube 110 having a hollow portion capable of flowing fluid inside and a cell collection filter 200 provided below the tube 110 and 120 . Here, the tubes 110 and 120 are shown as being composed of two first tubes 110 and a second tube 120, but they may be composed of one single tube or three or more parts.

Further, a tube may be further coupled to the lower side of the second tube 120 to which the cell collection filter 200 is coupled. That is, the cell collection filter 200 may be inserted into the middle portion of the tube. Therefore, in the specification or claims of the present invention, if the cell collection filter 200 is installed on the lower side of the tube, the cell collection device 100 in which the cell collection filter 200 is provided in the middle of the tube .

Although the first tube 110 and the second tube 120 are fixedly coupled to each other by interference fit between the coupling portion 112 and the second tube body 121, But it is also possible that the first tube 110 and the second tube 120 are coupled with each other by, for example, a coupling by a thread-like shape, a bonding, a fusion or the like.

A tube 110 of the cell collection device 100; 120, and the target cells can be collected and collected by the size selectivity of the cell collection filter 200. The fluid can be supplied to the inside of the cell collection device 100 by a pipette capable of discharging a fixed amount of fluid and can be supplied from a syringe / syringe, a blood collection tube, .

The fluid may be, for example, body fluids, or any other form of liquid or liquid material that requires capture of target cells or target material. As an example, the fluid may be a bodily fluid including a bodily fluid tumor cell, in which case the hematoma tumor cell becomes the target cell and the other blood cells (leukocytes, red blood cells) become non-target cells.

Although the cell collection device 100 is shown in the form of a cylinder in the drawing, it is not necessarily limited to such a shape, but may be formed of a polygon such as a quadrangle.

4, the cell trapping filter 200 includes a filter body 210 made of metal and a plurality of rectangular pores 220 arranged in a matrix shape in the filter body 210. In this figure, the size of the pore 220 is exaggerated, but considering the size of the target cell such as the body fluid tumor cell, the pore 220 is smaller in size than the illustrated one, and the number is much larger. In the present specification and drawings, the x direction indicates the horizontal direction and the y direction indicates the vertical direction.

On the other hand, assuming that the pores 220 are arranged in a matrix, the arrangement of the pores 220 in the transverse direction and the longitudinal direction are not necessarily the same, and the pores 220 in the first, third, fifth, And the second, fourth, and sixth rows of pores 220 may be arranged in a staggered manner.

FIG. 5 is a partial cross-sectional view illustrating a target cell collection process. FIG. The pores 220 formed in the filter body 210 are smaller than the diameter of the target cell 2 and larger than the diameter of the non-target cell 3. However, even if the length of the pores 220 is smaller than the diameter of the target cell 2, if the difference is too small, that is, when the pore 220 has a size similar to that of the target cell 2, (2) may be damaged or deformed. Details thereof will be described later.

FIG. 6 is a cutaway perspective view showing a part of the cell trapping filter of FIG. 4; FIG.

The thickness of the filter main body 210 of the cell collection filter 200 is t, the length of the pores 220 in the transverse direction is a, the length of the pores 220 in the longitudinal direction is b, The distance between adjacent two pores 220 along the transverse direction is denoted by l and the distance between two adjacent pores 220 along the longitudinal direction of the cell trapping filter 200 is denoted by m, Should satisfy the following relationship. When this relationship is satisfied, it is possible to recover at least 80% of microscopic target cells such as hematologic tumor cells, and the standard deviation thereof becomes 10% or less.

1. The ratio a / b of a and b is 0.8 to 1.2

2. The ratio l / m of 1 and m is 0.8 to 1.2

3. The ratio of t and a or the ratio t / b of t and b (where x is a or b) is from 0.5 to 1.8

4. The ratio a / l of a and l is 0.9 to 1.6

5. The ratio b / m of b to m is 0.9 to 1.6

Here, the ratio t / x (x is a or b) shown in the above 3 is particularly important for the recovery rate of target cells, and the ratio of a / l and b / m is also important in terms of recovery rate and stability of cell collection filter 200 (Non-deformability). The meaning of each numerical range is as follows.

When the ratio between the transverse length a of the pores 220 and the longitudinal length b of the pores 220, that is, a / b is less than 0.8 or more than 1.2, The length of the target is a relatively long rectangular shape. In this case, it is not suitable for filtration of target cells which are basically circular, and may cause cell deformation.

Next, the distance l between two adjacent pores 220 along the transverse direction of the cell collection filter 200 and the distance between two adjacent pores 220 along the longitudinal direction of the cell collection filter 200 (m), that is, 1 / m is less than 0.8 or more than 1.2, the distribution of a plurality of pores is non-uniformly arranged in any one direction, .

Next, the ratio of the thickness t of the filter body 210 of the cell collection filter 200 to the length or length a or b of the pores 220, that is, t / x, where x is a Or b) is less than 0.5, the error that the target cell passes through the filter becomes large. When t / x is more than 1.8, the error that the non-target cell can not pass through the filter becomes large, There is a greater risk of injury.

The filter body 210 is made of metal, for example, stainless steel, nickel, aluminum, copper, or the like. Although the metal cell collection filter 200 is relatively resistant to the flow pressure of the fluid, if the thickness of the filter body 210 is less than 50% of the length of the pores 220, The target cells collected in the pores 220 may be damaged or deformed while being temporarily deformed and returning to the original shape by the elastic restoring force. There may also be a change in the activity of the cells, which may result in a lower accuracy of cancer diagnosis, for example, by humoral tumor cells (target cells).

On the other hand, when the thickness of the filter body 210 is greater than 80% of the length of the pores 220, the thickness of the filter body 210 becomes excessively large so that non-target cells such as blood cells do not pass through the pores 220 I can not.

For example, when the transverse direction length a and longitudinal direction length b of the pores 220 are respectively 5 μm (micrometers), the thickness t of the filter body 210 is 2.5 μm to 9 μm If the thickness t is less than 2.5 占 퐉 or exceeds 9 占 퐉, the above-described problem arises.

Next, when the ratio of the distance a between the two pores 220 adjacent to each other along the transverse direction of the cell trapping filter 200, that is, a / l is less than 0.9, If the ratio a / l exceeds 1.6, the total volume of the cavities (pores) becomes too large as compared with the total volume of the filter body 210 The rigidity of the filter main body 210 can not be maintained. In this case, the risk of deformation of the filter main body 210 at the time of filtering becomes large.

On the other hand, the ratio of the length (b) in the longitudinal direction of the pore 220 to the distance (m) between two adjacent pores 220 along the longitudinal direction of the cell trapping filter 200, that is, b / If the ratio b / m is more than 1.6, the total volume of the cavity becomes too large as compared with the total volume of the filter body 210 The rigidity of the filter main body can not be maintained.

When the filter main body 210 of the cell collection filter 200 is a polymer, it is difficult to reduce the thickness of the filter. In order to collect the cells, the fluid must be filtered by applying pressure. In this process, the filter body 210 is deformed by the pressure due to the pressure, and the deformation of the filter body 210 causes the cells May be caught or damaged.

Accordingly, in the present invention, the filter main body 210 is made of metal, thereby increasing deformation resistance due to fluid pressure. This makes it possible to reduce the thickness of the filter main body 210. The thickness of the filter main body 210 is set such that the size a of the pores a and the size l of the pores are in a certain ratio The recovery rate of target cells can be greatly increased.

On the other hand, the length a of the pores 220 in the transverse direction and the length b of the pores 220 in the transverse direction may be 40 to 70% of the diameter of the target cells. When the ratio is less than 40%, the selectivity to target cells and non-target cells is lowered. That is, the rate at which non-target cells pass through the pores can be lowered. On the contrary, when the ratio is more than 70%, the percentage of the target cells passing through the pores becomes high, and the target cells become trapped in the pores, and the recovery rate of the target cells decreases. On the other hand, when backwashing to increase the recovery rate, the target cells are damaged or the activity is decreased.

Specifically, in the experiment in which fluid pressure of 100 mmHg was applied to body fluid tumor cells having a diameter of 7.5 to 15 탆, the body fluid tumor cells could pass through the pores 220 having a diameter of 8 탆. When the size of the pores 220 is set to a certain level or more, the distance between the pores 220 becomes large. For example, when the distance l (m) between the pores 220 is 7.5 Mu] m or more, the bacterium tumor cells located between the pores 220 may not be removed from the surface of the filter body 210 by backwashing (i.e., may not be recovered). Here, back washing refers to the flow of the fluid in the direction opposite to the flow of the fluid at the time of collecting the body fluid tumor cells. If the pressure is increased during backwashing of fluids to increase the recovery rate of hematologic tumor cells, the risk of damage to hematologic tumor cells will increase.

Therefore, it is inappropriate to make the length of the pore 220 in the transverse direction longer than the diameter of the target cell any larger than the diameter of the target cell. For the recovery of the target cell of 80% or more and the standard deviation of 10% or less, Or less.

On the other hand, when the length of the pore 220 in the transverse direction is less than 40% of the diameter of the target cell, the selectivity to the target cell and the non-target cell is lowered, and the size of the pore 220 becomes too small So that the distance between the adjacent pores 220 is also reduced. In this case, it is difficult to manufacture the cell collection filter 200, and the cell collection filter 200 may be damaged during backwashing.

The filter body 210 may be made of nickel or a nickel alloy. The effect when the filter main body 210 is made of metal is as described above. For example, the filter body 210 can be obtained by plating nickel on a wafer by electroforming and then separating the nickel layer, but the present invention is not limited to such a manufacturing method. For example, it is also possible to use an etching method using MEMS technology to form micrometer-sized pores 220.

On the other hand, although not shown, it is also possible to form a hydrophilic thin film layer or a hydrophilic thin film layer on the surface of the filter main body 210. In this case, even if the pressure is relatively small, the fluid can pass through the pores 220, the thickness of the filter body 210 can be reduced, and the risk of damage or deformation of the cell trapping filter 200 at the time of filtering is low .

FIG. 7 is a fluorescence staining image in which multiple tumor cells in recovered body fluid are identified as biomarkers (CK, Vimentin, CD45). DAPI (4,6-diamidino-2-phenylindole) is a fluorescent dye that specifically binds to the A: T base pair of DNA. The DAPI solution is diluted 1: 100 in the recovered fluid and incubated at room temperature for 10 minutes Cells treated with biomarkers (CK, Vimetin, CD45) can then be observed using a fluorescence microscope. The number of cells stained with DAPI was 282, and the amount of cells identified by the biomarker was 38, indicating that the yield was 13.5%.

FIG. 7 shows the results of staining of multiple tumor cells in recovered body fluid with biomarkers CK (cytokeratin), vimentin, CD45, DAPI (4,6-diamidino-2-phenylindole) for counterstaining, It is a photograph confirmed with a microscope. CK was used to select multiple tumor cells as a marker of specific tumor cells, vimentin was used as an epithelial cell marker, and CD45 was used to distinguish it from multiple tumor cells by excluding CD45 positivity as a common white blood cell antigen. Thus, multiple tumor cells can be DAPI + / CK + / vimentin + / CD45- cells. It was confirmed that the multiple tumor cells recovered using the tumor cell separator showed a recovery rate of 13.5%.

8 is a graph comparing the recovery rates of multiple tumor cells using a cell collection device. A to C are less than 10% in terms of a multiple tumor cell isolation ratio based on existing documents, but it can be confirmed that multiple tumor cells can be obtained more efficiently as 13.5% by using the above cell collection device. 8 is a graph comparing the recovery rates of multiple tumor cells in body fluid using a tumor cell separating apparatus. A to C showed recovery rates of less than 8% at the recovery rate when multiple tumor cells were separated using the methods of the existing literature, while the recovery rate was 13.5% when the tumor cell separation apparatus was used , It was confirmed that multiple tumor cells can be obtained more efficiently than the conventional methods.

It will be understood by those skilled in the art that the foregoing description of the present invention is for illustrative purposes only and that those of ordinary skill in the art can readily understand that various changes and modifications may be made without departing from the spirit or essential characteristics of the present invention. will be. It is therefore to be understood that the above-described embodiments are illustrative in all aspects and not restrictive. For example, each component described as a single entity may be distributed and implemented, and components described as being distributed may also be implemented in a combined form.

The scope of the present invention is defined by the appended claims, and all changes or modifications derived from the meaning and scope of the claims and their equivalents should be construed as being included within the scope of the present invention.

1: Cell separator
10: Pipetting module
20: Operation module
100: cell collection device
200: Cell collection filter
210:
220: Handwork

Claims (7)

As a humoral tumor cell collection filter,
A plurality of rectangular pores arranged in a matrix form are provided in a filter body made of metal,
The thickness of the filter body is t, the length of the pores in the transverse direction is a, the length of the pores in the longitudinal direction is b, the distance between adjacent pores along the transverse direction of the filter is l, The ratio a / b of a and b is 0.8 to 1.2, the ratio l / m of 1 and m is 0.8 to 1.2, and the ratio of t and a or the ratio of t and b Wherein the ratio t / x (where x is a or b) is 0.5 to 1.8. The method according to claim 1,
Wherein the ratio a / l of a and l is 0.9 to 1.6, and the ratio b / m of b and m is 0.9 to 1.6.
The method according to claim 1,
Wherein the a or b has a size of 40 to 70% with respect to the diameter of the target cell.
The method according to claim 1,
Wherein the filter body is made of nickel or a nickel alloy.
As a body fluid tumor cell collection device,
A tube having a hollow portion through which fluid can flow inside,
And a humoral tumor cell collection filter provided on the lower side of the tube, according to any one of claims 1 to 4.
6. The method of claim 5,
And a plurality of bacterium tumor cell collecting filters arranged sequentially from the upstream side to the downstream side in the flow direction of the fluid,
Wherein the bacterium tumor cell collection filter disposed on the upstream side has the shape pores larger in size than the filter disposed on the downstream side,
And a storage layer for temporarily storing the fluid is provided between the filters.
The method according to claim 6,
Wherein the number of the shape pores of the humorous tumor cell collection filter disposed on the upstream side is smaller than the number of the shape pores of the humorous tumor cell collection filter disposed on the downstream side.

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