JP2015188323A - Cell-capturing metal filter, cell-capturing metal filter sheet, manufacturing method of cell-capturing metal filter sheet, and cell-capturing device - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a cell-capturing metal filter by which cell-capturing metal filters can be efficiently mass-produced, a cell-capturing metal filter sheet, a manufacturing method of the cell-capturing metal filter sheet, and a cell-capturing device.SOLUTION: According to a cell-capturing metal filter sheet 10, separating the cell-capturing metal filter sheet 10 on which a plurality of filter regions 22 are formed along a separation line L makes it possible to easily obtain the plurality of filter regions 22 comparing to a case of individually manufacturing the plurality of filter regions 22, so that filters can be efficiently mass-produced.

Description

  The present invention relates to a cell capture metal filter for capturing cells contained in a cell dispersion, a cell capture metal filter sheet provided with the cell capture metal filter, a method for producing the cell capture metal filter sheet, and the cell capture The present invention relates to a cell trapping device including a metal filter.

Blood contains many blood cell components such as red blood cells, white blood cells, and platelets, and the number is said to be 3.5 to ⁹ × 10 ^{9 in} 1 mL of blood. In contrast, for example, only a few circulating cancer cells in the blood, which are tumor cells infiltrated into blood vessels from primary tumors or metastatic tumors, are present in 1 mL of blood.

  Circulating cancer cells in the blood circulate in the peripheral bloodstream of humans, so early detection of cancer and early development of effective medicines are possible if the circulating cancer cells in the blood can be captured in the same state as in the bloodstream. It becomes. For this reason, a filter for efficiently capturing predetermined cells from blood cell components has been studied.

  Such a filter can be manufactured, for example, by the method described in Patent Document 1 below. In Patent Document 1 below, a copper substrate on which a resist pattern is formed is plated to form a metal plating layer, and then the copper substrate is removed by chemical dissolution to obtain a plating layer that becomes a metal filter. Is described.

International Publication No. 2013/054786

  However, if the metal filter described in Patent Document 1 is to be mass-produced as a metal filter for capturing cells, repeating the process of removing the copper substrate after metal plating of the copper substrate may complicate the production process. There is sex.

  Accordingly, the present invention aims to provide a cell-trapping metal filter, a cell-trapping metal filter sheet, a method for producing a cell-trapping metal filter sheet, and a cell-trapping device that can efficiently mass-produce cell-trapping metal filters. And

  The cell-trapping metal filter sheet according to the present invention is a filter sheet in which a plurality of filter regions in which a plurality of through holes are formed in the thickness direction of a sheet whose main component is a metal are provided apart from each other, and the plurality of filter regions A separation line is provided to allow the two to be separated from each other.

  In the cell-trapping metal filter sheet according to the present invention, by separating the sheet on which the plurality of filter regions are formed along the separation line, the plurality of filters can be easily manufactured as compared with the case where the plurality of filters are individually manufactured. Therefore, the filter can be mass-produced efficiently. Furthermore, according to the above filter sheet, a plurality of filters can be obtained by separating a plurality of filter regions based on a separable separation line. For example, the separation line described in the filter sheet As compared with the case where a plurality of filters are divided by a cutter or the like, a filter having a stable outer dimension can be obtained. Therefore, when the filter can be efficiently mass-produced, the yield as a filter can be improved.

  Moreover, it is preferable that the thickness of a sheet | seat is 10 micrometers-30 micrometers. When the thickness of the sheet is 10 μm to 30 μm, the sheet is excellent in handleability and can be easily separated along the cutting line.

  In addition, the separation line has a predetermined interval and is composed of a plurality of small holes provided continuously, and the predetermined interval between the adjacent small holes is preferably 0.1 mm to 0.7 mm. . In this case, in the cell-trapping metal filter sheet, the separation line is intermittently provided with the cell-trapping metal filter, so that the separation at the separation line can be easily performed.

  Further, the surface of the sheet is preferably plated with gold. Since the surface of the metal sheet is gold-plated, the adhesion to the cells trapped in the filter region becomes uniform, and it can be expected to improve the reproducibility of data.

  The cell-trapping metal filter according to the present invention is preferably obtained by separating the cell-trapping metal filter sheet along the separation line.

  Since the cell-trapping metal filter according to the present invention is obtained by separating the cell-trapping metal filter sheet along the separation line, a cell-trapping metal filter having substantially the same external dimensions can be efficiently produced.

  A cell capture device according to the present invention includes a lid member having an introduction flow path for introducing a test liquid into the interior, and a storage member having a discharge flow path for discharging the test liquid to the outside. Preferably, the cell capture metal filter is provided on the flow path inside the housing between the introduction flow path and the discharge flow path so that the test solution passes through the through hole.

  In the cell capture device according to the present invention, the test solution introduced into the inside from the introduction channel passes through the cell capture metal filter and is discharged from the discharge channel to the outside of the housing. Further, desired cells in the test solution that have passed through the cell-trapping metal filter are captured in the filter region. Since the above device is manufactured using a cell capture filter having excellent mass productivity, it is possible to improve the mass productivity of the device.

  The method for producing a cell-trapping metal filter sheet according to the present invention includes a step of laminating a photoresist on a metal foil, and a plurality of first light-transmitting regions each formed by a plurality of light-transmitting portions on the photoresist. A step of superposing and exposing a photomask having a second light-transmitting region having a light-transmitting portion formed in a substantially linear shape so as to partition each of the plurality of first light-transmitting regions; Removing the uncured part to form a photoresist pattern, forming a metal plating pattern lower than the height of the photoresist pattern by metal plating between the photoresist patterns, and removing the metal foil by chemical dissolution. A step of obtaining a structure composed of a metal plating pattern and a photoresist pattern, and removing the photoresist pattern from the structure, Beauty includes obtaining a metal plating pattern having a through hole corresponding to the second light transmitting region.

  In the method for producing a cell-trapping metal filter sheet according to the present invention, both a filter region and a separation line can be produced using a single photoresist, so that a filter sheet in which a plurality of filter regions are formed can be more efficiently produced. Can be produced. Moreover, the cell-trapping metal filter having the filter region can be easily separated by separating the cell-trapping metal filter sheet with a separation line. Moreover, when the separation line is formed in a substantially straight line between adjacent filter regions, the outer dimensions of the cell trapping sheet can be made more stable when the cell trapping sheet is separated. In this case, since the outer dimensions are stabilized, the yield as the cell-trapping metal filter sheet can be improved. Therefore, a cell capture metal filter can be manufactured efficiently.

  According to the present invention, it is possible to provide a cell-trapping metal filter, a cell-trapping metal filter sheet, a method for producing a cell-trapping metal filter sheet, and a cell-trapping device capable of efficiently mass-producing a cell-trapping metal filter. it can.

It is a schematic perspective view of the cell trapping device concerning this embodiment. It is a schematic plan view of the cell trapping device shown in FIG. FIG. 3 is a sectional view taken along line III-III in FIG. 2. It is a figure explaining the structure of a cell capture metal filter. It is a figure explaining the through-hole formed in the filter area | region of a cell capture metal filter. It is a schematic top view explaining the structure of the cell capture metal filter sheet which concerns on this embodiment. It is the elements on larger scale of the separation line of a cell capture metal filter sheet. (A)-(h) is process drawing explaining the manufacturing method of the cell capture metal filter sheet shown in FIG. (A)-(g) is process drawing explaining the other manufacturing method of the cell capture metal filter sheet shown in FIG. FIG. 10 (A) is a diagram for explaining a modification of the separation line of the cell capture metal filter sheet of the present invention, and FIG. 10 (B) is a modification of the separation line of the cell capture metal filter sheet of the present invention. It is another figure to explain.

  DESCRIPTION OF EMBODIMENTS Hereinafter, embodiments for carrying out the present invention will be described in detail with reference to the accompanying drawings. In the description of the drawings, the same elements are denoted by the same reference numerals, and redundant description is omitted. Further, the drawings are schematic diagrams for helping understanding, and are different from actual ones in dimensions, size ratios, and the like. In addition, the “process” in this specification does not only indicate an independent process, but even if it cannot be clearly distinguished from other processes, the term is used as long as the intended action of the process is achieved. included. Moreover, the numerical range shown using "to" shows the range which includes the numerical value described before and behind "to" as a minimum value and a maximum value, respectively.

[Cell capture device]
First, the cell trapping device 1 that traps cells contained in a cell dispersion will be described with reference to FIGS. FIG. 1 is a schematic perspective view of a cell trapping device 1 according to this embodiment. FIG. 2 is a schematic plan view of the cell trapping device 1 shown in FIG. 3 is a cross-sectional view taken along the line III-III in FIG.

  The cell trapping device 1 according to the present embodiment includes a transparent resin casing 2 and a cell trapping metal filter 20 that allows a cell dispersion to be a test solution to pass therethrough. The cell-trapping metal filter 20 is made of a sheet whose main component is a metal, and a plurality of through holes are formed in the thickness direction of the sheet. When the cell dispersion liquid passes through the filter region 22 in which a plurality of through holes are formed, the cells to be captured are captured.

  As the cell dispersion, blood, body fluid, or the like can be used. In addition, it is most convenient to use peripheral blood circulating in the body, and in this case, blood circulating cancer cells (CTC) can be captured by the cell capturing metal filter 20. CTC (Circulating Tumor Cell) is a cell that circulates in a human body through blood vessels and lymphatic vessels. If CTCs can be captured in the same state as in the bloodstream, early detection of cancer and early development of effective medicines are possible.

  The housing 2 includes a lid member 3 and a storage member 4. Furthermore, a cell trapping metal filter 20 is provided between the lid member 3 and the storage member 4. In the present embodiment, a configuration in which the cell trapping metal filter 20 is attached to the storage member 4 will be described.

  The lid member 3 has an introduction flow path 5 for introducing the cell dispersion into the interior and a recess 3a. The introduction channel 5 communicates with the recess 3a through an introduction port 5a provided in the recess 3a. The recess 3a includes a filter region so as to include all of the filter regions 22 provided with a plurality of through holes 22a in the cell trapping metal filter 20 attached to the storage member 4 when the cell trapping device 1 is viewed from above. 22 (see FIG. 2). The recess 3a functions as a space (introduction region) for introducing the cell dispersion liquid from the introduction flow path 5 in order for the cell dispersion liquid to pass through the cell trapping metal filter 20 (filter region 22 in the present embodiment). .

  The storage member 4 has a discharge channel 6, a recess 4a, and a recess 4b for discharging the cell dispersion from the inside to the outside. The discharge channel 6 communicates with the recess 4a through a discharge port 6a provided in the recess 4a. The concave portion 4a includes a filter region so as to include all of the filter region 22 provided with a plurality of through holes 22a in the cell trapping metal filter 20 attached to the storage member 4 when the cell trapping device 1 is viewed from above. 22 (see FIG. 2). The concave portion 4 a functions as a space (discharge region) for guiding the cell dispersion liquid that has passed through the cell trapping metal filter 20 to the discharge channel 6. Further, the storage member 4 is formed with a recess 4b as an attachment region (attachment region) for attaching the cell-trapping metal filter 20. In addition, the recessed part 3a and the recessed part 4a may be formed so that a part of filter area | region 22 in which the through-hole 22a was provided among the cell trapping metal filters 20 may be included.

  Since the concave portion 3a of the lid member 3 and the concave portion 4a of the storage member 4 are configured to face each other, a combination of the concave portion 3a and the concave portion 4a provides a space for the cell dispersion to flow. Provided inside the housing 2. By introducing the cell dispersion liquid from the introduction flow path 5 connected to the space inside the housing 2 and discharging the cell dispersion liquid from the discharge flow path 6 similarly connected to the space, the introduction flow path 5 A flow path of the cell dispersion liquid is formed toward the discharge flow path 6.

  In the present embodiment, the introduction port 5a of the lid member 3 is arranged at a position outside the observation region where the filter region 22 is located when the cell capture device 1 is viewed from above, and the introduction channel 5 It extends along the in-plane direction of the metal filter 20. By having such a configuration, it is possible to avoid the presence of a structure that obstructs the field of view when observing the filter region 22 of the cell trapping metal filter 20 from the outside of the cell trapping device 1. Therefore, the cell capture device 1 can be directly and stably fixed to the pedestal of the microscope, and can be observed without disassembling the cell capture device 1. The in-plane direction refers to all directions in the plane of the cell trapping metal filter 20 and is all directions along a plane parallel to the plane of the cell trapping metal filter 20. Further, “along the in-plane direction” means a direction that forms an angle of 60 ° or less, preferably 45 ° or less, more preferably 30 ° or less with respect to the in-plane direction. The direction in which the introduction flow path 5 and the discharge flow path 6 are connected to the space inside the housing 2 is not limited to the in-plane, and may be a direction perpendicular to the plane.

  As shown in FIG. 2, the housing 2 is substantially rectangular when viewed from above, and preferably has a size of 5 mm × 5 mm to 100 mm × 100 mm. Further, the thickness of the housing 2 is preferably 5 mm to 30 mm. The lid member 3 is preferably made of a material having translucency with respect to light having a wavelength used for detecting cells to be observed, particularly light in the visible light region. Examples of the material of the lid member 3 include, but are not limited to, polymers such as glass, quartz glass, plastic (particularly acrylic resin), and polydimethylsiloxane.

  When the material of the housing 2 is made of a translucent member, it is not necessary to take out the cell trapping metal filter 20 (filter region 22 in the present embodiment) that has passed the cell dispersion liquid from the cell trapping device 1. It is possible to prevent misjudgment caused by adhesion of dust to the cell trapping metal filter. In addition, since it is not necessary to expose the cell dispersion liquid, which may be contaminated with various pathogenic bacteria and viruses, it is possible to reduce complexity in ensuring work safety.

  The lid member 3 and the storage member 4 are not necessarily made of the same material, but are preferably the same material from the viewpoint that stress applied to the fitting portion at the time of assembly is equally applied to the lid member side and the storage member side. The material of the housing 2 is preferably a low autofluorescent acrylic resin, and particularly preferably polymethylmethacrylate because the device can be mass-produced. In the case where the housing 2 is made of a polymer such as acrylic resin or polydimethylsiloxane, it is preferable to produce it by injection molding from the viewpoint of production efficiency. In general, when observing cancer cells or the like, the target cells are stained with a fluorescent reagent, and then irradiated with ultraviolet or visible light having a wavelength of 300 to 800 nm to observe fluorescence. I do. Therefore, it is preferable to select a material having low autofluorescence as the lid member 3 so that the material itself does not emit when irradiated with light in the above wavelength range (this is referred to as “low autofluorescence”). In general, an organic polymer having an aromatic ring, such as a resin such as polystyrene or polycarbonate, has strong autofluorescence and is often not suitable for the above purpose.

  The introduction flow path 5 and the discharge flow path 6 are preferably made of resin such as polypropylene (PP). The outer diameters of the introduction flow path 5 and the discharge flow path 6 are preferably 0.4 mm to 2.4 mm, and the inner diameters are preferably 0.2 mm to 2.2 mm. Moreover, it is preferable that the internal diameter of the inlet 5a connected with the recessed part 3a and the internal diameter of the discharge port 6a connected with the recessed part 4a are 0.4 mm-2.5 mm.

  When the introduction flow path 5 and the discharge flow path 6 are made of a transparent resin, it is preferable from the viewpoint that the passage of the cell dispersion liquid can be confirmed. The housing, the lid member, and the storage member may be made of different resins.

  Further, as shown in FIG. 3, the housing 2 is formed by fixing the lid member 3 and the storage member 4. The shape of the housing 2 is not particularly limited. After passing the cell dispersion through the filter region 22 of the cell trapping metal filter 20 housed inside, the through hole 22a of the filter region 22 is observed from the outside, In order to observe the substance remaining on the surface of the cell trapping metal filter, it is preferable that the upper and lower surfaces of the surface facing the main surface of the cell trapping metal filter 20 are flat and parallel to each other.

  Moreover, it is preferable that the lid member 3 and the storage member 4 forming the housing 2 in the cell trapping device 1 are welded. Welding refers to bonding these materials directly by melting part of the material itself at a high temperature. Welding is sometimes called fusing, heat bonding, or heat sealing. Examples of the welding method include thermal welding, ultrasonic welding, and high-frequency welding. After the cell-trapping metal filter 20 is placed in the recess 4b (attachment region), the periphery thereof is welded by heat or ultrasonic treatment to fix the lid member 3 and the storage member 4. Thereby, the airtightness of the cell trapping device can be obtained with certainty, and high liquid sealability can be ensured when the cell dispersion liquid is allowed to flow into the cell trapping device. Moreover, since the joining by welding can be performed in a short time, the productivity is excellent. Among the above-described welding methods, ultrasonic welding or high-frequency welding is particularly preferable because only a necessary portion of the material can be melted in a shorter time. When the cell capture metal filter 20 that has captured cells is taken out of the cell capture device 1 and observed, for example, when it is conceivable to disassemble the device after cell capture, the lid member 3 and the storage member 4 are, for example, a clip. It may be fixed by being sandwiched between various fixing members.

  The cell capture device 1 according to the present embodiment may have other shapes. For example, the shape of the space for the cell dispersion to flow may be changed from a rectangle to a substantially circle (for example, an ellipse). That is, the shapes of the lid member and the storage member may be elliptical. The cell trapping device may change the shape of the cell trapping metal filter or the shape of the region functioning as the cell trapping metal filter depending on the shape of the space formed inside.

  An example of a method for using the cell capture device 1 will be described. Hereinafter, an example in which the presence or absence of CTC in the cell dispersion liquid is detected using the cell capture device 1 will be described.

  First, the cell dispersion liquid is introduced into the introduction channel 5 of the cell trapping device, passed through the cell trapping metal filter 20, and then discharged from the discharge channel 6. Thereby, cells containing CTC may be concentrated on the cell capture metal filter 20, and it may be confirmed whether CTC is present in the concentrated cells. Examples of the introduction of the cell dispersion liquid into the introduction channel 5 include a method using pressurization or decompression, a method using a peristaltic pump, and the like. Here, “concentration” means that the existence ratio of the number of cells to be separated and concentrated with respect to the number of white blood cells increases before and after the test solution is passed through the cell capture device. Further, the concentration may be performed by using means such as heating, freezing, pressurization, and decompression.

  When CTC is concentrated by the above method, not only CTC but also blood cells such as leukocytes are simultaneously concentrated. For this reason, it is necessary to confirm whether or not the collected cells contain epithelial cells derived from the primary tumor focus. For example, after concentrating CTC by the above-mentioned method, it can be confirmed that it is an epithelial cell by staining with an antibody against a fluorescently labeled epithelial cell marker. Examples of the antibody against the epithelial cell marker include an anti-Cytokeratin antibody.

  For example, the concentrated cells can be stained and observed as follows. A formalin solution is introduced from the introduction flow path 5 of the cell trapping device 1 after concentration of cells to protect and fix the state of the cells on the cell trapping metal filter 20, and after washing, the staining solution is washed with a nonionic surfactant. After allowing the cells to enter the cells, an anti-Cytokeratin antibody solution is introduced into the cells and allowed to stand for a predetermined time. Subsequently, a washing buffer is introduced into the introduction channel 5 of the cell capture device, and unreacted antibodies are washed away. Subsequently, the cell trapping device 1 is directly fixed to the microscope base and observed with a fluorescence microscope. Before introducing the antibody solution into the cell capture device 1, a blocking buffer for suppressing non-specific reaction of the antibody may be introduced.

  Moreover, you may confirm that it is CTC by collect | recovering the cells concentrated by said method and analyzing a gene. The cells can be collected, for example, by introducing a buffer from the discharge channel side of the cell capture device and collecting from the introduction channel side. For example, mutations in genes such as p53, K-RAS, H-RAS, N-RAS, BRAF, and APC can be analyzed to confirm that it is CTC. In addition, the results of these gene analyzes can also be used for the subsequent determination of the patient's treatment policy. Or you may confirm that it is CTC by measuring the telomerase activity etc. of the cell concentrated by said method.

  After the detection of the presence or absence of CTC in the cell dispersion is completed, a buffer is introduced from the discharge flow channel 6 side of the cell capture device and discharged from the introduction flow channel 5 side, thereby being captured by the cell capture metal filter 20. It is also possible to wash away the cells and reuse the cell trapping device 1.

[Cell capture metal filter]
Next, the cell trapping metal filter according to this embodiment will be described. In the present embodiment, the cell trapping metal filter 20 is obtained by being separated from the cell trapping metal filter sheet 10 described later. FIG. 4 is a diagram for explaining the structure of the cell-trapping metal filter 20.

  As shown in FIG. 4, the cell trapping metal filter 20 has a filter region 22 in which a plurality of through holes 22a (through holes) are formed. The through hole 22 a is formed in the thickness direction of the metal sheet 21.

  The shape of the through hole 22a on the surface of the metal sheet 21 is a rectangle or a rounded rectangle (hereinafter, these are collectively referred to as “substantially rectangular”). A plurality of through holes 22a are formed in the filter region 22 with a predetermined interval.

  In FIG. 4, XY coordinate axes along the main surface of the cell-trapping metal filter 20 are shown for explanation. In the cell-trapping metal filter 20 of FIG. 4, the longitudinal direction of the shape of the through hole 22a is formed along the X-axis direction.

  The material of the metal sheet 21 forming the cell trapping metal filter 20 is mainly composed of metal. The main component refers to the component having the largest proportion of the material forming the metal sheet. By using a metal as the main component of the material of the cell-trapping metal filter 20, the variation in the size of the through-hole 22a can be reduced. With this configuration, it is possible to separate and concentrate the cells to be captured with high separation accuracy.

  In addition, since metal is more rigid than other materials such as plastic, its size and shape are easily maintained even when force is applied from the outside. At this time, among the components contained in the cell dispersion, a component that is slightly larger than the pore diameter of the through-hole and easily deformable than CTC (for example, if the cell dispersion is blood, white blood cells and the like) are deformed and passed. It is considered that high-precision separation and concentration are possible.

  Examples of the metal material used for the metal sheet 21 include, but are not limited to, gold, silver, copper, aluminum, tungsten, nickel, chromium, and alloys of these metals. In addition, the metal may be used alone, or may be used as an alloy with another metal or a metal oxide in order to impart functionality. From the viewpoint of price and availability, it is preferable to use nickel, copper, gold, and a metal containing these as a main component, and it is particularly preferable to use a metal containing nickel as a main component. Moreover, when the metal sheet 21 is formed from a material whose main component is nickel, it is preferable that the nickel surface is plated with gold. Gold plating can prevent oxidation of the filter surface. For this reason, the adherence of the capture target cells to the filter becomes uniform, and the reproducibility of the data can be improved.

  The thickness of the cell trapping metal filter 20 is preferably 10 μm to 30 μm. When the film thickness is in the above range, the cell trapping metal filter 20 is easy to handle and is suitable for precision processing.

The size of the filter region 22 of the cell-trapping metal filter 20 ^is preferably 25mm ² ~1000mm 2. More preferably 25mm ² ~225mm ^2, more preferably 25 mm 2 100 mm ^2. When the size of the filter region 22 is 1000 mm ² or less, the dead space is reduced. If it is 25 mm ² or more, the processing time is shortened. For example, when concentrating CTC from 1mL of blood, the size of the filter region 22 is suitable 25mm ² ~1000mm ^2.

  Next, the shape of the through hole 22a provided in the cell trapping metal filter 20 will be described. Of the size of the through hole 22a having a substantially rectangular shape, the range of the length of the short side is approximately 5.0 μm to 15.0 μm. On the other hand, the length of the long side of the through hole 22a can be appropriately changed within a range in which the through hole 22a does not intersect the outer edge of the cell trapping metal filter 20, and the range is approximately 10 μm to 5 mm. The hole diameter of the through hole 22a may be changed according to the size of the cell to be captured.

  The plurality of through-holes 22a are preferably arranged close to each other in the same direction. If comprised in this way, the improvement of the aperture ratio shown by the area of the through-hole (single hole or through-hole) per unit area in the filter surface can be aimed at.

  In the filter region 22, the opening ratio of the through hole 22a is preferably 5% to 50%, more preferably 5% to 40%, and further preferably 5% to 30%. The aperture ratio refers to the ratio of the area occupied by the through hole 22a to the area of the region functioning as a filter, and can be calculated by measuring using a spectrophotometer. Here, the area of the region functioning as a filter refers to the smallest region among rectangles formed so as to abut on the plurality of through holes 22a and include all the through holes 22a. The aperture ratio is preferably as large as possible from the viewpoint of preventing clogging, but when it is 50% or less, the strength of the filter region 22 can be sufficiently secured. Moreover, when it is 5% or more, clogging hardly occurs.

  Here, with reference to FIG. 5, the modification of a through-hole is demonstrated. FIG. 5 is a diagram for explaining the through hole 22 a of the filter region 22. As a typical modification of the shape of the through hole, as shown in FIG. 5, (A) a circle, (B) a rectangle, (C) a rounded rectangle (the corner of the end is rounded), (D) Rounded rectangle (rectangular short side is arc-shaped), (E) Wave shape (three rounded rectangular single holes are connected to each other at the end), (F ) Circular wave shape (5 semicircular grooves are alternately facing each other and connected at the end). The shape of the through hole is not limited to the example shown in FIG. 5. For example, it may be a wave shape in which four or more round holes of a rounded rectangle are connected, or it is not a rounded rectangle but a rectangle with rounded corners. It can also be set as the connection through-hole of the shape which connected two or more single holes.

[Cell capture metal filter sheet]
The cell trapping metal filter sheet 10 constituting the cell trapping metal filter 20 according to the present embodiment will be described. The cell capture metal filter sheet 10 is a sheet for efficiently producing a plurality of cell capture metal filters 20. FIG. 6 is a schematic top view illustrating the configuration of the cell-trapping metal filter sheet 10 according to the present embodiment. FIG. 7 is a partially enlarged view of the separation line L of the cell trapping metal filter sheet 10.

  As shown in FIG. 6, the cell-trapping metal filter sheet 10 is provided with a plurality of filter regions 22 separated from each other. The cell-trapping metal filter sheet 10 is provided with a separation line L between the filter regions 22 so that the filter regions 22 can be separated from each other. In the cell capture metal filter sheet 10, the cell capture metal filter 20 is obtained by separating along the separation line L. The filter region 22 of the cell-trapping metal filter sheet 10 is preferably provided in the approximate center of the cell-trapping metal filter 20 after being separated along the separation line L.

  In the filter region 22, a plurality of through holes 22 a are formed in the thickness direction of the metal sheet 21, and when the cell trapping metal filter sheet 10 is separated by the separation line L, the filter region 22 of the cell trapping metal filter 20. Function as. For this reason, each cell capture metal filter 20 can be used for the cell capture device 1.

  Similar to the metal sheet 21 of the cell-trapping metal filter 20, the cell-trapping metal filter sheet 10 is mainly composed of metal. Examples of the metal material include, but are not limited to, gold, silver, copper, aluminum, tungsten, nickel, chromium, and alloys of these metals.

  Moreover, it is preferable that the surface of the cell-trapping metal filter sheet 10 is gold-plated. Since the surface of the filter can be prevented from being oxidized by gold plating, the adherence of the cells to be captured and blood cell components to the filter is uniform, and the reproducibility of data can be achieved.

  Further, as shown in FIG. 7, the separation line L includes a plurality of small holes 31 that are continuously provided with a predetermined interval. In the present embodiment, the small holes 31 are provided with the small holes 31 adjacent to each other at substantially equal intervals. Preferably, the interval a in which the small holes 31 are formed is preferably 0.1 mm to 0.7 mm, and more preferably 0.1 mm to 0.5 mm. More preferably, the pitch b between the small holes 31 is about 0.5 mm, and the diameter of the small holes 31 is preferably about 0.2 mm. However, the interval a of the small holes 31, the pitch b between the small holes 31, and the diameter of the small holes 31 are not limited thereto.

  When the separation line has a plurality of continuous small holes 31 formed at predetermined intervals, stress is concentrated on the separation line L when the cell-trapping metal filter sheet 10 is folded in accordance with the separation line. . At this time, the cell-trapping metal filter sheet 10 is separated along the separation line L. For this reason, the cell capture metal filter 20 can be easily separated by the separation line L. Moreover, when the predetermined space | interval of the mutually adjacent small holes 31 is 0.1 mm-0.7 mm, when the cell capture | acquisition metal filter sheet 10 is mountain-folded according to a separation line, stress tends to concentrate on a separation line. Become. For this reason, the cell capture metal filter sheet can be more easily separated by the separation line L.

[Method for producing cell capture metal filter sheet]
A method for producing the cell-trapping metal filter sheet will be described.

  The method of manufacturing a metal filter according to the embodiment includes a step of laminating a photoresist on a metal foil, a plurality of first light-transmitting regions each formed by a plurality of light-transmitting portions on the photoresist, and a plurality of light-transmitting regions. A step of overlaying and exposing a photomask having a second light-transmitting region in which the light-transmitting portions are formed in a substantially linear shape so as to partition the first light-transmitting regions, and developing and uncured portions of the photoresist Forming a photoresist pattern by removing the metal, forming a metal plating pattern lower than the height of the photoresist pattern by metal plating between the photoresist patterns, removing the metal foil by chemical dissolution, A step of obtaining a structure composed of a plating pattern and a photoresist pattern; and removing the photoresist pattern from the structure to form a first light-transmissive region and a second light-transmissive region And a step of obtaining a metal plating pattern having a through hole corresponding to the band, the.

  (A)-(h) of FIG. 8 is process drawing explaining the manufacturing method of the cell capture metal filter sheet 10. FIG.

  FIG. 8A shows a state in which the metal foil 52 is laminated on the carrier layer 51. In the step shown in FIG. 8B, a photoresist 53 made of a photosensitive resin composition is formed on the metal foil 52 (a step of laminating a photoresist). Subsequently, in the step shown in FIG. 8C, the photoresist 53 is irradiated with actinic rays (UV light) through the photomask 54, and the exposed portion is photocured to form a cured photoresist (photograph). A step of exposing the mask in an overlapping manner). Subsequently, in the step shown in FIG. 8D, the photoresist 53 other than the cured product is removed to form photoresist patterns 53a and 53b. Reference numeral 53b in FIG. 8D is a portion that remains after the uncured photoresist is removed, and is a portion where a small hole is formed in a later step. (Step of forming a photoresist pattern). 8E, a plating pattern (plating layer) 55 is formed on the metal foil 52 on which the photoresist patterns 53a and 53b made of a cured product are formed. (Process of forming a metal plating pattern). Subsequently, as shown in FIG. 8F, the metal foil 52 and the carrier layer 51 are peeled off. (Step of obtaining a structure). Subsequently, in the step shown in FIG. 8G, the metal foil 52 is removed by chemical dissolution. As a result, photoresist patterns 53a and 53b and a plating pattern 55 made of a cured photoresist remain. Subsequently, in the step shown in FIG. 8H, the photoresist patterns 53a and 53b made of the cured photoresist are removed, and the metal filter made of the plating pattern 55 is collected. The cell trapping metal filter 20 has a through hole 22a. (Step of obtaining a metal plating pattern).

  (A)-(g) of FIG. 9 is process drawing explaining the other manufacturing method of the cell capture metal filter sheet 10. FIG.

  The manufacturing method shown in FIG. 9 is different from the manufacturing method shown in FIG. 8 in that a metal substrate 62 is used instead of the metal foil 52. In this case, the cell-trapping metal filter sheet 10 is manufactured by the same method as the manufacturing method shown in FIG. 8 except that there is no step of peeling the metal foil 52 and the carrier layer 51 shown in FIG. Can do. However, since the substrate 62 is thicker than the metal foil 52, the chemical dissolving agent and time used in the step of removing the substrate 62 by chemical dissolution in the melting step are increased as compared with the case of removing the metal foil 52. .

  Hereinafter, each process will be described in more detail.

(Lamination process)
First, a state in which the metal foil 52 is laminated on the carrier layer 51 is shown. As the metal foil 52, a metal foil that can be removed by etching can be used. Specifically, a foil of copper, nickel, nickel / chromium alloy, or the like is used, and a copper foil is preferable. The copper foil can be easily removed by chemical etching, and the adhesive strength with the photoresist is superior to other materials. It is preferable to use a carrier layer 51 made of a copper-clad laminate with a metal foil 52 pasted to such an extent that it can be peeled off in a later step, because it is excellent in workability and handling in the process of manufacturing a cell-trapping metal filter. . Specifically, peelable copper foil (manufactured by Hitachi Chemical Co., Ltd.) can be used as the above configuration. The peelable copper foil is a copper foil composed of at least two layers of an ultrathin copper foil and a carrier layer.

  FIG. 8B is a view showing a state in which a photoresist 53 made of a photosensitive resin composition is formed on the metal foil 52. As the photoresist 53, either a negative type or a positive type can be used, but a negative type photoresist is preferable. The negative photoresist preferably contains at least a binder resin, a photopolymerizable compound having an unsaturated bond, and a photopolymerization initiator. In addition, when using a positive photoresist, the exposed portion of the photoresist layer exposed to actinic rays is increased in solubility in the developer, so that the exposed portion is removed during the development process. Will be. Hereinafter, a case where a negative photoresist is used will be described.

  The thickness of the finally obtained cell-trapping metal filter sheet 10 is equal to or less than the thickness of the photoresist pattern. For this reason, it is necessary to form a photoresist layer having a thickness suitable for the thickness of the target cell-trapping metal filter 20. For example, when producing a cell-trapping metal filter having a thickness of 15 μm or less, it is preferable to use a photoresist having a thickness of 15 μm. In the case of producing a cell-trapping metal filter having a thickness of 15 μm or more and 25 μm or less, it is preferable to use a photoresist having a thickness of 25 μm. Further, it is preferable to use a photoresist having a thinner film thickness as the hole diameter of the through hole becomes smaller.

  Lamination of the photoresist 53 on the metal foil 52 is performed, for example, by removing the protective film of the sheet-like photosensitive element composed of the support film, the photoresist and the protective film, and then heating the photoresist 53 on the metal foil 52. This is done by crimping. Thereby, the laminated body which consists of metal foil 52, the photoresist 53, and the support film, and these were laminated | stacked in order is obtained.

  This lamination operation is preferably performed in a reduced pressure atmosphere from the viewpoint of adhesion and followability. On the other hand, there are no particular limitations on the conditions such as the heating temperature and pressure for the photoresist 53 and / or the metal foil 52 at the time of pressure bonding, but it is preferably performed at a temperature of 70 ° C. to 130 ° C., and at a pressure of about 100 kPa to 1000 kPa. It is preferable to crimp. In addition, in the pressure bonding of the photoresist, the metal foil may be preheated in order to improve the lamination property. Note that the support film may be provided with a photomask function. In that case, the support film may be used as a photomask by moving to the next process as it is. Otherwise, the photomask is overlaid in the next process. Remove the support film before.

(Step of exposing)
Next, the exposure process will be described. After a photomask 54 having a translucent portion is overlaid on the photoresist 53 on the metal foil 52, an actinic ray is irradiated, and the exposed portion is photocured to form a cured photoresist.

  The photomask includes a plurality of first light-transmitting regions each formed by a plurality of light-transmitting portions and a second light-transmitting portion in which the light-transmitting portions are formed in a substantially linear shape so as to partition the plurality of first light-transmitting regions. And an optical region. In the photomask, the first light transmission region is a region corresponding to the through hole 22 a formed in the filter region 22. The hardened | cured material hardened | cured with the light which permeate | transmitted the 1st translucent area | region is formed as the through-hole 22a through the process mentioned later. Further, the second light transmissive region is a region corresponding to the separation line L formed in the cell trapping metal filter sheet 10. The hardened | cured material hardened | cured with the light which permeate | transmitted the 2nd translucent area | region is formed as the parting line L through the process mentioned later.

  Examples of the exposure method include a method (mask exposure method) of irradiating an image with active light through a negative or positive mask pattern called an artwork. Alternatively, a method of irradiating actinic rays in an image form by a direct drawing exposure method such as an LDI (Laser Direct Imaging) exposure method or a DLP (Digital Light Processing) exposure method may be employed.

  As the actinic ray light source, a known light source can be used. For example, a carbon arc lamp, a mercury vapor arc lamp, a high pressure mercury lamp, a xenon lamp, a gas laser such as an argon laser, a solid laser such as a YAG laser, a semiconductor laser, etc. Those that effectively emit ultraviolet rays, visible light, and the like are used.

The wavelength of the actinic ray (exposure wavelength) is preferably in the range of 350 nm to 410 nm, and more preferably in the range of 390 nm to 410 nm. The exposure is preferably performed under a vacuum of 600 mmHg or less. Exposure is preferably carried out in the range of ^{0.01J / cm 2 ~10J / cm 2} , and more preferably carried out in the range of ^{0.01J / cm 2 ~5J / cm 2} .

(Process for forming a photoresist pattern)
By removing a portion of the photoresist 53 other than the cured product of the photoresist from the metal foil 52, photoresist patterns 53 a and 53 b made of the cured photoresist are formed on the metal foil 52. When the support film or photomask is present on the photoresist, the support film or photomask is removed, and then the portion other than the cured product of the photoresist is removed (developed). Development methods include wet development and dry development, but wet development is widely used.

  The photoresist pattern 53a formed in the present embodiment is for forming the through hole 22a provided in the cell trapping metal filter 20. The photoresist pattern 53a has a substantially rectangular shape. The range of the length of the short side of the substantially rectangular shape is approximately 5.0 μm to 15.0 μm, and the length of the long side of the substantially rectangular shape is the cell capture metal filter 20 on which the photoresist pattern 53a is formed. The range can be appropriately changed within a range that does not intersect the outer edge. For example, the range is approximately 10 μm to 5 mm. The hole diameter of the photoresist pattern 53a may be changed according to the size of the through hole 22a to be formed.

  The photoresist pattern 53b is for forming the small holes 31 provided in the cell-trapping metal filter 20. The photoresist pattern 53b is provided continuously with a predetermined interval. The predetermined interval between the adjacent photoresist patterns 53b is, for example, 0.1 mm to 0.7 mm. In this case, in the formed cell capture metal filter sheet 10, the small holes 31 are provided intermittently, thereby functioning as a separation line L for separating the cell capture metal filter 20.

  In the case of wet development, development is performed by a known development method using a developer corresponding to the photoresist. Examples of development methods include dipping, paddle, spraying, brushing, slapping, scrapping, rocking immersion, etc. From the viewpoint of improving resolution, the high-pressure spraying method is most suitable. Yes. You may develop by combining 2 or more types of these image development methods.

  Examples of the developer include an alkaline aqueous solution, an aqueous developer, an organic solvent developer, and the like. The alkaline aqueous solution is safe and stable when used as a developer, and has good operability. Examples of the base of the alkaline aqueous solution include alkali metal hydroxides such as lithium, sodium or potassium hydroxide; carbonates or bicarbonates of lithium, sodium, potassium or ammonium; alkali metals such as potassium phosphate and sodium phosphate Phosphate: alkali metal pyrophosphates such as sodium pyrophosphate and potassium pyrophosphate are used.

  Examples of the alkaline aqueous solution include a dilute solution of 0.1% by mass to 5% by mass of sodium carbonate, a dilute solution of 0.1% by mass to 5% by mass of potassium carbonate, and a dilute solution of 0.1% by mass to 5% by mass of sodium hydroxide. A dilute solution of 0.1 mass% to 5 mass% sodium tetraborate or the like is preferable. The pH of the alkaline aqueous solution is preferably in the range of 9 to 11, and the temperature is adjusted according to the alkali developability of the photoresist. In the alkaline aqueous solution, a surfactant, an antifoaming agent, a small amount of an organic solvent for promoting development, and the like may be mixed.

The portions other than the cured product of the photoresist 53 are removed by development, and photoresist patterns 53a and 53b made of a cured product of the photoresist are formed on the metal foil 52, and then about 60 ° C. to 250 ° C. as necessary. by performing the heating or 0.2J ^/ cm ² ~10J ^/ cm 2 about the exposure, it may be further hardened photoresist pattern.

  The photoresist pattern preferably has an aspect ratio (height / short side length) of the height of the photoresist pattern and the length of the short side of 1 to 10 and preferably 2 to 7. More preferably, it is 3 or more and 5 or less. When the aspect ratio exceeds 10, the shape becomes unstable and the photoresist pattern tends to collapse, resulting in a decrease in the yield of manufacturing the cell-trapping metal filter.

  The preferable shape in the case of forming a substantially rectangular photoresist pattern will be further described. In the photomask 54, when the extending direction of the substantially rectangular light-transmitting portion is the longitudinal direction, the plurality of light-transmitting portions are close to each other along the short direction perpendicular to the longitudinal direction of the light-transmitting portion. In some cases, the corners of the formed photoresist pattern are rounder than the design of the light-transmitting portion of the photomask 54. This is because the developer cannot sufficiently penetrate between the hardened portions of the photoresist during development.

(Process of forming metal plating pattern)
After development in the step of forming a photoresist pattern, metal plating is performed on the metal foil 52 to form a metal plating pattern 55. Examples of the plating method include solder plating, nickel plating, and gold plating. This plating layer will eventually become a metal filter, and the photoresist pattern will be removed in the subsequent process to become the through hole of the metal filter. Therefore, plating should be performed below the height of the photoresist pattern so as not to block the photoresist pattern. is important.

  Examples of metal species for metal plating include, but are not limited to, noble metals such as gold and silver, base metals such as aluminum, tungsten, nickel and chromium, and alloys of these metals. The metal may be used alone, or may be used as an alloy with another metal or an oxide of a metal in order to impart functionality. Among these, it is preferable to use nickel and a metal containing nickel as a main component because it prevents corrosion and the like and is excellent in workability and cost. Here, the main component refers to a component occupying the largest proportion of the material.

(Step of obtaining a structure)
After the metal plating pattern 55 is formed, the metal foil 52 is chemically dissolved and removed. Thereby, it is possible to collect the structure composed of the metal plating pattern 55 that becomes the metal filter and the photoresist patterns 53a and 53b without depending on the manual work (hand peeling). For this reason, a metal filter can be manufactured without causing damage such as wrinkles, creases, scratches, and curls, and deformation of fine through holes. As a chemical solubilizer that dissolves the metal foil, MEC BRIGHT SF-5420B (trade name, manufactured by MEC Co., Ltd.), copper selective etching solution-CSS (Nippon Chemical Industry Co., Ltd.), or the like can be used.

(Process to obtain metal plating pattern)
Subsequently, the photoresist patterns 53a and 53b are removed with a stronger alkaline aqueous solution than the alkaline aqueous solution used for development, for example. As this strongly alkaline aqueous solution, for example, a 1% by mass to 10% by mass sodium hydroxide aqueous solution or a potassium hydroxide aqueous solution is preferably used, and a 1% by mass to 5% by mass sodium hydroxide aqueous solution or a potassium hydroxide aqueous solution is used. It is more preferable. By removing the resist pattern (cured product of the photoresist), only the metal plating pattern 55 can be recovered. This metal plating pattern 55 becomes a metal filter. Examples of the resist pattern removal method include an immersion method, a spray method, a method using ultrasonic waves, and the like. These methods may be used alone or in combination.

  Therefore, the cured product of the photosensitive resin composition and the plating pattern 55 remain. Furthermore, only the plating pattern 55 can be recovered by peeling off the resist pattern (cured product of the photosensitive resin composition). This plating pattern 55 is the cell-trapping metal filter sheet 10. By this step, the through hole 22a in the cell trapping metal filter sheet 10 is formed from the photoresist pattern 53a. Further, a separation line L in the cell trapping metal filter sheet 10 is formed due to the photoresist pattern 53b. Thus, the through hole corresponding to the first light transmitting region is formed as the through hole 22a, and the through hole corresponding to the second light transmitting region is formed as the separation line L.

  The cell trapping metal filter according to the present embodiment is obtained by the above-described steps.

  As described above, the cell-trapping metal filter sheet 10 according to the present embodiment is a cell-trapping metal filter sheet in which a plurality of filter regions 22 in which a plurality of through holes are formed in the thickness direction of a sheet whose main component is metal are provided apart from each other. 10 and a separation line L is provided that allows the plurality of filter regions 22 to be separated from each other.

  In such a cell-trapping metal filter sheet 10, by separating the sheet on which the plurality of filter regions 22 are formed along the separation line L, a plurality of filter regions 22 are produced in comparison with the case where the plurality of filter regions 22 are individually manufactured. Therefore, the filter can be mass-produced efficiently. Furthermore, according to the cell capture metal filter sheet 10, a plurality of filters can be obtained by separating the plurality of filter regions 22 based on the separable separation lines L. Compared with the case where a plurality of filters are divided by a cutter or the like along the separation line L, a filter having a stable outer dimension can be obtained. Therefore, the filter can be mass-produced efficiently and the yield as a filter can be improved.

  Moreover, it is preferable that the thickness of the cell capture | acquisition metal filter sheet 10 which concerns on this embodiment is 10 micrometers-30 micrometers. When the thickness of the cell-trapping metal filter sheet 10 is 10 μm to 30 μm, the sheet can be easily cut along the separation line L while being excellent in handleability of the sheet.

  The separation line L has a predetermined interval and is composed of a plurality of small holes 31 provided continuously. The predetermined interval between the adjacent small holes 31 is 0.1 mm to 0.7 mm. It is preferable. In this case, in the cell capture metal filter sheet 10, the separation line L is intermittently provided with the cell capture metal filter 20, so that the separation at the separation line L can be easily performed.

  Moreover, it is preferable that the surface of the cell-trapping metal filter sheet 10 is plated with gold. Since the surface is gold-plated, the adhesion to the cells captured by the filter region 22 becomes uniform, and it can be expected to improve the reproducibility of data.

  The cell-trapping metal filter 20 according to the present embodiment is preferably obtained by separating the cell-trapping metal filter sheet 10 along the separation line L. Since such a cell-trapping metal filter 20 is obtained by separating the cell-trapping metal filter sheet 10 along the separation line L, the cell-trapping metal filter 20 having substantially the same external dimensions can be efficiently manufactured. .

  The cell capture device 1 according to this embodiment includes a lid member 3 having an introduction channel 5 for introducing a cell dispersion (test solution) into the inside, and a discharge channel for discharging the cell dispersion to the outside. The cell dispersion liquid is provided so as to pass through the through-hole 22 a on the flow path inside the case 2 between the case 2 having the storage member 4 having 6 and the introduction flow path 5 and the discharge flow path 6. It is preferable to include the obtained cell-trapping metal filter 20.

  In such a cell trapping device 1, the cell dispersion introduced into the inside from the introduction channel 5 passes through the cell trapping metal filter 20 and is discharged from the discharge channel 6 to the outside of the housing 2. Further, desired cells in the cell dispersion liquid that have passed through the cell trapping metal filter 20 are trapped in the filter region 22. Since the cell trapping device 1 is manufactured using the cell trapping metal filter 20 excellent in mass productivity, the mass productivity of the cell trapping device 1 can be improved.

  The method for manufacturing the cell-trapping metal filter sheet 10 according to the present embodiment includes a step of laminating a photoresist 53 on the metal foil 52, and a plurality of second portions formed respectively on the photoresist 53 by a plurality of light transmitting portions. Exposing a photomask 54 having one light-transmitting region and a second light-transmitting region in which a light-transmitting portion is formed in a substantially linear shape so as to partition each of the plurality of first light-transmitting regions; A step of developing and removing uncured portions of the photoresist to form the photoresist patterns 53a and 53b, and a metal lower than the height of the photoresist patterns 53a and 53b by metal plating between the photoresist patterns 53a and 53b, respectively. From the metal plating pattern and the photoresist pattern, the step of forming the plating pattern and the metal foil 52 are removed by chemical dissolution. And a step of obtaining a structure that, by removing the photoresist pattern from the structure, and obtaining a metal plating pattern having a through hole corresponding to the first light transmitting region and a second light transmitting region.

  In such a method of manufacturing a cell trapping metal filter sheet, both the filter region 22 and the separation line L can be manufactured using a single photoresist 53, so that the cell trapping metal having a plurality of filter regions 22 formed therein. The filter sheet 10 can be produced more efficiently. Moreover, the cell-trapping metal filter 20 having the filter region 22 can be easily separated by separating the cell-trapping metal filter sheet 10 with a separation line. Moreover, when the separation line L is formed in a substantially straight line between the adjacent filter regions 22, the outer dimensions of the cell trapping metal filter 20 can be made more stable when the cell trapping metal filter 20 is cut off. . In this case, since the external dimensions are stabilized, the yield as the cell-trapping metal filter sheet 10 can be improved. Therefore, the cell trapping metal filter 20 can be manufactured efficiently.

  As mentioned above, although embodiment of this invention was described, this invention is not limited to the said embodiment, A various change can be made.

  For example, in the above-described embodiment, a case has been described in which the separation line L includes a plurality of small holes that have a predetermined interval and are continuously provided, but the separation line is not limited thereto. Here, a modified example of the separation line will be described. FIG. 10 (A) is a diagram for explaining a first modification of the separation line of the cell-trapping metal filter sheet of the present invention, and FIG. 10 (B) is a diagram of the separation line of the cell-trapping metal filter sheet of the present invention. It is a figure explaining the 2nd modification.

  FIG. 10A is a cross-sectional view of the cell-trapping metal filter sheet according to the first modification of the separation line. As shown in FIG. 10 (A), the separation line may be constituted by a recess 76 that is partially formed in the thickness direction of the cell-trapping metal filter sheet 75. And the 1st modification of a parting line is selective in the thickness of the hardened | cured material formed in said manufacturing method by making the process of forming the hardened | cured material of a photoresist into a process of multiple times, for example. It can be obtained by changing. Thereby, since the thickness of a gold plating pattern can be changed selectively, a parting line can be partially formed as a recess 76. Even in this case, it can be separated along the separation line in the same manner as the separation line L of the cell capture metal filter sheet according to the above embodiment, and the cell capture metal filter can be mass-produced efficiently. Moreover, since the separation line of the cell-trapping metal filter sheet is not constituted by a through hole, the filter sheet rigidity can be ensured. Therefore, not only can a plurality of cell capture metal filters be obtained easily, but also a cell capture metal filter sheet with improved handling properties can be obtained.

  FIG. 10B is a cross-sectional view of the cell-trapping metal filter sheet according to the second modified example of the separation line. As shown in FIG. 10B, the diameter of the small hole 86 that forms the parting line may not be substantially constant. That is, the separation line may be composed of small holes 86a and 86b having different diameters. Further, the arrangement of the small holes 86a and the small holes 86b having different sizes is arbitrary. And the 2nd modification of a parting line forms the hardened | cured material which has different length in an in-plane direction in the said manufacturing method, for example by changing and changing the magnitude | size of a through-hole partially. And it can obtain by selectively changing the length of the in-plane direction of the hardened | cured material formed by this. Thereby, the magnitude | size of the small hole 86 formed in the gold plating pattern of a cell capture metal filter sheet can be formed selectively. Even in this case, it can be separated along the separation line in the same manner as the separation line L of the cell capture metal filter sheet according to the above embodiment, and the cell capture metal filter can be mass-produced efficiently. Moreover, since the separation line of the cell capture | acquisition metal filter sheet | seat can be comprised by the through-hole which was arbitrarily arranged, the said filter sheet | seat rigidity can be ensured. Therefore, not only can a plurality of cell capture metal filters be obtained easily, but also a cell capture metal filter sheet with improved handling properties can be obtained.

DESCRIPTION OF SYMBOLS 1 ... Cell capture device, 10 ... Cell capture metal filter sheet, 20 ... Cell capture metal filter, 21 ... Metal sheet, 22 ... Filter area | region, 22a ... Through-hole, 31 ... Each small hole (cut line), L ... Cut line .

Claims (7)

A filter sheet in which a plurality of filter regions in which a plurality of through holes are formed in the thickness direction of a sheet whose main component is a metal are provided apart from each other,
A cell-trapping metal filter sheet provided with a separation line that allows the plurality of filter regions to be separated from each other.   The cell-trapping metal filter sheet according to claim 1, wherein the sheet has a thickness of 10 μm to 30 μm. The separating line has a predetermined interval and is composed of a plurality of small holes provided continuously,
The cell capture metal filter sheet according to claim 1 or 2, wherein the predetermined interval between the small holes adjacent to each other is 0.1 mm to 0.7 mm.   The cell-trapping metal filter sheet according to any one of claims 1 to 3, wherein a surface of the sheet is plated with gold.   The cell capture metal filter obtained by isolate | separating the cell capture metal filter sheet as described in any one of Claims 1-4 along the said separation line. A housing having a lid member having an introduction flow path for introducing the test liquid into the interior, and a storage member having a discharge flow path for discharging the test liquid to the outside;
The cell trapping metal filter according to claim 5, wherein the test liquid is provided on a flow path inside the housing between the introduction flow path and the discharge flow path so as to pass through a through-hole.
A cell capture device comprising: Laminating a photoresist on a metal foil;
On the photoresist, a plurality of first light-transmitting regions each formed by a plurality of light-transmitting portions and a light-transmitting portion are formed in a substantially linear shape so as to partition the plurality of first light-transmitting regions. And exposing the photomask having the second light-transmitting region,
Developing and removing uncured portions of the photoresist to form a photoresist pattern; and
Forming a metal plating pattern lower than the height of the photoresist pattern by metal plating between the photoresist patterns;
Removing the metal foil by chemical dissolution to obtain a structure comprising the metal plating pattern and the photoresist pattern;
Removing the photoresist pattern from the structure to obtain the metal plating pattern having through holes corresponding to the first light-transmitting region and the second light-transmitting region;
A method for producing a cell-trapping metal filter sheet comprising:

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