KR20130067200A - Extremely high aspect ratio filter for capturing cell - Google Patents

Abstract

PURPOSE: A filter with a high aspect ratio for capturing cells is provided to prevent blockage of a flow channel due to captured cells or particles by acquiring an enough space. CONSTITUTION: A filter(100) comprises an inlet(122), an outlet(123), a flow channel(124), and a filter part. A sample flows in through the inlet and flows out through the outlet. The flow channel has a first bottom side and a second bottom side facing each other to allow the sample to flow between the inlet and outlet. The filter part is arranged in the flow channel to capture a target cell or a target particle in the sample. The filter part comprises: a barrier which protrudes towards the first bottom side from the second bottom side; and a gap formed between the barrier and the first bottom side.

Description

Extremely high aspect ratio filter for capturing cell

The disclosed embodiments relate to a cell capture filter having a high aspect ratio, and more particularly to clogging a flow path by trapped cells or particles while being able to easily capture cells or particles of a predetermined size or more in a sample. ), And to reduce the stress on the captured cells or particles.

Because cancer is important for early detection, many studies are being conducted to find a fast, simple and accurate test method. Recently, a method of diagnosing cancer by capturing circulating tumor cells (CTCs) contained in blood from blood has been proposed. However, CTCs are very difficult to capture because they are so small that one in 10 ⁹ cells is found. For example, less than about 5 CTCs may be found in about 7.5 ml of blood in breast cancer, and less than about 3 CTCs in about 7.5 ml of blood in colorectal cancer. Therefore, it is important to capture rare CTCs without loss for accurate cancer diagnosis. In addition, because CTC is easily killed, capture should be made while minimizing the adverse effects on the cells.

Capture of CTCs may use, for example, a filter that flows red and white blood cells in the blood and filters out only the CTCs. Such a filter typically has a structure in which a plurality of complex patterns in the form of pillars are formed in a microchannel through which blood can flow. Relatively small red blood cells and white blood cells can then pass between the patterns, but large CTCs can be trapped between the patterns. However, in the filter having such a structure, the flow path may be blocked by the captured CTC. Once occlusion occurs, stress on the CTC may damage the CTC, and white blood cells may be trapped along with the CTC, resulting in decreased assay efficiency and increased assay time.

Provides a filter that can easily capture cells or particles of a predetermined size or more in the sample, while preventing the blockage of the flow path by the captured cells or particles and reducing the stress on the captured cells or particles. .

Filter according to one type of the present invention, the sample inlet; An outlet through which the sample is discharged; A flow passage having a first bottom surface and a second bottom surface facing each other such that a sample flows between the inlet and the outlet; And a filter part disposed in the flow path to capture target cells or target particles in the sample flowing through the flow path, wherein the filter part comprises a first bottom from the second bottom surface of the flow path so as to block the flow path. It may include a barrier protruding toward the surface, and a gap formed between the barrier and the first bottom surface of the flow path.

The size of the gap may be smaller than the size of the target cells or target particles in the sample.

For example, an aspect ratio between the width of the filter portion and the gap may be at least 1,000: 1.

In one embodiment, the barrier may have an inclined sidewall.

The filter portion may be disposed closer to the outlet than the inlet.

In one embodiment, the flow path includes a first end connected to the inlet, a second end connected to the outlet, and a central portion between the first end and the second end, wherein the first end is the inlet. It may have a tapered shape so as to gradually widen toward the center from, and the second end may have a tapered shape so as to become narrower toward the outlet from the center.

The filter may further include a fluid resistance part disposed in the flow path between the filter part and the inlet.

The filter may further include a fine channel formed between the fluid resistance part and the first end of the flow path.

For example, the fluid resistance portion may have a rhombus or diamond shape.

In one embodiment, the fluid resistance portion may be formed to protrude from the second bottom surface of the flow path.

In addition, a filter according to another type of the present invention comprises: a first substrate having a first surface; A second substrate having a second surface bonded to the first surface of the first substrate; An inlet and an outlet formed through the first substrate and the second substrate, respectively; A flow path formed by etching the second surface of the second substrate between the inlet and the outlet; And a filter part disposed in the flow path to capture target cells or target particles in the sample flowing through the flow path, wherein the filter part comprises: a barrier protruding from the bottom surface of the flow path to intersect the flow path; A groove formed by etching an area on a first surface of the first substrate corresponding to the barrier; And a gap formed between the groove and the barrier.

For example, the width of the groove may be wider than the width of the top surface of the barrier.

The filter may further include a fluid resistance portion disposed in the flow path between the filter portion and the inlet, wherein an upper surface of the fluid resistance portion and an upper surface of the barrier have the same height as the second surface of the second substrate. Can be.

In addition, the filter according to another embodiment of the present invention, the sample inlet; An outlet through which the sample is discharged; A flow passage having a first bottom surface and a second bottom surface facing each other such that a sample flows between the inlet and the outlet; And at least two filter portions disposed in the flow passage to capture target cells or target particles in the sample flowing through the flow passage, wherein the at least two filter portions are parallel to each other along a direction in which the sample flows in the flow passage. Each filter portion may include a barrier projecting from the second bottom surface of the flow path toward the first bottom surface to intercept the flow path, and a gap formed between the barrier and the first bottom surface of the flow path. Can be.

In addition, a filter according to another type of the present invention comprises: a first substrate having a first surface; A second substrate having a second surface opposite the first surface of the first substrate and bonded to the first substrate; An inlet formed through a central portion of the first substrate or the second substrate; A flow passage connected to the inlet and formed in a space between the first substrate and the second substrate; And a filter part disposed in the flow path to capture target cells or target particles in the sample flowing through the flow path, wherein the filter part may be formed along the periphery of the first substrate and the second substrate.

For example, the filter unit may include a barrier formed to protrude from the second surface along a circumferential portion of the second surface of the second substrate; Grooves engraved in the first surface along a peripheral portion of the first surface of the first substrate corresponding to the barrier; And a gap formed between the groove and the barrier.

The filter may further include a plurality of separators protruding from the second surface of the second substrate, and the plurality of separators may be disposed radially about the inlet.

For example, each of the separators may be connected to the barrier.

In one embodiment, the flow path may include a plurality of flow paths separated from each other by the plurality of separation membranes.

In addition, each flow path formed between two adjacent membranes may gradually widen from the inlet toward the barrier.

Since the disclosed cell capture filter has a high aspect ratio, even if there are trapped cells or particles in any part, it may provide enough space for other cells to bypass. Therefore, the blockage of the flow path by the trapped cells or particles can be prevented. In addition, since there is almost no blockage of the flow path, stress may be applied to the captured cells, thereby preventing the cells from being damaged. In addition, the disclosed cell capture filter has a structure that is easy to analyze the captured cells. In addition, the disclosed cell capture filter is easy to manufacture from inexpensive and common materials such as plastic or glass.

1 is a schematic perspective view of a cell capture filter according to an embodiment.
FIG. 2 is a schematic exploded perspective view of the cell capture filter shown in FIG. 1. FIG.
FIG. 3 is a schematic cross-sectional view of two substrates of the cell capture filter shown in FIG. 1.
4 is a schematic cross-sectional view illustrating a state in which two substrates illustrated in FIG. 3 are bonded to each other.
5 is a schematic cross-sectional view of a cell capture filter according to another embodiment.
6 is a schematic partial cross-sectional view showing the operation of the cell capture filter shown in FIG.
FIG. 7 is a schematic plan view illustrating an operation of the cell capture filter illustrated in FIG. 1.
8 is a schematic partial cross-sectional view and a partial plan view showing an exemplary operation of the cell capture filter shown in FIG.
9 is a partial cross-sectional view of a filter unit of a cell capture filter according to another embodiment.
10 and 11 are schematic exploded perspective views of a cell capture filter according to another embodiment.
FIG. 12 is a schematic cross-sectional view of the cell capture filter shown in FIG. 10.

Hereinafter, with reference to the accompanying drawings, it will be described in detail for the cell capture filter having a high aspect ratio. In the following drawings, like reference numerals refer to like elements, and the size of each element in the drawings may be exaggerated for clarity and convenience of explanation.

First, FIG. 1 is a schematic perspective view of a cell capture filter 100 according to an embodiment. Referring to FIG. 1, the cell capture filter 100 according to an exemplary embodiment includes an inlet 122 through which a sample to be inspected is introduced, an outlet 123 through which the sample to be inspected is discharged, and the inlet 122 and an outlet 123. A flow path 124 formed to flow a sample between) and a filter unit 130 formed across the flow path 124 to capture target cells or target particles in the sample flowing through the flow path 124. have. As shown in FIG. 1, the filter unit 130 may be disposed closer to the outlet 123 than the inlet 122.

In addition, the cell capture filter 100 according to an embodiment further includes a fluid resistance part 125 disposed close to the inlet 122 in the flow path 124 between the inlet 122 and the filter part 130. It may include. Due to the fluid resistance portion 125, as shown in FIG. 1, the sample introduced from the inlet 122 has two narrow microchannels 126 formed between the fluid resistance portion 125 and the inner wall of the flow path 124. Through the flow toward the edge of the flow path (124). The sample may then flow from the edge of the flow path 125 to the center as indicated by the arrow. The fluid resistance unit 125 may control the speed of the sample introduced into the inlet 122 and the distribution of the stream line. For example, the fluid resistance part 125 may reduce the speed of the sample by preventing the sample introduced from the inlet 122 from flowing directly into the flow path 124, and may increase the speed of the sample in the flow path 124. It can be kept within a certain range. In addition, the fluid resistance unit 125 may allow the streamline of the sample to be evenly distributed in the flow path 124 and the length of each streamline may be similar. Therefore, the sample may flow evenly along the flow path 124 by the fluid resistance unit 125, and it is possible to prevent the sample from concentrating on a specific region of the filter unit 130.

As shown in FIG. 1, the fluid resistance part 125 may have a diamond shape or a diamond shape, but is not limited thereto. For example, the shape of the fluid resistance unit 125 may be a polygon such as a triangle, a square, or the like, and may also be a circle, oval, fan, streamline, or a combination of the above shapes.

The cell capture filter 100 according to the present embodiment includes, for example, the inlet 122, the outlet 123, the flow path 124, the fluid resistance unit 125, the filter unit 130, and the like. It can be formed by joining two substrates (110, 120) having a flat surface. 2 is a schematic exploded perspective view of the cell capture filter 100 according to the present embodiment showing the surface structure of the substrate (110, 120).

Referring to FIG. 2, firstly, the first substrate 110 has a flat first surface 111. The first substrate 110 may have a rectangular shape in which the width W is twice or more wider than the length L. FIG. For example, the width W of the first substrate 110 may be about 3 cm and the length L may be about 1.5 cm. The first surface 111 may be formed with a fine groove 115 constituting a part of the filter unit 130. The groove 115 may be formed in a long and narrow straight shape along the width direction of the first substrate 110. For example, the groove 115 may be formed by etching the first surface 111 of the first substrate 110 by wet etching. The first substrate 110 may be made of transparent glass or transparent plastic material, but is not necessarily limited thereto. For example, the material of the first substrate 110 may be acrylate, polymethylacrylate, polymethylmethacrylate (PMMA), polycarbonate, polystyrene, polyimide. , Epoxy resin, polydimethylsiloxane (PDMS), parylene, and the like.

The second substrate 120 also has a flat second surface 121. The second substrate 120 may also have the same width W and length L as the first substrate 110. However, if desired, the second substrate 120 may be larger or smaller than the first substrate 110. The second substrate 120 may be made of a material such as transparent glass, quartz, plastic, or polymer so that the captured cells or particles can be observed.

As illustrated in FIG. 2, an inlet 122 and an outlet 123 may be formed through the second substrate 120. A flow path 124 is formed between the inlet 122 and the outlet 123. For example, the flow path 124 may be formed by etching the second surface 121 by a wet etching method. In addition, the fluid resistance part 125 and the barrier 127 protrude from the bottom of the flow path 124 in the flow path 124. For example, the fluid resistance portion 125 and the barrier 127 may be part of the second surface 121 through a mask (not shown) when etching the second surface 121 to form the flow path 124. The region may be formed so as not to be etched. Thus, the upper surface of the fluid resistance portion 125 and the barrier 127 may be flush with the second surface 121 of the second substrate 120.

On the other hand, the flow path 124 is the first end 124a which is a region connected to the inlet 122, the second end 124b which is a region connected to the outlet 123, and the first end 124a and the first It may have a central portion 124c which is an area between the two ends 124b. As shown in FIG. 2, the first end 124a and the second end 124b may be formed in a tapered shape. For example, the first end 124a may gradually widen from the inlet 122 toward the central portion 124c. In addition, the second end 124b may become narrower toward the outlet 123 from the central portion 124c. The central portion 124c may have a width W1 that is much wider than the length L1. For example, the ratio of the width W1 to the length L1 of the central portion 124c may be 3: 1 or more, and may be 100: 1 or less. In this case, the flow velocity of the sample can be prevented from being too fast and the pressure applied to the flow path 124 can be reduced.

As shown in FIG. 2, the fluid resistance part 125 may be disposed closer to the inlet 122 than the outlet 123. In addition, the fluid resistance part 125 may have a tapered shape to a degree similar to that of the first end 124a of the flow path 124. As described above, the fluid resistance portion 125 may have a rhombus, diamond, or other polygonal shape. Therefore, two narrow fine channels 126 may be formed between the fluid resistance part 125 and the inner wall of the flow path 124. Both edges of the fluid resistance portion 125 oppose both inner walls of the flow path 124. Accordingly, the sample introduced from the inlet 122 may flow along the microchannel 126 and then be provided to both edges of the flow path 124. Thereafter, the sample may be evenly distributed in the central portion 124c of the flow path 124 and flow toward the outlet 123.

As shown in FIG. 2, the barrier 127 may be disposed closer to the outlet 123 than to the inlet 122. The barrier 127 is formed in an area corresponding to the groove 115 formed in the first surface 111 of the first substrate 110, so that the first substrate 110 and the second substrate 120 are bonded to each other. The barrier 127 and the groove 115 may be opposed to each other. Like the groove 115, the barrier 127 may also be formed in a long and narrow straight line along the width direction of the second substrate 120. The barrier 127 may be formed to completely block the flow path 124.

3 is a schematic cross-sectional view of two substrates 110 and 120 of the cell capture filter 100 having the above-described structure, and FIG. 3A is a cross-sectional view of the second substrate 120 cut in the AA ′ direction. 3B is a cross-sectional view of the first substrate 110 cut in the BB 'direction. Referring to FIG. 3A, an inlet 122 and an outlet 123 are formed through the second substrate 120, and a flow path 124 is formed between the inlet 122 and the outlet 123. It is. In addition, the fluid resistance part 125 and the barrier 127 protrude from the bottom of the flow path 124 in the flow path 124. The height of the fluid resistance 125 and the barrier 127 may be the same height of the second surface 121. In addition, referring to FIG. 3B, minute grooves 115 are formed in regions corresponding to the barrier 127 on the first surface 111 of the first substrate 110.

4 is a schematic cross-sectional view illustrating a state in which the first substrate 110 and the second substrate 120 are bonded to each other. Referring to FIG. 4, the first surface 111 of the first substrate 110 and the second surface 121 of the second substrate 120 may be bonded to each other. Then, the upper surface of the fluid resistance portion 125 may be completely in contact with the first surface 111 of the first substrate 110. On the other hand, because the groove 115 is formed in the region of the first surface 111 of the first substrate 110 opposite the barrier 127, there is a minute gap between the barrier 127 and the groove 115. Done. The size of the gap can be determined by the depth of the groove 115. For example, the gap may be formed to be smaller than the diameter of the target cell or target particle to be captured. That is, the depth of the groove 115 formed in the first surface 111 of the first substrate 110 may be smaller than the diameter of target cells or target particles to be captured. In addition, in consideration of an alignment error between the first substrate 110 and the second substrate 120, the width of the groove 115 may be wider than the width of the upper surface of the barrier 127. The groove 115 and the barrier 127 constitute the filter unit 130 of the cell capture filter 100.

Although FIG. 2 to FIG. 4 show the inlet 122 and the outlet 123 formed on the second substrate 120, this is only one example. As shown in FIG. 5, in another embodiment, the inlet 122 and the outlet 123 may be formed through the first substrate 110 instead of the second substrate 120. That is, the flow path 124, the fluid resistance part 125, and the barrier 127 are formed in the second substrate 120, and the inlet 122, the outlet 123, and the groove 115 are the first substrate 110. It may be formed in.

6 is a schematic partial cross-sectional view showing only the filter unit 130 in order to exemplarily explain the operation of the cell capture filter 100 according to the present embodiment. Referring to FIG. 6, the barrier 127 and the groove 115 are disposed to face each other, and the groove 115 has a predetermined depth D. Thus, a gap corresponding to the depth D of the groove 115 may be formed between the top surface 127b of the barrier 127 and the bottom of the groove 115. The gap may be about 8 um, for example, when trying to capture CTC. In addition, as shown in FIG. 6, the width W3 of the bottom of the groove 115 may be greater than the width W2 of the upper surface 127b of the barrier 127. Accordingly, when the first substrate 110 and the second substrate 120 are bonded to each other, the first substrate 110 and the second substrate 120 do not need to be precisely aligned. Even though there are some alignment errors, the top surface 127b of the barrier 127 is directly in contact with the first surface 111 of the first substrate 110 because the barrier 127 can be sufficiently disposed in the groove 115. May not be contacted.

Meanwhile, the sidewall 127a of the barrier 127 does not need to be perpendicular to the bottom of the flow path 124 and may be formed to be inclined. Thus, it is not necessary to form the barrier 127 in the same manner as deep reactive ion etching (DRIE), and the barrier 127 may be formed by simply wet etching. Likewise, the grooves 115 may also be formed by simple wet etching. Therefore, the manufacturing process of the cell capture filter 100 can be simplified and manufacturing time and manufacturing cost can be reduced.

In FIG. 6, it is assumed that the left side faces the inlet 122 and the right side faces the outlet 123. For example, when a blood sample is introduced through the inlet 122, the blood sample flows along the flow path 124 to the outlet 123. The flow path 124 may have a first bottom surface 124d formed by the first substrate 110 and a second bottom surface 124e formed by the second substrate 120. The height H of the flow path 124, that is, the distance between the first bottom surface 124d and the second bottom surface 124e disposed opposite each other, may be, for example, about 50 μm so that the blood sample can flow easily. have. To this end, when etching the second surface 121 of the second substrate 120 may be etched to a depth of about 50um. As described above, the filter unit 130 having a minute gap formed by the barrier 127 and the groove 115 is located in the flow path 124. For example, the barrier 127 protrudes from the second bottom surface 124e toward the first bottom surface 124d, and a gap is formed between the barrier 127 and the first bottom surface 124d. Therefore, the blood sample passes through the filter unit 130 while flowing through the flow path 124 to the outlet 123. In this case, as shown in FIG. 6, the red blood cells 151 in the blood sample may pass through the filter unit 130 because they have a flat disk shape having a diameter of about 7 to 8 μm and a thickness of about 1 to 2 μm. On the other hand, the CTC 152 having a diameter of about 20 μm and larger than the gap may not be passed through the gap and may be captured by the filter 130.

In the case of the cell capture filter 100 according to the present embodiment, since the filter unit 130 has a very large aspect ratio, even if target cells such as the CTC 152 or other target particles are captured, the filter unit 130 may be trapped. It may not be blocked. 7 is a schematic plan view showing an exemplary operation principle of the cell capture filter 100 according to this embodiment. Referring to FIG. 7, the blood sample provided from the inlet 122 is introduced toward the edge of the flow path 124 through the microchannel 126 formed by the fluid resistance 125. The blood sample then flows toward the outlet 123 while spreading evenly from the edge of the flow path 124 to the center. The barrier 127 is disposed in front of the outlet 123. The width of the barrier 127 is equal to the width of the flow path 124 so that the barrier 127 completely obstructs the flow path 124. Thus, the CTCs 152 in the blood sample are caught by the barrier 127 while flowing along the flow path 124.

As described above, since the gap between the top surface 127b of the barrier 127 and the bottom of the groove 115 is about 8um and the width of the barrier 127 may be close to about 3cm, the filter portion 130 The aspect ratio is very large, about 30,000: 8. Here, the aspect ratio 30,000: 8 is only one example, and the actual value may vary depending on the type of the target or the inspection environment, but may be about 1,000: 1 or more. Thus, even if the CTCs 152 block a portion of the barrier 127, there is sufficient free space for the blood sample to bypass. As a result, the captured CTCs 152 are rarely damaged by the stress generated by the multiple CTCs 152 gathered at the same position on the barrier 127 at once. In addition, even if a large number of CTCs 152 are caught in a plurality of areas on the barrier 127, the resulting increase in flow rate and oil pressure is not significant, so that the captured CTCs 152 are damaged by stress caused by the increase in flow rate and oil pressure. It rarely happens. For example, since the maximum number of CTCs 152 captured in one blood sample test is about 100, the diameter of the CTCs 152 (about 20 um) and the width of the flow path 124 (eg, about 3 cm) are determined. In consideration, the width of the flow path 124 reduced by the captured CTCs 152 does not significantly affect the flow rate and the hydraulic pressure.

In addition, the cell capture filter 100 according to the present embodiment is also convenient for observing the captured CTCs 152. Whether the CTCs 152 have been captured and the number of captured CTCs 152 can be known by observing under a microscope along the edge of the barrier 127 which is simply formed in a straight line. Since the second substrate 120 is made of a transparent material, it is possible to place the cell capture filter 100 directly on the microscope stage and observe it.

In addition, in the case of the cell capture filter 100 according to the present embodiment, as shown in FIG. 8, since the sidewall 127a of the barrier 127 is formed to be inclined, the cells captured by the filter unit 130 are inclined. Their diameter can be seen. That is, the larger the size of the cell, the farther from the centerline of the barrier 127 shown in FIG. Therefore, the diameters of the cells captured from the distances d1 and d2 from the centerline of the barrier 127 can be roughly calculated, and the type of cells can be confirmed therefrom.

So far, the cell capture filter 100 has been described as including only one filter unit 130 having one barrier 127 and one groove 115, but a plurality of barriers 127 and a plurality of grooves. A plurality of filter units 130 each having 115 may be formed. 9 is a partial cross-sectional view of the filter unit 130 of the cell capture filter 100 according to another embodiment including a plurality of filter unit 130.

Referring to FIG. 9, a plurality of parallel barriers 127 are formed on the surface of the second substrate 120 along a direction in which a sample flows in the flow path 124, and each of the plurality of barriers 127 opposes the barriers 127. Side by side grooves 115 are formed on the surface of the first substrate 110. 9 shows three barriers 127 and three grooves 115 arranged side by side, but this is only one example. If necessary, two barriers 127 and grooves 115 may be formed, or four or more barriers 127 and grooves 115 may be formed. According to this embodiment, by forming the filter unit 130 in multiple stages, it is possible to improve the recovery rate of the target cells or target particles in the sample. That is, based on the direction in which the sample flows, target cells or target particles that have passed through the barrier 127 at the front may be captured by the barrier 127 disposed thereafter.

On the other hand, it has been described that the filter unit 130 is disposed only on one side of the cell capture filter 100, but the present invention is not limited thereto. For example, FIGS. 10 and 11 show schematic exploded perspective views of a cell capture filter 200, 300 according to another embodiment in which a filter portion is formed along a circumferential portion thereof. First, in the case of the rectangular cell capture filter 200 illustrated in FIG. 10, the filter units 215 and 227 are formed on all four sides of the cell capture filter 200. In addition, in the case of the cell capture filter 300 of the circular shape shown in Fig. 11, circular filter portions 215 and 227 are formed along the circumferential portion. The shapes of the cell capture filters 200 and 300 shown in FIGS. 10 and 11 are merely exemplary, and the cell capture filter may be formed in the shape of a polygon such as a triangle or a pentagon. According to the present embodiment, since the filter parts 215 and 227 are formed along the entire circumference of the cell capture filter 200 and 300, the aspect ratio of the filter parts 215 and 227 can be further increased.

Referring to FIG. 11, the cell capture filter 200 may include a first substrate 210 having a first flat surface 211 and a second substrate 220 having a second flat surface 221. . The first substrate 210 and the second substrate 220 may be bonded such that the first surface 211 and the second surface 221 face each other. The first surface 211 of the first substrate 210 is formed with fine grooves 215 engraved along the periphery thereof. In addition, the second surface 221 of the second substrate 220 is formed with a barrier 227 protruding from the second surface 221 along the peripheral portion thereof. When the first substrate 210 and the second substrate 220 are bonded to each other, the groove 215 and the barrier 227 may be disposed to face each other. Accordingly, there is a minute gap between the barrier 227 and the groove 215 as much as the depth of the groove 215. The width of the groove 215 may be wider than the width of the barrier 227 in consideration of an alignment error between the first substrate 210 and the second substrate 220.

In addition, an inlet 222 may be formed through the center of the second substrate 220. In the second surface 221, a plurality of separation membranes 225 protruding from the inlet 222 in the diagonal direction of the second substrate 220 may be formed. Each separator 225 may be connected to the barrier 227 near a vertex of the second substrate 220. A flow path 224 connected to the inlet 222 and flowing a sample may be formed between two adjacent separators 225. Accordingly, a plurality of flow paths 224 separated from each other may be formed by a plurality of separators 225 disposed radially about the inlet 222. Each flow path 224 has a shape that gradually widens from the inlet 222 toward the barrier 227. The sample provided through the inlet 222 flows to each of the plurality of flow paths 224, and the sample may be evenly spread in the flow path 224 because the width of the flow path 224 gradually increases along the direction in which the sample flows. . In the case of the cell capture filter 200 illustrated in FIG. 10, no separate outlet is formed, and the sample may be finally discharged through the edge of the cell capture filter 200.

FIG. 12 is a schematic cross-sectional view of the cell capture filter 200 shown in FIG. 10, and is taken along the line AA ′ of FIG. 10. Referring to FIG. 12, a groove 215 formed in the first substrate 210 and a barrier 227 protruding from the second substrate 220 are disposed to face each other. In the cross-sectional view of FIG. 12, a filter portion consisting of a barrier 227 and a groove 215 is shown at both end portions of the cell capture filter 200. A flow path 224 is formed in the space between the filter units on both sides and between the first substrate 210 and the second substrate 220. Although not shown in the cross-sectional view of FIG. 12, the surface of the separator 225 protruding from the second substrate 220 is bonded to the surface of the first substrate 110, so that the flow path 224 is separated into several zones. Can be. 10 and 12 show that the inlet 222 penetrates the second substrate 220 and is connected to the flow path 224, but as in the embodiment of FIG. 5, the inlet 222 penetrates the first substrate 210. Inlet 222 may be formed.

The detailed structure of the cell capture filter 200 described above with reference to FIGS. 10 and 12 may be applied to the cell capture filter 300 shown in FIG. 11 as it is. The cell capture filter 300 shown in FIG. 11 differs only in that it is circular. Also, in the case of the cell capture filter 300 illustrated in FIGS. 10 and 11, the filter unit may be formed in multiple stages as illustrated in FIG. 9.

To date, exemplary embodiments of cell capture filters with high aspect ratios have been described and illustrated in the accompanying drawings in order to facilitate understanding of the present invention. It should be understood, however, that such embodiments are merely illustrative of the present invention and not limiting thereof. And it is to be understood that the invention is not limited to the details shown and described. Since various other modifications may occur to those of ordinary skill in the art.

100, 200, 300 ... filter 210, 110 ... first substrate
111, 211 ..... First Surface 115, 215 ..... Home
120, 220 .... second substrate 121, 221 ... second surface
122, 222 ..... inlet 123 ..... outlet
124, 224..Euro 125..Fluid resistance
126 ..... fine channel 127, 227..barrier
130 ..... Filter 225 ..... Membrane

Claims (28)

An inlet through which the sample is introduced;
An outlet through which the sample is discharged;
A flow passage having a first bottom surface and a second bottom surface facing each other such that a sample flows between the inlet and the outlet; And
And a filter unit disposed in the flow path to capture target cells or target particles in the sample flowing through the flow path.
And the filter part includes a barrier projecting from the second bottom surface of the flow path toward the first bottom surface to intercept the flow path, and a gap formed between the barrier and the first bottom surface of the flow path. The method of claim 1,
The size of the gap is smaller than the size of the target cells or target particles in the sample. The method of claim 1,
And an aspect ratio between the width of the filter portion and the gap is at least 1,000: 1. The method of claim 1,
Said barrier having a sloped sidewall. The method of claim 1,
And the filter portion is disposed closer to the outlet than the inlet. The method of claim 1,
The flow path includes a first end connected to the inlet, a second end connected to the outlet, and a central portion between the first end and the second end,
The first end has a tapered shape so as to gradually widen from the inlet toward the central portion,
And the second end has a tapered shape so as to become narrower from the central portion toward the outlet. The method according to claim 6,
And a fluid resistance portion disposed in the flow path between the filter portion and the inlet. The method of claim 7, wherein
And a microchannel formed between the fluid resistance portion and the first end of the flow path. The method of claim 7, wherein
The fluid resistance portion is a filter in the form of diamond or diamond. The method according to claim 6,
And the fluid resistance part protrudes from the second bottom surface of the flow path. A first substrate having a first surface;
A second substrate having a second surface bonded to the first surface of the first substrate;
An inlet and an outlet formed through the first substrate and the second substrate, respectively;
A flow path formed by etching the second surface of the second substrate between the inlet and the outlet; And
And a filter unit disposed in the flow path to capture target cells or target particles in the sample flowing through the flow path.
The filter unit:
A barrier protruding from the bottom surface of the flow path so as to block the flow path;
A groove formed by etching an area on a first surface of the first substrate corresponding to the barrier; And
And a gap formed between the groove and the barrier. The method of claim 11,
The size of the gap is smaller than the size of the target cells or target particles in the sample. The method of claim 11,
And an aspect ratio between the width of the filter portion and the gap is at least 1,000: 1. The method of claim 11,
Said barrier having a sloped sidewall. 15. The method of claim 14,
And the width of the groove is wider than the width of the top surface of the barrier. The method of claim 11,
The flow path includes a first end connected to the inlet, a second end connected to the outlet, and a central portion between the first end and the second end,
The first end has a tapered shape so as to gradually widen from the inlet toward the central portion,
And the second end has a tapered shape so as to become narrower from the central portion toward the outlet. 17. The method of claim 16,
And a fluid resistance portion disposed in the flow path between the filter portion and the inlet. The method of claim 17,
And a microchannel formed between the fluid resistance portion and the first end of the flow path. The method of claim 17,
The fluid resistance portion is a filter in the form of diamond or diamond. 17. The method of claim 16,
And the fluid resistance part protrudes from the bottom surface of the flow path. 17. The method of claim 16,
And a top surface of the fluid resistance portion and a top surface of the barrier have the same height as the second surface of the second substrate. An inlet through which the sample is introduced;
An outlet through which the sample is discharged;
A flow passage having a first bottom surface and a second bottom surface facing each other such that a sample flows between the inlet and the outlet; And
And at least two filter units disposed in the flow path to capture target cells or target particles in the sample flowing through the flow path.
The at least two filter parts are arranged in parallel with each other along a direction in which a sample flows in the flow path,
Each filter portion includes a barrier projecting from the second bottom surface of the flow path toward the first bottom surface to intercept the flow path, and a gap formed between the barrier and the first bottom surface of the flow path. A first substrate having a first surface;
A second substrate having a second surface opposite the first surface of the first substrate and bonded to the first substrate;
An inlet formed through a central portion of the first substrate or the second substrate;
A flow passage connected to the inlet and formed in a space between the first substrate and the second substrate;
And a filter unit disposed in the flow path to capture target cells or target particles in the sample flowing through the flow path.
And said filter portion is formed entirely along the periphery of said first and second substrates. 24. The method of claim 23,
The filter unit:
A barrier protruding from the second surface along a circumferential portion of the second surface of the second substrate;
Grooves engraved in the first surface along a circumferential portion of the first surface of the first substrate corresponding to the barrier; And
And a gap formed between the groove and the barrier. 25. The method of claim 24,
And a plurality of separators protruding from the second surface of the second substrate, wherein the plurality of separators are disposed radially about the inlet. The method of claim 25,
Filters are connected to the barrier. The method of claim 25,
And the flow path includes a plurality of flow paths separated from each other by the plurality of separation membranes. The method of claim 27,
Each flow path formed between two adjacent membranes is gradually wider from the inlet toward the barrier.

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