Separation chip
The separation chip addresses particle order reversal in dielectrophoresis by employing closely arranged electrodes and insulating layers, enhancing separation efficiency and analysis accuracy while reducing sample waste.
Patent Information
- Application Number
- PCT/JP2024/043573
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2023-12-27
- Filing Date
- 2024-12-10
- Publication Date
- 2025-07-03
AI Technical Summary
Existing separation chips for cells in blood face issues with particle order reversal during dielectrophoresis, leading to inefficiencies in separation and analysis.
The separation chip design includes electrode portions arranged closely together, with specific angular and spatial relationships, and an insulating layer configuration to maintain the order of dielectric particles moving along the electrodes, enhancing the dielectrophoretic force and reducing particle overtaking.
This design effectively suppresses particle order reversal, improving the accuracy of cell separation and analysis, reducing sample loss, and minimizing environmental impact by optimizing fluid usage.
Smart Images

Figure JP2024043573_03072025_PF_FP_ABST
Abstract
Description
Separation Chip
[0001] The present invention relates to a separation chip.
[0002] Conventionally, separation chips that separate specific cells from blood have been known (see, for example, Patent Document 1). Patent Document 1 describes a chip equipped with a DEP (dielectrophoresis) unit that separates and recovers cells and the like by dielectrophoresis. The DEP unit includes a pair of opposing comb-shaped electrodes provided on a flow path. Dielectrophoresis is induced by applying an AC voltage between the pair of electrodes. By appropriately adjusting the applied AC voltage and frequency, desired cells such as CTCs (circulating tumor cells) are induced and separated.
[0003] Japanese Patent Application Laid-Open No. 2020-99256
[0004] In a separation chip such as that described in Patent Document 1, particles are attracted to one of a pair of electrodes and move along the electrodes. At this time, the particles are attracted to the edge of the upper surface of the electrode and move along the edge of the upper surface of the electrode. Then, the particles leave the electrode and move downstream in the flow channel.
[0005] Specifically, when particles move along the edge of the upper surface of the electrodes, the particles move in two rows between the pair of electrodes, and at this time, the subsequent particle may overtake the preceding particle between the pair of electrodes, causing the order of the particles to change.
[0006] The present invention has been made in view of the above-mentioned problems, and an object of the present invention is to provide a separation chip that can prevent the order of particles moving along an electrode from being changed.
[0007] A separation chip according to a first aspect of the present invention is used to capture specific dielectric particles contained in a liquid. The separation chip includes a substrate and a plurality of electrode portions. The plurality of electrode portions are arranged on one surface of the substrate, have at least an electrode, and extend in a first direction. The plurality of electrode portions are arranged adjacent to each other in a second direction intersecting the first direction. A flow path is provided on one side of the plurality of electrode portions, through which the liquid flows in a flow direction intersecting the first direction. The distance between adjacent electrode portions in the second direction is less than twice the particle size of the specific dielectric particles.
[0008] In an aspect of the present invention, the electrode portion may have an insulating layer covering the electrode, and the distance between the insulating layers adjacent to each other in the second direction may be less than twice the particle diameter of the specific dielectric particles.
[0009] In one aspect of the present invention, the distance between the electrodes adjacent to each other in the second direction may be less than twice the particle diameter of the specific dielectric particles.
[0010] In one aspect of the present invention, the distance between the electrode portions adjacent to each other in the second direction may be 1.5 times or less the particle diameter of the specific dielectric particles.
[0011] In one aspect of the present invention, the distance between the electrode portions adjacent to each other in the second direction may be equal to or less than the particle diameter of the specific dielectric particle.
[0012] In one aspect of the present invention, when viewed in a plan view, a first particle that is one of the specific dielectric particles contacts one of the electrode units adjacent in the second direction, and a second particle that is another of the specific dielectric particles contacts the other of the electrode units adjacent in the second direction and the first particle, the angle formed by a line connecting the center of the first particle and the center of the second particle and the first direction is defined as φ. The angle formed by the first direction and the flow direction is defined as θ. The separation chip may satisfy 0°≦φ+θ≦60° or 120°≦φ+θ≦180°.
[0013] A separation chip according to a second aspect of the present invention is used to capture specific dielectric particles contained in a liquid. The separation chip includes a substrate and a plurality of electrode units. The plurality of electrode units are arranged on one surface of the substrate and extend in a first direction. The plurality of electrode units are arranged adjacent to each other in a second direction intersecting the first direction. A flow path is provided on one side of the plurality of electrode units through which the liquid flows in a flow direction intersecting the first direction. The electrode unit includes an electrode arranged on one surface of the substrate and an insulating layer covering the electrode. The one surface of the electrode has a first region and a second region different from the first region. The thickness of the insulating layer on the first region is smaller than the thickness of the insulating layer on the second region. The length of the first region in the second direction is less than twice the particle size of the specific dielectric particles.
[0014] In one aspect of the present invention, the length of the first region in the second direction may be 1.5 times or less the particle diameter of the specific dielectric particle.
[0015] In one aspect of the present invention, the length of the first region in the second direction may be equal to or less than the particle diameter of the specific dielectric particle.
[0016] In one aspect of the present invention, when viewed in a plan view, when a first particle that is one of the specific dielectric particles contacts one of the second regions adjacent in the second direction, and a second particle that is another of the specific dielectric particles contacts the other of the second regions adjacent in the second direction and the first particle, the angle formed by a line connecting the center of the first particle and the center of the second particle and the first direction is defined as φ. The angle formed by the first direction and the flow direction is defined as θ. The separation chip may satisfy 0°≦φ+θ≦60° or 120°≦φ+θ≦180°.
[0017] In one aspect of the present invention, the insulating layer may have an opening connecting the first region and the flow path. The first region may be connected to the flow path through the opening. The first region may be located closer to the substrate than the second region.
[0018] According to the present invention, it is possible to provide a separation chip that can prevent the order of particles moving along the electrodes from being changed.
[0019] 1 is a plan view schematically showing the structure of a dielectrophoresis device including a separation chip according to an embodiment of the present invention; FIG. 2 is an enlarged cross-sectional view schematically showing the structure around the teeth of the separation chip according to an embodiment of the present invention; FIG. 3 is a plan view schematically showing the structure around the electrode parts of the separation chip and dielectric particles; FIG. 4 is a view for explaining the effect of setting the distance between adjacent electrode parts in a second direction to 1.5 times the particle size of the dielectric particles or less; FIG. 5 is a view for explaining the effect of suppressing the timing at which a plurality of dielectric particles separate from the electrode parts from being close to each other; FIG. 6 is a plan view schematically showing the structure around the electrode parts and dielectric particles of a separation chip according to a first modified example of the present invention; FIG. 7 is an enlarged cross-sectional view schematically showing the structure around the teeth of the separation chip according to a second modified example of the present invention; FIG. 8 is an enlarged cross-sectional view schematically showing the structure around the teeth of the separation chip according to the second modified example of the present invention; 10A and 10B are plan views schematically showing the structure of the periphery of an electrode portion of a separation chip according to a fourth modified example of the present invention, and dielectric particles;
[0020] Hereinafter, embodiments of the present invention will be described with reference to the drawings. In the drawings, the same or corresponding parts are designated by the same reference characters and description thereof will not be repeated.
[0021] A dielectrophoresis device 1 including a separation chip 100 according to one embodiment of the present invention will be described with reference to Figures 1 to 5. Figure 1 is a plan view schematically showing the structure of a dielectrophoresis device 1 including a separation chip 100 according to one embodiment of the present invention.
[0022] As shown in FIG. 1 , a dielectrophoresis device 1 according to one embodiment of the present invention includes a separation chip 100 and a voltage control device 500. The dielectrophoresis device 1 applies a dielectrophoretic force to dielectric particles P1 contained in a sample liquid (specimen liquid), thereby separating the dielectric particles P1 from other particles P2 and collecting the dielectric particles P1. The sample liquid is not particularly limited, but may be, for example, blood. The dielectric particles P1 are not particularly limited, but may be, for example, cells, proteins, nucleic acids, or microorganisms. The cells are, for example, cancer cells. The sample liquid may also be seawater, saline, pure water, or a chemical. The other particles P2 are, for example, dielectric particles of a different type from the dielectric particles P1, or non-dielectric particles. As an example, the sample liquid is blood, the dielectric particles P1 are cancer cells, and the other particles P2 are white blood cells. The sample liquid is an example of the "liquid" in the present invention.
[0023] The separation chip 100 is used to capture specific dielectric particles P1 contained in a liquid. Specifically, the separation chip 100 applies a dielectrophoretic force to the dielectric particles P1 contained in the sample liquid, thereby separating the dielectric particles P1 from other particles P2 and collecting the dielectric particles P1. The diameter of the dielectric particles P1 (hereinafter sometimes referred to as particle size) is, for example, several μm or more and 20 μm or less. That is, in this embodiment, the minimum particle size of the dielectric particles P1 is several μm, and the maximum particle size is 20 μm. Furthermore, in this embodiment, the average particle size of the dielectric particles P1 is approximately 10 μm.
[0024] The separation chip 100 includes a substrate 101, a flow channel 110, and a separation electrode 120. The flow channel 110 includes a supply unit 111, a separation flow channel 112, and a collection unit 113. In this embodiment, the supply unit 111 includes a first supply unit 1111 and a second supply unit 1112. A sample liquid is introduced into the first supply unit 1111. A transport liquid is introduced into the second supply unit 1112. The transport liquid is, for example, a liquid that does not contain particles. The transport liquid is not particularly limited, but may be, for example, a liquid culture medium. Each of the first supply unit 1111 and the second supply unit 1112 has, for example, an opening. The first supply unit 1111 is connected, for example, to a supply source of the sample liquid by a tube. The second supply unit 1112 is connected, for example, to a supply source of the transport liquid by a tube.
[0025] The separation channel 112 extends, for example, in a straight line in a predetermined direction. A sample liquid flows through the separation channel 112. In this embodiment, the sample liquid and a transport liquid flow through the separation channel 112. Specifically, the separation channel 112 connects the first supply unit 1111 and the second supply unit 1112 to the collection unit 113. The sample liquid introduced into the first supply unit 1111 and the transport liquid introduced into the second supply unit 1112 flow through the separation channel 112 toward the collection unit 113.
[0026] In this embodiment, the collection unit 113 has a first collection unit 1131 and a second collection unit 1132. The first collection unit 1131 and the second collection unit 1132 are each connected to the downstream end of the separation channel 112. The first collection unit 1131 collects particles P2 other than the dielectric particles P1. The second collection unit 1132 collects the dielectric particles P1 that have passed through the separation channel 112. Each of the first collection unit 1131 and the second collection unit 1132 may have, for example, an opening. The first collection unit 1131 may, for example, supply a sample liquid containing the particles P2 to the outside. The second collection unit 1132 may, for example, supply a transport liquid containing the dielectric particles P1 to the outside.
[0027] The separation chip 100 includes a channel cover 105. The channel cover 105 is disposed on a substrate 101. The channel cover 105 has an area smaller than that of the substrate 101. In other words, the channel cover 105 is disposed on a portion of the substrate 101. The channel cover 105 has a recess that forms a channel 110. The channel 110 is formed by the substrate 101 and the channel cover 105.
[0028] The separation electrode 120 is formed of a conductive metal. In this embodiment, the concept of metal includes alloys. The separation electrode 120 is disposed at least in the separation channel 112. In other words, the separation electrode 120 overlaps at least the separation channel 112. The separation electrode 120 includes a first electrode 121 and a second electrode 122. The first electrode 121 and the second electrode 122 have, for example, comb-like shapes that face each other. The first electrode 121 and the second electrode 122 do not have to have a comb-like shape.
[0029] The first electrode 121 has a plurality of teeth 1211, a first connection portion 1212, a second connection portion 1213, and a pad portion 1214. The teeth 1211 are an example of the "electrode" in the present invention.
[0030] Each of the multiple tooth portions 1211 has a generally rectangular cross-sectional shape. Each of the multiple tooth portions 1211 extends generally linearly. The multiple tooth portions 1211 are arranged generally parallel to one another. The multiple tooth portions 1211 extend in a first direction X. The multiple tooth portions 1211 are arranged at predetermined intervals in a second direction Y that intersects with the first direction X. In this embodiment, the second direction Y is perpendicular to the first direction X. Hereinafter, the second direction Y may be referred to as the width direction. The flow path 110 extends along a flow direction D in which the liquid flows. The flow direction D intersects with the first direction X. In this embodiment, the flow direction D is inclined with respect to the first direction X. Therefore, the flow direction D also intersects with the second direction Y and is also inclined with respect to the second direction Y.
[0031] The first connection portion 1212 connects the multiple tooth portions 1211 to each other. The multiple tooth portions 1211 and the first connection portion 1212 form a comb-tooth shape. The multiple tooth portions 1211 are arranged, for example, across the separation channel 112 in a planar view. The first connection portion 1212 is arranged outside the separation channel 112 in a planar view. The multiple tooth portions 1211 and the first connection portion 1212 are covered by the channel cover 105.
[0032] The second connection portion 1213 connects the first connection portion 1212 and the pad portion 1214. At least a portion of the second connection portion 1213 is covered by the flow path cover 105. At least a portion of the pad portion 1214 is arranged outside the flow path cover 105 in a plan view. In the present embodiment, the second connection portion 1213 is covered by the flow path cover 105. A portion of the pad portion 1214 is arranged outside the flow path cover 105 in a plan view. In this way, since at least a portion of the pad portion 1214 is not covered by the flow path cover 105, the pad portion 1214 can be easily electrically connected to the voltage control device 500.
[0033] The second electrode 122 has a plurality of teeth 1221, a first connection portion 1222, a second connection portion 1223, and a pad portion 1224. The teeth 1221 are an example of the "electrode" in the present invention.
[0034] Each of the multiple tooth portions 1221 has a generally rectangular shape in cross section. Furthermore, each of the tooth portions 1221 extends generally linearly. The multiple tooth portions 1221 are arranged generally parallel to one another. Furthermore, the multiple tooth portions 1221 are arranged generally parallel to the multiple tooth portions 1211. The first connection portion 1222 connects the multiple tooth portions 1221 to one another. The multiple tooth portions 1221 and the first connection portion 1222 form a comb-tooth shape. The multiple tooth portions 1221 are arranged, for example, across the separation channel 112 in plan view. The first connection portion 1222 is arranged outside the separation channel 112 in plan view. The multiple tooth portions 1221 and the first connection portion 1222 are covered by the channel cover 105.
[0035] The second connection portion 1223 connects the first connection portion 1222 and the pad portion 1224. At least a portion of the second connection portion 1223 is covered by the flow path cover 105. At least a portion of the pad portion 1224 is arranged outside the flow path cover 105 in a plan view. In the present embodiment, the second connection portion 1223 is covered by the flow path cover 105. A portion of the pad portion 1224 is arranged outside the flow path cover 105 in a plan view. In this way, since at least a portion of the pad portion 1224 is not covered by the flow path cover 105, the pad portion 1224 can be easily electrically connected to the voltage control device 500.
[0036] The voltage control device 500 is electrically connected to the pad portion 1214 and the pad portion 1224. The voltage control device 500 applies an AC voltage according to the type of dielectric particles P1 to the first electrode 121 and the second electrode 122 via the pad portion 1214 and the pad portion 1224. The AC voltage according to the type of dielectric particles P1 is, for example, a voltage with a frequency that generates an electric field that specifically acts on the dielectric particles P1 with a dielectrophoretic force (attractive force), and is large enough not to destroy the dielectric particles P1.
[0037] Specifically, the frequency of the AC voltage is set so that a positive dielectrophoretic force (attractive force) acts on the dielectric particle P1 due to the electric field between the first electrode 121 and the second electrode 122. Therefore, a positive dielectrophoretic force acts on the dielectric particle P1, and the dielectric particle P1 is attracted to the tooth portions 1211 and 1221. Hereinafter, the tooth portions 1211 and 1221 may be referred to as tooth portions 1201. The tooth portions 1201 are an example of an "electrode" in the present invention.
[0038] The dielectric particles P1 then flow downstream (toward the collection unit 113) along the tooth portions 1201. Specifically, the dielectric particles P1 flow along the tooth portions 1201 toward one side in the first direction X (toward the first connection portion 1212). The dielectric particles P1 then leave the tooth portions 1201 and flow downstream in the flow direction D along a side wall 1051 (described later) on the second supply unit 1112 and second collection unit 1132 side (upper side in FIG. 1 ) of the flow path cover 105. The dielectric particles P1 are then collected in the second collection unit 1132.
[0039] On the other hand, the frequency of the AC voltage is set so that the dielectrophoretic force does not act on, or barely acts on, the other particles P2. Therefore, the other particles P2 pass through the separation channel 112 and are collected in the collection section 113.
[0040] Continuing to refer to Fig. 1, the voltage control device 500 will be described. The voltage control device 500 includes a power supply unit 510 and a control unit 520.
[0041] The control unit 520 controls the power supply unit 510. The control unit 520 includes, for example, a processor and a storage device. The processor is, for example, a CPU (Central Processing Unit) or an MPU (Micro Processing Unit). The storage device stores data and computer programs. The storage device includes a main storage device such as a semiconductor memory and an auxiliary storage device such as a semiconductor memory, a solid-state drive, and / or a hard disk drive. The storage device may also include removable media. The storage device corresponds to an example of a non-transitory computer-readable storage medium.
[0042] The power supply unit 510 generates an AC voltage according to the dielectric particles P1 to be separated, and applies the AC voltage to the first electrode 121 and the second electrode 122 via the pad unit 1214 and the pad unit 1224. The power supply unit 510 is, for example, a signal generator such as a function generator.
[0043] By applying an AC voltage corresponding to the dielectric particles P1 to the first electrode 121 and the second electrode 122 by the power supply unit 510, a dielectrophoretic force (attractive force) acts on the dielectric particles P1. As a result, the dielectric particles P1 are attracted to the tooth portions 1201 (the tooth portions 1211 and 1221) and move along the tooth portions 1201, and the dielectric particles P1 are separated from the other particles P2. In this embodiment, the dielectric particles P1 are collected in the second collection unit 1132, and the other particles P2 pass through the separation channel 112 and are collected in the first collection unit 1131.
[0044] The voltage control device 500 may have a function of measuring electrical characteristics (such as impedance) between the first electrode 121 and the second electrode 122. The voltage control device 500 may also be configured by, for example, a source measure unit.
[0045] Next, the structure of the separation chip 100 will be further described with reference to Fig. 2. Fig. 2 is an enlarged cross-sectional view that schematically shows the structure around the teeth portion 1201 of the separation chip 100 of this embodiment.
[0046] 2, the separation chip 100 includes a substrate 101, a separation electrode 120, a channel cover 105, and an insulating film 103. The substrate 101 is, for example, a glass substrate. The material of the substrate 101 is, for example, quartz glass. However, the material of the substrate 101 is not limited to quartz glass. The substrate 101 has, for example, a substantially rectangular flat plate shape. However, the shape of the substrate 101 is not limited to a flat plate shape.
[0047] The separation electrode 120 is disposed on one surface 1011 of the substrate 101. The material of the separation electrode 120 is, for example, a metal such as aluminum, copper, and / or titanium. However, the material of the separation electrode 120 may be a metal other than aluminum, copper, and / or titanium. For example, the material of the separation electrode 120 may be a metal such as indium, tin, molybdenum, silver, chromium, tantalum, and / or silicon. The material of the separation electrode 120 may also be a material other than a metal, and may include, for example, an oxide such as a metal oxide, or a semiconductor. The surface of the separation electrode 120 may be oxidized. The separation electrode 120 may also be formed of, for example, indium tin oxide (ITO). The material of the separation electrode 120 is not particularly limited as long as the separation electrode 120 is conductive.
[0048] The separation electrode 120 has a generally rectangular cross-sectional shape. The separation electrode 120 has one surface 1205 and a pair of side surfaces 1206. The one surface 1205 is the surface on one side of the separation electrode 120 (the side opposite to the substrate 101). In this embodiment, the one surface 1205 of the separation electrode 120 is the surface that is visible when the separation electrode 120 is viewed from the flow channel 110 side. In this embodiment, the one surface 1205 of the separation electrode 120 is a surface that is generally parallel to one surface 1011 of the substrate 101.
[0049] The pair of side surfaces 1206 are connected to the one surface 1205. The pair of side surfaces 1206 extend from the ends of the one surface 1205 in the second direction Y toward the substrate 101.
[0050] The insulating film 103 covers at least a part of one surface 1205 of the separated electrode 120. In this embodiment, the insulating film 103 covers one surface 1205 and a pair of side surfaces 1206 of the tooth portion 1201. The insulating film 103 also covers the separated electrode 120 and a portion of one surface 1011 of the substrate 101 where the separated electrode 120 is not arranged. Note that the insulating film 103 does not cover at least the portions of the pad portions 1214 and 1224 that are connected to the voltage control device 500.
[0051] The insulating film 103 has insulating properties. The insulating film 103 is made of, for example, an oxide film such as a silicon oxide film, a nitride film such as a silicon nitride film, or a resin. In this embodiment, the insulating film 103 is a silicon oxide film. The thickness and material of the insulating film 103 affect the electric field generated by the separation electrode 120. In other words, the thickness and material of the insulating film 103 can control the electric field generated by the teeth 1201 of the separation electrode 120. The insulating film 103 also functions as a protective film that suppresses electrochemical reactions between the teeth 1201 of the separation electrode 120 and the sample solution.
[0052] In this embodiment, the insulating film 103 has a plurality of cover portions 1031 and a connection portion 1035. The cover portions 1031 are portions of the insulating film 103 that cover the tooth portions 1201. Specifically, the cover portions 1031 are portions of the insulating film 103 that are arranged on one surface 1205 and a side surface 1206 of the tooth portions 1201. The connection portions 1035 are portions of the insulating film 103 that connect adjacent cover portions 1031 to each other. The cover portions 1031 are an example of an "insulating layer" in the present invention.
[0053] In this embodiment, the electrode unit 12 is configured by the tooth portion 1201 and the cover portion 1031. In other words, the separation chip 100 includes a plurality of electrode units 12, and each electrode unit 12 has a tooth portion 1201 and a cover portion 1031. Therefore, the electrode units 12 extend along the first direction X. The plurality of electrode units 12 are arranged adjacent to each other in the second direction Y. A flow path 110 is provided on one side of the plurality of electrode units 12.
[0054] The thickness of the tooth portion 1201 of the electrode portion 12 is not particularly limited. The tooth portion 1201 has a thickness of, for example, several nanometers or more and several micrometers or less. The width of the tooth portion 1201 is not particularly limited. The tooth portion 1201 has a width of, for example, several tens of micrometers or more and several hundred micrometers or less. Furthermore, the thickness of the cover portion 1031 of the electrode portion 12 is not particularly limited. The cover portion 1031 has a thickness of, for example, several hundred nanometers or more and several micrometers or less.
[0055] On the other hand, the distance between adjacent electrode portions 12 and the distance between adjacent tooth portions 1201 have a predetermined size, as will be described later. The detailed structure of the electrode portion 12 will be described later.
[0056] The channel cover 105 is disposed on, for example, one surface 1033 of the insulating film 103. A portion of the channel cover 105 may be disposed on one surface 1011 of the substrate 101. The channel cover 105 covers one side (the side opposite to the substrate 101) of the separation electrode 120 and the insulating film 103. The channel cover 105 also forms the channel 110. Specifically, the channel cover 105 includes a sidewall 1051 (see FIG. 1 ) and a ceiling 1052. The sidewall 1051 and the ceiling 1052 form the channel 110 through which the sample liquid and the transport liquid flow. The sidewall 1051 surrounds at least a portion of the separation electrode 120 in a plan view.
[0057] The material of the flow path cover 105 is not particularly limited, but is, for example, a silicone-based resin. In this embodiment, the material of the flow path cover 105 is PDMS (polydimethylsiloxane). When the flow path cover 105 is made of PDMS, plasma treatment is performed on the surfaces of the flow path cover 105, the insulating film 103, and the substrate 101, so that the flow path cover 105 is firmly bonded to the insulating film 103 and the surface of the substrate 101.
[0058] Next, the detailed structure of the electrode portion 12 will be described. As shown in FIG. 2 , the distance L12 between the electrode portions 12 adjacent to each other in the second direction Y (the distance in the second direction Y) is less than twice the particle size of the dielectric particles P1. In this embodiment, the distance L12 between the electrode portions 12 adjacent to each other in the second direction Y is the same as the distance L1031 between the cover portions 1031 adjacent to each other in the second direction Y. In this embodiment, the distance L12 is less than twice the maximum particle size of the dielectric particles P1. In this case, the distance L12 is less than 40 μm. Alternatively, the distance L12 may be less than twice the average particle size of the dielectric particles P1. In this case, the distance L12 is less than 20 μm.
[0059] The distance L12 is preferably 1.5 times or less the particle diameter of the dielectric particles P1. In this embodiment, the distance L12 may be 1.5 times or less the maximum particle diameter of the dielectric particles P1. In this case, the distance L12 is 30 μm or less. The distance L12 may also be 1.5 times or less the average particle diameter of the dielectric particles P1. In this case, the distance L12 is 15 μm or less.
[0060] Furthermore, the distance L12 is preferably equal to or less than the particle size of the dielectric particles P1. In this embodiment, the distance L12 may be equal to or less than the maximum particle size of the dielectric particles P1. In this case, the distance L12 is 20 μm or less. The distance L12 may be equal to or less than the average particle size of the dielectric particles P1. In this case, the distance L12 is 10 μm or less.
[0061] The distance L12 is greater than 0 μm. In this embodiment, the distance L12 is, for example, 2 μm or greater.
[0062] The distance L1201 between adjacent tooth portions 1201 in the second direction Y may be less than twice the particle size of the dielectric particles P1. In this embodiment, the distance L1201 may be less than twice the maximum particle size of the dielectric particles P1. In this case, the distance L1201 is less than 40 μm. The distance L1201 may also be less than twice the average particle size of the dielectric particles P1. In this case, the distance L1201 is less than 20 μm.
[0063] Furthermore, the distance L1201 may be 1.5 times or less the particle size of the dielectric particles P1. In this embodiment, the distance L1201 may be 1.5 times or less the maximum particle size of the dielectric particles P1. In this case, the distance L1201 is 30 μm or less. Furthermore, the distance L1201 may be 1.5 times or less the average particle size of the dielectric particles P1. In this case, the distance L1201 is 15 μm or less.
[0064] Furthermore, the distance L1201 may be equal to or less than the particle size of the dielectric particles P1. In this embodiment, the distance L1201 may be equal to or less than the maximum particle size of the dielectric particles P1. In this case, the distance L1201 is 20 μm or less. Furthermore, the distance L1201 may be equal to or less than the average particle size of the dielectric particles P1. In this case, the distance L1201 is 10 μm or less.
[0065] The distance L1201 is greater than 0 μm. In this embodiment, the distance L1201 is, for example, 2 μm or greater.
[0066] Next, we will explain the dielectrophoretic force (attractive force) acting on the dielectric particles P1 due to the electric field between the first electrode 121 and the second electrode 122. Note that the electric field is strong at the corners of the electrodes, and the gradient of the electric field strength is large. For this reason, in Figure 2, to make it easier to understand the invention, an image of the area where the force (attractive force) that attracts the dielectric particles is strong is shown by a dashed line.
[0067] ∇E between two tooth portions 1201 2 (where ∇E denotes the gradient of the electric field strength) is the gradient of ∇E around the corner 127 adjacent to the two teeth 1201. 2 is estimated to be largest. Therefore, the dielectric particle P1 is attracted to the corner portion 127. Therefore, the dielectric particle P1 is attracted to the width direction end portion of the electrode portion 12. At this time, in this embodiment, since the distance L12 between adjacent electrode portions 12 is small, the dielectric particle P1 is attracted to both adjacent tooth portions 1201. Therefore, the dielectrophoretic force acting on the dielectric particle P1 can be increased. Note that even if the frequency and voltage are changed, the position to which the dielectric particle P1 is attracted does not change.
[0068] More specifically, the dielectrophoretic force is expressed by the following general formula (1):
[0069] [Math 1] F=2πr 3 ε m Re[K(ω)]∇E 2 ...(1)
[0070] where F denotes the dielectrophoretic force, r denotes the radius of the dielectric particle, and ε m denotes the real part of the permittivity of the surrounding medium. ω denotes the angular frequency. K(ω) denotes the Clausius-Mossotti function.
[0071] In the above formula (1), ∇E 2As can be seen from the inclusion of the term, the dielectrophoretic force is generated in a region where the AC electric field is non-uniform (hereinafter, sometimes referred to as a non-uniform electric field generation region). A non-uniform AC electric field region refers to a region where the spacing between electric field lines changes. In this embodiment, a non-uniform electric field is generated around the corners 127 located at the widthwise ends of the tooth portion 1201. Therefore, the dielectric particles P1 are attracted to the corners 127.
[0072] Next, the flow (movement) of the dielectric particles P1 through the separation chip 100 of this embodiment will be described with reference to Figures 1 and 3. Figure 3 is a plan view schematically showing the structure around the electrode unit 12 of the separation chip 100 and the dielectric particles P1. Note that in Figure 3, for ease of understanding, the electrode unit 12 is hatched and the flow path cover 105 and the like are omitted.
[0073] As shown in Figure 1, when a sample liquid containing dielectric particles P1 and particles P2 is introduced into the first supply section 1111 and a transport liquid is introduced into the second supply section 1112, the dielectric particles P1 and particles P2 flow downstream along the side wall 1051 of the flow path cover 105 on the first supply section 1111 and first collection section 1131 side (the lower side of Figure 1).
[0074] Since the dielectrophoretic force does not act on the particle P2 or acts only slightly on the particle P2, the particle P2 passes through the electrode unit 12. The particle P2 then flows downstream along the side wall 1051 of the flow path cover 105 on the first supply unit 1111 and first collection unit 1131 side (the lower side in FIG. 1 ), and is collected in the first collection unit 1131.
[0075] On the other hand, a dielectrophoretic force acts on the dielectric particles P1, so that the dielectric particles P1 are attracted to the teeth 1201 and move along the teeth 1201 toward the sidewall 1051 on the second supply unit 1112 and second collection unit 1132 side (upper side in FIG. 1 ).
[0076] At this time, as shown in FIG. 3, in this embodiment, the plurality of dielectric particles P1 move between the adjacent electrode portions 12 in a substantially line.
[0077] Then, the plurality of dielectric particles P1 are released from the electrode unit 12 in order of particle arrival at the side wall 1051 on the second supply unit 1112 and second collector 1132 side (upper side in FIG. 3 ). Thereafter, as shown in FIG. 1 , the dielectric particles P1 flow downstream along the side wall 1051 on the second supply unit 1112 and second collector 1132 side (upper side in FIG. 1 ) of the flow path cover 105, and are collected in the second collector 1132.
[0078] In this embodiment, as described above, the distance L12 between adjacent electrode portions 12 in the second direction Y is less than twice the particle size of the dielectric particle P1. Therefore, when the dielectric particle P1 moves along the electrode portions 12 between adjacent electrode portions 12, it is possible to prevent the subsequent dielectric particle P1 from overtaking the preceding dielectric particle P1. Therefore, it is possible to prevent the order of the dielectric particles P1 moving along the electrode portions 12 from being changed.
[0079] Furthermore, by setting the distance L12 to less than twice the particle size of the dielectric particle P1, the dielectric particle P1 is attracted to both of the adjacent electrode portions 12. Therefore, the dielectrophoretic force acting on the dielectric particle P1 can be increased.
[0080] Furthermore, by using the separation chip 100 of this embodiment, for example, when analyzing cells (dielectric particles P1) moving in a line by irradiating them with laser light (also known as flow cytometry), it is possible to prevent the order of the cells from being changed, thereby improving the accuracy of the analysis.
[0081] Furthermore, for example, by providing a mechanism that hydrodynamically or electromagnetically changes the flow direction of cells (dielectric particles P1) downstream of the electrode unit 12 of the separation chip 100 of this embodiment, the accuracy of cell sorting can be improved. As a result, it is possible to reduce the loss of cells (dielectric particles P1) and the amount of sample liquid used. This also contributes to reducing the environmental impact.
[0082] Furthermore, as described above, the electrode portion 12 has the cover portion 1031, and the distance L1031 between the cover portions 1031 adjacent to each other in the second direction Y is less than twice the particle size of the dielectric particle P1. Therefore, even when the electrode portion 12 has the cover portion 1031, the distance L12 between the adjacent electrode portions 12 can easily be set to less than twice the particle size of the dielectric particle P1.
[0083] Furthermore, as described above, the distance L1201 between the tooth portions 1201 adjacent to each other in the second direction Y may be less than twice the particle size of the dielectric particles P1. With this configuration, even if there is variation in the thickness of the cover portion 1031, the distance L12 between the adjacent electrode portions 12 can be reliably set to less than twice the particle size of the dielectric particles P1.
[0084] Furthermore, as described above, the distance L12 between the electrode portions 12 adjacent to each other in the second direction Y may be 1.5 times or less the particle diameter of the dielectric particles P1. This configuration effectively prevents the order of the dielectric particles P1 moving along the electrode portions 12 from being changed. The effect of setting the distance L12 to 1.5 times or less the particle diameter of the dielectric particles P1 will be described later.
[0085] Furthermore, as described above, the distance L12 between the electrode portions 12 adjacent to each other in the second direction Y may be equal to or less than the particle size of the dielectric particles P1. This configuration can further prevent the order of the dielectric particles P1 moving along the electrode portions 12 from being changed.
[0086] Next, the effect of setting the distance L12 between adjacent electrode parts 12 in the second direction Y to 1.5 times or less the particle size of the dielectric particle P1 will be described with reference to Fig. 4. Fig. 4 is a diagram for explaining the effect of setting the distance L12 between adjacent electrode parts 12 in the second direction Y to 1.5 times or less the particle size of the dielectric particle P1.
[0087] As shown in FIG. 4 , in a planar view, a first particle (hereinafter sometimes referred to as a dielectric particle P11) that is one of the dielectric particles P1 is in contact with one of the electrode units 12 adjacent in the second direction Y (the upstream electrode unit 12), and a second particle (hereinafter sometimes referred to as a dielectric particle P12) that is another of the dielectric particles P1 is in contact with the other of the electrode units 12 adjacent in the second direction Y (the downstream electrode unit 12) and the dielectric particle P11. Furthermore, a line connecting the center P111 of the dielectric particle P11 and the center P121 of the dielectric particle P12 is denoted as L1. Furthermore, the angle formed by the line L1 and the first direction X is denoted as φ (where 0°≦φ≦180°), the particle diameter of the dielectric particle P1 is denoted as R, and the distance between adjacent electrode units 12 is denoted as d. In this case, the distance d (= distance L12) satisfies the following formula (2).
[0088] [Math 2] d=R(1+sinφ)...(2)
[0089] Here, when viewed from the first direction X, if the overlap width W1 between the dielectric particles P11 and P12 is R / 2 or more, the subsequent dielectric particle P12 will hardly overtake the preceding dielectric particle P11 when the dielectric particles P11 and P12 move along the electrode portion 12. In other words, the order of the dielectric particles P11 and P12 will hardly be reversed.
[0090] When the overlap width W1 is R / 2 or more, Rsinφ is R / 2 or less. In other words, Rsinφ≦R / 2 is satisfied. In this case, the angle φ is 0°≦φ≦30°, and the distance d is d≦1.5R according to the above formula (2).
[0091] Therefore, by setting the distance L12 (= distance d) between adjacent electrode portions 12 in the second direction Y to 1.5 times or less the particle size R of the dielectric particle P1, the order of the dielectric particle P11 and the dielectric particle P12 can be effectively prevented from being reversed when the dielectric particles P11 and the dielectric particles P12 move along the electrode portion 12.
[0092] Next, with reference to Fig. 5, the effect of being able to suppress the timing at which the plurality of dielectric particles P1 are separated (released) from the electrode portion 12 from becoming too close will be described. Fig. 5 is a diagram for explaining the effect of being able to suppress the timing at which the plurality of dielectric particles P1 are separated (released) from the electrode portion 12 from becoming too close. The positional relationship between the dielectric particles P11 and P12 is the same as in Fig. 4.
[0093] 5, the angle between the first direction X and the flow direction D is defined as θ (where 0°≦θ<90°). The distance in the flow direction D between the leading dielectric particle P11 and the trailing dielectric particle P12 is defined as x. In this case, the distance x satisfies the following formula (3):
[0094] [Math 3] x=R|cos(φ+θ)|...(3)
[0095] Here, |cos(φ+θ)| indicates the absolute value of cos(φ+θ).
[0096] Here, if the distance x is R / 2 or more, a sufficient time difference can be ensured between the timing at which the dielectric particle P11 separates from the electrode portion 12 and the timing at which the dielectric particle P12 separates from the electrode portion 12. Therefore, the order of the dielectric particle P11 and the dielectric particle P12 is rarely reversed.
[0097] When the distance x is equal to or greater than R / 2, φ+θ satisfies 0°≦φ+θ≦60° or 120°≦φ+θ≦180° from the above formula (3).
[0098] Therefore, by configuring the separation chip 100 to satisfy 0°≦φ+θ≦60° or 120°≦φ+θ≦180°, the order of the dielectric particles P11 and P12 can be effectively prevented from being reversed when the dielectric particles P11 and P12 move away from the electrode portion 12.
[0099] (First Modification) Next, a separation chip 100 according to a first modification of the present invention will be described with reference to Fig. 6. Fig. 6 is a plan view schematically showing the structure around the electrode unit 12 and the dielectric particles P1 of the separation chip 100 according to the first modification of the present invention. In Fig. 6, for ease of understanding, the electrode unit 12 is hatched and the flow channel cover 105 and the like are omitted. In the first modification, an example will be described in which only two electrode units 12 are provided, unlike the above embodiment.
[0100] As shown in FIG. 6 , in the separation chip 100 of the first modified example, unlike the above embodiment, the first electrode 121 has one tooth portion 1211. The second electrode 122 has one tooth portion 1221. In other words, the separation chip 100 of the first modified example has only two electrode portions 12. Therefore, unlike when there are three or more electrode portions 12, there is only one path along which the dielectric particles P1 move along the electrode portions 12. Therefore, it is easy to make the order of the dielectric particles P1 moving in a substantially single line between the electrode portions 12 the same as the order of the dielectric particles P1 moving away from the electrode portions 12 along the side wall 1051.
[0101] The other structures and effects of the first modified example are similar to those of the above embodiment.
[0102] (Second Modification) Next, a separation chip 100 according to a second modification of the present invention will be described with reference to Figures 7 to 9. Figure 7 is an enlarged cross-sectional view schematically showing the structure around the tooth portion 1201 of the separation chip 100 according to the second modification of the present invention. In the second modification, unlike the above embodiment and the first modification, an example will be described in which an opening 1032 is formed in the cover portion 1031 of the insulating film 103.
[0103] 7 , in the second modified example, one surface 1205 of the tooth portion 1201 has a first region 12051 and a second region 12052 that is different from the first region 12051. Specifically, the one surface 1205 has the first region 12051 located in the center in the width direction and a pair of second regions 12052 that are located outward in the width direction from the first region 12051.
[0104] In the second modified example, unlike the above embodiment and the first example, the distance L12 between adjacent electrode parts 12 is at least twice the maximum particle size of the dielectric particles P1.
[0105] The insulating film 103 covers at least a portion of one surface 1205 of the tooth portion 1201. In the second modified example, the thickness of the insulating film 103 on the first region 12051 of the tooth portion 1201 is smaller than the thickness of the insulating film 103 on the second region 12052 of the tooth portion 1201. In the second modified example, the thickness of the insulating film 103 on the first region 12051 of the tooth portion 1201 is zero. Note that the thickness of the insulating film 103 on the first region 12051 does not have to be zero.
[0106] Specifically, the insulating film 103 has an opening 1032 that connects the first region 12051 of the tooth portion 1201 and the flow path 110. That is, in the second modified example, the insulating film 103 is not formed on the first region 12051. The opening 1032 is located on the first region 12051 and penetrates the insulating film 103.
[0107] Here, in the second modified example, the width W121 in the second direction Y of the first region 12051 is less than twice the particle size of the dielectric particles P1. Note that the width W121 in the second direction Y of the first region 12051 is the same size as the width in the second direction Y of the opening 1032. In this embodiment, the width W121 is less than twice the maximum particle size of the dielectric particles P1. In this case, the width W121 is less than 40 μm. The width W121 may also be less than twice the average particle size of the dielectric particles P1. In this case, the width W121 is less than 20 μm. The width W121 of the first region 12051 is an example of the "length in the second direction of the first region" in the present invention.
[0108] Furthermore, it is preferable that the width W121 of the first region 12051 is 1.5 times or less the particle size of the dielectric particles P1. In this embodiment, the width W121 may be 1.5 times or less the maximum particle size of the dielectric particles P1. In this case, the width W121 is 30 μm or less. Furthermore, the width W121 may be 1.5 times or less the average particle size of the dielectric particles P1. In this case, the width W121 is 15 μm or less.
[0109] Furthermore, it is preferable that the width W121 is equal to or smaller than the particle size of the dielectric particles P1. In this embodiment, the width W121 may be equal to or smaller than the maximum particle size of the dielectric particles P1. In this case, the width W121 is equal to or smaller than 20 μm. Furthermore, the width W121 may be equal to or smaller than the average particle size of the dielectric particles P1. In this case, the width W121 is equal to or smaller than 10 μm.
[0110] The width W121 is greater than 0 μm. In the second modified example, the width W121 is, for example, 2 μm or greater.
[0111] The other configurations of the second modified example are similar to those of the above embodiment and the first modified example.
[0112] Next, the dielectrophoretic force (attractive force) acting on the dielectric particles P1 due to the electric field between the first electrode 121 and the second electrode 122 will be described with reference to Fig. 8. Fig. 8 is an enlarged cross-sectional view schematically showing the structure around the teeth 1201 of the separation chip 100 according to a second modified example of the present invention. In Fig. 8, to make the invention easier to understand, an image of the region where the force (attractive force) that attracts the dielectric particles is strong is shown by a dashed line.
[0113] 8, in the separation chip 100 of the second modification, the thickness of the insulating film 103 on the first region 12051 of the tooth portion 1201 is smaller than the thickness of the insulating film 103 on the second region 12052 of the tooth portion 1201. Therefore, by adjusting the voltage value and frequency applied between the tooth portions 1201, the ∇E 2 Therefore, the dielectric particles P1 are attracted to the first region 12051 of the tooth portion 1201. Here, the dielectric particles P1 are attracted to the center of the tooth portion 1201 in the width direction.
[0114] In this case, in the second modified example, since the width W121 (see Figure 7) of the first region 12051 is small, the dielectric particle P1 is attracted by both the dielectrophoretic force generated at the upstream end of the first region 12051 and the dielectrophoretic force generated at the downstream end of the first region 12051.
[0115] Next, the flow (movement) of the dielectric particles P1 through the separation chip 100 of the second modified example will be described with reference to Fig. 9. Fig. 9 is a plan view schematically showing the structure around the electrode unit 12 of the separation chip 100 and the dielectric particles P1. Note that in Fig. 9, for ease of understanding, the insulating film 103 on the electrode unit 12 is hatched, and the flow path cover 105 and the like are omitted.
[0116] 9, as in the above embodiment, a dielectrophoretic force acts on the dielectric particles P1. As a result, the dielectric particles P1 are attracted to the electrode unit 12 and move along the electrode unit 12 toward the sidewall 1051 on the second supply unit 1112 and second collection unit 1132 side (upper side in FIG. 1).
[0117] At this time, in the second modified example, the plurality of dielectric particles P1 move in a substantially single line on the first region 12051 of the tooth portion 1201. That is, in the second modified example, the plurality of dielectric particles P1 can be moved along the center of the tooth portion 1201 in the width direction.
[0118] The other flow (movement) of the dielectric particles P1 in the second modified example is the same as in the above embodiment.
[0119] Next, we will briefly explain the effect of setting the width W121 of the first region 12051 to 1.5 times or less the particle diameter of the dielectric particle P1. The effect of setting the width W121 of the first region 12051 to 1.5 times or less the particle diameter of the dielectric particle P1 is similar to the effect of setting the distance L12 between the electrode portions 12 to 1.5 times or less the particle diameter of the dielectric particle P1, as described with reference to FIG.
[0120] 4 are replaced with two second regions 12052, and the region between the two electrode portions 12 is replaced with a first region 12051. That is, in a planar view, a first particle (dielectric particle P11) that is one of the dielectric particles P1 is in contact with one side of the second region 12052 adjacent to it in the second direction Y (the upstream second region 12052), and a second particle (dielectric particle P12) that is another one of the dielectric particles P1 is in contact with the other side of the second region 12052 adjacent to it in the second direction Y (the downstream second region 12052) and the dielectric particle P11. In this case, as in the above embodiment, it can be seen that by setting the width W121 of the first region 12051 to 1.5 times or less the particle size of the dielectric particle P1, it is possible to effectively prevent the order of the dielectric particles P11 and P12 from being swapped when the dielectric particles P11 and P12 move along the first region 12051. Therefore, detailed explanation will be omitted.
[0121] 5, in the second modified example, the separation chip 100 is configured to satisfy 0°≦φ+θ≦60° or 120°≦φ+θ≦180°. Therefore, when the dielectric particles P11 and the dielectric particles P12 move away from the first region 12051, the order of the dielectric particles P11 and the dielectric particles P12 can be effectively prevented from being reversed.
[0122] Other effects of the second modified example are similar to those of the above embodiment.
[0123] (Third Modification) Next, a separation chip 100 according to a third modification of the present invention will be described with reference to Figures 10 and 11. Figure 10 is an enlarged cross-sectional view schematically showing the structure around the tooth portion 1201 of the separation chip 100 according to the third modification of the present invention. In the third modification, an example will be described in which the tooth portion 1201 has a generally concave shape in cross section, unlike the above-described embodiment, first example, and second modification.
[0124] As shown in FIG. 10 , in the third modified example, one surface 1205 of the tooth portion 1201 has a first region 12051 and a second region 12052 different from the first region 12051, as in the second modified example.
[0125] Here, in the third modified example, a step 12053 is formed on one surface 1205 of the tooth portion 1201. Furthermore, in the third modified example, the electrode portion 12 and the tooth portion 1201 have a concave shape in cross section. Specifically, a pair of second regions 12052 extend inward in the width direction from a pair of side surfaces 1206. The first region 12051 is disposed between the pair of second regions 12052 and approximately parallel to the second regions 12052. The first region 12051 is disposed closer to the substrate 101 than the pair of second regions 12052. The tooth portion 1201 has a pair of connection surfaces 1251, which connect the pair of second regions 12052 and the first region 12051. The first region 12051 and the pair of connection surfaces 1251 form a recess 1260 in the tooth portion 1201.
[0126] As in the second modification, the insulating film 103 covers at least a portion of one surface 1205 of the tooth portion 1201. Furthermore, the thickness of the insulating film 103 on the first region 12051 of the tooth portion 1201 is smaller than the thickness of the insulating film 103 on the second region 12052 of the tooth portion 1201. In the third modification, the thickness of the insulating film 103 on the first region 12051 of the tooth portion 1201 is zero.
[0127] Specifically, similar to the second modification, the insulating film 103 has an opening 1032 that connects the first region 12051 of the tooth portion 1201 to the flow path 110. The opening 1032 is located on the first region 12051 and penetrates the insulating film 103.
[0128] Furthermore, the insulating film 103 is not formed on at least a part of the connection surface 1251. In other words, at least a part of the connection surface 1251 is connected to the flow channel 110 without the insulating film 103. In this embodiment, the insulating film 103 is not formed on the connection surface 1251.
[0129] The other configurations of the third modified example are the same as those of the second modified example.
[0130] Next, the effect of forming the electrode portion 12 and the tooth portion 1201 of the separation chip 100 of the third modified example in a concave shape will be described with reference to Fig. 11. Fig. 11 is an enlarged cross-sectional view that schematically shows the structure around the tooth portion 1201 of the separation chip 100 of the third modified example. In Fig. 11, to make the invention easier to understand, an image of an area where the force that attracts the dielectric particles (attractive force) is strong is shown by a dashed line.
[0131] As shown in FIG. 11 , in the separation chip 100 of the third modification, by forming a step 12053 and / or a recess 1260 on one surface 1205 of the tooth portion 1201, the AC electric field can be made more non-uniform around a predetermined position on one surface 1205 of the tooth portion 1201 compared to the separation chip 100 of the second modification shown in FIGS. 7 and 8 . In other words, the rate of change of the electric field strength (the gradient of the electric field strength) around a predetermined position on one surface 1205 of the tooth portion 1201 can be made larger. This makes it possible to further strengthen the dielectrophoretic force. In particular, the rate of change of the electric field strength (the gradient of the electric field strength) is large at the corner where the first region 12051 and the connection surface 1251 meet and at the corner where the connection surface 1251 and the second region 12052 meet.
[0132] Other effects of the third modified example are similar to those of the second modified example.
[0133] (Fourth Modification) Next, a separation chip 100 according to a fourth modification of the present invention will be described with reference to Fig. 12. Fig. 12 is a plan view schematically showing the structure around the electrode unit 12 and the dielectric particles P1 of the separation chip 100 according to the fourth modification of the present invention. In Fig. 12, for ease of understanding, the insulating film 103 on the electrode unit 12 is hatched, and the flow channel cover 105 and the like are omitted. In the fourth modification, unlike the second and third modifications, an example in which only three electrode units 12 are provided will be described.
[0134] As shown in FIG. 12 , in the separation chip 100 of the fourth modified example, unlike the second and third modified examples, for example, the first electrode 121 has one tooth portion 1211. Furthermore, for example, the second electrode 122 has two tooth portions 1221. In other words, the separation chip 100 of the fourth modified example has only three electrode portions 12. Therefore, unlike when four or more electrode portions 12 are provided, the dielectric particles P1 move along only one path along the electrode portions 12. Therefore, the order of the dielectric particles P1 moving in a substantially single line on the central electrode portion 12 can easily be made the same as the order of the dielectric particles P1 moving away from the electrode portion 12 along the side wall 1051.
[0135] In addition, ∇E 2 is generated at the central electrode portion 12. 2 , the dielectric particles P1 are not captured by the electrode portions 12 arranged on both sides in the width direction.
[0136] The other structures and effects of the fourth modified example are similar to those of the second and third modified examples.
[0137] (Fifth Modification) Next, a separation chip 100 according to a fifth modification of the present invention will be described with reference to Fig. 13. Fig. 13 is a plan view schematically showing the structure of the separation chip 100 according to the fifth modification of the present invention. In the fifth modification, unlike the above embodiment, an example will be described in which the separation chip 100 includes, for example, HDF (Hydrodynamic filtration) 200.
[0138] As shown in FIG. 13 , in the fifth modified example, the separation chip 100 further includes an HDF 200. The HDF 200 is disposed upstream of the separation electrode 120. The HDF 200 functions as a hydrodynamic filter. For example, the HDF 200 is a microchannel intended for separating and / or concentrating fine particles. The HDF 200 has a plurality of branch channels 201 branching off from the separation channel 112. The HDF 200 is configured by the plurality of branch channels 201 and a portion of the separation channel 112. The plurality of branch channels 201 are disposed, for example, so as to extend perpendicular to the separation channel 112. Furthermore, the plurality of branch channels 201 are disposed, for example, at approximately equal intervals along the direction in which the separation channel 112 extends.
[0139] The liquid flowing through the separation channel 112 flows into the plurality of branch channels 201. Also, some of the particles contained in the liquid flowing through the separation channel 112 flow into the plurality of branch channels 201. Specifically, particles having a particle size smaller than a predetermined size flow into the branch channels 201, while particles having a particle size equal to or greater than the predetermined size proceed substantially straight through the separation channel 112 without flowing into the branch channels 201. In other words, the HDF 200 separates particles having a particle size smaller than a predetermined size from the liquid flowing through the separation channel 112. In the fifth modified example, the dielectric particles P1 do not flow into the branch channels 201 of the HDF 200, but proceed substantially straight through the separation channel 112.
[0140] In the fifth modification, as described above, the separation chip 100 further includes the HDF 200. Therefore, the HDF 200 can separate particles smaller than a predetermined size from particles contained in the sample liquid, and then the separation electrode 120 can separate the dielectric particles P1 from particles equal to or larger than the predetermined size.
[0141] The other structures and effects of the fifth modified example are similar to those of the above-described embodiment and the first to fourth modified examples.
[0142] The above describes embodiments of the present invention with reference to the drawings. However, the present invention is not limited to the above embodiments and can be embodied in various forms without departing from the spirit and scope of the present invention. Furthermore, various inventions can be formed by appropriately combining multiple components disclosed in the above embodiments. For example, some components may be omitted from all components shown in the embodiments. Furthermore, components from different embodiments and variations may be appropriately combined. The drawings mainly show each component in a schematic manner to facilitate understanding. The thickness, length, number, spacing, etc. of each illustrated component may differ from the actual components due to the convenience of drawing. Furthermore, the materials, shapes, dimensions, etc. of each component shown in the above embodiments are merely examples and are not particularly limited. Various modifications are possible within a scope that does not substantially deviate from the effects of the present invention.
[0143] For example, in the above embodiment, an example has been described in which the electrode portion 12 has the tooth portion 1201 and the cover portion 1031, but the present invention is not limited to this. For example, the electrode portion 12 does not have to have the cover portion 1031. In other words, the separation chip 100 does not have to be provided with the insulating film 103.
[0144] Furthermore, for example, in the above embodiment, an example has been described in which the first direction X is inclined with respect to the flow direction D, but the present invention is not limited to this. For example, the first direction X may be parallel to the flow direction D.
[0145] The present invention can be used in the field of separation chips.
[0146] 12: Electrode portion 100: Separation chip 101: Substrate 110: Flow path 1011: One side 1031: Cover portion (insulating layer) 1201, 1211, 1221: Tooth portion (electrode) 1205: One side 12051: First region 12052: Second region D: Flow direction L1: Straight line L12, L1031: Distance P1: Dielectric particle (specific dielectric particle) P11: Dielectric particle (specific dielectric particle, first particle) P111, P121: Center P12: Dielectric particle (specific dielectric particle, second particle) R: Particle size W121: Width (length) X: First direction Y: Second direction θ: Angle φ: Angle
Claims
1. A separation chip used for capturing specific dielectric particles contained in a liquid, comprising: a substrate; and a plurality of electrode portions disposed on one surface of the substrate, having at least electrodes and extending in a first direction, wherein the plurality of electrode portions are disposed adjacent to each other in a second direction intersecting the first direction, a flow path through which the liquid flows in a flow direction intersecting the first direction is provided on one side of the plurality of electrode portions, and a distance between the electrode portions adjacent to each other in the second direction is less than twice the particle size of the specific dielectric particles.
2. The separation chip according to claim 1, wherein the electrode portion has an insulating layer covering the electrode, and a distance between the insulating layers adjacent to each other in the second direction is less than twice the particle size of the specific dielectric particles.
3. The separation chip according to claim 2, wherein a distance between the electrodes adjacent to each other in the second direction is less than twice the particle size of the specific dielectric particles.
4. The separation chip according to claim 1, wherein a distance between the electrode portions adjacent to each other in the second direction is 1.5 times or less the particle size of the specific dielectric particles.
5. The separation chip according to claim 4, wherein a distance between the electrode portions adjacent to each other in the second direction is equal to or less than the particle size of the specific dielectric particles.
6. In a plan view, when a first particle, which is one of the specific dielectric particles, contacts one of the electrode portions adjacent to each other in the second direction, and a second particle, which is another one of the specific dielectric particles, contacts the other of the electrode portions adjacent to each other in the second direction and the first particle, an angle formed between a straight line connecting the center of the first particle and the center of the second particle and the first direction is φ, and an angle formed between the first direction and the flow direction is θ, then the separation chip according to any one of claims 1 to 5 satisfies 0° ≦ φ + θ ≦ 60° or 120° ≦ φ + θ ≦ 180°.
7. A separation chip used for capturing specific dielectric particles contained in a liquid, comprising: a substrate; and a plurality of electrode portions disposed on one surface of the substrate and extending in a first direction, wherein the plurality of electrode portions are disposed adjacent to each other in a second direction intersecting the first direction, a flow path through which the liquid flows in a flow direction intersecting the first direction is provided on one side of the plurality of electrode portions, the electrode portion has an electrode disposed on one surface of the substrate and an insulating layer covering the electrode, one surface of the electrode has a first region and a second region different from the first region, the thickness of the insulating layer on the first region is smaller than the thickness of the insulating layer on the second region, and the length of the first region in the second direction is less than twice the particle diameter of the specific dielectric particles.
8. The separation chip according to claim 7, wherein the length of the first region in the second direction is 1.5 times or less the particle diameter of the specific dielectric particles.
9. The separation chip according to claim 8, wherein the length of the first region in the second direction is equal to or less than the particle diameter of the specific dielectric particles.
10. In a plan view, when a first particle, which is one of the specific dielectric particles, contacts one of the second regions adjacent in the second direction, and a second particle, which is another one of the specific dielectric particles, contacts the other of the second regions adjacent in the second direction and the first particle, the angle formed by a straight line connecting the center of the first particle and the center of the second particle and the first direction is φ, and the angle formed by the first direction and the flow direction is θ, then 0° ≤ φ + θ ≤ 60° or 120° ≤ φ + θ ≤ 180°. The separation chip according to any one of claims 7 to 9.
11. The insulating layer has an opening connecting the first region and the flow path, the first region is connected to the flow path through the opening, and the first region is located closer to the substrate side than the second region. The separation chip according to any one of claims 7 to 9.
Citation Information
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