Flow path device and method for controlling flow path device

Abstract

This flow path device (1) comprises: a substrate (2); a flow path (8) that is formed on the substrate (2), extends in a first direction, and can circulate a substance (S); a first electrode (9a) and a second electrode (9b) that are disposed on one side of the flow path (8) in a second direction intersecting the first direction; and a third electrode (9c) and a fourth electrode (9d) that are disposed on the other side of the flow path (8) in the second direction. Voltages applied to the first electrode (9a), the second electrode (9b), the third electrode (9c), and the fourth electrode (9d) are controlled to thereby adjust the position of the substance (S) in the flow path (8).

Description

Flow path device and method for controlling the flow path device

[0001] The present invention relates to a flow path device and a method for controlling the flow path device.

[0002] Non-Patent Document 1, for example, discloses a device for separating specific particles, such as cells, from other particles by dielectrophoresis. In this device, a sample solution containing suspended particles is flowed through a flow channel formed on a glass substrate. When an AC voltage is applied to multiple pairs of electrodes adjacent to the flow channel, an electric field is formed within the flow channel between adjacent pairs of electrodes. This electric field acts on the particles with an attractive force (positive dielectrophoretic force) or a repulsive force (negative dielectrophoretic force), causing the specific particles to move within the flow channel.

[0003] Niccolo Piacentini et al., “Separation of platelets from other blood cells in continuous-flow by dielectrophoresis field-flow-fractionation,” Biomicrofluidics. September 21, 2011, 5(3): 034122-034122-8.

[0004] In Non-Patent Document 1, the electrodes are planar electrodes in which multiple pairs of electrodes are formed along the surface of a glass substrate. With these planar electrodes, an electric field is formed that crosses the flow path along the surface of the glass substrate. This electric field is formed only between adjacent pairs of electrodes. Since there is a restriction on the distance between adjacent pairs of electrodes, the range in which the electric field acts is limited. Therefore, it is expected that it will not be possible to move certain particles within the flow path.

[0005] Therefore, an object of the present invention is to provide a flow channel device and a method for controlling the flow channel device that can adjust the position of a substance in a flow channel with high precision.

[0006] A flow path device according to one aspect of the present invention comprises a substrate, a flow path formed in the substrate and extending in a first direction, capable of circulating a substance, a first electrode and a second electrode arranged on one side of the flow path in a second direction intersecting the first direction, and a third electrode and a fourth electrode arranged on the other side of the flow path in the second direction, and adjusts the position of the substance within the flow path by controlling voltages applied to the first electrode, the second electrode, the third electrode, and the fourth electrode.

[0007] In the flow channel device according to one aspect of the present invention, the first electrode faces the third electrode in the second direction, and the second electrode faces the fourth electrode in the second direction.

[0008] In a flow path device according to one aspect of the present invention, the difference in voltage value between the first electrode and the second electrode and the difference in voltage value between the third electrode and the fourth electrode are made different from each other, so that the substance moves within the flow path toward the side with the smaller difference in voltage value.

[0009] In a flow path device according to one aspect of the present invention, the difference in voltage value between the first electrode and the third electrode and the difference in voltage value between the second electrode and the fourth electrode are made different from each other, so that the substance moves within the flow path toward the side with the smaller difference in voltage value.

[0010] In the flow channel device according to one aspect of the present invention, the base material constitutes a flexible printed circuit board.

[0011] In a flow channel device according to one aspect of the present invention, the first electrode and the second electrode face one side of the flow channel, and the third electrode and the fourth electrode face the other side of the flow channel.

[0012] A method for controlling a flow path device according to one aspect of the present invention includes a flow path device comprising a substrate, a flow path formed in the substrate and extending in a first direction, capable of circulating a substance, a first electrode and a second electrode arranged on one side of the flow path in a second direction intersecting the first direction, and a third electrode and a fourth electrode arranged on the other side of the flow path in the second direction, the method comprising the step of adjusting the position of the substance within the flow path by controlling voltages applied to the first electrode, the second electrode, the third electrode, and the fourth electrode.

[0013] In a method for controlling a flow channel device according to one aspect of the present invention, the first electrode faces the third electrode in the second direction, and the second electrode faces the fourth electrode in the second direction.

[0014] In one embodiment of the method for controlling a flow path device of the present invention, the difference in voltage value between the first electrode and the second electrode and the difference in voltage value between the third electrode and the fourth electrode are made different from each other, thereby causing the substance to move within the flow path toward the side with the smaller difference in voltage value.

[0015] In one embodiment of the method for controlling a flow path device of the present invention, the difference in voltage value between the first electrode and the third electrode and the difference in voltage value between the second electrode and the fourth electrode are made different from each other, thereby causing the substance to move within the flow path toward the side with the smaller difference in voltage value.

[0016] According to the present invention, it is possible to provide a flow channel device and a method for controlling a flow channel device that can adjust the position of a substance in a flow channel with high precision.

[0017] 3 is a perspective view schematically showing the structure of a flow channel device 1 according to one embodiment of the present invention. FIG. 4 is a plan view schematically showing the structure of a flow channel device 1 according to one embodiment of the present invention. FIG. 5 is a cross-sectional view taken along line 3-3 in FIG. 2. FIG. 6 is a cross-sectional view taken along line 4-4 in FIG. 2. FIG. 7 is a diagram showing an example of an analysis result obtained by analysis software. FIG. 8 is a diagram showing another example of an analysis result obtained by analysis software. FIG. 9 is a diagram showing yet another example of an analysis result obtained by analysis software. FIG. 10 is a diagram showing yet another example of an analysis result obtained by analysis software. FIG. 11 is a diagram showing yet another example of an analysis result obtained by analysis software. FIG. 12 is a diagram showing yet another example of an analysis result obtained by analysis software. FIG. 13 is a partial plan view corresponding to FIG. 2 and schematically showing the structure of a flow channel device 1 according to a modified example.

[0018] An embodiment of the present invention will be described below with reference to the accompanying drawings. FIG. 1 is a perspective view schematically illustrating the structure of a flow channel device 1 according to an embodiment of the present invention. FIG. 2 is a plan view schematically illustrating the structure of the flow channel device 1. FIG. 3 is a cross-sectional view taken along line 3-3 in FIG. 2. FIG. 4 is a cross-sectional view taken along line 4-4 in FIG. 2. This flow channel device 1 is a device for aligning (focusing) substances containing specific particles such as cells using, for example, dielectrophoresis, and then separating (sorting) one substance from another. Note that, for convenience, the terms "up" and "down" are used in the following description, but these terms do not necessarily correspond to up and down in the direction of gravity.

[0019] 1 to 4 , the flow path device 1 includes a substrate 2. The substrate 2 is formed, for example, from a thin plate having a rectangular outline in a plan view. The substrate 2 defines side surfaces 2a and 2b on its long sides, which are parallel to each other. In the flow path device 1, a first direction, i.e., a longitudinal direction, is defined parallel to the side surfaces 2a and 2b. The substrate 2 has a laminate structure in which multiple layers are stacked. Specifically, the substrate 2 includes a base 3, a first cover 4 and a second cover 5 stacked on the front and back surfaces of the base 3, which face each other, a first covering member 6 stacked on the front surface of the first cover 4, and a second covering member 7 stacked on the back surface of the second cover 5. The base 3, the first cover 4, the second cover 5, the first covering member 6, and the second covering member 7 are adhered to each other with an adhesive or the like.

[0020] The substrate 2 is formed, for example, from a flexible printed circuit (FPC). The base 3, first cover 4, second cover 5, first covering member 6, and second covering member 7 are all formed from a flexible, transparent material. That is, the substrate 2 as a whole is flexible. In this example, the base 3, first cover 4, and second cover 5 are all formed from a resin material such as polyimide. The first covering member 6 and second covering member 7 are also formed from a resin material such as polydimethylsiloxane (PDMS). The thickness of the substrate 2 is set to, for example, about 100 μm.

[0021] The flow channel device 1 has a flow channel 8 formed in a substrate 2. The flow channel 8 extends longitudinally along the front and back surfaces of the substrate 2. In this example, as shown in FIG. 2 , the flow channel 8 has a first portion 81 extending linearly from one end to the other end, and a pair of second portions 82, 82 connected at one end to the other end of the first portion 81. The first portion 81 extends, for example, parallel to the side surfaces 2 a, 2 b of the substrate 2. The second portions 82, 82 branch into two from the other end of the first portion 81 and extend linearly to the other end, gradually moving away from each other as they move away from the other end of the first portion 81. As shown in FIGS. 3 and 4 , the flow channel 8 is formed in the base 3, the first cover 4, and the second cover 5. The upper surface of the flow channel 8 is covered with a first covering member 6, and the lower surface of the flow channel 8 is covered with a second covering member 7.

[0022] A channel inlet 83 that opens to the surface of the substrate 2 is formed at one end of the first portion 81. A channel outlet 84 that opens to the surface of the substrate 2 is formed at the other end of each second portion 82. The channel inlet 83 and the channel outlet 84 are formed in the first covering member 6. On the other hand, no openings such as an inlet or an outlet are formed in the second covering member 7. As will be described later, a sample solution in which a substance such as fine particles is suspended is introduced into the channel 8 from the channel inlet 83. The sample solution introduced into the channel 8 flows through the channel 8 at a predetermined flow rate and is then recovered from the two channel outlets 84, 84, respectively. For example, sample solutions containing different types of substances are recovered from the two channel outlets 84, 84. In this way, the channel device 1 can separate (sort) different types of substances from each other.

[0023] 2 and 3, four electrodes (respectively, first to fourth electrodes) 9a to 9d are disposed adjacent to a flow channel inlet 83 in the first portion 82 of the flow channel 8. In this example, electrodes 9a and 9b are disposed along a side surface 8a on one side of the flow channel 8 defined by the side surface 2a of the substrate 2. Similarly, electrodes 9c and 9d are disposed along a side surface 8b on the other side of the flow channel 8 defined by the side surface 2b of the substrate 2. Each of the electrodes 9a to 9d extends along the first portion 81 of the flow channel 8 over a predetermined range in the longitudinal direction. In this example, each of the electrodes 9a to 9d has, for example, a rectangular outline in a plan view. Each of the electrodes 9a to 9d has, for example, the same area in a plan view. Furthermore, an upper surface 8c and a lower surface 8d are defined in the flow channel 8.

[0024] As shown in FIG. 3 , electrodes 9a and 9c are formed on the surface of the base 3. In this example, electrodes 9a and 9c are exposed on the side surfaces 8a and 8b of the flow channel 8, respectively. The side surfaces 8a and 8b are defined parallel to each other. On the other hand, electrodes 9b and 9d are formed on the back surface of the base 3. In this example, electrodes 9b and 9d are exposed on the side surfaces 8a and 8b of the flow channel 8, respectively. Thus, electrodes 9a and 9c face each other in a second direction, i.e., a lateral direction, that intersects (in this example, perpendicular to) the longitudinal direction, with the flow channel 8 in between. Similarly, electrodes 9b and 9d face each other in the lateral direction of the flow channel 8 with the flow channel 8 in between. Electrodes 9a and 9c and electrodes 9b and 9d are arranged spaced apart from each other by the thickness of the base 3.

[0025] 1 to 3, the flow path device 1 has a pair of first conductive pads 10, 10 and a pair of second conductive pads 11, 11 that are exposed within cutouts 2c formed in the surface of the substrate 2. The cutouts 2c are formed in the first cover 4 and the first covering member 6 (see FIG. 3). The first conductive pads 10, 10 are formed on the surface of the base 3. One of the first conductive pads 10 is electrically connected to the electrode 9a, while the other first conductive pad 10 is electrically connected to the electrode 9b. A conductive pattern 12 formed along the surface of the base 3 is used to electrically connect one of the first conductive pads 10 formed on the surface of the base 3 to the electrode 9a.

[0026] A conductive pattern 13 formed along the front and rear surfaces of the base 3 is used to electrically connect the other first conductive pad 10 formed on the front surface of the base 3 to the electrode 9b formed on the rear surface of the base 3. As shown in Fig. 3, the conductive pattern 13 extends from the other first conductive pad 10 along the front surface of the base 3, and then extends along the rear surface of the base 3 via a through-hole via 14 that penetrates the base 3. In this way, the conductive pattern 13 electrically connects the other first conductive pad 10 formed on the front surface of the base 3 to the electrode 9b formed on the rear surface of the base 3.

[0027] Similarly, second conductive pads 11, 11 are formed on the surface of the base 3. One second conductive pad 11 is electrically connected to electrode 9c, while the other second conductive pad 11 is electrically connected to electrode 9d. A conductive pattern 15 formed along the surface of the base 3 is used for the electrical connection between one second conductive pad 11 and electrode 9c. Furthermore, conductive patterns 16 formed on the front and back surfaces of the base 3 are used for the electrical connection between the other second conductive pad 11 and electrode 9d. The conductive pattern 15 extends from the other second conductive pad 11 along the surface of the base 3, and then extends along the back surface of the base 3 via a through-hole via 17 that penetrates the base 3.

[0028] A single power supply 18 is connected to the pair of first conductive pads 10, 10. Similarly, a single power supply 19 is connected to the pair of second conductive pads 11, 11. The power supply 18 is an AC power supply that can apply a voltage of a variable value at a variable frequency between the electrodes 9a and 9b. Similarly, the power supply 19 is an AC power supply that can apply a voltage of a variable value at a variable frequency between the electrodes 9c and 9d. These power supplies 18 and 19 allow different voltage values ​​to be set for the electrodes 9a to 9d.

[0029] 2 and 4 , two electrodes 21a and 21b are arranged in the first portion 81 of the flow channel 8 adjacent to the flow channel outlet 84. In this example, the electrodes 21a and 21b are arranged along the side surface 8a of the flow channel 8. Both the electrodes 21a and 21b extend along the first portion 81 of the flow channel 8 over a predetermined range in the longitudinal direction. In this example, the electrodes 21a and 21b each have, for example, a rectangular outline in a plan view. The electrodes 21a and 21b each have, for example, the same area in a plan view. As shown in FIG. 4 , the electrode 21a is formed on the surface of the base 3. In this example, the electrode 21a is exposed on the side surface 8a of the flow channel 8. On the other hand, the electrode 21b is formed on the back surface of the base 3. In this example, the electrode 21b is also exposed on the side surface 8a of the flow channel 8.

[0030] 1, 2, and 4, the flow channel device 1 has a pair of third conductive pads 22, 22 that are exposed in cutouts 2c formed in the surface of the substrate 2. The third conductive pads 22, 22 are formed in the cutouts 2c, the first cover 4, and the first covering member 6 (see FIG. 4). The third conductive pads 22, 22 are formed on the surface of the base 3. One third conductive pad 22 is electrically connected to the electrode 21a, while the other third conductive pad 22 is electrically connected to the electrode 21b. A conductive pattern 23 formed along the surface of the base 3 is used to electrically connect one third conductive pad 22 formed on the surface of the base 3 to the electrode 21a.

[0031] A conductive pattern 24 formed along the front and rear surfaces of the base 3 is used to electrically connect the other third conductive pad 22 formed on the front surface of the base 3 to the electrode 21b formed on the rear surface of the base 3. The conductive pattern 24 extends from the other third conductive pad 22 along the front surface of the base 3, and then extends along the rear surface of the base 3 via a through-hole via 25 that penetrates the base 3. In this way, the conductive pattern 24 electrically connects the other third conductive pad 22 formed on the front surface of the base 3 to the electrode 21b formed on the rear surface of the base 3.

[0032] A power supply 26 is connected to the pair of third conductive pads 22, 22. The power supply 26 is an AC power supply that can apply, for example, a voltage of a variable voltage value at a variable frequency between the electrodes 21 a and 21 b. Note that the electrodes 9 a to 9 d, the first conductive pad 10, the second conductive pad 11, the conductive pattern 12, the conductive pattern 13, the through-hole via 14, the conductive pattern 15, the through-hole via 16, the electrodes 21 a and 21 b, the third conductive pad 22, the conductive pattern 23, the conductive pattern 24, and the through-hole via 25 are all formed of a conductive material such as copper.

[0033] As described below, the flow channel device 1 can adjust the position of a substance in a direction perpendicular to the longitudinal direction within the flow channel 8 by controlling the voltage values ​​applied to the electrodes 9a-9d and the electrodes 21a and 21b. A first position adjustment region A1 corresponding to the region where the electrodes 9a-9d extend and a second position adjustment region A2 corresponding to the region where the electrodes 21a and 21b extend are defined in the first portion 81 of the flow channel 8 along the longitudinal direction of the flow channel 8 (see FIG. 2). Specifically, in the first position adjustment region A1, substances are aligned (focused) in the direction perpendicular to the longitudinal direction. Furthermore, in the second position adjustment region A2, different types of substances are separated (sorted) from each other in the direction perpendicular to the longitudinal direction. In this example, the first position adjustment region A1 and the second position adjustment region A2 may extend to approximately the same length along the longitudinal direction.

[0034] The flow channel device 1 further includes an imaging device and a light source (neither of which are shown). Both the imaging device and the light source may be disposed, for example, facing the front surface of the substrate 2, or may be disposed facing the back surface of the substrate 2. The imaging device can capture an image of the flow channel 8 illuminated by the light source. For example, a substance flowing through the flow channel 8 may be fluorescently dyed in advance, and fluorescence observation of the substance may be performed by observing the fluorescence emitted from the substance when illuminated by the light source. The imaging device may be disposed facing the front surface of the substrate 2, while the light source may be disposed facing the back surface of the substrate 2. Conversely, the imaging device may be disposed facing the back surface of the substrate 2, while the light source may be disposed facing the front surface of the substrate 2.

[0035] Next, the usage of the flow channel device 1 will be described. For example, a sample solution containing two types of substances, such as microparticles of cells, with different dielectric constants and a solution for suspending these substances is prepared. A buffer solution may be mixed into the solution at a predetermined concentration to adjust the solution's dielectric constant. The sample solution is injected into the flow channel 8 through the flow channel inlet 83 of the substrate 2. For example, negative pressure is applied to the flow channel outlet 84, and the sample solution that flows through the flow channel 8 at a predetermined flow rate is extracted. At this time, a voltage of a predetermined value is applied to electrodes 9a-9d and electrodes 21a and 21b. As a result, in the first position adjustment region A1, all substances can be aligned in a line at a predetermined position within the flow channel 8. Meanwhile, in the second position adjustment region A2, in this example, two types of substances with different dielectric constants can be separated in opposite directions along the short side of the flow channel 8.

[0036] The following describes the case of aligning materials in a line (focusing) in the first position adjustment region A1. The inventors conducted a simulation using, for example, analysis software to set the voltage values ​​to be applied to electrodes 9a to 9d. Figure 5 shows an example of the analysis results obtained using the analysis software. Figure 5 is a partially enlarged cross-sectional view of the substrate 2 taken along a virtual plane perpendicular to the longitudinal direction. This figure illustrates a flow path 8 and four electrodes 9a to 9d adjacent to the flow path 8. In this example, a voltage of X*sinωt [V] was applied to electrodes 9a and 9d. X was set to 30. Electrodes 9b and 9c are ground (Gnd) electrodes. That is, the voltage values ​​of electrodes 9b and 9c are 0 [V].

[0037] In FIG. 5 , arrow A represents the dielectrophoretic force generated in the flow channel 8. The length and thickness of arrow A represent the magnitude of the dielectrophoretic force. The direction of arrow A represents the direction of the dielectrophoretic force. As can be seen from FIG. 5 , when the same voltage value (30 V in this case) is applied to electrodes 9 a and 9 d, i.e., when the difference in voltage value between electrodes 9 a and 9 b is equal to the difference in voltage value between electrodes 9 c and 9 d, a dielectrophoretic force is generated from each of electrodes 9 a to 9 d generally toward the center of flow channel 8. Note that the center of flow channel 8 corresponds to the midpoint between the thickness direction of flow channel 8, defined between the upper surface 8 c and the lower surface 8 d of flow channel 8, and the width direction of flow channel 8, defined between the side surfaces 8 a and 8 b of flow channel 8, in the cross section of flow channel 8 shown in FIG. 5 .

[0038] As shown in FIG. 5 , in the flow channel 8, in the regions adjacent to the electrodes 9a to 9d, the dielectrophoretic force is generated radially from the electrodes 9a to 9d in the thickness direction. As the flow channel 8 moves toward the intermediate position in the thickness direction, the dielectrophoretic force is generated toward the center of the flow channel 8. Similarly, as the flow channel 8 moves toward the intermediate position in the width direction, the dielectrophoretic force is generated toward the center of the flow channel 8. This dielectrophoretic force is relatively large in the regions adjacent to the electrodes 9a to 9d, but decreases as the flow channel 8 moves from the electrodes 9a to 9d toward the center of the flow channel 8. Furthermore, a substantially similar dielectrophoretic force is generated in the region adjacent to the side surface 8a of the flow channel 8 (the region adjacent to electrodes 9a and 9b) and the region adjacent to the side surface 8b of the flow channel 8 (the region adjacent to electrodes 9c and 9d). In this case, the substance S flowing longitudinally within the flow channel 8 is aligned along the center of the flow channel 8. Note that although the substance S is illustrated as being circular, it may have various shapes other than circular.

[0039] FIG. 6 shows another example of the analysis results obtained by the analysis software. As shown in FIG. 6, in this analysis simulation, a voltage value of X×sinωt [V] was set to electrode 9a, Gnd to electrode 9b, a voltage value of X×(1−a)×sinωt [V] to electrode 9c, and a voltage value of X×a×sinωt [V] to electrode 9d. X was set to 30. Parameter a determines the ratio of the voltage values ​​of electrodes 9c and 9d. Here, parameter a was set to 2 / 3. Under these conditions, the voltage value of electrode 9a was set to 30 [V], the voltage value of electrode 9b was set to 0 [V], the voltage value of electrode 9c was set to 10 [V], and the voltage value of electrode 9d was set to 20 [V]. In other words, the difference in voltage value between electrode 9a and electrode 9b (30 [V]) was set to be greater than the difference in voltage value between electrode 9c and electrode 9d (10 [V]).

[0040] As shown in Figure 6, in this example, the dielectrophoretic force was generated in the flow channel 8 in approximately the same direction as in the example of Figure 5. Furthermore, in the region adjacent to the side surface 8a of the flow channel 8, a dielectrophoretic force of approximately the same magnitude as in the example of Figure 5 was generated. On the other hand, because the difference in voltage value between electrodes 9a and 9b (30 [V]) was greater than the difference in voltage value between electrodes 9c and 9d (10 [V]), the dielectrophoretic force in the region adjacent to the side surface 8b of the flow channel 8 was reduced compared to the example of Figure 5. Due to this difference in the magnitude of the dielectrophoretic force in the width direction of the flow channel 8, it was confirmed that the substance S flowing in the longitudinal direction within the flow channel 8 was aligned and biased away from the center of the flow channel 8 toward the side surface 8b of the flow channel 8 in the width direction of the flow channel 8, compared to the example of Figure 5.

[0041] FIG. 7 shows yet another example of analysis results obtained by the analysis software. In this example, only the value of parameter a was changed under the conditions of FIG. 6 . Specifically, parameter a was set to a smaller value than in the example of FIG. 6 , i.e., 7 / 12. The voltage value of electrode 9a was set to 30 [V], the voltage value of electrode 9b to 0 [V], the voltage value of electrode 9c to 12.5 [V], and the voltage value of electrode 9d to 17.5 [V]. Compared to FIG. 6 , the difference between the voltage values ​​of electrode 9c and electrode 9d was reduced by half. In other words, the difference between the voltage values ​​between electrode 9a and electrode 9b and the voltage values ​​between electrode 9c and electrode 9d was further increased compared to FIG. 6 . As a result, the dielectrophoretic force was further reduced in the region adjacent to the side surface 8b than in the case of FIG. 6 . It was confirmed that the substance S flowing in the longitudinal direction within the channel 8 was aligned with a greater bias from the center of the channel 8 toward the side surface 8b of the channel 8 in the width direction of the channel 8 compared to the case of FIG. 6 .

[0042] FIG. 8 shows yet another example of the analysis results obtained by the analysis software. In this example, the voltage values ​​of electrodes 9a to 9d were set inversely to those of the example shown in FIG. 5 in the width direction of the flow channel 8. That is, a voltage value of X×(1−a)×sinωt [V] was set for electrode 9a, a voltage value of X×a×sinωt [V] was set for electrode 9b, a voltage value of X×sinωt [V] was set for electrode 9c, and a voltage value of Gnd was set for electrode 9d. As in the example shown in FIG. 5, X was set to 30, and the parameter a was set to 2 / 3. In this case, the voltage value of electrode 9a was set to 10 [V], the voltage value of electrode 9b was set to 20 [V], the voltage value of electrode 9c was set to 30 [V], and the voltage value of electrode 9d was set to 0 [V].

[0043] In this case, as shown in FIG. 8 , the dielectrophoretic force generated in the example of FIG. 6 was generated in a manner that was reversed in the width direction of the flow channel 8. Specifically, in the region adjacent to the side surface 8 a, a dielectrophoretic force of the same magnitude as that generated in the region adjacent to the side surface 8 b in the example of FIG. 5 was generated. On the other hand, in the region adjacent to the side surface 8 b, a dielectrophoretic force of the same magnitude as that generated in the region adjacent to the side surface 8 a in the example of FIG. 5 was generated. In other words, the dielectrophoretic force was smaller in the region adjacent to the side surface 8 b than in the region adjacent to the side surface 8 a. Due to this difference in the magnitude of the dielectrophoretic force in the width direction of the flow channel 8, it was confirmed that the substance S flowing in the longitudinal direction within the flow channel 8 was aligned and biased toward the side surface 8 a of the flow channel 8 in the width direction of the flow channel 8 from the center of the flow channel 8, compared to the case of FIG. 5 .

[0044] FIG. 9 shows yet another example of analysis results obtained by the analysis software. In this example, only the value of parameter a was changed under the conditions of the example of FIG. 8 . Specifically, parameter a was set to a smaller value than in the example of FIG. 8 , i.e., 7 / 12. The voltage value of electrode 9a was set to 12.5 [V], the voltage value of electrode 9b to 17.5 [V], the voltage value of electrode 9c to 30 [V], and the voltage value of electrode 9d to 0 [V]. That is, compared to the example of FIG. 8 , the difference between the voltage values ​​of electrode 9c and electrode 9d was reduced by half. As a result, the dielectrophoretic force in the region adjacent to the side surface 8a was further reduced than in the example of FIG. 8 . It was confirmed that the substance S flowing in the longitudinal direction within the flow channel 8 was aligned with a greater bias toward the side surface 8a of the flow channel 8 in the width direction of the flow channel 8 from the center of the flow channel 8 compared to the example of FIG. 8 .

[0045] According to the analytical simulations shown in Figures 5 to 9, when the parameter a is 1, i.e., when the voltage values ​​of electrodes 9a and 9d are X and electrodes 9b and 9c are Gnd, i.e., when the voltage values ​​of electrodes 9a and 9d are maximum and the voltage values ​​of electrodes 9b and 9c are minimum, the substance S aligns at the center of the flow channel 8. On the other hand, when the parameter a is 0.5 (1 / 2), the voltage values ​​of electrodes 9c and 9d are the same, and the difference in the voltage values ​​of electrodes 9c and 9d is zero. In other words, the difference between the difference in the voltage values ​​between electrodes 9a and 9b and the difference in the voltage values ​​between electrodes 9c and 9d is maximum. In this case, the substance S moves to its maximum extent in the width direction of the flow channel 8.

[0046] Based on the above, when the parameter a is set to 0.5<a<1, that is, the difference between the difference in voltage value between electrodes 9a and 9b and the difference in voltage value between electrodes 9c and 9d is smaller than the maximum value. Specifically, the voltage value of electrode 9a is maximum, the voltage value of electrode 9b is minimum, and the voltage values ​​of electrodes 9c and 9d are greater than the minimum value and less than the maximum value. Under these conditions, the substance S moves from the center of the flow channel 8 in the width direction of the flow channel 8. Furthermore, in the flow channel device 1, the voltage value X applied to electrodes 9a to 9d is preferably set to 5≦X≦50 [V]. However, the numerical range of this voltage value X may be changed as appropriate depending on the substance, such as cells, solution, etc., used in the flow channel device 1.

[0047] FIG. 10 shows another example of the analysis results obtained by the analysis software. In this analysis simulation, a voltage value of X×sinωt [V] was set to electrode 9a, a voltage value of X×(1−b)×sinωt [V] was set to electrode 9b, a voltage value of Gnd was set to electrode 9c, and a voltage value of X×b×sinωt [V] was set to electrode 9d. Here, X was set to 30. Parameter b is a parameter that determines the ratio of the voltage values ​​of electrodes 9b and 9d. Here, parameter a was set to 3 / 4. Under these conditions, the voltage value of electrode 9a was set to 30 [V], the voltage value of electrode 9b was set to 7.5 [V], the voltage value of electrode 9c was set to 0 [V], and the voltage value of electrode 9d was set to 22.5 [V]. In other words, the difference in voltage value between electrode 9a and electrode 9c (30 [V]) was set to be greater than the difference in voltage value between electrode 9b and electrode 9d (15 [V]).

[0048] As shown in Figure 10, in this example, the direction of the dielectrophoretic force was generally the same as in the example of Figure 5, but it was directed toward a position slightly closer to the lower surface 8d of the flow channel 8 in the thickness direction. That is, in the flow channel 8, the dielectrophoretic force directed toward the lower surface 8d of the flow channel 8 in the thickness direction was greater than the dielectrophoretic force directed toward the upper surface 8c. Meanwhile, almost no difference in the magnitude of the dielectrophoretic force was observed between the region adjacent to the side surface 8a of the flow channel 8 and the region adjacent to the side surface 8b of the flow channel 8. It was confirmed that due to this difference in the dielectrophoretic force in the thickness direction of the flow channel 8, the substance S was biased and aligned toward the lower surface 8d of the flow channel 8 in the thickness direction of the flow channel 8 from the center of the flow channel 8.

[0049] FIG. 11 shows another example of analysis results obtained by the analysis software. In this example, only the value of parameter b was changed under the conditions of FIG. 10 . Specifically, parameter b was set to a smaller value than in the example of FIG. 10 , i.e., 7 / 12. The voltage value of electrode 9a was set to 30 [V], the voltage value of electrode 9b to 12.5 [V], the voltage value of electrode 9c to 0 [V], and the voltage value of electrode 9d to 17.5 [V]. Compared to FIG. 10 , the difference between the voltage values ​​of electrode 9b and electrode 9d was reduced to less than half. In other words, compared to FIG. 10 , the difference between the voltage values ​​between electrode 9a and electrode 9c and the voltage values ​​between electrode 9b and electrode 9d was further increased. As a result, the dielectrophoretic force directed toward the upper surface 8c in the thickness direction of the flow channel 8 was further reduced. It was confirmed that the substance S was aligned with a further bias toward the lower surface 8d of the flow channel 8 in the thickness direction of the flow channel 8 from the center of the flow channel 8, compared to the case of FIG. 10 .

[0050] FIG. 12 shows yet another example of the analysis results obtained by the analysis software. In this example, the voltage values ​​of electrodes 9a to 9d were set inversely to those of the examples shown in FIGS. 10 and 11 in the width and thickness directions of the flow channel 8. That is, a voltage value of X×b×sinωt [V] was set for electrode 9a, Gnd for electrode 9b, a voltage value of X×(1-b)×sinωt for electrode 9c, and a voltage value of X×sinωt for electrode 9d. As in the example shown in FIG. 10, X was set to 30, and parameter b was set to 3 / 4. In this case, the voltage value of electrode 9a was set to 22.5 [V], the voltage value of electrode 9b was set to 0 [V], the voltage value of electrode 9c was set to 7.5 [V], and the voltage value of electrode 9d was set to 30 [V].

[0051] As shown in Figure 12, the dielectrophoretic force generated in the example of Figure 10 was generated so as to be roughly reversed in the width direction and thickness direction of the flow channel 8. Specifically, the direction of the dielectrophoretic force was directed toward a position slightly closer to the upper surface 8c of the flow channel 8 in the thickness direction. That is, the dielectrophoretic force directed toward the upper surface 8c of the flow channel 8 in the thickness direction was greater than the dielectrophoretic force directed toward the lower surface 8d. Meanwhile, almost no difference in the magnitude of the dielectrophoretic force was observed between the region adjacent to the side surface 8a of the flow channel 8 and the region adjacent to the side surface 8b of the flow channel 8. It was confirmed that due to this difference in the dielectrophoretic force in the thickness direction of the flow channel 8, the substance S was biased and aligned toward the upper surface 8c of the flow channel 8 in the thickness direction of the flow channel 8 from the center of the flow channel 8.

[0052] FIG. 13 shows yet another example of analysis results obtained by the analysis software. In this example, only the value of parameter b was changed under the conditions of the example of FIG. 12 . Specifically, parameter b was set to a smaller value than in the example of FIG. 12 , i.e., 7 / 12. The voltage value of electrode 9a was set to 17.5 [V], the voltage value of electrode 9b to 0 [V], the voltage value of electrode 9c to 12.5 [V], and the voltage value of electrode 9d to 30 [V]. That is, compared to the example of FIG. 12 , the difference between the voltage values ​​of electrode 9c and electrode 9d was reduced to less than half. As a result, the dielectrophoretic force directed toward the lower surface 8d in the thickness direction of the flow channel 8 was further reduced. It was confirmed that the substance S was aligned with a further bias toward the upper surface 8c of the flow channel 8 in the thickness direction of the flow channel 8 from the center of the flow channel 8, compared to the case of FIG. 12 .

[0053] According to the analytical simulations shown in Figures 10 to 13, when the parameter b is 1, i.e., when the voltage values ​​of electrodes 9a and 9b are X and electrodes 9b and 9d are Gnd, i.e., when the voltage values ​​of electrodes 9a and 9b are maximum and the voltage values ​​of electrodes 9c and 9d are minimum, the substance S aligns at the center of the flow channel 8 as shown in Figure 5. On the other hand, when the parameter b is 0.5 (1 / 2), the voltage values ​​of electrodes 9b and 9d are the same, and the difference in the voltage values ​​of electrodes 9b and 9d is zero. In other words, the difference between the difference in the voltage values ​​between electrodes 9a and 9c and the difference in the voltage values ​​between electrodes 9b and 9d is maximum. In this case, the substance S moves to its maximum extent in the thickness direction of the flow channel 8.

[0054] According to the above, when the parameter b is set to 0.5<b<1, that is, the difference between the difference in the voltage value between the electrodes 9a and 9c and the difference in the voltage value between the electrodes 9b and 9d is smaller than the maximum value. Specifically, the voltage value of the electrode 9a is the maximum value, the voltage value of the electrode 9c is the minimum value, and the voltage values ​​of the electrodes b and 9d are greater than the minimum value and smaller than the maximum value. Under this condition, the substance S moves from the center of the flow channel 8 in the thickness direction of the flow channel 8.

[0055] 14 and 15 are diagrams showing yet another example of the analysis results obtained by the analysis software. In this example, movement in the width direction of the flow channel 8 and movement in the thickness direction are combined. Specifically, in the example of FIGS. 14 and 15, movement in the width direction toward the side surface 8b of the flow channel 8 and movement in the thickness direction toward the bottom surface 8d of the flow channel 8 are combined. In this example, a voltage value of X×sinωt was set to electrode 9a, a voltage value of X×(1−c)×sinωt was set to electrode 9b, a voltage value of X×(1−c)×sinωt was set to electrode 9c, and a voltage value of X×c×sinωt was set to electrode 9d.

[0056] In both the examples of Figures 14 and 15, X was set to 30. In the example of Figure 14, the parameter c was set to 3 / 4. Under these conditions, the voltage value of electrode 9a was set to 30 [V], the voltage value of electrode 9b was set to 7.5 [V], the voltage value of electrode 9c was set to 7.5 [V], and the voltage value of electrode 9d was set to 22.5 [V]. In the example of Figure 15, the parameter c was set to 2 / 3. Under these conditions, the voltage value of electrode 9a was set to 30 [V], the voltage value of electrode 9b was set to 10 [V], the voltage value of electrode 9c was set to 10 [V], and the voltage value of electrode 9d was set to 20 [V].

[0057] As shown in Figure 14, in this analysis simulation, the magnitude of the dielectrophoretic force in the region adjacent to electrode 9d was smaller than the dielectrophoretic force in the regions adjacent to electrodes 9a, 9b, and 9c. Therefore, it was confirmed that the substance S was aligned with a bias toward the side surface 8b in the width direction and toward the lower surface 8d in the thickness direction from the center of the flow channel 8. Furthermore, as shown in Figure 15, in this analysis simulation, the magnitude of the dielectrophoretic force in the region adjacent to electrode 9d was even smaller than the dielectrophoretic force in the region adjacent to electrodes 9a, 9b, and 9c. Therefore, it was confirmed that the substance S was aligned with a bias toward the side surface 8b in the width direction and toward the lower surface 8d in the thickness direction from the center of the flow channel 8.

[0058] 14 and 15 , by combining movement in the width direction and movement in the thickness direction, the substance S can be biased and aligned in any direction in the width direction and thickness direction of the flow channel 8. Specifically, when the parameter c is set to 0.5<c<1, that is, when the voltage value of electrode 9a is maximum, the voltage values ​​of electrodes 9b and 9c are minimum, and the voltage value of electrode 9d is equal to or greater than the minimum value and smaller than the maximum value, the substance S moves from the center of the flow channel 8 in the width direction and thickness direction of the flow channel 8. By appropriately setting voltage values ​​that satisfy this condition for electrodes 9a to 9d, the substance S can be biased and aligned also toward the side surface 8a in the width direction and toward the bottom surface 8c in the thickness direction.

[0059] Next, we will explain the case where multiple substances with different dielectric constants are separated from one another in the second position adjustment region A2 (focusing). As described above, the sample solution contains two types of substances, such as microparticles, such as cells, with different dielectric constants. In the second position adjustment region A2, a voltage of a predetermined value is applied between the electrodes 21a and 21b. In this example, for example, the voltage value of the electrode 21a is set to 30 V, and the voltage value of the electrode 21b is set to Gnd. As a result, a dielectrophoretic force similar to the dielectrophoretic force generated in the region adjacent to the side surface 8a of the flow channel 8 in FIG. 5 is generated.

[0060] Here, the sample solution contains two types of substances S having different dielectric constants. For example, a negative dielectrophoretic force (repulsive force) acts toward the side surface 8b on a substance S having a dielectric constant smaller than that of the solution. On the other hand, a positive dielectrophoretic force (attractive force) acts toward the side surface 8a on a substance S having a dielectric constant larger than that of the solution. As a result, in the second position adjustment region A2, the two types of substances S can be separated into a substance S flowing along the side surface 8a and a substance S flowing along the side surface 8b. The substance S flowing along the side surface 8a is extracted from the channel outlet 84 via one of the second portions 82. On the other hand, the substance S flowing along the side surface 8b is extracted from the channel outlet 84 via the other second portion 82. In this way, two types of substances S having different dielectric constants can be separated (sorted) from each other.

[0061] In the flow channel device 1 described above, by controlling the voltage values ​​of the electrodes 9a-9d arranged on both sides of the flow channel 8 in the short direction in the first position adjustment region A1, the alignment position of the substance S within the flow channel 8 can be adjusted with high precision in the width direction, thickness direction, or both the width direction and thickness direction of the flow channel 8. For example, in the second position adjustment region A2, the electrodes 21a and 221b are arranged on the side surface 8a, and as a result, the dielectrophoretic force increases as the substance S approaches the side surface 8a. Therefore, by biasing and aligning the substance S toward the side surface 8a in the first position adjustment region A1, a greater dielectrophoretic force can be applied to the substance S in the second position adjustment region A2. As a result, the substance S can be separated with higher precision in the second position adjustment region A2. For example, even when the flow rate of the sample solution is high, the separation of the substance S can be more reliably performed.

[0062] Furthermore, for example, in the second position adjustment region A2, if a pair of electrodes is formed only on the side surface 8a of the flow channel 8 and on the back surface of the base 3, it is expected that the dielectrophoretic force generated by this pair of electrodes will be large at positions adjacent to the side surface 8a and the bottom surface 8d of the flow channel 8. In this case, in the first position adjustment region A1, it is preferable to align the substance S by biasing it toward the side surface 8a and the bottom surface 8d in the width direction and thickness direction.

[0063] FIG. 16 corresponds to FIG. 2 and is a partial plan view schematically illustrating the structure of a flow channel device 1A according to a modified example. As shown in FIG. 16, a single power supply 27 may be electrically connected to the first conductive pads 10 and the second conductive pads 20. The power supply 27 is electrically connected to the first conductive pads 10 and the second conductive pads 20 via variable resistors VR1, VR2, VR3, and VR4, respectively. By using two variable resistors in this manner, the voltage values ​​of the electrodes 9a to 9d can be controlled using a single power supply 27. This configuration reduces the number of power supplies, thereby reducing the manufacturing cost of the flow channel device 1A. However, this configuration can also be used when adjusting the position of the substance S in the width direction.

[0064] Although the present invention has been described above through the above embodiments, the technical scope of the present invention is not limited to the scope described in the above embodiments. It will be apparent to those skilled in the art that various modifications and improvements can be made to the above embodiments. It is clear from the claims that such modifications and improvements can also be included within the technical scope of the present invention.

[0065] The above-described embodiments are intended to facilitate understanding of the present invention and are not intended to limit the present invention. Furthermore, the above-described embodiments do not limit the applications to which the present invention is applied, and the present invention may include any applications. The components of the above-described embodiments, as well as their arrangement, materials, conditions, shapes, sizes, etc., are not limited to those exemplified and may be modified as appropriate.

[0066] For example, the present invention includes differences that occur during implementation, such as manufacturing tolerances. Furthermore, within the scope of technical inconsistency, components shown in different embodiments can be partially substituted or combined. Furthermore, each configuration can be appropriately and selectively combined to achieve at least some of the above-described problems and effects.

[0067] REFERENCE SIGNS LIST 1, 1A Flow path device, 2 Base material, 2a, 2b Side surface, 2c Notch, 3 Base, 4 First cover, 5 Second cover, 6 First covering member, 7 Second covering member, 8 Flow path, 8a, 8b Side surface, 8c Upper surface, 8d Lower surface, 81 First portion, 82 Second portion, 83 Flow path inlet, 84 Flow path outlet, 9a to 9d Electrodes (first electrode to fourth electrode), 10 First conductive pad, 11 Second conductive pad, 12 Conductive pattern, 13 Conductive pattern, 14 Through-hole via, 15 Conductive pattern, 16 Conductive pattern, 17 Through-hole via, 18 Power supply, 19 Power supply, 21a Electrode, 21b Electrode, 22 Third conductive pad, 23 Conductive pattern, 24 Conductive pattern, 25 Through-hole via, 26 Power supply, 27 Power supply, A Arrow, A1 First position adjustment region, A2 Second position adjustment region, S Material, VR1 to VR4 variable resistors

Claims

1. A flow path device comprising: a substrate; a flow path formed in the substrate, extending in a first direction, and capable of passing a substance; a first electrode and a second electrode arranged on one side of the flow path in a second direction intersecting the first direction; and a third electrode and a fourth electrode arranged on the other side of the flow path in the second direction, wherein the position of the substance within the flow path is adjusted by controlling voltages applied to the first electrode, the second electrode, the third electrode, and the fourth electrode.

2. The flow path device according to claim 1, wherein the first electrode faces the third electrode in the second direction, and the second electrode faces the fourth electrode in the second direction.

3. A flow path device as described in claim 2, wherein the difference in voltage value between the first electrode and the second electrode and the difference in voltage value between the third electrode and the fourth electrode are made different from each other, thereby causing the substance to move within the flow path toward the electrode with the smaller difference in voltage value.

4. A flow path device as described in claim 2, in which the difference in voltage value between the first electrode and the third electrode and the difference in voltage value between the second electrode and the fourth electrode are made different from each other, thereby causing the substance to move toward the electrode with the smaller difference in voltage value within the flow path.

5. The flow channel device according to claim 1, wherein the substrate constitutes a flexible printed circuit board.

6. A flow path device according to any one of claims 1 to 5, wherein the first electrode and the second electrode face one side of the flow path, and the third electrode and the fourth electrode face the other side of the flow path.

7. A flow path device comprising a substrate, a flow path formed in the substrate and extending in a first direction, capable of circulating a substance, a first electrode and a second electrode arranged on one side of the flow path in a second direction intersecting the first direction, and a third electrode and a fourth electrode arranged on the other side of the flow path in the second direction, the method comprising the step of adjusting the position of the substance within the flow path by controlling voltages applied to the first electrode, the second electrode, the third electrode, and the fourth electrode.

8. The method for controlling a flow path device according to claim 7, wherein the first electrode faces the third electrode in the second direction, and the second electrode faces the fourth electrode in the second direction.

9. A method for controlling a flow path device as described in claim 8, wherein the difference in voltage value between the first electrode and the second electrode and the difference in voltage value between the third electrode and the fourth electrode are made different from each other, thereby causing the substance to move within the flow path toward the electrode with the smaller difference in voltage value.

10. A method for controlling a flow path device as described in claim 8, wherein the difference in voltage value between the first electrode and the third electrode and the difference in voltage value between the second electrode and the fourth electrode are made different from each other, thereby causing the substance to move within the flow path toward the electrode with the smaller difference in voltage value.

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