JP5383138B2 - Liquid feeding structure with electrowetting valve, microanalysis chip and analyzer using the same - Google Patents

Description

  The present invention relates to a liquid feeding structure capable of controlling the flow of a liquid, and further relates to a microanalysis chip and a microanalyzer for performing a microchemical analysis.

  The immunoassay is known as an important analysis / measurement method in the medical field, biochemical field, measurement field such as allergen and the like. However, the conventional immunoassay has a problem that the operation is complicated and it takes more than a day for the analysis.

  Under such circumstances, a micro-analysis chip has been proposed that shortens the analysis time and simplifies the analysis operation by forming a micro-order channel on the substrate and immobilizing antibodies or the like in the micro-channel. Yes.

  When performing analysis using such a micro analysis chip, it is necessary to introduce a solution into the micro analysis chip from the inlet, cause the solution to react in the micro analysis chip, and discharge the solution from the outlet to the outside of the micro analysis chip. is there. Conventionally, external power such as a pump has been used to transfer the solution in the micro analysis chip. However, since the pump is larger than the micro analysis chip, it is difficult to downsize the entire apparatus.

  For this reason, a technique for incorporating a micropump into a chemical analyzer using a microfabrication technique has been proposed (for example, Patent Document 1). However, the incorporation of a micropump requires a complicated and advanced machining technique. Further, in addition to the volume of the micropump, a built-in volume of peripheral elements for driving the pump is required, so that it is not always possible to achieve sufficient compactness.

JP 2006-220606 A

  On the other hand, a liquid feeding method using a capillary force is known as a liquid feeding method that does not use a micropump. FIG. 24 shows the basics of a conventional microchannel structure using capillary force. In FIG. 24, reference numeral 110 is a main substrate, reference numeral 111 is a lid substrate, reference numeral 114 is a flow path, reference numeral 112 is an injection hole, and reference numeral 113 is a discharge hole. When the liquid is dropped into the injection hole 112, the solution moves through the flow path 114 by the capillary force and moves to the discharge hole 113. Therefore, the liquid can be moved from the 112 side to the 113 side without requiring an external force such as a pump. Since this method does not use a pump, a minute liquid feeding system can be easily constructed, but has a problem that liquid feeding is uncertain.

  Patent Document 2 describes a technique for controlling a minute liquid feeding system. This document proposes a method of using a valve (electrowetting valve) using an electrowetting technique in order to control the liquid transfer in a micro analysis chip that transfers a liquid by capillary force.

JP 2005-199231 A

  The principle of the electrowetting valve will be described with reference to FIG. When the liquid is introduced into the chip, the liquid flows through the flow path 114 by capillary force, flows over the reference electrode 131 and reaches the working electrode 132, but the surface of the working electrode 132 is covered with a hydrophobic film, When no voltage is applied, the contact angle with the liquid is designed to be large. Furthermore, the flow path width and flow path height of the part are designed to be sufficiently small in order to stop the liquid flow. For this reason, the surface tension of the said part (working electrode part) and flow resistance couple | bond together, and a liquid cannot pass a flow path. That is, when voltage application is OFF, the valve is closed.

  On the other hand, when a voltage is applied, the liquid is negatively charged by the reference electrode 131. In the working electrode 132, a virtual capacitor is formed between the working electrode 132 and the liquid, and the effect of attracting the liquid to the working electrode 132 is reduced. That is, apparently the hydrophilicity of the surface of the working electrode 132 is increased. Thereby, the liquid can pass through the flow path. That is, when voltage application is ON, the valve is opened.

  When using an electrowetting valve, in order to stop the liquid reliably, the hydrophobicity and hydrophilicity of the flow path in the part where the working electrode is provided are adjusted so that the liquid is reliably supplied when the voltage application is OFF. Need to be designed to stop. On the other hand, in order to flow a liquid, a voltage is applied between a pair of electrodes (reference electrode 131 and working electrode 132) via the liquid to charge the liquid, thereby forming a virtual capacitor between the reference electrode and the working electrode. For this purpose, it is necessary that the liquid is always in contact with both electrodes. This is because if the liquid is not in contact with both electrodes, the flow cannot be controlled by the presence or absence of voltage application.

  However, in the method of flowing the liquid using the capillary force, if the hydrophilicity of the working electrode is increased in order to make the liquid flow smooth, it becomes difficult to stop the liquid flow. On the other hand, if the hydrophobicity of the working electrode is increased in order to make it easier to stop the flow of the liquid, the liquid stops before the working electrode (before contacting the working electrode). You will not be able to move forward.

  Therefore, it is not easy to accurately control the “advance” and “stop” of the liquid in the liquid feeding structure that does not include the driving device.

  The present invention has been made in order to solve the above-described problems, and an object of the present invention is to reliably perform “advance” and “stop” of a liquid in a micro flow channel that allows the liquid to flow using capillary force. An object of the present invention is to provide a liquid feeding structure that can be controlled, a microanalysis chip and a microanalyzer using the same.

The present invention for solving the above problems is that the upstream end of the working electrode is made hydrophilic in order to make sure that the upstream end is in contact with the liquid, and a hydrophobic portion is provided downstream from the vicinity of the upstream end. Has characteristics. As a specific method,
(1) The upstream end of the working electrode surface is hydrophilic.
(2) Increasing the hydrophilic material ratio on the inner wall surface of the flow path so that the pressure due to the surface tension generated in the liquid is positive in the flow path cross section including the upstream end of the working electrode
(3) A hydrophobic structure that increases the liquid contact surface is provided in a flow path region other than the upstream end of the portion where the working electrode is formed.
The measures are taken.

  In addition, said (1)-(3) can be combined suitably.

  The invention relating to the flow path structure with an electrowetting valve relating to the above (1) is the first invention, the invention relating to the flow path structure having an electrowetting valve relating to the above (2) is the second invention, the above (3) The invention relating to the flow path structure with an electrowetting valve is referred to as a third invention. Moreover, the invention concerning the microanalysis chip and the analysis apparatus using the channel structure with an electrowetting valve according to the first to third inventions will be sequentially described as fourth to fifth inventions, respectively.

  A first invention for solving the above-mentioned problems is a flow channel structure with an electrowetting valve in which an electrowetting valve for controlling the flow of a liquid in the flow channel is arranged. In a state in which a working electrode formed in a specific area in the path and a reference electrode formed on the upstream side of the specific area where the working electrode is formed and no voltage is applied to both electrodes The working electrode is at least partially hydrophobic, and at least the vicinity of the upstream end of the working electrode is hydrophilic.

  The liquid flow in the microchannel using the capillary force will be described. The force of flowing liquid due to capillary force is greatly affected by the contact angle between the channel wall surface and the liquid (see FIG. 21). When the flow path wall surface is made of a uniform material and the cross-sectional shape perpendicular to the flow direction of the flow path is a circle, the pressure P acting on the liquid is σ, the interface tension of the gas-liquid interface, and the contact angle of the flow path wall Is represented by equation 1 in FIG. That is, when cos θ is positive, the liquid can travel in the flow path, while when cos θ is 0 or negative, the liquid cannot travel through the flow path and stops. That is, in order to flow the liquid using the capillary force, it is essential to use a material whose cos θ is positive (hydrophilic).

  When the channel wall surface is hydrophobic, cos θ is 0 or negative, and a pressure P that does not flow liquid is generated. Therefore, on the wall surface where both hydrophilicity and hydrophobicity exist, it is possible to design a state in which the capillary phenomenon occurs and a state in which the capillary phenomenon does not occur. In the case of the channel structure as shown in FIG. 22, in the channel shape where the channel height is h and the width is w, the contact angle θ1 of the main substrate, the contact angle of the lid substrate is θ2, and the interface tension at the gas-liquid interface Where σ is, the interfacial tension acting on the upper surface of the flow path is F1, the interfacial tension acting on the lower surface is F2, and the interfacial tension acting on both the left and right sides is F3, respectively. 3 and Equation 4 Since the pressure P acting on the flow path is obtained by dividing the sum of F1, F2, and F3 by the cross-sectional area wh, the pressure P acting on the flow path in this case has a relationship represented by Expression 5 in FIG.

  When the pressure P becomes a positive value, a capillary phenomenon occurs and the liquid moves forward. When the pressure P becomes a negative value, the capillary action does not occur and the movement of the liquid stops. Using this relationship and the difference in the degree of hydrophilicity between the working electrode and the lid substrate, the pressure due to the surface tension generated in the liquid in the flow path in which the working electrode is formed can be adjusted.

  In the above, the case where the shape of the cross section of the flow path orthogonal to the flow direction is rectangular has been described, but the flow path shape is not limited to this, and may be a circular shape, an elliptical shape, a semicircular shape, an inverted triangular shape, etc. There may be. Even if the cross-sectional shape of the flow path is other than rectangular, the interfacial tension for each specific region of the cross-section can be obtained, and the pressure P acting on the entire flow path can be obtained by accumulating the interfacial tension according to the composition ratio ( (See Equation 5 in FIG. 23).

  From this principle, in order to control the flow of the liquid by the electrowetting valve (“advance” / “stop”), the pressure P acting on the liquid in the flow channel region where the working electrode 131 is provided in the state where no voltage is applied. May be designed to be 0 or negative and positive when a voltage is applied (see FIG. 16). However, if the entire surface of the working electrode is hydrophobic, the liquid contacts the working electrode surface. There is a risk of stopping before that.

  Therefore, in the present invention, the working electrode 132 includes a highly hydrophobic region (P is a 0 or negative region) 135 and a hydrophilic region (P is a positive region) 134 including the upstream end (FIG. 3). reference).

  In this configuration, in the state where no voltage is applied, the liquid reliably contacts the hydrophilic region (P is a positive region) 134 of the working electrode 132, and the region having higher hydrophobicity (P is 0 or negative). It will advance to the vicinity of the boundary of (region) 135, and will stop before or slightly ahead of the highly hydrophobic region. In other words, with this configuration, the contact between the working electrode and the liquid is ensured even when the flow of the liquid is in the “stopped” state. Therefore, when a voltage is applied to both electrodes, the voltage is applied to the liquid, and the capacitor effect Occurs. This capacitor effect reduces the contact angle of the liquid with the electrode surface and allows the liquid to pass over the hydrophobic region 135 on the working electrode. That is, the flow of the liquid can be controlled by the presence or absence of voltage application.

  Here, hydrophilicity refers to a case where the contact angle measured at 1 atm and 25 ° C. is less than 90 ° using pure water (25 ° C.) having a specific resistance greater than 18 mΩ · cm. In this case, the contact angle of the pure water is 90 ° or more. However, the cosine, which is a component acting in the flow direction of the contact angle, varies greatly around 90 °. Since the present invention relates to a structure that allows a liquid to flow using capillary force, the “hydrophilicity” in the above configuration preferably has a contact angle with respect to pure water of 85 ° or less, more preferably 75 ° or less, Preferably it is 60 degrees or less. When the “hydrophilicity” in the above configuration is 60 ° or less, the “hydrophobicity” of the working electrode surface can be 65 ° or more.

  Here, the electrode configuration of the electrowetting valve only needs to include at least one reference electrode and at least one working electrode. Therefore, the number of reference electrodes may be two or more, and the number of working electrodes may be two or more. In addition to the working electrode and the reference electrode, one or more counter electrodes may be provided to suppress the flow of current to the reference electrode and stabilize the potential of the reference electrode.

  In the above-described configuration of the present invention, the flow path may have a structure in which a hydrophobic region and a hydrophilic region always exist in a cross-sectional view orthogonal to the flow direction.

  With this structure, the liquid flow can be controlled more reliably. Here, the structure in which the hydrophobic region and the hydrophilic region always exist in a cross-sectional view orthogonal to the flow direction is that the flow path is composed of the hydrophobic region and the hydrophilic region, and this structure is applied even when a voltage is applied. It means a structure that satisfies the conditions. However, when a voltage is applied, the hydrophilic region is apparently increased.

  In the first aspect of the invention, the flow channel structure with an electrowetting valve includes at least a main substrate on which the flow channel groove is formed, a lid substrate on which the reference electrode and the working electrode are formed, And the main substrate and the lid substrate are superposed on each other.

  In the above configuration, the main substrate can be made of a hydrophobic material, and the lid substrate can be made of a hydrophilic material.

  In the above configuration, the main substrate may be made of polydimethylsiloxane, and the lid substrate may be made of glass.

  With these configurations, the first invention structure can be easily realized.

  In the configuration of the first invention, the constituent material of the working electrode is hydrophobic, and the surface near the upstream end of the working electrode is subjected to a hydrophilic treatment, or the constituent material of the working electrode is hydrophilic. It can be said that the electrode surface excluding the surface near the upstream end is hydrophobized.

  Also with these configurations, the first invention can be easily realized.

  The constituent material of the working electrode is hydrophobic or hydrophilic basically means that the conductive material itself that functions as an electrode is hydrophobic or hydrophilic. When a film or the like is formed homogeneously, it means the properties of this film or the like.

  As a hydrophilic treatment method, it is convenient to employ at least one selected from the group consisting of hydrophilic treatment, plasma treatment, UV treatment, and surface roughness control.

  As a method for the hydrophobic treatment, it is convenient to employ at least one selected from the group consisting of treatment with a hydrophobic treatment agent, formation of a hydrophobic film, and control of surface roughness. In particular, a simple method may be exemplified by using gold (contact angle: 60 ° to 85 °) as the conductive material and covering the gold surface except the upstream end with a hydrophobic film.

  According to a second aspect of the present invention for solving the above problem, in the flow path structure with an electrowetting valve in which an electrowetting valve for controlling the flow of the liquid in the flow path is arranged, the electrowetting valve In a state in which a working electrode formed in a specific area in the path and a reference electrode formed on the upstream side of the specific area where the working electrode is formed and no voltage is applied to both electrodes The surface of the working electrode is hydrophobic, the pressure due to the surface tension generated in the liquid in the cross section of the channel including the upstream end of the working electrode is positive, and the channel in the region where the working electrode is formed In addition, there is a portion where the pressure due to the surface tension generated in the liquid is zero or negative.

  In the above configuration, the surface of the working electrode is hydrophobic when the voltage application is OFF, and the pressure due to the surface tension generated in the liquid in the flow path at the upstream end of the working electrode is positive. At least the upstream end of the electrode comes into reliable contact with the liquid. Further, since there is a portion where the pressure due to the surface tension generated in the liquid is zero or negative in the flow path in the region where the working electrode is formed, the liquid surely stops in this region. When the voltage application is ON, the liquid flows according to the same principle as in the first invention.

  In the second invention configuration, the flow channel structure with an electrowetting valve includes at least a main substrate on which the flow channel groove is formed, a lid substrate on which the reference electrode and the working electrode are formed, And the main substrate and the lid substrate are superposed on each other.

  In the above configuration, the main substrate can be made of a hydrophobic material, and the lid substrate can be made of a hydrophilic material.

  In the above configuration, the main substrate may be made of polydimethylsiloxane, and the lid substrate may be made of glass.

  With these configurations, the second invention structure can be easily realized.

  The said structure WHEREIN: The groove width in the said working electrode upstream end can be set as a structure larger than the groove width in the part in which the pressure by the said surface tension is 0 or negative.

  The said structure WHEREIN: The groove height in the said working electrode upstream end can be set as the structure smaller than the groove height in the part in which the pressure by the said surface tension is 0 or negative.

  In the configuration in which a channel groove is provided in a hydrophobic substrate and a lid is covered with a hydrophilic substrate on which an electrode is formed, as shown in FIGS. 6 and 7, when the groove width at the upstream end of the working electrode is increased, the corresponding amount is increased. The hydrophilic area resulting from the hydrophilic substrate is increased, and the ratio of the hydrophilic area of the flow path at the upstream end of the working electrode is increased. Further, as shown in FIGS. 9 and 10, when the groove height at the upstream end of the working electrode is reduced, the ratio of the hydrophilic region due to the hydrophilic substrate without fluctuation is increased. Therefore, when the above configuration is adopted, the pressure due to the surface tension generated in the liquid in the flow path at the upstream end of the working electrode is positive, and the flow path in the region where the working electrode is formed has a surface tension generated in the liquid. It is easy to design so that there is a portion where the pressure is zero or negative.

  According to a third aspect of the present invention for solving the above problems, in the flow channel structure with an electrowetting valve in which an electrowetting valve for controlling the flow of the liquid in the flow channel is disposed, the electrowetting valve In a state in which a working electrode formed in a specific area in the path and a reference electrode formed on the upstream side of the specific area where the working electrode is formed and no voltage is applied to both electrodes The working electrode is hydrophilic at least in the vicinity of the upstream end portion, and a hydrophobic structure that increases the liquid contact surface of the flow path is provided in a region other than the upstream end of the working electrode. To do.

  In the above configuration, in the region where at least the vicinity of the upstream end of the working electrode is hydrophilic and the hydrophobic structure that increases the liquid contact surface of the flow path is provided, the flow path is formed by the hydrophobic structure. The hydrophobic material ratio in the cross section increases. By utilizing this, when the voltage application is OFF, the liquid can be stopped in the hydrophobic structure forming region. When the voltage application is ON, the liquid flows according to the same principle as in the first invention.

  As such a hydrophobic structure that increases the liquid contact surface, at least one of a pillar, a hole, and a groove is suitable.

  Also in the third invention, the same substrate configuration as in the first and second inventions can be adopted.

  A fourth invention is a microanalysis chip provided with any of the above-described channel structures with an electrowetting valve as an essential element.

  A fifth invention is an analyzer equipped with the micro-analysis chip as an essential element.

  As described above, according to the present invention, a flow channel structure with an electrochlorowetting valve that can reliably open and close the flow of a liquid can be realized. Although the flow channel structure of the present invention has a simple structure, it is possible to perform liquid feeding control with high reliability. Therefore, the micro-analysis chip and the analysis apparatus using the same are remarkably effective in improving usability and downsizing.

  The best mode for carrying out the present invention will be described below in detail with reference to the drawings.

(Embodiment 1)
The present embodiment relates to the first invention.
The liquid feeding structure concerning this Embodiment is shown in FIGS. FIG. 1A is a diagram illustrating the entire structure of the liquid feeding structure, FIG. 1B is a conceptual diagram illustrating a main substrate, and FIG. 1C is a conceptual diagram illustrating a lid substrate. FIG. 2 is a cross-sectional view taken along broken line 140 in FIG. FIG. 3 is a plan view showing a flow path in the vicinity of the working electrode.

  As shown to Fig.1 (a), the liquid feeding structure concerning this Embodiment is the main board | substrate 111 (polydimethylsiloxane (PDMS): contact angle 100 degrees-120 degrees), and the lid | cover board | substrate 110 (glass: contact). The angle is 5 ° to 30 °).

  The main substrate 111 has an injection hole 112 for injecting liquid into the chip, a discharge hole 113 for discharging the liquid to the outside of the chip, and a groove for the flow path 114 connecting the injection hole 112 and the discharge hole 113. It is formed (see FIG. 1C).

  On the lid substrate 110, an electrowetting valve reference electrode 131, a working electrode 132, a lead electrode 133 extending each electrode, and an external connection terminal electrode 136 are formed. Here, the entire reference electrode 131 intersects with the channel 114 (channel width> reference electrode width), and the working electrode 132 partially intersects with the channel 114 (channel width <working electrode width). (See FIG. 1B).

  As can be seen from FIGS. 1 and 2, the flow path 114 has a constant flow path width (groove width) and flow path height (groove height).

  As shown in FIG. 3, the working electrode surface has a hydrophilic region 134 near the upstream end and a remaining hydrophobic region 135.

  The thickness of the main substrate 111 is about 0.1 mm to 10 mm, and the diameters of the through hole 112 and the through hole 113 may be 10 μm or more. The channel width and the channel height are both 50 μm in this embodiment.

  In addition, a hydrophobic PDMS substrate is used as the main substrate 111, and a hydrophilic glass substrate is used as the lid substrate 110. However, the present invention is not limited to this, and is appropriate depending on the use application of the liquid feeding structure. It is better to select the material. For example, when a detection unit that performs optical detection is incorporated in the liquid feeding structure, a transparent or translucent material that emits little light by excitation light is used as one or both of the main substrate 111 and the lid substrate 110. It is desirable.

  Examples of such a transparent or translucent material include glass, quartz, thermosetting resin, thermoplastic resin, and film. Of these, silicon resins, acrylic resins, and styrene resins are preferable from the viewpoints of transparency and moldability. Examples of plastic materials that emit less light by excitation light include fluorescence of fluorine-based plastic materials such as fluorinated polymethyl methacrylate in which hydrogen atoms of polymethyl methacrylate are replaced with fluorine atoms, and additives such as catalysts and stabilizers. Examples thereof include polymethyl methacrylate using a member that does not emit.

  On the other hand, it is necessary to form electrodes on the surface of the lid substrate 110 and / or the main substrate 111 in order to perform electrical control and electrical measurement within the liquid delivery structure flow path. For this reason, it is preferable that one or both of the main substrate 111 and the lid substrate 110 be a material capable of forming an electrode. As a material capable of forming an electrode, glass, quartz, silicon and the like are preferable from the viewpoint of productivity and reproducibility.

  Note that since it is difficult to form electrodes on the uneven portion, it is preferable to form electrodes on the flat lid substrate 110 instead of the main substrate 111 having uneven portions due to the grooves.

(Pressure acting on the flow path)
In this embodiment in which both the hydrophilicity (inner wall surface due to the glass substrate) and the hydrophobicity (inner wall surface due to the PDMS substrate) exist on the inner wall surface of the flow path, the pressure P acting on the flow path is as follows: Can be sought. In the channel cross-sectional view shown in FIG. 22, the channel height 161 is h, the channel width 162 is w, the contact angle of the main substrate 111 is θ1, the contact angle of the lid substrate 110 is θ2, and the interfacial tension at the gas-liquid interface. Where σ is the interfacial tension acting on the upper surface of the flow path is F1, the interfacial tension acting on the lower surface is F2, and the interfacial tension acting on the left and right surfaces is F3, these are shown in FIG. It is obtained by Equation 4. Since the pressure P acting on the flow path is obtained by dividing the sum of F1, F2, and F3 by the cross-sectional area wh, the pressure P acting on the flow path in this case is obtained by Expression 5 in FIG. When the pressure P becomes a positive value, a capillary phenomenon occurs and the liquid advances. When the pressure P becomes 0 or a negative value, the capillary phenomenon does not occur and the liquid stops.

  Although the case where the shape of the channel cross section orthogonal to the flow direction is rectangular has been described above, the channel cross sectional shape is not limited to this. A circular shape, an elliptical shape, a semicircular shape, an inverted triangular shape, or the like may be used. Even if the cross-sectional shape of the flow path is other than rectangular, the interfacial tension for each specific region of the cross-section is obtained, and the pressure P acting on the entire flow path is obtained by accumulating the interfacial tension according to the composition ratio (see FIG. 23 formulas 2-5).

(Operating principle of electrowetting valve)
FIG. 4 shows the flow of liquid in the flow path of the liquid feeding structure according to the present embodiment. 4A shows a state where the voltage application is OFF, and FIG. 4B shows a state where the voltage application is ON.

  As shown in FIGS. 3 and 4, the working electrode 132 is formed so as to cover the flow path portion of the hydrophilic lid substrate 110 constituting one surface of the inner wall surface of the flow path, and the upstream end of the working electrode 132. The surface of the region 135 other than the vicinity is covered with a hydrophobic film (tetrafluoroethylene film). Therefore, in the region 135 where the hydrophobic film of the working electrode 132 is formed, the entire inner wall surface (four surfaces) of the flow channel becomes hydrophobic, and the groove width and the groove depth of the flow channel 114 provided with the working electrode 132 are Each is as narrow as 50 μm. Therefore, when the voltage application is OFF, the liquid cannot pass through the region 135 of the electrowetting valve working electrode 132.

  On the other hand, when a voltage is applied between the working electrode 132 and the reference electrode 131 (about 0.8 V to 1.5 V), the liquid can pass through the working electrode 132 (FIG. 4B). )reference).

  This will be described with reference to FIG. The liquid injected from the injection hole 112 flows through the flow path 114 while in contact with the electrowetting valve reference electrode 131, and an electrowetting valve provided in a specific area of the flow path 114 (area where the liquid is to be stopped). It reaches the working electrode 132 portion. The electrowetting valve working electrode 132 is made of gold (contact angle: 60 ° to 85 °), and the region 135 other than the vicinity of the upstream end of the working electrode is a hydrophobic membrane or a near-hydrophobic membrane having low hydrophilicity ( The contact angle is 60 to 90 °. Therefore, when no voltage is applied, the contact angle with the liquid is 60 ° or more. As a result, the pressure P generated by the surface tension becomes 0 or minus, and the liquid flow is stopped (see FIG. 4A). That is, when voltage application is OFF, the valve is closed.

  On the other hand, when a voltage is applied to the extraction electrode 133, the liquid that has passed over the reference electrode 131 is negatively charged, a virtual capacitor is formed between the working electrode 132 and the liquid, and the liquid is applied to the working electrode 132. Gravitate. As a result, the contact angle of the liquid with respect to the working electrode is reduced. For example, the contact angle is about 40 °. That is, apparently, the hydrophilicity is enhanced over the entire surface of the working electrode, and the influence of the hydrophilicity is increased, so that the pressure (capillary force) generated by the surface tension becomes positive. As a result, the liquid can pass through the region 135 (see FIG. 4B). That is, when voltage application is ON, the valve is opened.

  Thus, in order to operate the electrowetting valve with certainty, it is necessary to design the liquid to stop when at least part of the working electrode is in contact with the liquid when the voltage application is OFF. .

  In the present embodiment, in order to satisfy such a condition, as shown in FIG. 3, a hydrophilic region 134 near the upstream end and a remaining hydrophobic region 135 are provided on the surface of the working electrode. That is, when the contact angle of the hydrophilic region 134 is D1 and the contact angle of the hydrophobic region 135 is D2, there is a relationship of D1 <90 ° ≦ D2.

  Based on the above principle, in order to accurately turn the liquid flow on and off with the electrowetting valve, adjustment is made so that the influence of the hydrophilic part and the hydrophobic part cancel each other when the voltage application is turned off. Therefore, it is necessary to make at least a part of the inner wall surface of the flow path hydrophobic and the rest hydrophilic. When a hydrophilic substrate (glass substrate) is used as the lid substrate and a hydrophobic substrate (PDMS substrate) is used as the main substrate for forming the channel for the channel, the influence of hydrophobicity is reduced by narrowing the channel width. Since it can be increased (works in the direction in which the capillary force decreases), the flow of the liquid can be accurately controlled by balancing the change in the contact angle of the surface of the working electrode 132 with this. In the state where the voltage application is OFF, the capillary structure acts on the hydrophilic region 134 and the capillary region does not act on the hydrophobic region 135 in the liquid feeding structure. The flow path height h (161) and the flow path width w (162), which are the variables of Equation 5 of 23, are set. For this purpose, the channel width and the channel height of the channel 114 are preferably 10 μm or more and 300 μm or less, respectively, for example, the channel width and the channel height are each 100 μm or less.

  Further, when the contact angle of the hydrophobic film on the surface of the working electrode 132 or the near-hydrophobic film having low hydrophilicity is made appropriate and the contact angle of the surface of the working electrode 132 is decreased by applying a voltage, the effect of the hydrophobic wall surface It is designed to increase the effect of the hydrophilic wall surface. The degree of hydrophobicity or low hydrophilicity is, for example, a contact angle of 60 ° to 145 °, preferably 90 ° to 120 °.

  Here, as a method of providing the hydrophilic region 134 and the hydrophobic region 135 on the surface of the working electrode 132, (1) a hydrophobic material is used as a constituent material of the working electrode and the region 134 is treated to be hydrophilic. (2) A method of using a hydrophilic material as a constituent material of the working electrode and treating the region 135 to be hydrophobic can be used. In this embodiment, hydrophilic gold (contact angle: 60 ° to 85 °) is used for the working electrode itself, and a tetrafluoroethylene (contact angle: 100 ° to 120 °) film is formed so that the region 135 becomes hydrophobic. (Adopting (2) above).

  For example, as the method (1), it is preferable to use a hydrophobic conductive polymer as a constituent material of the working electrode. Further, oxygen plasma treatment, UV treatment, or the like can be used as the hydrophilic treatment. The hydrophilicity can also be enhanced by applying a surfactant or a reagent having a hydrophilic functional group to the surface. Moreover, hydrophilicity can also be improved by controlling the roughness of the surface.

  As the method (2), it is preferable to use conductive gold as a constituent material of the working electrode. And it can hydrophobize by forming a hydrophobic film | membrane in surfaces other than the upstream end vicinity of a working electrode. Specifically, a hydrophobic material is applied or a film having a hydrophobic functional group is formed on the surface. Moreover, hydrophobicity can also be improved by controlling the surface roughness.

  As the hydrophobic film, a tetrafluoroethylene film or a natural oxide film (hydrophobic film with a contact angle of 60 to 85 °) formed by being left in the air can be used to easily control the thickness of the film. Therefore, it is preferable. In the case of a natural oxide film, it is difficult not to form only the region near the upstream end. Therefore, it is preferable to hydrophilize the region near the upstream end after the film is formed on the entire surface.

  In the above, a configuration including two regions, the hydrophilic region 134 in the vicinity of the upstream end and the remaining hydrophobic region 135 is illustrated, but the hydrophilic region is located downstream of the hydrophobic region 135. It may be formed.

  The width and height of the flow path 114 of the liquid feeding structure shown in FIG. 1 are not particularly limited, but are preferably set to dimensions that allow the liquid to permeate due to liquid wetting and capillary force. The channel height is preferably set to about 1 μm to 5 mm, and the channel width is preferably set to about 1 μm to 5 mm.

  This liquid delivery structure uses, for example, an upstream region of the working electrode as a region for mixing the liquid, and an antibody or the like is immobilized in a region downstream of the working electrode, and a liquid containing an antigen is allowed to flow in this region. It can be used as a microanalysis chip in which a liquid containing a labeled antibody to which a fluorescent dye is attached is allowed to react and an antigen-antibody reaction is performed, and the region is irradiated with excitation light and the amount of antigen is measured by the amount of fluorescence.

  “Hydrophilicity” and “hydrophobicity” of the inner wall surface of each flow path can be easily realized by using a hydrophilic substrate or a hydrophobic substrate as a substrate material. It is not limited to those derived from the properties of the substrate material itself. For example, “part of the inner wall surface of the flow path is hydrophobic” can be realized by applying a hydrophilic treatment to a part of the flow path that is hydrophobic. Further, “a part of the inner wall surface of the flow path may be made hydrophobic” by subjecting a part of the substrate surface made of a hydrophilic material to a hydrophobic treatment such as formation of a hydrophobic film. As the hydrophilization treatment, for example, oxygen plasma treatment or UV treatment can be used. Alternatively, hydrophilicity may be enhanced by applying a surfactant or a reagent having a hydrophilic functional group to the surface. On the other hand, as the hydrophobizing treatment, there are a hydrofluoric acid treatment and a method of forming a tetrafluoroethylene film.

(Embodiment 2)
Embodiment 2 relates to the second invention.
The liquid feeding structure according to the present embodiment is shown in FIG. FIG. 5A is a diagram showing the entire structure of the liquid feeding structure, FIG. 5B is a conceptual diagram showing a main substrate, and FIG. 5C is a conceptual diagram showing a lid substrate.

  As shown in FIG. 5A, the liquid feeding structure according to the present embodiment includes a main substrate 111 (polydimethylsiloxane (PDMS): hydrophobic) and a lid substrate 110 (glass: hydrophilic). It is a superposed structure.

  In the second embodiment, the surface of the working electrode 132 is made hydrophobic without providing the hydrophilic region near the upstream end and the remaining hydrophobic region, and instead of the channel in the region where the working electrode 132 is formed. Except that the width is changed between the upstream end and the downstream side (the upstream end is wider than the downstream side), it is the same as in the first embodiment. Therefore, the substrate configuration, the flow path, the injection hole, and the like are the same as those in the first embodiment, and the description thereof is omitted.

  The surface of the working electrode is entirely covered with a hydrophobic film. Regarding the arrangement of the working electrode, the upstream end has a flow path width> the working electrode width, and the downstream side has a flow path width <the working electrode width. .

(Operating principle of electrowetting valve)
FIG. 6 is an enlarged view showing the vicinity of the working electrode of the liquid feeding structure according to the present embodiment.

  The flow path width is w1 (142) at the upstream end of the working electrode 132, the flow path width is w2 (143), the working electrode width is w3 (144), and the flow path height is h at the downstream portion.

  At this time, in the flow path near the upstream end of the working electrode, the influence of the inner wall surface of the hydrophobic substrate 111 on the pressure is (w1 + 2h), and the influence of the inner wall surface of the hydrophilic substrate 110 on the pressure is (w1-w3). And the influence of the surface of the working electrode 132 on the pressure is (w3). On the other hand, in the channel in the region where the downstream channel width is w2, the influence of the inner wall surface of the hydrophobic substrate 111 on the pressure is (w2 + 2h), and the influence of the surface of the working electrode 132 on the pressure is ( w2). Therefore, the pressure P1 acting on the flow path at the upstream end of the working electrode 132 is calculated with reference to Equation 5 in FIG. The pressure P2 acting on the flow path in the region where the flow path width on the downstream side of the working electrode is w2 is calculated with reference to Equation 5 in FIG.

  At this time, if the pressure P1 is positive and the pressure P2 is designed to be 0 or negative, even if the surface of the working electrode 132 is hydrophobic when the voltage application is OFF, the pressure P1 acting on the flow path The working electrode upstream end reliably comes into contact with the liquid. Further, since the pressure P2 is 0 or negative, the liquid is surely stopped when the voltage application is OFF (the valve is closed).

  When the voltage application is ON, the liquid flows through the working electrode in the region having the flow path width w2 according to the same principle as described in the first embodiment (the valve is opened). .

  In the case of the flow channel structure as shown in FIG. 5, a configuration in which the downstream end of the working electrode extends to a portion where the flow channel width is located in the downward direction in the drawing may be adopted. In this case, the pressure acting on the flow path in the portion where the flow path width is wide may be positive.

(Modification 1 of Embodiment 2)
For example, as shown in FIG. 7, a structure in which the flow path width in the vicinity of the working electrode 132 is rapidly changed (the angle of the contour line of the flow path is 90 °) may be employed.

(Modification 2 of Embodiment 2)
The main substrate may be hydrophilic and the lid substrate may be hydrophobic. In this case, the design is as follows.

  In this configuration, the smaller the channel width, the greater the influence of hydrophilicity, so the capillary force increases. Therefore, as shown in FIG. 8, in order to stop the liquid, it is necessary to make the flow path width w4 (142) at the upstream end of the working electrode smaller than the flow path width w5 (143) on the downstream side. In this embodiment, in order to simplify the description, the working electrode width w6 (144) is set larger than the downstream flow path width w5, but may be w6 ≦ w5.

  In this configuration, in the flow path near the upstream end of the working electrode, the influence of the inner wall surface of the hydrophilic substrate on the pressure is (w4 + 2h), and the influence of the surface of the working electrode on the pressure is (w4). On the other hand, in the channel in the region where the downstream channel width is w2, the influence of the inner wall surface of the hydrophobic substrate on the pressure is (w5 + 2h), and the influence of the surface of the working electrode on the pressure is w5. . For this reason, the pressure P3 acting on the flow path at the upstream end of the working electrode is calculated with reference to Equation 5 in FIG. 23 after adding the two components. The pressure P4 acting on the flow channel on the downstream side of the working electrode is calculated with reference to Equation 5 in FIG. 23 after adding the two components.

  At this time, by designing the pressure P3 to be positive and the pressure P4 to be 0 or negative, when the voltage application is OFF, the working electrode upstream end is reliably brought into contact with the liquid, and the pressure on the working electrode is ensured. The liquid can be stopped.

(Modification 3 of Embodiment 2)
As shown in FIG. 9, a configuration in which the flow path height is changed may be employed.

  In the liquid feeding structure in which the main substrate is hydrophobic and the lid substrate excluding the electrode 132 is hydrophilic, the flow path height at the upstream end of the working electrode 132 is h1 (151), as shown in FIG. Let the flow path height of the part be h2 (152). Therefore, the pressure P5 acting on the flow path at the upstream end of the working electrode may be set to a positive value, and the pressure P6 acting on the flow path on the downstream side may be designed to be 0 or a negative value. In this configuration, the relationship of h1 <h2 is established.

(Modification 4 of Embodiment 2)
In the third modification, as shown in FIG. 10, a structure in which the flow path height is changed stepwise may be adopted.

(Modification 5 of Embodiment 2)
In the modified examples 3 and 4, the main substrate may be hydrophilic and the lid substrate may be hydrophobic. In this case, the design is as follows.

  In the said structure, the influence of hydrophilicity becomes large and the capillary force becomes large, so that flow path height is large. Therefore, as shown in FIG. 11, when the flow path height at the upstream end of the working electrode 132 is h3 (151) and the flow path height at the downstream portion is h4 (152), the action is performed using h3 and h4. The pressure P7 acting on the flow path at the upstream end of the electrode and the pressure P8 acting on the flow path on the downstream side are calculated so that the pressure P7 is positive and the pressure P8 is 0 or negative. At this time, h3> h4 is established.

(Modification 6 of Embodiment 2)
Alternatively, the inner wall surface of the channel at the upstream end of the working electrode may be hydrophilized and / or the inner wall surface of the channel on the downstream side of the working electrode may be hydrophobized without changing the channel width or the channel height.

  The examples described in the second embodiment (including modifications) may be combined as appropriate.

(Embodiment 3)
The present embodiment relates to the third invention.
FIG. 12 shows a liquid feeding structure according to the third embodiment. In the present embodiment, a hydrophobic structure 149 that increases the liquid contact surface is provided on the downstream side (hydrophobic substrate 111 side) of the working electrode. For this reason, in the flow path of the portion where the hydrophobic structure 149 is provided, the hydrophobic structure 149 further affects the inner wall surface of the flow path, and the hydrophobicity is increased. When the voltage application is OFF, the pressure acting on the flow path at the upstream end of the working electrode is positive, and the pressure acting on the flow path in the region where the hydrophobic structure 149 is formed becomes 0 or negative (the expression of FIG. 23). 5), the liquid contacts the upstream end of the working electrode 132 and stops at the region where the hydrophobic structure 149 is formed. When the voltage application is ON, the liquid flows through the hydrophobic structure 149 formation region.

  As the hydrophobic structure 149, a structure that increases the liquid contact surface such as a pillar, a hole, and a groove can be arbitrarily adopted. In this embodiment, the liquid is surely stopped in the region where the hydrophobic structure 149 is provided by designing the area of the part in contact with the liquid and the area of the part in contact with the gap space in the structure. Can do.

(Embodiment 4)
In the fourth embodiment, two electrowetting valves shown in the first embodiment are arranged in series.

  FIG. 13 shows a liquid feeding structure according to the fourth embodiment. A description of the configuration of each part and design requirements for stopping the liquid will be omitted.

  In this configuration, the liquid can be controlled in two stages by the flow path 114. Three or more may be arranged in series.

(Embodiment 5)
In the fifth embodiment, two electrowetting valves shown in the second embodiment are arranged in parallel.

  FIG. 14 shows a liquid feeding structure according to this embodiment. In the present embodiment, the two injection holes 112a and 112b, the second flow paths 151a and 151b that are continuous with the injection holes, and the flow path width that is continuous with the liquid storage flow path than the liquid storage flow path, respectively. Narrow third flow paths 152a and 152b, a first flow path 114 continuous with the two third flow paths, and a discharge hole 113 continuous with the first flow path are provided.

  Here, the reference electrodes 131a and 131b are formed in the second flow paths 151a and 151b, respectively, and the working electrodes 132a and 132b are the second flow paths 151a and 151b and the third flow paths 152a and 152a, respectively. It is formed in a region where the switching with 152b is performed. The substrate configuration is the same as that of the second embodiment. That is, the upstream end of the working electrode is positioned in the second flow path (the portion where the influence of the hydrophilic substrate is large) having a large flow path width, and the downstream region is the third flow path (the hydrophilic substrate) having a small flow path width. Is located in the area where the influence of is small. For this reason, two electrowetting valves according to the fifth embodiment are arranged in parallel to obtain the same effect as in the second embodiment.

  In this configuration, different solutions can be sequentially fed into the first flow path. Three or more may be arranged in parallel, or may be used in combination with the configuration of the fourth embodiment.

(Embodiment 6)
Embodiment 6 relates to a micro-analysis chip using the liquid-feeding structure of the present invention. As shown in FIG. 15, the microanalysis chip according to the third embodiment has an injection hole 112, flow paths 114a to 114e, and a discharge hole 113 (see FIG. 15).

  Furthermore, in this embodiment, a working electrode is formed in the flow path 114b, and a reference electrode is formed in the flow path 114a. For this reason, the flow of the liquid can be controlled by designing the same as in the second embodiment. The flow path 114d is provided with a detection unit. Moreover, the detection part should just be a part which has the function which can detect a target substance. Since both are not particularly restricted, the reaction unit and the detection unit are not shown in FIG.

  Moreover, the detection part is provided in the narrow flow path 114d. With this structure, the liquid that has entered the flow path 114d having a narrower width than the flow path 114c accelerates the flow and flows uniformly without traffic congestion, so that the detection accuracy increases. In addition, since the passage of the detection target substance is reduced, the detection accuracy is also enhanced from this aspect.

  In addition, the detection method in the detection unit includes a method of measuring the amount of electricity using an electrode (electrochemical method), an optical method of irradiating light from the outside and measuring reflected light and transmitted light, etc. In any method, the effect of preventing the liquid flow from being jammed (an improvement in detection accuracy and detection reproducibility) can be obtained.

  As described above, according to the sixth embodiment, it is possible to easily and quickly detect a target substance with a simple structure and realize a microanalysis chip excellent in detection accuracy.

(Embodiment 7)
The seventh embodiment is the same as the first embodiment except that the counter electrode 137 is provided in order to stabilize the potential of the reference electrode 131 (see FIG. 16). By providing the counter electrode 137, it is possible to prevent a current flow to the reference electrode 131 serving as a potential reference, and to stabilize the potential of the reference electrode. This effect makes it possible to electrically drive the electrowet valve with higher accuracy.

(Embodiment 8)
The eighth embodiment is a further development of the microanalysis chip according to the sixth embodiment. Details of a specific configuration of the microanalysis chip according to the eighth embodiment will be sequentially described.

(overall structure)
FIG. 17 shows an overall configuration diagram of the microanalysis chip according to the embodiment. As shown in FIG. 17, the microanalysis chip according to the eighth embodiment is continuous with the first injection hole 2001 for the first liquid, the second injection hole 2002 for the second liquid, and these injection holes. The first liquid reservoir 2003, the second liquid reservoir 2004, the injection paths 2005 and 2006 that continue to these liquid reservoirs, the mixer section 2007, the first narrow path 2009, the first flow path 2008, the first The second channel 2011, the second channel 2010, the third channel 2013, the third channel 2016, and the discharge hole 2014 are provided. The first channel 2008 is provided with a reaction unit 2017. In addition, a detection unit 2012 is provided in the second flow path 2010.

  A working electrode is formed in each of the injection paths 2005 and 2006, and a reference electrode is formed in each of the first and second liquid reservoirs 2003 and 2004. That is, this embodiment uses the fifth embodiment.

  Further, an external connection terminal 2015 is provided at the end of the chip.

  When the first liquid is injected from the first injection hole 2001, the first liquid is injected into the first liquid reservoir 2003. Similarly, when the second liquid is injected into the second injection hole 2002, the second liquid is injected into the second liquid reservoir 2004.

  The working electrode and the reference electrode can stop or start the inflow of the injected liquid into the mixer unit 2007. The mixer unit 2007 has a structure capable of mixing the first liquid and the second liquid.

  A first flow path 2008 is connected to the mixer unit 2007 via a first bottleneck 2009. In the reaction section 2017 provided in the first flow path 2008, a substance that reacts with the substance to be detected contained in the solution is disposed.

  In the example of FIG. 17, the mixer section and the reaction section are connected via the first bottleneck 2009, but may be directly connected without passing through the first bottleneck 2009.

  The second flow path 2010 is connected to the first flow path 2008 via the second narrow path 2011, and the detection section 2012 is provided in the second flow path 2010. The detection unit is configured to detect the substance to be detected directly or indirectly. Note that in the case where the detection target substance can be directly detected, the second flow path 2010 can be omitted.

  This micro analysis chip requires an external connection terminal 2015, and can be connected to an external power source, input an electrical control signal, output a detection signal, and the like via the terminal. As a result, since a control circuit such as a power supply or an IC can be externally attached, the chip can be made compact accordingly.

  The micro analysis chip according to the seventh embodiment will be further described.

<Liquid injection>
The first liquid and the second liquid are injected from the injection hole 2001 for the first liquid and the injection hole 2002 for the second liquid, respectively. Thereby, each liquid can be inject | poured into the liquid reservoir parts 2003 and 2004. FIG.

  The injection holes 2001 and 2002 are open to the outside (atmosphere) and have such a size (for example, 2 mmΦ) that capillary force does not work. When the size is such that the capillary force does not work, the liquid can be smoothly injected even if the injection hole is hydrophobic. The injection holes 2001 and 2002 may be of such a size that capillary force works, but in this case, it is necessary to perform a hydrophilic treatment on the injection holes so that the liquid can be injected smoothly.

  The liquid can also be injected by connecting a cartridge filled with liquid into the injection hole. In this case, it is preferable that an air vent clearance is secured in the injection hole or a separate air vent hole is provided so that the liquid in the cartridge can sufficiently flow into the flow path system.

  Although the example of FIG. 17 has a structure having two injection holes, the number of injection holes is not limited to two, and may be three or more. For example, a sample containing a substance to be detected in the first liquid injection hole, a reagent in the second liquid injection hole, a standard sample in the third liquid injection hole, and a fourth liquid use For example, a cleaning liquid may be injected into the injection hole.

  When the fourth injection hole for injecting the cleaning liquid is provided, the cost performance of the chip can be improved by cleaning the inside of the chip and repeatedly using it. In addition, the contamination of the sample or the like can be reduced by injecting the cleaning liquid from the first liquid injection hole or the like before and after the detection processing to clean the inside of the flow path. Thereby, detection errors can be reduced.

<Mixer section>
The mixer unit is configured to sufficiently mix the first liquid and the second liquid. For example, a micro pillar structure may be provided in the mixer section so that the liquid flowing in from the first opening / closing valve and the second opening / closing valve is naturally mixed. Also, a T-shaped mixer, a Manz mixer, a mixer using a three-dimensional meandering channel, and the like can be provided.

  Although the example of FIG. 17 is a case where two liquids are mixed, you may comprise so that three or more liquids may be mixed. In this case, in order to control the injection of the third liquid and the inflow timing, it is preferable to form electrodes similarly to the other liquid reservoirs and injection paths.

<First channel>
The first flow path 2008 functions as a reaction region for performing a reaction. The reaction section 2017 provided in the first flow path 2008 may be the whole of the first flow path 2008 or a part thereof. In the reaction unit 2017, for example, molecules that specifically recognize and react with a target substance contained in the sample solution are arranged. When the substance to be detected is an antigen, the antibody may be immobilized on the reaction part. In order to detect a substance to be detected, a sandwich method of enzyme immune reaction can be used. In this case, an antigen is reacted with an enzyme-labeled antibody (secondary antibody), and a complex in which the antigen and the enzyme-labeled antibody are bound to each other. To do. This complex is immobilized in advance in the reaction part and reacted with an antibody (primary antibody). Next, a substrate is introduced, reacted with an enzyme labeled with the secondary antibody, and an electrochemically active substance generated by the reaction is electrochemically detected on the electrode of the detection unit. In the reaction unit, a substance that can be detected by the detection unit is generated according to the amount of the substance to be detected. The detection means in the reaction unit may be an optical means.

<External connection terminal>
The external connection terminal 2015 is used to input drive power and drive information to the chip from the outside, and to output detection results and the like to the outside. When a gold thin film is used for the formation of the terminal, the external connection terminal can be formed in the same manner as the electrowetting valve and the detection electrode, so that the production efficiency is good. Of course, other conductive materials such as copper, iron or aluminum may be used instead of gold.

<Two-layer structure>
The micro analysis chip according to the eighth embodiment has a two-layer structure in which a first substrate (main substrate) 2101 and a second substrate (lid substrate) 2102 are overlapped. Each layer structure of the two-layer structure will be described with reference to FIG.

  The first substrate (main substrate) 2101 preferably has high transparency and processability, and preferably has hydrophobicity in order to control the movement of the liquid. Such a substrate is preferably made of polydimethylsiloxane (PDMS). On the other hand, the second substrate (lid substrate) is preferably made of a material that is easy to form an electrode. When the first substrate is hydrophobic, it needs to be hydrophilic. As such a substrate, a substrate made of glass, quartz, silicon or the like is preferable.

  The first substrate and / or the second substrate have the above hydrophilic or hydrophobic characteristics, and are transparent or translucent with little emission of excitation light in order to measure the target substance using fluorescence or UV light. It is desirable to use the material. As such a material, the material described in Embodiment 1 or the material proposed in Japanese Patent Laid-Open No. 2003-149252 can be used.

  The following processing is performed on each substrate. For the first substrate (main substrate), a first liquid injection hole 2001, a second liquid injection hole 2002, and a discharge hole are opened upward. Further, the liquid reservoirs 2003 and 2004, the injection channels 2005 and 2006, the mixer unit 2007, the first channel 2008, the first channel 2009, the second channel 2010, the second channel 2011, the third channel 2013, the third A concave groove for the flow channel 2016 is formed.

  For the second substrate (lid substrate) 2102, an electrode 2105, an electrode 2106, and a detection electrode 2112 are formed on the surface, and an external connection terminal 2015 is formed on the end of the second substrate. Furthermore, a lead line for connecting each electrode to the external connection terminal 2015 is formed. Each electrode may be formed using a known method.

  The two substrates 2101 and 2102 processed as described above are bonded to each other with the processed surface inside. Thereby, the micro analysis chip according to the eighth embodiment is completed.

(Embodiment 9)
Embodiment 9 relates to a portable handheld microanalyzer. The contents of the eighth embodiment will be described with reference to FIG. FIG. 19 is a conceptual diagram for explaining the outline of the portable handy-type microanalyzer according to the ninth embodiment.

  This handheld microanalyzer is composed of a microanalysis chip 2302 and a control handy device 2301 for driving and controlling the microanalysis chip. The micro analysis chip 2302 is the same micro analysis chip as described in the eighth embodiment. Therefore, detailed description of the micro analysis chip is omitted here.

  As shown in FIG. 19, a chip connection port 2303 into which the external connection terminal 2015 of the micro analysis chip 2302 similar to that described in the seventh embodiment is inserted is provided below the control handy device 2301. An external input / output terminal (not shown) that is electrically connected to the external connection terminal 2015 is provided at the back of the chip connection port. When the external connection terminal 2015 of the micro analysis chip is inserted into the chip connection port 2303, the external input / output terminal in the control handy device 2301 and the external connection terminal of the micro analysis chip 2302 are electrically connected.

  The control handy device 2301 has a display unit 2304 that can display the measurement result of the analysis chip (amount of the substance to be detected, etc.), and various data for specifying the measurement parameters. An input unit 2305 is provided. As the input unit 2305, for example, a touch panel structure can be adopted.

  Further, although not shown, the control handy device 2301 incorporates an information processing system such as a CPU that can process data and an I / O logic circuit that processes input information and output information.

  The micro analysis chip 2302 is connected to the control handy device 2301, various data are input, and a measurement start button is pressed. As a result, solutions such as reagent liquids and sample liquids (test liquids) that have been previously provided in the microanalysis chip and that have stopped flowing into the flow path by the open / close valve sequentially enter the flow path. As a result, a predetermined reaction is performed in each flow path to become a detectable substance to reach the detection unit, where an electrical signal corresponding to the amount of the substance to be detected is generated. This electrical signal is output from the external connection terminal 2015 to the outside.

  The signal output from the external connection terminal 2015 is received by an external input terminal of a control handy device electrically connected to the external connection terminal 2015, and this signal is based on software information stored in advance in the control handy device. analyse. Thereby, the quantity or type of the substance to be detected can be specified.

  As the control handy device, for example, a portable electronic device such as a mobile phone or a PDA can be used. Here, a mobile phone will be described as an example. For example, the above-described chip connection port is provided in a mobile phone having a computer function, and analysis software for processing data transmitted from the micro analysis chip is stored in this mobile phone. This mobile phone normally functions as a mobile phone, and can function as a handy device for control if necessary.

  The operation method is illustrated. Connect the micro analysis chip to the mobile phone, input various data using the buttons on the mobile phone, and then press the button set as the measurement start button. As a result, the reagent solution or test solution that has been prepared in advance in the microanalysis chip and has stopped flowing into the flow path by the open / close valve is advanced into the flow path. Thereafter, the analysis chip sequentially operates to output an electric signal corresponding to the amount of the substance detected by the detection unit to the mobile phone. The computer of the mobile phone analyzes this signal in software to identify the amount and type of the substance to be detected. This is displayed on the mobile phone display. Also, upon receiving an instruction from the operator, the analysis information is transmitted to a remote place using the transmission function.

  In this way, by using a portable device, it is possible to realize a microanalyzer that is excellent in cost performance and convenient and easy to use.

  The signal transmission method between the analysis chip and the portable electronic device may be any method and form as long as electrical signals can be exchanged between the two, and it is not necessarily required to be a method via the chip connection port as described above. Absent.

(Embodiment 10)
In the microanalyzer according to the tenth embodiment, each function such as sampling of a sample (test solution), analysis of detection data, and output of analysis results is formed on a plurality of substrates, and these are stacked and integrated. The present invention relates to a body type microanalyzer.

  FIG. 20 shows a plan view of the integrated microanalyzer. As shown in FIG. 20, this integrated microanalyzer includes a sample collection unit 2401, a liquid channel unit 2402, a drive analysis processing unit 2403, an input / output logic processing unit 2404, and an input / output unit 2405, each on one substrate. Is formed. However, all the elements may be formed on one substrate, or each related element may be formed on one substrate.

  In the sample collection unit 2401, a needle included in a capillary tube is arranged, and blood or a sample is collected by inserting the needle into a human body or a sample body. The needle is preferably a minimally invasive microprobe because the pain is alleviated when the needle is inserted into a human body or the like and a body fluid such as blood is extracted. In addition, the sample collection unit 2401 may be provided with a non-invasive collection device, for example, sweat on the skin surface, saliva in the oral cavity, tears, urine, or the like together with or in place of the needle.

  Moreover, as the liquid flow path part 2402, the flow path structure similar to the liquid feeding structure and the micro analysis chip in the first to fourth embodiments is used. Of these, the channel structure described in the third embodiment is preferably used. The capillary tube of the needle disposed in the sample collection unit 2401 is connected to the liquid reservoir 2414 of the liquid flow channel unit 2402 so that the sample flows into the liquid reservoir due to the capillary phenomenon of the capillary provided in the needle. It is configured.

  The liquid channel portion 2402 is manufactured using a substrate such as polydimethylsiloxane (PDMS), polymethyl methacrylate (PMMA), polycarbonate, polytetrafluoroethylene, or vinyl chloride. A plurality of detection units may be arranged in the liquid flow path unit 2402. Moreover, it is good also as a structure where several flow-path systems (liquid feeding structure for microanalysis) coexist.

  The drive analysis processing unit 2403 is provided with a CPU, a memory, a battery (not shown), and the like, and is connected to a detection unit of the liquid flow path unit 2042, an I / O logic circuit described later, and the like. Since this embodiment is an integrated type that includes all elements, a CPU and a memory are provided in the drive analysis processing unit 2403 so that on-off valve control corresponding to various measurements, measurement data processing, and the like can be performed. In the memory, valve control sequence information corresponding to various measurements and processing information of measurement data are stored.

  Based on the information stored in advance, the drive analysis processing unit 2403 opens the open / close valve at the start of measurement and allows a reagent solution, a sample solution (test solution), etc. to flow into the flow path, and the electrical detected by the detection unit is detected. The signal is processed to identify the amount or type of substance to be detected. As described above, the drive analysis processing unit 2403 is configured to control the micro analysis chip and output measurement data obtained by the micro analysis chip to an I / O logic circuit (described below). Note that the drive analysis processing unit 2403 can be configured in the same manner as the lid substrate 2102 of FIG. 18 in the eighth embodiment, and can incorporate the drive control elements described in the ninth embodiment.

  The input / output logic processing unit 2404 has an I / O logic circuit, and this I / O logic circuit is connected to the CPU of the drive analysis processing unit 2403 and each button of the input / output unit via the electrical connection line and Connected to the display. The input / output logic processing unit 2404 cooperates with the CPU of the drive analysis processing unit 2403 to process I / O data, display the measurement result on the display (LCD) of the input / output unit, and The micro analysis chip is controlled based on the electric signal input by the input button. This control includes at least control of the on-off valve and control of the detection unit electrode.

  The input / output unit 2405 is provided with an input button for giving an instruction to the CPU and a display (LCD). The display is not limited to the LCD (liquid crystal display) but may be an organic EL display module or the like.

  The display performs a display operation by driving the drive driver circuit in cooperation with the I / O logic circuit and the CPU. As the display format, for example, various display formats such as numerical display, graph display, “present / none” display, and time-change display can be adopted.

  Further, although not shown in FIG. 20, the input / output unit can be provided with a terminal for processing input / output with the outside or a wireless transceiver. By doing so, it is possible to connect to a personal computer, a PDA terminal, etc., and to connect to a network, which increases convenience.

  The micro analysis chip device according to the tenth embodiment can perform measurement and output from collection of a sample with a single device. In particular, according to the micro-analysis chip device of the tenth embodiment that incorporates a wireless transceiver that enables bidirectional exchange of information with the outside, for example, measurement results relating to human health measured at home can be immediately transmitted to the hospital via the network. Can be sent to a health care center or the like, thereby making it possible to receive advice on prompt and accurate diagnosis and treatment. That is, according to the tenth embodiment, it is possible to provide a small and highly convenient micro-analysis chip device that can be used anytime, anywhere, by anyone.

(Example)
Next, the present invention will be described with reference to examples, but the scope of the present invention is not limited to the examples.

  The liquid feeding structure has the same configuration as that of the first embodiment, and is configured by overlapping two substrates (main substrate 111 and lid substrate 110).

  A resin molding method using a mold was used to form the groove for the flow path 114 in the main substrate. The mold was manufactured by forming a resist pattern on a silicon substrate by a photolithography method and then performing an etching by a dry etching process method. The prepared mold form was placed, and silicon rubber (polydimethylsiloxane, Zilpot 184 manufactured by Toray Dow Corning Co., Ltd.) was poured until the thickness became 2 mm, and heated at 100 ° C. for 15 minutes to be cured. After curing, the mold and the cured silicon rubber were separated, and the silicon rubber was shaped into a length of 20 mm, a width of 10 mm, and a thickness of 2 mm to produce an upper substrate. The channel width was 50 μm and the channel height was 50 μm.

  The lid substrate was prepared by cutting a quartz substrate having a thickness of 600 μm into a length of 25 mm and a width of 15 mm with a dicing saw. The dimensions of the reference electrode 131 were designed to be 800 μm × 300 μm, the working electrode 132 was designed to be 1000 μm × 1000 μm, the dimension of the external connection terminal electrode 136 was 1000 mm × 1000 mm, and the line width of the extraction electrode 133 was designed to be 200 μm. The reference electrode 131 and the working electrode 132 were formed by patterning a resist by a photolithography method, forming a titanium layer (or chromium layer) of 50 nm and a gold layer of 100 nm by a sputtering method, and forming them on the resist and the resist by a lift-off method. The titanium layer and the gold layer were removed, and an electrode patterned in a desired shape was formed. Thereafter, a downstream region (region having a flow direction of 100 μm from the downstream end) of the surface of the working electrode 132 was covered with tetrafluoroethylene to form a hydrophobic film.

  The main substrate and the lid substrate were bonded together to produce a liquid feeding structure according to the example.

(Comparative example)
A liquid delivery structure was produced in the same manner as in the above example except that a tetrafluoroethylene hydrophobic membrane was formed on the entire surface of the working electrode.

  A test was conducted to flow the liquid through the liquid feeding structures according to the examples and comparative examples. In the example, when a fluorescent dye (fluorescein isocyanate: FITC) solution was dropped into the injection hole, the solution entered the liquid feeding structure by capillary action. Thereafter, the upstream end of the working electrode of the electrowetting valve was wetted, and the liquid flow was stopped when the liquid reached the hydrophobic film forming portion. When a voltage was applied to the working electrode and the reference electrode, the liquid passed over the working electrode, and the liquid could flow until there was no solution in the flow path.

  On the other hand, in the comparative example, the liquid flow stopped immediately before reaching the upstream end of the working electrode, and the liquid flow did not resume when voltage was applied.

  From the above, it can be seen that the liquid flow can be reliably controlled in the liquid feeding structure of the example.

  As described above, according to the present invention, the reference electrode and the working electrode are arranged in the flow path, and the liquid electrode can be reliably contacted with the upstream end of the working electrode even when no voltage is applied. The flow of the liquid in the flow path can be controlled with a simple technique. Such a flow channel structure can be applied as a microanalysis chip or the like used for antigen analysis and has great industrial significance.

FIG. 1 is a plan view of a liquid feeding structure according to the first embodiment. FIG. 2 is a cross-sectional view of FIG. FIG. 3 is an enlarged view of the vicinity of the working electrode of the liquid feeding structure according to the first embodiment. FIG. 4 is a conceptual diagram illustrating a liquid flow of the liquid feeding structure according to the first embodiment. FIG. 5 is a plan view of the liquid feeding structure according to the second embodiment. FIG. 6 is an enlarged view of the vicinity of the working electrode of the liquid feeding structure according to the second embodiment. FIG. 7 is an enlarged view of the vicinity of the working electrode of the liquid feeding structure according to the first modification of the second embodiment. FIG. 8 is an enlarged view of the vicinity of the working electrode of the liquid feeding structure according to the second modification of the second embodiment. FIG. 9 is a cross-sectional view illustrating a liquid feeding structure according to Modification 3 of Embodiment 2. FIG. 10 is a cross-sectional view illustrating a liquid feeding structure according to Modification 4 of Embodiment 2. FIG. 11 is a cross-sectional view illustrating a liquid feeding structure according to Modification 5 of Embodiment 2. FIG. 12 is an enlarged view of the vicinity of the working electrode of the liquid feeding structure according to the third embodiment. FIG. 13 is a plan view showing a liquid delivery structure according to the fourth embodiment. FIG. 14 is a plan view showing a liquid feeding structure according to the fifth embodiment. FIG. 15 is a plan view showing a liquid feeding structure according to the sixth embodiment. FIG. 16 is a plan view showing a liquid feeding structure according to the seventh embodiment. FIG. 17 is a diagram of the micro analysis chip according to the eighth embodiment. FIG. 18 is a diagram illustrating a two-layer configuration of the microanalysis chip according to the ninth embodiment. FIG. 19 is a diagram illustrating the microanalyzer according to the tenth embodiment. FIG. 20 is a diagram for explaining a stacked structure of the microanalyzer according to the eleventh embodiment. FIG. 21 is a diagram illustrating the contact angle. FIG. 22 is a cross-sectional view showing the flow channel structure. FIG. 23 is an equation for calculating the pressure. FIG. 24 is a plan view of a liquid feeding structure according to a conventional technique.

Explanation of symbols

110 Lid substrate 111 Main substrate 112 Injection hole 113 Discharge hole 114 Channel 131 Reference electrode 132 Working electrode 133 Extraction electrode 134 Hydrophilic region 135 Hydrophobic region 136 External connection terminal electrode 137 Counter electrode 149 Hydrophobic structure

Claims (22)

In the channel structure with an electrowetting valve in which an electrowetting valve that controls the flow of the liquid in the channel is arranged,
The electrowetting valve has a working electrode formed in a specific area in the flow path, and a reference electrode formed upstream of the specific area where the working electrode is formed,
In a state where no voltage is applied to both electrodes, at least a part of the surface of the working electrode is hydrophobic, and at least the vicinity of the upstream end of the surface of the working electrode is hydrophilic.
A flow path structure with an electrowetting valve characterized by the above. In the channel structure with an electrowetting valve according to claim 1, the channel is a structure in which a hydrophobic region and a hydrophilic region always exist in a cross-sectional view orthogonal to the flow direction.
A flow path structure with an electrowetting valve characterized by the above. In the flow path structure with an electrowetting valve according to claim 2,
The channel structure with the electrowetting valve includes at least a main substrate on which the channel groove is formed,
A lid substrate on which the reference electrode and the working electrode are formed;
The main substrate and the lid substrate are overlaid,
A flow path structure with an electrowetting valve characterized by the above. In the flow path structure with an electrowetting valve according to claim 3,
The main substrate is made of a hydrophobic material,
The lid substrate is made of a hydrophilic material,
A flow path structure with an electrowetting valve characterized by the above. In the flow path structure with an electrowetting valve according to claim 4,
The main substrate is made of polydimethylsiloxane,
The lid substrate is made of glass;
A flow path structure with an electrowetting valve characterized by the above. In the channel structure with an electrowetting valve according to any one of claims 1 to 5,
The constituent material of the working electrode is hydrophobic,
The surface near the upstream end of the working electrode has been subjected to a hydrophilic treatment,
A flow path structure with an electrowetting valve characterized by the above. In the flow path structure with an electrowetting valve according to claim 6,
The flow channel structure with an electrowetting valve, wherein the hydrophilization treatment is at least one selected from the group consisting of treatment with a hydrophilic treatment agent, plasma treatment, UV treatment, and control of surface roughness. In the channel structure with an electrowetting valve according to any one of claims 1 to 5,
The constituent material of the working electrode is hydrophilic,
The working electrode surface excluding the surface near the upstream end is hydrophobized,
A flow path structure with an electrowetting valve characterized by the above. The flow path structure with an electrowetting valve according to claim 8,
The flow channel structure with an electrowetting valve, wherein the hydrophobizing treatment is at least one selected from the group consisting of treatment with a hydrophobic treatment agent, formation of a hydrophobic film, and control of surface roughness. In the channel structure with an electrowetting valve in which an electrowetting valve that controls the flow of the liquid in the channel is arranged,
The electrowetting valve has a working electrode formed in a specific area in the flow path, and a reference electrode formed upstream of the specific area where the working electrode is formed,
In a state where no voltage is applied to both electrodes, the working electrode is hydrophobic,
The pressure due to the surface tension generated in the liquid is positive in the cross section of the flow path including the upstream end of the working electrode, and the pressure due to the surface tension generated in the liquid is 0 or 0 in the flow path in the region where the working electrode is formed. There is a negative part,
A flow path structure with an electrowetting valve characterized by the above. The flow path structure with an electrowetting valve according to claim 10,
The channel structure with the electrowetting valve includes at least a main substrate on which the channel groove is formed,
A lid substrate on which the reference electrode and the working electrode are formed;
The main substrate and the lid substrate are overlaid,
A flow path structure with an electrowetting valve characterized by the above. In the flow path structure with an electrowetting valve according to claim 11,
The main substrate is made of a hydrophobic material,
The lid substrate is made of a hydrophilic material,
A flow path structure with an electrowetting valve characterized by the above. The flow path structure with an electrowetting valve according to claim 12,
The main substrate is made of polydimethylsiloxane,
The lid substrate is made of glass;
A flow path structure with an electrowetting valve characterized by the above. In the channel structure with an electrowetting valve according to claim 12 or 13,
The groove width at the upstream end of the working electrode is larger than the groove width at the portion where the pressure due to the surface tension is 0 or negative,
A flow path structure with an electrowetting valve characterized by the above. The channel structure with an electrowetting valve according to any one of claims 12 to 14,
The groove height at the upstream end of the working electrode is smaller than the groove height at the portion where the pressure due to the surface tension is 0 or negative,
A flow path structure with an electrowetting valve characterized by the above. In the channel structure with an electrowetting valve in which an electrowetting valve that controls the flow of the liquid in the channel is arranged,
The electrowetting valve has a working electrode formed in a specific area in the flow path, and a reference electrode formed upstream of the specific area where the working electrode is formed,
In a state where no voltage is applied to both electrodes, at least the vicinity of the upstream end of the working electrode is hydrophilic,
A hydrophobic structure that increases the liquid contact surface of the flow path is provided in a region other than the upstream end of the working electrode.
A flow path structure with an electrowetting valve characterized by the above. The flow path structure with an electrowetting valve according to claim 16,
The hydrophobic structure is at least one of a pillar, a hole, and a groove;
A flow path structure with an electrowetting valve characterized by the above. The channel structure with an electrowetting valve according to claim 16 or 17,
The channel structure with the electrowetting valve includes at least a main substrate on which the channel groove is formed,
A lid substrate on which the reference electrode and the working electrode are formed;
The main substrate and the lid substrate are overlaid,
A flow path structure with an electrowetting valve characterized by the above. The channel structure with an electrowetting valve according to claim 18,
The main substrate is made of a hydrophobic material,
The lid substrate is made of a hydrophilic material,
A flow path structure with an electrowetting valve characterized by the above. The channel structure with an electrowetting valve according to claim 19,
The main substrate is made of polydimethylsiloxane,
The lid substrate is made of glass;
A flow path structure with an electrowetting valve characterized by the above.   An analysis chip comprising the flow channel structure with an electrowetting valve according to any one of claims 1 to 20 as an essential element.   An analysis apparatus comprising the analysis chip according to claim 21 as an essential element.