WO2009107608A1 - Liquid supply structure and micro-analysis chip using the same - Google Patents

Liquid supply structure and micro-analysis chip using the same Download PDF

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Publication number
WO2009107608A1
WO2009107608A1 PCT/JP2009/053283 JP2009053283W WO2009107608A1 WO 2009107608 A1 WO2009107608 A1 WO 2009107608A1 JP 2009053283 W JP2009053283 W JP 2009053283W WO 2009107608 A1 WO2009107608 A1 WO 2009107608A1
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WO
WIPO (PCT)
Prior art keywords
liquid
flow path
liquid reservoir
feeding structure
channel
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Application number
PCT/JP2009/053283
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French (fr)
Japanese (ja)
Inventor
俊明 北川
理伸 三枝
スンジン チョ
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シャープ株式会社
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Publication of WO2009107608A1 publication Critical patent/WO2009107608A1/en

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N2035/1027—General features of the devices
    • G01N2035/1034—Transferring microquantities of liquid
    • G01N2035/1039—Micropipettes, e.g. microcapillary tubes
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N2035/1027—General features of the devices
    • G01N2035/1048—General features of the devices using the transfer device for another function
    • G01N2035/1058—General features of the devices using the transfer device for another function for mixing
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N2035/1027—General features of the devices
    • G01N2035/1048—General features of the devices using the transfer device for another function
    • G01N2035/1062—General features of the devices using the transfer device for another function for testing the liquid while it is in the transfer device

Definitions

  • the present invention relates to a liquid feeding structure of a microanalysis chip used for trace chemical analysis of biological materials and substances in the natural environment, and more specifically, relates to a liquid feeding structure using a capillary force as a driving force. Is.
  • Immunoassay is known as an important analysis / measurement method in the medical field, biochemical field, measurement field such as allergen, and the like.
  • the conventional immunoassay has a problem that the operation is complicated and the analysis takes more than a day.
  • 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.
  • FIG. 18 shows an example of a micro analysis chip using such capillary force.
  • a method of discharging the solution filled in the flow path for example, as shown in Patent Document 2, a method of discharging by installing an absorber that absorbs the solution at the discharge port has been proposed.
  • the liquid 300 is injected into the injection port 413 of the micro analysis chip shown in FIG. 20 (a) (FIG. 20 (b)).
  • the liquid flows through the channels 414, 415, and 416, is absorbed by the absorber provided at the end of the channel 416, and is discharged out of the chip (FIGS. 20C and 20D).
  • FIGS. 20 (e) and 21 (b) when a gas-liquid interface is formed in the channel 415 having a width smaller than that of the main channel 416, the channel having a narrow width from the main channel 416.
  • P is typically expressed by the following equation assuming a flow path having a radius r.
  • the pressure P generated by the surface tension works, and the strong capillary force due to the absorber acts in the direction of the absorber, and each attracts liquid in the opposite direction. Therefore, at the interface between the main channel 416 and the absorber 411 where gas easily enters. The liquid is broken. As a result, the liquid flows backward and becomes stable in a state where a gap is generated between the liquid 300 and the absorber 411. For this reason, even if the absorber 411 having a strong capillary force is provided in the discharge portion, the absorber 411 cannot absorb the liquid 300, and the liquid in the chip cannot be completely discharged (FIG. 21C). reference).
  • the present invention has been made to solve the above-described problem, and an object of the present invention is to provide a liquid feeding structure capable of smoothly discharging a liquid even when a narrow flow path exists. .
  • a first aspect of the present invention for solving the above-described problems is a first flow path connected to an open hole opened to the outside, a liquid reservoir portion continuous with the first flow path, and a continuous portion of the liquid reservoir portion. And at least an absorbent body that is in direct contact with the terminal end of the second flow path, and the pressure due to the surface tension generated in the liquid in the first flow path is P1, and the liquid in the second flow path P3 ⁇ P1 ⁇ P2 is established, where P2 is the pressure due to the surface tension generated in the liquid reservoir and P3 is the pressure due to the surface tension generated in the liquid in the liquid reservoir.
  • the minimum distance between the opposing wall surfaces of the first channel is P2.
  • the minimum distance between the opposing wall surfaces of the second flow path is D2
  • the minimum distance between the opposing wall surfaces of the liquid reservoir is D3, D2 ⁇ D1 ⁇ D3 is adopted. Is simple.
  • a second aspect of the present invention for solving the above-described problems is a first flow path connected to an open hole that is open to the outside, a liquid reservoir portion that is continuous with the first flow path, and a continuous portion of the liquid reservoir portion. At least a second flow path and an absorber that is in direct contact with the end of the second flow path, wherein the first flow path and the second flow path have a hydrophilic contact surface with the liquid,
  • D1 the minimum distance between the opposing wall surfaces of the first channel
  • D2 the minimum distance between the opposing wall surfaces of the second channel
  • the minimum distance between the opposing wall surfaces of the liquid reservoir is D3, D2 ⁇ D1 ⁇ D3 is satisfied.
  • the minimum distance D2 between the opposing wall surfaces of the second channel is equal to or less than the minimum distance D1 between the opposing wall surfaces of the first channel, as shown in FIG.
  • a strong capillary force 501 acts in the reverse flow direction and the liquid flows backward, a gas-liquid interface is generated in the second flow path, and the capillary force 502 acts in the forward flow direction equal to or greater than the reverse flow direction. For this reason, the contact between the liquid and the absorber is maintained, and all the liquid can be discharged to the outside of the structure without remaining in the liquid feeding structure.
  • the first flow path may have two or more.
  • the apparatus further comprises a second liquid reservoir provided on the upstream side of the first flow path, and a third flow path provided on the upstream side of the second liquid reservoir.
  • a second liquid reservoir provided on the upstream side of the first flow path
  • a third flow path provided on the upstream side of the second liquid reservoir.
  • the apparatus further comprises a second liquid reservoir provided on the upstream side of the first flow path, and a third flow path provided on the upstream side of the second liquid reservoir.
  • a second liquid reservoir provided on the upstream side of the first flow path
  • a third flow path provided on the upstream side of the second liquid reservoir.
  • a second liquid reservoir is provided upstream of the liquid reservoir, and the second liquid reservoir is used. It is preferable to carry out the reaction.
  • a liquid feeding structure capable of completely discharging the liquid in the structure can be realized.
  • FIG. 1 is a plan view of a liquid feeding structure according to an embodiment.
  • FIG. 2 is a cross-sectional view of the liquid feeding structure according to the embodiment.
  • FIG. 3 is a conceptual diagram illustrating the flow of the liquid in the liquid feeding structure according to the embodiment.
  • FIG. 4 is a conceptual diagram illustrating a liquid flow in the first flow path and the second flow path of the liquid feeding structure according to the embodiment.
  • FIG. 5 is a plan view of the liquid feeding structure according to the first embodiment.
  • FIG. 6 is a conceptual diagram showing the structure of the electrode.
  • FIG. 7 is a plan view of the liquid feeding structure according to the second embodiment.
  • FIG. 8 is a conceptual diagram showing the operation of the electrowetting valve.
  • FIG. 1 is a plan view of a liquid feeding structure according to an embodiment.
  • FIG. 2 is a cross-sectional view of the liquid feeding structure according to the embodiment.
  • FIG. 3 is a conceptual diagram illustrating the flow of the liquid in the liquid feeding structure according to the embodiment
  • FIG. 9 is a plan view illustrating a modification of the liquid feeding structure according to the first embodiment.
  • FIG. 10 is a plan view showing a liquid feeding structure according to the second embodiment.
  • FIG. 11 is a plan view of a liquid feeding structure according to Comparative Example 1.
  • FIG. 12 is a plan view of a liquid feeding structure according to Comparative Example 2.
  • FIG. 13 is a diagram illustrating the microanalysis chip according to the third embodiment.
  • FIG. 14 is a diagram illustrating the micro-analysis chip according to the fourth embodiment.
  • FIG. 15 is a diagram illustrating the micro-analysis chip according to the fifth embodiment.
  • FIG. 16 is a diagram illustrating the microanalyzer according to the sixth embodiment.
  • FIG. 17 is a diagram illustrating the microanalyzer according to the seventh embodiment.
  • FIG. 18 is a plan view of a liquid feeding structure according to a conventional technique.
  • FIG. 19 is a plan view of a liquid feeding structure according to a conventional technique.
  • FIG. 20 is a conceptual diagram showing the flow of the liquid in the liquid feeding structure shown in FIG.
  • FIG. 21 is a conceptual diagram illustrating a liquid flow in the first flow path and the second flow path of the liquid feeding structure according to the conventional technology.
  • the liquid feeding structure 110 includes a first flow path 115 having an open hole 113 for introducing liquid into the chip, and a liquid reservoir portion continuous with the first flow path. 116, a second flow path 117 that is continuous with the liquid reservoir, and an absorber 111 that is in direct contact with the end of the second flow path.
  • the flow path 114 is not an essential component of the present invention.
  • the second channel 117 is set so that the size of the channel is the same from upstream to downstream.
  • the pressure due to the surface tension generated in the liquid in the first flow path is P1
  • the pressure due to the surface tension generated in the liquid in the second flow path is P2
  • the pressure due to the surface tension generated in the liquid in the liquid reservoir is P3.
  • the pressure due to the surface tension generated in the liquid in the first flow path is P1
  • the pressure due to the surface tension generated in the liquid in the second flow path is P2
  • the pressure due to the surface tension generated in the liquid in the liquid reservoir portion is set so that P3 ⁇ P1 ⁇ P2 is established
  • the minimum distance between the opposing wall surfaces of the first flow path is D1
  • the minimum distance between the opposing wall surfaces of the second flow path is It is preferable to adopt a configuration in which D2 ⁇ D1 ⁇ D3 is established, where D2 is the minimum distance between the opposing wall surfaces of the liquid reservoir. In this embodiment, D2 ⁇ D1.
  • FIG. 2 shows a cross-sectional view of the liquid feeding structure according to the present embodiment.
  • the upper substrate 201 on which the flow path 114, the liquid reservoir 116, the first flow path 115, and the second flow path 117 are formed, the flow path 114, the liquid reservoir 116, and the first flow path. 115, a lower substrate 202 that seals from below the second flow path 117 and on which the absorber 111 is placed.
  • the thickness of the upper substrate 201 is about 0.1 mm to 10 mm, and the thickness of the lower substrate 202 is about 0.01 mm to 10 mm.
  • the open hole 113 may be a through hole having a diameter of 10 ⁇ m or more.
  • the flow path 116 of the liquid feeding structure is used as a detection unit that performs optical detection, as one or both materials used for the substrate 201 and the substrate 202, for example, as proposed in Patent Document 3
  • 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.
  • electrochemical detection there are no such restrictions on materials.
  • the substrate 201 and the substrate 202 be a material capable of forming an electrode.
  • a material capable of forming an electrode glass, quartz, silicon and the like are preferable from the viewpoint of productivity and reproducibility. Note that with the current technology, it is difficult to form an electrode on an uneven portion, so it is preferable to form the electrode on a flat substrate 202.
  • the surface of the substrate 201 or 202 that is in contact with the liquid of the material is preferably hydrophilic so that the surface of the substrate material that is in contact with the liquid is easy to flow.
  • hydrophilic oxygen plasma treatment, UV treatment, or the like is used.
  • the hydrophilicity can also be enhanced by applying a surfactant or a reagent having a hydrophilic functional group to the surface.
  • a method of directly processing the substrate 201 for example, a method of machining, a method of laser processing, a method of etching with chemicals or gas, injection molding using a mold, press molding
  • methods such as casting for example, a method using a mold and a method using etching are preferable because of high reproducibility of the shape dimensions.
  • 3 and 4 show the flow of the liquid in the liquid feeding structure according to the present embodiment.
  • 3 (a) to 3 (e) are the same as in the prior art.
  • FIGS. 3E and 4B when the liquid flows back from the liquid reservoir 116 to the first flow path 115 by the capillary force, a gas-liquid interface is generated in the second flow path 117. . Since the channel width L2 of the second channel 117 is less than the channel width L1 of the first channel 115, the capillary force 502 acting on the second channel 117 has a capillary force 501 acting on the first channel 115. Counteract. For this reason, as shown in FIG.3 (f) and FIG.4 (c), a liquid will be discharged
  • the width and height of the flow channel 114, the liquid reservoir 116, the first flow channel 115, and the second flow channel 117 of the liquid feeding structure shown in FIG. 1 are not particularly limited, but the solution is affected by the wetness of the solution and the capillary force. Is set to a dimension that can penetrate.
  • the height is preferably set to about 1 ⁇ m to 5 mm.
  • the width is preferably set to about 1 ⁇ m to 5 mm.
  • an antibody or the like is immobilized in a liquid reservoir, an antigen-containing reaction is performed by flowing a liquid containing an antigen, and an antigen-antibody reaction is performed by flowing a liquid containing a labeled antibody to which a fluorescent dye is attached.
  • an antigen-containing reaction is performed by flowing a liquid containing an antigen
  • an antigen-antibody reaction is performed by flowing a liquid containing a labeled antibody to which a fluorescent dye is attached.
  • It can be used as a micro-analysis chip in which the liquid reservoir is irradiated with excitation light and the amount of antigen is measured by the amount of fluorescence.
  • a valve 140 may be provided in the first flow path.
  • the liquid delivery structure 110 includes an open hole 113, a third flow path 118, a second liquid reservoir 114, a first flow path 115, It has a liquid reservoir 116 that is continuous with one flow path, a second flow path 117 that is continuous with the liquid reservoir, and an absorber 111 that is in direct contact with the end of the second flow path.
  • the flow path 119 is not an essential component of the present invention.
  • the second flow path 117 has a pressure due to the surface tension generated in the liquid in the first flow path as P1, and a pressure due to the surface tension generated in the liquid in the second flow path as P2, and in the liquid reservoir When the pressure due to the surface tension generated in the liquid is P3, P3 ⁇ P1 ⁇ P2 is established. And a third flow path provided on the upstream side of the second liquid reservoir, wherein the pressure due to the surface tension generated in the liquid in the third flow path is P4, and the second liquid reservoir When the pressure due to the surface tension generated in the liquid in the section is P5, P5 ⁇ P4 ⁇ P2 is established.
  • the capillary force acting on the second flow path 117 is equal to or greater than the capillary force acting on the first flow path 115, and the capillary force acting on the second flow path 117 acts on the third flow path 118. Equal to or greater than the capillary force For this reason, similarly to the first embodiment, the liquid feeding is not stopped and the liquid can be smoothly poured.
  • an antibody or the like is fixed to the second liquid reservoir 114, an electrode is provided in the liquid reservoir 116, and the antigen-antibody reaction and enzyme labeling are provided in the second liquid reservoir 114. It can be used as a micro-analysis chip in which the reaction between the antibody and the antigen-antibody complex, the enzyme substrate reaction is performed, and the amount of the electrode active substance generated by the enzyme substrate reaction is detected by the electrode provided in the liquid reservoir 116.
  • FIG. 5 shows a liquid feeding structure according to this example.
  • the liquid feeding structure 110 is a flow connecting two open holes 113a and 113b, a liquid reservoir 116, two first flow paths provided with valves 141 and 142, and the open holes and the first flow path. It has the path
  • the liquid feeding structure is composed of two substrates as in the above embodiment, and is used for the production of the flow path 114, the liquid reservoir 116, the first flow path 115, and the second flow path 117 in the upper substrate.
  • a resist pattern was formed on a silicon substrate by a photolithography method, and then etching was performed by a dry etching process method.
  • the prepared mold form was placed, and silicon rubber (polydimethylsiloxane) (Zill pot 184 manufactured by Toray Dow Corning Co., Ltd.) was poured into the thickness until it became 2 mm, and heated at 100 ° C. for 15 minutes to be cured.
  • the width 103 of the channels 114a and 114b was set to 300 ⁇ m
  • the width of the liquid reservoir 116 was set to 600 ⁇ m
  • the width 100 of the first channels 115a and 115b was set to 50 ⁇ m
  • the width of the second channel 117 was set to 50 ⁇ m.
  • the flow path height was all 50 ⁇ m.
  • the lower substrate was produced by cutting a quartz substrate having a thickness of 600 ⁇ m into a length of 18 mm and a width of 16 mm with a dicing saw.
  • Two inlet holes 113 were formed in the upper substrate by punching to complete the substrate 201.
  • electrodes for the valves 141 and 142 and the detector 151 were prepared in advance.
  • the valves 141 and 142 were prepared by patterning a resist by a photolithography method, forming a titanium layer of 50 nm and a gold layer of 100 nm by a sputtering method, and then forming an electrode patterned by a lift-off method.
  • the valve may be other than the above as long as it can stop or start the inflow of liquid, such as a diaphragm type valve.
  • the detector 151 is manufactured by patterning a resist by a photolithography method, forming a titanium layer 50 nm and a gold layer 100 nm by a sputtering method, and then patterning the electrodes 152, 154, and 155 as shown in FIG. 6 by a lift-off method. 156 was formed.
  • the electrode 153 which is a part of the detection unit 151, after patterning a resist by a photolithography method, a silver layer of 1 ⁇ m is formed by a sputtering method, and a patterned electrode 153 is formed by a lift-off method.
  • the Ag surface was subjected to chlorination treatment to produce an Ag / AgCl layer electrode 153.
  • chlorination treatment a voltage of +100 mV for 50 seconds was applied to the electrode 153 in 0.1 M hydrochloric acid.
  • the upper substrate and the lower substrate are subjected to oxygen plasma treatment under the conditions of 100 W, oxygen flow rate of 30 sccm, and 60 seconds to increase the hydrophilicity of the substrate surface, and then the upper substrate and the lower substrate are bonded to each other by a self-adsorption action.
  • the absorbent body 111 made of cotton was placed on the downstream end of the liquid feeding structure according to the first example.
  • Comparative Example 1 As shown in FIG. 11, a liquid feeding structure 410 according to Comparative Example 1 was produced in the same manner as in Example 1 except that the second flow path was not formed.
  • the test which flows a liquid through the liquid feeding structure concerning Example 1 and Comparative Example 1 was conducted.
  • the liquid delivery structure according to Example 1 when a fluorescent dye (FITC) solution is dropped into the open hole, the solution 300 is filled in the liquid delivery structure by capillary action, and is absorbed from when the solution 300 reaches the absorber 111. The body 111 was able to absorb the solution in the flow channel and absorb it until there was no solution in the flow channel.
  • the absorber 411 started to absorb the solution in the channel from the time when the solution 300 reached the absorber 411, but a gas-liquid interface occurred in the first channel. At that time, the solution returned to the open hole side, and a gap was formed between the absorber 411 and the solution 300. Further liquid feeding stopped, and the solution 300 remained in the flow path.
  • FITC fluorescent dye
  • FIG. 13 is a top view of the micro analysis chip.
  • the liquid feeding structure according to the present embodiment includes an opening hole 2001 for the first liquid, an opening hole 2002 for the second liquid, third liquid reservoirs 2003 and 2004, a mixer 2007, 3 flow channel 2009, second liquid reservoir 2008, first flow channel 2011, first liquid reservoir 2010, second flow channel 2013, and the end of the second flow channel. And an absorber 111.
  • the first liquid When the first liquid is injected from the first liquid opening hole 2001, the first liquid is injected into the third liquid reservoir 2003. Similarly, when the second liquid is injected into the second liquid opening hole 2002, the second liquid is injected into the third liquid reservoir 2004.
  • a first valve 2005 and a second valve 2006 that can stop or start the flow of injected liquid into the mixer 2007 are connected to the first liquid reservoir and the second liquid reservoir, respectively.
  • the mixer 2007 has a configuration capable of sufficiently mixing the first liquid and the second liquid.
  • the second liquid reservoir 2008 is connected via the third flow path 2009.
  • the second liquid reservoir 2008 may have a configuration in which a substance that reacts with the substance to be detected contained in the solution is disposed.
  • the mixer and the reaction unit are connected via the third flow path 2009, but may be directly connected without passing through the third flow path 2009.
  • the first liquid reservoir 2010 is connected to the second liquid reservoir 2008 via the first flow path 2011.
  • the first liquid reservoir 2010 is provided with a detector 2012.
  • the detection unit has a configuration capable of directly or indirectly detecting the substance to be detected.
  • it when it is the structure which can detect a to-be-detected substance directly, it can be set as the structure which does not have the 1st liquid reservoir part 2010.
  • the absorber 2014 is connected to the first liquid reservoir 2010 via the second channel 2013.
  • the second channel 2013 has a capillary force equal to or greater than the capillary force of the first and third channels, and pulling the liquid to the absorber causes the first channel to be absorbed.
  • the liquid can be discharged without staying in the first and third flow paths.
  • an external connection terminal 2015 is provided. Input from the terminal to the power supply chip, input of an electrical control signal, output of a detection signal, and the like are performed.
  • the micro analysis chip itself does not need to be provided with a power supply, and therefore, a micro analysis chip with excellent cost performance can be realized.
  • injection part By injecting the first liquid and the second liquid from the first liquid opening hole 2001 and the second liquid opening hole 2002, respectively, the respective liquids are supplied to the third liquid reservoirs 2003 and 2004, respectively. Is injected.
  • the opening hole may be of such a size that capillary force does not work. In that case, the liquid can be sufficiently injected into the liquid reservoir even when the open hole is hydrophobic.
  • the opening hole may have a size that allows capillary force to work. In that case, by applying hydrophilicity to the open hole, the liquid can be injected into the liquid reservoir by capillary force.
  • the third liquid reservoirs 2003 and 2004 may have a space size that allows capillary force to work.
  • the height direction may be designed to be sufficiently small.
  • the open hole only needs to be open to the atmosphere.
  • the liquid can be injected by connecting a cartridge filled with liquid in advance in the open hole. Even in that case, it is preferable that the cartridge is open to the atmosphere at the connection ports of the open holes 2001 and 2002 or other portions so that the liquid can be sufficiently discharged when the liquid is injected.
  • the case where two open holes are provided will be described, but the number of open holes may be three or more as appropriate.
  • the sample containing the detection target in the first liquid open hole, the reagent in the second liquid open hole, the standard sample in the third liquid open hole, and the fourth liquid use
  • a cleaning liquid may be injected into the open hole.
  • the configuration is such that the cleaning liquid can be injected into the open hole, it can be used repeatedly, so that the cost performance is improved and the environmental load can be reduced.
  • valve The valve may be any valve that can stop or start the inflow of liquid, and may be a diaphragm valve finely formed by using the MEMS technology. When electrowetting valves are used, a working electrode and a reference electrode are required for each valve.
  • the electrowetting valve is a valve having a structure in which the flow of liquid is interrupted when no voltage is applied and the liquid is allowed to flow when a voltage is applied.
  • the principle of the electrowetting valve will be described with reference to FIG.
  • the liquid flows in the flow path 114 while being in contact with the electrowetting valve reference electrode 171.
  • the electrowetting valve working electrode 172 is covered with a hydrophobic film, and when no voltage is applied, the contact angle with the liquid increases to about 60 to 70 degrees.
  • the channel width and height are designed to be 50 ⁇ m, the liquid cannot pass through the first channel 115 due to the resistance of the liquid flowing through the first channel and the surface tension of the liquid.
  • the liquid when a voltage is applied, the liquid is negatively charged by the electrowetting valve reference electrode 171.
  • the liquid via the insulating film forms a virtual capacitor with the working electrode 172, and the liquid is attracted to the working electrode 172 to reduce the contact angle. For this reason, the liquid can pass through the first flow path 115 regardless of the resistance flowing through the flow path.
  • Each flow path of each valve has an optimal flow path space for each valve in order to appropriately stop or start inflow of liquid.
  • the mixer should just be comprised so that a 1st liquid and a 2nd liquid can fully be mixed.
  • a configuration in which mixing is performed by providing a micro-pillar structure in the vicinity of the inflow portion from the first valve and the second valve may be used.
  • There are various modes such as a T-shaped mixer, a Manz mixer, a mixer using a three-dimensional meandering channel, and any configuration may be used as long as it is configured to be sufficiently mixed.
  • the case where two liquids are mixed has been described.
  • three or more liquids may be appropriately mixed.
  • the second liquid reservoir 2008 functions as a reaction part that performs the reaction, and may be any structure as long as molecules that specifically recognize and react with the target substance contained in the sample solution are arranged.
  • the detection substance is an antigen
  • the antibody may be immobilized on the reaction part.
  • a sandwich method of enzyme immunoreaction is used. An antigen is reacted with an enzyme-labeled antibody (secondary antibody) to form a complex in which the antigen and the enzyme-labeled antibody are bound. The aforementioned complex is reacted with an antibody (primary antibody) immobilized in advance in the reaction part.
  • a substrate is introduced, reacted with an enzyme labeled with a secondary antibody, and an electrochemically active substance generated by the reaction is electrochemically detected on an electrode serving as a detection unit.
  • an electrochemically active substance generated by the reaction is electrochemically detected on an electrode serving as a detection unit.
  • a substance that can be detected by the detection part is generated according to the amount of the substance to be detected.
  • the 2nd flow path 2013 may use what kind of member and shape.
  • a hydrophilic material As long as the pressure by the surface tension which generate
  • hydrophilicity may be improved by performing oxygen plasma treatment.
  • a glass substrate is preferable because it has hydrophilicity.
  • the absorbent body may be any material that absorbs liquid, and examples thereof include polymer absorbent bodies, porous substances, hydrophilic meshes, sponge bodies, cotton, and filter paper.
  • the absorber is open to the atmosphere at the connection portion of the absorber and the second flow path or other portions so that the absorber can efficiently absorb.
  • the absorber may protrude partly in the second flow path. In that case, the absorber including the second flow path up to the protruding portion is partly absorbed, and the second flow path is reduced accordingly.
  • An external connection terminal 2015 is provided. Input from the terminal to the power supply chip, input of an electrical control signal, output of a detection signal, and the like are performed. If a gold electrode is used, it may be used in combination with other valves and detection electrodes, and the process may be simplified. Alternatively, a conductive material containing a material such as platinum, aluminum, or copper may be used.
  • the micro analysis chip itself does not need to be provided with a control circuit such as a power source or an IC, and therefore a chip with excellent cost performance can be provided.
  • the micro analysis chip includes an upper layer 2101 and a lower layer 2102.
  • the upper layer preferably has high transparency and processability and is preferably formed using PDMS.
  • the lower layer may be a silicon substrate as a material capable of forming electrodes for electrical control or the like.
  • One or both of the materials used for the upper layer 2101 and the lower layer 2102 are desirably transparent or translucent as proposed in Patent Document 3, for example. This is because, in the case of application to a chip system that detects the fluorescence of the subject by irradiating the subject flowing in the channel with excitation light by using the inside of the microchip channel as the detection unit, the fluorescence that has passed through the reaction unit This is because it is necessary to detect UV and UV.
  • the transparent or translucent material glass, quartz, thermosetting resin, thermoplastic resin, film and the like are preferable. Of these, silicon resins, acrylic resins, and styrene resins are preferable from the viewpoints of transparency and moldability.
  • one or both of the upper layer and the lower layer is a material capable of forming an electrode.
  • materials capable of forming electrodes substrate materials such as glass, quartz, and silicon are preferable from the viewpoint of productivity and reproducibility.
  • a first liquid opening hole 2001 and a second liquid opening hole 2002 are opened upward, and third liquid reservoirs 2003 and 2004, a first valve 2005 and a second liquid hole are opened in the lower part.
  • the flow path for providing the valve 2006, the mixer 2007, the second liquid reservoir 2008, the third flow path 2009, the first liquid reservoir 2010, the first flow path 2011, the second flow path 2013, etc. face downward. Opened and provided.
  • the absorber 2014 is arranged by providing a space opened on the lower side and filling the space. These bottom-opened portions are sealed at the bottom by the lower layer 2102 to form a space.
  • a first valve electrode 2105, a second valve electrode 2106, and a detection electrode 2112 are provided, and each is connected to an external connection terminal 2015.
  • the connection to the first valve electrode 2105 and the second valve electrode 2106 can be two terminals when an electrowetting valve is used and three terminals when a counter electrode is provided.
  • the detection electrode can have three terminals as described above.
  • the upper layer 2201, the middle layer 2202, and the lower layer 2203 are included.
  • the difference from the fourth embodiment is that the first liquid opening hole 2201 and the second liquid opening hole 2202 are divided into upper layers. Both the first liquid opening hole 2201 and the second liquid opening hole 2202 are formed as openings penetrating the 2201 layers.
  • the absorber 2214 is arranged by providing a space opened on the lower side and filling the space.
  • the middle layer can be formed in an open shape except for the second flow path 2213. If necessary, it can be formed in the same manner as the above-described structure opened on the lower side. In that case, the third liquid reservoirs 2203 and 2204 need to be opened on the upper side so as to be connected to the upper layer.
  • the second flow path 2213 is formed with an upper opening so as to connect to the upper layer.
  • the lower layer is the same as in the fourth embodiment.
  • FIG. 16 shows one embodiment of the microanalyzer.
  • the micro analyzer is a portable handy micro analyzer.
  • a chip connection port 2303 which is a connection port of the micro analysis chip 2302 described in the above embodiment is provided below the handy device 2301.
  • An external input / output terminal (not shown) that can be electrically connected to the external connection terminal of the micro analysis chip is provided in the back of the chip connection port 2303 in the handy device 2301, and the micro analysis chip 2302 is connected to the chip connection port 2303. Is inserted between the external input / output terminal in the handy device 2301 and the external connection terminal of the micro analysis chip 2302.
  • a display unit 2304 that can display the amount of a substance to be detected and an input unit 2305 that can input various data for starting and stopping measurement and specifying measurement parameters. Is provided.
  • 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 is built in the handy device.
  • valves such as reagents and samples (samples) that have been prepared in advance on the micro analysis chip and stopped by the valve
  • the inflow is sequentially started, and as a result, an electric signal corresponding to the amount of the substance to be detected detected by the detection unit is output from the external connection terminal of the micro analysis chip.
  • the handy device 2301 can be, for example, a portable electronic device such as a mobile phone or a PDA.
  • a mobile phone will be described as an example.
  • the mobile phone can be operated as a handy device by starting data processing analysis software for a micro analysis chip. That is, the mobile phone is virtually used as a handy device by dedicated software.
  • the external connection terminal of the micro analysis chip may be configured to be connectable to the external input terminal of the mobile phone.
  • the micro analysis chip By connecting the micro analysis chip to the mobile phone, inputting various data from the buttons on the mobile phone, and pressing the button set as the measurement start button, the micro analysis chip is prepared in advance and the flow is stopped by the valve Then, inflow of valves such as reagents and samples (samples) is started sequentially, and as a result, an electrical signal corresponding to the amount of the substance to be detected detected by the detection unit is output from the external connection terminal of the micro analysis chip.
  • the amount or type of the substance to be detected can be specified. Then, the measurement result is displayed on the display screen of the mobile phone.
  • a microanalyzer with excellent cost performance can be provided. Users can also take measurements wherever they need it. Many mobile users can enjoy the benefits when the mobile phone ownership rate rises and mobile phones become sufficiently widespread for the measurers (users). That is, the cost of the handheld device of the mobile phone holder is unnecessary. However, the cost of an electric circuit and data processing analysis software that can be operated on a mobile phone instead is required, but the measurer can download the data processing analysis software on the network, An electric circuit can be mounted in advance by increasing the functionality of the mobile phone. The user can use the mobile phone as a handy device at low cost. As described above, the mobile phone holder can easily prepare the handy device 2301, and after preparing the handy device, the sample (sample) can be analyzed only with the cost of the micro analysis chip 2302.
  • FIG. 17 shows an embodiment of a microanalyzer.
  • This microanalyzer is an independent microanalyzer capable of collecting a sample (sample) independently, analyzing detection data, and outputting.
  • the microanalyzer can independently constitute an independent microanalyzer capable of collecting a sample (sample) to analyzing and outputting detection data. That is, as shown in the figure, the 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 part is sequentially stacked or combined to form a microanalyzer.
  • the sample collection unit 2401 is provided with a needle penetrating a capillary tube, and blood or a sample can be collected by inserting or introducing a needle into a human body or a sample body.
  • a needle is preferable if it is a minimally invasive microprobe because pain is alleviated when a needle is inserted into a subject and a body fluid such as blood is extracted.
  • an absorbent body that collects noninvasive skin surface sweat, saliva in the oral cavity, tears, urine, and the like may be used.
  • the liquid flow path portion 2402 is formed with the flow path structure of the micro analysis chip described in the above embodiment.
  • the structure can be formed using the 2101 layer described in Embodiment 4 and the 2202 layer described in Embodiment 5.
  • the capillary tube of the sample collecting unit is connected to the second liquid reservoir 2414 of the liquid flow channel unit, and is configured such that the sample flows into the liquid reservoir due to the capillary phenomenon of the capillary provided on the needle.
  • the liquid channel part can be made using polydimethylsiloxane (PDMS), polymethyl methacrylate (PMMA), polycarbonate, polytetrafluoroethylene, vinyl chloride or the like. It is also possible to form a flow path structure having a plurality of detection sections in the liquid flow path section. It is also possible to form a plurality of channel structures.
  • PDMS polydimethylsiloxane
  • PMMA polymethyl methacrylate
  • polycarbonate polytetrafluoroethylene
  • vinyl chloride vinyl chloride
  • the drive analysis processing unit 2403 can be configured in the same manner as the micro analysis chip described in the above embodiment, and includes a CPU, a memory, a battery (not shown), and the like, and detects the liquid channel unit 2042. Are connected to an I / O logic circuit, etc., which will be described later, and valve control corresponding to various measurements, processing of measurement data, control of an input / output unit, and the like are possible. Further, the drive analysis processing unit 2403 can be configured using the 2102 layer described in the fourth embodiment and the 2203 layer described in the fifth embodiment. However, in this embodiment, since it can be used independently, a CPU and a data storage unit are provided, and valve control corresponding to various measurements, measurement data processing, and the like are possible.
  • the flow of a valve such as a reagent or sample (sample) that has stopped flowing in at the start of measurement is sequentially started, and as a result, an electric signal corresponding to the amount of the substance to be detected detected by the detection unit is sent to the CPU.
  • the amount or type of the substance to be detected can be specified.
  • data can be output to an I / O logic circuit connected to the CPU described below, and the measurement result can be displayed at the input / output unit.
  • the input / output logic processing unit 2404 has an I / O logic circuit connected to the CPU.
  • An electrical connection line connected to the I / O logic circuit is connected to each button or display unit of the input / output layer and can cooperate with the CPU to appropriately process the I / O data. That is, upon receiving various data and measurement start signals input in the display layer, the electrical signal output according to the non-detected substance of the sample detected in the liquid channel layer is processed, and the amount and type of the detected substance And the information is displayed on the display unit of the input / output layer.
  • the input / output layer 2405 is provided with various data input buttons and a display unit.
  • a liquid crystal display module or an organic EL display module can be used for the display unit. These can perform a display operation by driving the drive driver circuit in cooperation with the I / O logic circuit and the CPU.
  • the display can also be displayed with a time-dependent change using a numerical value display format or a graph. It can also be displayed in a format such as positive or negative.
  • the input / output layer can be provided with a terminal for processing input / output with the outside or a wireless transceiver.
  • a personal computer a PDA terminal, etc.
  • a network so that bidirectional information exchange is also possible.
  • health information obtained from the measurement results of the measurer can be networked with hospitals and health management centers, etc., so that information can be provided in both directions.
  • the measurer can enjoy advice, diagnosis, and treatment directly related to advanced medical care, and the medical provider can make appropriate diagnosis and treatment from abundant health information.
  • the liquid in the chip can be transferred by a simple method using an absorber and a channel having a small cross-sectional area without requiring external power.
  • a liquid-feeding structure can be applied as a micro-analysis chip or the like used for antigen analysis and has great industrial significance.

Abstract

This object aims to provide a liquid supply structure including flow passages having short widths and heights and capable of supplying a liquid without requiring an external power. The liquid supply structure comprises at least a first flow passage connected to an open hole opened to the outside, a liquid reservoir part provided continuously with the first flow passage, a second flow passage formed continuously with the liquid reserving part, and an absorber directly contacting with the terminal end of the second flow passage. The liquid supply structure is characterized in that P3<P1≤P2 is satisfied where a pressure caused by a surface tension generating in the liquid in the first flow passage is P1, a pressure caused by a surface tension generating in the liquid in the second flow passage is P2, and a pressure caused by a surface tension generating in the liquid reserved in the liquid reservoir part is P3.

Description

送液構造体及びこれを用いたマイクロ分析チップLiquid feeding structure and microanalysis chip using the same
　本発明は、生体物質や、自然環境における物質等の微量化学分析に用いられるマイクロ分析チップの送液構造に関するものであり、より具体的には、毛細管力を駆動力とした送液構造体に関するものである。 The present invention relates to a liquid feeding structure of a microanalysis chip used for trace chemical analysis of biological materials and substances in the natural environment, and more specifically, relates to a liquid feeding structure using a capillary force as a driving force. Is.
　免疫分析法は、医療分野、生化学分野、アレルゲンなどの測定分野等において、重要な分析・計測方法として知られている。しかし、従来の免疫分析法には、操作が煩雑である上に、分析に一日以上の時間を要するといった問題があった。 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 the analysis takes more than a day.
　このような中、基板にマイクロオーダーの流路を形成し、このマイクロ流路に抗体等を固定化することにより、分析時間の短縮化や分析操作の簡略化を図るマイクロ分析チップが提案されている。 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.
　マイクロ分析チップを用いて分析を行う場合、入口からマイクロ分析チップ内に溶液を導入し、該溶液をマイクロ分析チップ内で反応させ、出口からマイクロ分析チップ外に溶液を排出する必要がある。従来、マイクロ分析チップにおける溶液の移送には、ポンプなどの外部の動力源を用いていたが、ポンプはマイクロ分析チップに比べて大型であるため、装置全体の小型化が難しいという問題があった。比較的小型のマイクロポンプをマイクロ分析チップの内側や外側に配置する方法も提案されているが、複雑な微細加工技術を必要とするマイクロポンプ等が必要となるため、実用性に欠ける。 When performing analysis using 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. Conventionally, an external power source 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, there is a problem that it is difficult to downsize the entire apparatus. . A method of arranging a relatively small micropump inside or outside the microanalysis chip has also been proposed, but lacks practicality because a micropump or the like that requires a complicated microfabrication technique is required.
　ポンプを用いた溶液の移送方法よりも簡便な溶液の移送方法として、親水性処理した流路内の毛細管力を利用した技術が提案されている（たとえば、特許文献１参照。）。図１８にこのような毛細管力を利用したマイクロ分析チップの一例を示す。このようなマイクロ分析チップでは、入口４１３に溶液を滴下すると、毛細管力によって溶液が流路４１６を移動し、ポンプ等の外力を必要とせずに溶液を排出できる。流路内に充填された溶液を排出する方法として、たとえば、特許文献２に示すように、排出口に溶液を吸収する吸収体を設置して排出する方法が提案されている。 As a simpler solution transfer method than a solution transfer method using a pump, a technique using capillary force in a hydrophilically treated flow path has been proposed (for example, see Patent Document 1). FIG. 18 shows an example of a micro analysis chip using such capillary force. In such a microanalysis chip, when a solution is dropped at the inlet 413, the solution moves through the flow path 416 by capillary force, and the solution can be discharged without requiring an external force such as a pump. As a method of discharging the solution filled in the flow path, for example, as shown in Patent Document 2, a method of discharging by installing an absorber that absorbs the solution at the discharge port has been proposed.
特開２００６－２２０６０６号公報JP 2006-220606 A 特開２０００－２９７７６１号公報JP 2000-297761 A
　しかしながら、現在では、マイクロ分析チップ内に、バルブ、ミキサー、反応部、検出部等の要素を盛り込むことが必要とされているため、全ての流路の幅を一定に設定できない場合が多い。このため、図１９に示すように主流路４１６に比べ幅の狭い流路４１５が存在するような形態をとることが多い。このような形態のマイクロ分析チップの液の流れを図２０、図２１に示す。 However, at present, since it is necessary to incorporate elements such as a valve, a mixer, a reaction unit, and a detection unit in the micro analysis chip, there are many cases where the widths of all the channels cannot be set to be constant. For this reason, as shown in FIG. 19, the channel 415 having a narrower width than the main channel 416 is often used. The flow of the liquid of the microanalysis chip having such a configuration is shown in FIGS.
　図２０（ａ）に示すマイクロ分析チップの注入口４１３に液体３００を注入する（図２０（ｂ））。液体は流路４１４、４１５、４１６を流れ、流路４１６の端部に設けられた吸収体に吸収され、チップ外に排出される（図２０（ｃ）、（ｄ））。しかし、図２０（ｅ）、図２１（ｂ）に示すように、主流路４１６よりも幅の狭い流路４１５に気液界面が形成される状態になると、主流路４１６から幅の狭い流路４１５に向かう強い毛細管力（図中矢印）すなわち表面張力により発生する圧力Ｐが働く。Ｐは半径ｒの流路を想定した典型的な場合、次の式で表される。 The liquid 300 is injected into the injection port 413 of the micro analysis chip shown in FIG. 20 (a) (FIG. 20 (b)). The liquid flows through the channels 414, 415, and 416, is absorbed by the absorber provided at the end of the channel 416, and is discharged out of the chip (FIGS. 20C and 20D). However, as shown in FIGS. 20 (e) and 21 (b), when a gas-liquid interface is formed in the channel 415 having a width smaller than that of the main channel 416, the channel having a narrow width from the main channel 416. A strong capillary force (arrow in the figure) toward 415, that is, a pressure P generated by surface tension acts. P is typically expressed by the following equation assuming a flow path having a radius r.
　Ｐ＝２σlgcosθ／ｒの式（ここで、σlgは気液界面の界面張力、θは接触角、ｒは流路の半径） P = 2σ lg cos θ / r (where σ lg is the interfacial tension at the gas-liquid interface, θ is the contact angle, and r is the radius of the flow path)
　表面張力により発生する圧力Ｐが働き、さらに吸収体による強い毛細管力が吸収体方向に働き、それぞれが反対方向に液体を引合うため、気体が入りやすい主流路４１６と吸収体４１１との界面で液体が分断される。その結果、液体が逆流し、液体３００と吸収体４１１との間に隙間が生じた状態で安定となる。このため、毛細管力の強い吸収体４１１を排出部に設けても、吸収体４１１が液体３００を吸収することができなくなり、チップ内の液体を完全に排出することができない（図２１（ｃ）参照）。 The pressure P generated by the surface tension works, and the strong capillary force due to the absorber acts in the direction of the absorber, and each attracts liquid in the opposite direction. Therefore, at the interface between the main channel 416 and the absorber 411 where gas easily enters. The liquid is broken. As a result, the liquid flows backward and becomes stable in a state where a gap is generated between the liquid 300 and the absorber 411. For this reason, even if the absorber 411 having a strong capillary force is provided in the discharge portion, the absorber 411 cannot absorb the liquid 300, and the liquid in the chip cannot be completely discharged (FIG. 21C). reference).
　本発明は、上記問題を解決するためになされたものであって、幅の狭い流路が存在する場合においても円滑に液体を排出することができる送液構造体を提供することを目的とする。 The present invention has been made to solve the above-described problem, and an object of the present invention is to provide a liquid feeding structure capable of smoothly discharging a liquid even when a narrow flow path exists. .
　上記課題を解決するための第１の本発明は、外部に開放された開放孔に接続された第１流路と、前記第１流路に連続する液溜め部と、前記液溜め部に連続する第２流路と、前記第２流路の終端に直接接する吸収体と、を少なくとも備え、前記第１流路における液体に発生する表面張力による圧力をＰ１とし、前記第２流路における液体に発生する表面張力による圧力をＰ２とし、前記液溜め部における液体に発生する表面張力による圧力をＰ３とするとき、Ｐ３＜Ｐ１≦Ｐ２が成立する、ことを特徴とする。 A first aspect of the present invention for solving the above-described problems is a first flow path connected to an open hole opened to the outside, a liquid reservoir portion continuous with the first flow path, and a continuous portion of the liquid reservoir portion. And at least an absorbent body that is in direct contact with the terminal end of the second flow path, and the pressure due to the surface tension generated in the liquid in the first flow path is P1, and the liquid in the second flow path P3 <P1 ≦ P2 is established, where P2 is the pressure due to the surface tension generated in the liquid reservoir and P3 is the pressure due to the surface tension generated in the liquid in the liquid reservoir.
　この構成によると、第２流路における液体に発生する表面張力による圧力Ｐ２が第１流路における液体に発生する表面張力による圧力Ｐ１以上であるため、図４に示すように、第１流路に気液界面が生じ、逆流する方向に強い毛細管力５０１が働いて液が逆流した場合に、第２流路に気液界面が生じ、逆流方向への力と同等以上の順流方向への毛細管力５０２が作用する。このため、液体と吸収体との接触が維持され、送液構造体内部に液がとどまることなく、全ての液体を構造体外部に排出できる。 According to this configuration, since the pressure P2 due to the surface tension generated in the liquid in the second flow path is equal to or higher than the pressure P1 due to the surface tension generated in the liquid in the first flow path, as shown in FIG. When a strong capillary force 501 acts in the reverse flow direction and the liquid flows backward, a gas-liquid interface is generated in the second flow path, and the capillary in the forward flow direction is equal to or greater than the force in the reverse flow direction. A force 502 acts. For this reason, the contact between the liquid and the absorber is maintained, and all the liquid can be discharged to the outside of the structure without remaining in the liquid feeding structure.
　第２流路における液体に発生する表面張力による圧力をＰ２が第１流路における液体に発生する表面張力による圧力をＰ１以上とするためには、前記第１流路の向かい合う壁面間の最小距離をＤ１とし、前記第２流路の向かい合う壁面間の最小距離をＤ２とし、前記液溜め部の向かい合う壁面間の最小距離をＤ３とするとき、Ｄ２≦Ｄ１＜Ｄ３が成立する構成を採用することが簡便である。 In order to set the pressure due to the surface tension generated in the liquid in the second channel to P2 or more, the minimum distance between the opposing wall surfaces of the first channel is P2. Is set to D1, the minimum distance between the opposing wall surfaces of the second flow path is D2, and the minimum distance between the opposing wall surfaces of the liquid reservoir is D3, D2 ≦ D1 <D3 is adopted. Is simple.
　上記課題を解決するための第２の本発明は、外部に開放された開放孔に接続された第１流路と、前記第１流路に連続する液溜め部と、前記液溜め部に連続する第２流路と、前記第２流路の終端に直接接する吸収体と、を少なくとも備え、前記第１流路および前記第２流路は液体との接触面が親水性であって、前記第１流路の向かい合う壁面間の最小距離をＤ１とし、前記第２流路の向かい合う壁面間の最小距離をＤ２とし、前記液溜め部の向かい合う壁面間の最小距離をＤ３とするとき、Ｄ２≦Ｄ１＜Ｄ３が成立することを特徴とする。 A second aspect of the present invention for solving the above-described problems is a first flow path connected to an open hole that is open to the outside, a liquid reservoir portion that is continuous with the first flow path, and a continuous portion of the liquid reservoir portion. At least a second flow path and an absorber that is in direct contact with the end of the second flow path, wherein the first flow path and the second flow path have a hydrophilic contact surface with the liquid, When the minimum distance between the opposing wall surfaces of the first channel is D1, the minimum distance between the opposing wall surfaces of the second channel is D2, and the minimum distance between the opposing wall surfaces of the liquid reservoir is D3, D2 ≦ D1 <D3 is satisfied.
　この構成によると、第２流路の向かい合う壁面間の最小距離Ｄ２が第１流路の向かい合う壁面間の最小距離Ｄ１以下であるため、図４に示すように、第１流路に気液界面が生じ、逆流する方向に強い毛細管力５０１が働いて液が逆流した場合に、第２流路に気液界面が生じ、逆流方向と同等以上の順流方向への毛細管力５０２が作用する。このため、液体と吸収体との接触が維持され、送液構造体内部に液がとどまることなく、全ての液体を構造体外部に排出できる。 According to this configuration, since the minimum distance D2 between the opposing wall surfaces of the second channel is equal to or less than the minimum distance D1 between the opposing wall surfaces of the first channel, as shown in FIG. When a strong capillary force 501 acts in the reverse flow direction and the liquid flows backward, a gas-liquid interface is generated in the second flow path, and the capillary force 502 acts in the forward flow direction equal to or greater than the reverse flow direction. For this reason, the contact between the liquid and the absorber is maintained, and all the liquid can be discharged to the outside of the structure without remaining in the liquid feeding structure.
　上記構成において、前記第１流路を２以上有する構成とすることができる。 In the above configuration, the first flow path may have two or more.
　抗原を含む液を注入する用途の開放孔、標識付き抗体を含む液を注入する用途の開放孔、基質を含む液を注入する用途の開放孔といったように、２つ以上の開放孔を設ける場合、それぞれの開放孔から液溜め部に送る流路にバルブ等を設ける必要があり、このバルブを設ける流路の向かい合う壁面間の最小距離を、液溜め部よりも小さくする必要がある。上記構成を採用すると、このような送液構造体においても構造体内の液体を完全に排出することが可能となる。 When two or more open holes are provided, such as an open hole for injecting a liquid containing an antigen, an open hole for injecting a liquid containing a labeled antibody, or an open hole for injecting a liquid containing a substrate In addition, it is necessary to provide a valve or the like in the flow path sent from each open hole to the liquid reservoir, and it is necessary to make the minimum distance between the opposing wall surfaces of the flow path provided with this valve smaller than that of the liquid reservoir. If the said structure is employ | adopted, also in such a liquid feeding structure, it will become possible to discharge | emit completely the liquid in a structure.
　上記構成において、前記第１流路の上流側に設けられた第２の液溜め部と、前記第２の液溜め部の上流側に設けられた第３流路と、をさらに備え、前記第３流路における液体に発生する表面張力による圧力をＰ４とし、前記第２の液溜め部における液体に発生する表面張力による圧力をＰ５とするとき、Ｐ５＜Ｐ４≦Ｐ２が成立し、前記第３流路、前記第２の液溜め部、前記第１流路、前記液溜め部、前記第２流路が直列に並んでいる構成とすることができる。 In the above configuration, the apparatus further comprises a second liquid reservoir provided on the upstream side of the first flow path, and a third flow path provided on the upstream side of the second liquid reservoir. When the pressure due to the surface tension generated in the liquid in the three flow paths is P4 and the pressure due to the surface tension generated in the liquid in the second liquid reservoir is P5, P5 <P4 ≦ P2 is established, and the third The flow path, the second liquid reservoir, the first flow path, the liquid reservoir, and the second flow path may be arranged in series.
　上記構成において、前記第１流路の上流側に設けられた第２の液溜め部と、前記第２の液溜め部の上流側に設けられた第３流路と、をさらに備え、前記第３流路の向かい合う壁面間の最小距離をＤ４とし、前記第２の液溜め部の向かい合う壁面間の最小距離をＤ５とするとき、Ｄ２≦Ｄ４＜Ｄ５が成立し、前記第３流路、前記第２の液溜め部、前記第１流路、前記液溜め部、前記第２流路が直列に並んでいる構成とすることができる。 In the above configuration, the apparatus further comprises a second liquid reservoir provided on the upstream side of the first flow path, and a third flow path provided on the upstream side of the second liquid reservoir. When the minimum distance between the opposing wall surfaces of the three flow paths is D4 and the minimum distance between the opposing wall surfaces of the second liquid reservoir is D5, D2 ≦ D4 <D5 is established, and the third flow path, The second liquid reservoir, the first flow path, the liquid reservoir, and the second flow path may be arranged in series.
　検出を液溜め部で行い、反応を液溜め部よりも上流側で行うという用途で用いる場合、液溜め部よりも上流側に第２の液溜め部を設け、この第２の液溜め部で反応を行わせることが好ましい。この場合、バルブ等を設けるために第２の液溜め部よりも上流側に第２の液溜め部に作用する毛細管力よりも大きな毛細管力の作用する第３流路を配置する必要がある。この第３流路においても毛細管力による液の逆流、送液の停止が生じるおそれがあるが、Ｐ４≦Ｐ２又はＤ２≦Ｄ４とすることにより、これを防止することができる。 When the detection is performed in the liquid reservoir and the reaction is performed upstream of the liquid reservoir, a second liquid reservoir is provided upstream of the liquid reservoir, and the second liquid reservoir is used. It is preferable to carry out the reaction. In this case, in order to provide a valve or the like, it is necessary to dispose a third flow path that acts on a capillary force larger than the capillary force acting on the second liquid reservoir on the upstream side of the second liquid reservoir. Even in the third flow path, there is a possibility that the back flow of the liquid due to the capillary force and the stoppage of the liquid feeding may occur, but this can be prevented by setting P4 ≦ P2 or D2 ≦ D4.
　上記いずれかの送液構造体を有するマイクロ分析チップを用いると、液の流れが途絶えることなく連続して反応させることができるマイクロ分析チップを実現できる。 When a microanalysis chip having any one of the liquid feeding structures described above is used, a microanalysis chip that can be continuously reacted without interruption of the liquid flow can be realized.
　上記で説明したように、本発明によると、構造体内の液体を完全に排出することのできる送液構造体を実現することができる。 As described above, according to the present invention, a liquid feeding structure capable of completely discharging the liquid in the structure can be realized.
図１は、実施の形態にかかる送液構造体の平面図である。FIG. 1 is a plan view of a liquid feeding structure according to an embodiment. 図２は、実施の形態にかかる送液構造体の断面図である。FIG. 2 is a cross-sectional view of the liquid feeding structure according to the embodiment. 図３は、実施の形態にかかる送液構造体の液の流れを示す概念図である。FIG. 3 is a conceptual diagram illustrating the flow of the liquid in the liquid feeding structure according to the embodiment. 図４は、実施の形態にかかる送液構造体の第１流路及び第２流路における液の流れを示す概念図である。FIG. 4 is a conceptual diagram illustrating a liquid flow in the first flow path and the second flow path of the liquid feeding structure according to the embodiment. 図５は、実施例１にかかる送液構造体の平面図である。FIG. 5 is a plan view of the liquid feeding structure according to the first embodiment. 図６は、電極の構造を示す概念図である。FIG. 6 is a conceptual diagram showing the structure of the electrode. 図７は、実施例２にかかる送液構造体の平面図である。FIG. 7 is a plan view of the liquid feeding structure according to the second embodiment. 図８は、エレクトロウエッティングバルブの動作を示す概念図である。FIG. 8 is a conceptual diagram showing the operation of the electrowetting valve. 図９は、実施の形態１にかかる送液構造体の変形例を示す平面図である。FIG. 9 is a plan view illustrating a modification of the liquid feeding structure according to the first embodiment. 図１０は、実施の形態２にかかる送液構造体を示す平面図である。FIG. 10 is a plan view showing a liquid feeding structure according to the second embodiment. 図１１は、比較例１にかかる送液構造体の平面図である。FIG. 11 is a plan view of a liquid feeding structure according to Comparative Example 1. 図１２は、比較例２にかかる送液構造体の平面図である。FIG. 12 is a plan view of a liquid feeding structure according to Comparative Example 2. 図１３は、実施の形態３にかかるマイクロ分析チップを示す図である。FIG. 13 is a diagram illustrating the microanalysis chip according to the third embodiment. 図１４は、実施の形態４にかかるマイクロ分析チップを示す図である。FIG. 14 is a diagram illustrating the micro-analysis chip according to the fourth embodiment. 図１５は、実施の形態５にかかるマイクロ分析チップを示す図である。FIG. 15 is a diagram illustrating the micro-analysis chip according to the fifth embodiment. 図１６は、実施の形態６にかかるマイクロ分析装置を示す図である。FIG. 16 is a diagram illustrating the microanalyzer according to the sixth embodiment. 図１７は、実施の形態７にかかるマイクロ分析装置を示す図である。FIG. 17 is a diagram illustrating the microanalyzer according to the seventh embodiment. 図１８は、従来技術にかかる送液構造体の平面図である。FIG. 18 is a plan view of a liquid feeding structure according to a conventional technique. 図１９は、従来技術にかかる送液構造体の平面図である。FIG. 19 is a plan view of a liquid feeding structure according to a conventional technique. 図２０は、図１９に示す送液構造体の液の流れを示す概念図である。FIG. 20 is a conceptual diagram showing the flow of the liquid in the liquid feeding structure shown in FIG. 図２１は、従来技術にかかる送液構造体の第１流路及び第２流路における液の流れを示す概念図である。FIG. 21 is a conceptual diagram illustrating a liquid flow in the first flow path and the second flow path of the liquid feeding structure according to the conventional technology.
符号の説明Explanation of symbols
１１０　送液構造体
１１１　吸収体
１１３　開放孔
１１４　流路（第２の液溜め部）
１１５　第１流路
１１６　液溜め部
１１７　第２流路
１１８　第３流路
１１９　流路
１４０　バルブ
１５１　検出部
２０１　上部基板
２０２　下部基板
５０１　毛細管力
５０２　毛細管力 110 Liquid feed structure 111 Absorber 113 Open hole 114 Flow path (second liquid reservoir)
115 First channel 116 Liquid reservoir 117 Second channel 118 Third channel 119 Channel 140 Valve 151 Detection unit 201 Upper substrate 202 Lower substrate 501 Capillary force 502 Capillary force
　以下に、本発明を実施するための最良の形態を、図面を用いて詳細に説明する。 Hereinafter, the best mode for carrying out the present invention will be described in detail with reference to the drawings.
　（実施の形態１）
　本実施の形態にかかる送液構造体１１０は、図１に示すように、液体をチップ内に導入する開放孔１１３を備えた第１流路１１５と、第１流路に連続する液溜め部１１６と、前記液溜め部に連続する第２流路１１７と、第２流路の終端に直接接する吸収体１１１と、を有している。なお、流路１１４は、本発明の必須の構成要素ではない。 (Embodiment 1)
As shown in FIG. 1, the liquid feeding structure 110 according to the present embodiment includes a first flow path 115 having an open hole 113 for introducing liquid into the chip, and a liquid reservoir portion continuous with the first flow path. 116, a second flow path 117 that is continuous with the liquid reservoir, and an absorber 111 that is in direct contact with the end of the second flow path. The flow path 114 is not an essential component of the present invention.
　ここで、第２流路１１７は、流路の大きさが上流から下流に渡って同じとなるように設定されている。また、第１流路における液体に発生する表面張力による圧力をＰ１とし、第２流路における液体に発生する表面張力による圧力をＰ２とし、液溜め部における液体に発生する表面張力による圧力をＰ３とするとき、Ｐ３＜Ｐ１≦Ｐ２が成立する。このため、第２流路１１７に作用する毛細管力は、第１流路１１５に作用する毛細管力と同等以上となる。 Here, the second channel 117 is set so that the size of the channel is the same from upstream to downstream. The pressure due to the surface tension generated in the liquid in the first flow path is P1, the pressure due to the surface tension generated in the liquid in the second flow path is P2, and the pressure due to the surface tension generated in the liquid in the liquid reservoir is P3. Then P3 <P1 ≦ P2. For this reason, the capillary force acting on the second flow path 117 is equal to or greater than the capillary force acting on the first flow path 115.
　このように、第１流路における液体に発生する表面張力による圧力をＰ１とし、第２流路における液体に発生する表面張力による圧力をＰ２とし、液溜め部における液体に発生する表面張力による圧力をＰ３とするとき、Ｐ３＜Ｐ１≦Ｐ２が成立するように設定するためには、第１流路の向かい合う壁面間の最小距離をＤ１とし、前記第２流路の向かい合う壁面間の最小距離をＤ２とし、前記液溜め部の向かい合う壁面間の最小距離をＤ３とするとき、Ｄ２≦Ｄ１＜Ｄ３が成立する構成を採用することが好ましい。本実施の形態では、Ｄ２＜Ｄ１としている。 As described above, the pressure due to the surface tension generated in the liquid in the first flow path is P1, the pressure due to the surface tension generated in the liquid in the second flow path is P2, and the pressure due to the surface tension generated in the liquid in the liquid reservoir portion. Is set so that P3 <P1 ≦ P2 is established, the minimum distance between the opposing wall surfaces of the first flow path is D1, and the minimum distance between the opposing wall surfaces of the second flow path is It is preferable to adopt a configuration in which D2 ≦ D1 <D3 is established, where D2 is the minimum distance between the opposing wall surfaces of the liquid reservoir. In this embodiment, D2 <D1.
　図２に、本実施の形態にかかる送液構造体の断面図を示す。図２に示すように、流路１１４、液溜め部１１６、第１流路１１５、第２流路１１７が形成されている上部基板２０１と、流路１１４、液溜め部１１６、第１流路１１５、第２流路１１７の下方からシールし、吸収体１１１を載置する下部基板２０２と、からなる。上部基板２０１の厚みは０．１ｍｍ～１０ｍｍ程度であり、下部基板２０２の厚みは０．０１ｍｍ～１０ｍｍ程度である。開放孔１１３は直径が１０μｍ以上の貫通孔でよい。 FIG. 2 shows a cross-sectional view of the liquid feeding structure according to the present embodiment. As shown in FIG. 2, the upper substrate 201 on which the flow path 114, the liquid reservoir 116, the first flow path 115, and the second flow path 117 are formed, the flow path 114, the liquid reservoir 116, and the first flow path. 115, a lower substrate 202 that seals from below the second flow path 117 and on which the absorber 111 is placed. The thickness of the upper substrate 201 is about 0.1 mm to 10 mm, and the thickness of the lower substrate 202 is about 0.01 mm to 10 mm. The open hole 113 may be a through hole having a diameter of 10 μm or more.
　送液構造体の流路１１６を、光学的検出を行う検出部として利用する場合には、基板２０１および基板２０２に用いられる一方または両方の材料として、例えば、特許文献３に提案されるような、透明または半透明の材料を用いることが望ましい。なぜなら、流路１１６内を流れる被検液に励起光を照射し、励起光により発生した蛍光を検出して目的物質の量を測定する必要があるため、蛍光の検出を妨げる材料を用いることができないためである。このような透明または半透明な材料として、ガラス、石英、熱硬化性樹脂、熱可塑性樹脂、フィルム等が挙げられる。なかでも、シリコン系樹脂、アクリル系樹脂、スチレン系樹脂は、透明性、成型性の観点から好ましい。なお、電気化学的検出を行う場合には、このような材料の制約はない。 When the flow path 116 of the liquid feeding structure is used as a detection unit that performs optical detection, as one or both materials used for the substrate 201 and the substrate 202, for example, as proposed in Patent Document 3 It is desirable to use a transparent or translucent material. This is because it is necessary to irradiate the test liquid flowing in the flow channel 116 with excitation light and detect the fluorescence generated by the excitation light to measure the amount of the target substance. This is because it cannot be done. 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. In addition, when performing electrochemical detection, there are no such restrictions on materials.
特開２００３－１４９２５２号公報JP 2003-149252 A
　他方、送液構造体流路内で電気的な制御や電気的な測定を行うためには、基板２０１または基板２０２の表面に電極を形成する必要がある。このため、基板２０１または基板２０２の一方または両方が電極形成可能な材料であることが好ましい。電極形成可能な材料としては、生産性、再現性の観点からガラス、石英、シリコン等が好ましい。なお、現在の技術では、凹凸のある部分に電極を形成することは難しいので、平坦な基板２０２に電極を形成することが好ましい。 On the other hand, it is necessary to form electrodes on the surface of the substrate 201 or the substrate 202 in order to perform electrical control or electrical measurement in the liquid delivery structure flow path. For this reason, it is preferable that one or both of the substrate 201 and the substrate 202 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 with the current technology, it is difficult to form an electrode on an uneven portion, so it is preferable to form the electrode on a flat substrate 202.
　基板２０１または基板２０２の材料の液体が接する面は、液体が流れ易くするために、基板材料の液体と接する面を親水性とすることが好ましい。液体が接する面を親水性にするためには、酸素プラズマ処理やＵＶ処理などが用いられる。また界面活性剤や親水性の官能基を持つ試薬を表面に塗布することによっても親水性を高めることができる。 The surface of the substrate 201 or 202 that is in contact with the liquid of the material is preferably hydrophilic so that the surface of the substrate material that is in contact with the liquid is easy to flow. In order to make the surface in contact with the liquid hydrophilic, oxygen plasma treatment, UV treatment, or the like is used. The hydrophilicity can also be enhanced by applying a surfactant or a reagent having a hydrophilic functional group to the surface.
　流路や液溜め部の形成には、例えば、基板２０１に直接加工を行う方法、機械加工による方法、レーザー加工による方法、薬品やガスによるエッチングによる方法、金型を用いた射出成型、プレス成型、鋳造による方法等がある。中でも、金型を用いる方法、エッチングを用いる方法は形状寸法の再現性が高く好ましい。 For forming the flow path and the liquid reservoir, for example, a method of directly processing the substrate 201, a method of machining, a method of laser processing, a method of etching with chemicals or gas, injection molding using a mold, press molding There are methods such as casting. Among them, a method using a mold and a method using etching are preferable because of high reproducibility of the shape dimensions.
　図３、図４に、本実施の形態にかかる送液構造体の液の流れを示す。図３（ａ）～（ｅ）までは、従来と同様である。しかし、図３（ｅ）、図４（ｂ）に示すように、毛細管力によって液溜め部１１６から第１流路１１５に液が逆流したときに、第２流路１１７に気液界面が生じる。第２流路１１７の流路幅Ｌ２は、第１流路１１５の流路幅Ｌ１未満であるため、第２流路１１７に働く毛細管力５０２が、第１流路１１５に働く毛細管力５０１を打ち消す。このため、図３（ｆ）、図４（ｃ）に示すように、液体が完全に送液構造体外に排出されることとなる。 3 and 4 show the flow of the liquid in the liquid feeding structure according to the present embodiment. 3 (a) to 3 (e) are the same as in the prior art. However, as shown in FIGS. 3E and 4B, when the liquid flows back from the liquid reservoir 116 to the first flow path 115 by the capillary force, a gas-liquid interface is generated in the second flow path 117. . Since the channel width L2 of the second channel 117 is less than the channel width L1 of the first channel 115, the capillary force 502 acting on the second channel 117 has a capillary force 501 acting on the first channel 115. Counteract. For this reason, as shown in FIG.3 (f) and FIG.4 (c), a liquid will be discharged | emitted completely out of a liquid feeding structure.
　図１に示される送液構造体の流路１１４、液溜め部１１６、第１流路１１５、第２流路１１７の幅と高さは特に限定はしないが、溶液の濡れと毛細管力よって溶液が浸透していくことが可能な寸法に設定される。高さに関して好ましくは、１μｍ～５ｍｍ程度に設定される。幅に関して好ましくは１μｍ～５ｍｍ程度に設定される。 The width and height of the flow channel 114, the liquid reservoir 116, the first flow channel 115, and the second flow channel 117 of the liquid feeding structure shown in FIG. 1 are not particularly limited, but the solution is affected by the wetness of the solution and the capillary force. Is set to a dimension that can penetrate. The height is preferably set to about 1 μm to 5 mm. The width is preferably set to about 1 μm to 5 mm.
　このような送液構造体は、例えば液溜め部に抗体等を固定化し、抗原を含む液を流して抗原抗体反応させ、さらに蛍光色素を付けた標識抗体を含む液を流して抗原抗体反応させ、液溜め部に励起光を照射してその蛍光の量により抗原の量を測定するというマイクロ分析チップとして利用できる。 In such a liquid feeding structure, for example, an antibody or the like is immobilized in a liquid reservoir, an antigen-containing reaction is performed by flowing a liquid containing an antigen, and an antigen-antibody reaction is performed by flowing a liquid containing a labeled antibody to which a fluorescent dye is attached. It can be used as a micro-analysis chip in which the liquid reservoir is irradiated with excitation light and the amount of antigen is measured by the amount of fluorescence.
　また、図９に示すように第１流路にバルブ１４０を設けてもよい。 Further, as shown in FIG. 9, a valve 140 may be provided in the first flow path.
　（実施の形態２）
　本実施の形態にかかる送液構造体１１０は、図１０に示すように、開放孔１１３と、第３の流路１１８と、第２の液溜め部１１４と、第１流路１１５と、第１流路に連続する液溜め部１１６と、前記液溜め部に連続する第２流路１１７と、第２流路の終端に直接接する吸収体１１１と、を有している。なお、流路１１９は、本発明の必須の構成要素ではない。 (Embodiment 2)
As shown in FIG. 10, the liquid delivery structure 110 according to the present embodiment includes an open hole 113, a third flow path 118, a second liquid reservoir 114, a first flow path 115, It has a liquid reservoir 116 that is continuous with one flow path, a second flow path 117 that is continuous with the liquid reservoir, and an absorber 111 that is in direct contact with the end of the second flow path. The flow path 119 is not an essential component of the present invention.
　ここで、第２流路１１７は、第１流路における液体に発生する表面張力による圧力をＰ１とし、前記第２流路における液体に発生する表面張力による圧力をＰ２とし、前記液溜め部における液体に発生する表面張力による圧力をＰ３とするとき、Ｐ３＜Ｐ１≦Ｐ２が成立する。また、前記第２の液溜め部の上流側に設けられた第３流路と、をさらに備え、前記第３流路における液体に発生する表面張力による圧力をＰ４とし、前記第２の液溜め部における液体に発生する表面張力による圧力をＰ５とするとき、Ｐ５＜Ｐ４≦Ｐ２が成立する。このため、第２流路１１７に作用する毛細管力は、第１流路１１５に作用する毛細管力と同等以上となり、且つ第２流路１１７に作用する毛細管力は、第３流路１１８に作用する毛細管力と同等以上となる。このため、上記実施の形態１と同様に、送液の停止が起こらず、スムースに液を流しきることができる。 Here, the second flow path 117 has a pressure due to the surface tension generated in the liquid in the first flow path as P1, and a pressure due to the surface tension generated in the liquid in the second flow path as P2, and in the liquid reservoir When the pressure due to the surface tension generated in the liquid is P3, P3 <P1 ≦ P2 is established. And a third flow path provided on the upstream side of the second liquid reservoir, wherein the pressure due to the surface tension generated in the liquid in the third flow path is P4, and the second liquid reservoir When the pressure due to the surface tension generated in the liquid in the section is P5, P5 <P4 ≦ P2 is established. For this reason, the capillary force acting on the second flow path 117 is equal to or greater than the capillary force acting on the first flow path 115, and the capillary force acting on the second flow path 117 acts on the third flow path 118. Equal to or greater than the capillary force For this reason, similarly to the first embodiment, the liquid feeding is not stopped and the liquid can be smoothly poured.
　本実施の形態にかかる送液構造体は、第２の液溜め部１１４に抗体等を固定化し、液溜め部１１６に電極を設け、第２の液溜め部１１４で抗原抗体反応、酵素標識付き抗体と抗原－抗体複合体との反応、酵素基質反応を行わせ、酵素基質反応により生じた電極活性物質の量を液溜め部１１６に設けられた電極で検出するというマイクロ分析チップとして利用できる。 In the liquid delivery structure according to the present embodiment, an antibody or the like is fixed to the second liquid reservoir 114, an electrode is provided in the liquid reservoir 116, and the antigen-antibody reaction and enzyme labeling are provided in the second liquid reservoir 114. It can be used as a micro-analysis chip in which the reaction between the antibody and the antigen-antibody complex, the enzyme substrate reaction is performed, and the amount of the electrode active substance generated by the enzyme substrate reaction is detected by the electrode provided in the liquid reservoir 116.
（実施例）
　次に、実施例により本発明の説明を行うが、本発明の範囲はこれらの実施例に限定されるものではない。 (Example)
EXAMPLES Next, although an Example demonstrates this invention, the scope of the present invention is not limited to these Examples.
（実施例１）
　図５に、本実施例にかかる送液構造体を示す。
　送液構造体１１０は、２つの開放孔１１３ａ、１１３ｂと、液溜め部１１６と、バルブ１４１、１４２がそれぞれ設けられた２つの第１流路と、開放孔と第１流路とを繋ぐ流路１１４ａ、１１４ｂと、第２流路１１７と、第２流路の下流側末端に設けられた吸収体１１１と、を有している。 Example 1
FIG. 5 shows a liquid feeding structure according to this example.
The liquid feeding structure 110 is a flow connecting two open holes 113a and 113b, a liquid reservoir 116, two first flow paths provided with valves 141 and 142, and the open holes and the first flow path. It has the path | routes 114a and 114b, the 2nd flow path 117, and the absorber 111 provided in the downstream end of the 2nd flow path.
　上記送液構造体は、上記実施の形態と同様に２つの基板から構成されており、上部基板内の流路１１４、液溜め部１１６、第１流路１１５、第２流路１１７の作製には、金型による樹脂成型方法を用いた。金型の作成には、シリコン基板にフォトリソ法によりレジストパターン形成後、ドライエッチングプロセス法によるエッチングを行った。作製された金型型枠を設置し、シリコンゴム（ポリジメチルシロキサン）（東レダウコーニング社製ジルポット１８４）を厚みが２ｍｍになるまで流し込み、１００℃、１５分の加熱を行い、硬化させた。硬化後、金型と硬化したシリコンゴムを分離させ、シリコンゴムを縦１５ｍｍ、横１０ｍｍ、厚み２ｍｍに整形し、上部基板を作製した。流路１１４ａ、１１４ｂの幅１０３を３００μｍ、液溜め部１１６の幅を６００μｍ、第１流路１１５ａ、１１５ｂの幅１００を５０μｍ、第２流路１１７の幅を５０μｍに設定した。流路高さは全て５０μｍとした。下部基板は、厚み６００μｍの石英基板をダイシングソーで縦１８ｍｍ、横１６ｍｍに切断して作製した。 The liquid feeding structure is composed of two substrates as in the above embodiment, and is used for the production of the flow path 114, the liquid reservoir 116, the first flow path 115, and the second flow path 117 in the upper substrate. Used a resin molding method using a mold. In forming the mold, a resist pattern was formed on a silicon substrate by a photolithography method, and then etching was performed by a dry etching process method. The prepared mold form was placed, and silicon rubber (polydimethylsiloxane) (Zill pot 184 manufactured by Toray Dow Corning Co., Ltd.) was poured into the thickness until it 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 15 mm, a width of 10 mm, and a thickness of 2 mm to produce an upper substrate. The width 103 of the channels 114a and 114b was set to 300 μm, the width of the liquid reservoir 116 was set to 600 μm, the width 100 of the first channels 115a and 115b was set to 50 μm, and the width of the second channel 117 was set to 50 μm. The flow path height was all 50 μm. The lower substrate was produced by cutting a quartz substrate having a thickness of 600 μm into a length of 18 mm and a width of 16 mm with a dicing saw.
　上部基板に２箇所の入口穴１１３をポンチ加工によって形成して、基板２０１を完成させた。下部基板にはあらかじめ、バルブ１４１、１４２、検出部１５１用の電極を作製した。バルブ１４１、１４２の作製には、フォトリソ法によりレジストをパターニング後、スパッタ法によってチタン層５０ｎｍ、金層１００ｎｍを形成後、リフトオフ法によってパターニングされた電極を形成した。バルブは上記以外であっても、ダイアフラム型バルブなど液体の流入を停止、または開始できるものであれば良い。 Two inlet holes 113 were formed in the upper substrate by punching to complete the substrate 201. On the lower substrate, electrodes for the valves 141 and 142 and the detector 151 were prepared in advance. The valves 141 and 142 were prepared by patterning a resist by a photolithography method, forming a titanium layer of 50 nm and a gold layer of 100 nm by a sputtering method, and then forming an electrode patterned by a lift-off method. The valve may be other than the above as long as it can stop or start the inflow of liquid, such as a diaphragm type valve.
　同様に検出部１５１の作製にはフォトリソ法によりレジストをパターニング後、スパッタ法によってチタン層５０ｎｍ、金層１００ｎｍを形成後、リフトオフ法によってパターニングされた、図６に示すような電極１５２、１５４、１５５、１５６を形成した。検出部１５１の一部である電極１５３の作製には、フォトリソ法によりレジストをパターニング後、スパッタ法によって銀層を１μｍ形成し、リフトオフ法によってパターニングされた電極１５３を形成した。電極１５３作製後、Ａｇの表面の塩化処理を行い、Ａｇ／ＡｇＣｌ層の電極１５３を作製した。塩化処理には０．１Ｍ塩酸中で電極１５３に＋１００ｍＶ、５０秒の電圧印加を行った。上部基板と下部基板に１００Ｗ、酸素流量３０ｓｃｃｍ、６０秒の条件で酸素プラズマ処理を行い基板表面の親水性を高めた後、上部基板と下部基板とを自己吸着作用によって貼り合わせ、第２流路の下流側末端にコットン製の吸収体１１１を載置し、実施例１にかかる送液構造体を作製した。 Similarly, the detector 151 is manufactured by patterning a resist by a photolithography method, forming a titanium layer 50 nm and a gold layer 100 nm by a sputtering method, and then patterning the electrodes 152, 154, and 155 as shown in FIG. 6 by a lift-off method. 156 was formed. In order to manufacture the electrode 153 which is a part of the detection unit 151, after patterning a resist by a photolithography method, a silver layer of 1 μm is formed by a sputtering method, and a patterned electrode 153 is formed by a lift-off method. After the electrode 153 was produced, the Ag surface was subjected to chlorination treatment to produce an Ag / AgCl layer electrode 153. For the chlorination treatment, a voltage of +100 mV for 50 seconds was applied to the electrode 153 in 0.1 M hydrochloric acid. The upper substrate and the lower substrate are subjected to oxygen plasma treatment under the conditions of 100 W, oxygen flow rate of 30 sccm, and 60 seconds to increase the hydrophilicity of the substrate surface, and then the upper substrate and the lower substrate are bonded to each other by a self-adsorption action. The absorbent body 111 made of cotton was placed on the downstream end of the liquid feeding structure according to the first example.
（比較例１）
　図１１に示すように、第２流路を形成しなかったこと以外は、上記実施例１と同様にして、比較例１にかかる送液構造体４１０を作製した。 (Comparative Example 1)
As shown in FIG. 11, a liquid feeding structure 410 according to Comparative Example 1 was produced in the same manner as in Example 1 except that the second flow path was not formed.
　実施例１、比較例１にかかる送液構造体に液を流す試験を行った。実施例１にかかる送液構造体では、開放孔に蛍光色素（ＦＩＴＣ）溶液を滴下すると、毛細管現象により送液構造体内に溶液３００が満たされ、溶液３００が吸収体１１１に達した時点から吸収体１１１が流路内の溶液を吸収し、流路内の溶液が無くなるまで吸収を行うことができた。他方、比較例１にかかる送液構造体では、溶液３００が吸収体４１１に達した時点から吸収体４１１が流路内の溶液を吸収が始まったが、第１流路において気液界面生じた時点で開放孔側への溶液の戻りが生じて、吸収体４１１と溶液３００との間に空隙が生じ、これ以上の送液が停止して、溶液３００が流路内に残留した。 The test which flows a liquid through the liquid feeding structure concerning Example 1 and Comparative Example 1 was conducted. In the liquid delivery structure according to Example 1, when a fluorescent dye (FITC) solution is dropped into the open hole, the solution 300 is filled in the liquid delivery structure by capillary action, and is absorbed from when the solution 300 reaches the absorber 111. The body 111 was able to absorb the solution in the flow channel and absorb it until there was no solution in the flow channel. On the other hand, in the liquid delivery structure according to Comparative Example 1, the absorber 411 started to absorb the solution in the channel from the time when the solution 300 reached the absorber 411, but a gas-liquid interface occurred in the first channel. At that time, the solution returned to the open hole side, and a gap was formed between the absorber 411 and the solution 300. Further liquid feeding stopped, and the solution 300 remained in the flow path.
　よって、本発明によると、流路内に流路幅や流路高さの小さい流路が存在する場合においても、スムースに液体を流しきることができることがわかる。 Therefore, according to the present invention, it can be seen that even when a channel having a small channel width or channel height exists in the channel, the liquid can flow smoothly.
（実施の形態３）
　次に、本発明によるマイクロ分析チップの具体的なチップ構成について説明する。 (Embodiment 3)
Next, a specific chip configuration of the micro analysis chip according to the present invention will be described.
（マイクロ分析チップの構成）
（全体）
　図１３はマイクロ分析チップの上面図である。本実施の形態にかかる送液構造体は、第１の液体用の開放孔２００１と、第２の液体用の開放孔２００２と、第３の液溜め部２００３，２００４と、ミキサー２００７と、第３の流路２００９と、第２の液溜め部２００８と、第１の流路２０１１と、第１の液溜め部２０１０と、第２の流路２０１３と、第２流路の終端に直接接する吸収体１１１と、を有している。 (Configuration of micro analysis chip)
(The entire)
FIG. 13 is a top view of the micro analysis chip. The liquid feeding structure according to the present embodiment includes an opening hole 2001 for the first liquid, an opening hole 2002 for the second liquid, third liquid reservoirs 2003 and 2004, a mixer 2007, 3 flow channel 2009, second liquid reservoir 2008, first flow channel 2011, first liquid reservoir 2010, second flow channel 2013, and the end of the second flow channel. And an absorber 111.
　第１の液体用の開放孔２００１から第１の液体が注入されると第３の液溜め部２００３に第１の液体が注入される。第２の液体用の開放孔２００２も同様に、第２の液体が注入されると第３の液溜め部２００４に第２の液体が注入される。 When the first liquid is injected from the first liquid opening hole 2001, the first liquid is injected into the third liquid reservoir 2003. Similarly, when the second liquid is injected into the second liquid opening hole 2002, the second liquid is injected into the third liquid reservoir 2004.
　注入された液体のミキサー２００７への流入を停止または開始することのできる第１のバルブ２００５および第２のバルブ２００６がそれぞれ第１の液体溜めおよび第２の液体溜めに接続され設けられている。ミキサー２００７は第１の液体と第２の液体を充分に混合できる構成を有する。 A first valve 2005 and a second valve 2006 that can stop or start the flow of injected liquid into the mixer 2007 are connected to the first liquid reservoir and the second liquid reservoir, respectively. The mixer 2007 has a configuration capable of sufficiently mixing the first liquid and the second liquid.
　次に、第２の液溜め部２００８が、第３の流路２００９を介して接続されている。第２の液溜め部２００８では溶液に含まれる被検出物質と反応する物質が配置されている構成であればよい。当実施形態ではミキサーと反応部は第３の流路２００９を介して接続されているが、第３の流路２００９を介すことなく直接接続されていても構わない。 Next, the second liquid reservoir 2008 is connected via the third flow path 2009. The second liquid reservoir 2008 may have a configuration in which a substance that reacts with the substance to be detected contained in the solution is disposed. In the present embodiment, the mixer and the reaction unit are connected via the third flow path 2009, but may be directly connected without passing through the third flow path 2009.
　次に、第１の液溜め部２０１０が第１の流路２０１１を介して第２の液溜め部２００８と接続されている。第１の液溜め部２０１０には検出部２０１２が設けられている。検出部は被検出物質を直接的、または間接的に検出することができる構成を有している。なお、被検出物質を直接検出できる構成である場合は、第１の液溜め部２０１０を有さない構成とすることができる。 Next, the first liquid reservoir 2010 is connected to the second liquid reservoir 2008 via the first flow path 2011. The first liquid reservoir 2010 is provided with a detector 2012. The detection unit has a configuration capable of directly or indirectly detecting the substance to be detected. In addition, when it is the structure which can detect a to-be-detected substance directly, it can be set as the structure which does not have the 1st liquid reservoir part 2010. FIG.
　次に、吸収体２０１４が第２の流路２０１３を介して第１の液溜め部２０１０に接続されている。液体は吸収体により吸収されるが、第２の流路２０１３が前記第１および第３の流路の毛細管力と同等またはそれ以上の毛細管力を有し液体を吸収体へ引くことにより前記第１および第３の流路に液体が滞留することなく排出することができる。 Next, the absorber 2014 is connected to the first liquid reservoir 2010 via the second channel 2013. Although the liquid is absorbed by the absorber, the second channel 2013 has a capillary force equal to or greater than the capillary force of the first and third channels, and pulling the liquid to the absorber causes the first channel to be absorbed. The liquid can be discharged without staying in the first and third flow paths.
　さらに、外部接続端子２０１５が設けられる。当該端子より電源のチップへの入力や、電気的制御信号の入力や、検出信号の出力などを行う。 Furthermore, an external connection terminal 2015 is provided. Input from the terminal to the power supply chip, input of an electrical control signal, output of a detection signal, and the like are performed.
　マイクロ分析チップ自体には電源を設けなくても良く、そのためコストパフォーマンスに優れたマイクロ分析チップを実現できる。 The micro analysis chip itself does not need to be provided with a power supply, and therefore, a micro analysis chip with excellent cost performance can be realized.
（注入部）
　第１の液体用の開放孔２００１および第２の液体用の開放孔２００２より、それぞれ第１の液体および第２の液体を注入することにより、第３の液溜め部２００３、２００４にそれぞれの液体が注入される。 (Injection part)
By injecting the first liquid and the second liquid from the first liquid opening hole 2001 and the second liquid opening hole 2002, respectively, the respective liquids are supplied to the third liquid reservoirs 2003 and 2004, respectively. Is injected.
　上記開放孔は、毛細管力が働かない程度の大きさであっても構わない。その場合であれば、開放孔が疎水性を有する場合であっても液体溜めに液体が充分注入することができる。 The opening hole may be of such a size that capillary force does not work. In that case, the liquid can be sufficiently injected into the liquid reservoir even when the open hole is hydrophobic.
　また、上記開放孔は、毛細管力が働く程度の大きさであっても良い。その場合は開放孔に親水性を施すことによって、毛細管力により液体を液体溜めに注入することができる。 Further, the opening hole may have a size that allows capillary force to work. In that case, by applying hydrophilicity to the open hole, the liquid can be injected into the liquid reservoir by capillary force.
　第３の液溜め部２００３、２００４は毛細管力が働く程度の空間の大きさを有すると良い。この場合は高さ方向が充分小さく設計されていれば良い。 The third liquid reservoirs 2003 and 2004 may have a space size that allows capillary force to work. In this case, the height direction may be designed to be sufficiently small.
　また、開放孔は大気開放されていれば良い。 Moreover, the open hole only needs to be open to the atmosphere.
　なお、開放孔にあらかじめ液体を充填したカートリッジを接続する方法で液体を注入することもできる。その場合であっても、液体注入時にはカートリッジは液体を充分に排出できるよう、開放孔２００１、２００２の接続口またはそれ以外の部分で大気開放された構成を有すると良い。 It should be noted that the liquid can be injected by connecting a cartridge filled with liquid in advance in the open hole. Even in that case, it is preferable that the cartridge is open to the atmosphere at the connection ports of the open holes 2001 and 2002 or other portions so that the liquid can be sufficiently discharged when the liquid is injected.
　本実施例では２つの開放孔を有する場合を説明するが、開放孔は適宜３つ以上とすることもできる。その場合は第１の液体用の開放孔に検出対象を含む試料を、第２の液体用の開放孔に試薬を、第３の液体用の開放孔に標準試料を、第４の液体用の開放孔に洗浄液を注入する等とすることができる。 In the present embodiment, the case where two open holes are provided will be described, but the number of open holes may be three or more as appropriate. In that case, the sample containing the detection target in the first liquid open hole, the reagent in the second liquid open hole, the standard sample in the third liquid open hole, and the fourth liquid use For example, a cleaning liquid may be injected into the open hole.
　開放孔に洗浄液を注入することができる構成とする場合は繰り返し使用が可能となるため、コストパフォーマンスがよくなり、環境負荷も低減することができる。 When the configuration is such that the cleaning liquid can be injected into the open hole, it can be used repeatedly, so that the cost performance is improved and the environmental load can be reduced.
　さらに、繰り返し使用可能とするために、検出処理終了後に第１の液体用の開放孔等にさらに洗浄液を注入する構成とすると試料等の汚染を低減することができるため、繰り返しによる検出誤差が小さくなりなお良い。 Furthermore, in order to enable repeated use, if the cleaning liquid is further injected into the first liquid opening after the detection process is completed, contamination of the sample and the like can be reduced, so that detection errors due to repetition are small. It ’s good.
（バルブ）
　バルブは液体の流入を停止し、または、開始することができるものであれば良く、ＭＥＭＳ技術をもちいて微細に形成されたダイヤフラム型バルブであっても良い。エレクトロウエッティングバルブを用いる場合は、作用電極および参照電極がそれぞれのバルブに必要となる。 (valve)
The valve may be any valve that can stop or start the inflow of liquid, and may be a diaphragm valve finely formed by using the MEMS technology. When electrowetting valves are used, a working electrode and a reference electrode are required for each valve.
　エレクトロウエッティングバルブとは、電圧を印加しない場合には液の流れを遮断し、電圧を印加した場合には液を流す構造のバルブである。エレクトロウエッティングバルブの原理を、図８を用いて説明する。流路１１４中をエレクトロウエッティングバルブ用参照電極１７１上に接しながら液体が流入し、さらに流入を続けるとエレクトロウエッティングバルブ用作用電極１７２に液体が達する。エレクトロウエッティングバルブ用作用電極１７２は疎水性膜で被覆されており、電圧を印加していない場合は、液体との接触角が６０度から７０度程度と大きくなる。さらに、流路幅および高さが５０μｍに設計されているため、液体が第１流路を流れる抵抗と上記液体の表面張力と相まって第１流路１１５を液体は通過することができない。 The electrowetting valve is a valve having a structure in which the flow of liquid is interrupted when no voltage is applied and the liquid is allowed to flow when a voltage is applied. The principle of the electrowetting valve will be described with reference to FIG. The liquid flows in the flow path 114 while being in contact with the electrowetting valve reference electrode 171. When the liquid continues to flow, the liquid reaches the electrowetting valve working electrode 172. The electrowetting valve working electrode 172 is covered with a hydrophobic film, and when no voltage is applied, the contact angle with the liquid increases to about 60 to 70 degrees. Furthermore, since the channel width and height are designed to be 50 μm, the liquid cannot pass through the first channel 115 due to the resistance of the liquid flowing through the first channel and the surface tension of the liquid.
　一方、電圧を印加した場合は、エレクトロウエッティングバルブ用参照電極１７１により液体は負に帯電する。また、エレクトロウエッティングバルブ用作用電極１７２においては、絶縁膜を介した液体は作用電極１７２と仮想的なキャパシタを形成するようになり、作用電極１７２に液体が引き寄せられ接触角が小さくなる。このため、流路を流れる抵抗に関わらず、液体は第１流路１１５を通過することができるようになる。 On the other hand, when a voltage is applied, the liquid is negatively charged by the electrowetting valve reference electrode 171. In the electrowetting valve working electrode 172, the liquid via the insulating film forms a virtual capacitor with the working electrode 172, and the liquid is attracted to the working electrode 172 to reduce the contact angle. For this reason, the liquid can pass through the first flow path 115 regardless of the resistance flowing through the flow path.
　それぞれのバルブの流路は液体を適切に停止または流入を開始させるために、バルブごとに最適な流路空間を有している。 Each flow path of each valve has an optimal flow path space for each valve in order to appropriately stop or start inflow of liquid.
（ミキサー）
　ミキサーは第１の液体と第２の液体を充分混合できるように構成されていれば良い。第１のバルブおよび第２のバルブからの流入部付近にマイクロピラー構造を設けることにより混合するような構成でも良い。Ｔ字型ミキサー、Ｍａｎｚミキサー、３次元蛇行流路を用いたミキサーなど様々な態様があるが、充分混合できるように構成されていればどのような構成であってもよい。 (mixer)
The mixer should just be comprised so that a 1st liquid and a 2nd liquid can fully be mixed. A configuration in which mixing is performed by providing a micro-pillar structure in the vicinity of the inflow portion from the first valve and the second valve may be used. There are various modes such as a T-shaped mixer, a Manz mixer, a mixer using a three-dimensional meandering channel, and any configuration may be used as long as it is configured to be sufficiently mixed.
　本実施例では２液を混合する場合を説明したが、適宜、３液以上の液体を混合するように構成してもよい。その場合は、混合のタイミングを適宜調整できるよう流路内の適切な位置に第３の液体用の開放孔から第３のバルブを介して第２のミキサーに接続するように配置すると良い。 In this embodiment, the case where two liquids are mixed has been described. However, three or more liquids may be appropriately mixed. In this case, it is preferable to arrange the mixing liquid at an appropriate position in the flow path so as to be connected to the second mixer via the third valve from the third liquid opening hole so that the mixing timing can be appropriately adjusted.
（第２の液溜め部）
　第２の液溜め部２００８は、反応を行う反応部として機能するものであり、サンプル溶液に含まれる被検出物質を特異的に認識し反応する分子が配置されている構成であればよく、被検出物質が抗原である場合は、抗体を反応部に固定化すると良い。被検出物質を検出するためには、酵素免疫反応のサンドイッチ法を用いており、抗原を酵素標識抗体（二次抗体）と反応させ、抗原と酵素標識抗体が結合した複合体にさせる。前述の複合体を反応部に予め固定化されている抗体（一次抗体）と反応させる。次に基質を導入し、二次抗体に標識されている酵素と反応させ、反応により生成された電気化学的に活性のある物質を検出部である電極上で電気化学的に検出を行う。結果的に反応部では、検出部にて検出できる物質が被検出物質の量に応じて生成することとなる。 (Second liquid reservoir)
The second liquid reservoir 2008 functions as a reaction part that performs the reaction, and may be any structure as long as molecules that specifically recognize and react with the target substance contained in the sample solution are arranged. When the detection substance 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 immunoreaction is used. An antigen is reacted with an enzyme-labeled antibody (secondary antibody) to form a complex in which the antigen and the enzyme-labeled antibody are bound. The aforementioned complex is reacted with an antibody (primary antibody) immobilized in advance in the reaction part. Next, a substrate is introduced, reacted with an enzyme labeled with a secondary antibody, and an electrochemically active substance generated by the reaction is electrochemically detected on an electrode serving as a detection unit. As a result, in the reaction part, a substance that can be detected by the detection part is generated according to the amount of the substance to be detected.
　第１の液体として、スギ花粉由来のCryJ1抗原溶液とアルカリホスファターゼ（ＡＬＰ）酵素が標識されたスギ花粉由来のanti-CryJ1抗体１μＭ溶液の混合溶液を用いた場合、抗原の濃度を検量するためには、反応部にスギ花粉由来のanti-CryJ1抗体を固定化した。第２の液体すなわち試薬としてｐＡＰＰ（ｐ-Ａｍｉｎｏｐｈｅｎｙｌ　ｐｈｏｓｐｐｈａｔｅ）基質溶液１ｍＭを用い、反応部で酵素と反応して生成されるｐAP
（ｐ-Ａｍｉｎｏｐｈｅｎｏｌ）を検出部の電極で電気化学的に検出することができる。溶液１および溶液２の溶媒にはトリス緩衝溶液（ＴＨＡＭ（ｔｒｉｓ　ｈｙｄｒｏｘｙｍｅｔｈｙｌ　ａｍｉｎｏｍｅｔｈａｎｅ）：１０ｍＭ、ＮａＣｌ：１３７ｍＭ、ＭｇＣｌ：１ｍＭ、ＰＨ９．０）を用いた。 In order to calibrate the concentration of the antigen when a mixed solution of a cedar pollen-derived CryJ1 antigen solution and an alkaline phosphatase (ALP) enzyme-labeled anti-CryJ1 antibody 1 μM solution is used as the first liquid In the reaction part, an anti-CryJ1 antibody derived from cedar pollen was immobilized. PAP (p-Aminophenyl phosphate) substrate solution 1 mM is used as a second liquid, that is, a reagent, and pAP produced by reacting with an enzyme in the reaction part
(P-Aminophenol) can be detected electrochemically with the electrode of the detector. A Tris buffer solution (THAM (tris hydroxylmethylamine): 10 mM, NaCl: 137 mM, MgCl: 1 mM, PH 9.0) was used as a solvent for the solutions 1 and 2.
（第２の流路）
　第２の流路２０１３は、液体に発生する表面張力による圧力が第１の流路の液体に発生する表面張力による圧力以上であれば、どのような部材、形状を用いても構わない。また、毛細管力を強くするため、適宜親水性の材料を用いて形成するとなお良い。例えば、ＰＤＭＳ基板であれば、酸素プラズマ処理をほどこすと親水性を高めることができ良い。ガラス基板であれば親水性を有するため良い。 (Second flow path)
As long as the pressure by the surface tension which generate | occur | produces in the liquid is more than the pressure by the surface tension which generate | occur | produces in the liquid of a 1st flow path, the 2nd flow path 2013 may use what kind of member and shape. In order to increase the capillary force, it is better to use a hydrophilic material as appropriate. For example, in the case of a PDMS substrate, hydrophilicity may be improved by performing oxygen plasma treatment. A glass substrate is preferable because it has hydrophilicity.
（吸収体）
　吸収体とは、液体を吸収する材料であればよく、例えば、高分子吸収体、多孔性物質、親水性メッシュ、海綿体、綿、濾紙等を例示できる。 (Absorber)
The absorbent body may be any material that absorbs liquid, and examples thereof include polymer absorbent bodies, porous substances, hydrophilic meshes, sponge bodies, cotton, and filter paper.
　吸収体で効率的に吸収することができるよう、吸収体と第２の流路の接続部またはそれ以外の部分で、大気開放されていると良い。 It is preferable that the absorber is open to the atmosphere at the connection portion of the absorber and the second flow path or other portions so that the absorber can efficiently absorb.
　吸収体は第２の流路に一部を突出していてもよい。その場合は、一部でも突出した部分までの第２の流路も含めて吸収体となり、第２の流路はその分減少する。 The absorber may protrude partly in the second flow path. In that case, the absorber including the second flow path up to the protruding portion is partly absorbed, and the second flow path is reduced accordingly.
（外部接続端子）
　外部接続端子２０１５が設けられる。当該端子より電源のチップへの入力や、電気的制御信号の入力や、検出信号の出力などを行う。金電極をもちると、他のバルブや検出電極などと併用でき工程が簡易化されてよい。その他、白金、アルミニウムや、銅などの材料を含んだ導電性材料を用いて形成してもよい。 (External connection terminal)
An external connection terminal 2015 is provided. Input from the terminal to the power supply chip, input of an electrical control signal, output of a detection signal, and the like are performed. If a gold electrode is used, it may be used in combination with other valves and detection electrodes, and the process may be simplified. Alternatively, a conductive material containing a material such as platinum, aluminum, or copper may be used.
　上記構成をとることにより、マイクロ分析チップ自体には電源やＩＣなどの制御回路を設けなくても良く、そのためコストパフォーマンスに優れたチップを提供することができる。 By adopting the above configuration, the micro analysis chip itself does not need to be provided with a control circuit such as a power source or an IC, and therefore a chip with excellent cost performance can be provided.
（実施の形態４）
　次に、上記実施の形態４の場合のチップの層構成について図１４を用いて説明する。 (Embodiment 4)
Next, the layer structure of the chip in the case of Embodiment 4 will be described with reference to FIG.
　上記マイクロ分析チップは上層２１０１と下層２１０２からなる。
　上層は透明性および加工性が高いものが良くＰＤＭＳを用いて形成すると良い。また、下層は電気的制御等のための電極形成が可能な材料としてシリコン基板を用いると良い。 The micro analysis chip includes an upper layer 2101 and a lower layer 2102.
The upper layer preferably has high transparency and processability and is preferably formed using PDMS. The lower layer may be a silicon substrate as a material capable of forming electrodes for electrical control or the like.
　上層２１０１および下層２１０２に用いられる一方または両方の材料は、例えば、特許文献３に提案されるような、透明または半透明のものが望ましい。なぜなら、マイクロチップの流路内を検出部として、流路内を流れる被写体に励起光を照射し、被写体の蛍光を検出するするチップシステムなどへの応用をする場合では、反応部を通過した蛍光やＵＶの検出を行う必要があるからである。透明または半透明なものとして、ガラス、石英、熱硬化性樹脂、熱可塑性樹脂、フィルム等が好ましい。なかでも、シリコン系樹脂、アクリル系樹脂、スチレン系樹脂は、透明性、成型性の観点から好ましい。 One or both of the materials used for the upper layer 2101 and the lower layer 2102 are desirably transparent or translucent as proposed in Patent Document 3, for example. This is because, in the case of application to a chip system that detects the fluorescence of the subject by irradiating the subject flowing in the channel with excitation light by using the inside of the microchip channel as the detection unit, the fluorescence that has passed through the reaction unit This is because it is necessary to detect UV and UV. As the transparent or translucent material, glass, quartz, thermosetting resin, thermoplastic resin, film and the like are preferable. Of these, silicon resins, acrylic resins, and styrene resins are preferable from the viewpoints of transparency and moldability.
　また、例えばマイクロ分析チップ流路内で電気的な制御や電気的な測定を行うために、表面に電極を形成する必要がある。上層または下層の一方または両方が電極形成可能な材料であることが好ましい。電極形成可能な材料として、生産性、再現性の観点からガラス、石英、シリコン等の基板材料が好ましい。 Also, for example, in order to perform electrical control and electrical measurement in the micro analysis chip flow path, it is necessary to form electrodes on the surface. It is preferable that one or both of the upper layer and the lower layer is a material capable of forming an electrode. As materials capable of forming electrodes, substrate materials such as glass, quartz, and silicon are preferable from the viewpoint of productivity and reproducibility.
　上層は上部に第１の液体用の開放孔２００１および第２の液体用の開放孔２００２が上向きに開口され、下部に第３の液溜め部２００３、２００４、第１のバルブ２００５および第２のバルブ２００６を設ける流路、ミキサー２００７、第２の液溜め部２００８、第３の流路２００９、第１の液溜め部２０１０、第１の流路２０１１、第２の流路２０１３などが下向きに開口し設けられる。吸収体２０１４は下側に開口された空間を設けてそこに充填することで配置される。これらの下側に開口された部分は下層２１０２により底部を封じらされ、空間が形成される。 In the upper layer, a first liquid opening hole 2001 and a second liquid opening hole 2002 are opened upward, and third liquid reservoirs 2003 and 2004, a first valve 2005 and a second liquid hole are opened in the lower part. The flow path for providing the valve 2006, the mixer 2007, the second liquid reservoir 2008, the third flow path 2009, the first liquid reservoir 2010, the first flow path 2011, the second flow path 2013, etc. face downward. Opened and provided. The absorber 2014 is arranged by providing a space opened on the lower side and filling the space. These bottom-opened portions are sealed at the bottom by the lower layer 2102 to form a space.
　下層には、第１のバルブ用電極２１０５および第２のバルブ用電極２１０６、検出用電極２１１２が設けられる、それぞれが、外部接続端子２０１５に接続される。第１のバルブ用電極２１０５および第２のバルブ用電極２１０６への接続はエレクトロウエッティングバルブを用いる場合は２端子および対極を設けた場合３端子とすることができる。 In the lower layer, a first valve electrode 2105, a second valve electrode 2106, and a detection electrode 2112 are provided, and each is connected to an external connection terminal 2015. The connection to the first valve electrode 2105 and the second valve electrode 2106 can be two terminals when an electrowetting valve is used and three terminals when a counter electrode is provided.
　また、検出用電極は上記するように３端子とすることができる。 Also, the detection electrode can have three terminals as described above.
（実施の形態５）
　次に、上記実施の形態４とは異なるチップの層構成について図１５を用いて説明する。 (Embodiment 5)
Next, a layer configuration of a chip different from that in Embodiment Mode 4 will be described with reference to FIG.
　本実施の形態では上層２２０１、中層２２０２および下層２２０３からなる。
　上記実施の形態４と異なる点は、第１の液体用の開放孔２２０１および第２の液体用の開放孔２２０２が上層に分けて構成されている点である。第１の液体用の開放孔２２０１および第２の液体用の開放孔２２０２はともに、２２０１層を貫通する開口として形成される。吸収体２２１４は下側に開口された空間を設けてそこに充填することで配置される。 In this embodiment mode, the upper layer 2201, the middle layer 2202, and the lower layer 2203 are included.
The difference from the fourth embodiment is that the first liquid opening hole 2201 and the second liquid opening hole 2202 are divided into upper layers. Both the first liquid opening hole 2201 and the second liquid opening hole 2202 are formed as openings penetrating the 2201 layers. The absorber 2214 is arranged by providing a space opened on the lower side and filling the space.
　中層は第２の流路２２１３以外全て、開口した形状に形成することができる。必要であれば、下側に開口した上記構成と同様に形成することもできる。その場合、第３の液溜め部２２０３、２２０４は上層と接続できるよう上側にも開口しておく必要がある。 The middle layer can be formed in an open shape except for the second flow path 2213. If necessary, it can be formed in the same manner as the above-described structure opened on the lower side. In that case, the third liquid reservoirs 2203 and 2204 need to be opened on the upper side so as to be connected to the upper layer.
　第２の流路２２１３は、上層に接続するように上部が開口されて形成される。 The second flow path 2213 is formed with an upper opening so as to connect to the upper layer.
　下層は上記実施の形態４と同様である。 The lower layer is the same as in the fourth embodiment.
（実施の形態６）
　次に、本発明によるマイクロ分析装置の具体的な装置構成について説明する。 (Embodiment 6)
Next, a specific apparatus configuration of the microanalyzer according to the present invention will be described.
（ハンディー機器接続型）
　図１６にマイクロ分析装置の１実施形態を示す。マイクロ分析装置は、携帯可能なハンディ型マイクロ分析装置である。 (Handy device connection type)
FIG. 16 shows one embodiment of the microanalyzer. The micro analyzer is a portable handy micro analyzer.
　ハンディ機器２３０１の下部に上記実施形態で説明したマイクロ分析チップ２３０２の接続口であるチップ接続口２３０３が設けられている。マイクロ分析チップの外部接続端子と電気的に接続できる外部入出力端子（図示せず）が、ハンディ機器２３０１内のチップ接続口２３０３の奥に設けられており、チップ接続口２３０３にマイクロ分析チップ２３０２を挿入することにより、ハンディ機器２３０１内の外部入出力端子とマイクロ分析チップ２３０２の外部接続端子とが電気的に接続される。また、ハンディ機器には、被検出物質の量を表示することができる表示部２３０４、および、測定の開始、停止や、測定パラメータを特定するための様々なデータを入力することのできる入力部２３０５が設けられる。その他、ハンディ機器には、図示しないが、データを処理することのできるＣＰＵや入力情報および出力情報を処理するＩ／Ｏ論理回路などの情報処理システムが構築されている。 A chip connection port 2303 which is a connection port of the micro analysis chip 2302 described in the above embodiment is provided below the handy device 2301. An external input / output terminal (not shown) that can be electrically connected to the external connection terminal of the micro analysis chip is provided in the back of the chip connection port 2303 in the handy device 2301, and the micro analysis chip 2302 is connected to the chip connection port 2303. Is inserted between the external input / output terminal in the handy device 2301 and the external connection terminal of the micro analysis chip 2302. In addition, a display unit 2304 that can display the amount of a substance to be detected and an input unit 2305 that can input various data for starting and stopping measurement and specifying measurement parameters. Is provided. In addition, although not shown, 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 is built in the handy device.
　マイクロ分析チップをハンディ機器に接続し、各種データを入力し、測定開始ボタンを押すことにより、あらかじめマイクロ分析チップに準備されておりバルブで流入を停止されていた試薬や試料（サンプル）などのバルブ流入を順次開始し、結果として検出部において検出された被検出物質の量に応じた電気信号をマイクロ分析チップの外部接続端子から出力する。ハンディ機器においてマイクロ分析チップの外部接続端子と電気的に接続する外部入力端子より入力された電気信号を分析することにより、被検出物質の量または種類などを特定することができる。 By connecting the micro analysis chip to the handy device, inputting various data, and pressing the measurement start button, valves such as reagents and samples (samples) that have been prepared in advance on the micro analysis chip and stopped by the valve The inflow is sequentially started, and as a result, an electric signal corresponding to the amount of the substance to be detected detected by the detection unit is output from the external connection terminal of the micro analysis chip. By analyzing an electric signal input from an external input terminal electrically connected to an external connection terminal of the micro analysis chip in the handy device, the amount or type of the substance to be detected can be specified.
　ハンディ機器２３０１は、例えば、携帯電話やＰＤＡなどの携帯電子機器とすることができる。ここでは携帯電話を例に挙げて説明する。携帯電話で、マイクロ分析チップ用のデータ処理分析ソフトを起動させることでハンディ機器として動作させることができる。すなわち、専用ソフトにより仮想的に携帯電話をハンディ機器として利用する。マイクロ分析チップの外部接続端子は、携帯電話の外部入力端子に接続可能に構成すると良い。マイクロ分析チップを携帯電話に接続し、各種データを携帯電話のボタンより入力し、測定開始ボタンとして設定されたボタンを押すことにより、あらかじめマイクロ分析チップに準備されておりバルブで流入を停止されていた試薬や試料（サンプル）などのバルブ流入を順次開始し、結果として検出部において検出された被検出物質の量に応じた電気信号をマイクロ分析チップの外部接続端子から出力する。携帯電話においてマイクロ分析チップの外部接続端子と電気的に接続する外部入力端子より入力された電気信号を分析することにより、被検出物質の量又は種類などを特定することができる。そして測定結果を携帯電話の表示画面に表示する。 The handy device 2301 can be, for example, a portable electronic device such as a mobile phone or a PDA. Here, a mobile phone will be described as an example. The mobile phone can be operated as a handy device by starting data processing analysis software for a micro analysis chip. That is, the mobile phone is virtually used as a handy device by dedicated software. The external connection terminal of the micro analysis chip may be configured to be connectable to the external input terminal of the mobile phone. By connecting the micro analysis chip to the mobile phone, inputting various data from the buttons on the mobile phone, and pressing the button set as the measurement start button, the micro analysis chip is prepared in advance and the flow is stopped by the valve Then, inflow of valves such as reagents and samples (samples) is started sequentially, and as a result, an electrical signal corresponding to the amount of the substance to be detected detected by the detection unit is output from the external connection terminal of the micro analysis chip. By analyzing an electric signal input from an external input terminal that is electrically connected to an external connection terminal of the micro analysis chip in a mobile phone, the amount or type of the substance to be detected can be specified. Then, the measurement result is displayed on the display screen of the mobile phone.
　ハンディ機器を携帯電話とすることにより、コストパフォーマンスに優れたマイクロ分析装置を提供することができる。またユーザーは測定が必要な時にどこでも測定が可能になる。携帯電話の保有率が上昇し、測定者（ユーザー）に充分携帯電話が普及するようになると多くのユーザーが便益を享受することができる。すなわち、携帯電話保有者のハンディ機器のコストは不要となる。ただし、代わりに携帯電話で動作させることのできる電気的な回路やデータ処理分析ソフトのコストが必要となるが、測定者側では、データ処理分析ソフトをネットワーク上でダウンロードすることが可能であり、携帯電話の高機能化により電気的回路をあらかじめ搭載することができる。ユーザーは低コストで携帯電話をハンディ機器として利用することが可能となる。以上より、携帯電話保有者は容易にハンディ機器２３０１を準備でき、ハンディ機器を準備できた後は、マイクロ分析チップ２３０２のコストのみで試料（サンプル）の分析が可能となる。 By using a handy device as a mobile phone, a microanalyzer with excellent cost performance can be provided. Users can also take measurements wherever they need it. Many mobile users can enjoy the benefits when the mobile phone ownership rate rises and mobile phones become sufficiently widespread for the measurers (users). That is, the cost of the handheld device of the mobile phone holder is unnecessary. However, the cost of an electric circuit and data processing analysis software that can be operated on a mobile phone instead is required, but the measurer can download the data processing analysis software on the network, An electric circuit can be mounted in advance by increasing the functionality of the mobile phone. The user can use the mobile phone as a handy device at low cost. As described above, the mobile phone holder can easily prepare the handy device 2301, and after preparing the handy device, the sample (sample) can be analyzed only with the cost of the micro analysis chip 2302.
（実施の形態７）
　次に、本発明によるマイクロ分析装置の具体的な装置構成の別の実施形態について説明する。 (Embodiment 7)
Next, another embodiment of a specific device configuration of the microanalyzer according to the present invention will be described.
（独立型）
　図１７にマイクロ分析装置の１実施形態を示す。このマイクロ分析装置は独立して試料（サンプル）の採取、検出データの分析、および出力が可能な独立型マイクロ分析装置である。
　マイクロ分析装置は独立して試料（サンプル）の採取から検出データの分析および出力まで可能な独立マイクロ分析装置を構成することができる。すなわち、マイクロ分析装置は図示するように、サンプル採取部２４０１、液体流路部２４０２、駆動分析処理部２４０３、入出力論理処理部２４０４および出入力部２４０５より構成される。それぞれの部部分が順次積層されるか、または組み合わされることによりマイクロ分析装置となる。 (Independent type)
FIG. 17 shows an embodiment of a microanalyzer. This microanalyzer is an independent microanalyzer capable of collecting a sample (sample) independently, analyzing detection data, and outputting.
The microanalyzer can independently constitute an independent microanalyzer capable of collecting a sample (sample) to analyzing and outputting detection data. That is, as shown in the figure, the 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 part is sequentially stacked or combined to form a microanalyzer.
　サンプル採取部２４０１には、毛細管の貫通している針が設けられており、人体又は試料体に針を刺すまたは導入することにより血液や試料を採取することができる。針は、低侵襲のマイクロプローブであれば被検体に針を刺し血液等の体液を抽出する際に痛みが緩和されるため好ましい。また、針の代わりに非侵襲型の皮膚表面の汗、口腔内の唾液、涙や尿等を採取する吸収体であっても良い。 The sample collection unit 2401 is provided with a needle penetrating a capillary tube, and blood or a sample can be collected by inserting or introducing a needle into a human body or a sample body. A needle is preferable if it is a minimally invasive microprobe because pain is alleviated when a needle is inserted into a subject and a body fluid such as blood is extracted. Further, instead of a needle, an absorbent body that collects noninvasive skin surface sweat, saliva in the oral cavity, tears, urine, and the like may be used.
　次に液体流路部２４０２は、上記実施形態にて説明したマイクロ分析チップの流路構造が形成されている。特に実施の形態４で説明した２１０１層や実施の形態５で説明した２２０２層を用いて構成することができる。サンプル採取部の毛細管は液体流路部の第２の液溜め部２４１４と接続しており、針に設けられている毛細管の毛管現象によりサンプルが液溜め部に流入するように構成される。 Next, the liquid flow path portion 2402 is formed with the flow path structure of the micro analysis chip described in the above embodiment. In particular, the structure can be formed using the 2101 layer described in Embodiment 4 and the 2202 layer described in Embodiment 5. The capillary tube of the sample collecting unit is connected to the second liquid reservoir 2414 of the liquid flow channel unit, and is configured such that the sample flows into the liquid reservoir due to the capillary phenomenon of the capillary provided on the needle.
　液体流路部はポリジメチルシロキサン（ＰＤＭＳ）、ポリメタクリル酸メチル（ＰＭＭＡ）、ポリカーボネート、ポリテトラフルオロエチレン、塩化ビニル等を用いて作成することが可能である。当該液体流路部には複数の検出部を有する流路構造を形成することも可能である。また、流路構造を複数形成することも可能である。 The liquid channel part can be made using polydimethylsiloxane (PDMS), polymethyl methacrylate (PMMA), polycarbonate, polytetrafluoroethylene, vinyl chloride or the like. It is also possible to form a flow path structure having a plurality of detection sections in the liquid flow path section. It is also possible to form a plurality of channel structures.
　駆動分析処理部２４０３は上記実施形態にて説明したマイクロ分析チップと同様に構成することができ、ＣＰＵ、メモリ、およびバッテリー（図示せず）等が設けられており、液体流路部２０４２の検出部や、後で説明するＩ／Ｏ論理回路などと接続され、各種測定に対応したバルブコントロールや、測定データの処理や、出入力部の制御等が可能となっている。また、駆動分析処理部２４０３は、実施の形態４で説明した２１０２層や実施の形態５で説明した２２０３層を用いて構成することができる。ただし、当実施形態では、独立して使用できるため、ＣＰＵ及びデータ記憶部が設けられており、各種測定に対応したバルブコントロールや、測定データの処理等が可能となっている。ここで、測定開始時にバルブで流入を停止されていた試薬や試料（サンプル）などのバルブ流入を順次開始し、結果として検出部において検出された被検出物質の量に応じた電気信号をＣＰＵにて処理する。ＣＰＵにて電気信号を処理することにより、被検出物質の量または種類などを特定することができる。そして、次に説明するＣＰＵと接続されたＩ／Ｏ論理回路にデータを出力し、出入力部にて測定結果を表示することができる。 The drive analysis processing unit 2403 can be configured in the same manner as the micro analysis chip described in the above embodiment, and includes a CPU, a memory, a battery (not shown), and the like, and detects the liquid channel unit 2042. Are connected to an I / O logic circuit, etc., which will be described later, and valve control corresponding to various measurements, processing of measurement data, control of an input / output unit, and the like are possible. Further, the drive analysis processing unit 2403 can be configured using the 2102 layer described in the fourth embodiment and the 2203 layer described in the fifth embodiment. However, in this embodiment, since it can be used independently, a CPU and a data storage unit are provided, and valve control corresponding to various measurements, measurement data processing, and the like are possible. Here, the flow of a valve such as a reagent or sample (sample) that has stopped flowing in at the start of measurement is sequentially started, and as a result, an electric signal corresponding to the amount of the substance to be detected detected by the detection unit is sent to the CPU. To process. By processing the electrical signal with the CPU, the amount or type of the substance to be detected can be specified. Then, data can be output to an I / O logic circuit connected to the CPU described below, and the measurement result can be displayed at the input / output unit.
　入出力論理処理部２４０４は、ＣＰＵに接続されたＩ／Ｏ論理回路を有している。Ｉ／Ｏ論理回路に接続する電気接続線は、出入力層の各ボタン又は表示部等と接続されており、ＣＰＵと協働し、Ｉ／Ｏデータを適切に処理することができる。すなわち、表示層で入力された各種データおよび測定開始信号を受けると、液体流路層で検出された試料の非検出物質に応じて出力される電気信号を処理し、被検出物質の量や種類を特定し、出入力層の表示部に当該情報を表示する。 The input / output logic processing unit 2404 has an I / O logic circuit connected to the CPU. An electrical connection line connected to the I / O logic circuit is connected to each button or display unit of the input / output layer and can cooperate with the CPU to appropriately process the I / O data. That is, upon receiving various data and measurement start signals input in the display layer, the electrical signal output according to the non-detected substance of the sample detected in the liquid channel layer is processed, and the amount and type of the detected substance And the information is displayed on the display unit of the input / output layer.
　出入力層２４０５には、各種データ入力用ボタン及び表示部が設けられている。 The input / output layer 2405 is provided with various data input buttons and a display unit.
　表示部には、液晶表示モジュールまたは有機ＥＬ表示モジュール等を用いることができる。これらは、駆動ドライバー回路をＩ／Ｏ論理回路とＣＰＵが協働し駆動することで表示動作を行うことが可能である。表示は数値を表示する形式や、グラフを用いて経時変化と共に表示することもできる。また、陽性・陰性等といった形式で表示することもできる。 A liquid crystal display module or an organic EL display module can be used for the display unit. These can perform a display operation by driving the drive driver circuit in cooperation with the I / O logic circuit and the CPU. The display can also be displayed with a time-dependent change using a numerical value display format or a graph. It can also be displayed in a format such as positive or negative.
　さらに出入力層には図示しないが、外部との入出力を処理する端子、または、無線送受信機を設けることができる。そうすることにより、パソコンやＰＤＡ端末などと接続でき、さらに、ネットワークせつぞくもできるため、双方向の情報のやり取りをすることも可能となる。このように、双方向の情報のやり取りを行なうことにより、測定者の測定結果により得られる健康に関する情報を病院や健康管理センターなどとネットワーク接続し、双方向の情報提供ができるようになるため、高度な医療に直結したアドバイスや診断・治療を測定者は享受でき、医療提供側では豊富な健康情報からの適格な診断・治療が可能となる。 Furthermore, although not shown in the figure, the input / output layer 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, so that bidirectional information exchange is also possible. In this way, by exchanging information in both directions, health information obtained from the measurement results of the measurer can be networked with hospitals and health management centers, etc., so that information can be provided in both directions. The measurer can enjoy advice, diagnosis, and treatment directly related to advanced medical care, and the medical provider can make appropriate diagnosis and treatment from abundant health information.
　本発明は上述した各実施形態に限定されるものではなく、請求項に示した範囲で種々の変更が可能であり、異なる実施形態にそれぞれ開示された技術的手段を適宜組み合わせて得られる実施形態についても本発明の技術的範囲に含まれる。 The present invention is not limited to the above-described embodiments, and various modifications are possible within the scope shown in the claims, and embodiments obtained by appropriately combining technical means disclosed in different embodiments. Is also included in the technical scope of the present invention.
　以上説明したように、本発明によると、外部動力を必要とすることなく、吸収体と断面積の小さい流路を用いるという簡便な手法で、チップ内の液体を移送することができる。このような送液構造体は、抗原の分析に用いるマイクロ分析チップ等として応用が可能であり、産業上の意義は大きい。 As described above, according to the present invention, the liquid in the chip can be transferred by a simple method using an absorber and a channel having a small cross-sectional area without requiring external power. Such a liquid-feeding structure can be applied as a micro-analysis chip or the like used for antigen analysis and has great industrial significance.

Claims (7)

  1. 　外部に開放された開放孔に接続された第１流路と、
    　前記第１流路に連続する液溜め部と、
    　前記液溜め部に連続する第２流路と、
    　前記第２流路の終端に直接接する吸収体と、
    　を少なくとも備え、
    　前記第１流路における液体に発生する表面張力による圧力をＰ１とし、
    　前記第２流路における液体に発生する表面張力による圧力をＰ２とし、
    　前記液溜め部における液体に発生する表面張力による圧力をＰ３とするとき、
    　Ｐ３＜Ｐ１≦Ｐ２が成立する、
    　ことを特徴とする送液構造体。     A first flow path connected to an open hole opened to the outside;
    A liquid reservoir continuous with the first flow path;
    A second flow path continuing to the liquid reservoir;
    An absorber in direct contact with the end of the second flow path;
    Comprising at least
    The pressure due to the surface tension generated in the liquid in the first channel is P1,
    The pressure due to the surface tension generated in the liquid in the second flow path is P2,
    When the pressure due to the surface tension generated in the liquid in the liquid reservoir is P3,
    P3 <P1 ≦ P2 holds,
    A liquid delivery structure characterized by the above.
  2. 　外部に開放された開放孔に接続された第１流路と、
    　前記第１流路に連続する液溜め部と、
    　前記液溜め部に連続する第２流路と、
    　前記第２流路の終端に直接接する吸収体と、
    　を少なくとも備え、
    　前記第１流路および前記第２流路は液体との接触面が親水性であって、
    　前記第１流路の向かい合う壁面間の最小距離をＤ１とし、
    　前記第２流路の向かい合う壁面間の最小距離をＤ２とし、
    　前記液溜め部の向かい合う壁面間の最小距離をＤ３とするとき、
    　Ｄ２≦Ｄ１＜Ｄ３が成立する、
    　ことを特徴とする送液構造体。     A first flow path connected to an open hole opened to the outside;
    A liquid reservoir continuous with the first flow path;
    A second flow path continuing to the liquid reservoir;
    An absorber in direct contact with the end of the second flow path;
    Comprising at least
    The first flow path and the second flow path are hydrophilic in contact surface with the liquid,
    The minimum distance between the opposing wall surfaces of the first flow path is D1,
    The minimum distance between the opposing wall surfaces of the second flow path is D2,
    When the minimum distance between the opposite wall surfaces of the liquid reservoir is D3,
    D2 ≦ D1 <D3 holds,
    A liquid delivery structure characterized by the above.
  3. 　請求項１に記載の送液構造体において、
    　前記第１流路および前記第２流路は液体との接触面が親水性であって、
    　前記第１流路の向かい合う壁面間の最小距離をＤ１とし、
    　前記第２流路の向かい合う壁面間の最小距離をＤ２とし、
    　前記液溜め部の向かい合う壁面間の最小距離をＤ３とするとき、
    　Ｄ２≦Ｄ１＜Ｄ３が成立する、
    　ことを特徴とする送液構造体。     In the liquid feeding structure according to claim 1,
    The first flow path and the second flow path are hydrophilic in contact surface with the liquid,
    The minimum distance between the opposing wall surfaces of the first flow path is D1,
    The minimum distance between the opposing wall surfaces of the second flow path is D2,
    When the minimum distance between the opposite wall surfaces of the liquid reservoir is D3,
    D2 ≦ D1 <D3 holds,
    A liquid-feeding structure characterized by that.
  4. 　請求項１乃至３いずれかに記載の送液構造体において、
    　前記第１流路を２以上有する、
    　ことを特徴とする送液構造体。     In the liquid feeding structure in any one of Claims 1 thru | or 3,
    Having two or more first flow paths,
    A liquid-feeding structure characterized by that.
  5. 　請求項１に記載の送液構造体において、
    　前記第１流路の上流側に設けられた第２の液溜め部と、
    　前記第２の液溜め部の上流側に設けられた第３流路と、をさらに備え、
    　前記第３流路における液体に発生する表面張力による圧力をＰ４とし、
    　前記第２の液溜め部における液体に発生する表面張力による圧力をＰ５とするとき、
    　Ｐ５＜Ｐ４≦Ｐ２が成立し、
    　前記第３流路、前記第２の液溜め部、前記第１流路、前記液溜め部、前記第２流路が直列に並んでいる、
    　ことを特徴とする送液構造体。     In the liquid feeding structure according to claim 1,
    A second liquid reservoir provided on the upstream side of the first flow path;
    A third flow path provided on the upstream side of the second liquid reservoir, and
    The pressure due to the surface tension generated in the liquid in the third flow path is P4,
    When the pressure due to the surface tension generated in the liquid in the second liquid reservoir is P5,
    P5 <P4 ≦ P2 holds,
    The third flow path, the second liquid reservoir, the first flow path, the liquid reservoir, and the second flow path are arranged in series.
    A liquid-feeding structure characterized by that.
  6. 　請求項２又は３に記載の送液構造体において、
    　前記第１流路の上流側に設けられた第２の液溜め部と、
    　前記第２の液溜め部の上流側に設けられた第３流路と、をさらに備え、
    　前記第３流路の向かい合う壁面間の最小距離をＤ４とし、
    　前記第２の液溜め部の向かい合う壁面間の最小距離をＤ５とするとき、
    　Ｄ２≦Ｄ４＜Ｄ５が成立し、
    　前記第３流路、前記第２の液溜め部、前記第１流路、前記液溜め部、前記第２流路が直列に並んでいる、
    　ことを特徴とする送液構造体。     In the liquid feeding structure according to claim 2 or 3,
    A second liquid reservoir provided on the upstream side of the first flow path;
    A third flow path provided on the upstream side of the second liquid reservoir, and
    The minimum distance between the opposing wall surfaces of the third flow path is D4,
    When the minimum distance between the opposing wall surfaces of the second liquid reservoir is D5,
    D2 ≦ D4 <D5 holds,
    The third flow path, the second liquid reservoir, the first flow path, the liquid reservoir, and the second flow path are arranged in series.
    A liquid-feeding structure characterized by that.
  7. 　請求項１乃至６に記載の送液構造体を有することを特徴とするマイクロ分析チップ。 A microanalysis chip comprising the liquid feeding structure according to claim 1.
PCT/JP2009/053283 2008-02-26 2009-02-24 Liquid supply structure and micro-analysis chip using the same WO2009107608A1 (en)

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