WO2008004550A1 - analyseur de liquide - Google Patents

analyseur de liquide Download PDF

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Publication number
WO2008004550A1
WO2008004550A1 PCT/JP2007/063303 JP2007063303W WO2008004550A1 WO 2008004550 A1 WO2008004550 A1 WO 2008004550A1 JP 2007063303 W JP2007063303 W JP 2007063303W WO 2008004550 A1 WO2008004550 A1 WO 2008004550A1
Authority
WO
WIPO (PCT)
Prior art keywords
liquid
transported
flow
electrode
capturing means
Prior art date
Application number
PCT/JP2007/063303
Other languages
English (en)
Japanese (ja)
Inventor
Kunio Harada
Sakuichiro Adachi
Hideo Enoki
Hironobu Yamakawa
Nobuhiro Tsukada
Original Assignee
Hitachi High-Technologies Corporation
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Hitachi High-Technologies Corporation filed Critical Hitachi High-Technologies Corporation
Priority to JP2008523689A priority Critical patent/JP4651715B2/ja
Publication of WO2008004550A1 publication Critical patent/WO2008004550A1/fr

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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502769—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by multiphase flow arrangements
    • B01L3/502784—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by multiphase flow arrangements specially adapted for droplet or plug flow, e.g. digital microfluidics
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F25/00—Flow mixers; Mixers for falling materials, e.g. solid particles
    • B01F25/40—Static mixers
    • B01F25/42—Static mixers in which the mixing is affected by moving the components jointly in changing directions, e.g. in tubes provided with baffles or obstructions
    • B01F25/43—Mixing tubes, e.g. wherein the material is moved in a radial or partly reversed direction
    • B01F25/431—Straight mixing tubes with baffles or obstructions that do not cause substantial pressure drop; Baffles therefor
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F25/00—Flow mixers; Mixers for falling materials, e.g. solid particles
    • B01F25/40—Static mixers
    • B01F25/42—Static mixers in which the mixing is affected by moving the components jointly in changing directions, e.g. in tubes provided with baffles or obstructions
    • B01F25/43—Mixing tubes, e.g. wherein the material is moved in a radial or partly reversed direction
    • B01F25/431—Straight mixing tubes with baffles or obstructions that do not cause substantial pressure drop; Baffles therefor
    • B01F25/4317—Profiled elements, e.g. profiled blades, bars, pillars, columns or chevrons
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F25/00—Flow mixers; Mixers for falling materials, e.g. solid particles
    • B01F25/40—Static mixers
    • B01F25/42—Static mixers in which the mixing is affected by moving the components jointly in changing directions, e.g. in tubes provided with baffles or obstructions
    • B01F25/43—Mixing tubes, e.g. wherein the material is moved in a radial or partly reversed direction
    • B01F25/431—Straight mixing tubes with baffles or obstructions that do not cause substantial pressure drop; Baffles therefor
    • B01F25/43197—Straight mixing tubes with baffles or obstructions that do not cause substantial pressure drop; Baffles therefor characterised by the mounting of the baffles or obstructions
    • B01F25/431971—Mounted on the wall
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F33/00—Other mixers; Mixing plants; Combinations of mixers
    • B01F33/30—Micromixers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0673—Handling of plugs of fluid surrounded by immiscible fluid
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0627—Sensor or part of a sensor is integrated
    • B01L2300/0636—Integrated biosensor, microarrays
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0816—Cards, e.g. flat sample carriers usually with flow in two horizontal directions
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0415—Moving fluids with specific forces or mechanical means specific forces electrical forces, e.g. electrokinetic

Definitions

  • the present invention relates to an analyzer that detects the amount of a component contained in a sample.
  • the present invention relates to analysis techniques with very small samples.
  • a sample and a reagent are conventionally dispensed into a plastic or glass reaction container, and the mixture is mixed to irradiate light into a sample solution to measure the amount of components. It was. However, in recent years, a small amount of sample solution used for analysis has been demanded in order to reduce reagent costs and environmental burden.
  • Patent Document 1 As a method for transporting a very small amount of liquid, there is a technique for controlling the propagation of the liquid by injecting oil segmented with the liquid into the microchannel (for example, Patent Document 1). In addition, there is a technique for preventing mixing of an aqueous solution sample by introducing an immiscible liquid segment, an air segment, and a sample segment into a conduit using a piston or the like (for example, Patent Document 2). Furthermore, there is a technique for introducing a droplet into a hydrophobic liquid and electrostatically inducing the droplet to sort the droplet (for example, Patent Document 3).
  • Patent Document 4 Japanese Patent Application Laid-Open No. 2003-200041
  • Patent Document 2 U.S. Pat.No. 4,259,291
  • Patent Document 3 Japanese Patent Laid-Open No. 2005-37346
  • Patent Document 4 U.S. Pat.No. 4,390,403
  • the object of the present invention is to accurately transport a minute liquid and to accurately capture a sample or the like at a measurement position for analysis.
  • the liquid capturing means is used when the micro liquid is driven by the flow of the transport medium and the micro liquid is stopped at a desired position.
  • the liquid analyzer includes an introduction port for introducing the liquid to be transported, a medium flow generating section that generates a circulation flow for the transport medium for transporting the liquid to be transported, and the transported liquid.
  • a measuring unit that measures the liquid to be transported, and the transport liquid capturing means has a maximum width in a plane substantially perpendicular to the flow direction of the transport medium, and the transport of the flow path. Maximum width in a plane substantially perpendicular to the flow direction of the working medium It is characterized by Richi / J.
  • the liquid analysis method includes a first step of introducing the first transported liquid from the introduction port, and a first process of transporting the first transported liquid in the flow path by the flow of the transport medium.
  • One of the first transported liquid and the second transported liquid and the one captured by the transported liquid capturing means is brought into contact with the other transported liquid.
  • the micro liquid is transported by the flow of the transport medium, it is possible to reliably transport the micro liquid regardless of the difference in liquid properties. Further, when performing analysis and detection while transporting a sample, it is possible to determine the position by capturing a micro liquid such as a sample without stagnation of the flow of the transport medium. Thus, analysis and detection can be performed in parallel while transporting a plurality of micro liquids in parallel.
  • FIG. 1 to 6 are schematic views showing the configuration of the liquid analyzer
  • FIG. 1 is a plan view seen through the second substrate 5
  • FIG. 2 is taken along the line AA in FIG.
  • Fig. 3 is a cross-sectional view from the front side
  • Fig. 3 is a cross-sectional view from the side along B-B in Fig. 1
  • Fig. 4 is a cross-sectional view from the plane side along CC in Fig. 2.
  • FIG. 5 is a three-dimensional view of the whole
  • FIG. 6 is a three-dimensional view of the components shown in FIG.
  • the liquid analyzer in the present embodiment mainly includes the first substrate 1, the outer spacer 2, the inner spacer 3, the stirring mechanism 4, the second substrate 5, and the introduction port from the lower side.
  • Cylinder 6, medium flow generation unit 7, transported liquid recovery unit frame It consists of 8 parts, and after lamination, it is joined so that the liquid to be transported and the transport medium do not leak from the internal space.
  • the stirring mechanism 4 in the present embodiment represents structures (fins) for deforming and bonding the transported liquid side by side.
  • An agitation mechanism such as an ultrasonic agitation mechanism, a screw mechanism, or a mechanism that rotates a member such as a spatula may be used.
  • the medium flow generation unit 7 generates a liquid flow for a transfer medium for transferring a sample or the like. It is a part that has a pump or waterwheel-like member inside that discharges the medium taken in from one end and discharges it from the other end, and circulates in the medium, and the principle for generating the flow is not questioned.
  • the flow rate may be controllable according to the flow load.
  • the first substrate 1 has a transported liquid capturing means 9 for capturing a transported liquid such as a sample and a waste liquid capturing means 10 for capturing a waste liquid.
  • the transported liquid catching means 9 is arranged downstream of the introduction port cylinder (introduction port) 6 in the flow direction of the transport medium when the medium flow generation unit is regarded as the starting point in the flow direction of the transport medium.
  • the first substrate 1 and the second substrate 5 are made of a material that transmits light of a necessary wavelength for liquid transportation described later and detection of the amount of components contained in the sample. Only the portion of the substrate 1 and the second substrate 5 corresponding to the position of the transported liquid capturing means 9 may be a material that transmits light. Further, the transported liquid capturing means 9 is composed of an electrode, an electret region, or a combination of an electret region and an electrode, and is similar to the first substrate 1 and the second substrate 5. A material that transmits light is used. In the first embodiment, an example in which an electrode is used for the transported liquid capturing means 9 will be described. Therefore, the electrode is patterned on all the positions of the transported liquid capturing means 9 on the upper surface of the first substrate 1 shown in FIG.
  • insulating film of about 1 ⁇ m force and about 100 ⁇ m, and the surface of the insulating film is treated with water repellent treatment.
  • insulator material fluorine-based resin, SiO (quartz), SiN, Al 2 O (alumina), HfO are used.
  • Electrode materials include ITO, SnO, ZnO, ZnO + AlO + GaO.
  • Each electrode is arranged independently
  • each electrode is connected like the electrode 11 shown in FIG. 7, and is patterned so as to have the same potential.
  • the surface of the second substrate 5 shown in FIG. The counter electrode 12 is provided on the part of the electrode facing position or on the surface including all of the electrodes, and the surface is covered with an insulating film of about 0 .: L m to 100 m like the electrode, and further the insulating film The surface is treated with water repellency.
  • the counter electrode 12 that does not require the counter electrode 12 is not used, the liquid to be transported can be controlled with a simple configuration using only the electrode on the first substrate.
  • the drawing is simplified for easy folding, and the electrode and the counter electrode 12 are illustrated as being embedded in the first substrate 1 and the second substrate 5, respectively.
  • the configuration of the electrode of this example is patterned so that the electrode has the same potential as described above.
  • substantially only a pair of the electrode and the counter electrode 12 is provided.
  • one substrate is provided with an electrode group that is a plurality of separated electrodes that are turned on and off in synchronization by being supplied with the same potential, and the other substrate is connected to the electrode group.
  • Opposing electrodes are provided, and the electrode group and the opposing electrode form a pair of electrode groups.
  • the flow path 13 is a space 16 having a substantially rectangular cross section in the direction perpendicular to the flow except for the transported liquid recovery part 14 and the inlet 15.
  • a portion of the space 16 in the flow path 13 used for analysis and / or detection of the liquid to be transported is shown as an analysis region 17 in FIG.
  • the width W and height H, which are dimensions of a substantially rectangular cross section in the direction perpendicular to the flow, of the flow path 13 in the analysis region 17 are as shown in FIG.
  • the flow path of the liquid analyzer is filled with a transport medium in advance. (Filling of the transport medium 18 can be performed from the waste liquid port, for example, using the waste liquid port as the transport medium inlet / outlet port.) At that time, in order not to leave bubbles in the flow path 13, The flow path 13 and the medium flow generation section 7 are filled with the transfer medium 18 so that bubbles do not enter the flow path 13 after the flow is generated in the transfer medium 18 by the generation section 7.
  • the transported liquid capture means 9 is closer to the transport medium 18 than the liquid level. It is introduced so that the liquid level of the transport medium 18 in the transported liquid recovery unit 14 which is not located is the top.
  • the gas phase region that is not filled with the transport medium 18 and is in contact with the transport medium 18 may remain. Thereby, when bubbles are mixed at the time of introduction, the bubbles can be removed by letting gas escape to the gas phase region.
  • the transport medium to be used is silicone oil or fluorine-based oil or the like, which is a liquid having a dielectric constant lower than that of the transported liquid and does not react with the transported liquid. Thereafter, the medium flow generator 7 is driven to generate a flow as indicated by an arrow in FIG. The speed of the flow is a force that varies depending on the reaction time and measurement time at the time of analysis.
  • 8A to 8D are enlarged views of the introduction port and a part of the transported liquid capturing means 9 of FIG. 2, and the steps from the introduction of the sample and the reagent to the mixing are arranged in chronological order and are represented by a plurality of diagrams. .
  • the switch (voltage application control means) 19 is turned on, and a voltage is applied between the electrode 11 that is the transported liquid capturing means 9 and the counter electrode 12.
  • the first transported liquid 20 as the sample to be analyzed is introduced into the flow path 13 in the analysis region 17 from the inlet 15 using a pipetter (introducing means) 21 or the like.
  • the introduced first transported liquid 20 is attracted by the force of the force electrode 11 caused by the flow of the transport medium 18 and is captured on the electrode 11 as the transported liquid capturing means 9 as shown in FIG. 8B.
  • the second transported liquid 22, which is a reagent for analyzing the first transported liquid 20, is transferred from the inlet 15 to the analysis region 17 using a pipetter 21 or the like. Introduce into the channel 13.
  • the introduced second transported liquid 22 is caused to flow by the flow of the transport medium 18, but “is attracted by the electrostatic force of the electrode 11 and is captured by the electrode 11 as the transported liquid capturing means 9 as shown in FIG. 8D.
  • Mix with the first transported liquid 20 that has already been captured, where the pipettor for introducing the sample and the pipetter for introducing the reagent may be the same or different. Note that the order of introduction of the first transported liquid and the second transported liquid may be shifted first.
  • FIG. 9A and 9B are enlarged views of the introduction port and a part of the transported liquid capturing means 9 in FIG. 2, and the processes from mixing of the sample and reagent to analysis are arranged in time series and expressed in multiple diagrams. Speak.
  • the switch 19 is turned off, and the voltage applied between the electrode 1 1-1 as the transported liquid capturing means 9-1 and the counter electrode 12 is released and the electrode is released.
  • a voltage is again applied between the electrode 11-2 which is the transported liquid capturing means 9-2 and the counter electrode 12.
  • the first transported liquid 20 and the second transported liquid 22 are caused to flow by the flow of the transport medium 18, and are stirred by being subjected to physical deformation through the stirring mechanism 4 to become the reaction liquid 23.
  • the first transported liquid 20 and the second transported liquid 22 are attracted by the electrostatic force of the electrode 11-2, and as shown in FIG. 9B, the second transported liquid capturing means 9-2 Captured on some electrode 11-2.
  • a light source 25 and a light receiving unit 26 are arranged corresponding to the second transported liquid capturing means 9-2 and the positions corresponding to the transported liquid capturing means 9 subsequent to the second transported liquid capturing means 9-2.
  • the measurement light 27 is irradiated from the light source 25 through the second substrate 5, the reaction solution 23, and the first substrate 1, and is detected by the light receiving unit 26.
  • the components of the reaction solution 23 are analyzed, and as a result, the amount of the specific component contained in the first transported liquid 20 that is the sample to be analyzed is measured. can do.
  • the reaction results are measured by measuring the reaction proceeding in the reaction solution 23 over time, and finally determining the amount of the components. Then, in order to supply samples and reagents one after another into the liquid analyzer and sequentially analyze the components, switch 19 is repeatedly turned on and off, and reaction solution 23 is moved between the measurement units one after the other to measure. Do. As a result, multiple sample measurements can be performed in parallel, improving the throughput of the apparatus. At that time, when the reaction liquid 23 is present in each of the plurality of transported liquid capturing means 9, the electrode 11 is electrically integrated, so that the switches are turned off all at once, depending on the location of the flow path in the analysis region 17.
  • reaction liquids cannot be separated from the transported liquid capturing means 9 at the same time due to the difference in flow velocity.
  • a voltage is applied to the transported liquid capturing means 9 after the switch is turned off and all the reaction liquids 23 are separated, the timing at which each reaction liquid 23 is separated or each reaction liquid 23 is subjected to the next reaction. Even if the timing of reaching the transport liquid capturing means 9 is different, each reaction liquid can be reliably moved and captured.
  • FIGS. 10A to 10D are enlarged views of the display orientation of FIG. 3 returned to the horizontal direction.
  • the reaction liquid 23 for which the measurement has been completed is released from the capture of the last transported liquid capturing means 9 and is flowed to the position of FIG. 10A by the flow of the transport medium 18.
  • the height of the transported liquid recovery unit 14 is larger than the height H of the flow path 13, so that the first substrate 1 and the second substrate 5 are sandwiched until then.
  • the reaction liquid 23 becomes the waste liquid 28 in principle.
  • the diameter d of the waste liquid 28 that has been crushed into a disk shape and released into a spherical shape is larger than the height H, which is the gap between the first substrate 1 and the second substrate 5, so that the flow path 13 is closed. None enter the space 16 again. If the waste liquid 28 has a specific gravity smaller than that of the transport medium 18, it floats up in the transported liquid recovery unit 14, and is collected by suction with a sipper 29 or the like as shown in FIG. 10C.
  • the waste liquid 28 If the waste liquid 28 has a specific gravity greater than that of the transport medium 18, it will settle in the transported liquid recovery section 14, and is collected by suction with a sipper (collection means) 29 as shown in FIG. 10D.
  • a sipper (collection means) 29 When the waste liquid 28 has a specific gravity greater than that of the transport medium 18 and precipitates, a plurality of waste liquids 28 are collected into a large lump, and the closed space of the flow path 13 that is the gap between the first substrate 1 and the second substrate 5 Since there is a possibility of re-entering 16, it is preferable to provide a sedimentation portion 30 that is a depression region as shown in FIG. 10D.
  • the waste liquid trapping means 10 is for increasing the waste liquid trapping effect based on the same principle as the transported liquid trapping means 9 and is provided at a location on the top surface of the first substrate 1 where the transported liquid recovery unit 14 is located. It is In the case where an electrode is used for the waste liquid capturing means 10, the waste liquid is optically disposed by providing a measuring portion (not shown) similar to the above at a position corresponding to the waste liquid capturing means 10 with light transmission. It is possible to detect the amount.
  • FIG. 11 shows an enlarged part of the analysis region 17 in FIG.
  • the width X of the transported liquid capturing means 9 is smaller than W with respect to the width W of the flow path 13 in the analysis region 17, that is, W> X. Yes.
  • the maximum width of the transported liquid capturing means 9 is smaller than the maximum width of the flow path 13 in a plane substantially perpendicular to the direction of the transport medium flow. This is to prevent the transported liquid from blocking the flow path 13 when the transported liquid is captured by the transported liquid capturing means 9.
  • the liquid to be transported that has entered the flow path 13 in the analysis area 17 is sandwiched between the first substrate 1 and the second substrate 5. It is crushed into a disk with a diameter of D and a height of H.
  • the diameter D of the liquid to be transported is equal to the diameter D of the first liquid to be transported 20 which is a sample to be analyzed and the diameter D of the second liquid to be transported 22 which is a reagent.
  • the diameter D of the reaction liquid 23 after mixing and stirring the first transported liquid 20 and the second transported liquid 22 that are smaller than the width X of the liquid 13 and the width of the flow path 13 It is set to be smaller than W. That is, the maximum width of the reaction solution 23 is smaller than the maximum width of the flow path 13 on a surface substantially perpendicular to the direction of the flow of the transfer medium.
  • the width X of the transported liquid capturing means 9 is larger than the width W of the flow path 13 in the analysis region 17, if the diameter D of the transported liquid is small, the transported liquid stagnates on the spot. However, since the transport medium flows from the side, the transport medium does not stagnate. However, in this case, the transported liquid moves within the width X of the transported liquid capturing means 9, and the position in the width X direction is not fixed. Therefore, the measurement light 27 is not reliably irradiated to the reaction solution 23 at the measurement position, and the analysis accuracy is lowered.
  • the diameter D of the liquid to be transported is smaller than the width X of the liquid transport capturing means 9, the location is not fixed as described above.
  • the diameter D is smaller than the width X of the transported liquid capturing means 9.
  • its diameter D is set to be approximately the same as width X, and the first transported liquid captures the transported liquid. As long as it is on the means 9, the second liquid to be transported can come into contact with the first liquid to be mixed.
  • the transport medium is circulated inside the apparatus, and the liquid to be transported is transported in the circulation flow, thereby mixing with the reagent to be analyzed, stirring, moving to the measuring section, and collecting section. It is possible to automate the movement to a high speed with a simple configuration.
  • Example 2 In this embodiment, an electrode is used for the transported liquid capturing means 9 in the first embodiment, whereas an electret insulator is used for the transported liquid capturing means 9.
  • a part of the insulating film is an electret region.
  • the configuration in the present embodiment is basically the same as that in the first embodiment except for the wiring such as the electrode 11, the counter electrode 12, and the switch 19 for applying a voltage.
  • the liquid to be transported is captured in the region 31 in which only the range of the transported liquid capturing means 9 as shown in FIG.
  • An electret toy is a state in which a high voltage is applied while heating a polymer material so that the magnetic material is magnetized to the north and south poles, or is charged semipermanently by corona discharge (for example, Non-patent document 1). If electretized areas are used, polarization can be maintained as shown in Fig. 12A without a power supply.
  • the medium flow generation unit 7 The flow rate is controlled by the flow rate control unit, and the flow is temporarily generated so that the attractive force in the flow direction of the medium is captured and temporarily stronger than the electrostatic force.
  • the medium flow rate control unit performs control such as speeding up the rotation of the pump.
  • an electrode, a power source for applying a voltage to the electrode, and a control mechanism for the electrode are not required, so that the structure can be simplified and the cost can be reduced.
  • Non-Patent Document 1 Proceedings of the 9th Japan Power Society Energy Technology Symposium
  • the region where one electret is seen as viewed from the counter electrode and the region occupied by one electrode are arranged so as to at least partially overlap.
  • Example 1 the voltage is continuously applied between the electrode 11 and the counter electrode 12 while the transported liquid is captured, but in this example, as shown in FIG.
  • Example 2 the liquid to be transported is captured in the region where the electret is trapped, and a voltage that temporarily cancels electretization is applied between the electrode 11 and the counter electrode 12 as shown in FIG. 13B. Then, the captured transported liquid is released.
  • each reaction solution cannot be separated from each transported liquid capturing means 9 at the same time due to the difference in flow rate depending on the location of the flow path in the analysis region 17. It is possible. However, if the switch is turned off when the switch is turned on and all the reaction liquids 23 are separated, the next transported liquid capturing means 9 is already in a state where it can capture the reaction liquid 23. Even if the timing at which the reaction solution 23 is separated or the timing at which each reaction solution 23 reaches the next transported liquid capturing means 9 is different, each reaction solution can be reliably moved and captured.
  • the droplets are transported by the oil flow, captured by the electret toy region, and opened by voltage application. It is possible to extend the lifetime of the insulating film disposed on the electrode by reducing the time for applying the voltage to the electrode.
  • FIG. 14 shows an example of this.
  • a plurality of inlets and a plurality of analysis regions 17 are respectively arranged in branch paths that are branches.
  • the difference between this example and Example 1 to Example 3 is that it has a plurality of analysis regions 17 used for analyzing the liquid to be transported. That is.
  • the electrode shape is a force that allows a plurality of objects having the shape shown in FIG. 7 to be provided in the number of the analysis regions 17 as shown in FIG.
  • it may be integrated as shown in Fig. 15B, and parallel analysis may be performed almost simultaneously.
  • the shape of the transported liquid capturing means 9 of the electrode 11 can be round or square.
  • the electrode as in Example 3 may be used, as in Example 2 where an electrode may be used, as in Example 2, or an electret-cut area may be used. Or use a combination of the electret area and the combined area.
  • a plurality of analyzes can be performed in parallel in each of the plurality of regions.
  • the width X of the transported liquid capturing means is larger than W with respect to the width W of the flow path in the analysis region, so that the transported liquid is captured by the transported liquid capturing means.
  • the transported liquid does not block the flow path.
  • the transport medium overflows from the flow path and enters another flow path, disturbing the flow of the transport medium not only in one flow path but also in a plurality of flow paths.
  • FIG. 1 is a plan view showing a configuration of a liquid analyzer according to the present invention.
  • FIG. 2 is a cross-sectional view from the front showing the configuration of the liquid analyzer according to the present invention.
  • FIG. 3 is a cross-sectional view from the side showing the configuration of the liquid analyzer according to the present invention.
  • FIG. 4 is a cross-sectional view from the plane side of the liquid analyzer according to the present invention.
  • FIG. 5 is a three-dimensional view of a liquid analyzer according to the present invention.
  • FIG. 6 is a three-dimensional view showing the components shown in FIG. 5 in an exploded manner.
  • FIG. 7 is a diagram showing only electrodes of the liquid analyzer according to the present invention.
  • FIG. 8A is a partially enlarged view of a part of the transported liquid capturing means from the introduction locus in FIG.
  • FIG. 8B is a partially enlarged view of the introduction locus from FIG. 2 to a part of the transported liquid capturing means.
  • FIG. 2 is a partially enlarged view of the introduction locus of FIG. 2 up to a part of the transported liquid capturing means.
  • the introduction locus in FIG. 2 is also a partially enlarged view of a part of the transported liquid capturing means.
  • FIG. 9 is a partially enlarged view of the introduction locus of FIG. 2 and a part of the transported liquid capturing means.
  • FIG. 9 is a partially enlarged view from the introduction locus of FIG. 2 to a part of the transported liquid capturing means.
  • FIG. 10A is an enlarged view of the display orientation of FIG.
  • FIG. 10B is an enlarged view of the display orientation of FIG.
  • FIG. 10C is an enlarged view of the display orientation of FIG.
  • FIG. 10D is an enlarged view of the display orientation of FIG.
  • FIG. 11 is a partially enlarged view of the analysis region 17 in FIG.
  • [12A] Enlarged view of a cross section using an electretized insulator for the liquid feed capturing means.
  • [12B] An enlarged view of a cross section using an electretized insulator for the liquid feed capturing means.
  • FIG. 13A is an enlarged view of a cross section in which an insulator electretized and an electrode are used in combination for the liquid feed capturing means.
  • FIG. 13B is an enlarged view of a cross section in which an insulator electretized and an electrode are combined in the liquid feeding capturing means.
  • FIG. 14 is a plan view showing the configuration of a liquid analyzer according to the present invention, which is an example having a plurality of analysis regions.
  • [15A] A diagram showing an example of the electrode shape of the liquid analyzer shown in FIG.
  • FIG. 15B A diagram showing an example of the electrode shape of the liquid analyzer shown in FIG.

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  • Chemical & Material Sciences (AREA)
  • Dispersion Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Health & Medical Sciences (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)

Abstract

L'invention concerne un analyseur de liquide dans lequel de fines gouttelettes de liquide sont transportées au moyen d'un écoulement d'un fluide de transport et les fines gouttelettes de liquide sont mélangées/agitées et sont mesurées par une interception en une position souhaitée. Ainsi, les fines gouttelettes de liquide difficiles à transporter peuvent être transportées de façon précise et l'échantillon combiné avec un réactif peut être intercepté et analysé en une position de mesure.
PCT/JP2007/063303 2006-07-05 2007-07-03 analyseur de liquide WO2008004550A1 (fr)

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WO2010143295A1 (fr) * 2009-06-12 2010-12-16 株式会社島津製作所 Procédé d'amplification de gènes à multiples étapes
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