JP6595439B2 - Analysis tools and analysis systems - Google Patents

Description

  The present invention relates to an analysis tool and an analysis system.

  As an index indicating the state of a living body, glycation rates of various proteins are analyzed. Among them, the glycation rate of hemoglobin (Hb) in blood cells, particularly stable HbA1c (hereinafter sometimes abbreviated as “s-HbA1c”) reflects the past history of blood glucose levels in vivo, It is regarded as an important index in the diagnosis and treatment of diabetes. HbA1c is obtained by saccharification of the valine at the N-terminal of the β chain of HbA (α2β2).

  As one of Hb analysis techniques represented by s-HbA1c, electrophoresis is used. Patent Documents 1, 2, 3, 4, and 5 disclose that an additional component is added to the electrophoresis solution for the purpose of optimization of analysis and improvement of accuracy. In particular, Patent Documents 4 and 5 disclose chondroitin sulfate as an example of a component added to the electrophoresis solution. Further, Patent Document 6 describes an analysis method in which a sample is continuously supplied even during sample separation in electrophoresis in order to reduce the size of a chip used for analysis using electrophoresis.

  Blood, which is a representative example of the sample, is a sample derived from a living body. For this reason, for example, when blood collected from a patient is used as a sample, the collected blood can have various properties depending on the patient's medical condition and constitution. In addition, it is almost unclear what kind of analysis-inhibiting factors can be caused by the specific components of the additional components and analysis methods described above. This is the same even when a sample other than blood is used. In order to improve the analysis accuracy, it is preferable that such an analysis inhibiting factor is appropriately removed. However, removal of the analysis-inhibiting factor may affect electrophoresis in a capillary tube, for example.

JP 2006-145537 A Japanese National Publication No. 9-510792 Table 2010/010859 JP 2009-109230 A Table 2008/136321 Table 2008/136465

  The present invention has been conceived under the circumstances described above, and provides an analysis tool and an analysis system capable of performing more stable analysis while appropriately removing an analysis-inhibiting factor. Let that be the issue.

The analysis tool provided by the first aspect of the present invention is an analysis tool used for analyzing a sample by capillary electrophoresis, an introduction tank into which the sample is introduced, a capillary tube connected to the introduction tank , lead before Symbol introduction reservoir and said capillary tube, and a sudden expansion unit cross-sectional area sharply expands, that the pressure variation caused by the surface tension of the liquid which may occur in rapid expansion unit acts on liquid in the capillary tube Pressure fluctuation suppressing means for suppressing.

  In preferable embodiment of this invention, the auxiliary tank which has the said rapid expansion part is further provided.

  In a preferred embodiment of the present invention, a connection flow path for connecting the introduction tank and the sudden expansion portion is provided, and the capillary tube is connected between the introduction tank and the rapid expansion portion. It is connected to.

  In a preferred embodiment of the present invention, the pressure fluctuation suppressing means is a flat body that covers at least a part of the sudden expansion portion and allows gas to pass therethrough.

  In a preferred embodiment of the present invention, a part of the pressure fluctuation suppressing means is fixed to the sudden expansion portion.

  In a preferred embodiment of the present invention, the pressure fluctuation suppressing means is made of a resin that prevents the passage of liquid.

  In a preferred embodiment of the present invention, the flat body has a hydrophilic treatment surface facing the sudden expansion portion.

  In a preferred embodiment of the present invention, the pressure fluctuation suppressing means is made of a porous body that allows liquid to pass through.

  In a preferred embodiment of the present invention, the pressure fluctuation suppressing means is a hydrophilized region on the inner surface of the sudden expansion portion and subjected to a hydrophilization treatment.

  In preferable embodiment of this invention, the said pressure fluctuation suppression means is an open tank connected with the said auxiliary tank through the said connection flow path.

  In a preferred embodiment of the present invention, the auxiliary tank and the open tank are partitioned from each other.

  In a preferred embodiment of the present invention, the auxiliary tank and the open tank are connected to each other.

  In a preferred embodiment of the present invention, it is used as a disposable analysis tool.

  The analysis tool provided by the second aspect of the present invention includes the analysis tool provided by the first aspect of the present invention, and the analysis tool loaded with the analysis tool and performing analysis using electrophoresis in the capillary tube. And an analysis unit for performing.

  According to an aspect of the present invention, the liquid that has reached the sudden expansion portion is suppressed from being subjected to pressure fluctuation caused by surface tension on the capillary tube by the pressure fluctuation suppressing means. Thereby, it is possible to avoid that the liquid in the capillary tube exhibits an unintended movement behavior. Therefore, more stable analysis can be performed while appropriately removing the analysis-inhibiting factors.

  Other features and advantages of the present invention will become more apparent from the detailed description given below with reference to the accompanying drawings.

It is a top view which shows the analysis tool based on 1st Embodiment of this invention. It is sectional drawing which follows the II-II line | wire of FIG. It is sectional drawing which follows the III-III line of FIG. 1 is a system configuration diagram showing an analysis system based on a first embodiment of the present invention. It is a top view which shows the analysis method using the analysis tool of FIG. It is a top view which shows the analysis method using the analysis tool of FIG. It is sectional drawing which follows the VII-VII line of FIG. It is a graph which shows the example of an analysis result by the analysis method using the analysis tool of FIG. It is sectional drawing which shows an example of the analysis method using the analysis tool of a reference example. It is a graph which shows the example of an analysis result by the analysis method using the analysis tool of a reference example. It is a graph which shows the other example of an analysis result by the analysis method using the analysis tool of a reference example. It is sectional drawing which shows the analysis tool based on 2nd Embodiment of this invention. It is a graph which shows the example of an analysis result by the analysis method using the analysis tool of FIG. It is sectional drawing which shows the analysis tool based on 3rd Embodiment of this invention. It is sectional drawing which shows the analysis tool based on 4th Embodiment of this invention. It is a graph which shows the example of an analysis result by the analysis method using the analysis tool of FIG. It is sectional drawing which shows the analysis tool based on 5th Embodiment of this invention. It is a graph which shows the example of an analysis result by the analysis method using the analysis tool of FIG. It is sectional drawing which shows the analysis tool based on 6th Embodiment of this invention. It is a top view which shows the analysis tool based on 7th Embodiment of this invention. It is sectional drawing which follows the XXI-XXI line of FIG. It is a top view which shows the analysis tool based on 8th Embodiment of this invention. It is sectional drawing which follows the XXIII-XXIII line | wire of FIG. It is sectional drawing which shows the analysis tool based on 9th Embodiment of this invention.

  Hereinafter, preferred embodiments of the present invention will be specifically described with reference to the drawings.

  1 to 3 show an analysis tool based on the first embodiment of the present invention, and FIG. 4 shows an analysis system based on the first embodiment of the present invention. The analysis system C of this embodiment includes an analysis device B and an analysis tool A1. The analysis system C is a system that executes an analysis method based on electrophoresis for a sample. The sample is not particularly limited, but in the present embodiment, blood collected from a human body will be described as an example. Of the components contained in the sample, the component to be analyzed is defined as the analysis component.

  Examples of the analysis component include hemoglobin (Hb), albumin (Alb), globulins (α1, α2, β, γ globulins), fibrinogen, and the like. Examples of the hemoglobin include normal hemoglobin (HbA0), glycated hemoglobin, modified hemoglobin, fetal hemoglobin (HbF), and the like. Examples of the glycated hemoglobin include hemoglobin A1a (HbA1a), hemoglobin A1b (HbA1b), hemoglobin A1c (HbA1c), and GHbLys. Examples of the hemoglobin A1c include stable HbA1c (s-HbA1c) and unstable HbA1c. Examples of the modified hemoglobin include carbamylated Hb and acetylated Hb.

  The analysis tool A1 provides a place for analysis of a sample in a state of being loaded in the analysis apparatus B. In this embodiment, the analysis tool A1 is configured as a so-called disposable type analysis chip that is intended to be discarded after one or a specific number of analyses. As shown in FIGS. 1 to 3, the analysis tool A <b> 1 includes a main body 1, an introduction tank 2, a filter member 21, a discharge tank 3, a capillary tube 4, an electrode part 51, an electrode part 52, an auxiliary tank 6, and a communication channel 7. And a flat body 81. FIG. 1 is a plan view of the analysis tool A1. 2 is a cross-sectional view taken along line II-II in FIG. 3 is a cross-sectional view taken along line III-III in FIG.

  The main body 1 is a base of the analytical tool A1, and the material thereof is not particularly limited, and examples thereof include glass, fused silica, and plastic. In the present embodiment, the main body 1 has a configuration in which the upper base material 11 and the lower base material 12 are coupled to each other, but the main body 1 may be integrally formed.

  The introduction tank 2 is a tank into which a liquid containing a sample is introduced. In the present embodiment, the introduction tank 2 is formed on the upper base material 11 of the main body 1. Examples of the liquid containing the sample include a diluted specimen in which a sample such as blood is diluted with a predetermined diluent. This dilution may be executed by a tank (not shown) provided in the analysis tool A1, or may be executed by an analyzer B described later.

  The filter member 21 allows the liquid introduced into the introduction tank 2 to pass therethrough, and removes an analysis inhibiting factor contained in the liquid as in an example described later. In the present embodiment, the filter member 21 is provided at the bottom of the introduction tank 2. The specific configuration of the filter member 21 is not limited as long as it can appropriately remove the analysis-inhibiting factors. As a suitable example, for example, a cellulose acetate membrane filter (ADVANTEC, model Y100, thickness 95 μm) Can be mentioned.

  The discharge tank 3 is a tank located on the downstream side of the electroosmotic flow in the electrophoresis method. The discharge tank 3 is constituted by, for example, a through hole formed in the upper base material 11 of the main body 1.

  The capillary tube 4 connects the introduction tank 2 and the discharge tank 3 and is a place where an electroosmotic flow is generated in the electrophoresis method. The capillary tube 4 is constituted by, for example, a groove formed in the lower base 12 of the main body 1. The main body 1 may be formed with a recess or the like for accelerating light irradiation to the capillary tube 4 and emission of light transmitted through the capillary tube 4. The size of the capillary tube 4 is not particularly limited. For example, the capillary tube 4 has a width of 25 μm to 100 μm, a depth of 25 μm to 100 μm, and a length of 5 mm to 150 mm. The overall size of the analysis tool A1 is appropriately set according to the size of the capillary tube 4, the size and arrangement of the introduction tank 2, the discharge tank 3, the auxiliary tank 6, and the like.

The electrode part 51 and the electrode part 52 are for applying a voltage necessary for the electrophoresis method to the capillary tube 4 by conducting with the analyzer B. The electrode part 51 is provided on the same side as the introduction tank 2 with respect to the capillary tube 4. The electrode part 52 is provided on the same side as the discharge tank 3 with respect to the capillary tube 4. The specific configuration of the electrode unit 51 and the electrode unit 52 is not particularly limited as long as the electrode unit 51 and the electrode unit 52 are configured to apply a voltage to the liquid in the capillary tube 4 while being electrically connected to the analyzer B. In this embodiment, a case where a metal pipe is provided in the flow path will be described as an example. The flow path of the electrode part 51 is connected to the introduction tank 2, and the flow path of the electrode part 52 is connected to the discharge tank 3. An electrode or the like (not shown) of the analyzer B is in contact with the outside of the metal tube, and a liquid is in contact with the inner surface of the metal tube. In addition, as another example of the electrode part 51 and the electrode part 52, the tank etc. (illustration omitted) of the analyzer B may be inserted, and this electrode and the liquid may contact.

  The auxiliary tank 6 is a tank that is connected to the introduction tank 2 and the capillary tube 4 and has a rapid expansion portion 61. In the present embodiment, the auxiliary tank 6 is formed on the upper base material 11 of the main body 1. The sudden enlargement portion 61 is a portion where the cross-sectional area is steeply enlarged from the introduction tank 2 side toward the opening portion of the auxiliary tank 6. The steeply enlarged cross-sectional area of the rapidly expanding portion 61 means that a surface tension that causes a pressure fluctuation that can affect the behavior of the liquid in the capillary tube 4 can be generated in the analysis method described later. Say.

  The communication channel 7 is a channel that connects the introduction tank 2 and the auxiliary tank 6. In the present embodiment, the communication flow path 7 is configured by a groove provided in the upper base material 11 of the main body 1. Further, the capillary tube 4 is connected to the communication channel 7 between the introduction tank 2 and the discharge tank 3.

  The flat body 81 is an example of the pressure fluctuation suppressing means referred to in the present invention. The pressure fluctuation suppression means functions to suppress the pressure fluctuation caused by the surface tension of the liquid that may occur in the sudden expansion portion 61 from acting on the liquid in the capillary tube 4. In the present embodiment, the flat body 81 is a flat member in which the depth direction of the auxiliary tank 6 coincides with the thickness direction. Moreover, in this embodiment, the flat body 81 consists of resin which blocks | prevents passage of a liquid. An example of the resin is a PET resin. In the present embodiment, the flat body 81 is formed of a PET film (manufactured by Fujimori Kogyo Co., Ltd., model TCP188, thickness 188 μm). Moreover, in this embodiment, the flat body 81 is mounted in the aspect which plugs up the communication flow path 7 which leads to the auxiliary tank 6, and is not fixed to the auxiliary tank 6.

  In addition, the flat body 81 of the present embodiment has a hydrophilic treatment surface 812. The hydrophilic treatment surface 812 is a surface on which one surface of the flat body 81 is subjected to a hydrophilic treatment. The hydrophilic treatment surface 812 faces the rapid enlargement portion 61.

  The analyzer B is an apparatus that performs analysis by electrophoresis by loading the analysis tool A1. The analyzer B includes an electrode 91, an electrode 92, a light emitting unit 931, a light receiving unit 932, an introduction nozzle 94, a pressure nozzle 95, a pressure nozzle 96, a pump 97, a control unit 98, a diluting solution tank 991, and an electrophoresis solution tank 992. Yes. FIG. 4 schematically shows the components of the analyzer B for the sake of easy understanding.

  The electrode 91 and the electrode 92 are for applying a predetermined voltage to the capillary tube 4 in the electrophoresis method. The electrode 91 of this embodiment applies a voltage by contacting the electrode part 51 of the analysis tool A1. The electrode 92 applies a voltage by contacting the electrode part 52 of the analysis tool A1. Although the voltage applied to the electrode 91 and the electrode 92 is not specifically limited, For example, it is 0.5 kV-20 kV. For example, the electrode 91 and the electrode 92 are configured to freely move toward and away from the analysis tool A1 from a predetermined direction.

The light emitting unit 931 is a part that emits light for measuring absorbance in electrophoresis. The light emitting unit 931 includes an optical filter and a lens, such as an LED chip that emits light in a predetermined wavelength range. This optical filter attenuates light of a predetermined wavelength out of light from an LED chip or the like, and transmits light of other wavelengths. The lens is for condensing the light transmitted through the optical filter onto the analysis site of the capillary tube 4 of the analysis tool A1. Moreover, the light emission part 931 may comprise the slit. The slit is for removing excess light that may cause scattering or the like from the light collected by the optical filter.

  The light receiving unit 932 receives light transmitted through the analysis portion of the capillary tube 4 of the analysis tool A1, and includes, for example, a photodiode or a photo IC.

  The diluent tank 991 is a tank in which the diluent Ld is stored. The diluent Ld is for diluting the sample to a concentration suitable for analysis. Moreover, in this embodiment, the additional component for removing the analysis inhibition factor mentioned later is added to the dilution liquid Ld. The main agent of such diluent Ld is not particularly limited, and examples thereof include water and physiological saline. Preferred examples include liquids having components similar to electrophoresis solution Lm described later. Further, the diluent Ld is obtained by adding a cathodic group-containing compound to the main agent. The anionic group-containing compound is, for example, an anionic group-containing polysaccharide. The anionic group-containing polysaccharide is, for example, at least one polysaccharide selected from the group consisting of sulfated polysaccharides, carboxylated polysaccharides, sulfonated polysaccharides and phosphorylated polysaccharides. The carboxylated polysaccharide is preferably alginic acid or a salt thereof (for example, sodium alginate). The sulfated polysaccharide is, for example, chondroitin sulfate. There are seven types of chondroitin sulfate, A, B, C, D, E, H, and K, and any of them may be used. In the following description, the case where the diluted solution Ld is obtained by adding chondroitin sulfate to the main component, which is the same component as the electrophoresis solution Lm, will be described. The concentration of the anionic group-containing compound (chondroitin sulfate) is, for example, in the range of 0.01 to 5% by weight.

  The electrophoretic liquid tank 992 is a tank in which the electrophoretic liquid Lm is stored. The electrophoretic liquid Lm is a liquid for constituting a field where the electrophoresis method can be realized by filling the capillary tube 4 and the like. Such an electrophoretic solution Lm is not particularly limited, but is preferably one using an acid. Examples of the acid include citric acid, maleic acid, tartaric acid, succinic acid, fumaric acid, phthalic acid, malonic acid, and malic acid. Moreover, it is preferable that the electrophoresis solution Lm contains a weak base. Examples of the weak base include arginine, lysine, histidine, and tris. The pH of the electrophoresis solution Lm is, for example, in the range of pH 4.5-6. Examples of the buffer of the electrophoresis solution Lm include MES, ADA, ACES, BES, MOPS, TES, and HEPES. In addition, the cathodic group-containing compound described in the description of the diluent Ld is also added to the electrophoresis solution Lm. The concentration of the anionic group-containing compound (chondroitin sulfate) is, for example, in the range of 0.01 to 5% by weight.

  In the analysis system according to the present invention, a tank for storing the diluent Ld and the electrophoresis solution Lm may be provided in the analysis tool A1. In addition, the analysis tool A1 or the analysis apparatus B may be provided with a tank for mixing blood or the like as the sample with the diluent Ld.

  The introduction nozzle 94 sucks the diluted liquid Ld in the diluted liquid tank 991, the electrophoretic liquid Lm in the electrophoretic liquid tank 992, and the diluted specimen generated in the mixing tank (not shown), and introduces it to the appropriate place of the analytical tool A1. .

  The pressure nozzle 95 is a part that is in close contact with the introduction tank 2 of the analysis tool A1 and applies a predetermined pressure (positive pressure or negative pressure) to the introduction tank 2. The pressure nozzle 96 is a part that is in close contact with the discharge tank 3 of the analysis tool A1 and applies a predetermined pressure (positive pressure or negative pressure) to the discharge tank 3.

  The pump 97 is connected to the introduction nozzle 94, the pressure nozzle 95, and the pressure nozzle 96, and is a pressure generation source for realizing pressure application from the introduction nozzle 94, the pressure nozzle 95, and the pressure nozzle 96. In addition to the introduction nozzle 94, the pressure nozzle 95, and the pressure nozzle 96, the pump 97 may be connected to a pressure nozzle (not shown) for applying pressure from another part of the analysis tool A1.

  The control unit 98 controls each unit in the analyzer B. The control unit 98 includes a CPU, a memory, an interface, and the like, for example.

  Next, an analysis method using the analysis system C (analysis tool A1) will be described below. This analysis method includes, for example, a sample collection process, an electrophoresis liquid filling process, a mixing and introducing process, and an electrophoresis process.

<Sample collection process>
First, a sample is prepared. In the present embodiment, the sample is blood collected from a human body. The blood may be whole blood or hemolyzed blood.

<Electrophoresis solution filling step>
Next, the electrophoresis tube Lm is filled into the capillary tube 4. Specifically, as shown in FIG. 5, the electrophoresis solution Lm sucked from the electrophoresis solution tank 992 by the introduction nozzle 94 is introduced from the discharge tank 3. The capillary tube 4 is filled with the electrophoretic liquid Lm by applying a pressure with the pressure nozzle 96 as necessary. Moreover, it is preferable that the electrophoretic liquid Lm is also filled in the electrode part 52.

<Mixing introduction process>
Next, the sample and the diluent Ld are mixed. For example, a sample is spotted on a mixing tank provided in the analyzer B or the analysis tool A1. Further, the diluent Ld sucked from the diluent tank 991 by the introduction nozzle 94 is introduced into the mixing tank. Thereby, the diluted sample Sm obtained by diluting the sample with the diluent Ld is obtained. In addition, as a result of the inventors' research studies, in the mixing step, an agglomerate of subcomponents other than the analysis component among the components contained in the blood as the sample Sa and chondroitin sulfate which is an example of the cathodic group-containing compound Turned out to be generated. Moreover, as a specific example of this subcomponent, the knowledge that a lipid was mentioned, for example was acquired. The diluted sample Sm is sucked by the introduction nozzle 94 and introduced into the introduction tank 2 of the analysis tool A1. Then, by applying pressure to the introduction tank 2 by the pressure nozzle 95, the dilute sample Sm is filled in the communication channel 7 as shown in FIGS. At this time, the diluted sample Sm passes through the filter member 21. Thereby, the filter member 21 removes aggregates of the subcomponent (for example, lipid) and the cathodic group-containing compound (in this embodiment, chondroitin sulfate) contained in the diluted sample Sm. Further, the diluted sample Sm reaches the auxiliary tank 6 through the communication channel 7. At this time, it is preferable that the electrode portion 51 is also filled with the diluted sample Sm.

<Electrophoresis process>
Next, the electrode 91 is brought into contact with the electrode part 51, and the electrode 92 is brought into contact with the electrode part 52. Subsequently, a voltage is applied to the electrode unit 51 and the electrode unit 52 according to an instruction from the control unit 98. This voltage is, for example, 0.5 kV to 20 kV. As a result, an electroosmotic flow is generated, and the diluted sample Sm is gradually moved in the capillary tube 4. In addition, light emission from the light emitting unit 931 is started, and absorbance is measured by the light receiving unit 932. Then, the relationship between the elapsed time and the absorbance from the start of voltage application from the electrodes 91 and 92 is measured. Here, an absorbance peak corresponding to a component having a relatively fast moving speed in the diluted sample Sm appears when the elapsed time from the start of voltage application is relatively short. On the other hand, an absorbance peak corresponding to a component having a relatively slow moving speed in the diluted sample Sm appears when the elapsed time from the start of voltage application is relatively long. Thereby, analysis (separation measurement) of each component in diluted sample Sm is performed. Furthermore, an electropherogram is created by subjecting the measured absorbance to arithmetic processing (for example, differential processing, difference processing, etc. by the control unit 98). By calculating the peak height and peak area of this electropherogram, the component ratio and the like in the diluted sample Sm are obtained. Through the above steps, the analysis for the sample Sa (diluted sample Sm) is completed.

  In at least one of the mixing introduction step and the electrophoresis step, there is a time for the diluted sample Sm to contact the flat body 81 as shown in FIG. In the present embodiment, when the diluted sample Sm reaches the rapid enlargement portion 61 from the communication channel 7, it comes into contact with the hydrophilic treatment surface 812 of the flat body 81. Since the hydrophilic treatment surface 812 has been subjected to hydrophilic treatment, the diluted sample Sm immediately contacts the entire surface of the hydrophilic treatment surface 812. Further, the flat body 81 is placed on the bottom of the auxiliary tank 6. For this reason, when the pressure for further entering the diluted sample Sm into the auxiliary tank 6 is generated, the flat body 81 is slightly lifted upward in the figure, and a part of the diluted sample Sm enters the auxiliary tank 6. .

  More specifically, in the present embodiment, 1.5 μL of whole blood was collected from a human body as a sample. As diluent Ld, 38 mM citric acid, 0.95% (w / v) chondroitin sulfate C-sodium, 475 mM NDSB-201 (manufactured by Anatrac), 19 mM MES, 0.1% (w / v) Emulgen LS-110 (Manufactured by Kao Corporation), 0.02% (w / v) sodium azide, 0.025% (w / v) procrine 950 (Sigma Aldrich: registered trademark), and dimethylaminoethanol ( The sample was diluted with 60 μL of pH 6.0 using (for pH adjustment) to obtain a diluted sample Sm. As the electrophoretic solution Lm, 40 mM citric acid, 1.25% (w / v) chondroitin sulfate C-sodium, 20 mM piperazine, 0.1% (w / v) Emulgen LS-110 (manufactured by Kao Corporation), 0.02 % (W / v) sodium azide, 0.025% (w / v) procrine 950 (Sigma Aldrich: registered trademark), pH 5.0 using dimethylaminoethanol (for pH adjustment) What was used was used. In the light receiving unit 932, absorbance at 415 nm was measured. The electrophoresis time was 35 sec.

  Next, operations of the analysis tool A1 and the analysis system C will be described.

  According to the present embodiment, the diluted sample Sm, which is a liquid that has reached the rapid enlargement portion 61, contacts the flat body 81 as pressure fluctuation suppression means. Unlike the present embodiment, when the flat body 81 is not provided as in the analytical tool X that is the comparative example shown in FIG. 9, for example, the bulging shape in which the diluted sample Sm swells into the auxiliary tank 6 in the rapid expansion portion 61. It becomes. The bulging shape of the diluted sample Sm can frequently change depending on the pressure state applied to the diluted sample Sm. The introduction tank 2 is in a state of being blocked by a filter member 21 from which unnecessary components have been removed from the diluted sample Sm, and is difficult to cause the diluted sample Sm to flow backward. For this reason, the change in the bulging shape of the diluted sample Sm in the sudden expansion portion 61 becomes a pressure fluctuation and propagates throughout the diluted sample Sm. As a result, the electrophoretic liquid Lm and the diluted sample Sm in the capillary tube 4 may move unintentionally. In particular, when such pressure fluctuation occurs in the electrophoresis step, the specific component of the diluted sample Sm exhibits a movement behavior that deviates from the movement by electrophoresis. In the present embodiment, the provision of the flat body 81 suppresses the dilute sample Sm from taking a bulging shape that frequently changes. Thereby, it is possible to avoid that the electrophoretic liquid Lm and the diluted sample Sm in the capillary tube 4 exhibit unintended movement behavior. Therefore, more stable analysis can be performed while appropriately removing the analysis-inhibiting factors.

FIG. 8 is a graph showing an analysis result of the analysis method according to the present embodiment. The horizontal axis is the analysis time, and the vertical axis is the absorbance change rate. As understood from this analysis result, the analysis results show that peaks of L-HbA1c, S-HbA1c, and HbA0, which are specific components to be analyzed, clearly appear. On the other hand, FIG. 10 and FIG. 11 have shown the analysis result at the time of using the analytical tool X which is a comparative example shown in FIG. FIG. 10 shows a case where the diluted sample Sm overflows from the auxiliary tank 6, and FIG. 11 shows a case where the diluted sample Sm does not reach the opening of the auxiliary tank 6 or the rapid enlargement portion 61. In any case, the peak of the specific component as shown in FIG. 8 does not appear. This is because the electrophoretic liquid Lm in the capillary tube 4 and the diluted sample Sm showed unintended movement behavior due to pressure fluctuations caused by the surface tension of the diluted sample Sm.

  The flat body 81 is made of a resin that prevents the diluted sample Sm from passing therethrough. However, the flat body 81 is merely placed on the bottom of the auxiliary tank 6. For this reason, when the pressure which liquid-feeds diluted sample Sm is given, further preventing diluted sample Sm which reached | attained rapid expansion part 61 from taking a bulging shape, diluted sample Sm is rapidly sent to auxiliary tank 6. It is possible to pass through. This is preferable for avoiding excessive pressure fluctuations in the diluted sample Sm.

  Since the hydrophilization treatment surface 812 of the flat body 81 faces the rapid enlargement portion 61, the diluted sample Sm that has reached the rapid enlargement portion 61 quickly contacts the entire surface of the hydrophilic treatment surface 812. This is preferable for suppressing the behavior of the diluted sample Sm taking a bulging shape due to surface tension.

  12 to 24 show another embodiment of the present invention. In these drawings, the same or similar elements as those in the above embodiment are denoted by the same reference numerals as those in the above embodiment.

  FIG. 12 shows an analysis tool according to the second embodiment of the present invention. The analysis tool A2 of the present embodiment is different from the analysis tool A1 described above in that the flat body 81 does not have the hydrophilic treatment surface 812 that faces the rapid enlargement portion 61 in the above-described embodiment. FIG. 13 shows an analysis result of the analysis method using the analysis tool A2. Except for the configuration of the flat body 81, the conditions are the same as those of the analysis method using the analysis tool A1. Also according to this embodiment, it is understood that the peak of the specific component appears clearly, and the flat body 81 suppresses the pressure fluctuation caused by the surface tension.

  FIG. 14 shows an analysis tool according to the third embodiment of the present invention. The analysis tool A3 of the present embodiment is different from the analysis tool A1 and the analysis tool A2 described above in that a part of the flat body 81 is a fixing portion 811 fixed to the auxiliary tank 6. The fixing portion 811 is a portion in which a part of the flat body 81 is fixed to the bottom portion of the auxiliary tank 6 by, for example, heat welding or an adhesive. Thereby, the flat body 81 behaves like a valve body. Also according to the present embodiment, it is possible to suppress the pressure fluctuation caused by the surface tension from occurring in the diluted sample Sm that has reached the rapid expansion portion 61.

  FIG. 15 shows an analysis tool according to the fourth embodiment of the present invention. The analysis tool A4 of this embodiment is different from the above-described embodiment in that a flat body 81 is made of a porous body that allows the passage of liquid, like the filter member 21. As a specific material of the flat body 81, the same material as the filter member 21 may be used. In the present embodiment, the flat body 81 is placed on the bottom of the auxiliary tank 6.

  FIG. 16 shows an analysis result of the analysis method using the analysis tool A4. Except for the configuration of the flat body 81, the conditions are the same as those of the analysis method using the analysis tool A1. Also according to the present embodiment, it is understood that the peak of the specific component appears clearly, and the pressure fluctuation caused by the surface tension is suppressed by the flat body 81 made of a porous body.

  FIG. 17 shows an analysis tool according to the fifth embodiment of the present invention. In the analysis tool A5 of the present embodiment, the same porous body as the filter member 21 is used for the flat body 81 as in the analysis tool A4. However, the flat body 81 has a fixing portion 811 fixed to the bottom of the auxiliary tank 6. Since the flat body 81 is made of a porous body that allows liquid to pass therethrough, for example, the fixing portion 811 may be provided over the entire circumference of the flat body 81.

FIG. 18 shows an analysis result of the analysis method using the analysis tool A5. Except for the configuration of the flat body 81, the conditions are the same as those of the analysis method using the analysis tool A1. Also according to this embodiment, the peak of the specific component appears clearly, and it is understood that the pressure fluctuation caused by the surface tension is suppressed by the flat body 81 made of the porous body having the fixing portion 811.

  FIG. 19 shows an analysis tool according to the sixth embodiment of the present invention. In the analysis tool A6 of the present embodiment, a hydrophilized region 82 is provided on the inner surface of the rapid enlargement portion 61. The hydrophilic region 82 is an inner surface of the rapid enlargement portion 61 and has been subjected to a hydrophilic treatment. According to such an embodiment, the diluted sample Sm that has reached the rapid enlargement portion 61 exhibits a behavior that spreads quickly along the hydrophilized region 82. For this reason, taking the bulging shape by surface tension in the rapid expansion part 61 is suppressed. Such an embodiment can also suppress pressure fluctuations caused by the surface tension of the diluted sample Sm.

  20 and 21 show an analysis tool according to the seventh embodiment of the present invention. The analysis tool A7 of this embodiment is different from the above-described embodiment in that an open tank 83 is provided. The open tank 83 is partitioned from the auxiliary tank 6. The open tub 83 is connected to the auxiliary tub 6 via the communication flow path 7 and is a tub that opens upward in FIG. The illustrated open tank 83 has a rapid enlargement portion 831 and has the same shape as the auxiliary tank 6.

  In this embodiment, when the pressure fluctuation resulting from the surface tension occurs in the diluted sample Sm in the rapid enlargement portion 61, this pressure is released in the open tank 83 opened to the outside. For this reason, it is possible to suppress the pressure fluctuation caused by the surface tension from acting on the electrophoretic liquid Lm and the diluted sample Sm in the capillary tube 4. Therefore, more stable analysis can be performed while appropriately removing the analysis-inhibiting factors. In addition, when the pressure fluctuation resulting from the surface tension occurs in the sudden expansion portion 831, this pressure can be released in the auxiliary tank 6. Thus, the auxiliary tank 6 and the open tank 83 have a relationship in which their functions overlap.

  22 and 23 show an analysis tool according to the eighth embodiment of the present invention. In the analysis tool A8 of this embodiment, the auxiliary tank 6 and the open tank 83 are connected to each other, and the auxiliary tank 6 and the open tank 83 constitute one tank opened upward in the drawing of FIG. Yes. Also according to such an embodiment, a more stable analysis can be performed while appropriately removing an analysis-inhibiting factor.

  FIG. 24 shows an analysis tool according to the ninth embodiment of the present invention. The analysis tool A9 of this embodiment is different from the above-described embodiment in that the auxiliary tank 6 is not provided. In the present embodiment, the rapid enlargement portion 61 is configured by a portion where the communication channel 7 opens on the outer surface of the main body 1. A flat body 81, which is an example of a pressure fluctuation suppressing unit, is fixed to the sudden enlargement portion 61 with respect to the sudden enlargement portion 61 at a fixing portion 811. As the flat body 81, for example, a porous body that allows the passage of liquid is used as in the filter member 21, but also in this embodiment, the specific configuration of the pressure fluctuation suppressing means is the configuration in the above-described embodiment. Can be adopted as appropriate. Also according to such an embodiment, a more stable analysis can be performed while appropriately removing an analysis-inhibiting factor.

  The analysis tool and the analysis system according to the present invention are not limited to the above-described embodiments. The specific configuration of each part of the analysis tool and the analysis system according to the present invention can be varied in design in various ways.

A1 to A9: Analysis tool B: Analysis device C: Analysis system

1: Main body 2: Introducing tank 3: Discharging tank 4: Capillary tube 6: Auxiliary tank 7: Communication channel 11: Upper base material 12: Lower base material 21: Filter member 51: Electrode part 52: Electrode part 61: Rapid expansion Portion 81: Flat body 82: Hydrophilization region 83: Open tank 91: Electrode 92: Electrode 94: Introduction nozzle 95: Pressure nozzle 96: Pressure nozzle 97: Pump 98: Control unit 811: Fixing unit 812: Hydrophilization treatment surface 831 : Rapid enlargement section 931: Light emitting section 932: Light receiving section 950: Procrine 991: Dilution liquid tank 992: Electrophoresis liquid tank Ld: Dilution liquid Lm: Electrophoresis liquid Sa: Sample Sm: Dilution sample

Claims (12)

An analytical tool used for analyzing a sample by capillary electrophoresis,
An introduction tank into which the sample is introduced;
A capillary tube connected to the introduction tank ;
Sudden expansion unit Rutotomoni sectional area connected to the front Symbol introduction reservoir and the capillary tube is rapidly expanding, an auxiliary tank having,
A connecting flow path for connecting the introduction tank and the sudden expansion portion;
Pressure fluctuation suppressing means for suppressing pressure fluctuation caused by the surface tension of the liquid that may occur in the sudden expansion portion from acting on the liquid in the capillary tube;
With
The capillary tube is connected to the connection flow path between the introduction tank and the rapid expansion portion . The analysis tool according to claim 1 , wherein the pressure fluctuation suppressing means is a flat body that covers at least a part of the sudden expansion portion and allows gas to pass therethrough. The analysis tool according to claim 2 , wherein a part of the pressure fluctuation suppressing means is fixed to the sudden expansion portion. The analysis tool according to claim 2 or 3 , wherein the pressure fluctuation suppressing means is made of a resin that prevents a liquid from passing therethrough. The analysis tool according to claim 4 , wherein the flat body has a hydrophilic treatment surface facing the sudden expansion portion. The analysis tool according to claim 2 or 3 , wherein the pressure fluctuation suppressing means is made of a porous body that allows passage of liquid. The analysis tool according to claim 1 , wherein the pressure fluctuation suppressing means is a hydrophilized region on the inner surface of the sudden expansion portion and subjected to a hydrophilization treatment. The analysis tool according to claim 1 , wherein the pressure fluctuation suppressing means is an open tank connected to the auxiliary tank via the connection channel. The analysis tool according to claim 8 , wherein the auxiliary tank and the open tank are partitioned from each other. The analysis tool according to claim 8 , wherein the auxiliary tank and the open tank are connected to each other. The analysis tool according to any one of claims 1 to 10, which is used as a disposable type analysis tool. The analysis tool according to any one of claims 1 to 11 ,
An analysis unit that is loaded with the analysis tool and performs analysis using electrophoresis in the capillary tube;
An analysis system comprising: