JP2011107100A - Measuring instrument and analysis chip - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a simple measuring instrument can performing accurate quantitative measurement such as electrochemical analysis by pretreatment reaction even with respect a substance to be measured which cannot be directly subjected to electrochemical measurement such as protein. <P>SOLUTION: The measuring instrument for the substance to be measured includes a reaction part for performing pretreatment reaction, a waste liquid mechanism equipped with an absorbent member for removing the excessive liquid of the reaction liquid in the reaction part and a measuring part for measuring the substance to be measured. In the waste liquid mechanism, waste liquid time is regulated to ensure the time required in the pretreatment reaction in the reaction part. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

  The present invention relates to a measuring apparatus having a waste liquid mechanism used for measuring a substance to be measured.

  In recent years, the importance of detecting, detecting or quantifying biological substances such as DNA, enzymes, antigens, antibodies, proteins, viruses and cells, and chemical substances has increased in the fields of medicine, health, food, and drug discovery. Various biochips and microchemical chips (hereinafter collectively referred to as analysis chips) that can easily measure them have been proposed. The analysis chip is designed so that a series of experiments and analysis operations performed in the laboratory can be easily performed within a chip of several centimeters square and several millimeters to 1 cm thick. Therefore, it has many advantages such as low cost, high reaction rate, high throughput testing, and the ability to obtain test results immediately at the site where the sample is collected. Such an analysis chip is suitably used for biochemical tests such as blood tests.

  Currently, various methods are used for simple measurement of various substances derived from living bodies. In the medical field such as influenza test, pregnancy test, blood glucose level measurement, etc., it is simple and inexpensive, the demand for general public is high, and it has gained a big market. It is expected to form an increasingly large market in the future.

  In order to selectively capture bioactive substances that are present in trace amounts in biological samples (samples are solutions of unknown concentration) and perform highly sensitive analysis, enzyme sensors, enzyme test papers, etc., enzyme catalysts Reaction using high molecular recognition mechanism, radioimmunoassay (RIA), enzyme-linked immunosorbent assay (ELISA), immunosensor, luminescent enzyme immunoassay (CLEIA), surface Immunoassay using molecular recognition mechanism with high antigen-antibody reaction such as plasmon resonance (SPR), DNA microarray (DNA chip), surface plasmon-field enhanced fluorescence spectroscopy (SPFS), etc. , Hybridization using the high molecular recognition mechanism of DNA It is used.

In principle, the above-described molecular recognition mechanism can be used for molecular recognition itself. However, in order to extract it as a physical quantity or a chemical quantity, another contrivance is required. Many analytes such as proteins, neurotransmitters, and hormones rarely produce low-molecular-weight simple molecules in their chemical reactions, so they are redox like glucose, which is the analyte of blood glucose meters. It is difficult to connect to the production of high H ₂ O ₂ and consumption of O ₂ , and as a result, a complicated analysis process is often required. For example, cortisol, known as a stress hormone, is a hapten with a molecular weight of only 362.47, that is, a unitary antigen. Therefore, the sandwich method using a plurality of antibodies for molecular recognition cannot be applied, and the competition method must be applied. As a result, an analysis step of sample injection → competitive reaction with the substance to be measured-labeled substance complex → removal of unreacted substance → injection of enzyme substrate → reaction intensity measurement is required.

  In particular, if the “removal of unreacted substances” is not performed properly, the baseline of the detection signal becomes high, the difference from the detection signal after the reaction becomes small, and highly sensitive immunoassay, hybridization, etc. Despite applying the molecular recognition mechanism, the required analytical accuracy cannot be obtained.

  When attempting to measure a substance to be measured, such as a protein that cannot be directly measured electrochemically, using a simple method using an analytical chip, it is subjected to a pretreatment reaction necessary for electrochemical analysis. The problem is how to remove the excess of the reaction liquid (liquid containing the substance to be measured and the reagent) by a simple method.

  Therefore, the present invention can perform an accurate quantitative measurement such as an electrochemical analysis by performing a pretreatment reaction on a substance to be measured such as a protein that cannot be directly subjected to an electrochemical measurement. An object is to provide a simple measuring apparatus.

The present invention includes a reaction part for performing a pretreatment reaction, a waste liquid mechanism including an absorbent member for removing excess liquid of the reaction liquid in the reaction part, and a measurement part for measuring a substance to be measured. Prepared,
The waste liquid mechanism is an apparatus for measuring a substance to be measured, in which the waste liquid time is adjusted so that the time required for the pretreatment reaction in the reaction section can be secured.

  Here, “waste liquid time” refers to the time from the introduction of the reaction liquid into the reaction section until the start of the waste liquid (hereinafter abbreviated as “waste liquid start time”), and the excess liquid absorbed by the absorbent member. Time (hereinafter abbreviated as “absorption time”).

It is preferable that the reaction part, the measurement part, and the absorbent member are arranged on a substrate.
It is preferable that the absorption time is adjusted by the absorbent member changing the length of the ridgeline of the capillary trunk.

It is preferable to have a gap between the reaction part and the absorbent member.
The waste liquid start time is preferably adjusted by adjusting the size of the gap.

It is preferable to provide a guide member for guiding the reaction liquid to the absorbent member.
The guide member is a member that at least surrounds the reaction part in the horizontal direction, and preferably has an opening that serves as a flow path of the reaction liquid to the absorbent member.

  The absorbent member is preferably composed of a capillary part where absorption of the reaction solution is started and a water storage part other than that, and the absorption time is adjusted by adjusting the shape of the capillary part.

It is preferable that the shape seen from the upper surface of the said capillary part is a rectangle, a triangle, or a comb-tooth shape.
It is preferable that the said absorption member adjusts the said absorption time by adjusting the volume of the said water storage part.

It is preferable that the reaction part and the measurement part are integrated.
Further, the present invention includes a reaction part for performing a pretreatment reaction, and a waste liquid mechanism including an absorbent member for removing excess liquid of the reaction liquid in the reaction part, and the waste liquid mechanism includes the reaction The present invention also relates to an analysis chip used in a measurement apparatus for a substance to be measured, in which the waste liquid time is adjusted so that the time required for the pretreatment reaction in the section can be secured.

  The measuring apparatus according to the present invention includes a specific waste liquid mechanism using an absorbent member in order to waste excess reaction liquid introduced into the reaction section, and thus has a simple configuration without requiring any power. Thus, the excess liquid of the reaction liquid can be discharged while adjusting the waste liquid time of the reaction liquid introduced into the reaction section.

It is a figure which shows Embodiment 1 of this invention. (A) is a perspective view, (b) is a top view, and (c) is a longitudinal sectional view. (A)-(h) is a longitudinal cross-sectional view for demonstrating the waste-liquid mechanism used for this invention. It is a figure which shows Embodiment 2 of this invention. (A) is a perspective view, (b) is a top view. It is a figure which shows Embodiment 3 of this invention. (A) is a perspective view, (b) is a top view. (A)-(d) is a schematic cross section for demonstrating the waste-liquid mechanism in Embodiment 3 of this invention. (A)-(c) is a top view which shows the absorptive member of Embodiment 4 of this invention. It is a top view which shows Embodiment 5 of this invention. It is a graph which shows the liquid quantity change on the acrylic substrate in an Example.

  The measuring apparatus of the present invention is an apparatus for performing measurement for quantifying a substance to be measured after performing a pretreatment reaction of a reaction solution containing the substance to be measured and a reagent. And it is equipped with the waste liquid mechanism which absorbs and removes the surplus liquid of the reaction liquid introduced into the reaction part for performing the pretreatment reaction so that the time required for the pretreatment reaction in the reaction part can be secured. The waste liquid time of the reaction liquid is adjusted.

  For example, glucose present in blood or the like generates an oxidation-reduction current by a reaction catalyzed by the enzyme glucose oxidase or the like, and can be directly detected electrochemically by measuring this current. On the other hand, many of various proteins existing in living bodies are difficult to electrochemically quantify and qualify by causing a reaction that directly generates a redox current. For this reason, when measuring proteins and the like in living bodies using electrochemical measurement, the substance to be measured and the substance to be measured-enzyme label complex are subjected to a competitive reaction, and the enzyme is used to perform the electrochemical reaction. The detection method is used automatically. The present invention is a simple measuring apparatus capable of performing electrochemical analysis on a substance to be measured that cannot be directly detected electrochemically through an indirect pretreatment reaction.

  Therefore, the measuring apparatus of the present invention is suitably used when the substance to be measured is a substance that cannot be directly detected electrochemically. Specific examples of such substances to be measured include bioactive substances such as proteins such as enzymes, physiologically active substances such as nucleic acids and hormones, neurotransmitters, and low molecular compounds. Preferred are low molecular weight compounds, and more preferred are corticoids and derivatives thereof. Examples of the corticoid include cortisol, corticosterone, cortisone and the like, preferably cortisol.

  The reaction liquid is a liquid that is subjected to a pretreatment reaction necessary for quantitative measurement of a substance to be measured such as electrochemical analysis, and is a liquid that includes the substance to be measured and a necessary reagent. Specifically, for example, when a competition method is used as a pretreatment reaction and an antibody is held in the reaction part, an antigen (substance to be measured) and a complex of an antigen and a labeling substance that can be detected electrochemically (Hereinafter, may be abbreviated as “antigen (substance to be measured) -labeled substance complex”), or a washing liquid for removing excess antigen or target substance-labeled substance complex after antigen-antibody reaction Etc. are contained in the reaction solution.

  The reaction solution includes a sample. Here, the sample is a liquid containing a substance to be measured. Specifically, when the substance to be measured is contained in a biological component derived from a living body such as saliva, sweat, blood, etc., the liquid component derived from the living body itself. is there. The sample can be used as it is as a part of the reaction solution. Among these liquid components derived from living organisms, saliva and sweat are preferably used as samples in that non-invasive collection is possible. In the case where contaminants in the liquid component become a problem, a liquid dispersed or dissolved in the same medium as a developing cleaning liquid described later may be used as a sample after performing processing such as extraction or centrifugation. . From the viewpoint of simplicity of analysis, it is preferable to use a liquid component derived from a living body as a sample.

  In the measurement using the measuring apparatus of the present invention, for example, after a sample is introduced into the reaction part, a liquid containing a reagent necessary for the pretreatment reaction is introduced, and the pretreatment reaction is performed. Thereafter, if necessary, for example, a surplus substance to be measured and a substance to be measured-labeled substance complex that are not bound to the antibody are washed away, and a cleaning solution for removing the substance from the reaction part is introduced into the reaction part.

  The cleaning liquid is appropriately selected according to the type of the substance to be measured and the kind of the substance to be measured-labeled substance complex. For example, as a developing cleaning solution used when the substance to be measured is a corticoid and the substance to be measured-label substance complex is a corticoid-GOD complex, a phosphate buffer, HEPES, Tris buffer, Acetate buffer, etc. It is done. In particular, when the corticoid is cortisol, it is preferable to use a phosphate phosphate as a cleaning solution.

  In the pretreatment reaction in the present invention, the reaction solution (including the cleaning solution) is introduced excessively with respect to the volume of the reaction section, and therefore, it is necessary to remove (waste liquid) the excess reaction solution. Examples of the pretreatment reaction include a sandwich method in addition to the reaction using the above-described competitive reaction.

  The reaction part of the measuring device is a region where the reaction solution is held for at least the time required for the pretreatment reaction. Specifically, for example, a region including a sample pad for absorbing and holding the reaction solution for a certain period of time. Alternatively, a region surrounded by a partition so that the reaction solution can be held for a certain period of time can be mentioned. The method for introducing the reaction liquid into the reaction part is not particularly limited, and examples thereof include a dropping method.

  The reaction unit may contain a reagent such as a substance to be measured-labeled substance complex necessary for the pretreatment reaction, a reagent necessary for electrochemical analysis, and the like as necessary. For example, the reagent used when the pretreatment reaction is a competitive reaction utilizing an antigen-antibody reaction includes an antibody-labeling substance complex. An antigen-antibody reaction is performed with an antibody held on the electrode of the reaction part in a state where the complex and the antigen are in competition, and the label of the complex bound to the antibody is detected by electrochemical analysis or the like. As a result, quantitative measurement of the substance to be measured can be performed. Note that only one type of reagent may be held in the reaction unit, or two or more types of reagents may be held.

  Although an absorptive member will not be specifically limited if it is a member which can absorb an excess reaction liquid, For example, the member comprised by a hygroscopic fiber, a porous resin, a polymeric absorber, and sponge is mentioned. According to such a configuration, since the absorbent member is composed of hygroscopic fibers, porous resin, polymer absorbent body, or sponge, the surplus specimen adhering to the test piece is effective for the absorbent member itself. Can be absorbed. For example, if a non-woven fabric, which is a kind of hygroscopic fiber, is employed as a specific material for the absorbent member, a sufficient amount of the reaction solution can be absorbed between the fiber gaps in which the non-woven fabric is woven.

  Moreover, the absorptive member may be arrange | positioned so that replacement | exchange is possible. According to such a configuration, when the hygroscopic action of the absorbent member is weakened, it can be easily replaced with another new member, so that the user can perform a simple replacement operation. The waste liquid mechanism can be maintained.

  In the present invention, the reaction part and the absorbent member are preferably arranged on a substrate such as a plate-like body. The material of the substrate is not particularly limited. For example, acrylic resin such as polymethyl methacrylate (PMMA), polydimethylsiloxane (PDMS), polyethylene terephthalate (PET), polybutylene terephthalate (PBT), polycarbonate (PC), polystyrene ( PS), polypropylene (PP), polyethylene (PE), polyethylene naphthalate (PEN), polyarylate resin (PAR), acrylonitrile-butadiene-styrene resin (ABS), vinyl chloride resin (PVC), polymethylpentene resin (PMP) ), Polybutadiene resin (PBD), biodegradable polymer (BP), cycloolefin polymer (COP), and other organic materials; silicon, silicone, glass, quartz, and other inorganic materials. Among these, it is preferable to use a hydrophobic material that does not hinder the reaction and has good liquid drainage. As the hydrophobic material, acrylic resin, polydimethylsiloxane (PDMS), or the like can be preferably used.

  When the reaction part and the absorbent member are disposed on the substrate, it is preferable to have a gap between the reaction part and the absorbent member. The time from the introduction of the reaction liquid into the reaction part until the start of the waste liquid is affected by the distance between the reaction part and the absorbent member. For this reason, the total waste liquid time can be adjusted by adjusting the waste liquid start time by adjusting the gap distance. The distance of the gap can usually be changed within a range of about 5 mm or less. When the distance is increased, the waste liquid start time is delayed, and the entire waste liquid time is delayed. Further, when the gap distance is shortened, the waste liquid start time is increased, and the entire waste liquid time is increased.

  The guide member is a member for guiding the reaction liquid to the absorbent member. The guide member is a member that at least surrounds the reaction part in the horizontal direction, and preferably has an opening that serves as a flow path for the reaction liquid to move to the absorbent member.

  As the material of the guide member, it is preferable to use a material having low water absorption, and as the material having low water absorption, plastic, acrylic resin, or the like can be appropriately selected according to the reaction liquid (sample, reagent) or the like. . Further, by interposing silicon rubber, an O-ring or the like between the guide member and the electrode, leakage of the reaction liquid to other than the absorbent member may be prevented.

  When the measuring device is a measuring device for electrochemical measurement having an electrode under the reaction part, the guide member exposes the minimum necessary part of the electrode to the extent that the electrochemical measurement is not excluded, and the reaction part is It is preferable that it is a shape which covers. By doing in this way, since the volume of a reaction part becomes the minimum required, the collection amount of a measurement sample can be decreased more.

  As a material for such a guide member, it is particularly preferable to use polydimethylsiloxane (PDMS). PDMS is a kind of silicon rubber, and a micro structure can be manufactured by molding (molding), and a sub-micron structure can be transferred. Because of its self-adsorption property, it can be sealed by simply sticking it to the substrate when a large internal pressure is not required. It is a biocompatible material and does not adversely affect cells and tissues. Unlike glass and plastic chips, there is an advantage that it can be made relatively easily without requiring wet etching or high-temperature bonding.

  The electrodes usually include a working electrode (working electrode), a counter electrode (counter electrode), and a reference electrode (reference electrode). When performing an electrochemical analysis, a reagent necessary for electrochemical detection is added to the reaction solution after the pretreatment reaction, and then a current change corresponding to the potential change of the working electrode with respect to the reference electrode (working electrode and counter electrode). Change in current flowing between the two. Analyze (quantitatively, qualitatively) the substance to be measured by comparing the amount of electricity (coulomb amount), peak current value, or current differential value obtained by integrating the change in current with a calibration curve. Can do.

  For example, when a certain antigen is a substance to be measured, the labeling substance is glucose oxidase in a method for quantifying the antigen by detecting the ratio of the antigen bound to the antibody and the antigen-labeling substance complex (competitive method) In this case, by supplying a certain amount of glucose solution to the vicinity of the electrode surface, an oxidation reaction of glucose by glucose oxidase is performed, and a current change due to electrons released at that time is measured, whereby an antigen-antigen-labeling substance complex The antibody-to-antibody binding ratio can be measured, and the antigen can be quantitatively measured from the result.

  As the electrode material, various known electrode materials used for electrochemical analysis of a labeling substance can be used. Examples of the electrode material include platinum, carbon, gold, silver, palladium, ruthenium, and rhodium. It is done. In particular, when the reagent contained in the reaction solution is a substance to be measured-labeling substance complex and glucose oxidase is used as the labeling substance, platinum as a catalyst for the detection reaction (oxidation reaction by glucose oxidase) is included as a material. It is preferable to use an electrode. The electrode in the present invention includes an electrode in which an antibody is immobilized on the surface of the electrode as described later, and an electrode containing an electron mediator.

  Further, when the absorbent member is composed of a capillary part where absorption of the reaction liquid is started and a water storage part other than that, the waste liquid time of the reaction liquid is adjusted by adjusting the shape of the capillary part. It may be. Since the waste time of the reaction liquid is affected by the contact area of the reaction liquid and the capillary part of the absorbent member, the shape of the capillary part may be adjusted in consideration of this point.

  It is preferable that the shape seen from the upper surface of the said capillary part is a rectangle, a triangle, or a comb-tooth shape. By adopting such a shape, the absorption time is adjusted by changing the contact area between the reaction liquid and the capillary part of the absorbent member when absorbing the reaction liquid in the reaction part, and the waste liquid time is adjusted. Can do.

  Moreover, you may make it adjust the waste liquid time of a reaction liquid by adjusting the volume of the said water storage part of an absorptive member.

  If necessary, the waste liquid time may be adjusted so that the time required for the pretreatment reaction can be secured by combining two or more of the above-described configurations for adjusting the waste liquid time of the waste liquid mechanism.

  The present invention also relates to an analysis chip provided with the above-described reaction section and waste liquid mechanism. The analysis chip is a handy size measuring member used for analyzing a sample containing a substance to be measured (for example, detecting or quantifying the substance to be measured in the sample) by adopting an arbitrary measurement principle. Such an analysis chip can be used as a constituent member of the measurement apparatus of the present invention.

(Embodiment 1)
As shown in FIG. 1, the measurement apparatus of the present embodiment has an absorbent member 1 provided on a substrate 3 and a sample pad 2 that constitutes a reaction part (may also serve as a measurement part). ing. The substrate 3 is preferably made of a hydrophobic material. The sample pad 2 and the absorbent member 1 are disposed so as to have a gap between them. When the reaction solution 4 is dropped by adjusting the distance L of the gap, the reaction is performed. The time until the liquid 4 reaches the absorption start part 10 is adjusted. Thereby, it is possible to adjust the waste liquid start time of the reaction liquid.

  The waste liquid mechanism of the present invention will be described with reference to FIG. In FIG. 2, the sample pad 2 as shown in FIG. 1 is not shown, but the waste liquid mechanism of the present invention will be described in the same manner when the sample pad is provided. First, as shown in FIG. 2A, when a droplet 41 (for example, a cleaning solution) is dropped onto the reaction solution 4, the reaction solution 4 comes into contact with the absorbent member 1 as shown in FIG. When the capillary force acts on the contact portion, the balance of intermolecular forces inside the droplet is lost, and the absorption of the reaction solution 4 to the absorbent member 1 starts. The amount of liquid that begins to be absorbed is adjusted by changing the distance L between the position where the droplet 41 is dropped and the absorbent member 1.

  As shown in FIG. 2 (c), once the absorption of the reaction liquid 4 is started, the reaction liquid is in a state where the capillary force of the absorbent member 1 is larger than the horizontal component of the surface tension of the reaction liquid 4. 4 continues to be absorbed by the absorbent member 1 (FIG. 2D). And absorption is complete | finished when the horizontal direction component of the surface tension of the reaction liquid 4 and the direction of the capillary force of the absorptive member 1 become equal (FIG.2 (e)). Thereafter, the reaction solution 4 returns to a position away from the absorbent member 1 due to surface tension (FIGS. 2 (f) to (g)). Next, as shown in FIG. 2 (h), the reaction solution 4 is not absorbed by the absorbent member 1 until the reaction solution 4 reaches the absorption start solution amount 43. Thus, the waste liquid mechanism used in the present invention serves as a valve.

(Embodiment 2)
As shown in FIG. 3, the present embodiment is a form in which a guide member 5 having an opening 51 is provided in addition to the first embodiment. By providing the guide member 5, even when the distance between the sample pad 2 and the absorbent member 1 is increased, the reaction liquid is prevented from leaking to the peripheral part other than the absorbent member 1. It becomes possible to adjust so that it may be delayed more.

(Embodiment 3)
In the present embodiment, as shown in FIG. 4, the guide member 5 of the second embodiment has an opening 51 only in the lower part. Since the resistance when the reaction liquid passes through the opening 51 is increased by making the opening 51 only the lower part, the time until the reaction liquid passes through the opening 51 and reaches the absorbent member 1 can be delayed. It is possible to adjust to delay the time until the start of waste liquid further than in the second embodiment.

  The waste liquid mechanism in Embodiment 3 is demonstrated using FIG. In FIG. 5A, a reaction part (also serving as a measurement part) in which a reaction liquid 4 (for example, a liquid containing a substance to be measured and a reagent) larger than the amount of liquid that can be held by the sample pad 2 is surrounded by a guide member 5. The liquid droplet 41 (for example, a cleaning liquid) is further dropped. As shown in FIG. 5 (b), when the reaction liquid 4 reaches a liquid amount that exceeds the surface energy of the opening 51 of the guide member 5, it passes through the opening 51 and develops toward the absorbent member 1. Then, absorption by the absorbent member 1 is started. Once the liquid begins to be absorbed by the absorbent member 1, the effect of surface energy is lost, and a certain amount of the reaction liquid 4 is absorbed by the absorbent member 1 (absorbed reaction liquid 42), and the reaction liquid 4 in the reaction section. The amount of liquid is reduced to a certain amount. The fixed amount remaining in the reaction part is determined by the viscosity of the reaction solution, the surface tension, the water repellency of the substrate, the distance from the absorbent member 1 and the like. As shown in FIG. 5 (d), when the droplet 41 (for example, a detection solution for detecting a label) is dropped next, the reaction solution 4 reaches a certain amount exceeding the surface energy of the opening 51. Until then, the reaction liquid 4 is not absorbed by the absorbent member 1, and the reaction liquid 4 is held in the reaction section surrounded by the guide member 5. Thus, the waste liquid mechanism used in the present invention serves as a valve.

(Embodiment 4)
As shown in FIG. 6, the present embodiment is a form in which the waste liquid time is adjusted by adjusting the shape of the capillary portion 11, which is the part where the absorption of the reaction liquid is started in the absorbent member 1. 6A shows the absorbent member 1 in which the capillary part has a rectangular shape, FIG. 6B shows the absorbent member 1 in which the capillary part has a triangular shape, and FIG. 6C shows the capillary part. The absorbent member 1 which made the shape of this into the comb-tooth shape is shown. By making the shape of the capillary portion in this way, it is possible to slow down the speed at which the absorbent member 1 absorbs the reaction liquid, as compared with the case where the shape of the absorbent member is square, so that the waste liquid time is delayed. Can be adjusted to.

  In addition, also by adjusting the volume of the water storage part 12 which is parts other than the capillary part 11, the speed at which the absorptive member 1 absorbs the reaction liquid can be adjusted, and the waste liquid time can be adjusted.

(Embodiment 5)
In the present embodiment, the absorbent member 1 shown in FIG. 6A is installed in a state where the rectangular capillary portion 11 is in contact with the sample pad 2, and in addition to the guide member 5 similar to that of the second embodiment, the second embodiment is further provided. In this embodiment, a guide member 52 is provided. PDMS is preferably used as the second guide member. 52 Since the absorbent member 1 is in contact with the sample pad 2, the absorption start time of the absorbent member 1 is relatively fast, but the absorption rate is slowed by the shape of the capillary 11, so the waste liquid time is slowed as a whole. Can be adjusted.

  Further, the second guide member 52 is shaped so as to substantially contact the sample pad 2 and surround the sample pad 2, and by providing such a second guide member 52, the second guide member 52 reacts on the substrate 3 around the sample pad 2. Since the liquid is not retained, the reaction liquid can be minimized.

<Material>
An absorbent member was fixed on a substrate made of a hydrophobic acrylic resin, and its mass was measured. As the absorbent member (absorbing pad), a cellulose fiber sample pad (CFSP203000 manufactured by Millipore) having a size of 14 mm × 50 mm was used. In addition, as a board | substrate, what has the main surface of an area sufficiently larger than an absorptive member was used.

<Experiment method>
(1) 10 μL of pure water (instead of the reaction solution) is dropped at regular intervals (2.5 seconds) onto the substrate at a position 7 mm away from the end of the absorbent member in the longitudinal direction.
(2) When the absorption of pure water by the absorbent member starts, the dropping is stopped.
(3) When the absorption is completed, the entire mass is measured and the remaining liquid amount is examined, and then the dropping of pure water is restarted.
(4) The steps (1) to (3) are repeated.

<Experimental result>
The change in the amount of liquid on the acrylic substrate is shown in the graph of FIG. In addition, Table 1 shows the amount of pure water that begins to be absorbed in the repetition of the steps (1) to (3). As shown in FIG. 8, the first absorption start is when the amount of liquid on the substrate becomes 200 μL, and the amount of liquid remaining in the dropping part (corresponding to the reaction part) after absorption (waste liquid) is 40 μL. Thereafter, the absorption started when the liquid volume on the substrate was around 200 μL, and the absorption ended when the liquid volume on the substrate decreased to 30 to 40 μL. Moreover, as shown in Table 1, the absorption started when the dropping amount became about 200 μL for the first time, and the absorption started when the dropping amount became 160 to 170 μL for the second time and thereafter. From this result, in the waste liquid mechanism in the present invention, the waste liquid is discharged when the reaction liquid in the reaction part becomes a certain amount or more, and the liquid amount in the reaction part is discharged to a certain amount or less. Thereafter, it has a function that the waste liquid is not performed until the reaction liquid reaches a predetermined amount or more, and it is understood that it plays the role of an automatic valve.

  It should be understood that the embodiments and examples disclosed herein are illustrative and non-restrictive in every respect. The scope of the present invention is defined by the terms of the claims, rather than the description above, and is intended to include any modifications within the scope and meaning equivalent to the terms of the claims.

  DESCRIPTION OF SYMBOLS 1 Absorbing member, 10 Absorption start part, 11 Capillary part, 12 Water storage part, 2 Sample pad, 3 Substrate, 4 Reaction liquid, 41 Droplet, 42 Absorbed reaction liquid, 43 Absorption start liquid quantity, 5 Guide member, 51 opening part, 52 2nd guide member.

Claims (12)

A reaction section for performing a pretreatment reaction, a waste liquid mechanism having an absorbent member for removing excess liquid of the reaction liquid in the reaction section, and a measurement section for measuring a substance to be measured,
The waste liquid mechanism is one in which the waste liquid time is adjusted so that the time required for the pretreatment reaction in the reaction section can be secured.
The waste liquid time is a waste liquid start time that is a time from when the reaction liquid is introduced into the reaction section until the waste liquid is started, and an absorption time that is a time during which the surplus liquid is absorbed by the absorbent member. Is the sum of   The measurement apparatus according to claim 1, wherein the reaction unit, the measurement unit, and the absorbent member are disposed on a substrate.   The measuring apparatus according to claim 1, wherein the absorption time is adjusted by changing a length of a ridge line of an end portion in contact with the reaction portion.   The measuring apparatus according to claim 1, wherein a gap is provided between the reaction part and the absorbent member.   The measuring apparatus according to claim 4, wherein the waste liquid start time is adjusted by adjusting the distance of the gap.   The measuring apparatus according to claim 1, further comprising a guide member for guiding the reaction liquid to the absorbent member.   The measuring apparatus according to claim 6, wherein the guide member is a member that at least surrounds the reaction portion in a horizontal direction, and has an opening that serves as a flow path of the reaction solution to the absorbent member.   The said absorptive member consists of the capillary part by which absorption of the said reaction liquid is started, and a water storage part other than that, The said absorption time was adjusted by adjusting the shape of the said capillary part, The 1-7. The measuring apparatus in any one of.   The measuring apparatus according to claim 8, wherein a shape of the capillary portion viewed from the upper surface is a rectangle, a triangle, or a comb shape.   The said absorptive member consists of the capillary part of a measurement site | part vicinity, and a water storage part other than that, The said absorption time was adjusted by adjusting the volume of the said water storage part, The any one of Claims 1-9. Measuring device.   The measurement apparatus according to claim 1, wherein the reaction unit and the measurement unit are integrated.   A reaction part for performing a pretreatment reaction, and a waste liquid mechanism having an absorbent member for removing excess liquid of the reaction liquid in the reaction part, wherein the waste liquid mechanism is the pretreatment reaction in the reaction part An analysis chip used in a measurement device for a substance to be measured, in which the waste liquid time is adjusted so as to ensure the time required for the measurement.

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