Chemical titration method and chemical titration system

Abstract

To provide a technique that can perform more accurate chemical titration using a simpler device or easier method.SOLUTION: A chemical titration method that measures the concentration of a sample based on a hue indicated by an indicator added to a sample or titrant when the titrant is added to a sample, includes: a process in which the sample and the titrant are introduced into separate flow paths for titration; a process in which the flow path of the titrant is merged with the flow path of the sample; and a process in which the concentration of the sample is measured on the basis of a distance between a boundary where a color of the indicator changes and a reference point in a direction perpendicular to the flow direction of a flow path after merging, at a predetermined measurement location in the flow path after merging being the flow path on the downstream side of the merging point of the flow path of the sample and the flow path of the titrant.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention relates to a chemical titration method and a chemical titration system for measuring the concentration, etc., of a sample by utilizing a chemical reaction between the sample and a titrant. [Background technology]

[0002] When quantitatively analyzing a sample, a chemical titration technique is sometimes used. In conventional chemical titration, there is an example of flow injection titration using material diffusion, as shown in Figure 11. In this example, the sample is injected into a flow path of a titrant to which an indicator has been added, and after stirring with a stirrer, the concentration of the sample is measured by measuring the color distribution of the indicator in the flow direction in the downstream flow path (see, for example, Non-Patent Document 1).

[0003] However, in such flow injection titration, it takes a certain amount of time for the diffusion of the substance to occur sufficiently, and the equipment is large and the procedure is complicated, making on-site analysis difficult. Furthermore, the skill required for analysis is high, and the number of operators is limited.

[0004] In addition, titration methods using microfluidic devices have been proposed to reduce the scale of the equipment (see, for example, Non-Patent Documents 2 to 4). In these microfluidic devices, fine flow paths are formed on a substrate, and chemical reactions between the sample and titrant proceed within the flow paths. By using the microfluidic device, the amount of sample can be kept small, multiple chemical reactions can be integrated, and analysis time can be reduced. However, in order to perform chemical titration using a microfluidic device, a complex flow path design is required within the device, which can increase the design cost of the equipment. In addition, digital measurement is required for accurate concentration measurement, and there is a limit to simplifying the analysis method using chemical titration. [Prior art documents] [Non-patent literature]

[0005] [Non-Patent Document 1] Paper on flow injection titration: J. Ruzicka, EH Hansen, H. Mosbaek, Anal. Chim. Acta, 92, 235-249 (1977). [Non-Patent Document 2] Creation of material reaction fields using a cross-shaped microfluidic device C. Kanzaki, A. Inagawa, G. Fukuhara, T. Okada, M. Numata, ChemSystemsChem, 2, e2000006 (2020). [Non-Patent Document 3] Chemical titration methods using microfluidic devices. R. Ferrigno, JN Lee, X.Jiang, GM Whitesides, Anal. Chem. 76, 76, 2273 (2004). [Non-Patent Document 4] Chemical titration methods using microfluidic devices. H. Song, H. Li, MS Munson, TG Van Ha, RF Ismagilov, Anal. Chem. 78, 4839 (2006). Summary of the Invention [Problem to be solved by the invention]

[0006] In view of the above problems, an object of the present invention is to provide a technique that enables more accurate chemical titration using a simpler device or an easier method. [Means for solving the problem]

[0007] In order to solve the above problems, the present disclosure employs the following configuration: A chemical titration method for measuring the concentration of a sample based on the color tone of an indicator added to the sample or a titrant when a titrant is added to the sample, the method comprising the steps of: The sample and the titrant are respectively introduced into flow paths for titration, and the sample flow path is The titrant flow paths are joined together, This is a chemical titration method, characterized in that the concentration of a sample is measured based on the distance between a boundary at which the color of the indicator changes and a reference point in a direction perpendicular to the flow direction of the post-junction flow path, at a predetermined measurement point in the post-junction flow path, which is a flow path downstream of the junction of the sample flow path and the titration solution flow path.

[0008] In the present disclosure, the sample and the titrant are each introduced into a flow path for titration, and the flow path of the titrant is merged with the flow path of the sample to form a post-merged flow path. An indicator for titration is added to either or both of the sample and the titrant. In the present disclosure, the concentration of the sample is measured based on the distance between a boundary at which the color of the indicator changes and a reference point in a direction perpendicular to the flow direction of the post-merged flow path at a predetermined measurement point of the post-merged flow path. Here, the reference point is not particularly limited as long as the distance from the boundary at which the color of the indicator changes can be measured with high accuracy. For example, the reference point may be a wall surface on one side of the post-merged flow path at the measurement point. Alternatively, when the boundary at which the color of the indicator changes appears on both sides of the flow in the post-merged flow path, the reference point may be the boundary on one side at which the color tone of the indicator changes in the direction perpendicular to the flow direction of the post-merged flow path at the measurement point.

[0009] As described above, in the present disclosure, the flow paths of the sample and titrant are joined to form a joined flow path. In this joined flow path, the sample and titrant diffuse into each other and flow downstream while undergoing a chemical reaction. As a result, for example, the width of the color region showing the neutralization point (or equivalence point) of the indicator increases toward the downstream side.

[0010] In the present disclosure, the position of the boundary of the area of ​​a specific color tone indicated by the indicator at the measurement point is detected as the distance between the measurement point and the reference point, and the concentration of the sample is measured based on the distance. For example, if the concentration of the sample is high, the boundary of the area of ​​a specific color tone indicated by the indicator spreads faster in the post-junction flow path. Conversely, if the concentration of the sample is low, the boundary of the area of ​​a specific color tone indicated by the indicator spreads more slowly in the post-junction flow path. In other words, in the present disclosure, the concentration of the sample is measured based on the position of the boundary of the area of ​​a specific color tone indicated by the indicator at a specified measurement point in the post-junction flow path.

[0011] The position of the boundary, i.e., the distance between the boundary where the color of the indicator changes and the reference point in the direction perpendicular to the flow direction of the post-junction flow path at a specific measurement point in the post-junction flow path, can be detected with high accuracy from an image near the measurement point. Therefore, according to the present disclosure, the concentration of the sample can be measured with higher accuracy.

[0012] Furthermore, according to the present disclosure, if a simple flow path where the sample and titrant join is prepared, the concentration of the sample can be measured, and the concentration of the sample can be easily measured with a smaller and simpler device (e.g., a flow path element in which a flow path is formed). As a result, the device becomes easier to carry, and on-site analysis becomes easier. In addition, advanced technology is not required to measure the concentration, making it possible to expand the range of operators who can perform the analysis.

[0013] Furthermore, when measuring the color distribution of the indicator in the flow direction after the sample and titrant flow paths are joined, as in conventional methods, it is necessary to accurately detect the change in color spreading in the flow direction over a long period of time. However, according to the present disclosure, it is only necessary to detect the change in color in the direction perpendicular to the flow direction at the measurement point, making it possible to measure the concentration of the sample more quickly.

[0014] In the present disclosure, the flow path of the titrant is joined to the flow path of the sample from both sides of the flow path of the sample, In the post-junction flow path, at the measurement point, in a direction perpendicular to the flow direction of the post-junction flow path The concentration of the sample may be measured based on the distance between the boundaries at which the color tone of the indicator changes.

[0015] Here, the flow path of the titrant is merged with the flow path of the sample from both sides of the flow path of the sample. As a result, in the flow path after the merging, as the chemical reaction between the sample and the titrant progresses, a region of a specific color tone indicated by the indicator (for example, a region of a color tone indicating a neutralization point (or an equivalence point)) spreads on both sides in the width direction toward the downstream side. This makes it possible to measure the concentration of the sample by detecting the distance between the boundaries at the measurement point where the color tone of the indicator changes in the flow direction and the perpendicular direction of the flow path after the merging, without the need to define a specific reference point. Since the boundary at which the color tone of the indicator changes can be detected with high accuracy, according to the present disclosure, it is possible to improve the measurement accuracy of the concentration of the sample. In this case, the boundary on one side at the measurement point where the color tone of the indicator changes in the flow direction and the perpendicular direction of the flow path after the merging is considered to be the reference point.

[0016] In the present disclosure, a calibration curve showing a relationship between the distance at the measurement point and the concentration of the sample is prepared in advance, The concentration of the sample may be measured from the calibration curve and the distance detected at the measurement point.

[0017] In this way, by creating a calibration curve in advance that indicates the relationship between the distance at the measurement point and the concentration of the sample, it is possible to measure the concentration of the sample more accurately and easily.

[0018] In addition, in the present disclosure, an image of the flow in the post-junction flow path at the measurement point may be acquired, the acquired image may be converted into a grayscale image, and the distance may be calculated based on the luminance of each pixel in the grayscale image. Alternatively, the acquired image may be separated into RGB components, and the distance may be calculated based on the luminance of each pixel in an image of any of the separated RGB components. According to these, the distance can be calculated using an image in which the boundary is more easily detected, regardless of the type of indicator or the actual color tone, and the accuracy of the concentration measurement of the sample can be improved.

[0019] The present disclosure also provides a chemical titration system for measuring the concentration of a sample based on the color of an indicator added to the sample or the titrant when a titrant is added to the sample, the system comprising: a flow path element having a titration flow path in which the sample and the titration solution flow into each other and are joined to form a joined flow path; an image acquisition unit that acquires an image of the flow at a predetermined measurement point in the post-junction flow path in the flow path element; a distance detection unit that detects a distance between a boundary at which a color tone of the indicator changes and a reference point in a direction perpendicular to the flow direction of the post-junction flow path in the image acquired by the image acquisition unit; a concentration calculation unit that calculates a concentration of the sample based on the distance between a boundary at which a color tone of the indicator changes and a reference point detected by the distance detection unit; The present invention may be a chemical titration system comprising:

[0020] In the chemical titration system according to the present disclosure, in the flow path element, the flow path into which the titrant flows is joined to the flow path into which the sample flows from both sides of the flow path into which the sample flows; the distance detection unit detects a distance between boundaries at which a color of the indicator changes on both sides of the sample flow in a direction perpendicular to a flow direction of the post-junction flow path at the measurement point; The concentration calculation unit may calculate the concentration of the sample based on the distance between boundaries at which the color of the indicator changes on both sides of the sample flow detected by the distance detection unit.

[0021] In addition, the chemical titration system of the present disclosure further includes a storage unit in which a relationship between the distance at the measurement point and the concentration of the sample is stored, The concentration calculation unit may calculate the concentration of the sample based on the relationship between the distance at the measurement point and the concentration of the sample read from the memory unit, and the distance between the boundary where the color tone of the indicator changes detected by the distance detection unit and a reference point.

[0022] In addition, in the chemical titration system of the present disclosure, the distance detection unit may grayscale the image acquired by the image acquisition unit, and detect the distance based on the brightness of each pixel in the image after the grayscale conversion.

[0023] In addition, in the chemical titration system of the present disclosure, the distance detection unit may separate the image acquired by the image acquisition unit into RGB components, and detect the distance based on the brightness of each pixel in the image based on any of the separated RGB components.

[0024] The present invention can be achieved by combining the above-described configurations and processes as long as no technical contradiction occurs. Effect of the Invention

[0025] According to the present invention, it is possible to perform chemical titration with higher accuracy using a simpler device or an easier method. [Brief description of the drawings]

[0026] [Figure 1] FIG. 1 is a schematic diagram showing the configuration of a chemical titration system applicable to the chemical titration method according to the embodiment. [Diagram 2]FIG. 2 is a schematic diagram showing, in a simplified manner, a modified example of the shape of a flow channel in a plan view in a chemical titration system applicable to the chemical titration method according to the embodiment. [Diagram 3] 3A to 3D are flow charts for explaining the procedure for producing a flow channel element according to the embodiment. [Figure 4] 4A and 4B are diagrams for specifically explaining the procedure for calculating the concentration of a sample in the chemical titration method according to the embodiment. [Diagram 5] 5A to 5D are diagrams specifically illustrating another procedure for calculating the concentration of a sample in the chemical titration method according to the embodiment. [Figure 6] FIG. 6 is a graph showing the relationship between hydrochloric acid concentration and distance. [Figure 7] FIG. 7 shows images captured at predetermined measurement points for each titration using hydrochloric acid of each concentration. [Figure 8] FIG. 8 is a graph showing the relationship between the concentration of an aqueous acetic acid solution and the distance. [Figure 9] FIG. 9 shows images including predetermined measurement points for each titration using aqueous acetic acid solutions of different concentrations. [Figure 10] FIG. 10 is a schematic diagram showing in a simplified manner an example of the shape of a flow channel in a plan view in a chemical titration system applicable to a chemical titration method according to a modified example. [Figure 11] FIG. 11 is a schematic diagram showing an example of flow injection titration utilizing material diffusion, which is an example of chemical titration according to a conventional embodiment. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0027] [Embodiment] Hereinafter, specific embodiments of the present invention will be described with reference to the drawings. The materials, shapes, relative arrangements, and the like of the components described in the description are not intended to limit the scope of the present invention to those elements unless otherwise specified.

[0028] <Configuration> FIG. 1 is a schematic diagram showing the configuration of a chemical titration system 1 applicable to the chemical titration method according to the embodiment. As shown in FIG. 1, the chemical titration system 1 includes a flow channel element 11. The flow channel element 11 is an element formed between a glass substrate 116 and a resin cover 117, in which a sample injection port 111, a sample flow channel 112, two titrant injection ports 113, two titration flow channels 114, and a confluence flow channel 115, which is a flow channel where the titration flow channel 114 is confluent with the sample flow channel 112 from both sides of the sample flow channel 112. In this embodiment, a liquid sample is injected into the sample injection port 111, and a titrant is injected into the titrant injection port 113. The sample and the titrant flow in the sample flow channel 112 and the titrant flow channel 114 flow in the direction of the arrows, respectively, and confluence at a connection point between the sample flow channel 112 and the titration flow channel 114, causing a chemical reaction. The chemical reaction continues while flowing in the confluence flow channel 115. In the following, an example will be shown in which the sample is an acidic solution and the titrant is a basic solution.

[0029] In addition, an indicator for titration is added to either or both of the sample and the titrant. The indicator changes color due to a chemical reaction occurring in the post-junction flow path 115, so an operator using the chemical titration system 1 can visually confirm that a chemical reaction has occurred. When a chemical reaction occurs, the area where the chemical reaction between the sample and the titrant has occurred spreads in a direction perpendicular to the extension direction of the post-junction flow path 115 (i.e., the up-down direction in the orientation of FIG. 1), and the extent of the spread increases toward the downstream side of the post-junction flow path 115 (i.e., the right side in the orientation of FIG. 1). The area where the sample flows, the area where the titrant flows, and the area where the chemical reaction has occurred each show a unique color tone according to the indicator. That is, the width of the area of ​​the color tone indicating the point where the concentration of the sample and the concentration of the titrant are equivalent increases toward the downstream side of the post-junction flow path 115. The hatched area shown in FIG. 1 represents the area where the color of the indicator has changed due to the chemical reaction.

[0030] Here, in this embodiment, as described above, the sample is an acidic solution, the titrant is a basic solution, and the indicator changes color depending on the liquid property (i.e., pH). In this case, the above-mentioned chemical reaction is more specifically a neutralization reaction, and the point where the concentration of the sample and the concentration of the titrant become equivalent is more specifically a neutralization point. The indicator may be appropriately determined depending on the types of the acidic solution and the basic solution used in the titration. For example, when titrating with a combination of a strongly acidic solution and a strongly basic solution, such as hydrochloric acid and a sodium hydroxide aqueous solution, the liquid property at the neutralization point is neutral, so it is preferable to use a BTB solution as the indicator. When titrating with a combination of a weakly acidic solution and a strongly basic solution, such as an acetic acid solution and a sodium hydroxide aqueous solution, the liquid property at the neutralization point is basic, so it is preferable to use a phenolphthalein solution as the indicator.

[0031] By using the chemical titration system 1 and referring to the region where the color of the indicator has changed due to the chemical reaction, it is possible to measure the concentration of the sample based on the distance d between the boundaries where the color of the indicator changes in the direction perpendicular to the flow direction of the confluence flow channel 115 at a predetermined measurement point in the confluence flow channel 115, which is shown in a dashed circle in FIG. 1. The procedure for measuring the concentration of the sample is as follows. First, the predetermined measurement point is captured by the camera 12 so that the entire range of the distance d is included in the captured image. It is preferable that the camera 12 is capable of capturing an image that clearly shows the surface condition of the imaged object, such as a microscope camera. Next, the captured image is captured by the image capture unit 13, and the distance d is detected by the distance detection unit 14 based on this captured image. Then, the concentration of the sample can be calculated with high accuracy by the concentration calculation unit 15 based on the distance d. At this time, the concentration of the sample is calculated using data indicating the relationship between the distance d and the concentration of the sample stored in the memory unit 16. This procedure will be described in more detail below with reference to FIGS. 4A and 4B.

[0032] Since the boundary where the color tone of the indicator changes can be detected with high accuracy, the distance between the boundaries where the color tone of the indicator changes in the direction perpendicular to the flow direction of the post-junction flow path 115 at a predetermined measurement point does not necessarily have to be the distance d. For example, the distance d may be the distance between the lower wall surface of the post-junction flow path 115 and the upper boundary where the color of the indicator changes in Fig. 1. When the distance between the boundaries where the color of the indicator changes in the direction perpendicular to the flow direction of the post-junction flow path 115 is d as in this embodiment, the lower boundary where the color of the indicator changes can be considered as the reference point (point s shown in Fig. 1).

[0033] In addition, the flow channel element 11 is small and lightweight, and the length of the flow channel element 11 in the vertical direction in the direction shown in FIG. 1 may be, for example, several centimeters. Therefore, it is easy to use the flow channel element 11 even when it is preferable to carry it to the site, such as when performing environmental analysis of a river. It can also be applied to in-line analysis in a factory or the like. Since the concentration of a sample can be measured simply by flowing the sample and the titrant through the sample flow channel 112, the titration flow channel 114, and the post-merged flow channel 115 (hereinafter, these are also simply referred to as "flow channels"), advanced technology is not required, and the range of human resources that can be selected as an operator is expanded. In addition, the flow channel element 11 has a simple flow channel design, and the cost required for designing is very low. The shape of the flow channel in a plan view does not necessarily have to be a cross shape as shown in FIG. 1. For example, as shown simply in FIG. 2, the angle between the sample flow channel 112 and the titration flow channel 114 may not be a right angle. In the example shown in FIG. 2, the flows of the sample and titrant are less likely to be disturbed at the confluence of the sample flow channel 112 and the titration flow channel 114, and the flows of the sample and titrant in the post-confluence flow channel 115 can be stabilized.

[0034] In addition, in the method of chemical titration according to the conventional embodiment shown in FIG. 11, the sample needs to be sufficiently diffused in order to measure the concentration of the sample, which takes a long time. However, in the chemical titration method according to the present embodiment, it is only necessary to detect the change in color tone in the direction perpendicular to the flow direction of the post-junction flow path 115 at a specified measurement point, and the concentration of the sample can be measured more quickly and, as described above, with higher accuracy.

[0035] <Production method> 3A to 3D are flow diagrams for explaining the manufacturing procedure of the flow channel element 11 according to the embodiment. In the procedure according to this flow, first, as shown in FIG. 3A, a mold 2 is manufactured by, for example, a 3D printer. Next, as shown in FIG. 3B, a silicon elastomer 3 is molded to match the uneven shape of the mold 2. Next, as shown in FIG. 3C, the solidified silicon elastomer 3 is peeled off from the mold 2. This produces a resin cover 117. Note that since the silicon elastomer 3 is a material suitable for extrusion molding, it can be easily peeled off from the mold 2. In addition, the recess of the silicon elastomer 3 shown in FIG. 3C is a part corresponding to the cross section of the flow channel, and the shape of the cross section of the flow channel is rectangular to match the protrusion of the mold 2. By having the cross section of the flow channel have a rectangular shape, the sample and titration solution flowing through the flow channel are easily diffused. Finally, as shown in FIG. 3D, the silicon elastomer 3 and the glass substrate 116 are bonded to cover the recess of the silicon elastomer 3. Through the above flow, the flow channel element 11 is completed.

[0036] <Chemical titration method> 4A and 4B are diagrams for specifically explaining the procedure for calculating the concentration of a sample in the chemical titration method according to the embodiment. FIG. 4A is an image of a predetermined measurement point shown in FIG. 1 captured by a camera 12, acquired by an image acquisition unit 13, and grayscaled by a distance detection unit 14. Grayscaling creates a difference in pixel brightness between the area where the indicator has changed color and the area where it has not, making the boundary between these areas clear. The distance d shown in is the same as the distance d shown in FIG. 1 and is detected by grayscaling.

[0037] FIG. 4B is a graph of a calibration curve based on data showing the relationship between the concentration of a sample and the distance d stored in the memory unit 16. In FIG. 4B, the horizontal axis represents the concentration of the sample, and the vertical axis represents the distance d. The data showing the relationship between the concentration of the sample and the distance d is obtained by performing an experiment or the like to calculate the distance d for a predetermined concentration of the sample, and determining the relationship between the concentration of the sample and the distance d for a plurality of concentrations (four in FIG. 4B). This calibration curve data may be stored in the memory unit 16 as a table, or may be stored as a function showing the relationship between the concentration of the sample and the distance d. The concentration calculation unit 15 reads out this calibration curve data from the memory unit 16, and calculates the concentration of the sample corresponding to the distance d detected by the distance detection unit 14. Also, from the calibration curve, the greater the concentration of the sample, the greater the distance d at the same measurement point. That is, it is clear that the diffusion speed of the solute in the sample is high.

[0038] In the above example, the chemical titration system 1 automatically measures the concentration from the image acquisition unit 13 using the function of the concentration calculation unit 15, but part of the measurement may be performed manually. Instead of automatically calculating the concentration using the data stored in the storage unit 16, the concentration may be calculated manually using a calibration curve that has actually been created.

[0039] 5A to 5D show a procedure for accurately determining the distance d that is different from the procedure described with reference to FIG. 4A and FIG. 4B. FIG. 5A shows an image captured by the image capture unit 13 after estimating the pH of the neutralization point (or equivalence point) and injecting a buffer solution of that pH into the flow path element 11. Here, the pH of the buffer solution is about 7.0, and the buffer solution contains a BTB solution, so that in the captured image shown in FIG. 5A, the entire post-merged flow path 115 is actually green on average. Next, the captured image is separated into RGB components, and only the data of the R value is extracted. The average value of the R value at this time is set as a reference value. Then, as shown in FIG. 5B, a graph is created in which the horizontal axis represents the distance d and the vertical axis represents the brightness of pixels in the captured image based on the R component. The point indicated by the arrow in FIG. 5B represents the reference value.

[0040] Next, as explained with reference to FIG. 1, a sample is injected into the flow path element 11, and an image as shown in FIG. 5C is acquired by the image acquisition unit 13. Next, the acquired image is similarly separated into RGB components, and only the R value data is extracted. Then, as shown in FIG. 5D, a graph is created in which the horizontal axis represents distance d and the vertical axis represents the brightness of pixels in the captured image based on the R component, and two points whose brightness is equal to the reference point shown in FIG. 5B are plotted. Then, the distance between the two points shown in FIG. 5D (the distance indicated by the double-headed arrow) is detected as the distance d by the distance detection unit 14.

[0041] After the distance d is detected, it is possible to calculate the concentration of the sample corresponding to the distance d using a calibration curve created in advance, as described with reference to Fig. 4B. In addition, in the captured images of Fig. 5A and Fig. 5C, the component to be extracted is not limited to the R component, and may be the G component or the B component depending on the type of buffer solution.

[0042] Example The experimental results are shown below as examples. Figure 6 is a graph showing the relationship between the concentration of hydrochloric acid and the distance d. In the experiment to determine this relationship, the unit of concentration is mM, and the unit of distance d is mm. Five different concentrations of hydrochloric acid, 25 mM, 50 mM, 75 mM, 100 mM, and 150 mM, were used. For each concentration, the distance d was measured three times, and the average value and standard deviation of the three measurements were calculated. An aqueous sodium hydroxide solution was used as the titrant.

[0043] As described above, when titration is performed using a combination of hydrochloric acid as a sample and an aqueous sodium hydroxide solution as a titrant, and the relationship between the concentration of hydrochloric acid and the distance d is obtained for multiple concentrations (five in FIG. 6), a function (a linear function in FIG. 6) is obtained based on these relationships, and the distance d can be uniquely obtained for any concentration of hydrochloric acid based on this function. Also, as described above, the higher the concentration of hydrochloric acid, the larger the distance d at the same measurement point. In other words, it is clear that the diffusion speed of hydrogen chloride, which is a solute, is high. Also, FIG. 7 shows images captured at each time including a predetermined measurement point when titrating using hydrochloric acid of each concentration. It is also clear from FIG. 7 that the higher the concentration of hydrochloric acid, the larger the distance d.

[0044] FIG. 8 is a graph showing the relationship between the concentration of the acetic acid aqueous solution and the distance d. Five types of acetic acid aqueous solutions, 150 mM, 250 mM, 300 mM, 350 mM, and 400 mM, were used. Other conditions are the same as those in the experiment described with FIG. 6, and therefore will not be described. In the case of using a weakly acidic aqueous solution as the sample and a strongly alkaline aqueous solution as the titrant, the greater the concentration of the sample, the greater the distance d at the same measurement point, as in the experiment described with FIG. 6. FIG. 9 shows images including a predetermined measurement point for each titration using acetic acid aqueous solutions of each concentration. It is clear from FIG. 9 that the greater the concentration of hydrochloric acid, the greater the distance d. The concentration of the acetic acid aqueous solution calculated by the conventional chemical titration method was 364.6 mM, whereas the concentration of the acetic acid aqueous solution calculated by the chemical titration method according to the present embodiment under the same conditions was 363.7 mM. The relative error at this time was 0.27%.

[0045] [Embodiment 2] Another embodiment of the present invention will be described below with reference to Fig. 10. Note that the materials, shapes, and relative arrangements of components other than the flow path element 11a according to the embodiment shown in Fig. 10 are the same as those of the chemical titration system 1 according to the embodiment shown in Fig. 1, so that such components are omitted in Fig. 10 and only the flow path element 11a is shown.

[0046] As a difference from the flow path element 11 shown in FIG. 1, the flow path element 11a shown in FIG. 10 has a substantially Y-shaped shape in a plan view of the entire flow path element 11a. The flow path element 11a has one titrant inlet 113a and one titration flow path 114a through which the titrant injected into the titrant inlet 113a flows along the direction of the arrow. The titration flow path 114a merges with a sample flow path 112a, which is also included in the flow path element 11a and through which the sample injected into the sample inlet 111a flows along the direction of the arrow, and a post-merged flow path 115a is formed downstream from the merged point. The sample flow path 112a and the titration flow path 114a merge at an obtuse angle to each other, so that the flow path element 11a has a substantially Y-shaped shape in a plan view of the entire flow path element 11a. This makes it easier to smoothly form the boundary of the shaded area shown in FIG. 10, which represents the area where the color of the indicator has changed due to a chemical reaction.

[0047] In addition, in flow path element 11a, the lower wall surface of post-junction flow path 115a at a predetermined measurement point shown in a dashed circle in Fig. 10 can be considered as a reference point (point s2 shown in Fig. 10). That is, in flow path element 11a, the distance between the reference point and the upper boundary of the area where the color of the indicator has changed due to a chemical reaction at the predetermined measurement point can be expressed as d.

[0048] In the above embodiment, the method of identifying the boundary between the area where the indicator has changed color and the area where it has not changed color at the measurement point is to convert the image into grayscale or to decompose the image into any of the RGB components and detect the brightness. However, the method of identifying the boundary is not limited to this. For example, a reference light may be irradiated onto the post-junction flow path, and a color change may be detected based on a change in the light absorption characteristics, particularly in the ultraviolet or infrared region. In addition, the method of identifying the boundary may be based on a change in the refractive index, viscosity, or electrical conductivity in the post-junction flow path. Methods for detecting changes in temperature are also included. [Explanation of symbols]

[0049] 1. Chemical Titration System 11, 11a... Flow path element 111, 111a: Sample injection port 112, 112a: Sample flow path 113, 113a...Titrant inlet 114, 114a...Titration flow path 115, 115a...Flow path after merging 116: Glass substrate 117...Resin cover 12. Camera 13. Image acquisition section 14 Distance detection section 15...Concentration calculation section 16································ Storage section 2. Mold 3. Silicon elastomer

Claims

1. A chemical titration method for measuring the concentration of a sample by the color tone of an indicator added to the sample or the titrant when a titrant is added to the sample, comprising the steps of: The sample and the titrant are respectively introduced into flow paths for titration, and the flow path of the sample is joined to the flow path of the titrant; A chemical titration method, characterized in that the concentration of a sample is measured based on the distance between a boundary at which the color of the indicator changes and a reference point in a direction perpendicular to the flow direction of the post-junction flow path at a predetermined measurement point in the post-junction flow path, which is a flow path downstream of the junction of the sample flow path and the titrant flow path.

2. the flow path of the titrant is joined to the flow path of the sample from both sides of the flow path of the sample; 2. The chemical titration method according to claim 1, characterized in that the concentration of the sample is measured based on the distance between boundaries at which the color tone of the indicator changes in a direction perpendicular to the flow direction of the post-junction flow path at the measurement point in the post-junction flow path.

3. A calibration curve showing a relationship between the distance at the measurement point and the concentration of the sample is prepared in advance; 2. The chemical titration method according to claim 1, further comprising the step of determining a concentration of the sample from the calibration curve and the distance detected at the measurement point.

4. 2. The chemical titration method according to claim 1, further comprising the steps of: acquiring an image of the flow in the post-junction flow path at the measurement point; grayscaling the acquired image; and calculating the distance based on the brightness of each pixel in the grayscaled image.

5. 2. The chemical titration method according to claim 1, further comprising the steps of: acquiring an image of the flow in the post-junction flow path at the measurement point; separating the acquired image into RGB components; and calculating the distance based on the brightness of each pixel in the image for any of the separated RGB components.

6. A chemical titration system for measuring the concentration of a sample by the color tone of an indicator added to the sample or the titrant when a titrant is added to the sample, comprising: a flow path element having a titration flow path in which the sample and the titration solution flow into each other and are joined to form a joined flow path; an image acquisition unit that acquires an image of the flow at a predetermined measurement point in the post-junction flow path in the flow path element; a distance detection unit that detects a distance between a boundary at which a color tone of the indicator changes and a reference point in a direction perpendicular to the flow direction of the post-junction flow path in the image acquired by the image acquisition unit; a concentration calculation unit that calculates a concentration of the sample based on the distance between a boundary at which a color tone of the indicator changes and a reference point detected by the distance detection unit; A chemical titration system comprising:

7. In the flow path element, the flow path into which the titration solution flows is joined to the flow path into which the sample flows from both sides of the flow path into which the sample flows; the distance detection unit detects a distance between boundaries at which a color of the indicator changes on both sides of the sample flow in a direction perpendicular to a flow direction of the post-junction flow path at the measurement point; The concentration calculation unit is configured to calculate the concentration of the sample on both sides of the sample flow detected by the distance detection unit.

7. The chemical titration system of claim 6, wherein the concentration of the sample is calculated based on the distance between the boundaries where the drug changes color.

8. A storage unit storing a relationship between the distance at the measurement point and the concentration of the sample, 7. The chemical titration system according to claim 6, wherein the concentration calculation unit calculates the concentration of the sample based on the relationship between the distance at the measurement point and the concentration of the sample read from the memory unit, and the distance between the boundary where the color tone of the indicator changes and a reference point detected by the distance detection unit.

9. 7. The chemical titration system according to claim 6, wherein the distance detection unit grayscales the image acquired by the image acquisition unit, and detects the distance based on the luminance of each pixel in the image after the grayscale conversion.

10. The chemical titration system according to claim 6, characterized in that the distance detection unit separates the image acquired by the image acquisition unit into RGB components and detects the distance based on the luminance of each pixel in the image based on any one of the separated RGB components.

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