JP7262645B2 - Component analysis method and component analysis device - Google Patents

Description

The present invention relates to a component analysis method and a component analysis device using continuous sample introduction.

In a component analysis system using continuous sample introduction such as capillary electrophoresis, the vertical axis is the detection data such as absorbance obtained by the detector, and the horizontal axis is the time. , there is a technique of performing component analysis using a differentiated waveform such as an electropherogram obtained by differentiating this original waveform with respect to time.

Each peak appearing in the differential waveform corresponds to each component contained in the introduced sample. In addition, components can be identified by differences in the time at which the top of each peak was observed. Furthermore, the area occupied by each peak in the differential waveform serves as an indicator of the content of the component in the sample. For example, a differentiated waveform of a hemoglobin measuring system by continuous sample introduction using blood as a sample has a shape as shown in Patent Document 1 below.

JP 2018-72336 A

In a component analysis system by continuous sample introduction such as capillary electrophoresis, as described above, the component is identified by the peak observed in the differential waveform obtained by differentiating the absorbance curve along the time axis, and the peak Relative quantification of the component was performed based on the area occupied by the portion in the differential waveform. At that time, valleys (referred to as "bottoms") generated between peaks are often used as boundaries between the peaks, but the bottoms are often unclear. In particular, when the two peaks are fused, the lower of the two peaks may be absorbed by the higher peak, making it difficult to distinguish between the two peaks. was difficult or impossible to identify the bottom.

Embodiments of the present invention make it possible to clearly define the boundary between two peaks even when it is difficult to clearly define the boundary between two peaks in a differential waveform in a component analysis system using continuous sample introduction. The task is to

In a first aspect of the present disclosure, a sample solution continuously introduced into a channel is separated in the channel, and the sample solution is optically measured at a measurement position in the channel over time. A component analysis method comprising: a measuring step of obtaining measured values; and an analyzing step of analyzing a plurality of components contained in a sample based on the optically measured values, wherein the analyzing step comprises analyzing the optically measured values as a time axis. an original waveform acquisition step of acquiring an original waveform plotted on a two-dimensional plane along the , and a measurement value that is a waveform obtained by differentiating the original waveform along the axis of the optical measurement value orthogonal to the time axis A measurement value differentiation step of obtaining a differential waveform, and a measurement value boundary determination step of setting an optical measurement value corresponding to a shoulder peak of the measurement value differential waveform as a separation boundary between the plurality of components.

In a second aspect of the present disclosure, in the first aspect, the analysis step includes a time differentiation step of acquiring a time-differentiated waveform that is a waveform obtained by differentiating the original waveform along the time axis; With regard to the time-differentiated waveform, the value obtained by integrating the time-differentiated waveform for the integration interval having the adjacent integration boundaries as the integration boundaries at the time points corresponding to the separation boundaries is the component corresponding to the integration interval. and an integral quantification step of calculating the relative content of in said sample.

According to a third aspect of the present disclosure, in the first aspect, the analysis step calculates a distance of an interval having both ends of the separation boundary adjacent along the axis of the optical measurement value as the component corresponding to the interval. of is calculated as the relative content in the sample.

In the fourth aspect of the present disclosure, the sample solution continuously introduced into the channel is separated in the channel, and the sample solution is measured at the measurement position of the channel over time to obtain the optical measurement value. and an analysis step of analyzing a plurality of components contained in a sample based on the optical measurement values, wherein the analysis step includes the optical measurement values along the time axis An original waveform acquisition step of acquiring an original waveform plotted on a two-dimensional plane, a time differentiation step of acquiring a time-differentiated waveform that is a waveform obtained by differentiating the original waveform along the time axis, and the time differentiation an inverse differentiation step of obtaining an inverse differential waveform obtained by plotting the inverse of the waveform along the time axis; and determining a time boundary as a separation boundary between the plurality of components at a point corresponding to a shoulder peak of the inverse differential waveform. and

According to a fifth aspect of the present disclosure, in the fourth aspect, the analysis step includes, with respect to the time-differentiated waveform, the integration interval having the time point corresponding to the separation boundary as an integration boundary and the adjacent integration boundaries as both ends. an integral quantification step of calculating a value obtained by integrating the time-differentiated waveform as a relative content in the sample of the component corresponding to the integration interval.

In a sixth aspect of the present disclosure, in any one of the first to fifth aspects, a voltage is applied to the sample solution continuously introduced into the capillary tube as the channel to separate the sample solution. The optical measurements are obtained by capillary electrophoresis.

In a seventh aspect of the present disclosure, a channel into which a sample solution is continuously introduced and the sample solution separated in the channel are optically measured over time at a measurement position in the channel. A component analysis device comprising: a measurement unit that obtains optical measurement values; and an analysis unit that analyzes a plurality of components contained in a sample based on the optical measurement values, wherein the analysis unit analyzes the optical measurement values on a time axis. an original waveform acquisition unit that acquires an original waveform plotted on a two-dimensional plane along the , and a measured value that is a waveform obtained by differentiating the original waveform along the axis of the optical measurement value orthogonal to the time axis It has a measurement value differentiating section that obtains a differential waveform, and a measurement value boundary determination section that uses an optical measurement value corresponding to a shoulder peak of the measured value differential waveform as a separation boundary between the plurality of components.

In an eighth aspect of the present disclosure, in the seventh aspect, the analysis unit includes a time differentiation unit that acquires a time-differentiated waveform that is a waveform obtained by differentiating the original waveform along the time axis; With regard to the time-differentiated waveform, the value obtained by integrating the time-differentiated waveform for the integration interval having the adjacent integration boundaries as the integration boundaries at the time points corresponding to the separation boundaries is the component corresponding to the integration interval. and an integral quantification part that calculates the relative content in the sample of

In a ninth aspect of the present disclosure, in the seventh aspect, the analysis unit calculates the distance of the section having the separation boundaries adjacent along the axis of the optical measurement value as the component corresponding to the section of is calculated as the relative content in the sample.

In a tenth aspect of the present disclosure, a channel into which a sample solution is continuously introduced and the sample solution separated in the channel are optically measured over time at a measurement position in the channel. A component analysis device comprising: a measurement unit that obtains optical measurement values; and an analysis unit that analyzes a plurality of components contained in a sample based on the optical measurement values, wherein the analysis unit analyzes the optical measurement values on a time axis. an original waveform acquisition unit that acquires an original waveform plotted on a two-dimensional plane along the , a time differentiation unit that acquires a time-differentiated waveform that is a waveform obtained by differentiating the original waveform along the time axis; A reverse differentiation unit that acquires a reverse differential waveform obtained by plotting the reciprocal of the time differential waveform along the time axis, and a time point corresponding to the shoulder peak of the reverse differential waveform as a separation boundary between the plurality of components. and a time boundary determiner.

In the tenth aspect, the component analysis device of the eleventh aspect of the present disclosure is such that the analysis unit treats the time-differentiated waveform as an integration boundary at a time point corresponding to the separation boundary, and with adjacent integration boundaries as both ends. an integral quantification unit that calculates a value obtained by integrating the time-differentiated waveform for an integration interval as a relative content in the sample of the component corresponding to the integration interval.

In the embodiment of the present invention, in a component analysis system using continuous sample introduction, even if it is difficult to clearly define the boundary between two peaks in the differential waveform, it is possible to clearly define the boundary. becomes.

1 is a system schematic diagram showing a component analysis system that can be used to carry out the component analysis method of this embodiment; FIG. FIG. 2 is a plan view showing an analysis chip used in the analysis system of FIG. 1; 3 is a cross-sectional view taken along line III-III of FIG. 2; FIG. It is a block diagram which shows the hardware constitutions of a control part. It is a block diagram showing the functional composition of a component analyzer. 3 is a block diagram showing the functional configuration of an analysis unit in the first aspect; FIG. It is a flow chart showing the outline of the ingredient analysis method in the 1st mode. An example of the original waveform is indicated by a solid line. A time-differentiated waveform with respect to the original waveform in FIG. 8 is indicated by a dashed line. In FIG. 9, the measured value differential waveform with respect to the original waveform is added with a dotted line. FIG. 11 is a block diagram showing the functional configuration of an analysis unit in a second aspect; FIG. It is a flowchart showing the outline|summary of the component-analysis method in a 2nd aspect. FIG. 12 is a block diagram showing the functional configuration of an analysis unit in the third aspect; FIG. It is a flowchart showing the outline|summary of the component-analysis method in a 3rd aspect. The dotted line indicates the differential waveform of the measured value with respect to the original waveform in FIG. FIG. 11 is a block diagram showing the functional configuration of an analysis unit in the fourth aspect; FIG. It is a flowchart showing the outline|summary of the component-analysis method in a 4th aspect. In FIG. 9, an inverse differentiated waveform with respect to the time differentiated waveform is added with a dotted line. FIG. 12 is a block diagram showing the functional configuration of an analysis unit in the fifth aspect; FIG. FIG. 11 is a flow chart showing an outline of a component analysis method in the fifth aspect; FIG. The time-differentiated waveform obtained in the time-differential process shows the influence of the environmental temperature and the sample concentration during measurement. FIG. 21(A) shows the case of an environmental temperature of 23° C. and a low-concentration sample. FIG. 21B shows the case of the environmental temperature of 23° C. and the high-concentration sample. FIG. 21(C) shows the case of an environmental temperature of 8° C. and a low-concentration sample. FIG. 21(D) shows the case of an environmental temperature of 8° C. and a high-concentration sample. The time-differentiated waveform obtained in the time-differential process shows the influence of the environmental temperature and the sample concentration during measurement. FIG. 22(A) shows the case of an environmental temperature of 23° C. and a low-concentration sample. FIG. 22B shows the case of the environmental temperature of 23° C. and the high-concentration sample. FIG. 22(C) shows the case of an environmental temperature of 8° C. and a low-concentration sample. FIG. 22(D) shows the case of an environmental temperature of 8° C. and a high-concentration sample.

Embodiments of the present disclosure will be described below with reference to the drawings as appropriate.

<Component analysis system>
FIG. 1 shows a schematic configuration of a component analysis system A1 that can be used to execute the component analysis method according to this embodiment. A component analysis system A1 comprises a component analysis device 1 and an analysis chip 2 . The component analysis system A1 is a system that executes an analysis method by capillary electrophoresis on the sample Sa. As long as the sample Sa contains a component that can be analyzed by capillary electrophoresis and is soluble in such a solvent, it may be in any form, such as liquid, solid, or gas. , blood collected from a human body will be described as an example.

Among the components contained in the sample Sa, those to be analyzed include hemoglobin (Hb), albumin (Alb), globulin (α1, α2, β, γ globulin), fibrinogen, and the like. Examples of the hemoglobin include multiple hemoglobin species such as normal hemoglobin (HbA), mutated hemoglobin (HbA1c, HbC, HbD, HbE, HbS, etc.), and fetal hemoglobin (HbF). These components are suitable for analysis by capillary electrophoresis because mutations in amino acids, which are constituents, are likely to be electrically reflected in protein molecules. In the component analysis system A1 according to the present embodiment, these multiple hemoglobin species, that is, mutants of the same type of protein, are used as multiple components, and separation boundaries between these multiple components are determined.

Depending on the component to be analyzed, the sample may be pretreated with an appropriate reagent, or a preliminary separation treatment may be performed by another method (for example, chromatography method).

The analysis chip 2 holds the sample Sa, and provides an analysis field for the sample Sa in a state of being loaded in the component analyzer 1 . In this embodiment, the analysis chip 2 is configured as a so-called disposable analysis chip that is intended to be discarded after one analysis is completed. As shown in FIGS. 2 and 3, the analysis chip 2 includes a main body 21, a mixing tank 22, an introduction tank 23, a filter 24, a discharge tank 25, an electrode tank 26, a channel 27 and a communication channel . 2 is a plan view of the analysis chip 2, and FIG. 3 is a cross-sectional view taken along line III-III in FIG. Note that the analysis chip 2 is not limited to a disposable type, and may be used for multiple analyzes. In addition, the component analysis system of this embodiment is not limited to the configuration provided with the separate analysis chip 2 loaded in the component analysis device 1, and the component analysis device 1 has a functional part that performs the same function as the analysis chip 2. It may be a built-in configuration.

The main body 21 serves as a base for the analysis chip 2, and its material is not particularly limited, and examples thereof include glass, fused silica, and plastic. In this embodiment, the main body 21 has an upper part 2A and a lower part 2B shown in FIG. 3 which are separately formed and joined together. In addition, you may form the main body 21 not only in this but integrally, for example.

The mixing tank 22 is a place where the sample Sa and the diluent Ld are mixed. The mixing tank 22 is configured as a recess opening upward, for example, by a through hole formed in the upper portion 2A of the main body 21 . The introduction tank 23 is a tank into which the sample solution obtained by mixing the sample Sa and the diluent Ld in the mixing tank 22 is introduced. The introduction tank 23 is configured as a recess opening upward, for example, by a through hole formed in the upper portion 2A of the main body 21 .

The filter 24 is provided at the opening of the introduction tank 23 , which is an example of an introduction path to the introduction tank 23 . A specific configuration of the filter 24 is not limited, and a suitable example is a cellulose acetate membrane filter (manufactured by ADVANTEC, pore size 0.45 μm).

The discharge tank 25 is a tank positioned downstream of the channel 27 . The discharge tank 25 is configured as a recess opening upward, for example, by a through hole formed in the upper portion 2A of the main body 21 . The electrode tank 26 is a tank into which the electrode 31 is inserted in capillary electrophoresis. The electrode reservoir 26 is configured as a recess opening upward, for example, by a through hole formed in the upper portion 2A of the main body 21 . The communication channel 28 connects the introduction tank 23 and the electrode tank 26 and constitutes a conduction path between the introduction tank 23 and the electrode tank 26 .

The channel 27 is formed as a capillary tube connecting the introduction tank 23 and the discharge tank 25, and is a place where electro-osmotic flow (EOF) occurs in electrophoresis. Channel 27 is configured, for example, as a groove formed in lower portion 2B of main body 21 . The main body 21 may be appropriately formed with a concave portion or the like for facilitating irradiation of the flow path 27 with light and emission of the light transmitted through the flow path 27 . Although the size of the flow path 27 is not particularly limited, for example, the width is 25 μm to 100 μm, the depth is 25 μm to 100 μm, and the length is 5 mm to 150 mm. The overall size of the analysis chip 2 is appropriately set according to the size of the channel 27 and the size and arrangement of the mixing tank 22, the introduction tank 23, the discharge tank 25 and the electrode tank .

Note that the analysis chip 2 configured as described above is merely an example, and an analysis chip configured to allow component analysis by capillary electrophoresis can be appropriately employed.

The component analysis device 1 performs analysis processing for the sample Sa in a state loaded with the analysis chip 2 spotted with the sample Sa. The component analyzer 1 includes an electrode 31 , an electrode 32 , a light source 41 , an optical filter 42 , a lens 43 , a slit 44 , a detector 45 , a dispenser 6 , a pump 61 , a diluent tank 71 , a migration liquid tank 72 and a controller 8 . It has The light source 41, the optical filter 42, the lens 43 and the detector 45 constitute the measuring section 40 in this embodiment.

The electrodes 31 and 32 are for applying a predetermined voltage to the channel 27 in capillary electrophoresis. The electrode 31 is inserted into the electrode reservoir 26 of the analysis chip 2 , and the electrode 32 is inserted into the discharge reservoir 25 of the analysis chip 2 . Although the voltage applied to the electrodes 31 and 32 is not particularly limited, it is, for example, 0.5 kV to 20 kV.

The light source 41 is a part that emits light for measuring absorbance as an optical measurement value in capillary electrophoresis. The light source 41 has, for example, an LED chip that emits light in a predetermined wavelength range. The optical filter 42 attenuates light of a predetermined wavelength out of the light from the light source 41 and transmits light of other wavelengths. The lens 43 is for condensing the light that has passed through the optical filter 42 onto the analysis site of the flow path 27 of the analysis chip 2 . The slit 44 is for removing excess light that may cause scattering or the like from the light condensed by the lens 43 .

The detector 45 receives light from the light source 41 that has passed through the channel 27 of the analysis chip 2, and includes, for example, a photodiode and a photo IC.

Thus, the path along which the light emitted from the light source 41 reaches the detector 45 is the optical path. Then, an optical measurement value is measured for the solution flowing through the channel 27 (that is, either the sample solution or the electrophoretic solution, or a mixed solution thereof) at a measurement position 27A where the optical path intersects with the channel 27 . That is, at the measurement position 27A in the channel 27, the measurement unit 40 measures the optical measurement value of the sample solution. This optical measurement includes, for example, absorbance. The absorbance represents the degree to which the light in the optical path is absorbed by the solution flowing through the channel 27, and represents the absolute value of the common logarithm of the ratio of the incident light intensity and the transmitted light intensity. In this case, a general-purpose spectrophotometer can be used as the detector 45 . Even if the absorbance is not used, an optically measured value such as the value of the transmitted light intensity itself can be used in the present invention. In the following, the case of using absorbance as an optical measurement value will be described as an example.

The dispenser 6 dispenses desired amounts of the diluent Ld, the electrophoretic fluid Lm, and the sample solution, and includes, for example, a nozzle. The dispenser 6 can be freely moved between a plurality of predetermined positions in the component analyzer 1 by a driving mechanism (not shown). A pump 61 is a suction source and a discharge source for the dispenser 6 . Also, the pump 61 may be used as a suction source and a discharge source of a port (not shown) provided in the component analyzer 1 . These ports are used for filling the electrophoretic fluid Lm and the like. Also, a dedicated pump other than the pump 61 may be provided.

The diluent tank 71 is a tank for storing the diluent Ld. The diluent tank 71 may be a tank permanently installed in the component analyzer 1 , or may be one in which the component analyzer 1 is loaded with a container containing a predetermined amount of the diluent Ld. The migration liquid tank 72 is a tank for storing the migration liquid Lm. The electrophoresis liquid tank 72 may be a tank permanently installed in the component analyzer 1 , or may be a vessel in which a predetermined amount of the electrophoresis liquid Lm is sealed in the component analyzer 1 .

The diluent Ld is for generating a sample solution by being mixed with the sample Sa. The main agent of the diluent Ld is not particularly limited, and examples thereof include water and physiological saline, and preferred examples thereof include a liquid having components similar to those of the electrophoretic liquid Lm, which will be described later. Moreover, the diluent Ld may contain an additive, if necessary, in addition to the main agent.

The electrophoresis liquid Lm is a medium that fills the discharge tank 25 and the flow path 27 in the analysis step S20 by electrophoresis and causes an electroosmotic flow in the electrophoresis. The electrophoretic liquid Lm is not particularly limited, but one using an acid is desirable. Such acids are, for example, citric acid, maleic acid, tartaric acid, succinic acid, fumaric acid, phthalic acid, malonic acid, malic acid. In addition, the electrophoretic fluid Lm preferably contains a weak base. Examples of the weak base include arginine, lysine, histidine, tris and the like. The pH of the electrophoretic fluid Lm is in the range of pH 4.5-6, for example. Types of buffers for the electrophoretic liquid Lm include MES, ADA, ACES, BES, MOPS, TES, HEPES, and the like. Additives may also be added to the electrophoretic liquid Lm as necessary, in the same manner as described in the description of the diluent Ld.

The control section 8 controls each section in the component analysis device 1 . The control unit 8 has a CPU (Central Processing Unit) 81, a ROM (Read Only Memory) 82, a RAM (Random Access Memory) 83, and a storage 84, as shown in the hardware configuration of FIG. Each component is communicatively connected to each other via a bus 89 .

The CPU 81 is a central processing unit that executes various programs and controls each section. That is, the CPU 81 reads a program from the ROM 82 or the storage 84 and executes the program using the RAM 83 as a work area. The CPU 81 performs control of each configuration and various arithmetic processing according to programs recorded in the ROM 82 or the storage 84 .

The ROM 82 stores various programs and various data. The RAM 83 temporarily stores programs or data as a work area. The storage 84 is configured by a HDD (Hard Disk Drive), SSD (Solid State Drive), or flash memory, and stores various programs including an operating system and various data. In this embodiment, the ROM 82 or storage 84 stores programs and various data for executing the component analysis method according to this embodiment.

The component analysis apparatus 1 implements various functions as shown in FIG. 5 using the above hardware resources and the above configurations when executing the component analysis method according to this embodiment. In addition to the measurement unit 40 described above, these functions include analysis of a plurality of components contained in the sample Sa based on optical measurement values obtained by optically measuring the sample solution over time by the measurement unit 40. Also included is an analysis unit 800 that performs the analysis, which will be described later.

<First Aspect>
In the component analysis method according to the first aspect of the present disclosure, the sample solution continuously introduced into the channel 27 is separated in the channel 27, and the sample solution is separated at the measurement position 27A of the channel 27 over time. A measurement step S10 of optically measuring to obtain an optical measurement value, and an analysis step S20 of analyzing a plurality of components contained in the sample Sa based on the optical measurement value. An original waveform acquisition step S21 for obtaining an original waveform in which the measured values are plotted on a two-dimensional plane along the time axis, and a waveform obtained by differentiating the original waveform along the optical measurement value axis orthogonal to the time axis. a measurement value differentiation step S23 for obtaining a measurement value differential waveform, and a measurement value boundary determination step S24 for determining an optical measurement value corresponding to the shoulder peak of the measurement value differential waveform as a separation boundary between a plurality of components, including.

The component analyzer 1 in this embodiment comprises a channel 27 into which a sample solution is continuously introduced, and the sample solution separated in the channel 27 is optically measured at a measurement position 27A of the channel 27 over time. A measurement unit 40 that obtains an optical measurement value by measurement, and an analysis unit 800 that analyzes a plurality of components contained in the sample Sa based on the optical measurement value. An original waveform acquisition unit 801 that acquires an original waveform plotted on a two-dimensional plane along an axis, and a measurement value that is a waveform obtained by differentiating this original waveform along the optical measurement value axis orthogonal to the time axis. It has a measured value differentiating section 803 that acquires a differential waveform, and a measured value boundary determining section 804 that uses an optical measured value corresponding to the shoulder peak of the measured value differentiated waveform as a separation boundary between the plurality of components.

The functional configuration of the analysis unit 800 in this aspect is as shown in FIG. Hereinafter, the component analysis method in this embodiment will be described with reference to the flowchart of FIG.

In the measurement step S10 shown in FIG. 7, the sample solution is continuously introduced into the channel 27, the sample solution is separated in the channel 27 by voltage application, and the measurement position provided in the channel 27 is measured. An optical measurement is obtained by the measurement unit 40 when 27A is reached. Specifically, an electrode 31 and an electrode 32 are attached upstream and downstream of the channel 27, respectively, and a voltage is applied between them to subject the sample solution to electrophoresis by so-called capillary electrophoresis.

For example, when the component to be analyzed is hemoglobin as described above, its molecular surface is negatively charged. , the component to be analyzed is migrated towards electrode 32, which is the anode. At that time, the electrophoretic speed varies depending on the charged state of the molecular surface. That is, the stronger the negative charge on the surface of the molecule, the higher the migration speed. Therefore, at the stage when the sample solution is introduced into the channel 27, the component with a high migration speed reaches the measurement position 27A more quickly.

At the time when the component with low migration speed reaches the measurement position 27A, the component with high migration speed derived from the sample solution introduced later also reaches the measurement position 27A at the same time. That is, in the channel 27 , when the component with the high migration speed reaches the measurement position 27A first, the component continues to reach as long as the sample solution continues to be introduced into the channel 27 . In addition, the component with a lower migration speed reaches the measurement position 27A with a delay, but once it reaches the measurement position 27A, as long as the sample solution continues to be introduced into the flow channel 27, the component continues to reach the measurement position 27A. will continue to arrive.

In other words, at the measurement position 27A, components with high migration velocities reach first, and then components with lower migration velocities cumulatively reach the measurement position 27A. Therefore, the absorbance as an optical measurement value of the sample solution measured by the measurement unit 40 at the measurement position 27A monotonically increases cumulatively over time.

The original waveform acquisition unit 801 of the analysis unit 800 shown in FIG. 6 acquires the absorbance as an optical measurement value along one axis (for example, the Y axis) in the original waveform acquisition step S21 of the analysis step S20 shown in FIG. and plotted on a two-dimensional plane in contrast with the other time axis (for example, the X axis) to obtain an original waveform. This original waveform is represented as a solid line graph as shown in FIG. 8, for example. It should be noted that the optical measurement values in this aspect need only be acquired as data that can be plotted on a two-dimensional plane, and it is not essential to actually draw a graph based on such data. This also applies to other aspects referred to below.

When this original waveform is viewed along the time axis, the portion with a large gradient indicated by the solid line arrow in FIG. is. A portion with a small gradient as indicated by a dashed arrow indicates that the next component has not yet reached the measurement position 27A. That is, the portion of the original waveform with a large gradient indicates that the component in the sample solution has reached the measurement position 27A. Such a portion with a large gradient in the original waveform is a peak that appears in a waveform obtained by differentiating the original waveform along the time axis (referred to as a "time differentiated waveform"), as shown in the dashed line graph in FIG. represented as a waveform. These peak waveforms are identified as originating from each component. On the time axis, the component corresponding to the left peak waveform has a higher migration speed than the component corresponding to the right peak waveform.

Here, when there are a plurality of peak waveforms in the time-differentiated waveform, adjacent peak waveforms are partitioned by bottoms B, which are valley portions located therebetween. The peak top T of the peak waveform is the maximum value in the time-differentiated waveform, and corresponds to the portion of the original waveform where the slope becomes maximum corresponding to this maximum value. On the other hand, the bottom B is the minimum value in the time-differentiated waveform, and the original waveform has the minimum slope. In other words, in the original waveform, the portion with a steep slope corresponds to the peak top T, and the portion with a gentle slope corresponds to the bottom B.

On the other hand, when the original waveform shown in FIG. 8 is viewed from the optical measurement value axis (Y-axis), the slope of the portion corresponding to the peak top T becomes gentle, and the slope of the portion corresponding to the bottom B becomes steep. Become.

Focusing on this point is the measured value differentiation step S23 in the analysis step S20 shown in FIG. That is, in the measurement value differentiation step S23, the measurement value differentiation unit 803 of the analysis unit 800 shown in FIG. 6 differentiates the original waveform along the axis of the optical measurement value to Acquire a differential waveform of measured value.

As shown in FIG. 10, peak tops T ₁ ' to T ₆ ' in the measured value differential waveform correspond to bottoms B ₁ to B ₆ in the time differential waveform, respectively. In other words, the differential waveform of the measured value is expressed with the peak top and the bottom interchanged with respect to the time differential waveform. In other words, bottoms B ₁ to B ₆ in the time differential waveform are clearly expressed as peak tops T ₁ ' to T ₆ ' in the measured value differential waveform, respectively.

Then, the measured value boundary determining section 804 in the analyzing section 800 shown in FIG. 6 determines the peak tops T ₁ ′ to T ₆ ′ in the measured value boundary determining step S24 in the analyzing step S20 shown in FIG. The corresponding optical measurements s ₁ -s ₆ are defined as the component separation boundaries.

With the configuration of the first aspect described above, the bottoms B ₁ to B ₆ which should be identified as both ends of the peak waveform in the time differential waveform are replaced by the peak tops T ₁ ' to T ₆ in the measured value differential waveform. ' can be recognized respectively. The optical measurement values s ₁ to s ₆ corresponding to the peak tops T ₁ ' to T ₆ ' can be used as separation boundaries of the components contained in the sample Sa.

In order to acquire the peak tops T1 _' to _T6 ' in the differential waveform of measured values, it is not necessary to refer to the time differential waveform at all, but the time differential waveform is referred to in the above description and FIGS. It should be added here that the reason for this is to explain the significance of the peak tops T ₁ ' to T ₆ ' in the differential waveform of the measured value.

<Second Aspect>
The component analysis method according to the second aspect of the present disclosure, in addition to the configuration of the component analysis method according to the first aspect, includes an analysis step S20 in which a time-differentiated waveform, which is a waveform obtained by differentiating the original waveform along the time axis, and a value obtained by integrating the time-differentiated waveform for an integration interval with adjacent integration boundaries as both ends of the time-differentiated waveform, with the time point corresponding to the separation boundary as the integration boundary. It further includes an integration quantification step S28 of calculating the relative content in the sample Sa of the component corresponding to the integration interval.

In addition to the configuration of the component analysis device 1 in the first aspect, the component analysis device 1 in this aspect acquires a time-differentiated waveform, which is a waveform obtained by differentiating the original waveform along the time axis. A time differentiation unit 802, with respect to the time-differentiated waveform, uses the time point corresponding to the separation boundary as an integration boundary, and integrates the time-differentiated waveform for the integration interval having the adjacent integration boundaries at both ends, and an integral quantification unit 808 that calculates the relative content of the corresponding component in the sample Sa.

The functional configuration of the analysis unit 800 in this aspect is as shown in FIG. Hereinafter, the component analysis method in this embodiment will be described with reference to the flowchart of FIG.

The measurement step S10 shown in FIG. 12 is the same as in the first aspect.

The original waveform acquisition unit 801 of the analysis unit 800 shown in FIG. 11 acquires the absorbance as an optical measurement value along one axis (for example, the Y axis) in the original waveform acquisition step S21 of the analysis step S20 shown in FIG. and plotted on a two-dimensional plane in contrast with the other time axis (for example, the X axis) to obtain an original waveform. This original waveform is represented as a solid line graph as shown in FIG. 8, for example. This original waveform acquisition step S21 is the same as in the first mode.

11 is a waveform obtained by differentiating the original waveform along the time axis in the time differentiation step S22 of the analysis step S20 shown in FIG. Get the time differential waveform. This time-differentiated waveform is represented as a dashed line graph as shown in FIGS. 9 and 10. FIG. The relationship between the original waveform and the time-differentiated waveform is the same as described in the first aspect.

11 differentiates the original waveform along the optical measurement value axis in the measured value differentiation step S23 of the analysis step S20 shown in FIG. , to obtain a measured value differential waveform as shown in the dotted line graph in FIG. This measured differential waveform is also the same as in the first mode.

Next, in the measurement value boundary determination step S24 of the analysis step S20 shown in FIG. 12, the measurement value boundary determination unit 804 of the analysis unit ₈₀₀ shown in FIG. The optical measurements s ₁ to s ₆ corresponding respectively to ₆ ' are defined as component separation boundaries.

Then, the integral quantification unit 808 of the analysis unit 800 shown in FIG. 11 performs the peak top T ₁ ′ to The optical measurement values s ₁ to s ₆ respectively corresponding to T ₆ ′ are defined as separation boundaries, and the time points t ₁ to t ₆ corresponding to the bottoms B ₁ to B ₆ of the time-differentiated waveform corresponding thereto are defined as integration boundaries. . Then, the time-differentiated waveform is integrated for the integration interval having the adjacent integration boundaries at both ends, and the area occupied by the time-differentiated waveform in the integration interval is calculated. The value obtained as this area can be regarded as the relative content of the component corresponding to the integration interval (that is, the component recognized as the peak waveform in the time-differentiated waveform).

It should be noted here that the bottom _B3 in FIG. 10 is not necessarily recognized as a clear local minimum in the time differential waveform, but the corresponding peak top _T3 ' in the measured value differential waveform is can be clearly identified as the so-called shoulder peak in Therefore, the instant _t3 corresponding to this bottom _B3 can be clearly defined as the integration boundary _t3 corresponding to the separation boundary _s3 . Then, by integrating the time-differentiated waveform in the integration interval having both the integration boundary _t3 and the adjacent integration boundary _t4 , the peak waveform _P3 , which is not necessarily recognized as a clear peak, can be relatively included. It is possible to calculate the quantity. Of course, for other peak waveforms P ₁ , P ₂ , P ₄ and P ₅ recognized as distinct peaks, t ₁ to t ₂ , t ₂ to t ₃ , t ₄ to t ₅ and t ₅ to t ₆ respectively By similarly integrating the time-differentiated waveform with , it is possible to calculate the relative contents of each.

<Third Aspect>
In the component analysis method according to the third aspect of the present disclosure, in addition to the configuration of the component analysis method according to the first aspect, the analysis step S20 is performed on sections having separated boundaries that are adjacent along the axis of the optical measurement value. Further includes a displacement quantification step S25 for calculating the distance as a relative content in the sample Sa of the component corresponding to the section.

In addition to the configuration of the component analysis device 1 in the first aspect, the component analysis device 1 of the present aspect has the analysis unit 800 that measures the distance of the section having the separation boundaries adjacent along the axis of the optical measurement value as both ends. It further has a displacement quantification part 805 for calculating the relative content in the sample of the component corresponding to the interval.

The functional configuration of the analysis unit 800 in this aspect is as shown in FIG. Hereinafter, the component analysis method in this embodiment will be described with reference to the flowchart of FIG.

The measurement step S10 shown in FIG. 14 is the same as in the first aspect.

The original waveform acquisition unit 801 of the analysis unit 800 shown in FIG. 13 acquires the absorbance as an optical measurement value along one axis (for example, the Y axis) in the original waveform acquisition step S21 of the analysis step S20 shown in FIG. and plotted on a two-dimensional plane in contrast with the other time axis (for example, the X axis) to obtain an original waveform. This original waveform is represented as a solid line graph as shown in FIG. 8, for example. This original waveform acquisition step S21 is the same as in the first mode.

13 differentiates the original waveform along the optical measurement value axis in the measured value differentiation step S23 of the analysis step S20 shown in FIG. , to acquire a measured value differential waveform as shown in the dotted line graph in FIG. This measured differential waveform is also the same as in the first mode.

Next, in the measurement value boundary determination step S24 of the analysis step S20 shown in FIG. 14, the measurement value boundary determination unit 804 of the analysis unit ₈₀₀ shown in FIG. The optical measurements s ₁ to s ₆ corresponding respectively to ₆ ' are defined as component separation boundaries.

Then, in the displacement quantification step S25 of the analysis step S20 shown in FIG. 14, the displacement quantification unit 805 of the analysis unit 800 shown in FIG. , the distances D ₁ to D ₅ of sections demarcated by the separation boundaries s ₁ to s ₆ respectively corresponding to the peak tops T ₁ ' to T ₆ ' defined in the first embodiment described above. Calculated as the relative content of 15 correspond to the areas of the peak waveforms P ₁ to _{P 5 shown} in FIG. 10, _respectively . In this displacement quantification step S25, it is absolutely unnecessary to refer to the time-differentiated waveform.

<Fourth Aspect>
In the component analysis method according to the fourth aspect of the present disclosure, the sample solution continuously introduced into the channel 27 is separated in the channel 27, and the sample solution is separated at the measurement position 27A of the channel 27 over time. A measurement step S10 for obtaining an optical measurement value by measurement, and an analysis step S20 for analyzing a plurality of components contained in the sample Sa based on the optical measurement value. An original waveform acquisition step S21 of acquiring an original waveform plotted on a two-dimensional plane along the time axis, and a time differentiation step of acquiring a time-differentiated waveform obtained by differentiating the original waveform along the time axis. S22, an inverse differentiation step S26 of obtaining an inverse differential waveform obtained by plotting the reciprocal of this time-differentiated waveform along the time axis, and a separation boundary between a plurality of components at a point corresponding to the shoulder peak of this inverse differential waveform. and a time boundary determination step S27.

The component analyzer 1 in this embodiment comprises a channel 27 into which a sample solution is continuously introduced, and the sample solution separated in the channel 27 is optically measured at a measurement position 27A of the channel 27 over time. A measurement unit 40 that obtains an optical measurement value by measurement, and an analysis unit 800 that analyzes a plurality of components contained in the sample Sa based on the optical measurement value. An original waveform acquisition unit 801 that acquires an original waveform plotted on a two-dimensional plane along an axis, and a time differentiation unit 802 that acquires a time-differentiated waveform obtained by differentiating this original waveform along the time axis. , an inverse differentiation unit 806 that obtains an inverse differential waveform obtained by plotting the inverse of this time-differentiated waveform along the time axis, and a time point corresponding to the shoulder peak of this inverse differential waveform to separate the plurality of components. and a time boundary determination unit 807 as a boundary.

The functional configuration of the analysis unit 800 in this aspect is as shown in FIG. Hereinafter, the component analysis method in this embodiment will be described with reference to the flowchart of FIG.

The measurement step S10 shown in FIG. 17 is the same as in the first aspect.

The original waveform acquisition unit 801 in the analysis unit 800 shown in FIG. 16 acquires the absorbance as an optical measurement value on one axis (for example, the Y axis) in the original waveform acquisition step S21 in the analysis step S20 shown in FIG. and plotted on a two-dimensional plane in contrast with the other time axis (for example, the X axis) to obtain an original waveform. This original waveform is represented as a solid line graph as shown in FIG. 8, for example. This original waveform acquisition step S21 is the same as in the first mode.

16 is a waveform obtained by differentiating the original waveform along the time axis in the time differentiation step S22 of the analysis step S20 shown in FIG. Get the time differential waveform. This time-differentiated waveform is represented as a dashed line graph as shown in FIG. The relationship between the original waveform and the time-differentiated waveform is the same as described in the first aspect.

Next, the inverse differentiation unit 806 of the analysis unit 800 shown in FIG. is plotted along the time axis to obtain an inverse differential waveform as indicated by the dotted line in FIG. When plotting the reciprocal of the absorbance in the time differential waveform on a two-dimensional plane with the axis of the optical measurement value as one axis and the time axis as the other axis, it is not necessary to plot as an absolute value. It suffices to plot as a relative value to the extent that the correspondence with the time differential waveform becomes clear. In addition, the reciprocal of the absorbance here is also acquired as data that can be plotted on a two-dimensional plane, and it is not essential to actually draw a graph based on such data. .

Here, the peak top and bottom in the time differential waveform correspond to the bottom and peak top in the inverse differential waveform, respectively, as in the measured value differential waveform described in the first aspect. Therefore, as shown in FIG. 18, peak tops T ₁ ″ to T ₆ ″ in the inverse differential waveform correspond to bottoms B ₁ to B ₆ in the time differential waveform, respectively. In other words, bottoms B ₁ to B ₆ in the time differential waveform are clearly expressed as peak tops T ₁ ″ to T ₆ ″ in the inverse differential waveform, respectively.

That is, the time boundary determination unit 807 in the analysis unit 800 shown in FIG. 16 performs the time boundary determination step _S27 in the analysis step S20 shown in _FIG . The respective corresponding time points t ₁ -t ₆ are defined as separation boundaries of the components.

With the configuration of the fifth aspect described above, the bottoms B ₁ to B ₆ , which should be identified as both ends of the peak waveform in the time differential waveform, are replaced with the peak tops T ₁ ″ to T ₆ ″ in the inverse differential waveform. can be recognized as Time points t ₁ to t ₆ corresponding to the peak tops T ₁ ″ to T ₆ ″ can be used as separation boundaries of the components contained in the sample Sa.

<Fifth Aspect>
In the component analysis method according to the fifth aspect of the present disclosure, in addition to the configuration of the component analysis method according to the fourth aspect, the analysis step S20 includes, for the time-differentiated waveform, using the time point corresponding to the separation boundary as the integration boundary, and the adjacent integration an integration quantification step S28 of calculating the value obtained by integrating the time-differentiated waveform for the integration interval with the boundary as both ends as the relative content of the component corresponding to the integration interval in the sample Sa. .

In addition to the configuration of the component analysis device 1 in the fourth aspect, the component analysis device 1 in this aspect has an analysis section 800 for the time-differentiated waveform in which the time point corresponding to the separation boundary is an integration boundary, and the adjacent integration boundary is It further has an integration quantification unit 808 that calculates a value obtained by integrating the time-differentiated waveform for the integration interval serving as both ends as a relative content in the sample Sa of the component corresponding to the integration interval.

The functional configuration of the analysis unit 800 in this aspect is as shown in FIG. Hereinafter, the component analysis method in this embodiment will be described with reference to the flowchart of FIG. However, among the measurement step S10 and the analysis step S20 shown in FIG. 20, the original waveform acquisition step S21, the time differentiation step S22, the inverse differentiation step S26, and the time boundary determination step S27 are the same as in the fourth mode.

In the time boundary determination step S27 shown in FIG. 20, time points t ₁ to t ₆ respectively corresponding to _the peak tops T ₁ ″ to T ₆ ″ defined in _the fourth aspect in FIG. are separation boundaries corresponding to , and time points t ₁ to t ₆ as these separation boundaries are integration boundaries. Then, in the integration quantification step S28 of the analysis step S20 shown in FIG. 20, the integration quantification unit 808 of the analysis unit 800 shown in FIG. Integrate and calculate the area occupied by the time-differentiated waveform in this integration interval. The value obtained as this area can be regarded as the relative content of the component corresponding to the integration interval (that is, the component recognized as the peak waveform in the time-differentiated waveform).

It should be noted here that the bottom _B3 in FIG. 18 is not necessarily recognized as a clear local minimum in the time differential waveform, but the corresponding peak top T3 _″ in the inverse differential waveform is It can be clearly identified as a so-called shoulder peak, so that the time point _t3 corresponding to this bottom _B3 can be clearly defined as the integration boundary _t3 corresponding to the separation boundary _s3 , and this integration boundary t By integrating the time-differentiated waveform in the integration interval having both ends of the integration boundary _t4 adjacent to ₃ , it is possible to calculate the relative content of the peak waveform _P3 , which is not necessarily recognized as a clear peak. Of course, other peak waveforms P ₁ , P ₂ , P ₄ and P ₅ recognized as distinct peaks are also t ₁ to t ₂ , t ₂ to t ₃ and t ₄ to t ₅ respectively. , and t ₅ to t ₆ , and by similarly integrating the time-differentiated waveform, it is possible to calculate the respective relative contents.

<Others>
As another embodiment of the present invention, the above-described capillary is employed in which the sample solution is separated by some means other than voltage application (for example, chromatography) at the time of introduction into the channel. A component analysis method other than the capillary electrophoresis method, which performs measurement in a channel larger than the width of the tube, is also included.

Hereinafter, the effect of this embodiment on the influence of the environmental temperature and the concentration of the specimen on the identification of the peak waveform will be described using the blood of a certain subject as the sample Sa as an example.

FIGS. 21(A) to 21(D) show the effects of environmental temperature and sample concentration during measurement on the time-differentiated waveform obtained in the time-differentiating step S22. The environmental temperature was 23° C. in FIGS. 21(A) and 21(B), and the environmental temperature was 8° C. in FIGS. 21(C) and 21(D). In addition, in FIGS. 21(A) and 21(C), the sample Sa was diluted about 3 times in advance (low concentration sample), and in FIGS. 21(B) and 21(D), no dilution of sample Sa (high concentration sample) was used. In each figure, the peak α corresponds to the mutated hemoglobin HbA1c, and the regions separated by clear bottoms observed at both ends are indicated by hatching.

Under the normal temperature environment as shown in FIGS. 21A and 21B, regardless of the concentration of the sample Sa, the bottom portion corresponding to the boundary with the peak β adjacent to the low migration speed side (that is, the right side) is Clear.

However, as shown in FIGS. 21(C) and 21(D), when the environmental temperature is 8° C., the peak α and the peak β tend to be close to each other, and the boundary between the adjacent peaks α and β is somewhat unclear. become clear. In particular, in the case of a high-concentration sample as shown in FIG. 21(D), the peak β is absorbed by the peak α and becomes indistinguishable. In such a state, when trying to quantify the peak waveform simply by dividing it by the clear bottoms on both sides, the boundary between the peak γ on the side of the lower migration speed is set as a boundary, and it is hatched. The region is defined as the content of peak α. However, this region actually contains peak β. Therefore, when a high-concentration sample is measured at a low environmental temperature, the content of the component corresponding to a specific peak may be calculated higher than the actual amount.

FIGS. 22(A) to 22(D) show the same time-differentiated waveforms as those of FIGS. 21(A) to 21(D), respectively. Areas defined by the integration boundaries determined by the value boundary determination step S24 and the integration quantification step S28 are indicated by hatching.

The regions identified as peaks α in FIGS. 22A, 22B and 22C are different from the regions in FIGS. 21A, 21B and 21C, respectively. no. However, in FIG. 22 (D), the boundary between the peak α and the peak β that was fused can be clarified, and the content that seems reasonable compared to the region specified as the peak α in other figures quantity can be calculated.

As described above, according to the present embodiment, even when a high-concentration sample is measured at a low environmental temperature, it is possible to specify a more accurate peak waveform, thereby enabling more accurate quantification of the component. Do you get it.

INDUSTRIAL APPLICABILITY The present invention can be used for a component analysis system using continuous sample introduction, particularly a component analysis system using capillary electrophoresis.

A1 Analysis system Sa Sample Ld Dilution liquid Lm Electrophoresis liquid 1 Component analyzer 2 Analysis chip 2A Upper part 2B Lower part 21 Main body 22 Mixing tank 23 Introduction tank 24 Filter 25 Discharge tank 26 Electrode tank 27 Flow path 27A Measurement position 28 Communication flow Path 31 Electrode 32 Electrode 40 Measurement Unit 41 Light Source 42 Optical Filter 43 Lens 44 Slit 45 Detector 6 Dispenser 61 Pump 71 Dilution Liquid Tank 72 Electrophoresis Liquid Tank 8 Controller 81 CPU
82 ROMs
83 RAM
84 storage 89 bus 800 analysis unit 801 original waveform acquisition unit 802 time differentiation unit 803 measurement value differentiation unit 804 measurement value boundary determination unit 805 displacement quantification unit 806 inverse differentiation unit 807 time boundary determination unit 808 integral quantification unit S10 measurement step S20 analysis step S21 Original waveform acquisition step S22 Time differentiation step S23 Measured value differentiation step S24 Measured value boundary determination step S25 Displacement quantification step S26 Inverse differentiation step S27 Time boundary determination step S28 Integral quantification step

Claims (11)

a measuring step of separating the sample solution continuously introduced into the channel in the channel and optically measuring the sample solution at a measurement position in the channel over time to obtain an optical measurement value;
and an analysis step of analyzing a plurality of components contained in a sample based on the optical measurement values,
The analysis step includes
an original waveform acquisition step of acquiring the optical measurement value as an original waveform plotted on a two-dimensional plane along the time axis;
a measurement value differentiation step of acquiring a measurement value differential waveform, which is a waveform obtained by differentiating the original waveform along the optical measurement value axis orthogonal to the time axis;
a measurement value boundary determination step in which the optical measurement value corresponding to the shoulder peak of the measurement value differential waveform is a separation boundary between the plurality of components;
Ingredient analysis method including The analysis step includes
a time differentiation step of acquiring a time differentiated waveform, which is a waveform obtained by differentiating the original waveform along the time axis;
With respect to the time-differentiated waveform, a value obtained by integrating the time-differentiated waveform for an integration interval having adjacent integration boundaries as integration boundaries at points in time corresponding to the separation boundaries is calculated as the integration interval corresponding to the integration interval. an integral quantification step of calculating the relative content of the component in the sample;
The component analysis method according to claim 1, further comprising In the analysis step, displacement quantification is performed by calculating a distance of an interval having both ends of the separation boundary adjacent along the axis of the optical measurement value as a relative content of the component corresponding to the interval in the sample. The component analysis method according to claim 1, further comprising a step. a measuring step of separating the sample solution continuously introduced into the channel in the channel and measuring the sample solution over time at a measurement position in the channel to obtain an optical measurement value;
and an analysis step of analyzing a plurality of components contained in a sample based on the optical measurement values,
The analysis step includes
an original waveform acquisition step of acquiring the optical measurement value as an original waveform plotted on a two-dimensional plane along the time axis;
a time differentiation step of acquiring a time differentiated waveform, which is a waveform obtained by differentiating the original waveform along the time axis;
an inverse differentiation step of obtaining an inverse differentiated waveform obtained by plotting the inverse of the time differentiated waveform along the time axis;
a time boundary determining step in which a time point corresponding to the shoulder peak of the inverse differential waveform is a separation boundary between the plurality of components;
Ingredient analysis method including In the analysis step, with respect to the time-differentiated waveform, a value obtained by integrating the time-differentiated waveform for an integration interval having adjacent integration boundaries as integration boundaries at points in time corresponding to the separation boundaries is calculated as the integration 5. The component analysis method according to claim 4, further comprising an integral quantification step of calculating the relative content in the sample of the component corresponding to the interval. 6. Any one of claims 1 to 5, wherein the optical measurement value is obtained by capillary electrophoresis in which a voltage is applied to the sample solution continuously introduced into the capillary tube as the flow channel to separate the sample solution. The component analysis method described above. a channel into which the sample solution is continuously introduced;
a measurement unit that optically measures the sample solution separated in the channel over time at a measurement position in the channel to obtain an optical measurement value;
A component analyzer comprising an analysis unit that analyzes a plurality of components contained in a sample based on the optical measurement values,
The analysis unit
an original waveform acquisition unit that acquires the optical measurement value as an original waveform plotted on a two-dimensional plane along the time axis;
a measurement value differentiating unit that acquires a measurement value differential waveform, which is a waveform obtained by differentiating the original waveform along the optical measurement value axis orthogonal to the time axis;
a measurement value boundary determination unit that defines an optical measurement value corresponding to a shoulder peak of the measurement value differential waveform as a separation boundary between the plurality of components;
A component analyzer having The analysis unit
a time differentiating unit that obtains a time differentiated waveform that is a waveform obtained by differentiating the original waveform along the time axis;
With respect to the time-differentiated waveform, a value obtained by integrating the time-differentiated waveform for an integration interval having adjacent integration boundaries as integration boundaries at points in time corresponding to the separation boundaries is calculated as the integration interval corresponding to the integration interval. an integral quantification part that calculates the relative content of a component in the sample;
8. The component analyzer according to claim 7, further comprising: The analysis unit calculates the distance of the section having the separation boundaries adjacent along the axis of the optical measurement value as the relative content of the component corresponding to the section in the sample. 8. The component analyzer according to claim 7, further comprising a part. a channel into which the sample solution is continuously introduced;
a measurement unit that optically measures the sample solution separated in the channel over time at a measurement position in the channel to obtain an optical measurement value;
A component analyzer comprising an analysis unit that analyzes a plurality of components contained in a sample based on the optical measurement values,
The analysis unit
an original waveform acquisition unit that acquires the optical measurement value as an original waveform plotted on a two-dimensional plane along the time axis;
a time differentiating unit that obtains a time differentiated waveform that is a waveform obtained by differentiating the original waveform along the time axis;
an inverse differentiation unit that acquires an inverse differential waveform obtained by plotting the inverse of the time differential waveform along the time axis;
a time boundary determination unit that defines a separation boundary between the plurality of components at a point in time corresponding to the shoulder peak of the inverse differential waveform;
A component analyzer having With respect to the time-differentiated waveform, the analysis unit calculates a value obtained by integrating the time-differentiated waveform for an integration interval having the adjacent integration boundaries as the integration boundaries at the points in time corresponding to the separation boundaries. 11. The component analysis device according to claim 10, further comprising an integral quantification unit that calculates the relative content of the component corresponding to the interval in the sample.

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