JP6828621B2 - Detection device - Google Patents

Description

The present invention relates to a detection device including a flow cell for circulating a sample solution and configured to detect a sample in the sample solution based on a change in the amount of light passing through the flow cell.

Absorbance detectors and the like are known as detection devices for liquid chromatographs. The absorbance detector irradiates the flow cell through which the sample solution flows with light from a light source, detects the intensity of the light passing through the flow cell with an optical sensor, and obtains the absorbance at a specific wavelength, so that the flow cell in the flow cell flows through the sample solution. It quantifies and qualifies the components (see, for example, Patent Document 1).

Japanese Unexamined Patent Publication No. 2004-06119

When the detection device as described above is used, the ratio of noise contained in the measurement data such as absorbance may increase due to some factor. Since the magnitude of noise in the measurement data fluctuates due to various factors such as deterioration of the light source and optical system, insufficient degassing of the mobile phase solvent, and dirt on the flow cell and piping, it is not possible to identify the cause of the increased noise. It's not easy.

Therefore, when the noise in the measurement data becomes large, it is common practice to wash the flow cell for the time being and check whether or not there is a change in the magnitude of the noise. When cleaning the cell, it is necessary to perform work such as flowing the cleaning liquid through the cell for a long time, which takes time.

It is wasteful and inconvenient for the user to perform such cleaning work at a stage where it is unknown whether the cause of noise is dirt on the flow cell.

Therefore, an object of the present invention is to make it possible to easily determine whether or not the flow cell is dirty.

The detection device according to the present invention includes a light source, an optical system that generates measurement light and reference light based on the light emitted from the light source, and a flow cell for circulating a sample solution, and the flow cell is the measurement. A flow cell device provided so as to be arranged on an optical path of light, a measurement light passing through the flow cell, and the reference light not passing through the flow cell (the flow cell is not provided on the optical path). The light amount detection unit for detecting the light amount, and the light amount of the measured light and the reference light obtained based on the output signal of the light amount detection unit when the flow cell is in a blank state in which the sample solution does not flow. It is provided with a dirt determination unit configured to determine the presence or absence of dirt on the flow cell by comparing the ratio of the amount of light with the threshold value.

Here, the "blank state in which the sample solution is not flowed into the flow cell" includes not only a state in which no liquid is flowed in the flow cell but also a state in which a blank liquid containing no sample component is flowed in the flow cell.

The "threshold value" used to determine the presence or absence of dirt on the flow cell is obtained based on the ratio of the amount of measurement light and the reference light measured in the "initial state" and "blank state" where the flow cell is clean. Is. The values when the light amount of the measurement light and the light amount of the reference light are measured in the "initial state" and the "blank state" of the flow cell are defined as the "initial values" of the measurement light and the reference light, respectively.

The ratio of the amount of light measured and the amount of reference light when the flow cell is left blank is most affected by the dirt on the flow cell, and is hardly affected by the emission intensity of the light source. The ratio of the amount of measured light to the amount of reference light when the flow cell is in the "initial state" and the "blank state" is a unique value when the flow cell is clean, and is a standard indicating that the flow cell is clean. It is a value. If the ratio of the light intensity of the measurement light and the reference light measured with the flow cell in the blank state is different from this reference value, it is considered that the flow cell is contaminated. Therefore, a value obtained by adding an allowable range such as a measurement error to the reference value obtained from the initial values of the measurement light and the reference light can be used as a threshold value for determining the presence or absence of dirt.

The detection device according to the present invention made based on the above findings measures the amount of light of the measurement light and the reference light with the flow cell in a blank state, obtains the ratio of the amount of light, and sets the ratio as a predetermined threshold value. It has a function to determine whether or not the flow cell is dirty by comparing.

The above threshold value may be set in advance. In that case, the detection device is provided with a threshold value holding unit that holds a preset threshold value.

If the flow cell is provided with a holding unit that holds the initial values of the measured light and the reference light measured in the initial state and in the blank state, each time the flow cell is determined to be dirty. , The threshold value may be set from the ratio of those initial values.

Further, the detection device according to the present invention is configured to set the threshold value based on the ratio of the light amount of the measurement light and the light amount of the reference light when the flow cell is in the blank state. It is preferable to further include a value setting unit. Then, when the flow cell device is assembled to the detection device, the user can set a unique threshold value of the flow cell device by using the function of the threshold value setting unit. In this case, the threshold value set by the threshold value setting unit is held by the threshold value holding unit.

By the way, as the flow cell device, a different flow cell device may be used depending on the application (for example, the type of sample) or for each user who uses the detection device. In addition to the cell length and wall thickness of the flow cell mounted on each flow cell device, there are individual differences in the thickness of the transparent plate used as the incident window and the exit window due to manufacturing errors, so the flow cell is in the initial state. Moreover, there are individual differences in the light transmittance in the blank state. Therefore, even if the initial values of the light amounts of the measurement light and the reference light are measured by the same detection device, the ratios are not always the same. Therefore, the threshold value for determining whether or not the flow cell is contaminated is a unique value that differs for each flow cell device.

Therefore, in a preferred embodiment of the detection device according to the present invention, the flow cell device has unique cell identification information, and the threshold value holding unit sets the unique threshold value of the flow cell device to the cell identification information. It is configured to be associated with and retained. In that case, the dirt determination unit is based on the threshold value associated with the cell identification information of the currently used flow cell device held in the threshold value holding unit, and the flow cell of the flow cell device. It is configured to determine the presence or absence of dirt. As a result, even when the flow cell device is replaced with another one, it is determined whether or not the flow cell is dirty by using the threshold value unique to the flow cell device associated with the cell identification information of the flow cell device. Can be done.

Further, the threshold value holding unit itself may be mounted on the flow cell device and may hold the unique threshold value of the flow cell device. This means that the flow cell device itself holds its own threshold. Then, when the flow cell device is replaced with another one, it is possible to determine whether or not the flow cell is dirty by using the unique threshold value held by the flow cell device itself.

Also, the flow cell device may be used across multiple detectors. However, since the ratio of the light amount of the measurement light to the reference light varies depending on the detection device, it is necessary to determine whether or not the flow cell is dirty depending on which detection device measures the initial values of the measurement light and the reference light. The threshold can change. Therefore, if the threshold value set by a certain detection device is used, it may not be possible to correctly determine whether or not the flow cell is dirty. Therefore, when determining whether or not the flow cell is dirty, it is preferable that the flow cell device is prepared not only for each flow cell device but also for each detection device in which the flow cell device is installed.

Therefore, in a more preferable embodiment of the detection device according to the present invention, the detection device has unique detection device identification information, and the threshold value holding unit is unique when the flow cell device is used in the detection device. The threshold value is configured to be held in association with the detection device identification information, and the stain determination unit is associated with the detection device identification information of the detection device held in the threshold value holding unit. It is configured to determine whether or not the flow cell is dirty based on the threshold value. Then, the presence or absence of dirt on the flow cell can be determined by using a unique threshold value that can vary depending on the combination of the flow cell device and the detection device, and the presence or absence of dirt on the flow cell can be determined with higher accuracy. Can be done.

Further, it may further include an initial value holding unit that holds the initial values of the light amounts of the measurement light and the reference light when the flow cell is measured in the initial state and in the blank state. If information on the initial values of the light amounts of the measurement light and the reference light is retained, it is possible to further limit the noise factors of the measurement data. For example, dirt on the flow cell does not contribute to changes in the amount of reference light, so if the amount of reference light is lower than the initial value, the light emission intensity of the light source will decrease, and the light transmittance will decrease due to deterioration of the lens. It is conceivable that the reflectance may decrease due to fogging or deterioration of the mirror. In this way, if the initial values of the light amounts of the measurement light and the reference light are retained, not only the presence or absence of dirt on the flow cell is determined by comparing the ratio of the light amounts of the measurement light and the reference light with the threshold value, but also the measurement is performed. It is possible to predict another noise factor by using the amount of light or reference light itself.

In a more preferable embodiment of the detection device according to the present invention, when the stain determination unit determines that the flow cell is dirty, it is configured to notify the user to that effect. Any method of notification to the user may be used. For example, a method of displaying the fact on a display unit such as a liquid crystal display provided in the detection device or connected to the detection device, a method of turning on a lamp indicating an error, a method of issuing a warning sound, and the like can be mentioned.

In the detection device of the present invention, the flow cell is in a blank state, the amount of light of the measurement light and the reference light is measured, the ratio of the amount of light is obtained, and the ratio is compared with a predetermined threshold value to stain the flow cell. Since it has a function of determining whether or not it is present, it is possible to easily determine whether or not the flow cell is dirty.

It is a schematic block diagram which shows one Example of the detection apparatus. It is a figure which shows the concept of the apparatus configuration when a plurality of flow cell devices are used. It is a figure which shows the concept of the apparatus configuration when the threshold value holding part is mounted on a flow cell device. It is a figure which shows the concept of the apparatus composition at the time of using a flow cell device over a plurality of detection apparatuss. It is a flowchart which shows the setting procedure of the threshold value for determining the presence or absence of dirt of a flow cell. It is a flowchart which shows the determination procedure of the presence or absence of dirt of a flow cell.

Hereinafter, embodiments of the detection device according to the present invention will be described with reference to the drawings.

FIG. 1 shows an embodiment of the detection device.

The detection device 1 of this embodiment includes a measurement unit 2 and an arithmetic processing unit 4. The measuring unit 2 includes a light source 6, a slit 8, a mirror 10, a spectroscope 12, a beam splitter 14, a flow cell device 16, and photodetectors 20 and 22. The arithmetic processing unit 4 includes a dirt determination unit 26, a threshold value setting unit 28, a threshold value holding unit 30, and an initial value holding unit 32. A display unit 34 is connected to the arithmetic processing unit 4.

In the measuring unit 2, the light emitted by the light source 6 is reflected by the mirror 10 through the slit 8 and guided to the spectroscope 12 realized by a diffraction grating or the like. The spectroscope 12 is adjusted so as to split the light from the mirror 10 for each wavelength component and guide only the light of the measurement wavelength to the beam splitter 14 side. Some of the light of the measurement wavelength guided to the beam splitter 14 by the spectroscope 12 is reflected by the beam splitter 14 and incident on the light detection element 22 as reference light, and the remaining light is transmitted through the beam splitter 14. It becomes the measurement light.

The beam splitter 14 realizes an optical system that generates measurement light and reference light based on the light from the light source 6. The optical system that generates the measurement light and the reference light based on the light from the light source 6 is not limited to the beam splitter 14, and is measured by changing the reflection angle of the light from the light source 6 with time. It may be configured to generate light and reference light, or may be a light-shielding plate or the like having a hole for generating measurement light and a hole for generating reference light.

The flow cell device 16 includes a flow cell 18 for circulating a sample solution inside, and the flow cell 18 is provided so as to be arranged on an optical path of measurement light transmitted through the beam splitter 14. The measurement light that has passed through the flow cell 18 is incident on the photodetection element 20. The photodetectors 20 and 22 form a photodetector that detects the amount of light of the measurement light and the reference light. The detection signals obtained by the photodetectors 20 and 22 are taken into the arithmetic processing unit 4.

Further, the flow cell device 16 includes a storage medium 24 realized by a flash memory or the like. The storage medium 24 stores unique cell identification information or the like for identifying the flow cell device 16 from other flow cell devices. The information stored in the storage medium 24 is also taken into the arithmetic processing unit 4.

The arithmetic processing unit 4 is realized by a dedicated computer or a general-purpose personal computer. The dirt determination unit 26 and the threshold value setting unit 28 of the arithmetic processing unit 4 are functions obtained by executing a program stored in the arithmetic processing unit 4 by an arithmetic element such as a CPU. The threshold value holding unit 30 and the initial value holding unit 32 are functions realized by a part of the storage medium provided in the arithmetic processing unit 4.

The dirt determination unit 26 determines the ratio of the amount of measurement light and the amount of reference light (for example, reference light / measurement light) detected by the photodetectors 20 and 22 when the flow cell 18 is in a blank state in which the sample solution does not flow. It is configured to determine whether or not the flow cell 18 of the flow cell device 16 is contaminated by comparing with the threshold value of. The determination of the presence or absence of dirt on the flow cell 18 can be executed, for example, when checking the amount of emitted light of the light source 6 at the time of validation, which is executed when the detection device 1 is activated. When the dirt determination unit 26 determines that the flow cell 18 is dirty, the dirt determination unit 26 displays the fact on the display unit 34, lights a predetermined lamp, or emits a warning sound to the user. On the other hand, it is configured to promote cleaning of the flow cell 18.

The threshold value holding unit 30 holds a preset threshold value for determining whether or not the flow cell 18 is dirty. The threshold value held by the threshold value holding unit 30 may be set by the threshold value setting unit 28. The threshold value setting unit 28 determines whether or not the flow cell 18 of the flow cell device 16 is dirty, automatically or based on a command from the user, such as when the flow cell device 16 is installed in the detection device 1 for the first time. It is configured to set a threshold for.

For the threshold value, the flow cell 18 in the initial state where no dirt is generated is left in a blank state, the light amounts of the measurement light and the reference light are measured as the initial values of each, the ratio of the initial values is calculated, and the ratio is calculated. Can be set as a value with an allowable range added to. The threshold value set by the threshold value setting unit 28 is held by the threshold value holding unit 30. The initial values of the measurement light and the reference light used for setting the threshold value are held in the initial value holding unit 32.

The initial values of the measurement light and the reference light held in the initial value holding unit 32 are noise factors of the measurement data other than the dirt of the flow cell 18 (for example, a decrease in the emission intensity of the light source 6, deterioration of the mirror 10, cloudiness, etc.). Can be used to identify.

It is not always necessary to include both the threshold value holding unit 30 and the initial value holding unit 32. The initial value holding unit 32 may not be provided. Further, when the initial value holding unit 32 is provided, the threshold value can be obtained each time by using the initial values of the measurement light and the reference light held in the initial value holding unit 32. , The threshold value holding unit 30 may not be provided.

As shown in FIG. 2, a plurality of flow cell devices 16 are prepared, and measurement may be performed by exchanging with different flow cell devices 16 depending on the application (sample type, etc.) or for each user. In such a case, as a threshold value for determining the presence or absence of dirt on the flow cell 18, the initial values of the measurement light and the reference light are measured for each flow cell device 16, and a unique value set based on the ratio is measured. Is preferably used.

When determining the dirtiness of the flow cell 18 using the unique threshold value for each flow cell device 16, the threshold value holding unit 30 of the arithmetic processing unit 4 sets the threshold value set for each flow cell device 16. It is preferably configured to be associated and retained with the unique cell identification information of each flow cell device 16. In that case, the dirt determination unit 26 reads the cell identification information of the flow cell device 16 installed in the detection device 1, reads the threshold value associated with the cell identification information from the threshold value holding unit 30, and reads the threshold value of the flow cell 18. It is configured to use the threshold value for the presence or absence of dirt determination.

Further, as shown in FIG. 3, the threshold value holding unit 30 may be provided on the flow cell device 16 itself. In that case, the threshold value holding unit 30 can be realized by a part of the storage medium 24 provided in each flow cell device 16. In this case, the threshold value set by the threshold value setting unit 28 is held by the threshold value holding unit 30 of the flow cell device 16. Then, when the dirt determination unit 26 determines whether or not the flow cell 18 is dirty, the threshold value holding unit 30 of the flow cell device 18 reads out the unique threshold value of the flow cell device 18, and the determination is made using the threshold value. To do.

Although not shown in the figure, the initial value holding unit 32 may be provided to each flow cell device 16 in place of the threshold value holding unit 30 or in addition to the threshold value holding unit 30. When the initial value holding unit 32 is provided to each flow cell device 16 instead of the threshold value holding unit 30, the dirt determination unit 26 is held by the initial value holding unit 32 when determining whether or not the flow cell 18 is dirty. Based on the initial values of the measured light and the reference light, a threshold value is obtained each time, and the presence or absence of dirt is determined using the threshold value.

Further, as shown in FIG. 4, a specific flow cell device 16 may be used across a plurality of detection devices 1. In such a case, the threshold value for determining the presence or absence of contamination of the flow cell 18 varies depending on which detection device 1 measures the initial values of the measurement light and the reference light. Therefore, the threshold value holding unit 30 of the flow cell device 16 holds the threshold value set by each detection device 1 in association with the detection device identification information assigned to each detection device 1. preferable. In this case, the dirt determination unit 26 of each detection device 1 has a threshold associated with the detection device identification information of the detection device 1 among the threshold values held by the threshold value holding unit 30 of the flow cell device 16. The value is used to determine whether or not the flow cell 18 is dirty.

In the above case as well, the initial value holding unit 32 may be provided to each flow cell device 16 instead of the threshold value holding unit 30.

The threshold value for determining the presence or absence of dirt on the flow cell 18 can vary for each individual flow cell device 16 and for each detection device 1 for which the threshold value is set. In other words, there is a unique threshold value for each combination of the detection device 1 and the flow cell device 16. Therefore, the threshold value holding unit 16 that holds the threshold value associated with each combination of the detection device identification information and the cell identification information may be provided on either the detection device 1 side or the flow cell device 16 side. desirable.

Next, an example of the threshold value setting procedure will be described with reference to FIG. 1 using the flowchart of FIG.

The threshold value is set automatically or based on a command from the user, for example, when the flow cell device 16 is first contacted with the detection device 1. The threshold value is set with the light emission intensity of the light source 6 stable and the flow cell 18 in a blank state (step S1). The blank state means a state in which no liquid is flowing or a state in which a blank liquid containing no sample component is flowing. In that state, the threshold value setting unit 28 reads the output signals of the photodetection elements 20 and 22 and measures the light amounts of the measurement light and the reference light (step S2). The measured value becomes the initial value of the measurement light and the reference light.

The threshold value setting unit 28 calculates the ratio of the measured measurement light to the initial value of the reference light (for example, reference light / measurement light) (step S3). Then, a value obtained by adding a certain allowable range to the ratio of the measurement light and the reference light obtained by calculation is set as the threshold value (step S4). The threshold value set by the threshold value setting unit 28 is held (stored) in the threshold value holding unit 30, and the initial values of the measurement light and the reference light are held (stored) in the initial value holding unit 32. The threshold value varies depending on the required S / N, but the ratio of the measurement light to the reference light may be set to a constant value (for example, 0.5).

An example of a procedure for determining the presence or absence of dirt on the flow cell 18 using the threshold value set by the above procedure will be described with reference to FIG. 1 and the flowchart of FIG.

The determination of the presence or absence of dirt on the flow cell 18 is executed, for example, at the time of validation at the time of starting up the detection device 1. When the dirt determination is started, the dirt determination unit 26 reads out the unique threshold value of the flow cell device 16 from the threshold value holding unit 30 (step S11). The flow cell 18 is put into a blank state (step S12), and the light amounts of the measurement light and the reference light in a state where the emission intensity of the light source 6 is stable are measured (step S13).

The dirt determination unit 26 obtains the ratio of the measured light amount of the measurement light to the reference light (for example, reference light / measurement light) by calculation (step S14), and reads the ratio from the threshold value holding unit 30. (Step S15). If the ratio obtained by calculation is equal to or greater than the threshold value, it is determined that the flow cell 18 is dirty (step S16), and a display to that effect is displayed or a predetermined lamp is turned on. , A warning sound is emitted, or the like, prompting the user to clean the flow cell 18 (step S17). On the other hand, when the ratio obtained by calculation is smaller than the threshold value, it is determined that the flow cell 18 is not contaminated (step S18).

1 Detection device 2 Measuring unit 4 Arithmetic processing unit 6 Light source 8 Slit 10 Mirror 12 Spectrometer 14 Beam splitter 16 Flow cell device 18 Flow cell 20, 22 Photodetector (light amount detection unit)
24 Storage medium 26 Stain determination unit 28 Threshold setting unit 30 Threshold holding unit 32 Initial value holding unit

Claims (6)

Light source and
An optical system that generates measurement light and reference light based on the light emitted from the light source.
A flow cell device having a flow cell for circulating a sample solution and provided so that the flow cell is arranged on the optical path of the measurement light.
A light amount detection unit for detecting the respective light amounts of the measurement light that has passed through the flow cell and the reference light that has not passed through the flow cell.
The threshold holding part that holds the threshold and
The ratio of light amount of the light amount detector is obtained on the basis of the output signal the measurement light quantity and the reference light is compared with the threshold when the flow cell is in the blank state in which no flow of the sample solution A dirt determination unit configured to determine the presence or absence of dirt on the flow cell is provided .
The flow cell device has unique cell identification information and has unique cell identification information.
The threshold value holding unit is configured to hold the threshold value unique to the flow cell device in association with the cell identification information.
The stain determination unit stains the flow cell of the flow cell device based on the threshold value associated with the cell identification information of the currently used flow cell device held in the threshold holding unit. A detector that is configured to determine the presence or absence of . Further, a threshold value setting unit configured to set the threshold value based on the ratio of the light amount of the measurement light and the light amount of the reference light when the flow cell is put into the blank state is provided.
It said threshold holding portion, the is configured to hold the threshold set by the threshold setting unit, the detection apparatus according to claim 1. Light source and
An optical system that generates measurement light and reference light based on the light emitted from the light source.
A flow cell device having a flow cell for circulating a sample solution and provided so that the flow cell is arranged on the optical path of the measurement light.
A light amount detection unit for detecting the respective light amounts of the measurement light that has passed through the flow cell and the reference light that has not passed through the flow cell.
A threshold configured to set a unique threshold for the flow cell device based on the ratio of the light intensity of the measurement light to the light intensity of the reference light when the flow cell is left blank with no sample solution flowing. Value setting part and
A threshold value holding unit mounted on the flow cell device and holding the threshold value unique to the flow cell device set by the threshold value setting unit,
The ratio of the light amount of the measurement light and the light amount of the reference light obtained based on the output signal of the light amount detection unit when the flow cell is in the blank state in which the sample solution does not flow is compared with the threshold value. A detection device comprising a dirt determination unit configured to determine the presence or absence of dirt on the flow cell . The detection device has unique detection device identification information and has unique detection device identification information.
The threshold value holding unit is configured to hold the unique threshold value when the flow cell device is used in the detection device in association with the detection device identification information.
The dirt determination unit determines whether or not the flow cell is dirty based on the threshold value associated with the detection device identification information of the detection device held in the threshold value holding unit. The detection device according to claim 3 , which is configured. According to claim 1, the flow cell further includes an initial value holding unit that holds the light amount of the measured light and the light amount of the reference light measured in the initial state without dirt and in the blank state as their respective initial values. The detection device according to any one of 4 . The detection device according to any one of claims 1 to 5 , wherein the dirt determination unit is configured to notify the user when it determines that the flow cell is dirty.

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