JP2019015513A - Detector - Google Patents

Abstract

To facilitate determination on whether or not dirt exists in a flow cell.SOLUTION: A detector comprises: a light source; an optical system which generates measuring light and reference light on the basis of light emitted from the light source; a flow cell device which has a flow cell for causing a sample solution to flow therethrough and is provided so that the flow cell is disposed on a light path of the measuring light; a light amount detection unit which detects a light amount of each of the measuring light which passes through the flow cell and the reference light which does not pass through the flow cell (on a light path of which the flow cell is not provided); and a dirt determination unit which is configured to determine presence or absence of dirt in the flow cell by comparing a ratio of the light amount of the measuring light to the light amount of the reference light with a threshold value, the ratio being obtained on the basis of an output signal of the light amount detection unit when the flow cell is in a blank state where the sample solution does not flow.SELECTED DRAWING: Figure 1

Description

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

  An absorbance detector or the like is known as a detection device for a liquid chromatograph. The absorbance detector irradiates light from the light source to the flow cell through which the sample solution flows, detects the intensity of the light that has passed through the flow cell with an optical sensor, and obtains the absorbance at a specific wavelength. The components are quantified and qualitatively (see, for example, Patent Document 1).

JP 2004-061199 A

  When such a detection apparatus is used, the ratio of noise included in measurement data such as absorbance may increase due to some factors. The magnitude of the noise in the measurement data varies depending on various factors such as deterioration of the light source and optical system, insufficient degassing of the mobile phase solvent, and contamination of the flow cell and piping. It's not easy.

  For this reason, when the noise in the measurement data becomes large, it is common practice to clean the flow cell for the time being and check whether there is a change in the magnitude of the noise. When cleaning the cell, it is necessary to perform an operation such as flowing a cleaning liquid through the cell for a long time, which takes time.

  It is wasteful to perform such a cleaning operation at a stage where it is unknown whether the noise is caused by the contamination of the flow cell, which is inconvenient for the user.

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

  The detection apparatus according to the present invention includes a light source, an optical system that generates measurement light and reference light based on light emitted from the light source, and a flow cell for circulating a sample solution, and the flow cell includes the measurement A flow cell device provided so as to be disposed on the optical path of light, and each of the measurement light that has passed through the flow cell and the reference light that has not passed through the flow cell (no flow cell is provided on the optical path) A light amount detection unit for detecting a light amount, and a light amount of the measurement light and a reference light obtained based on an output signal of the light amount detection unit when the flow cell is in a blank state where no sample solution flows. A contamination determination unit configured to determine the presence or absence of contamination of the flow cell by comparing the ratio of the amount of light with a threshold value.

  Here, the “blank state where no sample solution is allowed to flow through the flow cell” includes not only a state where no liquid is allowed to flow through the flow cell but also a state where a blank solution containing no sample component is flowing through the flow cell.

  The “threshold value” used to determine whether or not the flow cell is dirty is obtained based on the ratio of the amount of measurement light and reference light measured in the “initial state” and “blank state” where the flow cell is not dirty. It is. A value when the light quantity of the measurement light and the light quantity of the reference light are measured in the “initial state” and the “blank state” of the flow cell is defined as “initial value” of each of the measurement light and the reference light.

  The ratio of the amount of measurement light and reference light when the flow cell is in a blank state is most affected by the contamination of the flow cell and hardly affected by the light emission intensity of the light source. When the flow cell is in the “initial state” and “blank state”, the ratio of the amount of measurement light to the reference light is a unique value when the flow cell is not contaminated, and is a standard indicating that the flow cell is not contaminated. Value. If the ratio between the measurement light and the reference light measured with the flow cell in the blank state is different from the reference value, it is possible that the flow cell is contaminated. Therefore, a value obtained by adding an allowable range such as a measurement error to a 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 contamination.

  The detection device according to the present invention made on the basis of the above knowledge measures the light amount of the measurement light and the reference light with the flow cell in a blank state, obtains the ratio of the light amounts, and sets the ratio as a predetermined threshold value. By comparing, it has a function of determining whether or not the flow cell is dirty.

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

  In addition, when the flow cell is provided with a holding unit that holds the initial values of the light amounts of the measurement light and the reference light that are measured in the initial state and in the blank state, each time the flow cell is checked for contamination, The threshold value may be set from the ratio of these initial values.

  Further, the detection device according to the present invention is configured to set the threshold based on a 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 in the detection apparatus, the user can set a unique threshold value of the flow cell device using the function of the threshold value setting unit. In this case, the threshold value set by the threshold value setting unit is held in the threshold value holding unit.

  By the way, a different flow cell device may be used for a flow cell device according to an application (for example, the kind of sample) or for each user who uses a detection apparatus. In addition to the cell length and wall thickness of the flow cell mounted on each flow cell device, there are individual differences due to manufacturing errors in the thickness of the transparent plate used as the entrance window and exit window. In addition, there is an individual difference 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 with the same detection device, the ratio is not always the same value. Therefore, the threshold value for determining whether or not the flow cell is contaminated is a unique value that is different for each flow cell device.

  Therefore, in a preferred embodiment of the detection apparatus according to the present invention, the flow cell device has unique cell identification information, and the threshold value holding unit uses the unique threshold value of the flow cell device as the cell identification information. It is configured to be held in association with. In that case, the stain determination unit is configured to determine whether the flow cell of the flow cell device is based on the threshold value associated with the cell identification information of the currently used flow cell device, which is held in the threshold value holding unit. It is comprised so that the presence or absence of dirt may be determined. As a result, even when the flow cell device is replaced with another one, the flow cell device's threshold value associated with the cell identification information of the flow cell device is used to determine whether the flow cell is dirty. Can do.

  Further, the threshold value holding unit itself may be mounted on the flow cell device and hold a unique threshold value of the flow cell device. This means that the flow cell device itself maintains 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 contaminated by using a unique threshold held by the flow cell device itself.

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

  Therefore, in a further preferred embodiment of the detection apparatus according to the present invention, the detection apparatus has unique detection apparatus identification information, and the threshold value holding unit is unique when the flow cell device is used in the detection apparatus. The threshold value is configured to be stored 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. The flow cell is configured to determine whether or not the flow cell is contaminated based on the threshold value. By doing so, it is possible to determine the presence or absence of contamination of the flow cell using a unique threshold that can vary depending on the combination of the flow cell device and the detection device, and to determine the presence or absence of contamination of the flow cell with higher accuracy. Can do.

  The flow cell may further include an initial value holding unit that holds 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 about the initial values of the light amounts of the measurement light and the reference light is held, it is possible to further limit the cause of noise in the measurement data. For example, since the dirt of the flow cell does not contribute to the change in the amount of reference light, if the amount of reference light is lower than the initial value, the light emission intensity decreases, the light transmittance decreases due to lens deterioration, It is conceivable that the reflectivity decreases due to fogging or deterioration of the mirror. In this way, if the initial values of the light intensity of the measurement light and the reference light are retained, the flow cell ratio is not only determined by comparing the ratio of the light intensity of the measurement light and the reference light with the threshold value, but also the measurement. It becomes possible to predict another noise factor using the light amount of the light or the reference light itself.

  In a further preferred embodiment of the detection apparatus according to the present invention, when the dirt determination unit determines that the flow cell is dirty, it is configured to notify the user to that effect. Any notification method may be used for the user. 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 lighting a lamp indicating an error, a method of generating a warning sound, and the like can be mentioned.

  In the detection device of the present invention, the flow cell is blanked, the light amounts of the measurement light and the reference light are measured, the ratio of the light amounts is obtained, and the ratio is compared with a predetermined threshold value. Since it has a function of determining whether or not there is a flow cell, 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 a detection apparatus. It is a figure which shows the concept of an apparatus structure in the case of using a some flow cell device. It is a figure which shows the concept of an apparatus structure at the time of mounting a threshold value holding part in a flow cell device. It is a figure which shows the concept of an apparatus structure in the case of using a flow cell device over several detection apparatuses. It is a flowchart which shows the setting procedure of the threshold value for determining the presence or absence of the stain | pollution | contamination of a flow cell. It is a flowchart which shows the determination procedure of the presence or absence of the stain | pollution | contamination of a flow cell.

  Embodiments of a detection apparatus according to the present invention will be described below with reference to the drawings.

  FIG. 1 shows an embodiment of the detection apparatus.

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

  In the measurement unit 2, the light emitted from 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 having the measurement wavelength to the beam splitter 14 side. A part of the light having the measurement wavelength guided to the beam splitter 14 by the spectroscope 12 is reflected by the beam splitter 14 and enters the light detection element 22 as reference light, and the remaining light passes through the beam splitter 14. Becomes measurement light.

  The beam splitter 14 implements an optical system that generates measurement light and reference light based on 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 the measurement is performed by changing the reflection angle of the light from the light source 6 over time. It may be configured to generate light and reference light, or may be a light shielding plate having a measurement light generation hole and a reference light generation hole.

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

  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 for identifying the flow cell device 16 from other flow cell devices. 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 when an arithmetic element such as a CPU executes a program stored in the arithmetic processing unit 4. The threshold value holding unit 30 and the initial value holding unit 32 are functions realized by a partial area of the storage medium provided in the arithmetic processing unit 4.

  The dirt determination unit 26 determines a ratio (for example, reference light / measurement light) of the light amount of the measurement light and the reference light detected by the light detection elements 20 and 22 when the flow cell 18 is in a blank state where 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. The determination of the presence or absence of contamination of the flow cell 18 can be performed, for example, at the time of checking the amount of light emitted from the light source 6 during validation performed when the detection device 1 is activated. When it is determined that the flow cell 18 is contaminated, 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. In contrast, the flow cell 18 is configured to be cleaned.

  The threshold holding unit 30 holds a threshold set in advance for determining whether 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 the flow cell 18 of the flow cell device 16 is contaminated automatically or based on a command from the user when the flow cell device 16 is first installed in the detection apparatus 1 or the like. It is configured to set a threshold for.

  The threshold value is obtained by measuring the light quantity of the measurement light and the reference light as the initial values by setting the flow cell 18 in the initial state in which no contamination occurs to a blank state, and calculating the ratio between the initial values. Can be set as a value with an allowable range taken into account. The threshold value set by the threshold value setting unit 28 is held in the threshold value holding unit 30. The initial values of the measurement light and the reference light used for setting the threshold 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 causes of noise in measurement data other than the contamination of the flow cell 18 (for example, a decrease in the light emission intensity of the light source 6, deterioration of the mirror 10 or cloudiness). Can be used to identify

  Note that both the threshold value holding unit 30 and the initial value holding unit 32 are not necessarily provided. The initial value holding unit 32 may not be provided. In addition, when the initial value holding unit 32 is provided, the threshold value can be obtained each time 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 may be prepared, and measurement may be performed depending on the application (specimen type or the like) or by switching to a different flow cell device 16 for each user. In such a case, the initial value of the measurement light and the reference light is measured for each flow cell device 16 as a threshold for determining whether the flow cell 18 is contaminated, and a unique value set based on the ratio Is preferably used.

  When determining the contamination of the flow cell 18 using a 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 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 apparatus 1, reads the threshold value associated with the cell identification information from the threshold value holding unit 30, and The threshold value is used for the presence / absence of contamination 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 partial area 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 in the threshold value holding unit 30 of the flow cell device 16. When the dirt determination unit 26 determines whether the flow cell 18 is dirty, the threshold value holding unit 30 of the flow cell device 18 is read from the threshold value unique to the flow cell device 18, and the determination is made using the threshold value. To do.

  Although not shown in the drawing, each flow cell device 16 may be provided with an initial value holding unit 32 instead of or in addition to the threshold 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 initial value holding unit 32 holds the dirt determination unit 26 when determining whether the flow cell 18 is dirty. Based on the initial values of the measurement 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 apparatuses 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 has measured the initial values of the measurement light and the reference light. Therefore, the threshold value holding unit 30 of the flow cell device 16 may hold 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 contamination 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 in the threshold value holding unit 30 of the flow cell device 16. The value is used to determine whether the flow cell 18 is dirty.

  Also in the above case, each flow cell device 16 may be provided with an initial value holding unit 32 instead of the threshold value holding unit 30.

  The threshold value for determining the presence or absence of contamination of the flow cell 18 may vary for each individual flow cell device 16 and further 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 apparatus 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 is provided on either the detection device 1 side or the flow cell device 16 side. desirable.

  Next, an example of the threshold setting procedure will be described with reference to the flowchart of FIG. 5 together with FIG.

  The threshold value is set automatically, for example, when the flow cell device 16 comes into contact with the detection apparatus 1 for the first time or based on a command from the user. The threshold is set by setting the light emission intensity of the light source 6 to be stable and setting the flow cell 18 in a blank state (step S1). The blank state refers to a state where no liquid is flowing or a state where a blank liquid containing no sample component is flowing. In this state, the threshold value setting unit 28 reads the output signals of the light detection 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 a ratio (for example, reference light / measurement light) between the measured measurement light and the initial value of the reference light (step S3). Then, a value obtained by adding a certain allowable range to the ratio between the measurement light and the reference light obtained by calculation is set as a 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 varies depending on the required S / N, but the ratio between the measurement light and the reference light may be determined to be a constant value (for example, 0.5).

  An example of a procedure for determining whether or not the flow cell 18 is dirty using the threshold value set by the above procedure will be described with reference to the flowchart of FIG. 6 together with FIG.

  The determination of whether the flow cell 18 is dirty is executed, for example, during validation when the detection device 1 is started up. When the contamination determination is started, the contamination determination unit 26 reads out a unique threshold value of the flow cell device 16 from the threshold value holding unit 30 (step S11). The flow cell 18 is set to a blank state (step S12), and the light amounts of the measurement light and the reference light in a state where the light emission intensity of the light source 6 is stable are measured (step S13).

  The dirt determination unit 26 calculates a ratio (for example, reference light / measurement light) between the measured measurement light and the reference light by calculation (step S14), and reads the ratio from the threshold holding unit 30. (Step S15). If the calculated ratio is equal to or greater than the threshold value, it is determined that the flow cell 18 is contaminated (step S16), and that fact is displayed on the display unit 34 or a predetermined lamp is turned on. The user is prompted to clean the flow cell 18 by making a warning sound or the like (step S17). On the other hand, if the calculated ratio is smaller than the threshold value, it is determined that the flow cell 18 is not contaminated (step S18).

DESCRIPTION OF SYMBOLS 1 Detection apparatus 2 Measurement part 4 Arithmetic processing part 6 Light source 8 Slit 10 Mirror 12 Spectroscope 14 Beam splitter 16 Flow cell device 18 Flow cell 20, 22 Photodetection element (light quantity detection part)
24 Storage Medium 26 Dirt Determination Unit 28 Threshold Setting Unit 30 Threshold Holding Unit 32 Initial Value Holding Unit

Claims (8)

A light source;
An optical system that generates measurement light and reference light based on light emitted from the light source;
A flow cell device having a flow cell for circulating a sample solution, the flow cell being disposed 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;
Comparing the ratio of the light quantity of the measurement light and the light quantity of the reference light obtained based on the output signal of the light quantity detection unit when the flow cell is in a blank state where no sample solution is flowing, with a threshold value And a contamination determination unit configured to determine whether the flow cell is contaminated or not. A threshold holding unit for holding the threshold;
The detection device according to claim 1, wherein the stain determination unit is configured to determine whether the flow cell is dirty using the threshold value held in the threshold value holding unit. Further comprising a threshold setting unit configured to set the threshold based on a ratio of the amount of the measurement light and the amount of the reference light when the flow cell is in the blank state;
The detection device according to claim 2, wherein the threshold value holding unit is configured to hold the threshold value set by the threshold value setting unit. The flow cell device has unique cell identification information;
The threshold holding unit is configured to hold the threshold unique to the flow cell device in association with the cell identification information;
The stain 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 stain of the flow cell of the flow cell device The detection device according to claim 2, wherein the detection device is configured to determine whether or not there is any.   The detection device according to any one of claims 2 to 4, wherein the threshold value holding unit is mounted on the flow cell device and holds the threshold value unique to the flow cell device. The detection device 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 stain 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 5, which is configured.   The apparatus further comprises an initial value holding unit for holding the light quantity of the measurement light and the light quantity of the reference light measured in the blank state in the initial state where the flow cell is not contaminated as the respective initial values. The detection device according to any one of claims 6 to 9.   The detection device according to any one of claims 1 to 7, wherein the stain determination unit is configured to notify the user when the flow cell is determined to be dirty.

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