JP2006162355A - Wavelength confirming method of apparatus with built in photometer and autoanalyzer - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a wavelength confirming method of an apparatus with built in photometer which can be executed on the spot, dispenses with the strict preparation/keeping control of a solution to be used and can be performed without using measuring instruments at all. <P>SOLUTION: In the wavelength confirming method of the apparatus with built in photometer, the characteristic data of a solution known in its spectral absorption characteristics and the actually measured data due to an autoanalyzer are used to confirm whether the wavelength of the photometer, which can extract a plurality of kinds of specific wavelengths in a discontinuous manner, incorporated in the autoanalyzer is changed as compared with the wavelength of the photometer at the time of production. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a wavelength confirmation method for a built-in photometer mounted on an automatic analyzer or the like, and an automatic analyzer to which the method is applied.

  Since data obtained by examining specimens collected from patients is indispensable for clinical diagnosis, automatic analysis systems for specimen examination are now widely used regardless of the scale of hospitals and laboratories. The accuracy in specimen test data is an important factor that affects the reliability of clinical diagnosis, and in recent years, a system has been introduced in which clinical laboratories are authorized as laboratories.

  When accrediting an examination room as a testing laboratory, the examination of whether or not accreditation is possible is conducted based on the international standard ISO15189. One of the technical requirements of international standards is to regularly monitor and verify that instrument functions, reagents and automated analysis systems are properly calibrated and operated.

  In an automatic analysis system for clinical examination, a test result is obtained using an automatic analyzer or a reagent that reacts with, for example, a patient sample as a test object. In order to measure and quantify a patient sample whose concentration is unknown, it is fundamental to measure a sample having a known concentration in advance as a calibrator and calculate the concentration of the patient sample based on the measured value.

  On the other hand, for inspection items that do not have a calibrator, the coefficient calculated based on the instrument's weighing and measurement physical factors, such as the amount of sample and reagent dispensed, the optical path length of the container for absorption measurement, the molecular absorption coefficient of the measurement solution, etc. Used to calculate the measurement result. Here, the main factors related to the molecular extinction coefficient are wavelength and wavelength purity, and management of physical factors such as wavelength is important in combination with dispensing, and monitoring of an appropriate state is required.

  When an automatic analyzer is installed, there is “Performance Confirmation Test Method Manual for General-purpose Automatic Analyzer” published by the Japan Society for Clinical Laboratory Automation as a method for confirming the performance of each function. This manual discloses (1) proportionality of absorbance, (2) repeatability of photometry, (3) apparent molar extinction coefficient, and (4) measured K-factor as confirmation items for performance related to photometry. ing. Among these confirmation items, only the “apparent molar extinction coefficient” shown in (3) has the possibility of estimating the wavelength accuracy in the light for photometry.

  This is to prepare a reaction indicator at a specified concentration, calculate the molar extinction coefficient from the measured absorbance, and perform measurement using the molar extinction coefficient, and determine the deviation from the target wavelength. The calibration is not performed, but if there is a deviation, the apparent molar extinction coefficient in that state is used.

  On the other hand, in general, a commercially available spectrophotometer uses an emission line of mercury for wavelength calibration. In JIS, the spectrophotometric analysis general rule (K0115), the wavelength accuracy or wavelength scale and wavelength scale calibration are measured by measuring absorption lines of emission lines emitted from a low-pressure mercury lamp or deuterium discharge tube or an optical filter for wavelength calibration. Is presented. The emission line shows the wavelength at which the intensity is maximum, the absorption curve shows the absorption maximum wavelength, the glass optical filter includes a neodymium filter, a holmium filter, and the solution filter includes a NIST holmium solution (SRM2034). .

The “spectrophotometer wavelength calibration method” disclosed in Japanese Patent Laid-Open No. 6-74823 uses a device equipped with an array-type light receiving element, and is a spectrophotometer that extracts wavelengths almost continuously. A method of using a calibration filter with a peak is shown.
JP-A-6-74823

  In a conventionally used method of obtaining an “apparent molar extinction coefficient” to predict a wavelength shift, it is a major technical problem and a drawback to prepare a reaction indicator having a specified concentration. Purifying and weighing the reaction indicator substance to prepare a prescribed concentration itself requires a high skill level, and it is difficult to ensure stability after preparation. If stability is taken into consideration, preparation at the measurement site is necessary. In that case, a correctly calibrated chemical balance is required, but not all facilities that have introduced automatic analyzers have such an environment. In addition, taking into account the fact that stability cannot be ensured, it is possible to obtain a measured value with a standard spectrophotometer on the site and obtain it as a control. Because a spectrophotometer is required, it is impossible to find it in all laboratories.

  Next, it is a general spectrophotometer calibration method, which is intended to continuously cover a certain wavelength range like a spectrophotometer, like a photometer built into an automatic analyzer. Those that extract only a specific wavelength cannot be used if they do not have a wavelength that matches the emission line such as mercury. Even if the same wavelength as that of the bright line can be taken out, considerable man-hours are required for bringing in the corresponding light source and power source and for attaching the light source in the field. The method using the absorption curve of an optical filter or a solution filter cannot be applied to a photometer having only a specific wavelength.

  The content described in Japanese Patent Laid-Open No. 6-74823 is basically a spectrophotometer capable of measuring almost continuous wavelengths and uses a special filter for calibration, but is incorporated into an automatic analyzer. It cannot be applied to photometers.

  In addition, bringing in a measuring instrument used for wavelength confirmation during manufacturing, such as a spectrum analyzer, is not suitable for frequent transportation due to the characteristics of the instrument. In addition, the automatic analyzer is dismantled on site and the photometer is taken out. It is not realistic to measure.

  An object of the present invention is to be able to be easily carried out in the field, and it is not necessary to strictly prepare and store a solution to be used, and to obtain a method that can be carried out without using any measuring instruments. is there.

  The problems with the conventional methods are the strict concentration adjustment of the measurement solution (reaction indicator), the stable storage management after the preparation, the necessity of calibrated measuring instruments, and the like.

  In order to solve these problems, the current wavelength of the automatic analyzer installed at the laboratory site is not directly obtained as a numerical value, but the amount of change from the initial set value is obtained. In addition, it is assumed that the change is not extreme, and is a small amount that hardly interferes with daily life because it is used for daily inspection. And the condition that the change in wavelength is the same amount in the same direction at each wavelength is set. The only amount that can be adjusted in relation to the wavelength in the same direction is the position of the photodiode array that receives the predetermined wavelength dispersed by the diffraction grating, and can handle multiple wavelengths. This is because the interval between the photodiodes is fixed and the movement in one direction is adjusted as a whole.

  In this method, one of the points is to use the spectral absorption characteristics of the solution (reaction indicator) to be measured. This is particularly the utilization of the rate of change of absorption with respect to the wavelength change in the vicinity of the wavelength to be confirmed.

  Regarding the relationship between the reaction indicator and the confirmation wavelength, it is necessary that a sufficiently large change in absorbance is observed as compared with the photometric accuracy, and it is important to select a substance whose absorption changes greatly with respect to the change in wavelength. Moreover, it is advantageous that the degree of change can be detected with high sensitivity when the wavelength increases in the same direction and when the wavelength that decreases decreases can be selected. This is especially important for those using absorbance ratios at multiple wavelengths.

  The point that does not require strict concentration adjustment of the measurement solution (reaction indicator) and stable storage management after the preparation is measurement of multiple wavelengths (mainly two wavelengths). This is based on the fact that when solutions having different concentrations are measured at each wavelength at which the solution absorbs, the absorbance ratio has a fixed relationship for each wavelength.

  Based on the above, the wavelength check method of the device built-in type photometer of the invention according to claim 1 is that the wavelength of the photometer incorporated in the automatic analyzer and capable of extracting a plurality of specific types of wavelengths is not continuous. It is characterized in that whether or not it has changed compared with the time of manufacture is confirmed by using the characteristic data of a solution having a known spectral absorption characteristic and the actual measurement data by the automatic analyzer.

  The invention according to claim 2 is the wavelength confirmation method of the device built-in type photometer according to claim 1, wherein the measurement is performed by removing a maximum absorption wavelength of the used solution and obtaining a large change in absorption with respect to wavelength change. It is characterized by using different types of wavelengths.

  The invention according to claim 3 is the wavelength confirmation method of the device built-in type photometer according to claim 1, in the case where there is actual measurement data of the solution after manufacture and before shipment, the measurement at the installation site in the market The amount of change in wavelength after shipment is calculated using the data and the absorption change rate obtained from the spectral absorption characteristics of the solution near the wavelength to be confirmed.

  The wavelength confirmation method for the device built-in type photometer described in claim 4 is that the wavelength of the photometer incorporated at the time of manufacture is confirmed using a separate measuring instrument such as a spectrum analyzer. Even if there is not, the ratio of the absorbance measured at a plurality of wavelengths including the wavelength of the target to be confirmed having absorption for the solution and the absorbance ratio at the wavelength in the vicinity thereof confirmed at the time of manufacture obtained from the absorption characteristics of the measured solution. And calculating the degree of wavelength change.

  The wavelength confirmation method for the device built-in photometer according to claim 5 is based on a combination of each of a plurality of types of wavelengths including a wavelength to be confirmed, when there is neither wavelength data at the time of manufacture nor measured data of the solution before shipment. Using the absorbance ratio data obtained from the absorption characteristics, the absorbance ratio of the plurality of wavelengths measured in the market is compared, and it is determined whether or not the current wavelength is within the standard.

  The invention according to claim 6 is an automatic analyzer to which the wavelength confirmation method for an apparatus built-in photometer according to any one of claims 1 to 5 is applied, wherein absorption characteristic data of a solution and wavelength confirmation data at the time of manufacture are obtained. It is memorized, and the degree of change in wavelength is automatically measured and displayed from solution measurement data at the operation site.

  In the present invention, the wavelength confirmation of a photometer incorporated in an automatic analyzer that has recently been required in recent years will be shipped in the future without considering such devices. Automatic analysis in which the current wavelength state is installed in the field by using different methods that can be used, such as equipment that is in operation, equipment that has been used for many years where no manufacturing data is stored. Since it can be confirmed using only the apparatus and a solution that does not require strict concentration control, the man-hours for preparation and measurement can be greatly reduced.

  The inspection in which the wavelength accuracy is important in the automatic analyzer does not have a calibrator and determines the concentration conversion coefficient based on physical factors of measurement and measurement by the device, and these are called device constants. Specifically, it may be used for enzyme activity measurement.

  As the measurement solution (reaction indicator), a solution whose absorption changes greatly with respect to the wavelength change of the wavelength to be confirmed is used.

  Here, an example in which paranitroaniline is used as a solution in order to confirm a change in wavelength of 410 nm will be described.

One of the enzyme items in clinical examination is γ-GTP, and the measurement wavelength of paranitroaniline, which is the substrate, is generally 405 nm or 410 nm. In this example, the measurement is performed at 410 nm. Will be explained.
(Embodiment 1)
First, as a first embodiment, at the time of shipment of the automatic analyzer, para-nitroaniline is reacted indicator indicates the case of performing the absorbance measurement with two wavelengths of concentration C _A (410nm / 340nm).

  An example of spectral absorption characteristics of the reaction indicator shown in FIG. 1 will be described as a model.

It is assumed that the actual wavelength measured by the automatic analyzer at the time of shipment is λ ₁ corresponding to 410 nm and λ ₂ corresponding to 340 nm. Further, the ratio of the change in absorption accompanying the wavelength change in the vicinity of 410 nm of paranitroaniline is obtained in advance from the spectral absorption characteristics of paranitroaniline, and this is α% / nm.

Similarly, β% / nm is obtained as the rate of change in absorption accompanying the change in wavelength near 340 nm. Eλ ₁ and Eλ ₂ are recorded as measured absorbances of λ ₁ and λ ₂ of paranitroaniline and concentration C _A. It is desirable to record the average value of multiple measurements.

After shipment, paranitroaniline is measured on site to confirm the wavelength when the equipment is installed on the market. The density at this time does not need to match that used at the time of shipment, and is set to density C _B. Assuming that the wavelength has shifted Δλ while the apparatus is installed and used, assume that the equivalent of 410 nm is λ _1X = λ ₁ + Δλ, and the equivalent of 340 nm is λ _2X = λ ₂ + Δλ. The absorbances measured in this state are E _B λ _1X and E _B λ _2X , respectively. Thus, lambda _1X and lambda absorbance _{E A λ 1X, E A λ} 2X at a concentration C _A used at the time of shipment at _2X, the number of the next 1, determined by the number 2.

λ_1Xにおける溶液の濃度Ｃ_BとＣ_Aの吸光度比はλ_2Xにおける吸光度比と同一であることから、数３が成立する。

Since the absorbance ratio of the solution concentrations C _B and C _A at λ _1X is the same as the absorbance ratio at λ _{2X, Equation} 3 holds.

これから数４に示すごとく、Δλを求めることができる。

As shown in Equation 4, Δλ can be obtained.

（実施の形態２）
次に、第２の実施の形態として、出荷前におけるパラニトロアニリンの測定データがないもので製造時の波長確認データが保管されている場合を説明する。

(Embodiment 2)
Next, as a second embodiment, a case where there is no measurement data of paranitroaniline before shipment and wavelength confirmation data at the time of production is stored will be described.

  When the wavelength for confirming the presence / absence and the degree of the wavelength change is 410 nm, the other wavelength is set to a wavelength at which the increase / decrease in absorption is opposite to the same wavelength change. In the case of paranitroaniline, it is 340 nm, for example.

  From the spectral absorption characteristics of paranitroaniline, A, which is the ratio of the absorbance at 340 nm to the absorbance at 410 nm wavelength, is recorded. Next, B, which is the ratio between the absorbance at 340-1 nm, that is, 339 nm, and the absorbance at 410-1 nm, that is, 409 nm, is obtained from the spectral absorption characteristics of the same paranitroaniline and recorded. Furthermore, C, which is the ratio of the absorbance at 340 + 1 nm, that is, 341 nm, and the absorbance at 410 + 1 nm, that is, 411 nm, is obtained and recorded.

  D, which is an absorbance obtained by measuring paranitroaniline at an arbitrary concentration on the site at wavelengths corresponding to 340 nm and 410 nm, is obtained.

  When the measurement result D is compared with B and C, and B ≦ D ≦ C, the wavelength change from the time of shipment is considered to be within ± 1 nm. Further, as shown in Table 1, a table of the ratio between “340 ± k” nm and “440 ± k” nm (k is a variable) is prepared, and k when it matches D is the change in wavelength. It is also good. For example, as shown in Table 1, if the data of the absorbance ratio at the confirmation wavelength at the time of manufacture is 0.8931 and the measurement data of the device installed in the field is 0.8031, the amount of change in wavelength is -2 nm. It becomes.

（実施の形態３）
さらに、第３の実施の形態として、出荷前のパラニトロアニリンの測定データがなく、製造時の波長確認データも保管されていない場合について説明する。

(Embodiment 3)
Furthermore, as a third embodiment, a case will be described in which there is no measurement data of paranitroaniline before shipment and wavelength confirmation data at the time of manufacture is not stored.

  In this case, since there is no data to be compared with the current situation, the amount of change in wavelength cannot be obtained. Using the spectral absorption characteristics of paranitroaniline, an absorbance ratio table at a wavelength near 340 nm and a wavelength near 410 nm is created (see Table 2).

表２では例えば製造時の波長正確性規格を３４０ｎｍと４１０ｎｍそれぞれ±１ｎｍとして規格内で取り得る３４０ｎｍと４１０ｎｍ相当波長での吸光度比をテーブルに太線で枠囲みをして示す。現地でパラニトロアニリンを３４０ｎｍと４１０ｎｍ相当の波長で測定し、その際における吸光度の比をこのテーブル内に当てはめてどのような状態にあるかを推定する。その際、同じ値をとる波長の組合せが複数あるため、各波長が同一方向に同じ量変化するという前提条件を用いて絞り込みを行なう。例えば、現地での測定結果が０．８４５４だった場合、一つには（３３９ｎｍ，４０９ｎｍ）の組合せであり、これは規格内といえるが、その他にも薄く網掛けした部分で０．８４５４を取り得る。出荷時に規格内に合った２波長が共に同一方向、同一量変化するという条件に合致するのは表２における破線で囲んだ２箇所だけである。これらは規格からの変化が±１ｎｍ以下であることが判定できる。

In Table 2, for example, the wavelength accuracy standards at the time of manufacture are set to ± 1 nm at 340 nm and 410 nm, respectively, and the absorbance ratios at wavelengths corresponding to 340 nm and 410 nm that can be taken within the standard are shown in a table with bold lines. Paranitroaniline is measured on site at wavelengths corresponding to 340 nm and 410 nm, and the ratio of absorbance at that time is applied to this table to estimate the state. At this time, since there are a plurality of combinations of wavelengths having the same value, the narrowing is performed using a precondition that each wavelength changes in the same direction by the same amount. For example, when the measurement result at the site is 0.8454, one is a combination of (339 nm, 409 nm), which can be said to be within the standard, but other than that, a thin shaded portion is 0.8454. I can take it. Only two places surrounded by a broken line in Table 2 meet the condition that two wavelengths that meet the standard at the time of shipment change in the same direction and in the same amount. From these, it can be determined that the change from the standard is ± 1 nm or less.

  As described above, in the wavelength confirmation method and automatic analyzer of the device built-in type photometer according to the present invention, only the solution in which the current wavelength state does not require strict concentration management with the automatic analyzer installed in the field. Since it can be confirmed by using, it is possible to greatly reduce the man-hours for preparation and measurement.

Diagram showing examples of spectral absorption characteristics of reaction indicators

Claims (6)

  Whether or not the wavelength of a photometer built in an automatic analyzer that can extract a plurality of specific wavelengths rather than continuously has changed compared to the time of manufacture of a solution with a known spectral absorption characteristic. A wavelength confirmation method for a device built-in photometer characterized by confirming using characteristic data and actual measurement data by the automatic analyzer.   The wavelength of the photometer with a built-in device according to claim 1, wherein the measurement uses a plurality of types of wavelengths from which the maximum absorption wavelength of the used solution is removed and a large change in absorption with respect to a change in wavelength is obtained. Confirmation method.   If there is actual measurement data of the solution after manufacturing and before shipment, use the rate of change in absorption obtained from the measured data at the installation site in the market and the spectral absorption characteristics of the solution near the wavelength to be confirmed. The method for confirming the wavelength of a built-in photometer according to claim 1, wherein the amount of change in wavelength of the device is calculated.   If the wavelength of the photometer incorporated at the time of manufacture is confirmed using a separate measuring instrument such as a spectrum analyzer, the wavelength of the object to be confirmed that has absorption for the solution is included even if there is no measured data on the solution before shipment. Built-in device that calculates the degree of wavelength change using the ratio of absorbance measured at multiple wavelengths and the absorbance ratio at the wavelength in the vicinity of the measured solution obtained from the absorption characteristics of the measurement solution. Wavelength confirmation method for type photometer.   If there is neither wavelength data at the time of manufacture nor actual measured data of the solution before shipment, the multiple measured in the market using absorbance ratio data obtained from the absorption characteristics obtained by combining each of a plurality of types of wavelengths including the wavelength to be confirmed. A method for confirming a wavelength of a built-in photometer, comprising comparing the absorbance ratio of wavelengths and determining whether or not the current wavelength is within a standard. The absorption characteristic data of the solution and the wavelength confirmation data at the time of manufacture are stored, and the degree of change in wavelength is automatically measured and displayed from the measurement data of the solution at the operation site. An automatic analyzer to which the wavelength confirmation method for a built-in photometer according to any one of the above is applied.

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