JPH10132735A - Automatic analyzing device - Google Patents

Abstract

PROBLEM TO BE SOLVED: To perform component analysis with higher reliability. SOLUTION: While rotating a disk 2, the dispensing of demineralized water into a cuvette 1 by a washing mechanism 13 and the measurement of absorbance of demineralized water in the cuvette 1 by a detecting mechanism are continuously performed to correct the reference current of each log amplifier in a converting unit 24 on the basis of measured results. In addition, as each of disks 2, 6, and 8 is rotated, the dispensing of a reagent into the cuvette 1 by a dispensing mechanism 5, the dispensing of the sample into the cuvette 1 by a dispensing mechanism 4, the stirring of the reagent and sample by a stirring mechanism 4, the measurement of absorbance of component elements of a sample solution in the cuvette 1 by a detecting mechanism, and the washing of the cuvette by the washing mechanism 13 are continuously performed. In addition, the detecting means converts to digital form the level value of intensity of each monochromatic light component sequentially calculated in the course of the passage of the cuvette 1 in front of a light source 15 with the rotation of the disk 2 by an integral A-D converter with an integrating characteristic to noise, and inputs into a CPU19.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an automatic biochemical analyzer used for analyzing components of a biological sample.

[0002]

2. Description of the Related Art Most of the component analysis of biological samples such as serum and urine in clinical tests is performed by an automatic chemical analyzer which is a development of a spectrophotometer.

As generally known, since the concentration of each component element and the absorbance of each component element contained in a sample solution (a reaction solution of a reagent and a sample) obey the Lambert-Beer law, This type of automatic chemical analyzer usually has a built-in Log amplifier circuit that executes a logarithmic conversion process shown in Expression 1 and calculates a level value Vo of a photocurrent value _If that is proportional to the luminous flux transmitted through the sample solution. Have been.

Vo = K · log (I _f / I _p ) (1) where I _p is a reference current value proportional to the standard luminous flux, and K is determined according to the resistance value of the circuit. It is a proportional constant (however, K> 0).

That is, a conventional automatic analyzer performs an optical system for detecting a photocurrent value proportional to a light flux transmitted through a sample solution, and a logarithmic conversion process represented by Formula 1 using the detected photocurrent value. And a Log amplifier circuit to be executed. Then, the number of light transmitted through the sample solution is m (usually 12) so that a monochromatic light component according to the inspection item can be selected.
Spectral element (for example, diffraction grating, etc.) that separates into monochromatic light components
An optical system includes a photodiode array (e.g., a silicon photosensor array or the like) for photoelectrically converting the received light beam of each monochromatic light component, and a plurality of Log amplifier circuits corresponding to each monochromatic light component. Is provided. The voltage Vo output from each Log amplifier circuit is
After each is input to the AD converter via the multiplexer, it is input to the CPU as the absorbance of the component element contained in the sample solution. Then, the CPU converts the absorbance of the component element into a concentration value of the component element by a conversion process using an appropriate conversion constant.

[0006] In component analysis of biological samples and the like, it is necessary to detect the photocurrent _{Ip in} a wavelength range from near ultraviolet to near infrared. , A halogen lamp having a continuous spectrum in a wavelength range of about 340 nm to about 800 nm is used.

[0007]

In an automatic chemical analyzer, the components of a sample solution filled in a cuvette are analyzed. It is premised that the cuvette is sufficiently clean before use, but occasionally, the cuvette may be partially stained. Further, a cuvette having a non-uniform thickness may be used, and the thickness of the liquid layer may be non-uniform. Therefore, there is a possibility that the measurement data fluctuates depending on the position where light passes through the cuvette.

Further, in order to detect the photocurrent _Ip in a wide wavelength range from near ultraviolet rays to near infrared rays, if the above-mentioned conventional automatic analyzer is used, it is necessary to prepare all Log amplifier circuits as a preparation. There is a problem that the reference current _Ip given to each Log amplifier circuit must be individually set so that the voltage output from the A / D converter falls within the rated range of the AD converter. That is, before starting the measurement,
Using pure water (absorbance: 0 ABS) as a reference solution, each L
While measuring the voltages Vo output from the log amplifier circuits with a voltmeter or the like, individually operate the trimmers for adjusting the reference currents to be applied to the respective log amplifier circuits.
It has been necessary to initialize the g amplifier circuit to a state where the lower limit voltage of the rated range of the AD converter is uniformly output. Therefore, the measurement could not be started smoothly.

In practice, the voltage output from all the log amplifier circuits is A, taking into account the difference between the light emitting state of the light source and the state of the cuvette during adjustment and measurement.
Initially set to a value slightly higher than the lower limit voltage of the rated range of the D converter (for example, about 2 V when the allowable range of the input voltage is 0 V to 10 V AD converter is used). Often.

Further, even if a sudden failure occurs in the device (for example, damage to the light source or the spectroscopic element) and the S / N ratio of the photocurrent _Ip is extremely reduced, the reference current I _{Since the} temporary measurement is completed depending on the adjustment of _f , there is a risk that an incorrect analysis result including an error will be referred to in a subsequent diagnosis, and a misdiagnosis will be made. Therefore, in order to prevent such a risk, it is necessary to constantly monitor whether or not the reference current is within a predetermined range during the measurement.

Accordingly, it is a first object of the present invention to provide an automatic analyzer that can easily perform a more reliable component analysis. A second object is to provide an automatic analyzer having a failure diagnosis function.

[0012]

In order to solve the above-mentioned problems, the present invention provides a method for calculating the concentration of a component element using the absorbance of the component element contained in a sample solution filled in a cuvette. An automatic analyzer having a means for irradiating the cuvette with light containing a plurality of monochromatic light components, a moving mechanism for relatively moving the light source and the cuvette, and from the light source to the cuvette. A light detector for detecting the intensity value of each monochromatic light component contained in the light transmitted through the sample solution filled in the cuvette via the cuvette while being irradiated with light; and the light detector Logarithmic converter for calculating the level value of the intensity of each monochromatic light component detected, respectively, time integration of the level value calculated by the logarithmic converter, respectively, the time proportional to the time integration value To provide an automatic analyzer, characterized in that it comprises an integration type AD converter to be supplied to said density calculation means as the absorbance of component elements contained in the sample solution.

With this configuration, the level value of the intensity of each monochromatic light component detected while scanning and irradiating the cuvette with light is digitally converted by the integrating AD converter. The error (particularly, the error due to the influence of partial contamination of the cuvette) included in the intensity of each monochromatic light component detected by the above is removed by the integration characteristic of the integration type AD converter. Therefore, by using the above time as the absorbance of the component elements contained in the sample solution, measurement data without fluctuation (that is, stable measurement data) can be obtained. That is, according to the present automatic analyzer, more reliable component analysis can be performed.

Prior to calculating the concentration of the component elements contained in the sample solution, a reference time proportional to the level value of the intensity of each monochromatic light component contained in the light transmitted through the reference solution is determined in advance. If the reference time is calculated and the logarithmic converter automatically corrects each reference value used for calculating the level value of the intensity of each monochromatic light component using this reference time, the user can perform complicated initial settings. (I.e., corresponding to the adjustment of the reference current given to each Log amplifier circuit) is not required.
Therefore, the measurement can be started smoothly.

Further, during the measurement, the intensity level of each monochromatic light component is calculated from the level value of the intensity of each monochromatic light component calculated by the logarithmic converter and a reference time used as a reference value when calculating this level value. By calculating back, and stopping the measurement when the intensity fluctuates beyond a predetermined range, it is possible to prevent the output of incorrect measurement data that causes a misdiagnosis. In addition, at this time, if a warning is issued by an alarm or the like and a failure diagnosis function for displaying a failure type determined according to the degree of fluctuation of the intensity of each monochromatic light component is added, the user can promptly recognize the failure of the device. And take appropriate measures.

[0016]

Embodiments of the present invention will be described below with reference to the accompanying drawings.

First, the basic configuration of the automatic analyzer according to the present embodiment will be described with reference to FIG.

The automatic analyzer comprises a measuring section A for measuring the absorbance of the component elements contained in the sample solution 25 (reaction liquid of the sample and the reagent) in the cuvette 1, and a component analysis process described later and the entire apparatus. And a processing unit B for executing the control processing and the like.

The measuring section A has a sample disk 6 on which a sample cup 7 filled with a sample is mounted, a reagent disk 8 on which a reagent bottle 9 filled with a reagent is mounted, and a cuvette 1 mounted thereon. Using the suction of the pump 10, the reagent dispensing mechanism 5 for dispensing the reagent from the reagent bottle 9 on the reagent disk 8 to the cuvette 1 on the reaction disk 2 using the suction of the reaction disk 2 A sample dispensing mechanism 4 for dispensing a sample from the sample cup 7 on the sample disk 6 to the cuvette 1 on the reaction disk 2, a stirring mechanism 12 for stirring the reagent dispensed into the cuvette 1 and the sample, A heating mechanism 3 (for example, a circulating constant temperature water tank or the like) for keeping the cuvette 1 warm to promote a chemical reaction between the cuvette 1 and the reagent, and a sample solution (a reaction liquid between the sample and the reagent) in the cuvette 1 Measure the absorbance of component elements A cleaning mechanism 13 for cleaning the cuvette 1 with pure water supplied from the pump 14 after the detection of components by the detection mechanism.

The processing section B includes a CPU 19, a memory 20 storing programs and various data in which component analysis processing and the like described later are defined, and an input device (for example, a keyboard 23) for receiving an input from a user. , Cuvette 1
Output device that outputs the result of component detection etc. of the sample solution 25 in the inside
(For example, a printer 21, a CRT 22, a speaker, and the like), which are interconnected by an interface bus 18.

Under the control of the CPU 19 of the processing unit B, the reagent dispensing mechanism 5 dispenses the reagent to the cuvette 1 with the rotation of each of the disks 2, 6, 8 and the sample dispensing mechanism 4 executes the cuvette. 1, a stirring process of the sample and the reagent in the cuvette 1 by the stirring mechanism 12, a measurement process of the absorbance of the component elements contained in the sample solution 25 in the cuvette 1 by the detection mechanism, and a washing process 13 The cleaning process of the cuvette 1 is performed continuously.

Now, in order to clarify the measurement principle of the automatic analyzer, the basic configuration of the detection mechanism will be described as shown in FIG.

The present detection mechanism transmits a light source 15 (for example, a halogen lamp or the like) for irradiating the cuvette 1 with light having a continuous spectrum to the cuvette 1 passing by the rotation of the reaction disk, and transmits the sample solution 25 filled in the cuvette 1. A spectroscopic element 16 (for example, a diffraction grating or a prism) for dispersing the incoming light, and a photodiode array 17 (for example, a silicon photosensor array or the like) for detecting the intensity distribution of a spectral line image formed by the spectroscopic element 16 And a conversion unit 24 for calculating a level value of the intensity of each spectral line image detected simultaneously by the photodiode array 17.

As shown in FIG. 3, the conversion unit 24 includes a microprocessor 32 for controlling data input / output to / from the CPU 19, and the photodiode array 1
7 Each photocurrent the If ₁ output from, ..., the level of the If _n values V
o _1, ..., Vo _n Log amplifier circuit 26a ₁ for calculating the (analog data), ..., and 26a _n, the microprocessor 3
Each Log amplifier circuit 26 according to the control signal from
a _1, ..., reference current Ip ₁ to 26a _n, ..., DA converter 33a ₁ to give Ip _n, ..., and 33a _n, each Log amplifier circuits 26a _1, ..., 26a _n analog data Vo ₁ output from, ... are configured to Vo _n from the AD converter 36 for digital conversion.

By configuring the detection mechanism in this way, the CPU 19 of the measuring section B can control the intensity of each monochromatic light component contained in the light transmitted through the sample solution 25 filled in the cuvette 1. Digital data of the level value (that is, data corresponding to the absorbance of the component elements contained in the sample solution 25 filled in the cuvette 1) is input.

In this embodiment, an integrating AD converter having a function of integrating an input signal is employed as an AD converter. And the integration type AD converter, the Log amplifier circuits 26a ₁ in accordance with a control signal from the microprocessor 32, ..., the output signal Vo ₁ in 26a _n, ..., integrating circuits 28a ₁ to the time integral of Vo _n , ..., and 28a _n, each integrator circuit in accordance with a control signal from the microprocessor 32 2
8a _1, ..., a multiplexer 29 which transfers the time series output signals from 28a _n, a gate circuit 30 which outputs only the clock pulse time proportional to the signal transferred from the multiplexer 29, the gate circuit 30 This is an AD converter including a counter 31 for measuring the number of clock pulses to be output.

By adopting such an integral type AD converter, each light is scanned and irradiated on the cuvette.
og amplifier circuit 26a _1, ..., analog data Vo ₁ coming outputted from 26a _n, ..., it is possible to remove random noise contained in Vo _n. Therefore, cuvette 1
Even if the output signal of the photodiode array 17 fluctuates due to local absorption of light such as dirt, the effect can be eliminated.

Each of the log amplifier circuits 26a to be subjected to the logarithmic conversion processing (see Equation 1) described in the section of the prior art.
_1, ..., as the 26a _n, both, Log amplifier circuit having a similar known circuit configuration of Log amplifier circuit incorporated in the conventional spectrophotometer, i.e., the two Log amplifier and two A Log amplifier circuit (see FIG. 4) including transistors is employed.

Next, a component analysis process using the automatic analyzer will be described.

When a command instructing the start of the component analysis processing is input from the input device 23, the present automatic measuring apparatus performs each of the Log amplifier circuits 26a ₁ ,.
Reference current Ip ₁ to give the 6a _n, ..., it executes the correction process of Ip _n. That is, the CPU 19 controls the reaction disk 2
While rotating the, the process of dispensing pure water into the cuvette 1 by the washing mechanism 13 and the process of measuring the absorbance of pure water in the cuvette 1 by the detection mechanism are continuously performed. During this time, the microprocessor 32 of the conversion unit 24 of the detection mechanism, the DA converter 33a _1, ..., controls 33a _n, the counter 3
1 so that a value equal to the lower limit value of the rating range of the integrating AD converter 36 is latched at 1
a ₁ ,..., 26a _n
p _1, ..., are respectively corrected within a predetermined range of Ip _n. As a result, the offset caused by the change in the measurement condition such as the brightness of the light source is offset, so that the rated range of the integrating AD converter 36 can always be utilized to the maximum. Each corrected reference current Ip
_1, ..., the value of Ip _n is stored in the memory 20 as the reference data in determining the device status in the component analysis.

After the above correction processing is completed, the automatic measuring apparatus executes the following component analysis processing under the control of the CPU 19. That is, while rotating the disks 2, 6, and 8, the reagent dispensing process to the cuvette 1 by the reagent dispensing mechanism 5, the sample dispensing process to the cuvette 1 by the sample dispensing mechanism 4, and the cuvette by the stirring mechanism 12 The process of stirring the sample and the reagent in the sample solution 1, the process of measuring the absorbance of the component elements contained in the sample solution 25 in the cuvette 1 by the detection mechanism, and the process of cleaning the cuvette 1 by the cleaning mechanism 13 are continuously executed.

Specifically, the reagent dispensing mechanism 5 sequentially dispenses the reagent in the reagent bottle 9 sent by the rotation of the reagent disk 8 to the cuvette 1 sent by the rotation of the reaction disk 2. On the other hand, the sample dispensing mechanism 4
However, the reagent in the sample cup 7 sent by the rotation of the sample disk 6 is sequentially dispensed to the cuvette 1 sent by the rotation of the reaction disk 2. Thereafter, the stirring mechanism 12 sufficiently stirs the reagent and the sample filled in the cuvette 1 sent by the rotation of the reaction disk 2. During this time, the cuvette 1 is kept at an appropriate temperature by the heating mechanism 3 so that the color reaction between the sample and the reagent in the cuvette 1 proceeds rapidly.

The detecting mechanism sequentially performs the process in which the cuvette 1 passes in front of the light source 15 by the rotation of the reaction disk 2 (ie, the process in which the light from the light source 15 is scanned and irradiated on the cuvette 1). After the calculated level value of the intensity of each monochromatic light component is converted into a digital value by an integrating AD converter 36 having an integrating characteristic with respect to random noise, the component elements contained in the sample solution 25 in the cuvette 1 are converted. Is input to the CPU 19 as the absorbance data of.

Then, the CPU 19 stores the input absorbance data in the memory 20 for each monochromatic light component, and when the operator inputs an inspection item, the CPU 19 outputs the data from the memory 20 according to the inspection item input by the operator. The absorbance data of the determined monochromatic light component is read out, and the absorbance data is converted into a density value by a conversion process using an appropriate conversion constant.

Then, the cleaning mechanism 13 includes the reaction disk 2
The cuvette 1 sent by the rotation of is washed.
The cleaned cuvette 1 is sent by the rotation of the reaction disk 2 and is used again.

As described above, the present automatic analyzer uses
It has a function to automatically execute a series of processes from the initial setting of the reference current supplied to the amplifier circuit to the cuvette cleaning process. Can significantly reduce the work load imposed on the user.

By the way, during the execution of such a component analysis process, the CPU 19 further outputs the reference data stored in the memory 20 (currently, each Log amplifier circuit 26).
a ₁ ,..., 26a _n
p _1, ..., using the values) of Ip _n, running constantly determination processing unit state shown below. That is, the CPU 19 determines that each of the Log amplifier circuits 26a ₁ ,.
the level of the intensity of each spectral line images a _n is calculated,
The reference data stored in the memory 20, by using the formula 1 mentioned in the description of the prior art, the photocurrent value the If ₁ output from the photodiode array 17, ..., sequentially calculated back the If _n and, each of the optical current value If _1, ..., fluctuations in the If _n ΔI
If f ₁ ,..., ΔIf _n exceeds the allowable range, it is determined that the device has failed. Then, the current component analysis process is stopped, and the determination result is output from the output device.
(E.g., generating an alarm sound from a speaker) to warn the operator. Therefore, it is possible to avoid a situation in which incorrect measurement data that may cause a misdiagnosis later due to a device failure is output. In addition, since the photocurrent shows a unique variation according to the type of failure, if failure information in which the failure type of the device is associated with variation data of the photocurrent is stored in the memory 20 in advance, this failure information and It is also possible to determine the type of failure of the device by using the photocurrent values If ₁ ,..., If _n calculated above. Then, if the type of device failure is output from the output device together with the warning, the operator can quickly and accurately respond to the device failure. In addition, each Lo
g amplifier circuit 26a _1, ..., reference current Ip ₁ to give the 26a _n, ..., by the correction processing of Ip _n, any one of Log amplifier circuit 26a _1, ..., the predetermined to 26a _n , Ip ₁ ,..., Ip
Also, when _n is given, the CPU 19
It determines that the device has failed and performs the same processing.

This concludes the description of the component analysis processing using the automatic analyzer.

The automatic analyzer does not need to be used in an independent form as described above. For example, an automatic analyzer installed in each place and an information processing apparatus installed in the center are mutually connected by a line using a modem, and at an appropriate timing, information on the apparatus state obtained by the above-described determination processing is transmitted to each of them. If the data is transferred from the automatic analyzer to the information processing device, the operating states of the plurality of automatic analyzers can be centrally managed in the center.

In this embodiment, the conversion unit 2
To reduce the size of 4, using a multiplexer 29, a plurality of integrating circuits 28a _1, ..., the output signal from 28a _n in time series by the single gate circuit 30 and one counter 31 if it is to process, there is a relatively margin in installation space conversion unit 24, the integrating circuit 28a ₁ without using a multiplexer, ..., 28a _n
Respectively connecting the gate circuit and a counter, a plurality of integrating circuits 28a _1, ..., it may be processed simultaneously output signals from 28a _n.

Further, the integrating circuit 28a _1, ..., a start trigger and stop trigger 28a _n as IRQ of the microprocessor, the integrating circuit 28a _1, ..., from the time when the start pulse 28a _n occurs If the clock pulse generated by the gate circuit until the stop pulse is generated is counted in parallel by a counter built in the microprocessor, the circuit configuration of the integrating AD converter 36 is further simplified. And the integral type A
The processing speed of the D converter 36 can be increased.

[0042]

According to the automatic analyzer according to the present invention, a more reliable component analysis can be performed with a simple operation. In addition, by adding the failure diagnosis function, various failures can be found at an early stage, and the intrusion of incorrect measurement data that causes a misdiagnosis can be avoided.

[Brief description of the drawings]

FIG. 1 is a diagram showing a basic configuration of an automatic analyzer according to an embodiment of the present invention.

FIG. 2 is a diagram illustrating a basic configuration of the Log amplifier circuit of FIG. 1;

FIG. 3 is a diagram showing a basic configuration of the conversion unit of FIG. 1;

FIG. 4 is a diagram showing a basic configuration of the Log amplifier of FIG. 2;

[Explanation of symbols]

REFERENCE SIGNS LIST 1 cuvette 1 2 reaction disk 3 heating mechanism 4 sample dispensing mechanism 5 reagent dispensing mechanism 6 sample disk 7 sample cup 8 reagent disk 9 reagent bottle 10, 11, 14 pump 12 Stirring mechanism 13 Cleaning mechanism 15 Light source 16 Spectral element 17 Photodiode array 18 Interface bus 19 CPU 20 Memory 21 Printer 22 CRT 23 Keyboard 24 Conversion unit 26a ₁ ,. . . , 26a _n ... Log amplifiers 28a ₁ ,. . . , 28a _n ... integrating circuit 29 ... multiplexer 30 ... gate circuit 31 ... counter 32 ... microprocessor _{33a 1, ..., 33a n ...} DA converter

Claims (4)

[Claims] 1. An automatic analyzer comprising a concentration calculating means for calculating the concentration of a component element from the absorbance of the component element contained in a sample solution filled in a cuvette, the analyzer comprising a plurality of monochromatic light components. A light source for irradiating the cuvette with light, a moving mechanism for relatively moving the cuvette and the light source, and while the cuvette is irradiated with light from the light source,
A photodetector for detecting the intensity of each monochromatic light component contained in the light transmitted through the sample solution filled in the cuvette via the cuvette, and the intensity of each monochromatic light component detected by the photodetector. A logarithmic converter for calculating the level value, respectively, and time-integrating the intensity level value of each monochromatic light component calculated by the logarithmic converter, respectively, and is proportional to the time integrated value of the intensity level value of each monochromatic light component. An automatic A / D converter for providing time to the concentration calculating means as an absorbance of a component element contained in the sample solution. 2. The automatic analyzer according to claim 1, wherein said integrating AD converter includes a plurality of integrating circuits for integrating, for each monochromatic light component, the level value of the intensity of the monochromatic light component with time; A multiplexer for transferring the time-integrated value of the intensity level value of each monochromatic light component calculated by each of the integrating circuits in time series; and the intensity level value of each monochromatic light component transferred in time series from the multiplexer. And an inverse integration circuit for sequentially calculating a time proportional to the time integral of the automatic analyzer. 3. The automatic analyzer according to claim 1, wherein the level value of the intensity of each monochromatic light component calculated by the logarithmic converter is a value of the intensity of each monochromatic light component detected by the photodetector. It is the logarithm of the ratio of the intensity to the reference value, and the automatic analyzer uses the time of the intensity level value of each monochromatic light component contained in the light transmitted through the reference solution having the absorbance as a predetermined reference. Storage means for storing a reference time proportional to the integral value; prior to the component analysis of the sample solution, the logarithmic converter uses the respective reference times stored in the storage means to control the intensity of each monochromatic light component. And a reference value correcting means for correcting a reference value used for calculating a level value of the reference value. 4. The automatic analyzer according to claim 3, wherein the level value of the intensity of each monochromatic light component calculated by the logarithmic converter and each reference time stored in the storage unit are used. Light amount calculating means for calculating the intensity of each monochromatic light component; fluctuation detecting means for detecting a fluctuation in the intensity value of each monochromatic light component calculated by the light amount calculating means; and a fluctuation detected by the fluctuation detecting means being a predetermined value. A determination unit that determines a failure of the automatic analyzer when the value exceeds the range; and a warning unit that outputs a determination result of the determination unit. An automatic analyzer, wherein calculation of the concentration of a component element contained in the sample solution is stopped.