JPS6234095B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to an automatic chemical analyzer capable of measuring both reaction end point and reaction rate.

[Prior art] Automatic chemical analyzers perform so-called reaction end point measurement, in which a sample and a reagent are reacted in a reaction tube until the reaction end point, and the reaction tube is measured colorimetrically. After the Union of Chemistry recommended that the standard measurement of enzyme activity should be the reaction rate method, which can be measured in a short time and is not affected by interfering substances, the reaction rate method became widely used. It became like that.

However, the detection circuit in the conventional automatic chemical analyzer can only perform measurements for either the reaction end point measurement or the reaction rate measurement, which is inconvenient.

Recently, automatic chemical analyzers (for example, the apparatus shown in Japanese Patent Application Laid-open No. 133480/1983) capable of carrying out both of these measurements have been developed.

In the detection circuit of such an automatic chemical analyzer, a reaction tube containing a test sample is placed in the optical path, and the light transmitted through the reaction tube is sent to an A/D converter via a photodetector and an amplifier. It is input here and converted to a digital signal. Then, the output of the A/D converter is counted by an up-down counter, and this counter output is further converted by a signal processing circuit into a signal corresponding to the density value, which is then displayed.

Now, the A/D converter of such a detection circuit is the sixth one.
As shown in the figure, a charge/discharge circuit 21, a comparator 22 that generates a match signal when the output of the photodetector D via the amplifier A and the discharge voltage of the charge/discharge circuit 21 match, a clock signal generator 23, and a clock signal generator 23; It consists of a gate circuit 24 that passes the clock signal from the clock signal generator 23 until a match signal is input from the comparator 22, and the clock signal passed by the gate circuit 24 is counted by an up-down counter 8. .

By the way, the charging/discharging circuit 21 of such an A/D converter
is used with a fixed time constant and reference voltage. That is, when measuring the reaction end point,
Regardless of whether the signal representing the transmittance of the reaction tube at the end point of the reaction (corresponding to the output of the photodetector D via the amplifier A) is within a wide range of transmittance from 0% to 100%, the predetermined measurement time is Since it is necessary to generate a matching signal from the comparator 22 during T ₀ and convert the output signal of the amplifier A into a digital signal, the time constant of the charge/discharge circuit 21 (time constant of the A/D converter) is The discharge curve is curve C in Figure 5a.
It is set as short as 1.

[Problems to be Solved by the Invention] On the other hand, in reaction rate measurement, it is necessary to obtain information corresponding to the change in transmittance during the progress of the reaction, that is, the amount indicated by, for example, L in FIG. 5a. When measuring the reaction rate, if this information is attempted to be obtained based on the discharge curve with a short time constant shown at C1 in FIG. 5a, the measurement accuracy will be insufficient. That is, the accuracy of this measurement is determined by how many clock pulses the time width ΔT corresponding to the unit change in transmittance ΔL corresponds to, and the higher the number, the higher the accuracy. I can say it. However, in the past, as is clear from Fig. 5a, this ΔT
Since the reaction rate was small, the measurement accuracy when measuring the reaction rate was insufficient.

The present invention solves these problems and provides an automatic chemical analyzer that can reliably convert and detect a wide dynamic range signal during reaction end point measurement into a digital signal, as well as perform reaction rate measurement with high precision. Its purpose is to provide circuits.

[Means for Solving the Problems] Therefore, the present invention provides a detector for detecting light transmitted through a reaction tube, a variable gain amplification circuit to which an output signal from the detector is supplied, and a variable amplification circuit for detecting light transmitted through a reaction tube. An A/D converter to which the output signal of the variable gain amplification circuit is supplied and whose A/D conversion reference voltage and A/D conversion time constant are variable, and an A/D converter for counting the output signal of the A/D converter. an up-down counter; a means for displaying the counted value of the up-down counter;
This is achieved by means for automatically controlling the D conversion reference voltage, the time constant of A/D conversion, and whether the up/down counter is counting up or down.

[Embodiment] FIG. 1 shows an embodiment of the present invention. In the drawing, 1 is a light source, and after light from the light source passes through a reaction tube 2, it is projected onto a photodetector 3. A plurality of reaction tubes 2 are attached to a rotary table 4, and new reaction tubes are sequentially placed between the light source 1 and the detector 3 by rotation of the table. 5 is a variable amplification factor amplifier, and the amplification factor of the amplifier 5 is controlled by an amplification factor control signal from a control device 6 such as a microcomputer. 6a is an input device such as a keyboard for inputting control commands to the control device. The output signal of the variable gain amplifier 5 is supplied to an A/D converter 7. The A/D converter 7 is capable of changing the A/D conversion reference voltage and the A/D conversion time constant, and these changes are made in accordance with the A/D conversion reference voltage control signal from the control device 6. This is done by a time constant control signal. The A/D converter is constructed as shown in FIG. In this figure, the same components as in FIG. 6 are denoted by the same numbers. That is, the reference voltage to be charged and the time constant for discharging the voltage are controlled by the reference voltage control signal and time constant control signal from the control device 6, respectively. A comparator 22 that generates a coincidence signal when the output signal value of the photodetector 3 and the discharge voltage value of the charge/discharge circuit 21 match, a clock signal generator 23, until a coincidence signal is input from the comparator 22.
It consists of a gate circuit 24 that passes the clock signal from the clock signal generator 23.

The output signal of the A/D converter 7 (the clock signal passed by the gate circuit 24) is supplied to an up-down counter 8. The up-down counter 8 performs up-counting or down-counting based on an up-count/down-count control signal from the control device 6. The output signal of the counter is converted in the signal processing circuit 9 into a signal corresponding to the concentration value of the test sample. The output signal of the signal processing circuit 9 is supplied to a display device 10 such as a line printer and displayed.

In the above-described configuration, a program for determining whether to measure the reaction end point or to measure the reaction rate for the samples contained in each of the reaction tubes 2 is inputted in advance by the input device 6a. As the turntable 4 rotates, the reaction tube 2 becomes the light source 1.
When each reaction tube is placed on the optical path toward the detector 3, a program for determining whether to perform reaction end point measurement or reaction rate measurement is read out for each reaction tube, and based on this command, the amplification factor control signal is is supplied to the variable gain amplifier 5, the A/D conversion reference voltage control signal and the time constant control signal to the A/D converter 7, and the up-count/down-count control signal to the up-down counter 8. .

That is, if a command to measure the sample contained in the reaction tube 2 by reaction end point measurement is issued, the amplification factor of the variable amplification factor amplifier 5 becomes a predetermined amplification factor common to the reaction end point measurement, and the difference between the sample and the reagent is The output signal of the detector 3 corresponding to the concentration at the end point of the reaction is amplified by the amplification factor and supplied to the A/D converter 7.

Now, when measuring the end point of a reaction, it is necessary to convert a signal with a wide dynamic range from the amplifier into a digital signal as described above. Therefore,
The time constant of the charging/discharging circuit ₂₁ (A/D converter 7
(A/D conversion time constant) is set short, and a voltage corresponding to 100% transmittance is set as the reference voltage (A/D conversion reference voltage) of the charging/discharging circuit 21. The output of the amplifier 5 is repeatedly converted into a digital signal every small time width by the A/D converter 7 whose time constant and reference voltage are set in this way.

The signal converted into a digital signal is supplied to an up-down counter 8. Since the up-down counter 8 is supplied with an up-count/down-count control signal from the control device 6 to command execution of up-counting, the digital signal from the A/D converter 7 in the up-down counter 8 is constant. Time is counted up, and the count value of the counter becomes the integral value of the digital signal value over the certain period of time. The counted value corresponds to the average value over the counting time of the signal obtained from the amplifier A if the integration time is constant, and based on the counted value, a signal corresponding to the concentration value based on the reaction end point measurement is generated by the signal processing device 9. The signal is output from the display device 10
will be displayed.

Furthermore, when a command is issued to measure the sample placed in the reaction tube 2 by reaction rate measurement, the amplification factor of the variable amplification factor amplifier 5 is determined by the detection signal obtained at the start of the reaction, for example, as shown by E ₀ in FIG. It changes automatically each time reaction rate is measured so that the signal value is amplified to a common signal value during reaction rate measurement. Therefore, when measuring the reaction rate, the output signal of the amplifier 5 is set at E ₀ as the initial value, and changes depending on the concentration change as the reaction progresses in the reaction tube 2, for example, as shown by dotted lines A, B, and C, depending on the reaction rate. It changes over time. Such a signal is supplied to the A/D converter 7, and A/D-converted it repeatedly for each small time width many times within a predetermined measurement time.

Now, in order to accurately measure the reaction rate, it is necessary to obtain a signal (corresponding to the output of the photodetector 3 via the amplifier 5) representing the transmittance during the progress of the reaction in a narrow range at a predetermined measurement time T ₀ . Change width L
All you have to do is find the curve C2 in Figure 5b.
As shown in , the time _constant of the charging/discharging circuit 21 (A/D
Set the A/D conversion time constant of converter 7 to be long,
Further, the voltage obtained by adding the maximum value of the width L from E ₀ is set as the reference voltage of the charging/discharging circuit 21 (reference voltage of A/D conversion). The A/D converter 7 whose time constant and reference voltage have been set in this manner converts a signal as shown by the solid line in FIG. 3 into a digital signal, and then supplies the digital signal to the up-down counter 8. In the up-down counter, the up-count/down-count control signal is used to repeatedly AD convert clock pulses sent from the converter 7 in small time widths for half time T/2 of the total counting time T in FIG. Count up. As a result, in Fig. 3, the diagonal line A
Counting is performed up to a count value corresponding to the area indicated by , and then down-counting is performed during the remaining time T/2. As a result, the count value of the up-down counter 8 corresponds to the area indicated by diagonal lines B in FIG. Since the area of this portion corresponds to the rate of change of the detection signal from the detector 3, the concentration measurement value based on the reaction rate measurement is displayed on the display device 10 based on the count value of the up-down counter 8. In this case, the time width corresponding to the unit change width ΔL is shown in Figure 5b.
As is clear from the above, ΔT' is considerably larger than the above ΔT, so that the measurement accuracy when measuring the reaction rate can be improved.

As described above, in the present invention, the amplification factor of the variable amplification factor amplifier and the up or down state of the up-down counter are controlled depending on whether the reaction rate is measured or the reaction end point is measured.
Since the A/D reference voltage of the A/D converter and the time constant of A/D conversion are controlled, this conventional device can reliably A/D convert and detect signals with a wide dynamic range when measuring the end point of a reaction. Highly accurate reaction rate measurements can be performed without impairing the properties of the

[Brief explanation of the drawing]

FIG. 1 is a diagram showing an embodiment of the present invention, FIG. 2 is a diagram illustrating a signal waveform to be A/D converted during reaction rate measurement, and FIG. 3 is a diagram illustrating a signal waveform to be A/D converted during reaction rate measurement. A diagram for explaining the count value of the up-down counter, Figure 4 is a partial detailed view of the apparatus shown in Figure 1, and Figures 5a and b are A when measuring the end point of the reaction and measuring the reaction rate, respectively. FIG. 6, which is a diagram used to explain the setting of the A/D conversion time constant and reference voltage of the A/D converter, shows a conventional A/D converter. 1: light source, 2: reaction tube, 3: photodetector, 4: rotary table, 5: amplifier, 6: control device, 6a:
Input device, 7: A/D converter, 8: Up-down counter, 9: Signal processing circuit, 10: Display device, 21: Charge/discharge circuit, 22: Comparator,
23: Clock signal generation circuit, 24: Gate circuit.

Claims (1)

[Claims] 1 A detector for detecting light transmitted through a reaction tube, a variable amplification circuit to which an output signal from the detector is supplied, and an A/D to which the output signal of the variable amplification circuit is supplied. Displays an A/D converter with variable conversion reference voltage and A/D conversion time constant, an up-down counter for counting output signals of the A/D converter, and a count value of the up-down counter. and an amplification factor of the variable amplification circuit, an A/D conversion reference voltage of the A/D converter, a time constant of the A/D conversion, and an up-down counter according to reaction rate measurement or reaction end point measurement. A detection circuit in an automatic chemical analyzer comprising means for automatically controlling whether the count is up or down.