JPS6010255B2 - Method for detecting agglutination reactions in blood, etc. - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for optically and electrically detecting the agglutination reaction state of blood or the like.

Medical science is currently making remarkable progress, and serology is no exception.

And the agglutination or concentration reaction test plays an important role in the serology. However, at present, these tests are manually operated and judged, and there is a considerable risk of erroneous judgments, such as differences in judgment due to individual differences and judgments changing from time to time even for the same person. The object of the present invention is to electronically perform the determination of an agglutination or agglomeration reaction test, thereby increasing the accuracy of the determination and the speed of the determination operation. The agglutinated or non-agglutinated specimen produced as a result of an agglutination reaction test conducted in a transparent container is observed using optical means such as bright field illumination or hawk field illumination, and then the sample is observed using a scanning optical device. When an electrical signal is obtained through photoelectric conversion, the following characteristics appear.

That is, in the agglomerated state, a coagulated soul and a liquid portion are generated, and a difference occurs in the output voltage between them. In particular, when cohesive souls and liquid portions alternate along the scanning line, the output signal fluctuates significantly. On the other hand, in a non-agglomerated state, the output voltage is approximately uniform over the entire surface of the reaction castle. This is because in the agglomerated state, there is a large difference in light transmittance and light scattering between the aggregate and the liquid part, and in the non-agglomerated state, there is not much difference in light transmittance and light scattering over the entire surface of the reaction castle. I think it's because there isn't. The present invention focuses on the difference between aggregation and non-aggregation reactions and distinguishes between both reactions.

In other words, a signal corresponding to the average value of the electrical signal is extracted from the electrical signal obtained by photoelectric conversion, and the fluctuation rate of the original signal with respect to the average value is determined, and the fluctuation rate is larger than that when it is not aggregated.
A fluctuation rate smaller than the fluctuation rate during aggregation is predetermined, and the time during which the fluctuation rate of the original signal becomes larger than this determined fluctuation rate is accumulated over the entire scanning time, and this is a value that can be determined to be substantially aggregation. In this case, it is determined that there is aggregation. According to the present invention, the electrical signal obtained by photoelectric conversion is f, and the signal corresponding to the minute interval average of f is f'. The generation time of f is accumulated over the entire scanning time.

Therefore, by rearranging the '1' formula by setting r>0, the following formula is obtained.
lf'-f l-nf'>0 [21 The formula [2] becomes the following formula when f'>f.

(r-f)-m'>0 glue (2) When f'<f, the equation becomes the following equation.

(f-f')-nf'>0 [4} From the above, we can focus on the method of paying attention to both the increase and decrease of the signal f, that is, the method based on formula (■), and the method that focuses only on the increase of the signal f. A method, that is, a method according to the '3l formula,
and a method that focuses only on the time when the signal f decreases ``i.e.
A method based on formula 4} can be considered.

Next, the above three methods will be explained with reference to the drawings showing examples. m Method of paying attention to both increases and decreases in signal f FIG. 1 is a block diagram of a device that uses electric signal 1 as an input signal to identify the presence or absence of aggregates.

Reference numeral 2 denotes a low-pass transmitter that passes only the low frequency components of the electrical signal 1.

The cutoff frequency of this low-pass waver is determined to be the lowest frequency among the frequency components included in the signal during the agglutination reaction but not included in the signal during the non-aggregation reaction. In addition, the output signal 3 of the wave transmitter 2 which passes the low frequency band is considered to be a signal corresponding to the average of the electric signal 1 over a minute interval in this circuit. Reference numeral 4 denotes a subtraction circuit that calculates the difference between the electrical signal 1 and the output signal 3 corresponding to the average of the signal 1 over a minute interval.

5 is a full-wave rectifier circuit that full-wave rectifies the output signal 6 of the subtraction circuit 4; 7 is a variable resistor that divides the output signal 3; and 8 is the output signal 9 of the full-wave rectifier circuit 5 and the variable resistor 7. Electrical signal 1 from
0 and outputs an electric signal 11 with a constant amplitude when the former is larger than the latter.

12 is a gate circuit controlled by a signal 13 from a separately provided control circuit.

In this circuit, the output signal 3 of the wave transmitter 2 which passes a low frequency band is considered to be the average of the minute interval of the original electric signal 1, but this idea does not hold true immediately after the start of scanning. Therefore, it is decided to ignore the signal for a certain period of time from the start of scanning, and a gate circuit 12 is provided for this purpose. Reference numeral 14 denotes an integrating circuit that integrates the output signal 15 of the gate circuit 12 over the entire scanning time, and is reset by a signal 16 from a separately provided control circuit at the end of the entire scanning.

A comparison circuit 17 compares the output signal 18 of the integrating circuit 14 with a signal 19 corresponding to a predetermined reference value, and outputs an output signal 20 with a constant amplitude indicating that aggregation is present when the former is larger than the latter.

The reference value signal 19 is set to a value sufficient to determine that there is substantial aggregation. FIGS. 2 and 3 show actual inspection examples.

Ao in Figure 2 is specimen a in an aggregated state on a transparent slope.
Alternatively, it is a plan view of a specimen (generally referred to as a specimen in this specification).

A, -F are graphs showing the relationship between the voltage of the output signal and time at each stage of detection when there is aggregation. A, indicates the output signal la of the photoelectric element generated when scanning is performed with a thin beam along the scanning line at Ao, which becomes the signal 1 input to the apparatus of FIG. A2 indicates the output signal 3a of the wave generator which passes a low frequency band and is considered to be a minute interval average of the original electrical signal la. (A2 shows the original electric signal la with a broken line.) A3 shows the output signal 6a of the subtraction circuit 4.
A4 indicates the output signal 9a of the full-wave rectifier circuit 5. (In the figure, an electric signal 10a obtained by dividing the power signal 3a shown in A2 by the variable resistor 7 is shown by a broken line.) A5 shows the output signal 11a of the comparator circuit 8. (A5
, a control signal 13 to the gate circuit 12 is shown by a dashed line. )A6 indicates the output signal 14a of the integrating circuit 14. A? shows the output signal 14a of the integrating circuit 14 during the total scanning time t. (The reference value 19 is indicated by a dashed line in A7.) A8 is the comparator 17 which means that there is aggregation.
The output signal 20a is shown. 3 is a plan view of specimen b in a non-aggregated state.

B and B5 are graphs showing the output signal at each stage in the case of a non-aggregation reaction in terms of voltage vs. time. B is B
1 shows the output signal lb of the photoelectric element generated when scanning along the scanning line bo at o, which becomes the electrical signal 1 of the apparatus of FIG. B2 is the output signal 3 of wave generator 2 that passes through the reduction
b. (The original exposure force number lb is shown by a broken line in &, but it overlaps with 3b in most parts.)
& indicates the output signal 6b of the subtraction circuit 4. B4 is the output signal 9b of the full-wave rectifier circuit. (B4 has output signal 3b
An electrical signal 10b obtained by dividing the voltage by a variable resistor is shown by a broken line. )B5 indicates the output signal 11b of the comparator circuit 8. (
In B5, a control signal 13 to the gate circuit 12 is shown by a dashed line. ) As can be seen from B5, gate circuit 1
There is no output signal of 2, therefore there is no output signal of the integrating circuit 14 either. Therefore, it is determined that there is no aggregation. (2} Signal f
This method can be achieved by inserting an inverting amplifier with an amplification factor of 1 in place of the full-wave rectifier circuit 5 in the apparatus shown in FIG.

In addition, as the low-pass wave generator 2, a low-pass wave generator with two cut-off frequencies (Fig. 4) may be used. In Fig. 4, 21 and 22 are diodes, 23 and 24 are resistors, and 25
is a capacitor. The cutoff frequency of this low-pass wave generator is determined by the resistor 23 and capacitor 25 when the signal f increases, and by the resistor 24 and the capacitor 25 when the signal f decreases.
It is determined by {3} Method of paying attention when the signal decreases A method of paying attention when the signal decreases can be achieved by removing the full-wave rectifier circuit 5 and the gate circuit 12 from the apparatus shown in FIG. 1 described above.

Further, as in the case of paying attention to the signal increase in the previous section, it is also possible to use the low-pass wave generator shown in FIG. 4. As described above, the present invention optically and electrically detects the state of the agglutination reaction of blood, etc., and determines whether it is agglutinated or non-agglutinated. Therefore, accurate determination can be made according to predetermined standards. Unlike judgments based on human experience, there is an extremely low risk of misjudgment, and it is possible to make judgments quickly, making it a great contribution to serology.

[Brief explanation of the drawing]

FIG. 1 is a block diagram showing an embodiment of an apparatus for carrying out the present invention, FIG. 2 Ao is a plan view of a sample in the case of agglutination,
A, ~A8 are diagrams showing the state of electrical output at each stage of detection, Figure 3 is a plan view of the sample in the case of non-aggregation, B
-B5 is a diagram showing the state of electrical output at each stage of detection, and FIG. 4 is a diagram showing an example of a wave generator that passes a low frequency band. 1, la, lb: electrical signal obtained by photoelectrically converting the sample, 2: wave generator that passes low frequency, 4: subtraction circuit, 5: full-wave rectifier circuit, 8:
Comparison circuit, 12: Gate circuit, 13: Control signal, 14:
Integrating circuit, 16: Control signal, 17: Comparing circuit, 19: Signal corresponding to reference value, 20: Output signal indicating presence of aggregation.
Figure 1 Figure 2 Figure 3 Figure 4

Claims (1)

[Claims] 1. Scan the specimen with a thin beam of light, photoelectrically convert the light that passed through the specimen in the entire scanning range, extract a first signal whose size corresponds to the amount of light transmitted through the specimen or the degree of light scattering, and A second signal corresponding to a minute interval average of the signal is extracted from the first signal, and a third signal is obtained by dividing the difference between the first signal and the second signal by the second signal, that is, the first signal. The rate of variation with respect to the small interval average is taken out, and the time during which the third signal is greater than a predetermined reference value is integrated over the entire detection time, and if the integrated time exceeds the predetermined reference value, it is determined that there is aggregation. A method for detecting an agglutination reaction of blood, etc., characterized by determining.