JPS6239375B2 - - Google Patents

Description

[Detailed description of the invention]

[Industrial Application Field] The present invention relates to a particle analysis method for statistically processing particle size distribution curves of particles such as blood cells. [Prior Art] Conventionally, in a particle analysis method in which particles such as blood cells suspended in a liquid are passed through micropores and detected based on the difference in electrical impedance between the liquid and the particles, Since the size of the generated particle signal is proportional to the size of the particle, various statistical processes regarding the size of the particle are performed, and the information is utilized, for example, in clinical medicine. Normally, when analyzing blood cells, etc.
Blood contains approximately 5 million blood cells per ^mm3 , and blood is diluted approximately 50,000 times with physiological saline to a concentration of approximately 100 cells/ ^mm3 .
Approximately 25,000 blood cells are measured one by one. In this case, it takes about 10 seconds to complete a series of measurements. Therefore, the simple average measurement time per piece is about 0.4 mm. [Problem to be solved by the invention] If this amount of time is required, analysis processing can be performed very easily using technology such as microcomputers that have come into use in many fields in recent years. Particles suspended in a liquid are not necessarily uniformly dispersed, and even in ordinary blood cell counters, the phenomenon of simultaneous passage, where two or more particles pass in succession, has become a problem. . Therefore, the problem is rather the shape of the detection micropores through which the particles pass and the speed at which the particles pass. Normally, when detecting particles such as blood cells of about 10 microns, the diameter of the detection hole is about 100 microns.
It is common for the particles to pass through at a speed of several meters/second. The time width of the particle signal obtained at this time is several microseconds to several tens of microseconds. Therefore, even if a high-speed A-D converter is used to screen the particle size and convert it into a digital signal, a device that performs a series of processing in a few microseconds and waits for the next signal will not be able to process the high-speed signal. Therefore, it is expensive and extremely uneconomical considering the average particle density. On the other hand, in a relatively easily constructed particle counting device, particles are detected by a common detector by changing the measurement threshold little by little, and the particles are counted in the form of a classification count for each, and then analyzed again after counting is completed. Although a method of processing is used, it is necessary to increase the permissible count value of each counting circuit provided in parallel, and the device becomes large-scale, so it cannot be said to be a very effective method. In particular, in order to improve the analysis accuracy, it is necessary to further increase the number of parallel devices, which has the drawback of making the device extremely expensive. In order to eliminate the above drawbacks, particles in a suspension are detected by a detection device that detects the difference in impedance between the liquid and the particles, and the detection circuit of the detection device converts the particles into an electrical pulse signal. By configuring a frequency divider circuit with an appropriate frequency division ratio to widen the pulse interval, analysis can be performed with high precision, and subsequent processing can be performed at low cost using an integrated microcomputer. The present inventor has already developed a particle analysis method that enables the
A patent application has been filed as (No. 135731). The present invention goes one step further and statistically processes the measurement results of the particle size distribution curve to create a new particle size distribution curve.
Alternatively, we provide a particle analysis method that makes it possible to obtain the particle size distribution curve of the required particle from the results of a mixture of two types of particles, or to predict and obtain the remaining distribution curve from a part of the curve. That is. [Means and effects for solving the problem] The particle analysis method of the present invention allows particles in a suspension to pass through the micropores of a detection device, detects them based on the difference in impedance between the liquid and the particles, and detects the particles. In a method of analyzing particles using particle signals, the particle signal is sent to multiple comparison circuits to discriminate the size of the particle signal, and then frequency-divided by multiple frequency divider circuits connected to each comparison circuit. , the pulse signal from the frequency dividing circuit is input in parallel to the input/output circuit, and the arithmetic circuit, read-only memory, read/write memory, and input device are connected to this input/output circuit, and the settings from the outside are connected to this input device. The method is characterized in that condition settings such as the setting of the analysis particle size range are input, and the arithmetic circuit obtains a statistically processed particle size distribution curve from the cumulative particle size distribution curve. [Example] Hereinafter, an example of the present invention will be described based on the drawings. FIG. 1 is a systematic explanatory diagram showing an example of an apparatus for implementing the particle analysis method of the present invention. Reference numeral 1 denotes a particle detection device that detects particles such as blood cells suspended in a liquid by passing through micropores based on the difference in electrical impedance between the liquid and the particles. Comparison circuit 2 is connected.
A plurality of frequency dividing circuits 3 are connected to each of these comparison circuits 2, and an input/output circuit 4 for inputting the outputs of the frequency dividing circuits in parallel is connected to these frequency dividing circuits 3. An input device 5 is connected to this input/output circuit 4 for inputting external settings and condition settings such as analysis particle size range settings. Write memory 8 and output circuit 10 are connected. Furthermore, a recording device 11 is connected to this output circuit 10, and a display device (display device) is connected as necessary.
12 are connected. The comparator circuit 2 is provided with voltage dividing resistors 15 and 16 for supplying voltages from the reference voltage generating circuits 13 and 14 and comparison voltages to each comparator circuit 2, respectively. In the particle analysis device configured as described above, the output signal of the particle detection device 1, which emits an electric signal proportional to the volume of the particle, is sent to a plurality of comparison circuits 2. Normally, about 50 to 100 comparison circuits 2 are used in parallel, so the comparison voltage is stepped.
It is divided into about 50 to 100 voltages.
Normally, a particle signal is given by a particle detection device with a pulse interval of 100 μsec on average, but the interval is not necessarily constant and the signal may be sent in a nearly continuous manner, so each pulse can be directly analyzed. To do this, an arithmetic circuit with an arithmetic speed on the order of several micrometers is required. To compensate for these drawbacks, the comparator circuit 2 is replaced with a frequency divider circuit 3 having an appropriate frequency division ratio between decimal and 100 decimal. They are connected to the comparator circuit 2 and input to the next input/output circuit 4 in parallel. The parallel pulse signals from the frequency divider circuit 3 are
This corresponds to each point in the area under the graph curve to construct a cumulative particle size distribution curve that has been appropriately averaged and frequency-divided, and the cumulative distribution curve is obtained by accumulating these points. In addition to signals related to the cumulative particle size distribution of particles, the input/output circuit 4 receives a signal 17 related to the quantitative determination of a liquid sample in which particles are suspended. This depends on whether the measurement is performed by analyzing a predetermined amount of suspended particles, by a predetermined time unit, or by measuring the total number of particles. However, since it has become common to obtain information such as the number of red blood cells in parallel, each measurement is an analysis of particles in a predetermined volume, and is performed over a period of several seconds to more than ten seconds. Suction analysis of a suspension of a predetermined amount of particles is often used. However, in cases where the number of particles per unit volume is rare, or where the number of particles is uneven as in the industrial field, it is better to end the analysis when a predetermined number of particles is reached to obtain more accurate information. This is desirable because you can grasp it. Furthermore, in cases where it is desired to determine changes over time in the distribution curve by repeated measurements, it is preferable to divide the measurement into short time units. For example, this is the case when observing the process of hemolysis of blood cells due to the addition of saponin. Furthermore, input/output circuit 4
A signal from the input device 5 for inputting external settings, for example, setting of the above-mentioned setting method or setting of conditions such as setting of analysis particle size range, is inputted to the input device 5 . As mentioned above, the input/output circuit 4 includes the arithmetic circuit 6,
It is electrically connected to the read-only memory 7, the read/write memory 8, and the output circuit 10, and performs various statistical processing, calculations, and the like. A recording device 11 is connected to the output circuit 10, and a display device 12 is connected as necessary to display recorded contents and other information. FIG. 2 shows an example of a cumulative particle size distribution curve. This curve is obtained as follows. That is, when the input/output circuit 4 receives a pulse for each frequency division ratio from each frequency dividing circuit 3, for example, one pulse for each pulse corresponding to 100 particles, the arithmetic circuit 6 receives a corresponding readout signal for each address. The operation of calling up the number stored in the write memory 8, adding one value, and writing it again is repeated until a predetermined measurement (based on volume, time, or number of particles as described above) is completed. As in the example shown in Table 1, each address stores the number of particles (cumulative value) corresponding to the respective address.

[Table] In Table 1, for example, address 1 is 1454, 10
The number of particles is shown at address 596 and 66 at address 55. When each address is sequentially called by the arithmetic circuit 6 and recorded by the recording device 11 through the output circuit 10, a cumulative particle size distribution curve as shown in FIG. 2 is obtained. Next, when the difference in the number of particles between each address is calculated, the result is as shown in Table 2.

〔Effect of the invention〕

As explained above, the particle analysis method of the present invention can calculate a regression curve from a particle size distribution curve using the least squares method and obtain various data. In addition, since all the data originates from the cumulative particle size distribution curve in Figure 2, information that cannot be obtained from the general particle size distribution curve in Figure 3, for example, when flat part 104 in Figure 2 is horizontally By extending to level zero, it is possible to easily calculate the number of single particles, and this is particularly effective when calculating the average particle volume. Furthermore, since the configuration of the apparatus for carrying out the method of the present invention starts from obtaining the cumulative particle size distribution, it is simplified and the time intervals of the processing pulses are averaged and separated in accordance with the calculation processing capacity of the calculation unit 6. Since the speed is reduced by the circumferential ratio, it is possible to use a low-speed microcomputer, which helps reduce costs, and it can be built into a conventional particle counting device. It has excellent characteristics.

[Brief explanation of the drawing]

Fig. 1 is a systematic explanatory diagram showing an example of an apparatus for carrying out the particle analysis method of the present invention, Figs. 2 to 8 are curve diagrams of processing examples, and Fig. 2 shows an example of a cumulative particle size distribution curve. Figure 3 is a curve diagram obtained by calculating the difference in the number of particles between each address in Figure 2, and Figure 4 is a curve diagram obtained by dividing and statistically organizing the left and right parts of the peak point in Figure 3. Fig. 5 is a curve diagram when only information on large particle sizes in the particle size distribution can be obtained due to the influence of noise, etc., and Fig. 6 is an estimation of the curve part that could not actually be measured in Fig. 5. Figure 7 is a distribution curve diagram of two or more types of particles with clearly different particle sizes, and Figure 8 is a curve diagram obtained by estimating the left side of the peak in Figure 7. . 1... Particle detection device, 2... Comparison circuit, 3...
Frequency dividing circuit, 4...Input/output circuit, 5...Input device,
6... Arithmetic circuit, 7... Read-only memory, 8...
Read/write memory, 10... Output circuit, 11... Recording device, 12... Display device, 13, 14
...Reference voltage generation circuit, 15, 16...Voltage dividing resistor, 17...Signal.

Claims (1)

[Scope of Claims] 1. A method in which particles in a suspension are passed through micropores of a detection device, detected based on the difference in impedance between the liquid and the particles, and analyzed based on the detected particle signals, comprising: is sent to multiple comparison circuits to discriminate the size of the particle signal, and then frequency-divided by multiple frequency divider circuits connected to each comparison circuit, and then the pulse signal from the frequency divider circuit is sent to an input/output circuit. input in parallel, connect the arithmetic circuit, read-only memory, read/write memory, and input device to this input/output circuit, and input condition settings such as external settings and analysis granularity range settings to this input device. A particle analysis method characterized in that the arithmetic circuit obtains a statistically processed particle size distribution curve from the cumulative particle size distribution curve.