JPS6229014B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a particle analyzer that electrically or optically detects particles such as blood cells suspended in a liquid and measures the particle size from the magnitude of the detection pulse. An object of the present invention is to provide a particle analyzer that can perform accurate particle size distribution measurements at low cost.

Conventionally, to measure the size distribution, or particle size distribution, of particles such as blood cells suspended in a liquid, the particles are first detected electrically or optically, and the detection pulse is proportional to the particle size. This is done by determining the height of the particle signal and determining the height distribution for thousands to tens of thousands of particles.
The methods are: (1) Direct AD conversion of particle signals.

(2) A method in which approximately 50 to 100 threshold circuits are provided and a counting circuit is subordinated to each threshold circuit.

(3) A method in which the threshold voltage of one threshold circuit is changed in steps, so that it operates as if 50 to 100 threshold circuits were lined up.

However, in method (1), particle signals do not always occur at regular intervals, generally exhibit a Poisson distribution, and are extremely fast, lasting several microseconds.
An AD conversion circuit is required, and the storage processing of digital values after conversion also needs to be fast. Considering that the average pulse interval of a particle signal is on the order of several hundred microseconds, this is a problem. It's the economy. Method (2) provides a sufficient response, but as a result, it is equivalent to arranging hundreds of particle counters with different threshold voltages, and although it is a precise measurement method, the circuit is large. , and are not necessarily low cost. Method (3) is very low cost, but on the other hand, particles of different sizes are not always uniformly dispersed in the liquid, and the conditions may differ between the first and second half of the measurement due to phenomena such as sedimentation. Accurate measurements may not always be possible due to problems such as blockage or clogging of the detection section.

The present invention has been made in view of the above points, and an object of the present invention is to provide a particle analyzer that can obtain more accurate measurement results while having a relatively simple circuit configuration.

Hereinafter, the configuration of the present invention will be explained based on the drawings. FIG. 1 is a systematic explanatory diagram showing one embodiment of the particle analyzer of the present invention. The particle analyzer of the present invention includes a particle detection device 1 that detects particles based on electrical or optical differences between the particles and a particle suspension liquid and generates a signal proportional to the size of the particles; A predetermined number of comparison circuits 2 from several to several dozen connected in parallel to the device 1, a counting circuit 3 that counts particle signals passing through each comparison circuit 2, and each counting circuit 3.
A temporary storage circuit 4 is connected to the temporary storage circuit 4, which holds the count value transferred at the same time as the counting of one step is completed until the measurement of the next step is completed, and the count value of the counting circuit 3 connected to this temporary storage circuit 4 is compared. Arithmetic circuit 5 that stores voltage in a predetermined memory corresponding to the voltage.
and a reference voltage generating circuit 6 connected to the comparator circuit 2 and generating a stepped voltage waveform having steps by evenly distributing the comparison voltage of each comparator circuit 2 over the entire voltage.
, a timing signal generation circuit 7 connected to the reference voltage generation circuit 6 and generating a timing signal at the rising edge of each step, a read-only memory 8 connected to the arithmetic circuit 5 and storing the operation order, etc.
It consists of a read/write memory 9, an input device 10, and an output device 11 for reading out the count value of the memory by the arithmetic circuit 5 and displaying and/or recording it. 1
2 is a display device, and 13 is a recording device.

The particle detection device 1 normally detects particles based on the difference in electrical impedance between the particles and the liquid by passing a suspended liquid through narrow passages (micropores), and detects the particles by detecting the size of the particles. A device is used that generates a signal proportional to The output pulses of this particle detection device 1 are simultaneously sent to a predetermined number of comparison circuits 2, such as 4 to 9, for example. A predetermined comparison voltage is applied to the comparison circuit 2, and when an input signal (particle pulse) larger than this comparison voltage is input, the comparison circuit 2 is turned on and outputs a pulse. A reference voltage generation circuit 6 that generates a comparison voltage generates a stepped voltage waveform having a predetermined number of steps, such as 50 to 100. This step-like waveform may monotonically increase, decrease, or repeat increases and decreases for each step, but it is ensured that each comparator circuit 2 has an evenly distributed comparison voltage. For example, as shown in Figure 2 (in this case
The comparison voltage ends in 99 steps (this is an example of 9 comparison circuits arranged in parallel), the comparison voltages to each comparison circuit 2 have a voltage difference separated by 10 steps, and start at the same time and complete 1 step at the same time. Finish the measurement. Therefore, since each comparator circuit 2 is uniformly distributed over a relatively wide range, it is possible to perform scanning that is approximately averaged, although some variation occurs between 10 steps. 3 is a counting circuit connected to each comparator circuit 2, and as soon as one step of counting is completed, the next temporary storage circuit 4 is connected.
The count value is transferred to and held until the next step measurement is completed. Reference voltage generation circuit 6
A timing signal is generated at the rising edge of each step through the timing signal generation circuit 7.
The counting circuit 3 starts and ends counting, the count value of the temporary memory circuit 4 is replaced, and the arithmetic circuit 5
The start of the calculation is specified. The arithmetic circuit 5 first reads 0, 10, 20, 30,
...The count values of each temporary memory circuit 4 are stored at address 90. The next steps are 1, 11, 21, 31,...
...The count value is stored at address 91. As described above, after address 99, the number returns to address 0 and rises again. By measuring the first 10 steps, all addresses are filled with count values, so from now on, temporary memory circuit 4 is used.
The counted value is read, and on the other hand, the numerical value stored in the read/write memory 9 is called, addition is performed, and the numerical value is stored again at the same address.

As mentioned above, if we focus only on the column of each comparison circuit 2, we are only looking at the count value at each step for steps 0 to 99, but in reality, we are looking at the average count value of 9 comparison circuits 2. In order to see the numbers, you can get detailed, averaged data. Therefore, even if phenomena such as non-uniform dispersion of the sample or sedimentation of particles or clogging occur, they will occur in each comparison circuit at the same time, making it much easier to scan than in the case of scanning with a single comparison circuit. Credibility arises. In addition, the measured value at each step is compared to the case where one particle is scanned, and the measurement time is extended by the number of dependent columns of the comparator circuit, and the number of particles at each step increases by that amount. You can see average data for many particles. When selecting the optimal conditions for the number of steps, measurement time, and array of comparison circuits, it is necessary to consider the recently diversified microcomputer technology that configures arithmetic circuits and the like.
In a normal device, the time required for the above calculation is on the order of tens to hundreds of microseconds, and if the speed is increased, the cost will increase significantly. Several tens of microseconds is not suitable for direct pulse analysis because particle detection pulse trains are on the order of several to hundreds of microseconds. However, like the present invention,
This is suitable for methods that perform calculations at fixed time intervals. Furthermore, after reading and writing with each timing pulse, other calculations can be performed, for example, the number of particles at each address that gradually increases can be displayed on a display device for monitoring. In this example,
If the measurement time is 5 seconds, there are 100 steps and 9 columns, so the time required for one step is 50 milliseconds, and there is a time of 5.6 milliseconds per column. However, there is plenty of room. When displaying and/or recording output graphically, it is necessary to clearly display and/or record subtle curve changes or inflection points, and for this reason the number of steps is usually at least 50 or
About 100 is necessary. If the number of steps is too small, to about 10, the trend in the graph may be grasped, but inflection points will be hidden, which is not desirable. On the other hand, the number of columns from the comparator circuit to the temporary storage circuit is a problem; if the number is too large, there will be no point in scanning in steps. It is thought to be in the range of 2-3 to 10 at most. As a comparison voltage scanning method other than this embodiment, each comparison circuit is in charge of each part of the divided steps, and the first comparison circuit is in charge of 0 to 9, the second comparison circuit is in charge of 10 to 19, and so on. ...There is a method in which the ninth comparison circuit is set to 90 to 99 and each repeats a predetermined number of times,
This is simpler than the circuit configuration described above. However, if the number of columns is 3 or 7, fractions will occur, so the number must be chosen so that they can be evenly covered.
In this case, accuracy is determined by the number of repetitions.

As described above, the count value of each step is stored in each address of the read/write memory 9, and the output device 11
is displayed and/or recorded on the display device 12 and/or recording device 13. Fig. 3 is an example in which the count values stored in the read/write memory 9 are directly displayed, and Fig. 4 is an example in which the difference between the count values at adjacent addresses is displayed as a percentage. The latter is known as the normal particle size distribution curve. Note that input device 1
In 0, various conditions for measurement are input, such as changing the time required for measurement, displaying the sample number at the same time as output, or outputting in the form of a cumulative particle size distribution curve or a normal particle size distribution. Input commands such as whether to output in the form of a curve.

As explained above, the particle analyzer of the present invention is capable of uniformly distributing the comparison voltages of a predetermined number of comparison circuits, from several to several dozen, to level voltages over the entire measurement range, and scanning in steps. According to
It has the advantage that it is low cost, has a simple configuration, and can perform highly accurate particle size distribution measurements.

[Brief explanation of the drawing]

Fig. 1 is a systematic explanatory diagram showing one embodiment of the particle analyzer of the present invention, Fig. 2 is a voltage waveform diagram generated by the reference voltage generation circuit, and Fig. 3 is the cumulative amount obtained by the particle analyzer of the present invention. A curve diagram showing an example of particle size distribution,
FIG. 4 is a curve diagram showing an example of particle size distribution. 1... Particle detection device, 2... Comparison circuit, 3...
Counting circuit, 4...Temporary storage circuit, 5...Arithmetic circuit, 6...Reference voltage generation circuit, 7...Timing signal generation circuit, 8...Read-only memory, 9...Read/write memory, 10... Input device, 11... Output device, 12... Display device, 13... Recording device.

Claims (1)

[Claims] 1. A particle detection device that detects particles based on the electrical or optical difference between the particles and the particle suspension liquid and generates a signal proportional to the size of the particles, and the number of particles connected in parallel to this particle detection device. A predetermined number of comparison circuits ranging from 1 to several dozen, a counting circuit that counts particle signals passing through each comparison circuit, and 1 particle connected to each counting circuit.
A temporary memory circuit that holds the counted value transferred at the same time as the counting of a step is completed until the measurement of the next step is completed, and a predetermined memory connected to this temporary memory circuit that compares the counted value of the counting circuit and corresponds to the voltage. an arithmetic circuit that is stored in the comparator circuit, a reference voltage generation circuit that is connected to the comparison circuit and generates a stepped voltage waveform having steps by evenly distributing the comparison voltage of each comparison circuit over the total voltage, and a reference voltage generation circuit that is connected to the reference voltage generation circuit. A timing signal generation circuit that generates a timing signal at the rising edge of each step, a read-only memory connected to the arithmetic circuit and storing the order of operations, a read/write memory, an input device, and the count values of the memory are processed by the arithmetic circuit. 1. A particle analysis device comprising: an output device for reading, displaying and/or recording.