JPH0147732B2 - - Google Patents

Description

[Detailed description of the invention]

[Industrial Application Field] 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. The present invention relates to a particle analyzer that can reduce the size and cost of the particles and directly determine the particle size distribution rather than the cumulative particle size distribution. [Prior Art] Conventionally, when analyzing particles such as blood cells, particles such as blood cells are detected electrically or optically, and the size of the detection pulse is proportional to the size of the particle. Setting a threshold level and providing a corresponding threshold circuit, determining the size of a particle pulse from the presence or absence of a particle pulse passing through each threshold circuit,
It is stored in memory circuits and analyzed. Normally, a so-called comparator (comparison circuit) is used as a threshold circuit, and multiple comparators are lined up and the comparison voltage of each comparator is set at a predetermined interval, and analysis is performed according to the output of each comparator. The number of comparators must be 50 to perform measurements.
100, etc., to reduce the voltage difference between each level. [Problems to be Solved by the Invention] In the conventional method and device described above, signals are input to each comparator simultaneously for all particle signals, there is no measurement error caused by the degree of dispersion of particles, and measurements can be made in a short time. However, it requires tens to hundreds of expensive comparators to be used in parallel, making the device expensive, making it difficult to adjust the comparison voltage of each comparator, and making the circuit complicated. It has some drawbacks. In addition to these shortcomings, when processing information regarding the particle size obtained from the comparator, the intervals between particle pulses are dispersed from tens of microseconds to hundreds of microseconds, and processing is difficult for a single pulse. When this occurs, it is necessary to take measures such as prohibiting the input of the next pulse or averaging the pulses, which further complicates the circuit configuration. In any case, if you want to read the size of each particle pulse in real time and process that information using a high-speed microcomputer, you will need a computer with a high-speed processing time of at least 30 microseconds or less. This results in a significant increase in cost and is extremely uneconomical considering that the average pulse interval is several hundred microseconds. Furthermore, in conventional particle analyzers, when obtaining a normal particle size distribution, it is necessary to first obtain a cumulative particle size distribution, which requires calculation time. The present inventors have provided a particle detection device, a comparison circuit,
A counting circuit, an arithmetic circuit, a staircase waveform generation circuit,
A timing signal generation circuit, a read-only memory,
We developed a particle analysis device that combines a read/write memory, an input device, a display device, and a recording device.
A patent application was filed as Japanese Patent Application No. 55-88979 on the same date as the present application. However, since the device disclosed in Japanese Patent Application No. 55-88979 uses only a one-level comparison circuit, it is still possible to directly obtain only the cumulative particle size distribution. There is a problem in that the calculation has to be performed from the beginning, which requires a corresponding amount of calculation time. The present invention has been made in view of the above points, and is a particle analyzer that can solve the above problems, can be manufactured at low cost, and can directly determine the particle size distribution without determining the cumulative particle size distribution. The purpose is to provide the following. [Means for Solving the Problems] The particle analyzer of the first invention of the present application will be described with reference to FIG. A particle detection device 1 that detects particles by detecting particles and generates a signal proportional to the particle size, and a particle detection device 1 that is connected in parallel to this particle detection device and has a plurality of continuous threshold values for particle signals from the particle detection device. A low-level comparison circuit 2 and a high-level comparison circuit 3 that allow particle signals larger than the input comparison voltage to pass through, counting circuits 4 and 5 that count particle signals that pass through these comparison circuits, and are connected to the counting circuit. an arithmetic circuit 8 connected to the comparison circuit and generating a comparison voltage shifted by one step; and a step waveform generation circuit 6 connected to the step waveform generation circuit to generate a timing pulse at the rising edge of a step of the step voltage waveform. a timing signal generation circuit 7 that generates timing signals for starting and stopping counting in the counting circuit and reading count values in the arithmetic circuit; a read-only memory 9 that is connected to the arithmetic circuit and stores arithmetic operations and control sequences; It is characterized by including a read/write memory 10, an input device 11, a display device 13, and/or a recording device 14. The device of the second invention of the present application, which will be described with reference to FIG. Particle detection device 1 that generates a signal
and a low level comparison circuit 2 which is connected in parallel to the particle detection device and has a plurality of continuous threshold values for particle signals from the particle detection device and passes particle signals larger than the input comparison voltage; Level comparison circuit 3, a delay circuit 15 connected to the low level comparison circuit to delay the output of the low level comparison circuit, and a delay circuit 15 connected to the high level comparison circuit to generate a pulse somewhat wider than the particle signal. a one-shot multivibrator 16, which is connected to the delay circuit and the one-shot multivibrator, and which uses the output of the one-shot multivibrator as a prohibition signal to determine whether or not to pass the signal output from the delay circuit; Counting circuit 18 for counting particle signals passing through the circuit
, an arithmetic circuit 8 connected to the counting circuit, a step waveform generation circuit 6 connected to the comparison circuit and generating a comparison voltage shifted by one step, and a step waveform generation circuit 6 connected to the step waveform generation circuit to generate a step of the step voltage waveform. A timing signal generating circuit 7 generates a timing pulse at the rising edge to generate a timing signal for starting and stopping counting in the counting circuit and reading counted values in the arithmetic circuit, and a timing signal generating circuit 7 connected to the arithmetic circuit and storing calculation and control sequences. It is characterized by including a read-only memory 9, a read/write memory 10, an input device 11, a display device 13, and/or a recording device 14. The device of the third invention of the present application, which will be described with reference to FIG. Particle detection device 1 that generates a signal
A low-level comparison circuit 2 and a high-level comparison circuit 2 are connected in parallel to the particle detection device and pass particle signals from the particle detection device that have a plurality of consecutive threshold values and are larger than the input comparison voltage. A comparison circuit 3, a peak position detection circuit 19 connected to the particle detection device so that the particle signal from the particle detection device enters in parallel with the comparison circuit, this peak position detection circuit, a low level comparison circuit, and a high level comparison circuit. A gate circuit 20 that is connected to the circuit and emits a signal when the signal output from the low level comparison circuit 2 is on and the signal output from the high level comparison circuit 3 is off, and a particle signal passing through this gate circuit. A counting circuit 18 for counting, an arithmetic circuit 8 connected to the counting circuit, and a staircase waveform generating circuit 6 connected to the comparing circuit and generating a comparison voltage shifted by one step.
and a timing signal generator that is connected to this staircase waveform generation circuit and generates a timing pulse at the rising edge of a step of the staircase voltage waveform, and generates a timing signal for starting and stopping counting in the counting circuit and reading counts in the arithmetic circuit. A circuit 7, a read-only memory 9 that is connected to the arithmetic circuit and stores arithmetic operations and control sequences, a read/write memory 10, an input device 11, a display device 13, and/or a recording device 14.
It is characterized by including the following. [Operation] Particle signals sent from the particle detection device 1 are sent to two comparators 2 and 3 simultaneously. On the other hand, the output of the staircase waveform generation circuit 6 is as shown in FIG.
The solid line a starting from voltage 0 and the one-dot chain line b have waveforms that are shifted by one step, and comparison voltages at so-called adjacent levels are applied to the comparators 2 and 3. The outputs of the comparators 2 and 3 enter counting circuits 4 and 5, respectively, and the number of pulses at each level of each step is counted. On the other hand, the timing pulse generation circuit 7 sends a timing signal to the counting circuits 4 and 5 and the arithmetic circuit 8 at the rising edge of each step of the voltage waveform, and starts counting in the counting circuits 4 and 5.
This is the timing for stopping counting and for the arithmetic circuit 8 to read the count values of the counting circuits 4 and 5. Note that the time for each step in FIG. 2 is 50 milliseconds even if the total measurement time is 5 seconds and the number of steps is 100, which is a sufficient time interval. Counting circuit 4, 5
The counted value of is read by the arithmetic circuit 8, but at the same time the difference between each counting circuit 4 and 5 is calculated by the arithmetic circuit 8.
The data is stored in the read/write memory 10 for each step. As described above, by changing the two levels stepwise and storing the number of signals of particles whose size falls between the two levels in the read/write memory 10 at each step, the particle size distribution can be directly calculated. get. [Example] Hereinafter, an example of the present invention will be described 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 this example 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 low level comparator 2 and a high level comparator 3 are connected in parallel to the device 1 and have a plurality of consecutive threshold values for particle signals from the particle detection device, and pass particle signals larger than the input comparison voltage. , these comparators 2,
Counting circuits 4 and 5 that count particle signals passing through 3
and an arithmetic circuit 8 connected to the counting circuits 4 and 5,
A staircase waveform generation circuit 6 is connected to the comparators 2 and 3 and generates a comparison voltage shifted by one step, and a counting circuit 4 is connected to the staircase waveform generation circuit 6 and generates a timing pulse at the rising edge of a step of the staircase voltage waveform. , 5, a timing signal generating circuit 7 generates a timing signal for starting and stopping counting, and reading the counted value of the arithmetic circuit 8.
, a read-only memory 9 connected to the arithmetic circuit 8 and storing arithmetic operations and control sequences, a read/write memory 10,
It includes an input device 11, a display device 13, and/or a recording device 14, and applies comparison voltages shifted by one step to two comparators 2 and 3 to count particles at each voltage step. A feature of this method is that the particle size distribution is directly measured from the difference between adjacent steps in the number of particles. The particle detection device 1 is usually a device that passes a suspension of particles through micropores, detects the particles based on the electrical difference between the particles and the liquid, and generates a signal proportional to the size of the particles. It will be done. Comparators 2, 3 pass particle pulse signals that are greater than the comparison voltage. The stepwise waveform generating circuit 6 generates two types of stepwise comparison voltages as shown in FIG. 2, which are sent to the timing pulse generating circuit 7, which generates timing pulses at the rising edge of the step of the stepwise voltage waveform. The input device 11 specifies calculation conditions, output conditions, or scales on the XY axes of the graph. Normally, particles such as blood cells have 1
Since it exists at a high density of several million particles per mm ³ , the concentration is too high to measure it one by one, so it is diluted tens of thousands of times. For example, 4.84 million red blood cells/ ^mm3 are 5
When diluted 10,000 times, there are 96.8 pieces in 1 ^mm3 .
For example, if we measure 0.25 cc of this liquid, or 250 mm ³ , we will measure 24,200 pieces, and if we further divide this by 1/50, we will get the original number.
We get 484 significant figures. Unit: 10,000 pieces/mm ³
If so, the original 4.84 million pieces/mm ³ will be obtained. moreover
If it takes 5 seconds to measure 24,200 pieces, the average pulse interval is about 0.2 milliseconds, but the pulse interval usually shows a Poisson distribution and ranges from several tens of microseconds to
It lasts several milliseconds. As the particle density increases, the pulse interval further becomes shorter, and two or more particles enter the detection region at the same time, resulting in a bimodal particle pulse or being detected as a single pulse. This is because the particle detection signal shows a sine square wave, and when blood cells of several microns are passed through a micropore of about 90 microns, the particle detection pulse width is about 30 microseconds, and therefore the detection circuit Of course, the response speed of the circuit that follows the detection circuit must be at least 30 microseconds or less, and must be able to respond in the range of several microseconds to several nanoseconds. For example, even if the detection circuit is connected to a microcomputer, which has become common in automatic analyzers in recent years, it will no longer be able to respond if particles are continuously detected. When processing one pulse, it is necessary to take measures such as prohibiting the input of the next pulse, and it cannot be said to be an accurate measurement method. Fortunately, commonly used pulse logic circuits, such as comparators and counter circuits, have processing speeds of several nanoseconds, so it is possible to effectively utilize these conventional elements before processing them with a microcomputer. By utilizing this, it is possible to reduce the speed to an averaged, slow signal. In order to perform the above processing, the particle signal sent from the particle detection device 1 is sent to two comparators 2 and 3 simultaneously. On the other hand, as shown in FIG. 2, the output of the step waveform generation circuit 6 has a waveform that is shifted by one step, as shown by the solid line a starting from voltage 0 and the dashed line b, so that they are at so-called adjacent levels. A comparison voltage of is given to comparators 2 and 3.
The outputs of the comparators 2 and 3 enter counting circuits 4 and 5, respectively, and the number of pulses at each level of each step is counted. On the other hand, the timing pulse generation circuit 7 sends a timing signal to the counting circuits 4 and 5 and the calculation circuit 8 at the rising edge of each step of the voltage waveform, and the counting circuits 4 and 5 start and stop counting, and the calculation circuit 8 This is the timing to read the count values of 4 and 5. Note that the time for each step in FIG. 2 is 50 milliseconds even when the total measurement time is 5 seconds and the number of steps is 100, which is a sufficient time interval. The count values of the counting circuits 4 and 5 are read by the arithmetic circuit 8, but at the same time, each counting circuit 4,
The difference of 5 is calculated by the arithmetic circuit 8 and stored in the read/write memory 10 for each step. The following table is an example of data written to the read/write memory 10. Note that each column in the vertical and horizontal directions represents an address.

【table】

〔Effect of the invention〕

As explained above, since the particle analyzer of the present invention uses two types of level comparison circuits, two types of level comparison circuits are used.
Reading/writing memory 10 for reading and writing the number of signals of particles whose size falls between two levels while changing the level stepwise.
By storing each step, the particle size distribution (rather than the cumulative particle size distribution) can be obtained directly. In addition, the particle analyzer of the present invention can scan the comparison voltage of the comparator with a stepped voltage waveform, measure the number of particles at each step, and analyze the particle size distribution. Since it can be averaged and extended, and subsequent circuits can be made up of extremely low-speed elements, it is cost-effective in terms of circuit configuration, and the entire device can be simplified and lowered in cost. In addition, since the output to the arithmetic circuit can be averaged at intervals of several milliseconds to several tens of milliseconds, it is possible to use a low-cost microcomputer that can process at low speeds, and in this respect, the device The overall size and cost can be reduced, and the device can be built into a conventional particle counting device, making it possible to provide a space- and cost-effective device. Furthermore, as described above, since information regarding the particle size distribution can be directly obtained, it has the effect of shortening calculation time.

[Brief explanation of drawings]

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 a staircase waveform generation circuit, FIG. 3 is a particle size distribution diagram, and FIGS. The figure is a systematic explanatory diagram showing another embodiment of the particle analyzer of the present invention. 1... Particle detection device, 2... Low level comparator, 3... High level comparator, 4, 5...
Counting circuit, 6... Staircase waveform generation circuit, 7... Timing signal generation circuit, 8... Arithmetic circuit, 9... Read-only memory, 10... Read/write memory, 11...
...Input device, 12...Output device, 13...Display device, 14...Recording device, 15...Delay circuit, 16
...One-shot multivibrator, 17...
Gate circuit, 18... Counting circuit, 19... Peak position detection circuit, 20... Gate circuit.

Claims (1)

[Claims] 1. A particle detection device that detects particles based on electrical or optical differences between particles and a particle suspension liquid and generates a signal proportional to the size of the particles, and this particle detection device. a low-level comparison circuit and a high-level comparison circuit that are connected in parallel and have a plurality of continuous threshold values for particle signals from the particle detection device and pass particle signals larger than an input comparison voltage;
A counting circuit that counts particle signals passing through these comparison circuits, and an arithmetic circuit connected to the counting circuit.
A staircase waveform generation circuit is connected to the comparator circuit and generates a comparison voltage shifted by one step, and a timing pulse is generated at the rising edge of the step of the staircase waveform, and the counting circuit starts counting and counts. A timing signal generation circuit that generates a timing signal for stopping and reading the count value of the arithmetic circuit, a read-only memory connected to the arithmetic circuit and storing the arithmetic and control sequences, a read/write memory, an input device, and a display device. and/or a recording device. 2. A particle detection device that detects particles based on electrical or optical differences between particles and a particle suspension liquid and generates a signal proportional to the size of the particles, and a particle detection device that is connected in parallel to this particle detection device. A low-level comparison circuit and a high-level comparison circuit that have a plurality of continuous threshold values for particle signals from the device and pass particle signals larger than an input comparison voltage;
a delay circuit connected to the low-level comparison circuit for somewhat delaying the output of the low-level comparison circuit; a one-shot multivibrator connected to the high-level comparison circuit for generating a pulse somewhat wider than the particle signal; A gate circuit that is connected to the delay circuit and the one-shot multivibrator and uses the output of the one-shot multivibrator as a prohibition signal to determine whether the signal output from the delay circuit passes or not, and counts the particle signals passing through this gate circuit. A counting circuit, an arithmetic circuit connected to the counting circuit, a staircase waveform generation circuit connected to the comparator circuit to generate a comparison voltage shifted by one step, and a step waveform generation circuit connected to the staircase waveform generation circuit to generate a step of the staircase voltage waveform. A timing signal generation circuit that generates a timing pulse at the rising edge to generate a timing signal for starting and stopping counting in the counting circuit and reading the count value in the arithmetic circuit, and a timing signal generation circuit that is connected to the arithmetic circuit and stores the calculation and control order. read-only memory,
A particle analysis device comprising a read/write memory, an input device, a display device and/or a recording device. 3 A particle detection device that detects based on the electrical or optical difference between particles and a particle suspension liquid and generates a signal proportional to the size of the particles, and a particle detection device that is connected in parallel to this particle detection device and generates a signal proportional to the particle size. A low level comparison circuit and a high level comparison circuit have a plurality of continuous threshold values for particle signals and pass particle signals larger than an input comparison voltage, and a particle signal from a particle detection device is connected to a comparison circuit. A peak position detection circuit connected to the particle detection device in parallel, a signal connected to this peak position detection circuit, a low level comparison circuit, and a high level comparison circuit and output from the low level comparison circuit are on, A gate circuit that emits a signal when the signal output from the high-level comparison circuit is off, a counting circuit that counts particle signals passing through this gate circuit, an arithmetic circuit connected to the counting circuit, and a comparator circuit connected to the comparison circuit. A staircase waveform generation circuit that generates a comparison voltage shifted by one step, and a counting circuit that generates a timing pulse at the rising edge of a step of the staircase voltage waveform to start and stop counting of the counting circuit and an arithmetic circuit. a timing signal generation circuit that generates a timing signal for reading the count value;
A particle analysis device comprising: a read-only memory, a read/write memory, an input device, a display device, and/or a recording device connected to an arithmetic circuit and in which arithmetic operations and control sequences are stored.