JPS6332143B2 - - Google Patents

Description

Detailed Description of the Invention [Industrial Application Field] The present invention utilizes the fact that the detection signal of a particle in a particle counter is proportional to the size of the particle, and directly detects the signal of particles such as blood cells one by one. The present invention relates to a device that easily and accurately measures the total volume of blood cells relative to the total volume of blood, that is, the hematocrit value, without performing AD conversion.

[Conventional technology]

Conventionally, when measuring the hematocrit value, the peak value of the blood cell signal (proportional to the volume of blood cells) which is the output of a particle detection device is held or detected, the height of the signal is AD converted for each blood cell signal, and then digitally converted. The amount was accumulated to obtain the hematocrit value. That is, blood is stored in a capillary tube and separated into a red blood cell layer and a serum layer by centrifugation, and the ratio of the red blood cell layer to whole blood is expressed as a hematocrit value, which is useful for diagnosing blood cell diseases. In recent years, with the advent of automatic particle counters, it has become possible to measure hematocrit values at the same time.

[Problem that the invention seeks to solve]

However, because it is necessary to detect and measure particles such as blood cells one by one, blood is usually diluted approximately 50,000 times with physiological saline, etc. A suspension of blood cells is passed through the micropores so that the pulse interval between each blood cell is on the order of several hundred microseconds, or 0.1 milliseconds, on average. However, particles such as blood cells in the diluted solution are not necessarily uniformly dispersed, and the pulse interval has a so-called Poisson distribution. That is, a phenomenon of simultaneous passage occurs in which two or more particles pass through the detection region almost simultaneously. Therefore, a high-speed AD conversion circuit with a processing speed of 10 microseconds or less must be used as the AD conversion circuit, which is expensive. On the other hand, in order to overcome the above-mentioned drawbacks, a method can be considered in which the peak value of the signal is processed in an analog manner, stored sequentially in an integrating circuit, and finally AD converted, but this method uses a low-speed AD conversion circuit. Although it can be constructed at a low cost, it requires a storage element for the analog quantity in the integrating circuit that has low leakage, and there are problems such as temperature drift, so it cannot necessarily be said to be an effective method in terms of accuracy. That is, the measurement time is several seconds, and during this time the voltage value is gradually charged and totaled without any error, but it is difficult to maintain the voltage value accurately and with an error of 1% or less until the end.

The present invention has been made in order to eliminate the above-mentioned drawbacks, and aims to provide an apparatus capable of measuring hematocrit values with a simple circuit configuration and high accuracy by improving an analog processing method. It is.

[Means for solving problems]

The hematocrit level measuring device of the present invention will be described with reference to FIG. 1. It detects particles such as blood cells suspended in a liquid based on electrical or optical differences between the liquid and the particles. A particle detection device 1 that converts into an electric signal proportional to the size, an integration circuit 3 that performs integration one after another according to the height of the signal from this particle detection device, and a determination of the amount of charge integrated by this integration circuit. a determination circuit 4 that issues an output signal when the amount of charge exceeds a predetermined amount; a conversion circuit 5 that repeatedly reduces the charge of the integrating circuit by a predetermined amount only when an output signal from the determination circuit appears; and this conversion circuit. The circuit 6 includes a counting circuit 6 that counts the number of times the charge is decreased by repeating the above.

In the device of the present invention, the conventional pulse 1
Instead of relying on individual AD conversions, a method is used in which a capacitor is temporarily charged, and after confirming the presence of charge in the capacitor, the capacitor is repeatedly discharged by a fixed amount. Therefore, the amount charged to a capacitor, etc. is an averaged voltage level within a predetermined range, and since discharge is always performed automatically, accuracy is dramatically improved, and the effects of temperature etc. are ignored. be done.

[Effect]

When the red blood cell detection signal from the particle detection device 1 is sent as a peak voltage by the preprocessing circuit 2 to the integrating circuit 3, information regarding the height of the blood cell signal is integrated one after another. When the integral value exceeds a predetermined value, the determination circuit 4 immediately activates the conversion circuit 5, and repeatedly reduces the integral value by a predetermined amount until the integral value becomes equal to or less than the predetermined value. Therefore, when the blood cell signals are averaged and input at approximately equal intervals, the determination circuit 4 operates intermittently.

By repeating the above operation, when a predetermined amount of suspended blood cells is measured, the finally obtained count value of the counting circuit 6 directly becomes the cumulative value of the blood cell signal size. The same results as measurements made with conventional high-speed AD conversion circuits can be obtained.

〔Example〕

Embodiments of the present invention will be described below based on the drawings. FIG. 1 shows an embodiment of the hematocrit value measuring device of the present invention. Reference numeral 1 denotes a particle detection device that detects particles such as blood suspended in a liquid based on electrical or optical differences between the liquid and the particles, and converts the detected particles into electrical signals proportional to the size of the particles. The particle detection device 1 normally passes particles suspended in a liquid through micropores, detects the particles based on the difference in electrical impedance between the particles and the particle suspension liquid, and generates an electrical signal proportional to the size of the particles. A device that does this is used. Reference numeral 2 denotes a preprocessing circuit connected to this particle detection device 1, which generates only a peak voltage value regardless of the pulse width of the particle signal, and uses a simple peak hold circuit or the like. In other words, it is simply used to send the peak voltage to the next integrating circuit 3, and the hold time is very short, and the time required is just to send the voltage value to the next stage. A rectifier circuit can also be used instead. The integrating circuit 3 performs integration one after another according to the height of the signal from the particle detection device, that is, it sequentially integrates the voltage value from the preprocessing circuit 2 at the previous stage, while the conversion circuit 5 repeatedly subtracts the voltage value by a predetermined amount. It is for going. 4 is a judgment circuit that judges the amount of charge integrated in the integration circuit 3 and issues an output signal when the amount of charge is greater than a predetermined amount; when the integrated value charged to the integration circuit 3 exceeds a predetermined range, it immediately converts. It operates circuit 5, and usually,
A comparator or the like is used. 5 is a judgment circuit 4
A conversion circuit that repeatedly reduces the charge in the integrating circuit by a predetermined amount only when an output signal from the judgment circuit 4 appears, and repeatedly reduces (discharges) the charge charged in the integrating circuit 3 by a fixed amount based on the signal from the judgment circuit 4. On the other hand, the number of times the charge of the conversion circuit 5 is reduced is sent as a count signal to the counting circuit 6. 7 is a display device connected to the counting circuit 6.

In the device configured as described above, the red blood cell detection signal from the particle detection device 1 is sent to the preprocessing circuit 2.
When the peak voltage is sent to the integrating circuit 3, information regarding the height of the blood cell signal is successively integrated.
When the integral value exceeds a predetermined value, the determination circuit 4 immediately activates the conversion circuit 5, and repeatedly reduces the integral value by a predetermined amount until the integral value becomes equal to or less than the predetermined value. Therefore, when the blood cell signals are averaged and input at approximately equal intervals, the determination circuit 4 operates intermittently. However, the intervals between normally detected blood cells are not necessarily uniform, and as shown in Figure 3A, which will be described later, the intervals between two or three cells in a row get wider, resulting in a so-called Poisson interval distribution of the detection signal. Because of the distribution, when two or more signals are input in succession, the integration circuit performs additional integration for the number of signals during that time, while subtraction by a predetermined amount is performed. However, on average, the integrated value of the integrating circuit 3 does not exceed a predetermined value, and a state in which the potential is flat intermittently occurs in the rest state (C in FIG. 3).

By repeating the above operation, when a predetermined amount of suspended blood cells is measured, the finally obtained count value of the counting circuit 6 directly becomes the cumulative value of the blood cell signal size. The same results as measurements made with conventional high-speed AD conversion circuits can be obtained. Moreover, even if two or three pulses or more pulses occur in succession, the information between them is stored in the integrating circuit, so the remaining information can be processed when the pulse interval occurs. In addition, it has the advantage of being able to perform a so-called averaging function and not requiring an expensive high-speed AD converter.

FIG. 2 shows a specific example of the integrating circuit 3, the determining circuit 4, and the converting circuit 5. An integral circuit 3 is formed by combining an operational amplifier 8 and a capacitor 9,
It enables constant current charging and discharging, and inputs it to the comparator 11 via the buffer amplifier 10.
A reference voltage is applied to the comparison terminal 12 of the comparator 11, and when this voltage is exceeded, a signal is sent to the next conversion circuit 5. The conversion circuit 5 includes an oscillation circuit 13 and a relay 14, and is configured such that the oscillation circuit 13 operates only when a signal from the comparator 11 is generated. The output waveform of the oscillation circuit 13 is preferably a rectangular wave output, and the relay 14 is a semiconductor relay that is stable in operation at relatively high speeds. The accuracy of the device of the invention depends not on the linearity of the integrating circuit 3, but rather on the accuracy of subtraction of the repeated integral values of the converting circuit 5. In other words, how to uniformly subtract a certain amount, and the oscillation circuit 1
3 has a relatively stable crystal oscillator built in, converts it into a rectangular wave signal, and further connects the stabilized reference voltage to the subtraction reference voltage terminal 15 connected to the contact side of the relay 14, and connects it to the resistor 16. The integrated value charged by one blood cell signal is repeatedly subtracted by a predetermined value several times to several tens of times by turning on and off the relay 14. On the other hand, when the number of samples, that is, the number of red blood cells measured in one measurement is large, and relatively high precision measurement is not required, the relay may be turned on and off once for several blood cell signals. However, sufficient accuracy can be obtained. In other words, in order to wait for several batteries to be charged, the operations are averaged as a so-called intermittent operation. In any case, according to the device of the present invention, by averaging uneven pulse signals through analog processing, there is no need for a conventional high-speed AD conversion circuit, and the repetitive charge of the conversion circuit is reduced. By counting the number of decreases, the cumulative value of the height of the total blood cell signal can be obtained, and the hematocrit value can be measured with sufficient accuracy.

FIG. 3 shows the signal conditions at points A, B, C, and D in FIG. 2. A indicates a signal sent from the preprocessing circuit 2 to the integrating circuit 3;
This shows how the peak voltage of the particle signal is held for a certain period of time and sent sequentially. B indicates a comparison voltage applied to the comparison terminal 12. C shows the output signal of the integrating circuit 3, and the voltage value is integrated in proportion to the magnitude of each peak voltage of A, and when it exceeds the comparison voltage B, the charge of the integrating circuit is reduced by a certain amount. Shows how it is reduced (discharged).

In the figure, the circled area indicates a state in which the battery is being charged while discharging because the next pulse is input during discharging. Therefore, the slope of the discharge characteristics is gentle only in this portion. A major feature of the present invention is that even while discharging in this manner, the next pulse input during discharging is not ignored, and charging can be performed accordingly.

Note that C ₁ and C ₂ represent the potential after discharge,
C ₁ and C ₂ are different as shown in Figure 3. Since it discharges a certain amount at a time, if there is no pulse input at all during discharge, C ₁ and C ₂ will have the same potential.

D indicates a rectangular wave signal with a constant time width T output from the oscillation circuit 13. This rectangular wave signal is output every time signal C exceeds comparison voltage B. During this fixed time width T, the relay 14 is turned on and the integrating circuit 3 is discharged.

〔Effect of the invention〕

As explained above, the hematocrit value measuring device of the present invention does not require a high-speed AD conversion circuit, so it can be manufactured at low cost. Even if two or more blood cell signals are input, no error occurs, and the hematocrit value can be measured with high accuracy with a simple signal configuration.

[Brief explanation of the drawing]

FIG. 1 is a systematic explanatory diagram showing one embodiment of the hematocrit value measuring device of the present invention, FIG. 2 is a systematic explanatory diagram showing specific examples of an integrating circuit, a judgment circuit, and a conversion circuit. It is an explanatory diagram showing the signal situation of each point A, B, C, and D in a figure. DESCRIPTION OF SYMBOLS 1... Particle detection device, 2... Preprocessing circuit, 3... Integrating circuit, 4... Judgment circuit, 5... Conversion circuit, 6... Counting circuit, 7... Display device, 8... Subtraction amplifier, 9... Capacitor, 10... Buffer amplifier, DESCRIPTION OF SYMBOLS 11... Comparator, 12... Comparison terminal, 13... Oscillation circuit, 14... Relay, 15... Reference voltage terminal, 16... Resistor.

Claims (1)

[Claims] 1. A particle detection device that detects particles such as blood cells suspended in a liquid based on the electrical or optical difference between the liquid and the particles and converts it into an electrical signal proportional to the size of the particle, and this particle detection device an integration circuit that performs integration one after another according to the height of the signal from the integration circuit, a determination circuit that determines the amount of charge integrated in this integration circuit and issues an output signal when the amount of charge is greater than a predetermined amount, and this determination circuit. A hematocrit value characterized in that it includes a conversion circuit that repeatedly reduces the charge of the integrating circuit by a predetermined amount only when an output signal from measuring device.