JPH0150856B2 - - Google Patents

Description

[Detailed Description of the Invention] [Industrial Application Field] The present invention provides a simple blood analyzer that has a simple structure and can be manufactured at low cost, and more specifically, a simple blood analyzer that can simultaneously measure hemoglobin and white blood cell count. The present invention relates to a blood analyzer that can be easily calibrated against drift and fluctuation.

[Conventional technology]

Conventionally, devices for measuring the components of blood, such as red blood cells, white blood cells, and hemoglobin, utilize the difference in electrical impedance between blood cells and the suspension to form a suspension of blood cells in a narrow space. On the other hand, hemoglobin was measured using a colorimeter. There is also a method of detecting blood cells based on the optical difference between the fluid and blood cells, but generally the suspension of blood cells must be passed through a narrow passage, and a capillary shape is used to facilitate optical detection. (For example, ``1973 Extra Edition Clinical Examination'' Vol. 17 (1973-11)
-1) pp. 1285-1286), or a method called the sheath method, in which a suspension of blood cells is passed through the center, and the surroundings are surrounded by fluid that does not contain blood cells.

[Problem that the invention seeks to solve]

Of the above optical methods, the former (described in the above-mentioned literature) is capable of quantifying the sample liquid to be measured and can be displayed as the number of blood cells per unit volume, but on the other hand, it narrows the passageway and Due to the need to detect all particles,
It also has the disadvantage that it must be made uniform, or that clogging is likely to occur. In the latter case, it is impossible to quantify the comparative liquid, so it is necessary to take measures such as keeping the flow rate constant, and it is also necessary to use a complicated configuration such as a sheath system, which is expensive. The drawback was that it turned into a device. In any case, there was a drawback that hemoglobin had to be measured separately using a separate flow cell.

The present invention has been made in order to eliminate the above-mentioned drawbacks, and the conventional simple particle counter measures the number of particles per unit time, frequency-voltage (F-
V) While display is performed using an analog meter through conversion, etc., in the present invention, it is directly displayed as a digital quantity by giving the same effect as dividing the cumulative value after a predetermined time. The purpose of this invention is to provide a blood analyzer that performs the following functions.

[Means for Solving the Problems] In order to achieve the above object, the blood analyzer of the present invention has a width of 2 to 10 mm and a depth of 200 microns to 2 mm, as shown in the drawings. Measurement having a groove-shaped hemoglobin colorimetric measurement passage 1 and a groove-shaped blood cell measurement passage 2 communicating with the colorimetric measurement passage 1 and having a width of 2 to 10 mm and a depth of 20 to 100 microns. A cell 3, an attachable/removable cell holder 6 which fixes the measurement cell and has light transmission windows 4 and 5 at positions corresponding to the colorimetric measurement passage 1 and the blood cell measurement passage 2, respectively; A light shielding plate 8 having a light emitting diode 7 in the center, a second condensing lens 10, a first prism 11, a first condensing lens 12, and a light source 13 are sequentially arranged in front of the light transmission window 5 of the measurement passage 2. , a second prism 1 is placed above the first prism 11 and in front of the light transmission window 4 of the colorimetric measurement passage 1.
4, an objective lens 15 and a light receiving element 16 for light detection provided behind the light transmission window 5 of the blood cell measurement passage 2, and a light transmission device of the colorimetric measurement passage 1. The light receiving element 17 for light detection provided at the rear of the window 4, the hemoglobin colorimetric detection circuit 18 connected to this light receiving element 17, and the signal for hemoglobin colorimetric measurement are used to detect a predetermined value after the blood cell suspension is introduced. A trigger circuit 20 that generates a signal to start measurement after a time of A detection circuit 22 for converting into a signal, a gate circuit 23 connected to this detection circuit, and a reference pulse generation circuit 24 connected to this gate circuit.
, a counting circuit 25 connected to the gate circuit 23 and the trigger circuit 20, an arithmetic circuit 26 connected to the counting circuit, and a timer 27 connected to the trigger circuit 20 and the arithmetic circuit 26 and operated by the trigger circuit. and a display circuit 28 connected to the arithmetic circuit 26.

The features of the blood analyzer of the present invention include, firstly, that a colorimetric cell and a particle counting cell are used in common to measure white blood cells and hemoglobin;
Second, the common cell is easy to install and remove, making it easy to remove dirt and troubles such as clogging. Third, the light-emitting diode responds at a relatively high speed, allowing particles to pass through. Since a simulated optical pulse similar to that used for the measurement is generated and calibration is performed using this, there are no errors due to drift or fluctuation.Fourthly, the measurement is cumulative over a relatively long period of time, such as 5 or 10 seconds. Since the measured values are determined by , averaged and highly reliable measured values can be obtained.

[Effect]

The light rays exiting the light source 13 are turned into parallel lines by the first condensing lens 12, changed to an upward right angle direction by the first prism 11, and then made parallel to the original traveling direction by the second prism 14 again. , illuminates the colorimetric measurement passage 1 and enters the photodetection light receiving element 17 via the filter 37. On the other hand, the second
The light beam converged on the blood cell detection passage 2 by the condensing lens 10 is shaped like a donut (ring) by a plate 38 provided with a black light-shielding plate 8 that absorbs light in the center.
The light flux 40 becomes a so-called dark field state.

The objective lens 15 has this donut-shaped light beam 40
It is installed in a so-called dark field where the light converges and spreads out again as a donut-shaped light beam, and only the scattered light accompanying the passage of blood cells passes through, and this scattered light is detected by the light receiving element 16. Furthermore, since a light emitting diode 7 is provided in the center of the light shielding plate 8 of the plate 38, a simulated light pulse similar to the scattered light produced by the passage of blood cells is generated, which is used for calibrating the apparatus. This pulse passes through the blood cell detection passage 2, passes through the objective lens 15, and is detected by the light receiving element 16.

In this way, the light receiving element 16 detects the scattered light caused by the passage of the blood cells, and the detection circuit 22 converts it into an electric pulse signal. The detection circuit 22 converts the converted pulse width into a pulse number, accumulates the counted value, and simultaneously measures white blood cells and hemoglobin corresponding to the blood cell count.

〔Example〕

Embodiments of the present invention will be described below based on the drawings. The blood analyzer of the present invention has a groove-shaped hemoglobin colorimetric measurement passage 1 having a wide width, which communicates with the colorimetric measurement passage 1, and a groove-shaped groove having a wide width and deeper than the colorimetric measurement passage 1. A measurement cell 3 having a small blood cell measurement passage 2, and light transmission windows 4, 5 for fixing the measurement cell 3 and at positions corresponding to the colorimetric measurement passage 1 and the blood cell measurement passage 2, respectively. A light-shielding plate 8 having a light-emitting diode 7 in the center is located in front of the light transmission window 5 of the blood cell measurement passageway 2 (on the right side in FIGS. 1 and 2). 2 condensing lens 10, first prism 11, first condensing lens 1
2. The light sources 13 are sequentially arranged, and the first prism 11
A light irradiation device comprising a second prism 14 disposed above and in front of the light transmission window 4 of the colorimetric measurement passage 1; and the left side in FIG. 2) and the objective lens 15 and light receiving element 16 for light detection.
, a light-detecting light-receiving element 17 provided behind the light-transmitting window 4 of the colorimetric measurement passage 1, and a hemoglobin colorimetric detection circuit 18 connected to this light-receiving element 17.
and a trigger circuit 20 that generates a measurement start signal after a predetermined time after the suspension of blood cells is introduced according to a signal for hemoglobin colorimetric measurement, and a display circuit 21 connected to this colorimetric detection circuit 18; A detection circuit 22 connected to the light receiving element 16 for measuring blood cells and detecting scattered light caused by passing blood cells and converting it into an electric pulse signal, a gate circuit 23 connected to this detection circuit 22, and a gate circuit 23 connected to this gate circuit 23. a reference pulse generation circuit 24, a counting circuit 25 connected to the gate circuit 23 and the trigger circuit 20;
and an arithmetic circuit 26 connected to this counting circuit 25.
and a timer 27 connected to the trigger circuit 20 and the arithmetic circuit 26 and operated by the trigger circuit 20.
and a display circuit 28 connected to an arithmetic circuit 26, which converts the pulse width converted by the detection circuit 22 into a pulse number, accumulates the counted value, and simultaneously measures white blood cells and hemoglobin corresponding to the blood cell count. This is how it was done.

The measurement cell 3 includes a cell body 30 and a cell cover 3.
As described above, the cell main body 30 is provided with a passage 1 for colorimetric measurement and a passage 2 for blood cell counting.
has a groove-like shape with a wide width.
The depth of the groove for colorimetry (the depth of the passage 1) is preferably as deep as possible as long as the amount of sample is allowed. On the other hand, the depth of the groove for blood cell counting (depth of passage 2)
is preferably about 50 microns, judging from the size of blood cells.

The depth and width of the passages 1 and 2 will be explained using design values as an example. The design value of the depth of the hemoglobin colorimetric measurement passageway 1 is 1 mm, with a lower limit of about 200 microns and an upper limit of about 2 mm, although there is no need to specify it. On the other hand, the depth of the blood cell measurement passageway 2 has a designed value of 50 microns, with a lower limit of about 20 microns and an upper limit of 10 microns. In addition, the design value of the width of both passages 1 and 2 is 5 mm, and the lower limit is about 2 mm, and there is no need to specify an upper limit.
It is about 10mm.

The measuring cell 3 is fixed to a cell holder 6 provided with a handle 32, and the respective passages 1, 2 are connected to the outside via nipples 33, 34. Further, the cell holder 6 can be pulled out upward along a rail 36 provided on the fixed base 35, and the measurement cell 3 can be taken out together with the cell holder 6 to the outside.

Next, to explain the optical system in detail, the light rays exiting the light source 13 are turned into parallel lines by the first condensing lens 12, changed direction upward by the first prism 11, and then redirected by the second prism 14. The light beam is oriented parallel to the traveling direction of the light beam, illuminates the colorimetric path 1, and enters the light-detecting light-receiving element 17 via the filter 37. On the other hand, the light beam converged on the particle detection passage 2 by the second condensing lens 10 becomes a donut-shaped (ring-shaped) light beam 40 by a plate 38 provided with a black light-shielding plate 8 that absorbs light in the center. A so-called dark field condition is formed. The objective lens 15 has this donut-shaped light beam 4.
It is installed in a so-called dark field where 0 converges and spreads out again as a doughnut-shaped light beam, and only the scattered light accompanying the passage of blood cells passes through, and this scattered light is detected by the light receiving element 16. Further, in the center of the light-shielding plate 8 of the plate 38, the light emitting diode 7 is provided as described above, and generates a simulated light pulse similar to the scattered light caused by the passage of blood cells, which is used for calibrating the apparatus. This pulse passes through the particle detection passage 2, passes through the objective lens 15, and is detected by the light receiving element 16. Therefore, even if the passage becomes dirty and the translucency changes, for example, correct measurements can be made by performing calibration.

FIG. 3 is a block diagram showing an example of the circuit, where 41 is a power source for the light source 13, and 42 is a power source for the light source 13.
is a light emitting diode 7 to produce a simulated light pulse.
This is the power source to turn on the light. The light receiving element 17 generates a detection signal for colorimetric measurement of hemoglobin, the colorimetric detection circuit 18 measures the hemoglobin, and the display circuit 21 displays the result. The light receiving element 16 detects the scattered light caused by the passage of the blood cells, and the detection circuit 22 converts the scattered light into an electric pulse signal. Reference numeral 24 denotes a reference pulse generation circuit, through which the reference pulse passes only when a pulse signal from blood cells is input to the gate circuit 23, and is counted by the counting circuit 25. FIGS. 4 and 5 show examples of detection pulses. In FIG. 4, particles at a relatively high concentration are detected, while in FIG. 5, particles at a low concentration are detected. If the flow rate of the suspension of blood cells passing through passage 2 is constant, it is sufficient to simply count the number of pulses and display the pulses within a predetermined time, but this does not necessarily mean that the flow rate is constant. It must be assumed that the flow rate will normally vary depending on the temperature and viscosity of the floating liquid, the degree of dirt on the measurement cell, etc. In particular, in the method of applying suction pressure to the outlet provided below the measurement cell 3 and flowing the sample from above the measurement cell 3, the suction pressure conditions change at the beginning and end of the measurement, and the flow rate is considered to be not constant. Should. The following method can be considered as a method to make the flow rate irrelevant. In other words, if T is the time from when one pulse appears until the next pulse comes, and t is the time from when a pulse occurs until it disappears, that is, the pulse width, then t/T is approximately proportional to the particle concentration. It has been known. Therefore, if the t of each particle and the T of the particle are accumulated and finally divided, a more averaged and highly accurate measurement result can be obtained. That is, In conventional simple particle counting devices, in order to display it on an analog meter, the equivalent of t _i is integrated (charged) with an analog voltage amount, and at the same time, discharge is performed at a predetermined time constant, so the amount of charge is measured. When the amount of charge is large, the meter swing becomes large, and when the amount of charge is small, the meter swing becomes small, and in both cases, the average value as the degree of charging and discharging per hour is indicated by the meter. However, blood cells of various sizes are not necessarily evenly distributed, and phenomena occur in which signals with different pulse widths sometimes enter continuously or sparsely at almost the same time. This caused a phenomenon where the meter vibrated, especially when the particle concentration was low.

In order to eliminate the above-mentioned drawbacks, in the blood analyzer of the present invention, the pulse width gate circuit 23 converts the reference pulse generated from the reference pulse generation circuit 24 into a pulse number corresponding to the pulse width of the whole blood cell signal. By accumulating the pulse signals from the reference pulse generation circuit 24, a cumulative value of the pulse width of the whole blood cell signal is obtained. This is independent of flow rate. On the other hand, the timer 27, like the counting circuit 25, is activated by a trigger circuit 20 that issues a signal to start measurement after a predetermined time after the suspension of blood cells is injected in response to a signal for colorimetric measurement of hemoglobin. After a predetermined time, the counting of the counting circuit 25 is stopped by the measurement end signal of the timer 27, and the counting of the counting circuit 25 is stopped by the measurement end signal of the timer 27, and the counting of the counting circuit 25 is stopped by the measurement end signal of the timer 27.
Then, division using equation (1) is performed, and the display circuit 28 displays the blood cell count. As is clear from equation (1), the blood cell count can be determined by accumulating t _i as long as the total measurement time is kept constant, and can be set to a convenient value such as 5 seconds or 10 seconds, for example. That is, if the measurement time is doubled, the cumulative value of t _i will naturally also be doubled, and the length of the measurement time is unrelated to the blood cell count. On the other hand, in order to convert the display value of the display circuit 28 into the number of raw blood cells and display it, the pulse rate of the reference pulse generation circuit 24 can be changed, and the light emitting diode 7 can be used to generate a simulated light pulse signal of blood cells. This is done by generating a signal and adjusting the count value of the counting circuit 25 to a predetermined value. Adjustment using the light emitting diode 7 is used not only to adjust the reference pulse generation circuit 24 but also to adjust the detection level of the detection circuit 22. For example, the adjustment using the light emitting diode 7 is used to adjust the detection level of the detection circuit 22. etc., to ensure that measurements are always taken at the correct level. Furthermore, the trigger circuit 20 starts the blood cell count measurement after a predetermined time after the liquid enters the measurement cell 3, thereby washing away the liquid due to air bubbles and contamination from the previous sample, and making it possible to measure only the intermediate liquid. It is for
The counting circuit 25 and timer 27 are started by effectively utilizing the change in the amount of light of the colorimetric cell. Note that a nipple 34 provided below the passage 2 for counting blood cells is connected to a suction pressure source via a waste liquid reservoir bottle (not shown).

In addition to detecting changes in the DC output level of the light-receiving element 17, the trigger circuit 20 can also detect minute AC signals generated when blood cells cross the colorimetric cell; The measurement of white blood cells and hemoglobin amounts is done at a diluted concentration of 100 to several hundred times, whereas the diluted concentration of red blood cells is tens of thousands of times, but the amount of blood cell particles suspended in each solution is approximately the same. It is valid. Simultaneous measurement of white blood cells and hemoglobin is possible by lysing only red blood cells and eluating hemoglobin.
This is done by suspending only white blood cells in a hemoglobin solution. Therefore, by simultaneously monitoring the DC level of the light-receiving element 17 and the AC component, it is possible to determine the red blood cell measurement that does not change significantly by comparing the DC level with that of white blood cells and hemoglobin even though there is an AC component, and to display hemoglobin. Circuit 21 can be deactivated. This is accomplished by sending a deactivation signal from trigger circuit 20 to display circuit 21, as indicated by line 43 in FIG.

〔Effect of the invention〕

As explained above, the blood analyzer of the present invention can measure hemoglobin and white blood cells simultaneously using optical means with a relatively simple configuration, and can also measure red blood cells. By sending a deactivation signal to the display circuit from Another advantage is that checks and calibrations can be performed by blinking the light emitting diode. Furthermore, when no liquid is injected into the measurement cell, no counting or measurement is performed and no unnecessary display is made. In addition, since the measurement cell has a groove-like passage with a wide width, and the measurement is performed in a part of the channel, there is no clogging and the measurement cell can be easily removed compared to when using a capillary tube. This has the effect of making cleaning easier.

[Brief explanation of drawings]

Fig. 1 is an explanatory diagram showing an example of the optical system in the blood analyzer of the present invention, Fig. 2 is an explanatory diagram showing an example of the surroundings of the measurement cell, Fig. 3 is an explanatory diagram showing an example of the circuit, and Fig. 4 is an explanatory diagram showing an example of the surroundings of the measurement cell. and FIG. 5 is an explanatory diagram showing an example of a detection pulse. 1... Passage for colorimetric measurement, 2... Passage for blood cell measurement, 3... Measurement cell, 4, 5... Window for light transmission, 6
...Cell holder, 7...Light emitting diode, 8...
Light shielding plate, 10...second condensing lens, 11...first
Prism, 12... First condensing lens, 13... Light source, 14... Second prism, 15... Objective lens, 16, 17... Light receiving element, 18... Colorimetric detection circuit, 20... Trigger circuit , 21...display circuit,
22...Detection circuit, 23...Gate circuit, 24...
... Reference pulse generation circuit, 25 ... Counting circuit, 26
... Arithmetic circuit, 27 ... Timer, 28 ... Display circuit, 30 ... Cell body, 31 ... Cell cover, 3
2...Toride, 33, 34...Nipple, 35...
Fixed stand, 36...Rail, 37...Filter, 3
8... Plate, 40... Luminous flux, 41, 42...
Power supply, 43...railway.

Claims (1)

[Claims] 1 A groove-shaped hemoglobin colorimetric measurement passage 1 having a width of 2 to 10 mm and a depth of 200 microns to 2 mm, and this colorimetric measurement passage 1
2~10mm width and 20~
A measuring cell 3 having a groove-shaped blood cell measuring passage 2 having a depth of 100 microns, and a measuring cell 3 having a groove-shaped blood cell measuring passage 2 with a depth of 100 microns; Transmission window 4,
5, a light shielding plate 8 having a light emitting diode 7 in the center in front of the light transmission window 5 of the blood cell measurement passage 2, a second condensing lens 10, and a first prism 11. , first condenser lens 1
2. The light sources 13 are sequentially arranged, and the first prism 11
A light irradiation device includes a second prism 14 disposed above and in front of the light transmission window 4 of the colorimetric measurement passage 1, and a light irradiation device provided behind the light transmission window 5 of the blood cell measurement passage 2. An objective lens 15, a light-receiving element 16 for light detection, a light-receiving element 17 for light detection provided behind the light transmission window 4 of the colorimetric measurement passage 1, and a hemoglobin colorimetric detection connected to this light-receiving element 17. A trigger circuit 20 that generates a measurement start signal after a predetermined time after the suspension of blood cells is introduced by the circuit 18 and a signal for colorimetric measurement of hemoglobin, and a display circuit 21 connected to the colorimetric detection circuit 18.
, a detection circuit 22 connected to the light-receiving element 16 for measuring blood cells and detecting scattered light caused by passing blood cells and converting it into an electric pulse signal, a gate circuit 23 connected to this detection circuit, and a gate circuit 23 connected to this gate circuit. a reference pulse generation circuit 24, a counting circuit 25 connected to the gate circuit 23 and the trigger circuit 20;
and an arithmetic circuit 26 connected to this counting circuit,
A blood analysis device comprising: a timer 27 connected to a trigger circuit 20 and an arithmetic circuit 26 and operated by the trigger circuit; and a display circuit 28 connected to the arithmetic circuit 26.