JPH0580048A - Method and apparatus for measuring blood - Google Patents

Abstract

PURPOSE:To display the density of a sample blood properly by measuring the intensity of reflected light at a plurality of points on a test paper to calculate a difference between a mean thereof and individual values of intensity of reflected light or a difference between the individual values of intensity of the reflected light. CONSTITUTION:The intensity of reflected light at a plurality of points of a test paper is measured. For example, a plurality of holes 3 are arranged at an equal interval on a non-transparent plate piece 2. The intensity of light reflected through the holes 3 is measured individually for each hole to calculate a difference between a mean for of a plurality of values of the intensity of the reflected light and the values of the intensity of the reflected light at the respective holes and a decision is performed on whether occult blood in the sample is due to hemolysis or not from the size of the difference. The display contents of a measuring device are corrected according the results of decision thereby enabling accurate decision and display not only for hemolysis but also for non-hymolysis.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for measuring blood in a sample and a measuring device used therefor.

[0002]

2. Description of the Related Art Color test papers in which a color indicator such as organic hydroperoxide and ortho-tolidine is carried on a filter paper are widely used for detecting occult blood in urine.
When occult blood is contained in urine, the organic hydroperoxide carried on the test paper is decomposed by the pseudoperoxidase action of hemoglobin in the urine to generate oxygen in the nascent stage, and the oxidative effect of this oxygen also carries it on the test paper. The existing color change indicator develops or changes color to signal the presence of occult blood. When the color indicator carried on the test paper is the above-mentioned ortho-tolidine, the color of the test paper changes from white before the test corresponding to the amount of occult blood to light blue to dark blue.

As is well known, there are two types of occult blood in urine: hemolysis in which hemoglobin contained in the membrane of erythrocytes is disintegrated and released, and non-hemolysis in which erythrocytes without membrane disruption are present as they are. There is. In hemolysis, hemoglobin is dissolved in urine to form an almost uniform occult hematuria (hemoglobin urine). Therefore, when the test strip is dipped in urine, the whole occult blood test portion of the test strip is covered. Hemoglobin is adsorbed substantially uniformly, and as shown in “hemoglobin urine” in FIG. 1, almost uniform color development is exhibited over the entire occult blood test portion 1 of the test paper. On the other hand, in non-hemolysis, hemoglobin does not leach from red blood cells, but floats in urine while being trapped in red blood cells (hemocyteuria), and red blood cells are adsorbed and held in spots only on specific parts of the test strip. Therefore, as shown in "hemocyteuria" in FIG. 1, the occult blood test portion 1 of the test paper is spotted and develops color.

When the detection result of occult blood in urine by the occult blood test strip is visually determined, it is possible to distinguish hemolysis from non-hemolysis and to determine the concentration of hemolysis or non-hemolysis relatively easily. That is, in the case of hemolysis, the overall color tone is compared with a standard color table for hemolysis (for hemoglobin urine) prepared in advance, and in the case of non-hemolysis, the density of colored spots (of the number of spots) By comparing (a little) with the standard color table for non-hemolysis (hemocyteuria) prepared in advance,
It is possible to determine the type of occult blood and the concentration (somewhat) of each occult blood.

On the other hand, in recent years, it has become widespread to measure the results of clinical tests using a test strip or the like by using a reading device without visual inspection, and detection and measurement of occult blood in urine. Is no exception. Then, in the case of using a reading device, light is irradiated to almost the entire surface of a specific test item of the test paper, the reflected light intensity is measured, the average value of the reflected light intensity is taken, and the test result is determined by the magnitude of the average value. It is common to display. For example, in the above-mentioned occult blood test paper carrying an organic hydroperoxide and an ortho-tolidine color change indicator, the reflected light intensity of the color development state appearing on the test paper is measured using the maximum absorption wavelength 630 nm of the blue dye. Then, the average value of the measured reflected light intensity values is taken, and the average value is displayed in four stages of − to 3+ using a calibration table stored in the reader in advance, and the detection result of occult blood in urine is measured.・ It is supposed to be displayed.

By the way, in the occult blood detection test using a test strip, in the case of hemolysis, as shown in "hemoglobin urine" in FIG. 1, almost uniform color development is exhibited over the entire occult blood test portion of the test strip. The average value of the reflected light intensity values can be obtained as a value that almost properly reflects the hemolytic concentration in the sample. However, in the case of non-hemolysis, as seen in “hemocyteuria” in FIG. 1, since the occult blood test portion of the test paper is spotted and develops color, the total area of the occult blood test portion of the test paper is As a result, the proportion of the colored (colored) portion with high reflected light intensity is small, while the proportion of the portion with low reflected light intensity without coloring is large, so whether the amount of hemoglobin contained in the sample is almost the same as in hemolysis. Even if it is higher than that, the average value of the measured reflected light intensity is often lower than in the case of hemolysis, there is a drawback that the amount of occult blood in the sample can not be accurately detected and measured. is there. This defect is more likely to occur as the amount of occult blood (non-hemolysis) in the sample decreases.

[0007]

From the above point of view, the inventors of the present invention are concerned with hemolysis and non-hemolysis in measuring the coloration state appearing on the occult blood test paper using a reflected light intensity measurement type reading device. Instead, I have continued my research to find a method and apparatus for appropriately measuring and displaying the concentration of occult blood appearing on a test strip. As a result, when measuring the reflected light intensity at multiple locations on the test paper, the difference between the average value of the multiple measured reflected light intensity values and the individual reflected light intensity values, or the measured individual reflected light intensity The difference between the values is small for hemolysis,
It was found that the individual reflected light intensity values are almost similar to each other, whereas the non-hemolytic values are extremely large, and there is a large variation between the individual reflected light intensity values. Then, when further research was conducted, the above difference between hemolysis and non-hemolysis was positively used to determine whether the occult blood in the sample was hemolytic or non-hemolytic depending on the magnitude of the difference. The present invention has been completed with the idea that it is possible to make a distinction and, moreover, if the display content of the measuring device is corrected according to the determination result, accurate determination and display can be performed not only for hemolysis but also for non-hemolysis.

Therefore, the present invention is a method for measuring the blood in a sample by measuring the reflected light intensity in the colored state appearing on the test paper, and measuring the reflected light intensity at a plurality of points on the test paper. , Calculate the difference between the average of multiple measured reflected light intensity values and the individual reflected light intensity values, or the difference between the measured individual reflected light intensity values, and test according to the difference. It is a blood measuring method characterized by determining whether blood detected on paper is hemolytic or non-hemolytic, and displaying the blood concentration appropriately based on the determination result.

Further, according to the present invention, a member for measuring reflected light intensity at a plurality of points on a test paper, a difference between an average value of a plurality of measured reflected light intensity values and an individual reflected light intensity value, or a measured value. It is provided with means for calculating a difference between the individual reflected light intensity values, means for determining whether or not the difference is a predetermined value or more, and means for appropriately displaying the blood concentration based on the determination result. It is a blood measuring device characterized by the above.

As described above, when the occult blood in the sample is non-hemolytic, the difference between the average value of the plurality of measured reflected light intensity values and the individual reflected light intensity, or the measured individual reflected light intensity Although the difference between the values is large, it can be determined that it is non-hemolytic, but in the actual determination, it is determined that it is non-hemolytic when the cumulative value of the calculated differences or the average value of the differences exceeds a predetermined value. The measuring device may be configured to do so. In this case, the "predetermined value" is a value obtained by conducting an experiment in advance according to various requirements such as the type of measuring device used, the type of test paper, the coloration state of the test paper, and the number of measurement points of the reflected light intensity on the test paper. It is better to obtain and set by performing the above. For example, when the difference between the measured average value of the plurality of reflected light intensity values and the individual reflected light intensity value or the average value of the differences exceeds 20% of the average value of the plurality of reflected light intensity values, Usually, it can be judged as non-hemolytic.

When the occult blood detected on the test paper is determined to be non-hemolytic, the actual measured value is compared with the authentic standard value for non-hemolytic pre-installed in the measuring device. The correction is performed so that the predetermined appropriate value and the determination result based on it are displayed on the display unit of the test strip reading device.

Specifically, for example, two calibration curves for hemolysis (for hemoglobin) and non-hemolysis (for blood cells) are stored in the reading device, and the determination obtained above whether hemolysis or non-hemolysis is performed. In accordance with the result, it is advisable to set the reader so as to display in accordance with the calibration curve for hemolysis in the case of hemolysis and according to the non-hemolysis calibration curve in the case of non-hemolysis.
The display method at that time is, for example, “hemoglobin (hemolysis) +”, “hemoglobin (hemolysis) 2+”, “hemocyte (non-hemolysis) +”, “hemocyte (non-hemolysis)” according to each result.
For example, it is convenient to separately display such that the type of occult blood, such as “3+”, and simultaneously display the magnitude of the concentration.

Usually, the measuring device for measuring the reflected light intensity of the color appearing on the color test paper and judging the result of the clinical test from the average value is not limited to the occult blood detection test, but also other test items (for example, Urinary protein, glucose, urobrinogen,
It is designed to be commonly used for detection tests of bilirubin, ketone bodies, etc.). And in these test items, the coloration state that appears as a result of the test is almost uniform as in the case of hemolysis, and the device is designed to match uniform coloration, so the coloration appears in spots. Then, the above correction is necessary.

In carrying out the method of the present invention, the detection and measurement device provided with each of the above-mentioned members may be newly manufactured and used, or a conventional color test paper reading device may be used. It may be used after being improved. In the case of improving the known reading device to be the measuring device of the present invention, the reading light intensity reading part in the conventional reading device is improved, and further, the reading device is provided with a plurality of measured reflected light intensity values. Means for obtaining the average value and calculating the difference between the average value of the reflected light intensity values and the individual reflected light intensity values, or the difference between the measured individual reflected light intensity values, and means for determining the magnitude of the difference A means for correcting / displaying the blood concentration appropriately based on the above determination result may be added.

When measuring the intensity of reflected light at a plurality of points on the test paper, the greater the number of measurement points (measurement points), the more accurately it can be determined whether hemolysis or non-hemolysis is performed.
However, if the number of measurement points is too large, the apparatus becomes complicated and expensive, so it is usually preferable to select a suitable number for each apparatus from three or more locations. In addition, in order to accurately determine hemolysis or non-hemolysis, how to select measurement points (eg position of measurement points, distribution state, interval between measurement points, area of one measurement point, etc.)
is important. The measurement point of the reflected light intensity is, for example, 4 to 10
When the number of the measuring points is small, it is preferable that the measuring points have substantially the same interval and the measuring points are evenly arranged in the vertical and horizontal directions.

Specific examples of the reflected light intensity reading member suitable for use in the apparatus of the present invention are shown in FIGS. FIG. 2 shows a shape-retaining opaque plate piece 2 made of plastic or other suitable material, provided with a plurality of holes (slits) 3 at equal intervals. The intensity is individually measured for each hole, the difference between the average value of the plurality of reflected light intensity values and the reflected light intensity value of each hole is calculated, and the magnitude of the difference is determined.

Further, FIG. 3 shows an opaque plate piece 4 which is also made of plastic or other appropriate material and has a shape-retaining property and is provided with a plurality of holes 5 (slits) at equal intervals. Is attached to the reader so that the plate plate 4 can be moved forward, backward, leftward and rightward as shown by the arrow in FIG. 4, and the reflected light intensity when the holes 5 are at the positions a, b, c and d of the test strip. Is measured, the difference between the average value of the reflected light intensity values and the reflected light intensity value from each hole is calculated, and the magnitude of the difference is determined.

Further, in the above case, the measured values of the reflected light intensity when the hole 5 is at the position a of the test paper are summarized (measured value A), and the reflection when the hole 5 is at the position b of the test paper is collected. Collect the measured values of the light intensity (measured value B), and further measure the measured value of the reflected light intensity when the hole 5 is at the position c of the test paper and the measured value of the reflected light intensity when it is at the position d of the test paper. Collected as a group (measured value C and measured value D), 4 measured values A
It is also possible to calculate the difference between the average value of the measured values D and the respective measured values A, B, C, D, and determine the hemolysis or non-hemolysis based on the difference.

FIG. 4 shows a reflected light intensity measuring member in which a plurality of optical fibers 6 are converged. When the reflected light intensity measuring member shown in FIG. 4 is arranged at a predetermined position on the test paper, a plurality of adjacent reflected light intensities on the test paper can be individually measured through the individual optical fibers 6 of the member. Also in this case, the difference between the average value of the plurality of reflected light intensity values measured through the plurality of optical fibers 6 and the reflected light intensity value from each optical fiber 6 is calculated, and the magnitude of the difference is compared with a predetermined value. , Determine hemolysis or non-hemolysis based on the comparison result,
In the case of non-hemolysis, the actually measured concentration is appropriately corrected and displayed on the display unit of the reading device, so that proper display can be performed for both hemolysis and non-hemolysis.

The above-mentioned reflected light intensity measuring member is used by being attached to the reflected light intensity reading portion of the reading apparatus main body, but in that case, it may be fixedly attached or detachably attached. The reflected light intensity measuring members shown in FIGS. 2 to 4 are merely examples, and the present invention is not limited thereto.

Further, in the present invention, when the reflected light intensity in the test is measured, for example, as shown in FIG. 2, over the entire occult blood test portion of the test paper, it is measured evenly at a large number of points. Can calculate the proportion of the portion where the reflected light intensity is almost uniform and the proportion of the portion where the reflected light intensity has a difference in intensity, and as a result, the proportion of hemolysis in occult blood in the sample and the proportion of non-hemolysis. It is possible to measure and.

[0022]

【Example】

Example 1 Opaque polyethylene plate piece 4
Prepare the reflected light intensity reading member shown in FIG. 3 in which (vertical × horizontal = 5 mm × 5 mm) 5 holes each in the vertical and horizontal directions are formed with square holes 5 of vertical × horizontal = 0.5 mm × 0.5 mm. Then, this reading member was attached to a reflected light intensity reading portion which can be moved in the front, rear, left and right of a reflected light intensity reading device (MCPD-200 manufactured by Otsuka Electronics Co., Ltd.) to prepare a measuring device of the present invention.

Separately, three types of urine containing hemolysis (hemoglobin urine) and urine containing red blood cells (hemocyteuria) were prepared as follows. Hemoglobin urine Hemoglobin urine 1: Hemoglobin content 0.03 mg /
ml hemoglobin urine 2: hemoglobin content 0.15 mg /
ml hemoglobin urine 3: hemoglobin content 0.75 mg /
ml blood cells urine blood cells urine 1: hemoglobin content 0.03 mg / ml
(Blood cells 10 cells / μl) Blood cells Urine 2: Hemoglobin content 0.15 mg / ml
(Blood cells 50 cells / μl) Blood cells Urine 3: Hemoglobin content 0.75 mg / ml
(250 blood cells / μl)

A urine occult blood test paper (Ulyace manufactured by Terumo Corp.) was dipped in each of the hemoglobin urine 1 to 3 and blood cell urine 1 to 3 prepared above for 1 second, and a reading test was performed 20 seconds later. For the reading test, the measuring device prepared above was used, each immersion test paper obtained above was placed in the reading part of the device, and the reflected light intensity reading member attached to the measuring device was moved to the left side as shown in FIG. 0 → top → right → bottom.
While moving by 5 mm, the reflected light intensity was measured when the 25 holes 5 came to the positions of a, b, c and d of the test paper, respectively, and the holes 5 showed the positions a, b, c and of the test paper. The measured values of the reflected light intensities at the time of d are grouped together, respectively, group a, group b, group c and group d.
It was measured as a measurement value for each. The results are shown in Table 1 below.
It was as follows.

[0025]

[Table 1] Hemoglobin urine blood cells urine 1 2 3 1 2 3 Hemoglobin content 0.03 0.15 0.75 0.03 0.15 0.75 (mg / ml) Reflected light intensity group a 0.0510 0.1385 0.2156 0.0382 0.1152 0.1936 group b 0.0492 0.1312 0.2101 0.0136 0.0834 0.1541 group c 0.0499 0.1348 0.2195 0.0299 0.0695 0.1829 group d 0.0523 0.1381 0.2119 0.0111 0.0653 0.1248 flat Average 0.0506 0.1357 0.2143 0.0232 0.0846 0.1639 Difference in maximum reflected light intensity from average 3% 3% 2% 65% 36% 24%

From the results shown in Table 1 above, in hemoglobin urine, the difference in the reflected light intensity value between groups a to d is extremely small, and the coloration state that appears on the test paper even when the measurement position of the reflected light intensity is different. It can be seen that it is almost uniform throughout and that it is the same for different hemoglobin contents in urine. On the other hand, in hematuria, there is a large difference in the reflected light intensity values between groups a to d, and there are spots in which the coloration state on the test paper is extremely uneven. It can be seen that the difference in light intensity value is more remarkable as the blood cell content (hemoglobin content) is lower. Furthermore,
From the results in Table 1, it can be seen that the measured value of the reflected light intensity is actually lower in the hemoglobin urine than in the hemoglobin urine, although the actual hemoglobin content is the same.

Therefore, from the above results, the reflected light intensity at a plurality of points on the test paper was measured, and the difference between the average value of the plurality of measured reflected light intensity values and the individual reflected light intensity values, or the measured value was measured. By calculating the difference between the individual reflected light intensity values, it is possible to determine whether the detected blood is hemolytic or non-hemolytic depending on the magnitude of the difference, and the determination result It can be seen that if the blood concentration is properly corrected and displayed based on this, accurate detection / display is possible even in the case of non-hemolysis.

In the above description, the detection test of occult blood in urine has been mainly described. However, the method and apparatus of the present invention are not limited to the measurement of occult blood in urine, and both hemolytic and non-hemolytic can be performed. It can be effectively used for measurement of blood in various contained samples. Further, the test paper used for detection of blood at that time is not limited to the urine occult blood test paper composed of the organic peroxidase and the ortho-tolidine coloring agent described above, and the blood in the sample is detected by the change in its coloration state. It can be used for any test paper to be tested, and the test result can be accurately measured and displayed.

[0029]

By adopting the measuring method and the measuring apparatus of the present invention, in the technique of measuring the coloration appearing on the occult blood test paper by using the reading apparatus of the reflected light intensity measurement type, only in the case of hemolysis. Even in the case of non-hemolysis, the concentration of occult blood appearing on the test paper can be properly detected and displayed.

[Brief description of drawings]

FIG. 1 is a diagram showing coloration states of urine occult blood test strips for hemoglobinuria (hemolysis urine) and hemoglobinuria (non-hemolysis urine).

FIG. 2 is a diagram showing an example of a reflected light intensity reading member of the present invention.

FIG. 3 is a diagram showing another example of the reflected light intensity reading member of the present invention.

FIG. 4 is a diagram showing still another example of the reflected light intensity reading member of the present invention.

[Explanation of symbols]

 1 occult blood test part of test paper 2 opaque plate piece 3 hole 4 opaque plate piece 5 hole 6 optical fiber

Claims (6)

[Claims] 1. A method for measuring blood in a sample by measuring the reflected light intensity in a colored state appearing on a test paper, which is measured by measuring the reflected light intensity at a plurality of points on the test paper. Calculate the difference between the average of multiple reflected light intensity values and each reflected light intensity value, or the difference between the measured individual reflected light intensity values, and detect the difference on the test paper according to the difference. A blood measuring method, comprising: determining whether the blood is hemolyzed or non-hemolysed, and displaying the blood concentration appropriately based on the determination result. 2. A test strip when the difference between the average value of the plurality of reflected light intensity values measured and the individual reflected light intensity values or the difference between the individual reflected light intensity values is a predetermined value or more. The blood measuring method according to claim 1, further comprising: determining that the blood detected in (1) is non-hemolytic, collating it with an authentic standard value created in advance, and displaying a predetermined appropriate value. 3. A member for measuring reflected light intensity at a plurality of points on a test paper, a difference between an average value of a plurality of measured reflected light intensity values and an individual reflected light intensity value, or a measured individual reflected light. Characterized by comprising means for calculating a difference between intensity values, means for determining whether or not the difference is a predetermined value or more, and means for appropriately displaying the blood concentration based on the determination result. Blood measuring device. 4. A difference between an average value of a plurality of measured reflected light intensity values and an individual reflected light intensity value or a difference between the measured individual reflected light intensity values is determined to be a predetermined value or more. The blood measuring apparatus according to claim 4, further comprising means for displaying a predetermined appropriate value by collating with a genuine standard value created in advance. 5. A member for measuring the reflected light intensity at a plurality of points of a test paper, which is composed of a plate-shaped body or a sheet having holes formed at equal intervals. 6. A member for measuring the intensity of reflected light at a plurality of points on a test paper, which is composed of a converging body of a plurality of optical fibers.