KR20080108745A - Technique and device to accurately measure very small volume of blood - Google Patents

Abstract

A method and a system for measuring a very small volume of blood are provided to measure a very small volume of blood precisely and conveniently by absorbing the blood into an absorption badge for converting a very small volume into a large area so as to calculate the same into a calibration curve. An absorption badge(200) absorbs a small amount of taken blood. An image scanner(300) scans the blood of the absorption badge to convert the same a digital image. A computer(400) is connected to the image scanner for analyzing the digital image.

Description

TECHNICAL AND DEVICE TO accurately measure very small volume of blood

Figure 1 is a schematic diagram of capillary suction principle for measuring a small amount of liquid volume

2 is a conceptual diagram of the absorption area conversion principle of blood volume

3 is a conceptual diagram of a digital image composed of dots

4 is a schematic configuration diagram of a microcapillary blood volume measuring system;

Fig. 5 is a graph of the calibration curve between the color point count value and the micropipette blood volume.

<Description of the symbols for the main parts of the drawings>

10: water (solution) 20: glass tube 100: capillary blood

101: coloring point 200: absorption medium 201: uncolored point

300: Image Scanner 400: Personal Computer and Program

The present invention relates to a method for measuring blood volume and a system thereof, and more particularly, to accurately measure a small amount of blood volume, which can be used for accurate evaluation of blood collection volume (volume) of a blood collection device, evaluation of academic fine blood collection volume, and the like. A method and a system used therefor.

In general, diabetic patients have to control their blood glucose values within an appropriate range by taking capillary blood every day and performing a self blood glucose test to measure blood glucose values. However, a blood glucose meter that measures blood glucose values from capillary blood requires a certain volume or more of blood depending on the device to test blood glucose.

In order to collect blood of a certain solution as described above, the finger portion of the human body is typically used. This is based on the fact that the capillary blood is collected from the finger in the blood glucose test. In this method, the capillary blood is sufficient. There is no failure. However, a lot of pain cells are also distributed in the finger region of the human body, so the blood collection pain is quite large, and therefore, even more suffering in diabetics who have to take blood almost every day.

In order to minimize the bleeding pain at the time of blood collection, methods for collecting capillary blood at an alternative site (not an finger) have been developed. Pain cells in the alternative area such as the arm, especially the forearm of the arm, are very As it is distributed less, almost no pain is felt even when puncturing the skin with a lancet, but a blood sampling method is used inside the arm.However, a small amount of blood is obtained because the capillaries are also distributed in the alternative arm. Techniques for inhaling with vacuum pressure have been used to maximize the amount of blood drawn as required (US Patent 6,152,942 and PCT WO 2005 / 030053A1).

However, even if the patient draws blood from the replacement site with the highest possible vacuum pressure within the range where the patient does not feel pain, very small volume (<few μL) of blood volume is often obtained. none.

Therefore, accurate measurement of blood volume, which varies according to body parts or lancing device, is essential for successful and efficient blood glucose test, and since the amount of blood collected from the replacement site is only a small amount, the performance of the blood collection device used for blood collection There is a need for precise measurement of the volume of blood for evaluation and quality control.

In addition, in the conventional blood volume measurement method, blood has a relatively high specific gravity and viscosity compared to water, but exhibits the same physical properties as general liquids, so that the volume is measured in a container such as a beaker with a volume graduation pre-set, which is at least measured. It can only be used to measure very large blood volumes of more than a few mL (= several thousand μL) because there is a limit to the size of the container.

In addition, a capillary suction principle may be used as a method of measuring a smaller amount of blood volume, and water is used to adsorb onto a glass surface, and as shown in FIG. (20) When the end is in contact with water (10) is adsorbed on the inner surface of the glass tube 20 is sucked in. At this time, since the inner diameter of the glass tube 20 is constant, the volume can be calculated by measuring the length (L: suction length) after sucking all the water 10.

That is, in FIG. 1, if the diameter of the glass tube 20 is D, the cross-sectional area A = π (D / 2) ^{2, and} thus the volume V becomes the cross-sectional area (A) and the suction length (L).

 π D2L

V = 4

Is solved for L

 4

L = πD2 ^V

 do.

Therefore, the smaller the diameter D of the glass tube 20, that is, the thinner the capillary suction is, the better the tube should be used. The diameter of the thinnest glass tube commercially available is at least 1 mm (Code No. 4360, manufactured by Marienfeld, Germany). )to be.

If you want to measure the volume of 1μL with the above product,

       4

L = 3.14 × 0.12cm2 ^{× 1 × 10-6 × 103 cm3}

= 0.1274cm _~ 1.3mm

It can be seen that the suction is about 1mm in length, and considering that the minimum length of a linear scale generally used is 1mm, it can be seen that the minimum volume that can be measured by capillary suction is about 1μL. If the volume is less than 1 μL, the suction length is also within 1 mm, making it almost impossible to measure the length (L).

That is, the resolution of the volumetric measurement is about 1 μL, which means that only volumes of 1 μL or more are visually measurable.

However, recently used high-performance blood glucose meters (e.g., TheraSens Co., Ltd.) can be tested for blood glucose with at least 0.3 μL of capillary blood. Is very common, so small blood volumes of less than 1 μL should be accurately measured for performance evaluation, quality control, and estimation of the success rate of alternative site blood glucose testing.

On the other hand, using the existing capillary suction principle can not be applied because only the volume measurement of 1μL or more can not be applied, and also a method and device that can measure a small amount of blood volume of less than 1μL in the alternative blood glucose test cheaply and handily Will be needed.

The present invention provides a method and system for easily and accurately measuring the volume of capillary blood of 1 μL or less by the necessity as described above. The purpose is to facilitate.

In order to achieve the object of the present invention as described above, the present invention, a trace amount of blood volume measurement method, after collecting a small amount of blood with a blood collection device to evaluate the performance, the collected blood is absorbed using an absorption medium and dried In addition, the present invention provides a method for measuring a small amount of blood, which consists of scanning a dried absorbent medium with an image scanner connected to a computer to obtain a digital image and then calculating the blood volume with an analysis program.

In the case of absorbing the blood collected using the absorption medium, the blood collected by the blood collection device may be absorbed by the absorption medium, or the absorption medium may be lightly contacted with the blood collection site to absorb the blood.

In addition, it is preferable to use the white absorbent medium because it is advantageous to recognize the color difference from the blood, and a computer is sufficient for the PC.

In addition, when scanning with the image scanner, it is preferable to extract only the red part of the blood as an image, and to select and count only the points where the size of the red part extracted as the image is greater than or equal to a predetermined threshold. The coefficient value is converted into the area according to the set proportion. In addition, the blood volume calculation is preferably to use a calibration curve by calculating the absorption area of the absorption medium.

The present invention also provides an absorption medium for absorbing blood collected by a system for measuring a small amount of blood volume, an image scanner for integrating the absorption medium into a digital image, a computer connected to the image scanner, and an image of an image scanner. A system is provided for measuring trace amounts of blood, consisting of an analysis program for analyzing the volume of blood.

The absorption medium in the above is preferably a white absorption medium, and the computer can use a PC.

Hereinafter, the present invention will be described in more detail with reference to the accompanying drawings.

In the present invention, an absorption medium is used to easily measure the trace liquid volume. Absorption medium is very good in water absorption, especially as shown in Figure 2, water as a main component of the capillary blood 100, the main component is contacted to the absorption medium 200, spreads in all directions, the absorption medium is absorbed solution in the biochemical laboratory It is frequently used for single use for removal.

In FIG. 2, when the area and thickness of the medium 200 that absorbed the volume of blood 100 V are S and d, respectively, the volume V is the product of these.

V = S

And solve for S

 V

S = d

Becomes The medium 200 is similar to a general paper except for absorbency, and since its thickness is very thin, a relatively large S value can be obtained in the process of dividing by a smaller value d even though V is small in the above equation. In other words, if a small volume V, which is difficult to measure directly, is absorbed in a thin medium and converted into an area, a large area S that can be easily measured can be obtained.

For example, if V = 1 μL and d = 10 μm, the S value is

  One μ L 1 × 10-6 × 103 cm3

S = 10 μm = 10 × 10-6 × 102 cm2 = 1cm2 = 100mm2

This results in a large area that can be measured sufficiently with the naked eye.

Therefore, as described above, a small amount of capillary blood is absorbed into the medium and converted into a relatively large area, and if the absorption area is accurately measured, the blood volume can be accurately measured.

In addition, since the medium is white and the blood is red, there is a marked difference in chromaticity. The absorption area can be clearly distinguished by the naked eye, but the blood is collected by a scanner commonly used for accurate and consistent area measurement. Scanning the absorbed media allows a computer to obtain digital images that can be easily analyzed, allowing accurate measurement of the absorbed area.

That is, since the digital image is made up of a set of discrete pixels, when the image of the medium on which the blood is absorbed is enlarged, the digital image is divided into blood colored dots 101 and uncolored dots 201 as shown in FIG. Therefore, by counting only the colored dots (blood 101), a volume V proportional to the absorption area S can be obtained. In order to automatically classify the colored dots 101, only a red component is extracted from an image, and then only the points having a red component size above a certain threshold are counted. You can use the program or easily write and use an independent program. Therefore, by automatically analyzing the scanned image of the medium with a computer program, the area of the blood absorbed area can be calculated. At this time, since a certain area consists of a certain number of points in the computer image, applying the number of points to the area shows the area of the medium occupied by the colored points, and by multiplying the thickness of the medium, the volume of blood finally absorbed is determined. You can measure accurately.

Figure 4 schematically shows a system for performing the above method, an example of its use,

Using a blood collection device to evaluate the performance, a small amount of blood (100) is taken from an alternative site such as an arm, and the white absorbent medium (200) slightly contacts the blood collection site to absorb all capillary blood and then dried. Scan the dried medium 200 with an image scanner 300 connected to the personal computer 400 to obtain a digital image, and then calculate the blood volume using an analysis program operated by the computer 400.

As described above, the system of the present invention can be configured only with an office scanner and a personal computer without the need for a separate measurement or analyzer, and the absorption medium is a very inexpensive disposable paper, enabling accurate measurement of trace volume of blood at low cost.

(Example)

In order to confirm that the present invention as described above is valid, it was carried out as follows.

First, a sufficient amount of venous blood was extracted from a normal person with a syringe, and a volume of blood was injected into a micro pipette (P10, Gilson, France), dropped onto a medium, and then dried.

Here, a constant blood volume was taken in a range of 0 to 1 μL in 0.1 μL steps, 1 to 2 μL in 0.2 μL steps, and 2 to 5 in 1 μL steps to obtain 5 absorption media for each volume.

All the absorbent media were scanned with a scanner to obtain a digital image, and then the number of colored pixels was counted using the Photoshop program version 7.0. The deviation was calculated.

A calibration curve was calculated by performing first- or second-order regression analysis between the average value of the colored point coefficients by volume and the volume of the micropipette.

Figure 5 is a graph showing the relationship between the color point coefficient value and the micropipette blood volume, the relationship between the two variables as a second function up to 0 ~ 1.5μL,

From 1.5 to 5 μL, the linear function was shown.

Correlation was more than 0.99 when calculating the calibration curve of FIG. 5 and the standard deviation of the values repeated five times at a constant blood volume was very small, especially at 1 μL or less, so that a consistent measurement was made. This means that counting the number of colored points and substituting them into the calibration curve yields an accurate blood volume.

That is, if the volume of blood collected by the device to be evaluated is calculated through the present invention and the color score is substituted into the calibration curve of FIG. 5, the volume of the collected blood can be accurately measured.

According to the present invention as described above, it is possible to easily and inexpensively configure a system capable of measuring a small amount of blood volume using only a white absorbent medium and a scanner, a personal computer and a counting program, which can be easily obtained, thereby using the blood in the absorbent medium. By converting the trace volume into a large area by absorbing it and calculating it as a calibration curve, it is possible to easily and accurately measure the trace volume of blood, which facilitates the performance evaluation and the quality control of blood collection devices used by diabetics. It is effective to accurately measure the amount of microscopic blood collection.

Although described above with reference to a preferred embodiment of the present invention, those skilled in the art can be variously modified and changed within the scope of the invention without departing from the spirit and scope of the invention described in the claims You will understand.

Claims (6)

A method of measuring a small amount of blood, which is obtained by absorbing a small amount of collected blood with an absorption medium and drying it, then scanning the dried absorption medium with an image scanner connected to a computer to obtain a digital image, and calculating the blood volume using an analysis program. A small amount of blood volume measurement method. The method of measuring a trace amount of blood according to claim 1, wherein said absorbent medium is a white absorbent medium. The method of claim 1, wherein the computer is a personal computer. The method of claim 1, wherein the digital image extracts only a red portion of blood as an image. A trace volume measurement system, comprising: an absorption medium for absorbing collected blood, an image scanner for digitally imaging the blood of the absorption medium, and a computer connected to the image scanner for analyzing an image of the image scanner, Trace amount volumetric system, characterized in that configured. 6. The trace volume system of claim 5, wherein the absorbent medium is a white medium and the computer is a personal computer.

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