KR101793668B1 - System for measuring concentration of sample using mobile device and method thereof - Google Patents
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- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
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- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/50273—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the means or forces applied to move the fluids
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- G01N35/08—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a stream of discrete samples flowing along a tube system, e.g. flow injection analysis
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Abstract
A system and method for measuring the concentration of a sample using a mobile device according to the present invention are disclosed. A system for measuring the concentration of a sample according to the present invention comprises: a microfluidic device having a microchannel therein, into which a measurement sample in the microchannel is injected; A measurement assisting device into which the microfluidic device is inserted; And a microchannel injecting measurement sample in the microfluidic device inserted into a lower end of the measurement assisting device at an upper end of the measurement assisting device, capturing an image of the microchannel, analyzing the acquired image, Of the mobile device.
Description
The present invention relates to a method for measuring the concentration of a sample, and more particularly, to a system and a method for measuring the concentration of a sample such as a hematocrit using a mobile device.
Generally, hematocrit refers to the volume of red blood cells contained in blood. Hematocrit is generally in the category of 37-47% for women and 45-52% for men. When hematocrit is low, symptoms such as anemia, restless legs syndrome, and headache appear, and when it is high, symptoms such as iron poisoning and cell oxidation appear. Since the electrical conductivity of red blood cells is lower than that of plasma, hematocrit should be measured primarily for electrochemical blood tests such as blood glucose measurement.
As a relatively simple measurement method, a hematocrit is measured by measuring the length of erythrocytes in the capillary to the total length of the blood sample by injecting a blood sample into the glass canal and rotating the blood at high speed .
However, in general hospitals or larger clinics, Coulter counting machines, Bayer ADVIA 120 analyzers, Sysmex analyzers and ABX analyzers are used. As described above, most automated hematocrit measuring devices measure the impedance generated when red blood cells pass between two electrodes or use an optical analysis method. The former measure the hematocrit by measuring the electrical impulses (shock potential) generated by the red blood cells. Individual volumes of red blood cells can be measured using the electrical impedance of red blood cells or the scattering properties of light.
However, there is a problem that it is difficult to use the measuring apparatuses for diagnosing the on-site diseases because the measuring apparatuses take a long time to measure or have large disadvantages. Therefore, it is required to develop a technique that can be easily and easily measured and can be quickly tested for diagnosis of on-site diseases.
SUMMARY OF THE INVENTION Accordingly, it is an object of the present invention to provide a microfluidic device having a measurement assisting device capable of fixing a microfluidic device, And measuring the concentration of the measurement sample based on the photographed image, and a method for measuring the concentration of the sample using the mobile device.
However, the objects of the present invention are not limited to those mentioned above, and other objects not mentioned can be clearly understood by those skilled in the art from the following description.
According to an aspect of the present invention, there is provided a system for measuring a concentration of a sample, comprising: a microfluidic device having a microchannel therein, into which a measurement sample in a microchannel is injected; A measurement assisting device into which the microfluidic device is inserted; And a microchannel injecting measurement sample in the microfluidic device inserted into a lower end portion of the measurement assisting device at an upper end of the measurement assisting device to acquire an image of the microchannel to analyze the acquired image, A mobile device that determines the concentration of the sample.
Preferably, the measurement assisting device comprises: a body part formed of a polyhedron which cuts off light from the outside and has a predetermined size of space; An insertion port formed at a lower end of the body to insert the microfluidic device; And a photographing hole formed on one side of the upper end of the body part for photographing a region including a microchannel into which the measurement sample in the microfluidic device is injected using the mobile device.
The measurement assisting device may further include a light diffusing part formed inside the upper end of the body part and diffusing the light generated from the mobile device or the optical device into the inside when photographing using the mobile device.
Preferably, the light diffusing unit includes a reflective member for reflecting light generated from the mobile device or the optical device; And a diffusion member formed on the reflection member and diffusing the light reflected from the reflection member.
Preferably, the reflective member is formed inside the upper end portion of the body portion, and is formed by a predetermined angle from the inside of the upper end portion of the body portion so as not to obscure a viewing angle for photographing using the mobile device.
Preferably, the diffusion member is formed in a hemispherical shape having one side of the diffusion direction in a concave shape for diffusing light reflected from the reflection member.
Preferably, the mobile device activates a mobile application, acquires the image using the activated mobile application, analyzes the acquired image, and displays the concentration of the measurement sample determined as a result of the analysis. do.
Preferably, the mobile device calculates a gray scale value of each of the pixels corresponding to the microchannel into which the acquired measurement sample is injected, calculates a relative gray scale value using the calculated gray scale value, And comparing the calculated relative gray scale value with a reference value to determine a concentration of the measurement sample corresponding to the reference value.
Preferably, the relative gray scale value is defined as a difference between a grayscale value of the microchannel and a grayscale value of the substrate in the obtained image.
Preferably, the measurement sample is a blood sample, and the concentration of the measurement sample is hematocrit, which is a concentration of red blood cells in the blood.
According to another aspect of the present invention, there is provided a method for measuring a concentration of a sample, comprising: activating a mobile application for measuring a cell concentration according to a user's operation; Capturing an image of a microchannel injected with a measurement sample in the microfluidic device inserted into a lower end of a measurement assisting device for blocking light from outside through the activated mobile application; And analyzing the obtained image and determining the concentration of the measurement sample as a result of the analysis.
Preferably, the acquiring step may include acquiring an image by photographing a microchannel into which a measurement sample in the microfluidic device inserted into a lower end of the measurement assisting device is injected at an upper end of the measurement assisting device through the mobile application, .
Preferably, the acquiring step diffuses the light generated from the mobile device or the optical device into the inside when capturing the image using the mobile device through the light diffuser formed inside the upper end of the measurement assisting device to acquire the image .
Advantageously, the determining comprises calculating a gray scale value of each of the pixels corresponding to the microchannel into which the measurement sample obtained is injected, calculating a relative gray scale value using the calculated gray scale value And comparing the calculated relative gray scale value with a reference value to determine a concentration of the measurement sample corresponding to the reference value.
Preferably, the relative gray scale value is defined as a difference between a grayscale value of the microchannel and a grayscale value of the substrate in the obtained image.
In accordance with the present invention, there is provided a microfluidic device including a measurement assisting device capable of fixing a microfluidic device, and the microchannel injected with the measurement sample in the microfluidic device fixed to the measurement assisting device is photographed, The concentration of the measurement sample can be easily measured without regard to time and place.
In addition, since the microfluidic device is fixed to a measurement assist device in which light from the outside is blocked from the outside, the microchannel injected with the measurement sample in the fixed microfluidic device is photographed. Therefore, There is an effect that can be obtained.
Also, since the present invention can acquire an image without being influenced by external light, it is possible to measure the concentration of an accurate measurement sample through the acquired image.
1 is a diagram illustrating a system for measuring the concentration of a sample according to an embodiment of the present invention.
2 is a view showing the structure of a measurement assisting apparatus according to an embodiment of the present invention.
3 is a view illustrating a structure of a microfluidic device according to an embodiment of the present invention.
4A to 4B are views showing an example of using a measurement assisting apparatus according to the present invention.
5 is a view showing a structure of a microfluidic device according to an embodiment of the present invention.
6A to 6C are views showing the shape of a microchannel according to an embodiment of the present invention.
7 is a diagram illustrating a detailed configuration of a mobile device according to an embodiment of the present invention.
8 is a diagram illustrating a screen of a mobile application according to an exemplary embodiment of the present invention.
9A to 9B are diagrams for explaining the principle of measuring the hematocrit of the blood.
Figures 10A-10B show the relationship between blood hematocrit and gray scale values.
11 is a diagram illustrating a method for measuring the concentration of a sample according to an embodiment of the present invention.
Hereinafter, a system and method for measuring the concentration of a sample using a mobile device according to an embodiment of the present invention will be described with reference to the accompanying drawings. The present invention will be described in detail with reference to the portions necessary for understanding the operation and operation according to the present invention.
In describing the constituent elements of the present invention, the same reference numerals may be given to constituent elements having the same name, and the same reference numerals may be given thereto even though they are different from each other. However, even in such a case, it does not mean that the corresponding component has different functions according to the embodiment, or does not mean that the different components have the same function. It should be judged based on the description of each component in the example.
Particularly, in the present invention, it is possible to provide a measurement assisting device capable of fixing a microfluidic device, and the microchannel injected with the measurement sample in the microfluidic device fixed to the measurement assisting device is photographed, And a new method for measuring the concentration is proposed.
Herein, a method of measuring hematocrit, which is a concentration of red blood cells in the blood, as a blood sample and a measurement sample, will be described as an example of the present invention.
1 is a diagram illustrating a system for measuring the concentration of a sample according to an embodiment of the present invention.
As shown in FIG. 1, a system for measuring the concentration of a sample according to the present invention may include a
The
The
When the
The
The
Here, the
2 is a view showing the structure of a measurement assisting apparatus according to an embodiment of the present invention.
2, the
The
Here, the body portion formed as a hexahedron is described as an embodiment of the present invention, but the present invention is not limited thereto, and various shapes of polyhedrons may be formed depending on functions and effects.
The
At this time, it is preferable that the
The photographing
In the photographing
At this time, the photographing
3 is a view showing a structure of a measurement assisting apparatus according to another embodiment of the present invention.
3, the
Since the object and function of the measurement assisting apparatus described in FIG. 2 are the same, detailed description will be omitted.
The
The
The
The diffusing
The light diffused from the
4A to 4B are views showing an example of using a measurement assisting apparatus according to the present invention.
Referring to FIG. 4A, a microfluidic device including a microchannel into which a blood sample is injected is inserted through an insertion port formed at one side of the measurement assisting device.
Referring to FIG. 4B, a region corresponding to the microchannel into which the blood is injected through the microfluidic device is photographed through the imaging hole formed in the upper end of the measurement assisting device.
5 is a view showing a structure of a microfluidic device according to an embodiment of the present invention.
5, the
The
The
The
The
At this time, the hematocrit, which is the ratio of the red blood cells contained in the blood sample, can be measured to determine the presence or absence of anemia. The higher the hematocrit, the higher the ratio of red blood cells in the blood sample, and the microchannels filled with the blood sample become redder. In order to maximize this color change, it is important to recognize red blood cells in the blood sample, so that the microchannels can be used to prevent overlapping of red blood cells, thereby minimizing the incidence of non-recognition of red blood cells.
6A to 6C are views showing the shape of a microchannel according to an embodiment of the present invention.
6A to 6C, the microchannel according to the present invention may be formed in a bent shape or a spiral shape. The bent shape may be a rectangular shape as a whole as shown in FIGS. 6A to 6B, As shown in FIG.
The hydraulic diameter inside the microchannels is preferably 500 탆 or less. Here, the hydrodynamic diameter is a concept designed so that when the water or the fluid flows through the tube, the cross section may flow not only in a circular shape but also partially in a circular shape so that it can be converted into a case where the tube is filled with 100% of a circular section.
The numerical acuity diameter D H used herein can be defined as the following equation (1).
[Equation 1]
D H = 4A / P
Here, A represents the cross-sectional area of the pipe, and P represents the circumference of the cross-section of the fluid on the cross section.
At this time, the microchannel can be manufactured using a low-cost polyethylmethacrylate (PCM) relay substrate so that it can be used for a disposable test.
The microchannel fabrication is performed by hot embossing to pattern the PMMA substrate with a thickness of 1 mm and then bonding the PMMA substrate with the unmodified PMMA substrate by a zero fusion bonding process to form a hydrodynamic diameter Mu] m or less.
At this time, since the microchannel can restrict overlapping of red blood cells when the hydrodynamic diameter is 500 mu m or less, the reliability of the hematocrit can be increased when the camera is photographed.
The
For example, the
The
At this time, the
The
One
Also, the concave shaped space formed by the
Such a reagent can be contained not only in the micropump but also in the microchannel.
7 is a diagram illustrating a detailed configuration of a mobile device according to an embodiment of the present invention.
7, the
The communication unit 310 is connected to a network based on wireless communication, and can transmit / receive various data. For example, the communication unit 310 may receive a mobile application for measuring cell density from a service server in conjunction with a service server through wireless communication.
The
The
The control unit 340 activates the mobile application according to the user's menu or key operation, operates the pre-installed image acquiring unit through the activated mobile application, photographs the microchannel of the microfluidic device disposed in the measurement assisting device, And the obtained image is analyzed, and the cell concentration of the hematocrit and the like can be measured as a result of the analysis.
The display unit 350 can display the image obtained by photographing the microchannel of the microfluidic device through the mobile application and the cell concentration as a result of analyzing the acquired image.
The storage unit 360 may store a mobile application, an acquired image, a measured cell concentration, and the like.
8 is a diagram illustrating a screen of a mobile application according to an exemplary embodiment of the present invention.
As shown in FIG. 8, the mobile device according to the present invention activates a mobile application and performs image acquisition, image analysis, and display of results through the activated mobile application.
For example, the mobile application includes a capture button, a process button, and a result button, and performs image acquisition, image analysis, and result display according to each button.
When the capture button is pressed, the mobile device photographs the microchannel into which the blood sample of the microfluidic device is injected, acquires the image as a result of the photographing, and displays the acquired image on the screen.
When the processing button is pressed, the mobile device can analyze the acquired image, for example, by measuring the cell concentration using an algorithm for calculating a relative gray scale value (relative GSV).
For example, the mobile device compares the calculated relative gray scale value with a reference value, and measures the cell concentration in the microchannel, that is, the hematocrit, based on the comparison result.
When the result button is pressed, the mobile device displays the cell concentration on the screen as a result of the analysis.
In the present invention, the cell density can be measured using a gray scale value (GSV) of each pixel in an image. The gray scale value can be obtained by the following equation (2).
&Quot; (2) "
Gray Scale Value = 1/3 (R + G + B)
Here, R, G, and B have red, green, and blue values of 0 to 255 in each pixel.
9A to 9B are diagrams for explaining the principle of measuring the hematocrit of the blood.
Referring to FIG. 9A, there is shown an image of a microchannel containing blood having 10%, 20%, 30%, and 40% hematocrit levels. Here, we want to measure the gray scale value of each pixel in the area indicated by the dashed box.
Referring to FIG. 9B, the y-axis grayscale values of each pixel in the selected region of the image are averaged and the average y-axis grayscale value is plotted along the x-axis distance.
The gray scale values of the microchannels including blood having different hematocrit levels are changed.
That is, since the substrate color of the device is white as shown in FIG. 9A, the gray scale value in the substrate area has red, green, and blue color components. On the other hand, the microchannels filled with blood have only one red color. Thus, the grayscale value of the microchannel on the graph is smaller than the grayscale value of the substrate.
Also, as the blood hematocrit increases, the gray scale value also decreases because the color elements of the green and blue are reduced.
Therefore, using these measurement results, the difference between the gray scale value of the microchannel and the gray scale value of the substrate is defined as the relative gray scale value of each microchannel.
Figures 10A-10B show the relationship between blood hematocrit and gray scale values.
Referring to FIG. 10A, a relative gray scale value according to a blood hematocrit is shown. That is, the relative gray scale value is proportional to the hematocrit.
Since the number of red blood cells in the microchannel increases with the hematocrit, the intensity of the red color increases and this results in a higher relative gray scale value.
Referring to FIG. 10B, as the depth of the microchannel increases, the relative gray scale value becomes higher. This is because the number of red blood cells in the unit area increases.
Referring to FIG. 10C, the correlation between the hematocrit and the relative gray scale value follows the Beer-Lambert Law. That is, since the mobile device measures the light reflected from the blood, the relative gray scale value increases logarithmically with the hematocrit in accordance with the Lambert law.
11 is a diagram illustrating a method for measuring the concentration of a sample according to an embodiment of the present invention.
As shown in FIG. 11, the microfluidic device including the microchannel into which the blood sample is injected may be inserted into the lower portion of the measurement assisting device through the insertion port provided at one side (S 1110).
Next, the mobile device activates the mobile application (S1120) and uses the activated mobile application to transmit the blood sample in the micro-pinch device through the imaging hole formed in the upper part of the measurement assisting device, And acquires the image as a result of the shooting (S1130).
Next, the mobile device analyzes the obtained image, analyzes the brightness of the blood sample in the microchannel as a result of the analysis, and measures the cell concentration as a result of the analysis (S1140).
Specifically, the mobile device may calculate the gray scale value of each of the pixels corresponding to the microchannel into which the blood sample is injected (S1141), and calculate the relative gray scale value using the calculated gray scale value (S1142).
Then, the mobile device compares the calculated relative gray scale with a predetermined reference value (S1143), and determines the cell concentration corresponding to the matching reference value according to the comparison result (S1144).
Next, the mobile device can display the measured cell concentration on the screen (S1150).
It is to be understood that the present invention is not limited to these embodiments, and all of the elements constituting the embodiments of the present invention described above may be combined or operated in one operation. That is, within the scope of the present invention, all of the components may be selectively coupled to one or more of them. In addition, although all of the components may be implemented as one independent hardware, some or all of the components may be selectively combined to perform a part or all of the functions in one or a plurality of hardware. As shown in FIG. In addition, such a computer program may be stored in a computer-readable medium such as a USB memory, a CD disk, a flash memory, etc., and read and executed by a computer to implement embodiments of the present invention. As the storage medium of the computer program, a magnetic recording medium, an optical recording medium, a carrier wave medium, or the like may be included.
It will be apparent to those skilled in the art that various modifications and variations can be made in the present invention without departing from the spirit or essential characteristics thereof. Therefore, the embodiments disclosed in the present invention are intended to illustrate rather than limit the scope of the present invention, and the scope of the technical idea of the present invention is not limited by these embodiments. The scope of protection of the present invention should be construed according to the following claims, and all technical ideas within the scope of equivalents should be construed as falling within the scope of the present invention.
100: Measurement support device
110:
120:
130: shooting hole
140: light diffusion portion
141: reflective member
142: diffusion member
200: microfluidic device
210:
220: inlet
230: Outlet
240: fine channel
250: Micro pump
300: Mobile device
310:
320:
330:
340:
350:
360:
Claims (15)
A reflecting member formed inside the upper end of the body part formed of a polyhedron having a predetermined size of space to shield light from the outside and reflecting the incoming light by being tilted by a predetermined angle from the inside of the upper end of the body part, And a diffusion member for diffusing the reflected light, wherein the microfluidic device is inserted into the lower end of the body part; And
The micro-channel injected from the upper end of the measurement assisting device inserted in the lower end of the measurement assisting device is imaged to acquire an image, and the acquired image is analyzed. As a result of the analysis, A mobile device for determining a concentration;
≪ / RTI >
Wherein the measurement assisting device comprises:
An insertion port formed at a lower end of the body to insert the microfluidic device; And
A photographing hole formed on one side of the upper end of the body for photographing a region including a microchannel into which the measurement sample in the microfluidic device is injected using the mobile device;
≪ / RTI >
A light diffusing part formed inside the upper end of the body part and including the reflection member and the diffusion member for diffusing the light generated from the mobile device or the optical device into the inside when taking pictures using the mobile device;
≪ / RTI >
Wherein the diffusion member
Wherein one side of the diffusion direction is formed in a concave hemispherical shape so as to diffuse the light reflected from the reflection member.
The mobile device includes:
Wherein the mobile application is activated to acquire the image using the activated mobile application, analyze the obtained image, and display the concentration of the measurement sample determined as a result of the analysis. For the system.
The mobile device includes:
Calculating a gray scale value of each of the pixels corresponding to the microchannel into which the measurement sample is acquired,
Calculates a relative gray scale value using the calculated gray scale value,
And comparing the calculated relative gray scale value with a reference value to determine a concentration of a measurement sample corresponding to a matching reference value.
The relative grayscale value may be determined by:
And the gray scale value of the microchannel in the acquired image is defined as the difference between the grayscale value of the substrate and the grayscale value of the microchannel in the acquired image.
Wherein the measurement sample is a blood sample and the concentration of the measurement sample is hematocrit, which is the concentration of red blood cells in the blood.
A light emitting diode (LED), which is formed inside a top portion of a polyhedron having a space of a predetermined size, shields light from outside through the activated mobile application and reflects the incoming light by being tilted by a predetermined angle from the inside of the upper end of the body Capturing an image of a microchannel into which a measurement sample in the microfluidic device inserted into the lower end of the body is injected, and a diffusion member formed on the reflection member and diffusing the reflected light; And
Analyzing the acquired image and determining the concentration of the measurement sample as a result of the analysis;
≪ / RTI >
Wherein the acquiring comprises:
And measuring the concentration of the sample by measuring the microchannel injected with the measurement sample in the microfluidic device inserted into the lower end of the measurement assisting device from the upper end of the measurement assisting device through the mobile application Way.
Wherein the determining comprises:
Calculating a gray scale value of each of the pixels corresponding to the microchannel into which the measurement sample is acquired,
Calculates a relative gray scale value using the calculated gray scale value,
And comparing the calculated relative gray scale value with a reference value to determine a concentration of a measurement sample corresponding to a matching reference value.
The relative grayscale value may be determined by:
And defining a difference between a grayscale value of the microchannel and a grayscale value of the substrate in the acquired image.
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Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
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US20090269837A1 (en) | 2003-03-01 | 2009-10-29 | The Trustees Of Boston University | System for assessing the efficacy of stored red blood cells using microvascular networks |
KR101222585B1 (en) | 2010-12-23 | 2013-01-16 | 고려대학교 산학협력단 | Apparatus and method of blood coagulation measurement using light transmission intensity, and micro stirring chip |
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Publication number | Priority date | Publication date | Assignee | Title |
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US20090269837A1 (en) | 2003-03-01 | 2009-10-29 | The Trustees Of Boston University | System for assessing the efficacy of stored red blood cells using microvascular networks |
KR101222585B1 (en) | 2010-12-23 | 2013-01-16 | 고려대학교 산학협력단 | Apparatus and method of blood coagulation measurement using light transmission intensity, and micro stirring chip |
Non-Patent Citations (1)
Title |
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Statistical Dynamics of Flowing Red Blood Cells by Morphological |
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