KR102291905B1 - Apparatus for red blood cell life test using speckle decorrelation time analysis - Google Patents

Abstract

The present invention relates to an erythrocyte lifetime test device using speckle decorrelation time analysis. A red blood cell life test apparatus according to an embodiment of the present invention includes: a laser unit for irradiating a laser to a blood sample containing red blood cells; a photographing unit which acquires a speckle image of the blood sample irradiated with the laser; and a controller that determines a speckle decorrelation time for the red blood cells from the speckle image and performs a functional test of the red blood cells based on the speckle decorrelation time for the red blood cells. have.

Description

Apparatus for red blood cell life test using speckle decorrelation time analysis

The present invention relates to a red blood cell life test device, and more particularly, to a red blood cell life test device using speckle uncorrelation time analysis.

Blood tests are being used as part of a method for diagnosing and treating diseases and making prognosis. A blood test is a useful test for diagnosing diseases by using the phenomenon that changes in blood components occur when there is a lesion in an organ or tissue throughout the body. It is classified into a morphological test method that examines phosphorus properties and status, a biochemical test method that measures various components in the blood by biochemical methods, and an immunoserological test method such as VDRL, TPHA, and FTA.

The morphological examination method examines the number of red blood cells, hemoglobin, hematocrit, counts calculated from these, white blood cell count, platelet count, reticulocyte count, etc. The type of white blood cells and the qualitative changes of various blood cells are investigated by staining the applied ones, and the bleeding time, coagulation time, capillary resistance, etc. are examined to diagnose bleeding tendency, blood diseases, infections, etc., and to determine the course and prognosis of various diseases. It's a test that will help.

However, such a conventional test method has to measure the characteristics of each red blood cell, and there is a problem that physical damage to the red blood cells may be caused by applying a strong pressure.

[Patent Document 1] Korean Patent No. 10-1749796

The present invention was created to solve the above problems, and an object of the present invention is to provide a red blood cell lifespan test using speckle uncorrelation time analysis.

Another object of the present invention is to provide a red blood cell life test apparatus for determining a speckle decorrelation time for red blood cells by analyzing a speckle image obtained from a blood sample irradiated with a laser.

Objects of the present invention are not limited to the objects mentioned above, and other objects not mentioned will be clearly understood from the description below.

In order to achieve the above objects, a red blood cell life test apparatus according to an embodiment of the present invention includes: a laser unit for irradiating a laser to a blood sample containing red blood cells; a photographing unit which acquires a speckle image of the blood sample irradiated with the laser; and a controller that determines a speckle decorrelation time for the red blood cells from the speckle image and performs a functional test of the red blood cells based on the speckle decorrelation time for the red blood cells. have.

In an embodiment, the controller may measure the lifespan of the red blood cells based on a speckle uncorrelation time for the red blood cells.

In an embodiment, the red blood cell life test device comprises: a microfluidic chip for moving the blood sample; It further includes, wherein the laser unit may irradiate the laser to the blood sample moving through the microfluidic chip.

In an embodiment, the microfluidic chip may include an injection unit into which the blood sample is injected, a movement channel through which the injected blood sample moves, and an outlet through which the moved blood sample is discharged.

In an embodiment, the red blood cell life test device includes: a vacuum unit coupled to the microfluidic chip to move the blood sample through vacuum pressure; may further include.

In an embodiment, the vacuum unit is coupled to a moving tube through which the discharged blood sample moves, a first valve coupled to the moving tube to open and close the flow of the blood sample, and the moving tube, to open and close the first valve Accordingly, it may include a vacuum pump for forming the inside of the moving tube in a vacuum state.

In an embodiment, the vacuum unit, coupled to the moving tube, may further include a buffer for buffering the movement of the blood sample.

In an embodiment, the vacuum pump forms the inside of the moving tube in a vacuum state after the first valve is closed, and the first valve opens after the inside of the moving tube is formed in a vacuum state. ), and the moving tube may move the blood sample based on the vacuum pressure generated as the first valve is opened.

Specific details for achieving the above objects will become clear with reference to the embodiments to be described in detail below in conjunction with the accompanying drawings.

However, the present invention is not limited to the embodiments disclosed below, but may be configured in various different forms, and those of ordinary skill in the art to which the present invention belongs ( Hereinafter, "a person skilled in the art") is provided to fully inform the scope of the invention.

According to an embodiment of the present invention, by analyzing the difference in the time that the speckle changes, the accuracy is relatively high in the red blood cell test, the operating price is low due to the configuration of the microfluidic chip and the simple system, and it is possible to measure in a short time. As a system, the inspection time can be shortened.

The effects of the present invention are not limited to the above-described effects, and the potential effects expected by the technical features of the present invention will be clearly understood from the following description.

1A is a diagram illustrating a functional configuration of a red blood cell life test apparatus according to an embodiment of the present invention.
1B is a diagram illustrating a microfluidic chip according to an embodiment of the present invention.
2 is a diagram illustrating a speckle image according to an embodiment of the present invention.
3A and 3B are diagrams illustrating red blood cells after a storage period according to an embodiment of the present invention.
4A and 4B are diagrams illustrating speckle decorrelation time graphs for various storage periods according to an embodiment of the present invention.
5A is a diagram illustrating a light transmittance graph according to an embodiment of the present invention.
5B is a diagram illustrating a red blood cell flow speed graph according to an embodiment of the present invention.
6A is a diagram illustrating a graph of light movement intensity with respect to speckle decorrelation time according to an embodiment of the present invention.
6B is a diagram illustrating a red blood cell flow speed graph with respect to a light movement intensity graph according to an embodiment of the present invention.
6C is a diagram illustrating a red blood cell flow speed graph with respect to speckle uncorrelation time according to an embodiment of the present invention.

Since the present invention can have various changes and can have various embodiments, specific embodiments are illustrated in the drawings and described in detail.

Various features of the invention disclosed in the claims may be better understood upon consideration of the drawings and detailed description. The apparatus, methods, preparations, and various embodiments disclosed herein are provided for purposes of illustration. The disclosed structural and functional features are intended to enable those skilled in the art to specifically practice the various embodiments, and are not intended to limit the scope of the invention. The terms and sentences disclosed are for the purpose of easy-to-understand descriptions of various features of the disclosed invention, and are not intended to limit the scope of the invention.

In describing the present invention, if it is determined that a detailed description of a related known technology may unnecessarily obscure the gist of the present invention, the detailed description thereof will be omitted.

Hereinafter, a red blood cell life test apparatus using speckle uncorrelation time analysis according to an embodiment of the present invention will be described.

FIG. 1A is a diagram illustrating a functional configuration of a red blood cell life test apparatus 100 according to an embodiment of the present invention. 1B is a diagram illustrating a microfluidic chip 120 according to an embodiment of the present invention. 2 is a diagram illustrating a speckle image according to an embodiment of the present invention.

1A and 1B , the red blood cell life test apparatus 100 may include a laser unit 110 , a microfluidic chip 120 , a vacuum unit 130 , a photographing unit 140 , and a control unit (not shown). have.

The laser unit 110 may irradiate a laser to a blood sample including red blood cells. In one embodiment, the microfluidic chip 120 may move the blood sample. In this case, the laser unit 110 may irradiate a laser to the blood sample moving through the microfluidic chip 120 .

In one embodiment, the microfluidic chip 120 includes an injection unit 122 through which a blood sample is injected, a movement channel 124 through which the injected blood sample moves, and a discharge unit 126 through which the moved blood sample is discharged. can do.

The vacuum unit 130 may be coupled to the microfluidic chip 120 to move the blood sample through vacuum pressure.

In an embodiment, the vacuum unit 130 is coupled to a moving tube 132 through which the discharged blood sample moves, a first valve 134 coupled to the moving tube 132 to open and close the flow of the blood sample, and the moving tube 132 . It may include a vacuum pump 136 for forming the inside of the moving pipe 132 in a vacuum state according to the opening and closing of the first valve 134 . For example, the first valve 134 may include a solenoid valve.

In one embodiment, the vacuum pump 136 may form the inside of the moving tube 132 in a vacuum state after the first valve 134 is closed. For example, the vacuum pump 136 may include a syringe pump.

The first valve 134 may be opened after the inside of the moving tube 132 is formed in a vacuum state. Accordingly, the moving tube 132 may move the blood sample based on the vacuum pressure generated when the first valve 134 is opened.

In an embodiment, the vacuum unit 130 may further include a buffer unit 138 coupled to the moving tube 132 to buffer the movement of the blood sample. In this case, the buffer 138 may be coupled to the moving pipe 132 through the second valve. For example, the second valve may comprise a three-way valve. The buffer unit 138 may include a container formed of an empty space.

The photographing unit 140 may acquire a speckle image of a blood sample irradiated with a laser. In this case, the speckle image may include a speckle pattern irregularly generated by interference generated when the laser is reflected or passed through the blood sample.

In an embodiment, the photographing unit 140 may include at least one of a lens, an iris, a polarizing plate, and a camera through which a laser irradiated onto a blood sample is projected.

The controller may determine a speckle decorrelation time for red blood cells from the speckle image.

In an embodiment, the controller may measure the function of the red blood cells based on the speckle uncorrelation time for the red blood cells. In an embodiment, the controller may measure the lifespan of the red blood cells based on the speckle uncorrelation time for the red blood cells.

2 is a diagram illustrating a speckle image according to an embodiment of the present invention.

Referring to FIG. 2 , the speckle image may include a speckle pattern irregularly generated by interference generated when a laser is reflected or passed through a blood sample.

The speckle image may be acquired at a specific period by the photographing unit 140 . In this case, the speckle decorrelation time may change the strain rate of the speckle pattern.

In an embodiment, the speckle decorrelation time may be determined based on Equation 1 below.

는 세기 자기상관성 함수(intensity autocorrelation function),

및

은 각 시간에 캡쳐된 세기(intensity), <>는 캡쳐된 모든 데이터의 평균 연산을 나타낸다. here,

is the intensity autocorrelation function,

and

is the intensity captured at each time, and <> represents the average operation of all captured data.

In an embodiment, the <Equation 1> may be related to a field autocorrelation function, and may be expressed as <Equation 2> below.

는 세기 자기상관성 함수,

은 전기장 자기상관성 필드(electrical field autocorrelation field),

는 수집 광학(collection optics) 및 캡쳐 파라미터(capture parameter)에 의해 결정되는 0 내지 1 사이의 실험 팩터(experimental factor)를 나타낸다(

=g₂(o)-1). here,

is the intensity autocorrelation function,

is the electric field autocorrelation field,

denotes an experimental factor between 0 and 1 determined by the collection optics and the capture parameter (

=g ₂ (o)-1).

또는 세기 변화

에 의해 생성될 수 있다. In this case, the autocorrelation function is the electrical signal

or change in intensity

can be created by

는 하기 <수학식 3>과 같이 나타낼 수 있다. In one embodiment, the electric field autocorrelation field

can be expressed as in Equation 3 below.

는 감쇠 시간(decay time),

,

, D는 확산계수(diffusion coefficient),

는 이송 평균자유행로(transport mean-free path), s는 경로 길이, P(s)는 경로 길이의 분포를 나타낸다. here,

is the decay time,

,

, D is the diffusion coefficient,

is the transport mean-free path, s is the path length, and P(s) is the distribution of path lengths.

는 하기 <수학식 4>와 같이 나타낼 수 있다. In one embodiment, the electric field autocorrelation field

can be expressed as in the following <Equation 4>.

는 Brownian motion으로부터의 이완 속도(relaxation rate),

는 Laminar flow로부터의 이완속도를 나낸다. 즉, <수학식 3>은 플로우가 고려되지 않고, <수학식 4>는 플로우가 고려됨을 확인할 수 있다. here,

is the relaxation rate from Brownian motion,

is the rate of relaxation from the laminar flow. That is, it can be confirmed that <Equation 3> does not consider the flow, and <Equation 4> considers the flow.

는 전단 플로우(shear flow)(

), 농도 감소(

), 입자 크기(r)의 증가에 의해 더욱 빠르게 감쇠됨을 확인할 수 있다. 다시 말해, 스페클 비상관성 시간의 변화는 플로우 레이트, 농도, 입자 크기에 의해 결정될 수 있다. That is, the electric field autocorrelation field through <Equation 5>

is the shear flow (

), decrease the concentration (

), it can be seen that the attenuation is faster with an increase in the particle size (r). In other words, the change in speckle uncorrelation time can be determined by the flow rate, concentration, and particle size.

3A and 3B are views illustrating red blood cells after a storage period according to an embodiment of the present invention. 4A and 4B are diagrams illustrating speckle decorrelation time graphs for various storage periods according to an embodiment of the present invention.

Referring to FIGS. 3A and 3B , it can be confirmed that red blood cells (RBCs) aggregate while the fibrinogen concentration decreases after the whole blood including red blood cells is cured for a certain period of storage. In this case, the erythrocytes before agglutination show a fast flow, but the aggregated erythrocytes show a slow flow.

At this time, referring to FIGS. 4A and 4B , it can be seen that the speckle non-correlation time gradually increases according to the preservation period of blood. For example, it can be seen that the speckle uncorrelation time sharply increases after 28 days. Therefore, by measuring the speckle uncorrelation time for red blood cells, the storage period and lifespan of red blood cells can be determined.

5A is a diagram illustrating a light transmittance graph according to an embodiment of the present invention. 5B is a diagram illustrating a red blood cell flow speed graph according to an embodiment of the present invention.

Referring to FIGS. 5A and 5B , it can be seen that the transmittance of light increases as the retention period of red blood cells increases. In addition, the blood flow rate was measured in real time, and it can be seen that the time to reach the end of the channel is delayed in the case of old red blood cells.

That is, according to various embodiments of the present invention, by analyzing the magnitude of the change in speckle of light, it is possible to measure the retention period of red blood cells in a short time. It may be possible to measure without driving.

미만의 혈액 양을 이용하여 1분 미만의 소요시간을 통해 적혈구의 수명을 측정할 수 있다. For example, according to the invention, 10

Using less than a blood volume, it is possible to measure the lifespan of red blood cells in less than 1 minute.

6A is a diagram illustrating a light movement intensity graph with respect to speckle decorrelation time according to an embodiment of the present invention. 6B is a diagram illustrating a red blood cell flow speed graph with respect to a light movement intensity graph according to an embodiment of the present invention. 6C is a diagram illustrating a red blood cell flow speed graph with respect to speckle uncorrelation time according to an embodiment of the present invention.

6A to 6C , a solid line indicates a linear correlation coefficient of a data point. The closer to the r value of 1 or -1, the more linear the scatter plot of each group variable (-1≤r≤1).

In addition, the average RBC flow speed may have a negative correlation with the relative light transmission intensity and the speckle uncorrelation time (r=-0.69, r=-0.67). ).

In an embodiment, the relative light movement intensity and speckle decorrelation time may have a positive linear correlation (r=0.67).

The above description is merely illustrative of the technical spirit of the present invention, and various changes and modifications may be made by those skilled in the art without departing from the essential characteristics of the present invention.

Accordingly, the embodiments disclosed in the present specification are not intended to limit the technical spirit of the present invention, but to illustrate, and the scope of the present invention is not limited by these embodiments.

The protection scope of the present invention should be interpreted by the claims, and all technical ideas within the scope equivalent thereto should be understood to be included in the scope of the present invention.

100: red blood cell life test device
110: laser unit
120: microfluidic chip
122: injection unit
124: moving channel
126: discharge unit
130: vacuum unit
132: moving pipe
134: first valve
136: vacuum pump
138: buffer
140: filming department

Claims (8)

a laser unit irradiating a laser to a blood sample including red blood cells;
a photographing unit which acquires a speckle image of the blood sample irradiated with the laser; and
determining a speckle decorrelation time for the red blood cells from the speckle image,
a controller configured to measure the lifespan of the red blood cells based on a speckle uncorrelation time for the red blood cells;
including,
wherein the speckle uncorrelation time is obtained at a specific period and used to change the rate of transformation of the speckle pattern for the red blood cells,
Red blood cell life test device.
delete According to claim 1,
a microfluidic chip for moving the blood sample;
further comprising,
The laser unit, irradiating the laser to the blood sample moving through the microfluidic chip,
Red blood cell life test device.
4. The method of claim 3,
The microfluidic chip,
an injection unit into which the blood sample is injected;
a movement channel through which the injected blood sample moves; and
a discharge unit through which the moved blood sample is discharged;
containing,
Red blood cell life test device.
5. The method of claim 4,
a vacuum unit coupled to the microfluidic chip to move the blood sample through vacuum pressure;
further comprising,
Red blood cell life test device.
6. The method of claim 5,
The vacuum unit,
a moving tube through which the discharged blood sample moves;
A first valve coupled to the moving tube to open and close the flow of the blood sample, and
A vacuum pump coupled to the moving pipe to form the inside of the moving pipe in a vacuum state according to the opening and closing of the first valve;
containing,
Red blood cell life test device.
7. The method of claim 6,
The vacuum unit,
A buffer unit coupled to the transfer tube to buffer the movement of the blood sample;
further comprising,
Red blood cell life test device.
7. The method of claim 6,
The vacuum pump, after the first valve is closed (close), forms the inside of the moving tube in a vacuum state,
The first valve is opened after the inside of the moving tube is formed in a vacuum state,
The moving tube moves the blood sample based on the vacuum pressure generated as the first valve is opened,
Red blood cell life test device.

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