KR101885964B1 - Method and Apparatus for Measuring the level of HbA1c Using Optical Properties of Red Blood Cell - Google Patents

Abstract

A method and apparatus for measuring the glycated hemoglobin concentration using the optical characteristics of red blood cells are presented. A method for measuring glycated hemoglobin using optical characteristics of red blood cells, comprising the steps of: placing a predetermined amount of blood on a medium; Irradiating the medium with a light source; Measuring intensity oscillation of light transmitted through or reflected from the medium; And analyzing the magnitude of the measured intensity of the light according to a predetermined criterion to determine the possibility of a diabetic patient.

Description

TECHNICAL FIELD The present invention relates to a method and an apparatus for measuring HbA1c concentration using the optical characteristics of red blood cells,

The following examples relate to a method and apparatus for measuring HbA 1c concentration using the optical properties of red blood cells. More particularly, the present invention relates to a method and an apparatus for measuring the glycated hemoglobin concentration that discriminates the possibility of a diabetic patient using the optical characteristics of diabetic red blood cells.

Diabetes is one of the major diseases that threatens human health. All diabetes types are caused by chronic hyperglycemia, or hyperglycemia, caused by a lack of metabolic loss through insulin or insulin, which ultimately results in retinopathy, neuropathy and nephropathy, severe depression, and dementia cardiovascular disease Diabetic complications from microvascular disease including diabetes mellitus. Since diabetes is closely related to diabetic complications, the deformation characteristics of red blood cells are important for understanding the pathophysiology of diabetes.

To diagnose diabetes, blood glucose levels are measured. However, the blood sugar level, physiological changes due to diet, physical activity, etc., is so large that an accurate diagnosis of diabetes should be made on an empty stomach. Diabetes mellitus testing, which measures glucose levels by drinking glucose solution, can be performed for the diagnosis of diabetes, but is not routinely recommended because of the influence of many factors.

It is important to maintain adequate blood glucose levels to reduce complications in patients treated with diabetes. Because the blood glucose level measured at one point may vary due to various factors, the most widely used test for determining long-term blood glucose control is the HbA1c test. Glycated hemoglobin is a form of glucose binding to hemoglobin normally present in red blood cells, and a high level of glycosylated hemoglobin when the blood sugar level is maintained high. Since glycated hemoglobin reflects the average blood glucose level for 3 months, it is useful for determining the long-term blood glucose control level.

Korean Patent Laid-open Publication No. 10-2014-0097041 discloses a technique relating to such a diabetic measurement apparatus and its manufacturing method.

The embodiments describe a method and apparatus for measuring HbA1c concentration using the optical characteristics of red blood cells. More specifically, the present invention relates to a method and apparatus for measuring HbA1c concentration using erythrocytes, A method and an apparatus for measuring a glycated hemoglobin concentration using the optical characteristics of an analyte.

Embodiments provide a method and an apparatus for measuring glycated hemoglobin using optical characteristics of a red blood cell of a diabetic patient, which determines whether or not diabetes is suspected by measuring light shake of blood after irradiating blood with light to check surface vibrations of red blood cells.

A method of measuring a glycated hemoglobin concentration using an optical characteristic of a red blood cell according to an embodiment of the present invention includes the steps of: placing a predetermined amount of blood on a medium; Irradiating the medium with a light source; Measuring light scattering vibration of light transmitted through or reflected from the medium; And analyzing the magnitude of the measured intensity of the light according to a predetermined criterion to determine the possibility of a diabetic patient.

The step of disposing a predetermined amount of blood on the medium may drop a predetermined amount of blood on the transparent slide.

The step of disposing a predetermined amount of blood on the medium may drop a predetermined amount of blood on a micro fluidic channel.

The step of disposing a predetermined amount of blood on the medium may drop a predetermined amount of blood on a fibrous non-uniform medium made of paper or a polymer.

The step of irradiating the medium with a light source may include irradiating the light source to transmit the medium and measuring light scattering vibration of light transmitted through or reflected from the medium includes transmitting light transmitted through the medium in which the blood is disposed, Or the vibration of diffracted light or refracted light diffracted or refracted through the medium.

The step of irradiating the medium with the light source may include irradiating the light source toward the medium and measuring the light scattering vibration of the light transmitted through or reflected from the medium includes vibrating the reflected light reflected by the medium on which the blood is disposed Can be measured.

The step of irradiating the medium with a light source may include irradiating the light source to be totally reflected on the medium and measuring light scattering vibration of light transmitted through or reflected from the medium, It is possible to measure the vibration of the scattered light generated in the blood arranged on the upper part of the blood.

The step of measuring the intensity vibration of the light transmitted through or reflected from the medium can confirm the surface vibration of the red blood cells from the light scattering vibration of the light transmitted or reflected by the medium through the measurement of the 3D refractive index tomography or the 2D time- .

In a diabetic diagnostic test according to another embodiment, a light source; A medium in which a predetermined amount of blood is disposed and which transmits or reflects the light source; And a measurement unit for measuring light scattering vibration of light transmitted through or reflected from the medium. The magnitude of the measured intensity of the light is analyzed according to a predetermined standard to determine the possibility of a diabetic patient.

The medium may be a transparent slide on which a predetermined amount of blood has been dropped.

The medium may be a microfluidic channel in which a predetermined amount of blood has been dropped.

The medium may be a fibrous non-uniform medium consisting of a paper or polymer dropping a predetermined amount of blood.

The light source is irradiated to transmit the medium, and the measuring unit can measure the vibration of the transmitted light transmitted through the medium on which the blood is disposed.

The light source is irradiated to transmit the medium, and the measuring unit can measure the vibration of the diffracted light or the refracted light that is diffracted or refracted through the medium in which the blood is disposed.

The light source is irradiated toward the medium, and the measurement unit can measure the vibration of the reflected light reflected by the medium in which the blood is disposed.

The light source is irradiated to be totally reflected on the medium, and the measurement unit can measure the vibration of the scattered light generated in the blood disposed on the medium as total reflection occurs in the lower part of the medium.

The measuring unit is configured to measure a time change of an optical signal scattered in red blood cells. The measurement unit measures a time-varying optical signal scattered from red blood cells, Can be confirmed.

According to the embodiments, it is possible to provide information on the glycosylated hemoglobin concentration by checking the surface vibrations of red blood cells by measuring light shake after irradiating the specimen with blood or blood diluted with light, and thereby detecting diabetic red blood cells A method and an apparatus for early diagnosis of a diabetes diagnosis using a characteristic or a risk group of diabetes can be provided.

Embodiments of the present invention provide a method and apparatus for measuring glycated hemoglobin concentration capable of being miniaturized, easily carried, and capable of being manufactured at low cost, by allowing blood to be contained in a medium, irradiating light, and determining susceptibility to diabetes through shaking of light .

1 is a view showing an example of a medium in an apparatus for measuring glycated hemoglobin using optical characteristics of erythrocytes according to an embodiment.
2 is a view showing another example of a medium in an apparatus for measuring glycated hemoglobin using optical characteristics of erythrocytes according to an embodiment.
3 is a view showing another example of a medium in an apparatus for measuring glycated hemoglobin using optical characteristics of erythrocytes according to an embodiment.
4 is a view showing an example of measurement of an apparatus for measuring glycated hemoglobin using optical characteristics of erythrocytes according to an embodiment.
5 is a view showing another example of measurement of an apparatus for measuring glycated hemoglobin using optical characteristics of erythrocytes according to an embodiment.
FIG. 6 is a diagram illustrating another example of measurement of an apparatus for measuring glycated hemoglobin using optical characteristics of erythrocytes according to an embodiment.
FIG. 7 is a diagram illustrating another example of measurement of an apparatus for measuring glycated hemoglobin using optical characteristics of erythrocytes according to an embodiment.
FIG. 8 is a flowchart illustrating a method of measuring the HbA1c concentration using the optical characteristics of erythrocytes according to an embodiment.
FIG. 9 is a diagram illustrating a reconstructed 3D refractive index tomographic image of healthy red blood cells and diabetic red blood cells according to an embodiment.
FIG. 10 is a diagram for explaining morphological and biochemical parameters for all erythrocytes measured in normal and diabetic patients according to one embodiment.
11 is a view for explaining a 2D cell membrane height map of healthy red blood cells and diabetic red blood cells according to one embodiment.
Figure 12 shows a box graph of cell membrane tremor for erythrocytes measured from diabetic patients according to one embodiment.
13 is a diagram for explaining various red blood cell parameters of healthy red blood cells and diabetic red blood cells according to one embodiment.

Hereinafter, embodiments will be described with reference to the accompanying drawings. However, the embodiments described may be modified in various other forms, and the scope of the present invention is not limited by the embodiments described below. In addition, various embodiments are provided to more fully describe the present invention to those skilled in the art. The shape and size of elements in the drawings may be exaggerated for clarity.

Below, we can present the optical characterization of diabetic RBCs using non-invasive methods using three-dimensional (3D) quantitative phase images. 3D refractive index and 2D time-series phase images were measured to quantitatively determine parameters that are morphological (volume, surface area and spherical formation), biochemical (hemoglobin concentration and content), and mechanical (membrane tremor) You can search. Through the ability to measure the characteristics of individual cells simultaneously, a systematic correlation analysis can be performed on the detected red blood cell parameters.

In this measure, diabetic patients have reduced cell spheroidicity and higher intracellular hemoglobin concentration and content of erythrocytes compared to healthy volunteers. In addition, the membrane deformability of diabetic red blood cells is much lower than that of healthy red blood cells. Normal red blood cells have a strong negative correlation between HbA1c and cell membrane tremor (oscillation) in the red blood cell cytoplasm, but red blood cells in diabetic patients are less likely. In these observations, it can be confirmed that the hemoglobin of hemoglobin and the glycation of the membrane protein due to hyperglycemia remarkably lower the cell membrane elasticity of the erythrocytes of diabetic patients.

Quantitative phase imaging (QPI) technology can be used to measure morphological, biochemical, and membrane mechanical parameters in individual red blood cells of diabetic patients. QPI is an interferometric imaging technique that can accurately and quantitatively measure living cells and tissues using refractive index (RI), a material's inherent optical property.

Recent QPI techniques have been used in a variety of biomedical applications, including malaria infection. Blood, nerve, and sickle cell disease can be quantitatively assayed for label-free live erythrocytes using QPI technology and provide information about the time series of the 3D refractive index (RI) monolayers and the 2D phase maps of individual cells .

Quantitative measurement of cell morphology (volume, surface area, and spherulization), biochemical (Hb concentration and content), and cell membrane mechanical (cell membrane tremor) parameters can be determined from the measured three-dimensional refractive index information of cells. In addition, correlation analysis between six measured RBC parameters can be systematically performed, and information on the independently measured HbA1c level can be analyzed.

To reconstruct the 3D shape of individually measured red blood cells, a QPI technique called common-path diffraction optical tomography (cDOT) can be used. cDOT adopts the principle of optical diffraction tomography to extract 3D refractive index information of cells and tissues in a manner similar to X-ray computerized tomography. The measured value of the cytoplasmic refractive index of erythrocytes Since the hemoglobin concentration is directly proportional to the hemoglobin concentration with known proportional count cells, the refractive index increase and the red blood cell refractive index value can be directly related to the hemoglobin concentration.

Hereinafter, an apparatus for measuring glycated hemoglobin using optical characteristics of red blood cells according to one embodiment will be described in detail.

An apparatus for measuring glycated hemoglobin using optical characteristics of erythrocytes according to an exemplary embodiment may include a light source, a medium, and a measurement unit. The apparatus for measuring glycated hemoglobin using optical characteristics of red blood cells according to an embodiment may further include a discriminator.

The light source can cause light to enter the sample. That is, the light source can irradiate the sample with light. For example, a laser can be used as a light source, and the light source can irradiate a laser beam onto a sample of blood or the like to be measured.

Here, the sample may be an object to be measured, for example, an object containing blood, red blood cells, or the like. For example, the sample may be a blood or blood diluted specimen.

The light source used may utilize a single wavelength laser.

The medium is capable of receiving or arranging a predetermined amount of blood and transmitting or reflecting the light source. For example, the medium is fibrous in paper or fiber form, and can be smeared with raised blood. Further, the medium is made of glass, plastic, or the like, and blood collected at the upper portion can be placed.

When the light is irradiated to the medium in which the blood is accommodated or placed, light may be scattered depending on the cell membrane vibrations (vibrations) of the red blood cells, and may be shaken in a specific pattern. Thus, it is possible to judge the possibility of a diabetic patient by measuring the shaking of the light through the measuring part and checking the surface vibrations of the red blood cells.

FIGS. 1 to 3 are views showing examples of a medium in an apparatus for measuring glycated hemoglobin using optical characteristics of erythrocytes according to an embodiment.

Referring to FIG. 1, the medium may be a transparent slide 100 having a predetermined amount of blood 110 dropped thereon. At this time, the transparent slide may be made of glass or plastic material.

Referring to FIG. 2, the medium may be a micro fluidic channel 200 that drops a predetermined amount of blood. The microfluidic channel can be fabricated using a flexible and rapid surface micromachining technique and can be made of glass or plastic material.

Referring to FIG. 3, the medium may be a fibrous non-uniform medium 300 made of a paper or polymer that has dropped a predetermined amount of blood.

The measuring part can measure the intensity vibration of light transmitted through or reflected from the medium. The measurement unit comprises a device capable of measuring a time change of an optical signal scattered in red blood cells. The measurement unit measures a 2D or 1D time-series optical signal scattered in the cell, Vibration can be confirmed.

In other words, the measuring unit is composed of a 2D image equipment or a 1D optical signal detector, and can measure a signal related to the surface vibrations of the red blood cells by measuring the intensity vibration of light transmitted through or reflected from the medium through time-series optical signal measurement. Here, the two-dimensional image equipment may be a CCD, a sCMOS image sensor, and the one-dimensional optical signal detector may be a photodetector, a photodiode, or the like.

For example, the measuring unit may be a CCD, and a CCD may be mounted to measure the shaking of the light to confirm the surface vibrations of the red blood cells. As described above, the device for measuring HbA1c using the optical characteristics of red blood cells can be implemented as a simple device using a laser light source and a CCD, so that the possibility of diabetic patients can be judged by primary screening.

According to current diagnostic criteria, diabetic patients have a glycated hemoglobin concentration of 6.5% or more, regardless of the degree of tremor is 40-50 nm. Therefore, a user such as a doctor may use the apparatus to determine that the measurement is normal when the blood is measured in the blood of 50 nm or more. That is, it is possible to judge the possibility of a diabetic patient by a quick primary diagnosis at a low cost.

FIGS. 4 to 7 are views showing measurement examples of an apparatus for measuring glycated hemoglobin using optical characteristics of erythrocytes according to an embodiment.

Referring to FIG. 4, the light source is irradiated to be totally reflected by the medium 400, and the measuring unit can measure the vibration of the scattered light generated in the blood 410 disposed on the upper part of the medium as the total reflection occurs in the lower part of the medium . In this case, the blood 410 is disposed on the upper part of the medium 400, and the blood 410 is totally reflected on the lower part, so that the measurement can be performed sensitively.

Referring to FIG. 5, the light source is irradiated to transmit the medium 500, and the measuring unit may measure the vibration of the transmitted light 520 transmitted through the medium 500 in which the blood is disposed. That is, the vibration of the blood contained in or disposed in the medium 500 is measured by measuring the vibration of the transmitted light 520 irradiated with the incident light 510 from the light source toward the medium 500 and transmitted through the medium 500 can do.

6, the incident light 610 is irradiated to the medium 600 to be transmitted through the light source, and the measuring unit can measure the vibration of the diffracted light 620 transmitted through the medium 600 in which the blood is disposed and diffracted have.

The measuring unit 600 irradiates the medium 600 with the incident light 610 from the light source and measures the vibration of the refracted light 620 through the medium 600 in which the blood is disposed. It is possible to measure the vibration of the blood accommodated or disposed in the living body.

Referring to FIG. 7, incident light 710 from the light source is irradiated toward the medium 700, and the vibration of the reflected light 720 reflected by the medium 700 in the measurement unit can be measured.

Meanwhile, the apparatus for measuring glycosylated hemoglobin using optical characteristics of red blood cells according to an embodiment may further include a discrimination unit.

The discriminator can determine the possibility of a diabetic patient by analyzing the intensity magnitude of the measured light intensity according to predetermined criteria. Here, the discriminator can be a system for judging whether or not the diabetic patient can be read. At this time, if there is no separate determination section, the user can determine the possibility of the diabetic patient according to the result measured by the measurement section.

According to the embodiments, it is possible to diagnose diabetes using an optical characteristic of diabetic red blood cells which discriminates the diabetes by identifying the suspicion of diabetes by accepting blood in the medium and irradiating the light and shaking the light, thereby promptly notifying the diabetic risk group In addition, this device can be miniaturized, can be carried easily, and can be manufactured at low cost.

FIG. 8 is a flowchart illustrating a method of measuring the HbA1c concentration using the optical characteristics of erythrocytes according to an embodiment.

Referring to FIG. 8, in the method of measuring the HbA1c concentration using the optical characteristics of erythrocytes according to an embodiment, a predetermined amount of blood is placed on a medium 810, a light source is irradiated on the medium 820, A step 830 of measuring the intensity of light transmitted through or reflected from the medium, and a step 840 of determining whether the diabetic patient is feasible by analyzing the magnitude of the measured intensity of the light according to a predetermined criterion .

Therefore, by checking the surface vibration of the red blood cells by measuring the shaking of the light after irradiating the blood with the light, it is possible to discriminate the diabetic first by the simple method.

Hereinafter, a method for measuring a glycated hemoglobin concentration using the optical characteristics of erythrocytes according to an embodiment will be described in more detail.

The method of measuring the HbA1c concentration using the optical characteristics of red blood cells according to an embodiment of the present invention can be more specifically illustrated by using an apparatus for measuring HbA1c concentration using the optical characteristics of red blood cells according to the embodiment described above. Meanwhile, an apparatus for measuring glycated hemoglobin using optical characteristics of erythrocytes according to an exemplary embodiment may include a light source, a medium, and a measurement unit. The apparatus for measuring glycated hemoglobin using optical characteristics of red blood cells according to an embodiment may further include a discriminator. Here, the method of measuring the HbA1c concentration using the optical characteristics of red blood cells according to one embodiment may be performed by the diabetes diagnostic system using the apparatus for measuring HbA1c concentration using the optical characteristics of red blood cells according to one embodiment.

In step 810, the sample to be measured may be placed on the medium. For example, the sample can be blood, wherein the blood can include red blood cells. That is, a predetermined amount of blood or diluted blood to be measured may be placed on the medium.

For example, the medium may be a transparent slide, and the blood to be measured may be placed on the medium by dropping a predetermined amount of blood on the transparent slide. At this time, the transparent slide may be made of glass or plastic.

As another example, the medium may be a micro fluidic channel, and a predetermined amount of blood may be dropped on the microfluidic channel to place the blood on the medium. The microfluidic channel may be made of glass or plastic.

As another example, the medium may be composed of a fibrous nonuniform medium, and a predetermined amount of blood may be dropped on a fibrous nonuniform medium to place the blood to be measured on the medium . In this case, the non-uniform medium of the fibrous shape may be composed of paper or a polymer or the like.

In step 820, light (laser) may be applied to the medium in the light source.

In step 830, the intensity of light transmitted through or reflected by the medium in the measurement unit can be measured.

For example, the light source may be irradiated so as to transmit the medium, and the vibration of the transmitted light transmitted through the medium in which the blood is disposed may be measured.

As another example, it is possible to irradiate a light source so as to transmit the medium, and to measure the vibration of the diffracted light or the refracted light that is diffracted or refracted through the medium in which the blood is arranged.

As another example, the light source may be irradiated toward the medium, and the vibration of the reflected light reflected on the medium in which the blood is disposed may be measured.

As another example, the light source may be irradiated so as to be totally reflected on the medium, and the vibration of the scattered light generated in the blood disposed on the upper part of the medium may be measured as total reflection occurs in the lower part of the medium.

Meanwhile, the apparatus for measuring glycosylated hemoglobin using optical characteristics of red blood cells according to an embodiment may further include a discrimination unit.

In step 840, the determination unit may determine the possibility of a diabetic patient by analyzing the intensity magnitude of the measured light intensity according to a predetermined criterion. Here, the discriminator can be a system for judging whether or not the diabetic patient can be read. At this time, if there is no separate determination section, the user can determine the possibility of the diabetic patient according to the result measured by the measurement section.

Non-invasive methods can be used to provide diabetes diagnostic techniques using the optical properties of diabetic red blood cells. In other words, the embodiments can determine the suspicion of diabetes by a simple method by checking the surface vibrations of the red blood cells by measuring the shaking of the light after irradiating the blood with light, so that the suspect of diabetes can be judged promptly at low cost.

FIG. 9 is a diagram illustrating a reconstructed 3D refractive index tomographic image of healthy red blood cells and diabetic red blood cells according to an embodiment.

Referring to FIGS. 9A and 9B, RI distribution and RI isosurface rendering of representative normal red blood cells and diabetic red blood cells reconstructed according to an exemplary embodiment are shown.

More specifically, a cross-sectional image (along the x-y, z-y, and x-z planes) of a 3D refractive index distribution tomogram of erythrocytes in healthy case (a1) and diabetes case (b1). Isosurfaces (n> 1.35) of the refractive index corresponding to red blood cells in the healthy case (a2) and the diabetic case (b2).

FIG. 9C can illustrate a flow chart for retrieval of six red blood cell parameters according to one embodiment.

Figure 9c shows the procedure required for the detection of quantitative erythrocyte parameters, wherein morphological parameters (cell volume, surface area, and spherical volume and surface area) can be obtained directly from tomography from the reconstructed 3D refractive index profile.

Here, sphericity is a dimensionless number defined by the normalized volume to surface area ratio, which indicates how close to the sphere the cell is. A perfect sphere and a flat disk have sphericity of 1 and 0, respectively. The cytoplasmic hemoglobin concentration of red blood cells (RBC) can be extracted from the measured refractive index values. The red blood cell cytoplasm is composed mainly of hemoglobin solution, and there is a linear relationship of known proportional constant between the refractive index of hemoglobin solution and hemoglobin concentration. The extracted hemoglobin concentration and cell volume provide information on the hemoglobin content in the cytoplasm.

Laser irradiation is set to be orthogonal to red blood cells, and a high-speed camera can continuously measure optical phase delay due to cell membrane tremors. And the dynamic membrane variation of each cell can be calculated from 2D phase variation and can mean the refractive index value from the reconstructed 3D refractive tomography. Thereafter, real-time red cell erosion information can be obtained from red blood cell refractive index information and continuously measured 2D cell membrane phase information. Recently, it has been known that such tremor of erythrocyte membrane is affected by various pathophysiological conditions.

In order to resolve the morphological and biochemical changes of human red blood cells by diabetes, three morphologic (volume, surface area, and spherical formation) and two biochemical (cytoplasmic hemoglobin concentration and Hemoglobin content) red blood cell parameters.

FIG. 10 is a diagram for explaining morphological and biochemical parameters for all erythrocytes measured in normal and diabetic patients according to one embodiment.

10, (a) volume, (b) surface area, (c) spherical shape, (d) cytoplasmic hemoglobin concentration, and hemoglobin concentration of morphological and biochemical parameters for all red blood cells measured in normal and diabetic patients, And (e) hemoglobin content. Each circle represents an individual erythrocyte measurement. Horizontal lines and error bars represent the calculated mean and sample standard deviation. The blue dotted line indicates the result of a complete blood count test.

As shown in FIG. 10A, there is no statistically significant difference in the volume distribution of healthy red blood cells and diabetic red blood cells. The mean volumes of healthy red blood cells and diabetic red blood cells were 90.5 ± 11.4 (mean ± SD) and 90.2 ± 10.9 fL, respectively. Diabetic erythrocytes may have a statistically higher surface area than some healthy red blood cells (p value <0.01).

The average surface areas of healthy red blood cells and diabetic red blood cells are 144.1 ± 17.4 and 148.2 ± 14.4 μm ^2, respectively. The calculated mean sphere values of healthy red blood cells and diabetic red blood cells were 0.68 ± 0.06 and 0.66 ± 0.05, respectively. Enlarged membrane surface area of diabetic red blood cells mainly accounts for a significant decrease in spherical red blood cells.

Figures 10d and 10e show the hemoglobin concentration and hemoglobin content of healthy red blood cells and diabetic red blood cells, respectively. Red blood cells in diabetic patients show significantly elevated cytoplasmic hemoglobin concentration compared to normal red blood cells (p value <0.001). The calculated mean hemoglobin concentrations of normal red blood cells and diabetic red blood cells are 33.4 ± 2.8 and 34.6 ± 2.7 g / dL, respectively.

The cytoplasmic hemoglobin content of diabetic RBCs has a p-value of about 0.03, which is slightly higher than that of normal red blood cells. The average hemoglobin content of normal healthy red blood cells and diabetic red blood cells was 30.3 ± 4.8 and 31.2 ± 4.8 pg, respectively.

The optical measurements for cytoplasmic hemoglobin content are in good agreement with the mean hemoglobin values of the blood donors, which can be measured independently using a complete blood counting machine (blue dotted line in FIG. 10).

The glycated hemoglobin (HbA1c) reflects the degree of hyperglycemia. The level of glycated hemoglobin is defined as the ratio of glycated hemoglobin to the total amount of hemoglobin in the blood. Since glycosylated hemoglobin is formed through the course of 120 days of nonenzymatic glycosylation, glycated hemoglobin is recognized as an effective means of estimating the individual glucose concentration over the last 3 months.

The mean values of membrane fluctuations for erythrocytes were 59.7 ± 6.2, 58.3 ± 4.9, 55.0 ± 5.4, 57.1 ± 7.4, 51.0 ± 6.8, and 49.6 ± 4.6 nm in the order of increasing glycosylated hemoglobin, In the order of increasing glycosylated hemoglobin, the patients were 45.1 ± 4.0, 46.9 ± 3.4, 48.8 ± 4.0, 47.6 ± 4.2, 43.0 ± 4.1, and 48.0 ± 5.0 nm, respectively.

We report a negative correlation between the measured hemoglobin concentration and the level of cell deformation index using a microcapillary model system, indicating that there is a negative correlation between measured erythrocyte membrane tremor and glycated hemoglobin.

11 is a view for explaining a 2D membrane height map of normal red blood cells and diabetic red blood cells according to one embodiment. 12 shows an example of a box graph of cell membrane tremor for erythrocytes measured from a diabetic patient according to one embodiment.

Referring to FIG. 12, a box graph of cell membrane tremor for erythrocytes measured from 6 healthy subjects and 6 diabetic patients in the order of increasing glycosylated hemoglobin is shown. The box is a median with upper and lower quartiles. The short horizontal line and the error bars on the graph of each box represent the mean value and the standard deviation of each individual cell measurement (N = about 40 per group).

13 is a view for explaining various erythrocyte parameters of healthy normal red blood cells and diabetic red blood cells according to one embodiment.

13 shows the scattering of various erythrocyte parameters of healthy red blood cells and diabetic red blood cells. The hemoglobin content versus cell volume (a1 - a3), cell membrane morphology (b1 - b3) And the cytoplasmic hemoglobin concentration (c1 - c3).

Thus, it is possible to quantitatively measure the 3D morphological, biochemical, and mechanical properties of diabetic red blood cells at the individual cell unit cell level. Previously, quantitative phase imaging technology was used to study red blood cell diabetes, but none of the existing techniques could comprehensively parameterize these parameters. All previous work combines biochemical and morphological information together and is limited to 2D-stage imaging and can not be retrieved.

As described above, the optical characterization of diabetic RBCs in diabetic patients can be presented by a non-invasive method using 3D quantitative phase images. (Volume, surface area, and spherical), biochemical (hemoglobin concentration and content), and mechanical (cell membrane tremor) parameters of the cell membrane can be quantitatively measured in individual cell units by measuring the 3D refractive index tomography and 2D time- . You can search at the cell level. Systematic correlation analysis of retrieved RBC parameters can also be performed through the ability to simultaneously measure the characteristics of individual cells.

In this measure, diabetic patients have reduced cell spheroidicity and higher intracellular hemoglobin concentration and content of erythrocytes compared to healthy volunteers. In addition, the membrane deformability of diabetic red blood cells was measured to be much lower than that of healthy erythrocytes. Healthy red blood cells have a strong correlation between high glycosylated hemoglobin and reduced cellular deformation in red blood cell cytoplasm, whereas diabetic red blood cells have no correlation. In addition, normal red blood cells have a strong negative correlation between HbA1c and cell membrane tremor in red blood cell cytoplasm, but red blood cells in diabetic patients are less severe. In these measurements, the hemoglobin and membrane protein glycation by hyperglycemia can be judged as a significant reduction of erythrocyte deformability by the deformability of erythrocytes in diabetic patients.

The apparatus described above may be implemented as a hardware component, a software component, and / or a combination of hardware components and software components. For example, the apparatus and components described in the illustrative embodiments may be implemented within a processor, a controller, an arithmetic logic unit (ALU), a digital signal processor, a microcomputer, a field programmable array (FPA) a programmable logic unit, a microprocessor, or any other device capable of executing and responding to instructions. The processing device may execute an operating system (OS) and one or more software applications running on the operating system. The processing device may also access, store, manipulate, process, and generate data in response to execution of the software. For ease of understanding, the processing apparatus may be described as being used singly, but those skilled in the art will recognize that the processing apparatus may have a plurality of processing elements and / As shown in FIG. For example, the processing apparatus may comprise a plurality of processors or one processor and one controller. Other processing configurations are also possible, such as a parallel processor.

The software may include a computer program, code, instructions, or a combination of one or more of the foregoing, and may be configured to configure the processing device to operate as desired or to process it collectively or collectively Device can be commanded. The software and / or data may be in the form of any type of machine, component, physical device, virtual equipment, computer storage media, or device , Or may be embodyed temporarily. The software may be distributed over a networked computer system and stored or executed in a distributed manner. The software and data may be stored on one or more computer readable recording media.

The method according to an embodiment may be implemented in the form of a program command that can be executed through various computer means and recorded in a computer-readable medium. The computer-readable medium may include program instructions, data files, data structures, and the like, alone or in combination. The program instructions to be recorded on the medium may be those specially designed and configured for the embodiments or may be available to those skilled in the art of computer software. Examples of computer-readable media include magnetic media such as hard disks, floppy disks and magnetic tape; optical media such as CD-ROMs and DVDs; magnetic media such as floppy disks; Magneto-optical media, and hardware devices specifically configured to store and execute program instructions such as ROM, RAM, flash memory, and the like. Examples of program instructions include machine language code such as those produced by a compiler, as well as high-level language code that can be executed by a computer using an interpreter or the like.

While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the invention is not limited to the disclosed exemplary embodiments. For example, it is to be understood that the techniques described may be performed in a different order than the described methods, and / or that components of the described systems, structures, devices, circuits, Lt; / RTI &gt; or equivalents, even if it is replaced or replaced.

Therefore, other implementations, other embodiments and equivalents to the claims are within the scope of the following claims.

Claims (14)

Irradiating a light source to a medium in which blood is accommodated or placed;
Measuring intensity oscillation of light transmitted through or reflected from the medium; And
Determining the possibility of a diabetic patient by analyzing the magnitude of the measured intensity of the light according to a predetermined criterion
Lt; / RTI &gt;
The step of measuring the intensity oscillation of light transmitted through or reflected from the medium may include:
The vibration of the diffracted light or the refracted light transmitted through the medium in which the blood is disposed or diffracted or refracted through the medium is measured, or the vibration of the reflected light reflected on the medium in which the blood is disposed is measured, Check the surface vibration,
The step of determining the possibility of a diabetic patient by analyzing the intensity magnitude of the light according to a preset reference,
And measuring the glycosylated hemoglobin concentration using the correlation of the glycosylated hemoglobin concentration in erythrocytes according to the surface vibration of the erythrocyte membrane to determine the possibility of the diabetic patient. The method according to claim 1,
Further comprising the step of placing a predetermined amount of blood on the medium,
Wherein the step of disposing a predetermined amount of blood on the medium comprises:
To drop a predetermined amount of blood on a transparent slide
And measuring the concentration of glycated hemoglobin using the optical characteristics of erythrocytes. The method according to claim 1,
Further comprising the step of placing a predetermined amount of blood on the medium,
Wherein the step of disposing a predetermined amount of blood on the medium comprises:
Dropping a predetermined amount of blood on a microfluidic channel
And measuring the concentration of glycated hemoglobin using the optical characteristics of erythrocytes. The method according to claim 1,
Further comprising the step of placing a predetermined amount of blood on the medium,
Wherein the step of disposing a predetermined amount of blood on the medium comprises:
Dropping a predetermined amount of blood on a fibrous non-uniform medium made of paper or polymer
And measuring the concentration of glycated hemoglobin using the optical characteristics of erythrocytes. The method according to claim 1,
Wherein the step of irradiating the medium with a light source comprises:
Irradiating the light source toward the medium in which the blood is received or placed in a non-invasive manner
And measuring the concentration of glycated hemoglobin using the optical characteristics of erythrocytes. The method according to claim 1,
Wherein the step of irradiating the medium with a light source comprises:
Irradiating the light source to be totally reflected on the medium,
The step of measuring the intensity oscillation of light transmitted through or reflected from the medium may include:
And measuring the vibration of the scattered light generated in the blood arranged on the upper part of the medium as the total internal reflection is generated in the lower part of the medium
And measuring the concentration of glycated hemoglobin using the optical characteristics of erythrocytes. A light source which is irradiated so that blood is permeated through a medium accommodated or arranged; And
A measurement unit for measuring intensity vibration of light transmitted through or reflected from the medium,
Lt; / RTI &gt;
The magnitude of the measured intensity of the light is analyzed according to a predetermined standard to determine the possibility of a diabetic patient,
Wherein the measuring unit comprises:
The vibration of the diffracted light or the refracted light transmitted through the medium in which the blood is disposed or diffracted or refracted through the medium is measured, or the vibration of the reflected light reflected on the medium in which the blood is disposed is measured, Check the surface vibration,
And determining the possibility of a diabetic patient by measuring the glycated hemoglobin concentration using the correlation of the glycated hemoglobin concentration in the red blood cell with the surface vibration of the erythrocyte cell membrane. 8. The method of claim 7,
Wherein the medium comprises:
A transparent slide with a predetermined amount of blood dropped
Wherein the hemoglobin concentration is measured using the optical characteristics of red blood cells. 8. The method of claim 7,
Wherein the medium comprises:
Being a microfluidic channel that has dropped a predetermined amount of blood
Wherein the hemoglobin concentration is measured using the optical characteristics of red blood cells. 8. The method of claim 7,
Wherein the medium comprises:
A fibrous nonuniform medium consisting of a paper or polymer dropped a predetermined amount of blood
Wherein the hemoglobin concentration is measured using the optical characteristics of red blood cells. 8. The method of claim 7,
Further comprising a determination unit,
Wherein,
The measured intensity of the intensity of light is analyzed according to a predetermined standard to determine the possibility of a diabetic patient and the concentration of glycated hemoglobin is measured using the correlation of the concentration of glycosylated hemoglobin in erythrocytes according to the surface vibration of the erythrocyte membrane To determine the likelihood of a diabetic patient
Wherein the hemoglobin concentration is measured using the optical characteristics of red blood cells. 8. The method of claim 7,
The light source includes:
Being irradiated towards the medium in which the blood is received or placed in a non-invasive manner
Wherein the hemoglobin concentration is measured using the optical characteristics of red blood cells. delete 8. The method of claim 7,
The light source includes:
Irradiated to be totally reflected on the medium,
Wherein the measuring unit comprises:
And measuring the vibration of the scattered light generated in the blood arranged on the upper part of the medium as total reflection occurs in the lower part of the medium
Wherein the hemoglobin concentration is measured using the optical characteristics of red blood cells.

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