KR102500415B1 - Non-invasive hba1c and blood glucose measurement method and device using two wavelengths - Google Patents

Abstract

The present invention relates to a non-invasive glycated hemoglobin and blood sugar measuring method by using two wavelengths and a device thereof, the method comprising: a step of collecting a pulse wave (PPG) signal of a measurement target; a step of calculating a first ratio equation by using the strength of the pulse wave signal from two wavelengths different from each other; a step of measuring oxygen saturation (SpO_2) of the measurement target by using the first ratio equation; a step of calculating a second ratio equation by applying the strength of the pulse wave signal at the two wavelengths to the Beer-Lambert's law or the photon diffusion theory; and a step of measuring the glycated hemoglobin or blood sugar of the measurement target by using the second ratio equation and the oxygen saturation. Therefore, glycated hemoglobin and blood sugar may be measured in a precise and easy manner.

Description

Non-invasive glycated hemoglobin and blood glucose measuring device and method using two wavelengths

The present invention relates to a non-invasive glycated hemoglobin measurement technology, and more particularly, to non-invasive glycated hemoglobin using two different wavelengths capable of measuring glycated hemoglobin or blood sugar accurately and easily non-invasively using two different wavelengths. and a method and device for measuring blood sugar.

Diabetes is a metabolic disease characterized by hyperglycemia caused by secretion or dysfunction of insulin necessary for blood sugar control in the body. Chronic hyperglycemia due to diabetes causes damage and malfunction of each organ of the body. In particular, it causes microvascular complications in the retina, kidneys, and nerves, and macrovascular complications such as arteriosclerosis, cardiovascular, and cerebrovascular diseases, resulting in mortality. increases

However, diabetes can reduce the rate of exacerbation or complications of diabetes due to glycemic control, weight loss, and medication. Therefore, diabetic patients need to frequently measure their own blood sugar levels to manage blood sugar levels, and periodically receive glycated hemoglobin (HbA1C) tests, which are a treatment index as important as blood sugar levels in diabetic patients.

The glycated hemoglobin (HbA1c) test is a test to see how much hemoglobin in red blood cells, which plays a role in transporting oxygen in the blood, is glycated. reflects Normal people naturally have glucose, so hemoglobin in our blood is glycated to some extent. Depending on the test method, there is a difference between normal values, but usually up to 5.6% is normal.

In the case of a diabetic patient, since the concentration of glucose in the blood increases, the level of glycated hemoglobin, that is, glycated hemoglobin, also increases. Therefore, the direction of future treatment is determined by looking at this result, which reveals the level of blood sugar management so far.

On the other hand, the conventional method of measuring glycated hemoglobin (HbA1c) is to obtain a capillary blood sample by collecting blood from a vein in the arm of the subject or piercing the fingertip with a small, sharp needle, and using the obtained blood to measure the concentration of glycated hemoglobin (HbA1c). was measured. This invasive glycated hemoglobin measurement method increases the burden of blood collection on measurement subjects, and has problems of providing inaccurate values when red blood cell lifespan is short, pregnancy, or renal disease.

Korean Patent Registration No. 10-0871074 (2008.11.24)

One embodiment of the present invention is to provide a method and apparatus for non-invasively measuring glycated hemoglobin and blood sugar using two different wavelengths, which can accurately and easily measure glycated hemoglobin or blood sugar non-invasively using two different wavelengths. .

Among the embodiments, a non-invasive method for measuring glycated hemoglobin and blood glucose using two wavelengths includes collecting a pulse wave (PPG) signal of a measurement subject; calculating a first ratio equation using the intensity of the pulse wave signal at two different wavelengths; Measuring the oxygen saturation (SpO2) of the measurement subject using the first ratio equation; Calculating a second ratio equation by applying the intensity of the pulse wave signal at the two wavelengths to Beer-Lambert's Law or Photon Diffusion Theory; and measuring glycated hemoglobin or blood sugar of the measurement subject using the second ratio equation and the oxygen saturation.

Calculating the first ratio equation may include calculating the first ratio equation through Equation 1 for the two wavelengths.

[Equation 1]

= d1 - d2이고, d1 및 d2는 각각 혈액이 혈관으로 들어갈 때와 나갈 때의 혈관의 직경이다.)(From here,

= d1 - d2, where d1 and d2 are the diameters of blood vessels when blood enters and leaves the blood vessels, respectively.)

The measuring of the oxygen saturation (SpO2) may include calculating the oxygen saturation (SpO2) through the following Equation 2 based on Equation 1 above.

[Equation 2]

The calculating of the second ratio equation may include defining a first property equation for absorbance of a specific wavelength according to the Beer-Lambert law; and generating the second ratio equation by applying each of the signals at the two wavelengths to the first property equation based on the Beer-Lambert law.

The calculating of the second ratio equation may include defining a second attribution equation related to transmittance or reflectance of a specific wavelength including a total absorption coefficient and a scattering coefficient according to the photon diffusion theory; and generating the second ratio equation by applying each of the signals at the two wavelengths to the second property equation based on the photon diffusion theory.

The measuring of glycated hemoglobin or blood sugar may include calculating the glycated hemoglobin or blood sugar through Equation 3 based on the second ratio equation and the oxygen saturation.

[Equation 3]

(Here, P is the concentration of glycated hemoglobin or blood sugar, R is the second ratio equation, SpO2 is oxygen saturation, and C ₁ to C ₈ are constant parameters, which are set to different values for glycated hemoglobin and blood sugar, respectively. )

The method may further include calibrating by inputting the glycated hemoglobin or blood sugar into a previously built calibration model.

Among the embodiments, a non-invasive HbA1c and blood glucose measuring apparatus using two wavelengths includes a signal collecting unit that collects a pulse wave (PPG) signal of a subject to be measured; a first ratio equation calculation unit calculating a first ratio equation using the intensity of the pulse wave signal at two different wavelengths; An oxygen saturation measurement unit for measuring the oxygen saturation (SpO2) of the measurement subject using the first ratio equation; a second ratio equation calculator calculating a second ratio equation by applying Beer-Lambert's Law or Photon Diffusion Theory to the intensity of the pulse wave signal at the two wavelengths; and a glycated hemoglobin/blood sugar estimator for measuring glycated hemoglobin or blood sugar of the measurement subject using the second ratio equation and the oxygen saturation.

The first ratio equation calculator may calculate the first ratio equation through Equation 4 for the two wavelengths.

[Equation 4]

= d1 - d2이고, d1 및 d2는 각각 혈액이 혈관으로 들어갈 때와 나갈 때의 혈관의 직경이다.)(From here,

= d1 - d2, where d1 and d2 are the diameters of blood vessels when blood enters and leaves the blood vessels, respectively.)

The oxygen saturation measurement unit may calculate the oxygen saturation (SpO2) through Equation 5 below based on Equation 4 above.

[Equation 5]

The second ratio equation calculation unit defines a first property equation related to the absorbance of a specific wavelength according to the Beer-Lambert law, and the signals at the two wavelengths are calculated according to the first property equation based on the Beer-Lambert law. It is possible to generate the second ratio equation by applying

The second ratio equation calculation unit defines a second property equation related to transmittance or reflectance of a specific wavelength including a total absorption coefficient and a scattering coefficient according to the photon diffusion theory, and calculates the second property equation based on the photon diffusion theory. The second ratio equation may be generated by applying each of the signals at the two wavelengths.

The disclosed technology may have the following effects. However, it does not mean that a specific embodiment must include all of the following effects or only the following effects, so it should not be understood that the scope of rights of the disclosed technology is limited thereby.

The method and apparatus for non-invasively measuring glycated hemoglobin and blood sugar using two wavelengths according to an embodiment of the present invention can accurately and easily measure glycated hemoglobin or blood sugar non-invasively using two different wavelengths.

1 is a diagram explaining a glycated hemoglobin and blood glucose measurement system according to the present invention.
FIG. 2 is a diagram illustrating an embodiment of a functional configuration of the HbAlc and blood glucose measurement apparatus of FIG. 1 .
3 is a flowchart illustrating an embodiment of a method for non-invasively measuring glycated hemoglobin and blood glucose according to the present invention.
4 is a diagram explaining the entire process of non-invasively measuring glycated hemoglobin and blood glucose according to the present invention.

Since the description of the present invention is only an embodiment for structural or functional description, the scope of the present invention should not be construed as being limited by the embodiments described in the text. That is, since the embodiment can be changed in various ways and can have various forms, it should be understood that the scope of the present invention includes equivalents capable of realizing the technical idea. In addition, since the object or effect presented in the present invention does not mean that a specific embodiment should include all of them or only such effects, the scope of the present invention should not be construed as being limited thereto.

Meanwhile, the meaning of terms described in this application should be understood as follows.

Terms such as "first" and "second" are used to distinguish one component from another, and the scope of rights should not be limited by these terms. For example, a first element may be termed a second element, and similarly, a second element may be termed a first element.

It should be understood that when an element is referred to as being “connected” to another element, it may be directly connected to the other element, but other elements may exist in the middle. On the other hand, when an element is referred to as being "directly connected" to another element, it should be understood that no intervening elements exist. Meanwhile, other expressions describing the relationship between components, such as “between” and “immediately between” or “adjacent to” and “directly adjacent to” should be interpreted similarly.

Expressions in the singular number should be understood to include plural expressions unless the context clearly dictates otherwise, and terms such as “comprise” or “having” refer to an embodied feature, number, step, operation, component, part, or these. It should be understood that it is intended to indicate that a combination exists, and does not preclude the possibility of the presence or addition of one or more other features, numbers, steps, operations, components, parts, or combinations thereof.

In each step, the identification code (eg, a, b, c, etc.) is used for convenience of explanation, and the identification code does not describe the order of each step, and each step clearly follows a specific order in context. Unless otherwise specified, it may occur in a different order than specified. That is, each step may occur in the same order as specified, may be performed substantially simultaneously, or may be performed in the reverse order.

The present invention can be implemented as computer readable code on a computer readable recording medium, and the computer readable recording medium includes all types of recording devices storing data that can be read by a computer system. . Examples of computer-readable recording media include ROM, RAM, CD-ROM, magnetic tape, floppy disk, and optical data storage devices. In addition, the computer-readable recording medium may be distributed to computer systems connected through a network, so that computer-readable codes may be stored and executed in a distributed manner.

All terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the present invention belongs, unless defined otherwise. Terms defined in commonly used dictionaries should be interpreted as consistent with meanings in the context of the related art, and cannot be interpreted as having ideal or excessively formal meanings unless explicitly defined in the present application.

1 is a diagram explaining a glycated hemoglobin and blood glucose measurement system according to the present invention.

Referring to FIG. 1 , the glycated hemoglobin and blood glucose measuring system 100 may include a user terminal 110 , a glycated hemoglobin and blood sugar measuring device 130 and a database 150 .

The user terminal 110 may directly measure a user's bio-signal or generate and provide related information, and may correspond to a computing device capable of checking results of non-invasive glycated hemoglobin and blood glucose measurement. For example, the user may input information about his/her own bio-signal through the user terminal 110 and directly check the measured HbA1c and blood glucose information through a visualization tool.

In one embodiment, the user terminal 110 may be implemented to directly measure a biosignal from the user. For example, the user terminal 110 may install and run a dedicated application for measuring bio-signals, and collect pulse wave signals related to the user's bio-signals through the application. As another example, the user terminal 110 may operate in conjunction with an external device capable of measuring biosignals. That is, the user terminal 110 can control the operation of the external device and can receive bio signals measured by the external device from the external device.

In addition, the user terminal 110 may be implemented as a smart phone, laptop computer, or computer capable of being connected to the glycated hemoglobin and blood glucose measuring device 130, but is not limited thereto, and may be implemented in various devices such as a tablet PC. there is. The user terminal 110 may be connected to the glycated hemoglobin and blood glucose measurement device 130 through a wired or wireless network, and a plurality of user terminals 110 may be simultaneously connected to the glycated hemoglobin and blood glucose measurement device 130.

The glycated hemoglobin and blood glucose measuring device 130 is a computer or computer capable of performing an operation of measuring glycated hemoglobin or blood sugar of a subject by selecting one of predefined non-invasive methods based on the biosignal of the subject. It can be implemented as a server corresponding to the program. The glycated hemoglobin and blood glucose measuring device 130 may be connected to the user terminal 110 through a wireless network such as Bluetooth or WiFi, and may transmit/receive data with the user terminal 110 through the network. In addition, the glycated hemoglobin and blood glucose measuring device 130 may be implemented to operate in conjunction with a separate external system (not shown in FIG. 1 ) in order to collect data or provide additional functions.

Here, it will be described that the HbAlc and blood glucose measurement device 130 is implemented and operated independently of the user terminal 110, but is not necessarily limited thereto, and the HbAlc and blood glucose measurement device 130 or the user terminal 110 As this logical configuration, it may be implemented in a form that is included in and operated in another device.

The database 150 may correspond to a storage device for storing various pieces of information necessary for the operation of the glycated hemoglobin and blood glucose measurement device 130 . For example, the database 150 may store information about bio-signals collected from the user, information used for Monte Carlo simulation or other non-invasive methods, but is not necessarily limited thereto, and may store glycated hemoglobin and blood sugar. The measurement device 130 may store information collected or processed in various forms in the process of accurately and easily and non-invasively measuring HbA1c or blood sugar using two different wavelengths.

Meanwhile, in FIG. 1, the database 150 is shown as a device independent of the HbAlc and blood glucose measuring device 130, but is not necessarily limited thereto, and is a logical storage device of the HbAlc and blood glucose measuring device 130. Of course, it can be implemented by being included in the glycated hemoglobin and blood glucose measuring device 130 .

FIG. 2 is a diagram explaining the functional configuration of the glycated hemoglobin and blood glucose measuring device of FIG. 1 .

Referring to FIG. 2 , the glycated hemoglobin and blood glucose measurement device 130 includes a signal collection unit 210, a first ratio equation calculation unit 230, an oxygen saturation measurement unit 250, and a second ratio equation calculation unit 270. , a glycated hemoglobin/blood sugar estimation unit 290 and a control unit (not shown in FIG. 2).

However, the glycated hemoglobin and blood glucose measurement device 130 according to an embodiment of the present invention does not have to include all of the above components at the same time, and some of the above components may be omitted or configured according to each embodiment. It may be implemented by selectively including some or all of them. Hereinafter, the operation of each component will be described in detail.

The signal collection unit 210 may collect a pulse wave (PPG) signal of a subject to be measured. That is, the signal collection unit 210 may measure and collect the pulse wave signal, which is one of the bio signals of the measurement subject, and may store and manage the pulse wave signal in the database 150 . Here, the biological signal is a biological signal generated from the activity of living cells and may correspond mainly to electric and magnetic signals, and since the size of the signal is very small, precision measurement technology may be required. For example, the bio-signal may include information that can be collected from a subject to be measured through various measuring devices, such as body temperature, pulse rate, blood pressure, respiration, blood sugar, brain wave, electrocardiogram, and oxygen saturation. Here, measuring and collecting a pulse wave signal of a subject to be measured will be described as an example.

In one embodiment, the signal collection unit 210 may perform a collection operation on the pulse wave signal in conjunction with the user terminal 110, and may operate in conjunction with an independent device for measuring the pulse wave signal, if necessary. The signal collection unit 210 may measure the pulse wave signal by directly contacting the body of the measurement target according to the type of measurement device.

In one embodiment, the signal collection unit 210 may perform a plurality of steps for non-invasively collecting a pulse wave signal from a subject to be measured. More specifically, the signal collection unit 210 irradiates light toward the body part through an LED module located on one side of the body part of the subject to be measured, and transmits light passing through the body part through an optical detection unit located in correspondence with the LED module. Alternatively, the steps of detecting the reflected light reflected from the body part and measuring the pulse wave signals based on the intensity change of the transmitted light or the reflected light may be performed.

Here, the LED module may be implemented as a light source capable of projecting light having a specific wavelength, and may be formed singly or in plurality, and when formed in plurality, each LED module may project light having a different wavelength. can In addition, the LED module may be installed on one side of the body part of the subject to be measured. For example, the LED module may be installed on one side of a body part such as a finger, wrist, wrist, forehead, cheek (cheek), ear, etc. of a subject to be measured, but is not necessarily limited thereto, and depending on installation conditions and skin thickness, the corresponding skin Of course, various body parts capable of detecting capillaries present below may be included.

In addition, the photo detector may correspond to a device capable of measuring light projected from the LED module. The light detection unit may be installed at a location corresponding to the location of the LED module. For example, the light detection unit may be installed at a point opposite to the position of the LED module, or may be installed at a point on the same plane as the position of the LED module. The optical detection unit may detect reflected light or transmitted light derived from incident light via a body part according to a relationship with the position of the LED module, and may measure the intensity of light. Accordingly, the signal collection unit 210 may observe a change in intensity of light measured by the photodetector and measure pulse wave signals based on the change in intensity of light.

The first ratio equation calculation unit 230 may calculate a first ratio equation using intensities of pulse wave signals at two different wavelengths among pulse wave signals. Here, the two wavelengths may correspond to different wavelength values. In addition, the first ratio equation may correspond to an equation for measuring oxygen saturation and may be defined as an equation for a ratio between the same variables defined for different wavelengths.

In one embodiment, the first ratio equation calculation unit 230 may calculate the first ratio equation through Equation 1 for the two wavelengths.

[Equation 1]

는 산소포화도에 관한 제1 비율 방정식이고, λ1 및 λ2는 서로 다른 파장이며, I₀는 입사광의 세기이고, I는 투과광의 세기이다. 또한,

및

는 각각 옥시 헤모글로빈 및 디옥시 헤모글로빈의 몰 흡광계수이고,

및

는 각각 옥시 헤모글로빈 및 디옥시 헤모글로빈의 몰 농도이다. 또한,

= d1 - d2이고, d1 및 d2는 각각 혈액이 혈관으로 들어갈 때와 나갈 때의 혈관의 직경이다.From here,

Is the first ratio equation for oxygen saturation, λ1 and λ2 are different wavelengths, I ₀ is the intensity of incident light, and I is the intensity of transmitted light. also,

and

are the molar extinction coefficients of oxyhemoglobin and deoxyhemoglobin, respectively;

and

are the molar concentrations of oxyhemoglobin and deoxyhemoglobin, respectively. also,

= d1 - d2, where d1 and d2 are the diameters of blood vessels when blood enters and leaves the blood vessels, respectively.

The oxygen saturation measurement unit 250 may measure the oxygen saturation (SpO 2 ) of the measurement subject using the first ratio equation. That is, the oxygen saturation measurement unit 250 may define the oxygen saturation as one unknown in the first ratio equation and then organize it into an equation related to the oxygen saturation, and apply specific values to each variable in the organized equation to determine the oxygen saturation. Specific measured values can be derived.

In one embodiment, the oxygen saturation measurement unit 250 may calculate the oxygen saturation (SpO2) through the following Equation 2 based on Equation 1 above.

[Equation 2]

Meanwhile, the oxygen saturation measurement unit 250 may calculate oxygen saturation using two different wavelengths, for example, by applying a simple curve fitting method to two different wavelengths. can be calculated.

The second ratio equation calculator 270 may calculate the second ratio equation by applying Beer-Lambert's Law or Photon Diffusion Theory to the two wavelengths. That is, the second ratio equation calculation unit 270 may generate a second ratio equation used for measurement of glycated hemoglobin or blood sugar based on two different wavelengths.

In one embodiment, the second ratio equation calculation unit 270 defines a first property equation for the absorbance of a specific wavelength according to the Beer-Lambert law, and based on the Beer-Lambert law, the first property equation at two wavelengths. A second ratio equation may be generated by applying each of the signals of . Here, the first property equation may correspond to an equation for absorbance among properties of a specific wavelength.

More specifically, Beer-Lambert's law can be expressed as Equation 3 below.

[Equation 3]

Here, A is absorbance, N is the number of types of hemoglobin, ε is the molar extinction coefficient, c is the molar concentration of the object through which light is transmitted, d is the light transmission distance, I ₀ is the intensity of the incident light, I is the intensity of the transmitted light.

Also, blood is a homogeneous mixture and may contain different types of hemoglobin. In an embodiment of the present invention, absorbance for oxy-hemoglobin (HbO), deoxy-hemoglobin (HHb), and glycated hemoglobin (HbA1c) can be calculated and utilized.

Accordingly, the second ratio equation calculation unit 270 may calculate the absorbance (A) through Equation 4 below when the incident light passes through the homogeneous mixture.

[Equation 4]

는 당화혈색소의 몰 흡광계수이고,

는 당화혈색소의 몰 농도이다.From here,

is the molar extinction coefficient of glycated hemoglobin,

is the molar concentration of glycated hemoglobin.

In addition, since the diameter of a blood vessel (ie, the penetration distance) repeats expansion and contraction according to the inflow of blood, a difference in the penetration distance (d) of incident light may occur according to the inflow of blood. Accordingly, the second ratio equation calculating unit 270 may derive the following Equation 5 as a first attribute equation for absorbance of a specific wavelength by substituting the change value of the transmission distance for Equation 4 above.

[Equation 5]

는 d₁과 d₂ 사이의 차이값으로 나타낼 수 있다.That is, when blood flows in and out of capillaries, blood vessels expand and contract repeatedly, so the thickness of a finger or the like can be slightly changed. As a result, there is a slight difference in the penetration distance of incident light passing through a finger can happen Accordingly,

can be expressed as a difference between d ₁ and d ₂ .

Thereafter, the second ratio equation calculation unit 270 may generate a second ratio equation by applying each of the signals at two different wavelengths to the first property equation, which is expressed as Equation 6 below. can

[Equation 6]

은 제1 파장값 λ₁을 갖는 입사광을 조사하였을 때

에 상응하는 흡광도이고,

은 제2 파장값 λ₂를 갖는 입사광을 조사하였을 때

에 상응하는 흡광도이다. 즉,

및

는 각각 d1에서의 흡광도와 d2에서의 흡광도의 차이에 상응할 수 있다.Here, λ ₁ and λ ₂ may have different wavelength values. For example, λ ₁ and λ ₂ may correspond to any one of 525 nm, 660 nm, and 950 nm, respectively. also,

When incident light having a first wavelength value λ ₁ is irradiated

is the absorbance corresponding to

When incident light having a second wavelength value λ ₂ is irradiated

is the absorbance corresponding to in other words,

and

may correspond to the difference between the absorbance at d1 and the absorbance at d2, respectively.

Meanwhile, Equation 6 above may be expressed as Equation 6-1 below.

[Equation 6-1]

In addition, the percentage definition of glycated hemoglobin (HbA1c) and oxygen saturation (SpO2) can be expressed as in Equation 6-2 below.

[Equation 6-2]

Also, the above Equation 6-2 can be expressed as the following Equation 6-3.

[Equation 6-3]

Also, the above Equation 6-3 can be expressed as the following Equation 6-4.

[Equation 6-4]

In addition, the above Equation 6-1 can be expressed as the following Equation 6-5 based on the above Equations 6-3 and 6-4.

[Equation 6-5]

이다.From here,

am.

Also, the above Equation 6-5 can be expressed as the following Equation 6-6.

[Equation 6-6]

,

이다.From here,

,

am.

In one embodiment, the second ratio equation calculation unit 270 defines a second property equation for transmittance or reflectance of a specific wavelength including a total absorption coefficient and a scattering coefficient according to the photon diffusion theory, and based on the photon diffusion theory A second ratio equation may be generated by applying each of the two wavelengths to the second property equation. Here, the second property equation may correspond to an equation related to transmittance or reflectance among properties of a specific wavelength.

More specifically, the total absorption coefficient and the total reduced scattering coefficient according to the photon diffusion theory can be expressed as Equations 7 and 8 below.

[Equation 7]

는 총 흡수계수이고, V_a, V_v 및 V_w는 각각 동맥혈 부피량, 정맥혈 부피량 및 물 부피량이고,

,

,

및

는 각각 동맥혈 흡수계수, 정맥혈 흡수계수, 물 흡수계수 및 기준조직 흡수계수이다.From here,

is the total absorption coefficient, V _a, V _v and V _w are arterial blood volume, venous blood volume and water volume, respectively;

,

,

and

are the arterial blood absorption coefficient, the venous blood absorption coefficient, the water absorption coefficient and the reference tissue absorption coefficient, respectively.

[Equation 8]

는 총 감소산란계수이며,

및

은 각각 감소된 혈액 산란계수 및 감소된 피부조직 산란계수이다.From here,

is the total reduced scattering coefficient,

and

are the reduced blood scattering coefficient and the reduced skin tissue scattering coefficient, respectively.

Meanwhile, blood is a homogeneous mixture and includes different types of hemoglobin, oxy-hemoglobin (HbO), deoxy-hemoglobin (HHb), and glycated hemoglobin (HbA1c).

), 정맥혈 흡수계수(

) 및 기준조직 흡수계수(

)는 각각 다음의 수학식 9 내지 11과 같이 표현될 수 있다.Therefore, the arterial blood absorption coefficient in Equation 7 above (

), venous blood absorption coefficient (

) and reference tissue absorption coefficient (

) can be expressed as in Equations 9 to 11, respectively.

[Equation 9]

는 동맥 산소포화도,

는 옥시 헤모글로빈 흡수계수,

는 디옥시 헤모글로빈 흡수계수,

는 당화혈색소 흡수계수이다.From here,

is the arterial oxygen saturation,

is the oxyhemoglobin absorption coefficient,

is the deoxyhemoglobin absorption coefficient,

is the glycated hemoglobin absorption coefficient.

[Equation 10]

는 정맥 산소포화도이다.From here,

is the venous oxygen saturation.

[Equation 11]

Meanwhile, Equations 9 and 10 above may be derived from Equation 12 below.

[Equation 12]

는 동맥 산소포화도(

)와 정맥 산소포화도(

)를 포함한다.From here,

is the arterial oxygen saturation (

) and venous oxygen saturation (

).

Thereafter, the second ratio equation calculation unit 270 may generate a second property equation for transmittance of a specific wavelength by applying spherical geometry to the total absorption coefficient and the total reduced scattering coefficient according to the photon diffusion theory. Since the arrangement of spherical geometry is a well-known technique that can be easily performed by those skilled in the art, a description thereof will be omitted. That is, the second ratio equation calculation unit 270 may derive a second property equation for transmittance of a specific wavelength as shown in Equation 13 below.

[Equation 13]

는 투과광의 세기이고, α는 감쇄계수이며,

는 PPG 신호의 피크(peak)값과 밸리(valley)값에서의 광의 세기의 차이이다. PPG 신호는 혈관 내에서의 혈액의 흐름에 따라 변화할 수 있고, 혈액이 모세혈관 내에 최대로 들어오는 밸리(valley) 시점에 최소값을 가질 수 있다. 즉, 모세혈관은 팽창하게 되어 광의 투과거리(d)는 증가할 수 있다. 이와 반대로, PPG 신호는 혈액이 모세혈관에서 최대로 나가는 피크(peak) 시점에 최대값을 가질 수 있다. 즉, 모세혈관은 수축하게 되어 광의 투과거리(d)는 감소할 수 있다. 한편, 감쇄계수는 총 흡수계수 및 총 감소산란계수에 의해 단순화될 수 있으며,

와 같이 표현될 수 있다.From here,

is the intensity of the transmitted light, α is the attenuation coefficient,

Is the difference between the intensity of light at the peak and valley values of the PPG signal. The PPG signal may change according to the flow of blood in the blood vessel, and may have a minimum value at a valley point in time when blood enters the capillary to the maximum. That is, the capillaries are expanded, so that the light transmission distance (d) can be increased. Conversely, the PPG signal may have a maximum value at a peak time when blood is maximally expelled from the capillaries. That is, capillaries are contracted, so that the light transmission distance (d) may decrease. On the other hand, the attenuation coefficient can be simplified by the total absorption coefficient and the total reduction scattering coefficient,

can be expressed as

Thereafter, the second ratio equation calculation unit 270 may generate a second ratio equation by applying each of the signals at two different wavelengths to the second attribute equation for transmittance, and the following Equation 14 can be expressed as

[Equation 14]

는 제1 파장값 λ₁을 갖는 입사광을 조사하였을 때의 투과도이고,

는 제2 파장값 λ₂를 갖는 입사광을 조사하였을 때의 투과도이다.From here,

Is the transmittance when incident light having a first wavelength value λ ₁ is irradiated,

Is transmittance when incident light having a second wavelength value λ ₂ is irradiated.

In addition, the second ratio equation calculation unit 270 applies spherical geometry to the total absorption coefficient and the total reduced scattering coefficient according to the photon diffusion theory in the same manner as the transmittance to generate a second property equation for the reflectivity of a specific wavelength. can That is, the second ratio equation calculation unit 270 may derive the second property equation for reflectivity of a specific wavelength as shown in Equation 15 below.

[Equation 15]

는 확산광의 세기이고,

는 PPG 신호의 피크(peak)값과 밸리(valley)값에서의 광의 세기의 차이이다.From here,

is the intensity of the diffuse light,

Is the difference between the intensity of light at the peak and valley values of the PPG signal.

Thereafter, the second ratio equation calculation unit 270 may generate a second ratio equation by applying each of the signals at two different wavelengths to the second property equation for reflectivity, and the following Equation 16 can be expressed as

[Equation 16]

는 제1 파장값 λ₁을 갖는 입사광을 조사하였을 때의 반사도이고,

는 제2 파장값 λ₂를 갖는 입사광을 조사하였을 때의 반사도이다.From here,

Is reflectivity when incident light having a first wavelength value λ ₁ is irradiated,

Is the reflectivity when incident light having the second wavelength value λ ₂ is irradiated.

The glycated hemoglobin/blood sugar estimator 290 may measure glycated hemoglobin or blood sugar of the measurement subject using the second ratio equation and oxygen saturation. In this case, the measurement process for blood sugar may be performed in the same manner as the measurement process for glycated hemoglobin, and the measurement process for glycated hemoglobin will be described in detail here.

In one embodiment, the glycated hemoglobin/blood sugar estimator 290 may calculate glycated hemoglobin or blood sugar through Equation 17 based on the second ratio equation (R) and oxygen saturation.

[Equation 17]

Here, P is the concentration of glycated hemoglobin or blood sugar, R is the second ratio equation, SpO2 is oxygen saturation, and C ₁ to C ₈ are constant parameters, each set to different values for glycated hemoglobin and blood sugar. That is, P _HbA1c is the concentration of glycated hemoglobin, and P _G is the concentration of blood glucose.

Thereafter, the glycated hemoglobin/blood sugar estimator 290 may calculate the glycated hemoglobin or blood sugar of the measurement subject based on P _HbA1c obtained through Equation 17 above. For example, the % value of glycated hemoglobin can be calculated through Equation 18 below.

[Equation 18]

%HbA1c = _PHbA1c × 100

Here, %HbA1c is the final % glycosylated hemoglobin level.

Meanwhile, the glycated hemoglobin/blood sugar estimator 290 may calculate the blood sugar of the measurement subject through the following Equations 19 to 22 based on the second ratio equation (R) and oxygen saturation, and the glycated hemoglobin described above Since it may correspond to the calculation process of , a detailed description thereof will be omitted.

[Equation 19]

및

는 각각 혈당의 몰 흡광계수 및 몰 농도이다.From here,

and

are the molar extinction coefficient and molar concentration of blood glucose, respectively.

[Equation 20]

[Equation 21]

[Equation 22]

= 150/64500 mol/dm³이고,

는 최종 혈당 수치이다.From here,

= 150/64500 mol/dm ³ ,

is the final blood glucose level.

In one embodiment, the glycated hemoglobin/blood sugar estimator 290 may perform calibration by inputting glycated hemoglobin or blood sugar into a previously built calibration model. In this case, the calibration model may generate a final predicted value for glycated hemoglobin or blood sugar as an output by using a reference value for glycated hemoglobin or blood sugar and an estimated value estimated by the glycated hemoglobin/blood sugar estimator 290 as inputs. there is. The glycated hemoglobin/blood sugar estimator 290 may determine the primarily estimated glycated hemoglobin or blood sugar as it is, but may additionally perform a correction operation to derive a more accurate result.

The control unit (not shown in FIG. 2 ) includes the signal collection unit 210, the first ratio equation calculation unit 230, the oxygen saturation measuring unit 250, the second ratio equation calculation unit 270, and the glycated hemoglobin/blood sugar estimation unit. Control flow or data flow between governments 290 may be managed.

3 is a flowchart illustrating a method for non-invasively measuring glycated hemoglobin and blood sugar according to the present invention.

Referring to FIG. 3 , the glycated hemoglobin and blood glucose measurement apparatus 130 may collect a pulse wave (PPG) signal of the measurement subject through the signal collection unit 210 (step S310). The glycated hemoglobin and blood glucose measurement apparatus 130 may calculate a first ratio equation using the intensities of pulse wave signals at two different wavelengths through the first ratio equation calculator 230 (step S330).

In addition, the glycated hemoglobin and blood glucose measuring device 130 may measure the oxygen saturation (SpO2) of the measurement subject using the first ratio equation through the oxygen saturation measuring unit 250 (step S350). The glycated hemoglobin and blood glucose measuring device 130 uses the second ratio equation calculation unit 270 to calculate the intensity of pulse wave signals at two wavelengths using Beer-Lambert's Law or Photon Diffusion Theory. A second ratio equation may be calculated by applying to (step S370). The glycated hemoglobin and blood glucose measuring device 130 may measure the glycated hemoglobin or blood sugar of the measurement subject using the second ratio equation and oxygen saturation through the glycated hemoglobin/blood sugar estimator 290 (step S390).

4 is a diagram explaining the entire process of non-invasively measuring glycated hemoglobin and blood glucose according to the present invention.

Referring to FIG. 4, the glycated hemoglobin and blood glucose measuring device 130 calculates SpO2 using two different wavelengths, and non-invasively measures glycated hemoglobin or blood sugar of a subject based on SpO2 and the two different wavelengths. can be measured At this time, various methods may be applied to calculate SpO2, and for example, a curve fitting method may be used. The process of estimating glycated hemoglobin or blood sugar may be performed based on Beer-Lambert's law or photon diffusion theory, and the glycated hemoglobin and blood glucose measuring device 130 uses signals at two different wavelengths collected from the measurement subject for each method. It is possible to more accurately determine an estimated value of glycated hemoglobin or blood sugar by applying the method.

Although the above has been described with reference to preferred embodiments of the present invention, those skilled in the art will variously modify and change the present invention within the scope not departing from the spirit and scope of the present invention described in the claims below. You will understand that it can be done.

100: glycated hemoglobin and blood glucose measurement system
110: user terminal 130: glycated hemoglobin and blood sugar measurement device
150: database
210: signal collection unit 230: first ratio equation calculation unit
250: oxygen saturation measurement unit 270: second ratio equation calculation unit
290: glycated hemoglobin/blood sugar estimation unit

Claims (12)

Non-invasive measurement using two wavelengths performed in a non-invasive measuring device using two wavelengths including a signal collection unit, a first ratio equation calculation unit, an oxygen saturation measurement unit, a second ratio equation calculation unit, and a glycated hemoglobin/blood sugar estimation unit. In the measurement method,
Collecting a pulse wave (PPG) signal of a subject to be measured through the signal collection unit;
calculating a first ratio equation defined as a ratio of intensity of the pulse wave signal at two wavelengths having different wavelength values through the first ratio equation calculation unit;
Through the oxygen saturation measuring unit, oxygen saturation is defined as one unknown in the first ratio equation, organized into equations related to the oxygen saturation, and then specific values are applied to each variable to determine the oxygen saturation (SpO2) of the subject to be measured. measuring;
Through the second ratio equation calculating unit, property equations for absorbance, transmittance, or reflectance among properties of a specific wavelength are defined according to Beer-Lambert's Law or Photon Diffusion Theory, and the property equation Calculating a second ratio equation defined as a ratio of the absorbance, transmittance, or reflectance by applying the intensity of the pulse wave signal at the two wavelengths; and
Through the glycated hemoglobin/blood sugar estimator, the concentration of glycated hemoglobin or blood sugar is calculated using the second ratio equation and the mathematical expression related to the oxygen saturation, and the glycated hemoglobin or blood sugar concentration calculated is used to determine the glycation rate of the measurement subject. A non-invasive measurement method using two wavelengths including; measuring hemoglobin or blood sugar.
According to claim 1,
Calculating the first ratio equation
A non-invasive measurement method using two wavelengths, characterized in that it comprises calculating the first ratio equation through the following Equation 1 for the two wavelengths.
[Equation 1]

(From here,

Is the first ratio equation for oxygen saturation, λ ₁ and λ ₂ are different wavelengths, I ₀ is the intensity of incident light, and I is the intensity of transmitted light. also,

and

are the respective wavelengths

It is the change in absorbance for (i = 1, 2) and the intensity of (incident or transmitted) light. also,

and

are the respective wavelengths

is the molar extinction coefficient of oxyhemoglobin and deoxyhemoglobin for

and

are the molar concentrations of oxyhemoglobin and deoxyhemoglobin, respectively. also,

= d1 - d2, where d1 and d2 are the diameters of blood vessels when blood enters and leaves the blood vessels, respectively.)
The method of claim 2, wherein the step of measuring the oxygen saturation (SpO2)
A non-invasive measurement method using two wavelengths, comprising the step of calculating the oxygen saturation (SpO 2 ) through the following Equation 2 based on Equation 1.
[Equation 2]

According to claim 1,
Calculating the second ratio equation
Defining a first property equation for absorbance of a specific wavelength according to the Beer-Lambert law; and
Generating the second ratio equation expressed by Equation 1-1 below by applying each of the signals at the two wavelengths to the first property equation based on the Beer-Lambert law Non-invasive measurement method using two characterized wavelengths.
[Equation 1-1]

(Where R is the second ratio equation,

Is when irradiating incident light having a first wavelength value λ ₁

The absorbance corresponding to ,

is the case when incident light having a second wavelength value λ ₂ is irradiated

is the absorbance corresponding to , I ₀ is the intensity of incident light, I is the intensity of transmitted light, and I(d1) and I(d2) represent the light intensity corresponding to d1 and d2, respectively.)
According to claim 1,
Calculating the second ratio equation
Defining a second property equation for transmittance or reflectance of a specific wavelength including a total absorption coefficient and a scattering coefficient according to the photon diffusion theory; and
Generating the second ratio equation expressed by Equation 1-2 below by applying each of the signals at the two wavelengths to the second property equation based on the photon diffusion theory. Non-invasive measurement method using two characterized wavelengths.
[Equation 1-2]

(Where R is the second ratio equation,

is the intensity of the transmitted light, α is the attenuation coefficient,

Is the difference between the intensity of light at the peak and valley values of the PPG signal,

Is the transmittance when incident light having a first wavelength value λ ₁ is irradiated,

Is transmittance when incident light having a second wavelength value λ ₂ is irradiated.

Is reflectivity when incident light having a first wavelength value λ ₁ is irradiated,

Is the reflectivity when incident light having the second wavelength value λ ₂ is irradiated.

is the total reduced scattering coefficient,

ego,

is the arterial blood absorption coefficient.)
According to claim 1,
The step of measuring glycated hemoglobin or blood sugar
The non-invasive measurement method using two wavelengths, characterized in that it comprises calculating the glycated hemoglobin or blood sugar through the following Equation 3 based on the second ratio equation and the oxygen saturation.
[Equation 3]

(Here, P is the concentration of glycated hemoglobin or blood sugar, R is the second ratio equation, SpO2 is oxygen saturation, and C ₁ to C ₈ are constant parameters, which are set to different values for glycated hemoglobin and blood sugar, respectively. )
According to claim 1,
The non-invasive measurement method using two wavelengths, characterized in that it further comprises; the step of calibrating by inputting the glycated hemoglobin or blood sugar into a previously built calibration model.
a signal collection unit that collects a pulse wave (PPG) signal of a measurement subject;
a first ratio equation calculator calculating a first ratio equation defined as a ratio of the intensity of the pulse wave signal at two wavelengths having different wavelength values;
Oxygen saturation measurement unit for measuring the oxygen saturation (SpO2) of the measurement subject by defining oxygen saturation as one unknown in the first ratio equation, organizing it into an equation for the corresponding oxygen saturation, and then applying a specific value to each variable;
According to Beer-Lambert's Law or Photon Diffusion Theory, property equations for absorbance, transmittance, or reflectance among the properties of a specific wavelength are defined, and the pulse wave at the two wavelengths is defined in the property equation. a second ratio equation calculator calculating a second ratio equation defined as a ratio of the absorbance, transmittance, or reflectance by applying the intensity of the signal; and
Glycated hemoglobin or blood sugar concentration is calculated using the second ratio equation and the equation related to the oxygen saturation, and the glycated hemoglobin or blood sugar of the measurement subject is measured based on the calculated glycated hemoglobin or blood sugar concentration. Non-invasive measuring device using two wavelengths including; blood sugar estimator.
The method of claim 8, wherein the first ratio equation calculator
Non-invasive measuring device using two wavelengths, characterized in that for calculating the first ratio equation through the following Equation 4 for the two wavelengths.
[Equation 4]

(From here,

Is the first ratio equation for oxygen saturation, λ ₁ and λ ₂ are different wavelengths, I ₀ is the intensity of incident light, and I is the intensity of transmitted light. also,

and

are the respective wavelengths

It is the change in absorbance for (i = 1, 2) and the intensity of (incident or transmitted) light. also,

and

are the respective wavelengths

is the molar extinction coefficient of oxyhemoglobin and deoxyhemoglobin for

and

are the molar concentrations of oxyhemoglobin and deoxyhemoglobin, respectively. also,

= d1 - d2, where d1 and d2 are the diameters of blood vessels when blood enters and leaves the blood vessels, respectively.)
10. The method of claim 9, wherein the oxygen saturation measuring unit
Non-invasive measuring device using two wavelengths, characterized in that for calculating the oxygen saturation (SpO 2 ) through the following Equation 5 based on Equation 4.
[Equation 5]

The method of claim 8, wherein the second ratio equation calculator
A first property equation for the absorbance of a specific wavelength is defined according to the Beer-Lambert law, and each of the signals at the two wavelengths is applied to the first property equation based on the Beer-Lambert law to obtain the following equation A non-invasive measuring device using two wavelengths, characterized in that for generating the second ratio equation expressed as 4-1.
[Equation 4-1]

(Where R is the second ratio equation,

Is when irradiating incident light having a first wavelength value λ ₁

The absorbance corresponding to ,

is the case when incident light having a second wavelength value λ ₂ is irradiated

is the absorbance corresponding to , I ₀ is the intensity of incident light, I is the intensity of transmitted light, and I(d1) and I(d2) represent the light intensity corresponding to d1 and d2, respectively.)
The method of claim 8, wherein the second ratio equation calculator
According to the photon diffusion theory, a second property equation related to the transmittance or reflectance of a specific wavelength including the total absorption coefficient and the scattering coefficient is defined, and based on the photon diffusion theory, the second property equation is defined at the two wavelengths. A non-invasive measuring device using two wavelengths, characterized in that for generating the second ratio equation expressed by Equation 4-2 by applying each of the signals.
[Equation 4-2]

(Where R is the second ratio equation,

is the intensity of the transmitted light, α is the attenuation coefficient,

Is the difference between the intensity of light at the peak and valley values of the PPG signal,

Is the transmittance when incident light having a first wavelength value λ ₁ is irradiated,

Is transmittance when incident light having a second wavelength value λ ₂ is irradiated.

Is reflectivity when incident light having a first wavelength value λ ₁ is irradiated,

Is the reflectivity when incident light having the second wavelength value λ ₂ is irradiated.

is the total reduced scattering coefficient,

ego,

is the arterial blood absorption coefficient.)

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