WO2019160272A1

WO2019160272A1 - Non-invasive blood glucose measurement method and non-invasive blood glucose measurement device

Info

Publication number: WO2019160272A1
Application number: PCT/KR2019/001554
Authority: WO
Inventors: 이병수
Original assignee: 주식회사 템퍼스
Priority date: 2018-02-19
Filing date: 2019-02-08
Publication date: 2019-08-22
Also published as: KR102033711B1; KR20190099602A

Abstract

Provided in the present invention are a non-invasive blood glucose measurement method and a non-invasive blood glucose measurement device using the method, the method comprising the steps of: emitting near-infrared rays at skin to be measured so as to raise the temperature of the skin; measuring a mid-infrared spectrum generated by the skin of which the temperature has been increased; and calculating blood glucose level by measuring, from the mid-infrared spectrum, skin temperature, having increased because of the near-infrared rays, and the composition ratio of the mid-infrared spectrum, wherein the mid-infrared spectrum comprises a spectrum of the light emitted by glucose in the blood flowing in the skin.

Description

Non-invasive blood sugar measuring method and non-invasive blood sugar measuring device

The present invention relates to a method and apparatus for measuring blood glucose, and more particularly, to a non-invasive blood sugar measuring method and a non-invasive blood sugar measuring apparatus capable of measuring blood glucose using infrared rays.

Invasive blood glucose measurement measures blood glucose levels by collecting blood from a user through a needle or injection. Thus, an invasive blood glucose meter causes physical pain due to blood collection to a user. In addition, if the invasive blood glucose meter is not cleanly managed, the user may be infected with bacteria and the measurement is difficult at all times, and thus it is difficult to effectively manage blood glucose.

On the other hand, non-invasive blood glucose measurement does not cause physical pain by measuring blood glucose without body blood, and can be measured at all times to effectively manage blood sugar. Various methods have been proposed and studied as non-invasive blood glucose measurement methods, but the methods proposed to be reliable include glucose measurement using infrared spectroscopy using Fourier transform infrared (FTIR) spectrum or Raman spectrum, blood glucose measurement using electromagnetic field, Blood glucose meters using exhalation and blood glucose meters using patches.

Among them, a blood glucose meter using infrared rays irradiates infrared rays of various wavelengths on the skin, and measures blood glucose levels by analyzing reflected light of the skin against infrared rays with a sensor. However, since the reflected light is different depending on various conditions such as skin condition, physical characteristics, and distribution of blood vessels, the amount of light measured by the sensor is severe and it is difficult to accurately measure blood glucose levels.

Disclosure of Invention The present invention has been made to solve various problems including the above problems, and an object thereof is to provide a non-invasive blood glucose measurement method and a non-invasive blood glucose measurement apparatus capable of accurately measuring blood glucose using low-cost infrared light. . However, these problems are exemplary, and the scope of the present invention is not limited thereby.

According to an aspect of the present invention, an optical non-invasive blood glucose measurement method is provided. The optical non-invasive blood glucose measurement method may include locally irradiating near-infrared light to a skin to be measured to locally increase the temperature of the skin; Measuring a mid-infrared spectrum emitted from the skin at elevated temperature; And calculating a blood glucose level by measuring a rising temperature of the skin by the near infrared rays and a constituent ratio of the mid infrared spectrum from the mid-infrared spectrum, wherein the mid-infrared spectrum is in the blood flowing inside the skin. It may include the wavelength band of the characteristic absorption line of glucose (glucose).

In the non-invasive blood glucose measurement method, the calculating step includes the steps of measuring the pulsation of the blood vessels located inside the skin and the water content of the skin by a bio-impedance analysis (BIA); Measuring humidity in the air by using a humidity sensor; Correcting the composition ratio of the mid-infrared spectrum with respect to the measured moisture content of the skin and the humidity in the air; And calculating a blood glucose level of dermal interstitial fluid from the corrected ratio of the mid-infrared spectrum.

In the non-invasive blood glucose measurement method, the near infrared light may be infrared light having a wavelength band (400nm ~ 6um) within 6㎛ or light of an infrared lamp having a 400nm to 6㎛ wavelength band.

In the non-invasive blood glucose measurement method, the infrared light having a wavelength band of less than 6㎛ may be a green light having a 532nm wavelength band and a near infrared light source having a wavelength range of 1.5㎛ 3㎛.

In the non-invasive blood glucose measurement method, the wavelength band of the mid-infrared ray may be a wavelength band of 8㎛ to 14㎛.

According to another aspect of the present invention, a non-invasive blood glucose measurement apparatus is provided. The non-invasive blood sugar measuring device may be in contact with the skin, the body is formed a light guide space in contact with the skin; An optical sensor module unit installed at one end of the light guide space to irradiate or receive light onto the skin; And a control unit for calculating a blood glucose level from the value measured by the optical sensor module unit, wherein the optical sensor module unit emits light that generates near infrared rays to measure glucose concentration in blood flowing inside the skin. module; And a spectrum analysis module configured to receive mid-infrared rays emitted from the skin and measure mid-infrared spectra.

In the non-invasive blood glucose measurement apparatus, each of the one side of the body is provided in contact with the skin, the first sensor for measuring the temperature of the skin and a second sensor for measuring the electrical conductivity of the skin may be further included. have.

In the non-invasive blood glucose measurement apparatus, the near-infrared rays generated by the light emitting module are irradiated to the skin at least once or more, and the mid-infrared rays radiated from the skin are reflected at least once or more to be induced into the spectrum analysis module. It may further include a reflective layer provided in the light guide space.

The non-invasive blood sugar measuring apparatus may further include a third sensor installed at one side of the reflective layer and measuring humidity of air in the light guide space.

In the non-invasive blood glucose measurement apparatus, in order to maintain the constant temperature of the light guide space, an air hole may be provided in at least a portion of the reflective layer.

In the non-invasive blood glucose measurement apparatus, it is provided on the other side of the body in contact with the skin, in order to maintain the constant temperature of the light guide space, may further include a thermoelectric element (TEC) and a fan (FAN).

The non-invasive blood glucose measurement apparatus may further include a collimator interposed between the optical sensor module unit and the reflector to suppress light incident at a high angle to prevent light of another wavelength band from being transmitted. .

The non-invasive blood glucose measurement apparatus may further include a constant temperature module unit interposed between the body and the light guide space in contact with the skin in order to maintain a constant temperature of the subject's palm and finger.

According to an embodiment of the present invention made as described above, non-invasive blood glucose measurement method and non-invasive blood sugar that can be irradiated with low-cost infrared light to the subject's skin, the blood sugar can be measured using the reflection spectrum reflected from the skin The measuring device can be implemented. In addition, it has the effect of calculating the exact blood glucose level in various environments. Of course, the scope of the present invention is not limited by these effects.

1 is a process flow chart listing the non-invasive blood glucose measurement method in order according to an embodiment of the present invention.

2 is a conceptual diagram illustrating a non-invasive blood glucose measurement apparatus according to an embodiment of the present invention.

Hereinafter, various embodiments of the present invention will be described in detail with reference to the accompanying drawings. The embodiments of the present invention are provided to more fully explain the present invention to those skilled in the art, and the following examples can be modified in various other forms, and the scope of the present invention is It is not limited to an Example. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art. In addition, the thickness or size of each layer in the drawings is exaggerated for convenience and clarity of description.

Generally, the skin is divided into epidermis and dermis. The epithelium has numerous capillaries and contains water, and in particular, the dermis contains blood vessels and nerve tissues such as arteries and veins. The near infrared rays are irradiated to the inside of the skin and are absorbed or reflected by the blood vessels or nerve tissue.

It is known that the blood glucose level of skin interstitial fluid correlates with the blood glucose level with an accuracy of about 97% or more. That is, if the blood glucose level of the skin interstitial fluid is accurately measured, the blood glucose level of the blood can be calculated with more than 97% accuracy. Means that.

Therefore, methods for measuring blood glucose levels of skin interstitial fluid have been studied. In the past, the results showed that blood glucose can be measured by measuring mid-infrared reflection spectrum by irradiating mid-infrared to the subject's skin. QCL (Quamtum cascade laser) used as the light source, spectroscopy equipment, infrared sensor, etc. are very expensive and have problems such as maintaining a low temperature (~ 77K) is not practical.

In order to solve this problem, the present invention uses a low-cost near-infrared light source instead of an expensive mid-infrared light source. However, since near-infrared light enters deep into the skin and does not reflect well, it is difficult to measure the spectrum reflected from the skin using near-infrared. The low-cost near-infrared light source is a light source that absorbs well into moisture, Hb, and HbO ₂ existing inside the skin. In general, the higher the wavelength of the near-infrared rays is, the more expensive it is and the output is low. It is preferable to use a laser light source.

Referring to FIG. 1, in the non-invasive blood glucose measurement method according to an embodiment of the present invention, a temperature of a skin is locally increased through near-infrared absorption of components that absorb near-infrared rays among components of the skin by irradiating near-infrared rays on the skin to be measured. Step (S10) blood glucose level by measuring the mid-infrared spectrum radiated from the skin tissue with the elevated temperature (S20) and by measuring the proportion of the skin's rise temperature and the mid-infrared spectrum by the near-infrared absorption of the skin from the mid-infrared spectrum It may include the step (S30) to calculate. The mid-infrared spectrum may include a spectrum of light emitted by glucose in the blood flowing inside the skin.

Specifically, when the near-infrared light source is used, since the spectrum reflected from the skin is difficult to measure, the near-infrared light may emit infrared light having a wavelength band of 6 μm or less or light of an infrared lamp having a wavelength range of 400 nm to 6 μm. I use it. The infrared light having a wavelength band of about 6 μm or less may use green light having a wavelength range of 532 nm and a near infrared light source having a wavelength range of 1.5 μm to 3 μm.

When the near-infrared light source is irradiated to the skin to be measured, near-infrared absorption may occur in some of the components of the skin to locally increase the temperature of the skin. The elevated temperature of the skin emits infrared light, and the spectrum of emitted mid-infrared radiation is associated with the characteristic absorption spectrum of the components of the skin. That is, according to Kirchhoff's law, when a material having an absorption line at a specific wavelength becomes high temperature, it emits the same light as the absorption wavelength band. Therefore, the infrared spectrum generated in the skin with elevated temperature reflects the components of the skin. That is, by measuring the mid-infrared spectrum of the locally heated skin, the components of the skin can be specified. Here, the wavelength band of the mid-infrared may be a wavelength band of 8㎛ to 14㎛.

From the mid-infrared spectrum, blood glucose levels can be calculated by measuring the temperature rise of the skin by the near-infrared and the composition ratio of the mid-infrared spectrum. Here, it is important to maintain constant temperature of the measurement system when measuring the mid-infrared spectrum. It is very important that the temperature of the system is kept constant because the radiation spectrum due to body temperature varies according to the skin component ratio of the individual and, for example, changes in body temperature, skin condition, internal component composition and moisture content. .

In particular, the spectrum of individual wavelength bands differs depending on the ratio of glucose having an absorption line in the 9.4 μm wavelength band. In the wavelength band of 8 µm to 14 µm, which is the wavelength band of the mid-infrared spectrum, it is also affected by moisture and humidity in the air.

Therefore, in the present invention, in order to calculate a more accurate blood sugar level, in the step of calculating the blood sugar level (S30) may include the step of considering the effects of moisture contained in the skin, including the temperature and humidity of the system. .

Specifically, the step of correcting, after measuring the rising temperature of the skin and the composition ratio of the mid-infrared spectrum, the pulsation of the halmac and the skin located inside the skin by Bio-impedance analysis (BIA) The moisture content of can be measured. Here, the pulsation of the blood vessel can be understood as blood flow (pulse of the blood vessel). The moisture in the skin can be measured and the humidity in the air can be measured using the humidity sensor. Since the pulsation of the blood vein is a factor influencing the amount of radiation, the mid-infrared spectrum should be measured between the pulsation and the pulsation to minimize the effect of the heart rhythm.

The blood glucose content of the dermal interstitial fluid is then calculated from the measured moisture content of the skin and the composition ratio of the mid-infrared spectrum with respect to the humidity in the air, and from the corrected composition ratio of the mid-infrared spectrum. Can be. The present invention can accurately measure blood glucose levels in consideration of external influences through the correction.

Hereinafter, a blood glucose measurement apparatus according to one embodiment of the present invention will be described in detail with reference to the accompanying drawings.

As shown in FIG. 2, the non-invasive blood glucose measurement apparatus 100 according to some embodiments of the present invention may be in contact with the skin, and the body 10 in which the light guide space A is formed to contact the skin. And an optical sensor module 20 installed at one end of the light guiding space A to irradiate or receive light onto the skin. In addition, although not shown in the drawing, it may further include a controller (not shown) for calculating the blood glucose level from the value measured by the optical sensor module unit 20.

The body 10 may include a first body 12 capable of supporting any part of a subject's body, a light guide space A, a second sensor body 20, a control unit, and the like. 14). The first body 12 and the second body 14 may be divided by the constant temperature module unit 80 to be described later.

Here, for example, the body 10 is a kind of a box shape in which the upper part of the body 10 which is in contact with a location where easy blood sugar measurement is made using infrared rays such as skin of the human body, for example, hands, feet, torso, ears, forehead, armpits, and thighs. The structure may be various block or frame structures made of synthetic resin or metal material and having sufficient strength and durability to protect the optical sensor module unit 20 described above. However, the shape of the body 10 is not limited to the drawings, and a wide variety of structures in which the light guide space A may be formed may be applied.

Meanwhile, the optical sensor module 20 receives a light emitting module (not shown) for generating near infrared rays and a mid-infrared ray received from the skin in order to measure glucose concentration in blood flowing inside the skin. It may include a spectrum analysis module (not shown) for measuring the spectrum.

Also, for example, the light emitting module may include a light source such as a low-cost high-power infrared LED or a laser that emits near infrared light. For example, the light emitting module may be applied with infrared light having a wavelength band of 6 μm or less or light of an infrared lamp having a wavelength band of 400 nm to 6 μm. However, the light emitting module is not necessarily limited to an infrared light emitting device, and an LED or a lamp capable of emitting light in all infrared frequency bands including a near infrared band may be applied.

In addition, for example, the spectrum analysis module may include at least one spectrum sensor and a spectroscope capable of receiving the mid-infrared light received from the skin to measure the mid-infrared spectrum. The spectral sensor is a multichannel sensor, and may include, in particular, a plurality of band pass filters and a sensor array selected within a wavelength range of 8.0 μm to 10.5 μm, which is the main absorption band of the glucose component. have.

The spectrometer may use a slit sensor scan, and the sensor array may be uniformly disposed without shifting a plurality of sensors in either direction.

The spectral sensor may be provided as a thermopile sensor capable of measuring temperature statically and dynamically as a thermal sensor or an infrared sensor, for example, without a problem of self-heating. These thermopile sensors form two different materials on one side of a junction and an open structure on one side, and if a temperature difference occurs between the contact portion and the open portion, the temperature difference is proportional to the magnitude of the temperature difference. It refers to a sensor that senses temperature by using the Seebeck effect, which generates thermoelectric power. The spectral sensor may also be a pyro-electric sensor or a bolometer.

For example, the controller may include an information processing device, a computing device, a computing device, a circuit board, an electronic component, a central processing device, a storage device, an input / output device, a display device, a computer, a laptop computer, a smartphone, a smart pad, Information terminals and the like.

On the other hand, the non-invasive blood glucose measurement apparatus 100 of the present invention is installed on any one side of the body in contact with the skin, the first sensor 32 for measuring the temperature of the skin and measuring the electrical conductivity of the skin It may further include a second sensor 34.

For example, the first sensor 32 and the second sensor 34 may be disposed on the first body 12 to which the skin is in contact, the first sensor 32 and the second sensor 34 at the same level. Can be formed. The first sensor 32 may be a temperature sensor for measuring the temperature of the skin, may use a sensor that is not affected by the temperature of the external environment, for example, may include an infrared temperature sensor.

The second sensor 34 is a sensor capable of measuring the electrical conductivity flowing to the skin. For example, the bio-impedance analysis (BIA) is used, but the electrical conductivity is measured to measure the moisture and blood of the skin. It may include a sensor that can measure the amount or flow of.

In addition, for example, the light guide space may be reflected so that the near-infrared rays generated by the light emitting module are reflected at least once on the skin, and the mid-infrared rays reflected from the skin are reflected at least one or more times and guided to the spectrum analysis module. It may further include a reflective layer 40 provided in A). For example, the reflective layer 40 may be formed by coating gold (Au) on the surface of the base material, and the upper portion is formed to be wider than the lower portion from the first body 12 to the second body 14 and gradually narrowed. Losing shape may be formed. However, the present invention is not limited to the drawings and may be formed in various forms on the inner wall surface of the light guide space A. FIG.

On the other hand, it is provided on any one side of the reflective layer 40, it may further include a third sensor 36 for measuring the humidity in the air in the light guide space (A). The third sensor 36 may measure not only humidity, but also temperature, and compensate for the amount of light absorption by moisture by measuring humidity and temperature in the air inside the apparatus.

For example, in order to maintain the constant temperature of the light guide space A, an air hole 50 may be provided in at least one portion of the reflective layer 40. The air hole 50 has a groove formed in a portion of the reflective layer 40 to maintain a constant temperature inside the device to allow air to enter and exit.

On the other hand, when not provided with a separate thermostat device by providing a temperature sensor inside the device may be measured by taking into account the effect of temperature through the correction by the control unit blood sugar. However, in order to efficiently measure blood glucose, the thermoelectric elements TEC, 62, 64 and the fan FAN, 66 are installed on the other side of the body 10 in contact with the skin. It may include. The thermoelectric elements 62 and 64 may include a first thermoelectric element 62 for maintaining a constant temperature of the device and a second thermoelectric element 64 for maintaining a constant temperature of the skin. A constant temperature inside the apparatus may be maintained using the fan 66 to facilitate the transfer of heat generated by the first thermoelectric element 62 and the second thermoelectric element 64.

In addition, for example, it may further include a collimator (70) interposed between the optical sensor module unit and the reflector to suppress the incident light at a high angle to prevent the transmission of light of a different wavelength band. Here, the elevation means that the incident angle is incident from a direction close to the direction perpendicular to the first body 12. The collimator 70 may be used as a guide for producing parallel light so that the spectrum reflected from the skin and emitted light is incident on the optical sensor module 20.

In addition, for example, in order to maintain a constant temperature of the subject's palm and fingers, the constant temperature module unit 80 interposed between the body and the light guide space in contact with the skin may be further included. The constant temperature module unit is formed on the lower surface of the first body 12 in contact with the skin in the non-invasive blood glucose measurement device 100 performs a function of maintaining a constant temperature of the entire skin. For example, the site of contact with the non-invasive blood glucose measurement apparatus 100 is mainly a hand, and the palm is placed on the first body 12 in a pin state. In this case, the constant temperature module unit 80 is a plate that performs a heating function or a cooling function, and performs a function of maintaining a constant temperature of the palm and fingers.

As described above, the non-invasive blood sugar measuring method according to an embodiment of the present invention increases the skin temperature by irradiating the skin with near-infrared rays having a radiation wavelength band within 6 μm, and generates the skin temperature from 8 μm. The mid-infrared spectrum of the wavelength range of 14 micrometers is measured. Afterwards, the skin rising temperature and the composition ratio of the spectrum by the irradiated light are measured from the measured mid-infrared spectrum, and the spectrum of skin moisture and humidity in the air is measured by measuring the pulse of the blood vessel, the moisture content of the skin, and the humidity in the air. By correcting the composition ratio of the blood glucose level of the interstitial fluid can be accurately derived.

Although the present invention has been described with reference to the embodiments shown in the drawings, this is merely exemplary, and those skilled in the art will understand that various modifications and equivalent other embodiments are possible. Therefore, the true technical protection scope of the present invention will be defined by the technical spirit of the appended claims.

Claims

Irradiating near-infrared rays on the skin to be measured to increase the temperature of the skin;

Measuring a mid-infrared spectrum generated from the skin at elevated temperature; And

Calculating a blood glucose level by measuring an increase temperature of the skin by the near infrared ray and a composition ratio of the mid infrared spectrum from the mid-infrared spectrum;

Including,

Wherein the mid-infrared spectrum includes a spectrum of light emitted by glucose in the blood flowing inside the skin,

Non-invasive blood glucose measurement method.
The method of claim 1,

The calculating step,

Measuring the pulsation of the halmac and the water content of the skin located inside the skin by bio-impedance analysis (BIA);

Measuring humidity in the air by using a humidity sensor;

Correcting the composition ratio of the mid-infrared spectrum with respect to the measured moisture content of the skin and the humidity in the air; And

Calculating a blood glucose level of dermal interstitial fluid from the corrected proportion of the mid-infrared spectrum;

Including,

Non-invasive blood glucose measurement method.
The method of claim 1,

The near infrared ray is infrared light having a wavelength band within 6 μm or light of an infrared lamp having a wavelength band of 400 nm to 6 μm,

Non-invasive blood glucose measurement method.
The method of claim 3, wherein

Infrared light having a wavelength band within 6 μm uses green light having a 532 nm wavelength band and a near infrared light source having a wavelength range of 1.5 μm to 3 μm,

Non-invasive blood glucose measurement method.
The method of claim 1,

The wavelength band of the mid-infrared is a wavelength band of 8 ㎛ to 14 ㎛,

Non-invasive blood glucose measurement method.
A body in contact with the skin and having a light guiding space in contact with the skin;

An optical sensor module unit installed at one end of the light guide space to irradiate or receive light onto the skin; And

And a control unit for calculating a blood sugar level from the value measured by the optical sensor module unit.

The optical sensor module unit,

A light emitting module for generating near infrared rays to measure glucose concentration in blood flowing inside the skin; And a spectrum analysis module configured to receive the mid-infrared light received from the skin and measure the mid-infrared spectrum.

Non-invasive blood glucose measurement device.
The method of claim 6,

Further installed on each side of the body in contact with the skin, further comprising a first sensor for measuring the temperature of the skin and a second sensor for measuring the electrical conductivity of the skin,

Non-invasive blood glucose measurement device.
The method of claim 6,

Reflecting layer provided in the light guide space so that the near-infrared rays generated by the light emitting module are irradiated to the skin at least once or more, and the mid-infrared rays emitted from the skin are reflected at least once or more to be guided to the spectrum analysis module Including more;

Non-invasive blood glucose measurement device.
The method of claim 8,

It is provided on any one side of the reflective layer, and further comprising a third sensor for measuring the humidity of the air in the light guide space,

Non-invasive blood glucose measurement device.
The method of claim 8,

In order to maintain the constant temperature of the light guide space, an air hole is provided in at least part of the reflective layer,

Non-invasive blood glucose measurement device.
The method of claim 10,

Is installed on the other side of the body in contact with the skin, in order to maintain the constant temperature of the light guide space, further comprises a thermoelectric element (TEC) and a fan (FAN),

Non-invasive blood glucose measurement device.
The method of claim 8,

It further comprises a collimator (Collimator) interposed between the optical sensor module unit and the reflector to suppress the incident light at a high angle to prevent the transmission of light of a different wavelength band,

Non-invasive blood glucose measurement device.
The method of claim 6,

In order to maintain a constant temperature of the subject's palms and fingers, further comprising a constant temperature module portion interposed between the body and the light guide space in contact with the skin,

Non-invasive blood glucose measurement device.