This application claims priority to and the benefit of Korean Patent Applications, No. 10-2022-0037822 filed on Mar. 28, 2022, No. 10-2022-0114890 filed on Sep. 13, 2022, and No. 10-2023-0025690 filed on Feb. 27, 2023, the disclosures of which are incorporated herein by reference in their entirety.
The present invention relates to a blood glucose measurement technology, and more particularly, to a blood glucose measurement apparatus and method capable of noninvasively measuring a blood-glucose concentration in biological tissue of the distal part such as an earlobe, a hand, or a foot of the human body, or any soft tissue.
Various techniques have been studied for non-drawing blood glucose measurements, which enable diabetic patients to avoid the pain of drawing blood. The non-drawing blood glucose measurement technique is largely classified into a minimally invasive method and a noninvasive method according to whether a glucose measurement sensor is inserted into biological tissue of the human body. The minimally invasive method uses a small probe or an implant-type sensor to measure a glucose concentration in interstitial fluid, which is body fluid between tissue cells outside the blood vessels, and thus can generally measure blood glucose without bleeding. The noninvasive measurement method is an innovative technique for measuring a glucose concentration outside the skin tissue without any tissue damage, and includes, for example, an in vitro body fluid-type noninvasive measurement technique for measuring the concentration of glucose contained in the body fluid discharged outside the body such as tears and sweat.
In order to measure a signal in biological tissue of the human body by the noninvasive measurement method, a physical signal needs to be applied thereto. For the applied physical signal, various types such as light, heat, electromagnetic, ultrasound, and fusion signals are used. A signal measurement sensor may be used in almost any part outside the human body, but is mainly being developed in a form that can be attached to or worn on a finger, an earlobe, an ear, a wrist, an arm, an abdomen, or the like. In particular, since the finger and the earlobe are considered as distal end tissues of the human body where the sensor is more conveniently worn and measured, many sensors currently on the market or being developed are being developed to have a form (for example, pivotal tongs) suitable for being worn on these biological tissues.
The present invention is directed to providing a noninvasive blood glucose measurement apparatus and method using multiple sensors capable of noninvasively measuring a blood-glucose concentration in biological tissue such as an earlobe or a finger of the human body.
The present invention is also directed to providing a probe for noninvasive blood glucose measurement developed for effective use of the noninvasive blood glucose measurement apparatus and method using multiple sensors.
Noninvasive blood glucose measurement is generally based on the measurement of reflection and transmission characteristics of a physical signal in soft tissue containing blood glucose. The soft tissue in the human body refers to tissue other than bone or cartilage, such as skin, muscle, fat, fibrous tissue, lymphatic tissue, and blood vessels, and the composition of the soft tissue has a significant effect on noninvasive blood glucose measurement. A finger, a hand, and an earlobe have long been used as tissue parts (biological tissue) of the human body suitable for noninvasive blood glucose measurement, in particular, the earlobe is composed of rough muscle tissue and adipose tissue, is very flexible, and has a large amount of blood supply, and thus is one of the suitable parts for noninvasive blood glucose measurement.
The gist of the present invention is to measure blood glucose on the basis of light reflection characteristics and characteristics of at least one of photoacoustic transmission and light transmission, which are derived by multiple types of measurement methods using multiple sensors for relatively thin soft tissue such as an earlobe in body tissue (hereinafter, the phrase “at least one of photoacoustic transmission and light transmission” and similar phrases are used interchangeably with the phrase “photoacoustic and/or light transmission” and similar phrases).
To this end, a noninvasive blood glucose measurement apparatus and method according to the present invention include a multi-sensor probe configured to measure blood glucose noninvasively by coming into contact with both sides of biological tissue, for example, an earlobe. The multi-sensor probe may further include at least one of a means for irradiating light of a multi-wavelength channel to a biological tissue, a means for receiving backscattered/reflected light (hereinafter referred to as a “light reflection signal”) that is generated as the irradiated light passes through the biological tissue, a means for receiving light (hereinafter referred to as a “light transmission signal”) that is irradiated and has passed through the biological tissue and/or a means for receiving a photoacoustic transmission signal generated and transmitted in biological tissues by irradiated light, and a means for measuring a temperature and/or a thickness.
In particular, in the present invention, a blood glucose level in the body may be measured noninvasively by distinguishing a wavelength region for a light reflection signal and a wavelength region for a photoacoustic and/or light transmission signal on the basis of scattering and absorption characteristics of near-infrared light for biological tissue of the human body and light transmission and absorption characteristics according to a change in glucose concentration and selectively applying a wavelength (or wavelength channel) having a high reactivity to glucose and a reference wavelength (or reference wavelength channel) having a low reactivity to glucose in each wavelength region. In this case, a ratio of a signal of the wavelength having a high glucose reactivity to a signal of the reference wavelength in two wavelength regions may show a signal change rate in opposite directions according to an increase in a blood glucose level.
That is, in the present invention, a blood glucose level may be evaluated more accurately and noninvasively by measuring the blood glucose level in a dual manner on the basis of different noninvasive blood glucose measurement methods in two wavelength regions with respect to the same region of biological tissue (e.g., an earlobe), and additionally reflecting at least one of temperature and thickness measurement results for the biological tissue (hereinafter, the phrase “at least one of the temperature and the thickness” and similar phrases are used interchangeably with the phrase “the temperature and/or the thickness” and similar phrases).
The present invention uses a combination of multiple types of non-invasive measurement methods using multiple sensors, and provides a solution differentiated from the related art as follows.
According to an aspect of the present invention, there is provided a noninvasive blood glucose measurement apparatus including a first light source unit disposed in a probe and configured to irradiate light of at least one wavelength to a biological tissue, a second light source unit disposed in the probe and configured to irradiate light of at least one wavelength, which is different from that of the light of the first light source unit, to the biological tissue, a first receiving unit disposed in the probe and configured to receive a transmission signal generated as the light irradiated to the biological tissue passes through the biological tissue, a second receiving unit configured to receive a light reflection signal generated as the light irradiated to the biological tissue is reflected by the biological tissue, and a measurement unit configured to measure light reflection characteristics of the biological tissue by using the light reflection signal received by the second receiving unit, measure transmission characteristics of the biological tissue by using the transmission signal received by the first receiving unit, and measure blood glucose of the biological tissue on the basis of the light reflection characteristics and the transmission characteristics.
Here, each of the first light source unit and the second light source unit may irradiate the biological tissue with light of two or more wavelength channels in a near-infrared wavelength region of 900 to 1700 nm in which an extinction coefficient, which is the sum of an absorption coefficient and a scattering coefficient, is relatively small as compared to other wavelength regions.
In the noninvasive blood glucose measurement apparatus of the present invention, the transmission signal received by the first receiving unit may be a photoacoustic transmission signal, and the measurement unit may be configured to measure photoacoustic transmission characteristics of the biological tissue by using the photoacoustic transmission signal received by the first receiving unit. Alternatively, the transmission signal received by the first receiving unit may be a light transmission signal, and the measurement unit may be configured to measure light transmission characteristics of the biological tissue by using the light transmission signal received by the first receiving unit.
In the noninvasive blood glucose measurement apparatus of the present invention, the second light source unit may irradiate light of a first wavelength channel, and light of a second wavelength channel having relatively a higher reactivity to glucose than the first wavelength channel, and the first light source unit may irradiate light of a third wavelength channel, and light of a fourth wavelength channel having a relatively higher reactivity to glucose than the third wavelength channel. In this case, the measurement unit may measure the light reflection characteristics of the biological tissue by combining a light reflection signal for the first wavelength channel and a light reflection signal for the second wavelength channel or the fourth wavelength channel. In addition, the measurement unit may measure the transmission characteristics of the biological tissue by combining a transmission signal for the third wavelength channel and a transmission signal for the second wavelength channel or the fourth wavelength channel.
The noninvasive blood glucose measurement apparatus of the present invention may further include a first sensor unit configured to measure a temperature of the biological tissue, wherein the measurement unit may measure the blood glucose of the biological tissue by reflecting (or using) the temperature of the biological tissue. In addition, the noninvasive blood glucose measurement apparatus of the present invention may further include a temperature sensor configured to monitor a temperature of at least one of the first light source unit, the second light source unit, the first receiving unit, and the second receiving unit, and a temperature sensor configured to monitor a change in ambient air temperature of the probe.
In addition, the noninvasive blood glucose measurement apparatus of the present invention may further include a second sensor unit configured to measure a thickness of the biological tissue, wherein the measurement unit may measure the blood glucose of the biological tissue by reflecting (or using) the thickness of the biological tissue.
Here, the second sensor unit may include a light-sending element disposed at a position of a first part of the probe, which is spaced apart from the biological tissue, two or more light-receiving elements disposed at different positions of the first part of the probe, which are spaced apart from the biological tissue, and a reflecting element disposed at a position of a second part of the probe, which is spaced apart from the biological tissue, and the measurement unit may be configured to measure the thickness of the biological tissue by measuring an intensity difference or ratio of light signals generated as light irradiated from the light-sending element is reflected by the reflecting element and then received by the two or more light-receiving elements. In addition, the second sensor unit may include a pressure sensor configured to measure a pressure applied by the probe to the biological tissue and output the measured pressure as an electrical signal, and the measurement unit may be configured to estimate the thickness of the biological tissue by using the electrical signal output from the pressure sensor.
In the noninvasive blood glucose measurement apparatus of the present invention, the second light source unit may include a light source element configured to irradiate light of different inclination angles to the biological tissue, and the second receiving unit includes a receiving element configured to receive the light reflection signal at different inclination angles at a position corresponding to the light source element.
In the noninvasive blood glucose measurement apparatus of the present invention, the measurement unit may measure the light reflection characteristics and the transmission characteristics of the biological tissue by distinguishing a wavelength region for measuring the light reflection characteristics and a wavelength region for measuring the transmission characteristics, and selectively applying at least one wavelength channel having a relatively low reactivity to glucose and at least one wavelength channel having a relatively high reactivity to glucose in the distinguished wavelength regions.
The probe of the noninvasive blood glucose measurement apparatus of the present invention has a new fastening structure, that is, fixed-type balanced fastening structure, in which a force (pressure) is always uniformly applied to each part of biological tissue. The probe may include an upper frame, a lower frame, and a moving frame that moves between the upper frame and the lower frame, and may have a structure in which the first and second light sources and the first and second receiving parts are installed in the upper and/or lower frames, so that the signal may be transmitted and detected more stably to the biological tissue. Specifically, the probe may include an upper frame, a lower frame spaced apart from the upper frame and fixed to the upper frame, and a moving frame that is located between the upper frame and the lower frame, has a space separated from the lower frame, into which the biological tissue is inserted, and moves between the upper frame and the lower frame so that the space separated from the lower frame is changed, wherein the moving frame may be configured to apply a pressure to the biological tissue by an elastic element placed between the moving frame and the upper frame. Here, the moving frame may further include a separation space expansion mechanism configured to widen the space separated from the lower frame when a force is applied against the elastic element. In the probe having such a configuration, the first light source unit, the second light source unit, and the second receiving unit may be installed in the upper frame, and the first receiving unit may be installed in the lower frame. In addition, the noninvasive blood glucose measurement apparatus may further include a pressure sensor between the elastic element and the upper frame.
According to another aspect of the present invention, there is provided a noninvasive blood glucose measurement method including irradiating light of one or more different wavelengths to a biological tissue, receiving a light reflection signal generated as the light irradiated to the biological tissue is reflected by the biological tissue, receiving a transmission signal generated as the light irradiated to the biological tissue passes through the biological tissue, and measuring light reflection characteristics of the biological tissue by using the light reflection signal, measuring transmission characteristics of the biological tissue by using the received transmission signal, and measuring blood glucose of the biological tissue on the basis of the light reflection characteristics and the transmission characteristics, wherein the transmission signal includes at least one of a photoacoustic transmission signal and a light transmission signal, and the transmission characteristics includes at least one of photoacoustic transmission characteristics and light transmission characteristics.
Here, the noninvasive blood glucose measurement method may further include measuring at least one of a temperature and a thickness of the biological tissue.
In the noninvasive blood glucose measurement method of the present invention, the estimating of the blood glucose may include deriving an average value by repeating the light reflection characteristics measurement and the transmission characteristics measurement multiple times, and deriving a blood glucose value by comparing the average value with a reference comparison table obtained in advance through prior learning data.
In addition, the noninvasive blood glucose measurement method of the present invention may further include repeatedly performing the deriving of the blood glucose value to output accumulated blood glucose value data for a predetermined period of time. As described above, the features briefly summarized with respect to the present invention are merely exemplary aspects of the detailed description for the embodiments of the present invention to be described later, and do not limit the scope of the present invention.
The above and other objects, features, and advantages of the present invention will become more apparent to those of ordinary skill in the art by describing exemplary embodiments thereof in detail with reference to the accompanying drawings, in which:
Hereinafter, a noninvasive blood glucose measurement apparatus and method according to embodiments of the present invention will be described with reference to the drawings. In the embodiments to be described below, for convenience of description, among biological tissue parts such as an earlobe, a part between fingers, and a part between toes, an earlobe is specified and described as a target biological tissue for measuring a blood-glucose concentration.
Terms used in the following description are used to merely describe exemplary embodiments of the present invention, but are not intended to limit the present invention. In the present specification, the singular forms include the plural forms unless the context clearly dictates otherwise. Further, it is noted that terms “comprises” and/or “comprising” used herein do not exclude the presence or addition of one or more other components, steps, operations, and/or elements in addition to stated components, steps, operations, and/or elements. In addition, the terms “reflection” and “transmission” as used herein in the description of a light signals are not intended to exclude absorption, multi-scattering characteristics in biological tissue.
Referring to
The first light source unit 27 may include light source elements of two or more different wavelength channels and an element for monitoring and/or controlling the output and/or temperature of the light sources, and irradiate light perpendicularly to the surface of the earlobe 10, but the present invention is not limited thereto.
The first light source unit 27 may irradiate light of a third wavelength channel having a relatively low reactivity to glucose and light of a fourth wavelength channel having a relatively high reactivity to glucose. Here, the low reactivity or high reactivity to glucose may mean relatively low or high reactivity when compared based on a certain value of reactivity to glucose or based on reactivity to glucose in a specific wavelength range, or may mean that a change in light absorbance is small below a predetermined value or the change is large above the predetermined value, and the criteria therefor may be determined by an individual or a business operator providing the corresponding technique.
The second light source unit 28 may include light source elements of two or more wavelength channels, and an element for monitoring and/or controlling the output and/or temperature of the light sources, and irradiate light to the surface of the earlobe 10 at a predetermined inclination angle, but the present invention is not limited thereto. The second light source unit 28 may include a plurality of light source elements capable of irradiating light to the earlobe at different inclination angles.
The second light source unit 28 may irradiate light of a first wavelength channel having a relatively low reactivity to glucose and light of a second wavelength channel having a relatively high reactivity to glucose. Here, the meaning of the low and high reactivities to glucose is similar to that described for the first light source unit 27 above.
Each of the first light source unit 27 and the second light source unit 28 may irradiate the earlobe with light of two or more wavelength channels in a near-infrared wavelength region of about 900 to 1700 nm in which an extinction coefficient that is the sum of an absorption coefficient and a scattering coefficient is the smallest.
In addition, the first receiving unit 23 includes an ultrasound sensor for receiving a photoacoustic transmission signal generated and transmitted as a light signal irradiated to the earlobe 10, which is a biological tissue, is absorbed in a part of the biological tissue. In addition or alternatively, the first receiving unit 23 may include a light-receiving sensor for receiving a light transmission signal generated as the light signal irradiated to the earlobe 10 is transmitted without being absorbed in the biological tissue.
The second receiving unit 24 may include a light-receiving element configured to receive a light reflection signal reflected while the light irradiated to the earlobe 10 passes through the earlobe 10. The light-receiving element may be aligned such that a surface (light-receiving surface) thereof has an inclination angle corresponding to a light-emitting angle of the second light source unit 28.
In addition, the first sensor unit 25 may include a temperature measuring element for measuring the temperature of the tissue by being in close contact with the skin of the earlobe 10.
The second sensor unit 26 may include a thickness measuring element for measuring a thickness of the biological tissue (i.e., the earlobe 10) between the first part 21 and the second part 22 of the probe.
In addition, the measurement unit 300 measures light reflection characteristics of the earlobe 10 using the light reflection signal received by the second receiving unit 24, and measures photoacoustic and/or light transmission characteristics of the earlobe 10 using the photoacoustic transmission signal (e.g., ultrasound signal) and/or the light transmission signal, which is received by the first receiving unit 23. Blood glucose of the earlobe 10 or a person concerned with the earlobe 10 is measured on the basis of the measured light reflection characteristics and photoacoustic and/or light transmission characteristics.
In this case, the measurement unit 300 may measure the light reflection characteristics and the photoacoustic and/or light transmission characteristics of the earlobe by distinguishing a wavelength region for measuring the light reflection characteristics and a wavelength region for measuring the photoacoustic and/or light transmission characteristics, and selectively applying at least one wavelength channel having a relatively low reactivity to glucose (reference wavelength channel) and at least one wavelength channel having a relatively high reactivity to glucose (blood glucose search wavelength channel) to the distinguished wavelength regions. According to an embodiment, the measurement unit 400 may measure the light reflection characteristics of the earlobe by combining a light reflection signal for the first wavelength channel and a light reflection signal for the second wavelength channel or the fourth wavelength channel, and may measure the photoacoustic and/or light transmission characteristics of the earlobe by combining a photoacoustic and/or light transmission signal for the third wavelength channel and a photoacoustic and/or light transmission signal for the second wavelength channel or the fourth wavelength channel.
Further, the measurement unit 300 may operate at least one of the light source units 27 and 28, the receiving units 23 and 24, and the sensor units 25 and 26 in the probe 200 according to a control timing, process the received signal, and store and output a measurement result. Furthermore, the measurement unit 300 may monitor an output intensity and a temperature of a multi-channel (multi-wavelength) light source included in the first and second light source units 27 and 28 and/or control a operation timing, a modulation frequency, an output intensity, a temperature, and the like.
According to an embodiment, the measurement unit 300 may sequentially process an ultrasound and/or light receiving signal of the first receiving unit 23 according to the control timing of the multi-channel light sources to derive and store a first result value for each wavelength channel. The measurement unit 300 may sequentially process a light reception signal of the second receiving unit 24 according to the control timing of the multi-channel light source to derive and store a second result value for each wavelength channel. The measurement unit 300 may sequentially process a temperature monitoring signal of the first sensor unit 25 according to the control timing of the multi-channel light source to derive and store a third result value for each wavelength channel. The measurement unit 300 may measure the thickness of the tissue between the first part 21 and the second part 22 of the probe 200 by operating the second sensor unit 26 at least once or more whenever a user wears the probe 200 on the earlobe 10 to derive and store a fourth result value. The measurement unit 300 may derive and store a first noninvasive blood glucose level for the blood glucose level in the tissue on the basis of a combination of the first to fourth result values derived from the first and second receiving units 23 and 24 and the first and second sensor units 25 and 26, and output the first noninvasive blood glucose level to the user interface 400.
The user interface 400 may include a display, a speaker, and a program for operating the same, which are integrated into a body of the noninvasive blood glucose measurement apparatus. Alternatively, the user interface 400 may include an external device such as a smartphone or a personal computer (PC) connected to the measurement unit 300 by a communication means, and a program application installed in the external device.
The user interface 400 may output the first noninvasive blood glucose level to the user, or may output a second blood glucose level by correcting the first noninvasive blood glucose level on the basis of personal data such as age, gender, and invasive blood glucose measurement data of the user. Furthermore, the user interface 400 may record blood glucose levels for each time and date, and compare the blood glucose levels with a currently measured blood glucose level to output a predicted blood glucose level.
In general, a light transmission in the biological tissue is attenuated due to scattering and absorption in various constituent materials constituting the tissue, and a transmittance is exponentially inversely proportional to the product of an extinction coefficient ae, which is the sum of an absorption coefficient aa and a scattering coefficient as, and a thickness t of the tissue. This may be expressed as Equation 1 below.
T˜exp(−ae*t); ae=aa+as [Equation 1]
In general, when light is transmitted in biological tissue, the extinction coefficient ae has a relatively small value in a near-infrared band having a wavelength in the range of 1100 to 1800 nm except for about 1490 nm, and thus the most excellent transmission characteristic may be expected along an optical path. Since the scattering coefficient as is much larger than the absorption coefficient aa in a region from about 480 to 1100 or about 1380 nm, optical characteristics in which light is not absorbed but scattered multiple times in the tissue are more easily used. A light signal that is multi-scattered in the biological tissue returns to an incident direction through a process of being repeatedly scattered backward or forward. Backscattering characteristics of a portion of the light signal may be measured by a reflection signal, and forward scattering characteristics of the incident light may be measured by a transmission signal.
Meanwhile, the generation of the photoacoustic signal for the biological tissue is based on the light absorption in the tissue component, and thus it is more advantageous for acoustic signal conversion in a local region with low light energy in the wavelength region having a relatively high absorption coefficient aa. As can be seen from the absorption coefficient graph 31 shown in
As can be seen from the graph 33 shown in
In the embodiment of the present invention, a wavelength region of 4 channels or more is used from a region of 900 to 1700 nm in which the extinction coefficient, which is the sum of the absorption coefficient 31 and the scattering coefficient 32, is the smallest, for the transmission of the visible light and infrared light spectrum to biological tissue. In particular, as shown in
When the characteristics of each wavelength section are described in more detail, the wavelength section I (301) has characteristics in which the light absorption coefficient is small, but the light scattering coefficient is relatively large, and a change in light absorbance according to a change in glucose concentration is relatively small, for the biological tissue of the human body. The wavelength section II (302) is a section having a relatively small extinction coefficient (the sum of the absorption coefficient and the scattering coefficient) compared to the wavelength section I (301) and has characteristics in which light absorbance is slightly and significantly decreased as the glucose concentration increases. The wavelength section III (303) is a section in which the extinction coefficient increases relatively greatly due to the increase in the absorption coefficient by moisture in the biological tissue of the human body, and has characteristics in which there is no change in light absorbance due to a change in glucose concentration. The wavelength section IV (304) is a section in which, as compared with the wavelength section II, the absorption coefficient is large and the scattering coefficient is small, but the extinction coefficient is similar, and has characteristics in which the light absorbance increases relatively greatly with the increase in glucose concentration. The wavelength section V (305) is a section in which, as compared with the other sections, the absorption coefficient is the smallest but the scattering coefficient is the largest, and has characteristics in which the light absorbance slightly increases with the increase in glucose concentration.
For the light source for each wavelength channel, a relatively inexpensive diode light source, such as a light-emitting diode (LED), a laser diode (LD), a super luminescent diode (SLD), or the like, may be selectively used. In addition, each light source may have a different spectral half-width. As an example, as shown in
Referring to
As described above, the apparatus according to the embodiment of the present invention is capable of measuring the blood glucose level while excluding the general characteristics of the biological tissue as much as possible by comparing and analyzing the measurement signals in the reference wavelength channels and the blood glucose search wavelength channels. Among various methods of comparing and analyzing measurement signals between the reference wavelength channels and the blood glucose search wavelength channels, as a simple example, the blood glucose level may be primarily derived from a difference or ratio of the two signals.
As shown in
Y1=aX+b(a>0) [Equation 2]
In addition, a trend line 322, which is obtained from ratio (λ4/λ3) data between the signal of the second reference wavelength λ3 and the signal of the second blood glucose search wavelength λ4 measured by the photoacoustic method, may be expressed by a proportional equation between another noninvasive glucose measurement value Y2 and an actual glucose concentration X as shown in Equation 3 below.
Y2=cX+d(c<0) [Equation 3]
The data shown in
As shown in
A light module for the first light source unit 27 may be composed of two LDs or LEDs emitting the second reference wavelength λ3 and the second blood glucose search wavelength λ4. Here, a collimator lens for condensing light or making parallel light by adjusting a divergence angle of emitted light may also be assembled to the first light source unit 27.
A light module for the second light source unit 28 may be composed of two LDs or LEDs emitting the first reference wavelength λ1 and the first blood glucose search wavelength λ2. Here, a collimator lens for condensing light or making parallel light by adjusting a divergence angle of emitted light may be assembled to the second light source unit 28.
As another example, the third blood glucose search wavelength λ5 may be used in place of the first blood glucose search wavelength λ2 or the second blood glucose search wavelength λ4. In addition, a thermistor for monitoring a temperature of an optical element mount may be assembled together on a thermoelectric cooling element (TEC) or a heater element for temperature control in the optical element in the light module.
The first receiving unit 23 may include an ultrasound sensor and/or a light transmission signal receiving photodiode, and the second receiving unit 24 may include a single photodiode capable of receiving all light signals of near-infrared wavelength channels λ1 to λ5, that is, light reflection signals transmitted through the earlobe 10 and reflected. In the description of
As shown in
As earlier described in
Unlike a conventional measurement method in which only transmission characteristics due to light scattering in the earlobe tissue are mainly received, in the present invention, light scattered in the tissue is additionally reflected from the surface (i.e., 231) of the ultrasound sensor 23 and is aligned so that the light can be absorbed and scattered again while passing through the tissue in the direction of the second receiving unit 24. The light scattering is largely divided into Rayleigh scattering due to particles smaller than the wavelength and Mie scattering due to particles larger than the wavelength. Generally the biological tissue is composed of cell tissues larger than the near-infrared wavelength, and thus the light scattering in the present invention occurs mainly according to a Mie scattering effect. The Mie scattering shows a characteristic in that energy scattered forward increases as a diameter of the particle relative to the wavelength increases. Accordingly, since a large portion of the energy multi-scattered in the biological tissue of the earlobe, which is several mm thick, is still distributed near the center of a light incident path, matching the inclination angles of the light transmission and reception is more advantageous for receiving light transmission energy sufficiently. To this end, as shown in
In
The thickness measurement sensor illustrated in the embodiment of
Light emitted from the light-sending element 73 has a radiation angle φ(72) of a predetermined size and is irradiated toward the reflection mirror 76. It is configured such that an intensity of a signal received by the receiving element 74 has the greatest value when a distance between the surface 211 of the first part of the probe and the surface 221 of the second part is d1, intensities of signals received by the receiving elements 74 and 75 have the same value when the distance is d2, and an intensity of a signal received by the receiving element 75 has the greatest value when the distance is d3.
Here, d1 and d3 mean the minimum thickness and the maximum thickness of the earlobe 10 to be measured, and the output radiation angle φ (72) of the light-sending element 73 may be set so that signals received by the light-receiving elements 74 and 75 have the same intensity at d2 corresponding to the intermediate value between d1 and d3.
The light-sending element 73 may output and irradiate a continuous wave or pulse wave having a certain intensity, and the measurement unit 300 (see
Although it has been described above with reference to
Referring to
Thereafter, light reflection characteristics and photoacoustic and/or light transmission characteristics are measured using a first wavelength channel and a second wavelength channel (S820). That is, by operating the second light source unit 28 to irradiate the first wavelength channel and the second wavelength channel to the earlobe 10, and receiving a photoacoustic and/or light transmission signal through the first receiving unit 23 and receiving a light reflection signal through the second receiving unit 24, light reflection characteristics and photoacoustic and/or light transmission characteristics for the first wavelength channel and the second wavelength channel are measured, and accordingly, a second result value is derived. In this case, in operation S820, a temperature of the earlobe, which is biological tissue, may also be measured.
Thereafter, light reflection characteristics and photoacoustic and/or light transmission characteristics are measured using a third wavelength channel and a fourth wavelength channel (S830). That is, by operating the first light source unit 27 to irradiate the third wavelength channel and the fourth wavelength channel to the earlobe, and receiving a photoacoustic signal and/or a light signal through the first receiving unit 23 and receiving a light reflection signal through the second receiving unit 24, light reflection characteristics and photoacoustic and/or light transmission characteristics for the third wavelength channel and the fourth wavelength channel are measured, and accordingly, a third result value is derived. In this case, in operation S830, a temperature of the earlobe may also be measured.
When the light reflection characteristics and the photoacoustic and/or light transmission characteristics for each of the first to fourth wavelength channels are measured through the above-described process, blood glucose of the earlobe is measured on the basis of the light reflection characteristics and the photoacoustic and/or light transmission characteristics measured by each of the first to fourth wavelength channels (S840). Here, it is possible to measure the blood glucose of the earlobe by reflecting the thickness and temperature measured for the earlobe. Furthermore, customized temperature and thickness correction may be automatically performed for each person to be measured.
The operation S840 is further described. A learning matrix is created and trained based on multi-data including the first to third result values derived through operations S810 to S830 described above and data log values stored in the noninvasive blood glucose measurement apparatus or terminal. That is, multi-data-based signal processing is performed, a final blood glucose level of the earlobe is evaluated on the basis of the signal processing, the evaluated blood glucose level of the biological tissue is accumulated in an existing data log, a new evaluation result is stored, and the new evaluation result is output to the corresponding user.
The measurement unit 300 may include and store user's invasive blood glucose measurement values for calibrating the noninvasive blood glucose measurement apparatus in the existing data log, and may also output new measurement data including existing data according to the requirements of the user interface 400.
Although a description is omitted in the method of
The noninvasive blood glucose measurement apparatus and method according to the embodiment described above may provide a noninvasive blood glucose measurement technique based on a multiple sensor-based technique, which is completely different from a conventional earlobe-type noninvasive blood glucose sensor, more accurately measure a blood-glucose concentration of biological tissue in a noninvasive manner by mutually combining light reflection characteristics together with photoacoustic and/or light measurement for biological tissue such as an earlobe, and the measured blood-glucose concentration may be corrected by reflecting the thickness and temperature of the biological tissue in the blood glucose measurement history as necessary.
More specifically, the device 900 of
As an example, The device 900 may include a communication circuit such as the sender-receiver 940 and perform communication with an external device based on this.
As an example, the processor 930 may be at least one of a general processor, a digital signal processor (DSP), a DSP core, a controller, a microcontroller, application specific integrated circuits (ASICs), field programmable gate array (FPGA) circuits, any other types of integrated circuits (ICs), and one or more processors related to state machine. That is, the processor may be a hardware/software component for controlling the above-described device 900. In addition, the processor 930 may modularize and perform functions of the measurement unit 300 and the user interface 400 of
The processor 930 may execute computer-executable instructions stored in the memory 920 in order to perform various essential functions of the noninvasive blood glucose measurement apparatus. As an example, the processor 930 may control at least one of signal coding, data processing, power control, input/output processing, and communication operation. In addition, the processor 930 may control a physical layer, a media access control (MAC) layer, and an application layer. In addition, as an example, the processor 930 may perform authentication and security procedures in an access layer and/or an application layer.
As an example, the processor 930 may perform communication with other apparatuses through the sender-receiver 940. As an example, the processor 930 may control the noninvasive blood glucose measurement apparatus to perform communication with other apparatuses via a network by executing the computer-executable instructions. That is, communication performed in the present invention may be controlled. As an example, the sender-receiver 940 may transmit a radio frequency (RF) signal through the antenna and transmit signals based on various communication networks. As an example, multiple input and multiple output (MIMO) technology, beamforming, and the like may be applied as antenna technology, and the present invention is not limited to the above-described embodiments. In addition, the signal transmitted/received through the sender-receiver 940 may be modulated and demodulated, and controlled by the processor 930.
Although exemplary methods of the present invention are represented in a series of steps for clarity of a description, the exemplary methods are not intended to limit the sequence of steps. Some steps may be performed simultaneously or may be performed in a different order as necessary. In order to implement the method presented by the present invention, an additional step may be added to the exemplary method, some steps may be omitted, or some steps are omitted and an additional step may be added to the exemplary method.
Various embodiments of the present invention are not listed in all possible combinations, but are for describing representative aspects of the present invention, and matters described in the various embodiments may be applied independently or may be applied as a combination of two or more.
In addition, various embodiments of the present invention may be implemented by hardware, firmware, software, or a combination thereof. In the case of implementing the present invention by hardware, the present invention may be implemented with one or more ASICs (Application Specific Integrated Circuits), DSPs (Digital Signal Processors), DSPDs (Digital Signal Processing Devices), PLDs (Programmable Logic Devices), FPGAs (Field Programmable Gate Arrays), general processors, controllers, microcontrollers, microprocessors, or the like.
The scope of the present invention includes software or machine-executable instructions (e.g., operating systems, applications, firmware, programs, or the like) that allow operations according to methods of various embodiments to be executed on a device or a computer, and a non-transitory computer-readable medium which stores such software and instructions and is executable on a device or a computer.
Now, an actual implementation form of the probe 200 (see
As mentioned above, basically, the probe may be implemented in a pivotal tongs structure as shown in
Light source units (27 and 28 of
Meanwhile, a probe 200b shown in the lower part of
The biological tissue inserted between the first part and the second part of the probe is generally an aggregate of inhomogeneous tissues and thus inevitably affects the measurement signal in a chaotic manner depending on the time of measurement or individual differences. In particular, signal detection capable of deriving a certain correlation with the concentration of a target material and a signal processing method therefor are very important even when an intensity of a signal detected by the probe using an optical method tends to be chaotic due to chaotic scattering according to inhomogeneity inside the biological tissue and the effect of temperature change.
A probe structure of the present invention for overcoming such a limitation will be described in detail below with reference to the accompanying drawings.
First,
Components of the balanced fastening-type probe fastened to biological tissue 1020 such as an earlobe largely include a lower frame 1021, a moving frame 1022, an upper frame 1023, an upper cover 1024, a lower cover 1025, a lower printed board assembly (PBA) 1026, an upper PBA 1027, a rubber boot 1028, and an electric wire interface 1029. The other components except for the moving frame 1022 are integrally assembled and have a fixed structure.
The upper frame 1023 and the lower frame 1021 are spaced apart from each other, and the upper frame 1023 and the lower frame 1021 are structurally fixed. In addition, the moving frame 1022 is located between the upper frame 1023 and the lower frame 1021 and forms a space separated from the lower frame 1021. The biological tissue 1020 is inserted into the separation space.
Since the moving frame 1022 is movable up and down between the upper frame 1023 and the lower frame 1021, the separation space is reduced or expanded by the movement of the moving frame 1022. Once the biological tissue 1020 is inserted into the separation space, the moving frame 1022 is pressed toward the biological tissue 1020 by an elastic force of elastic elements 1222 and 1223 such as compression spring, rubber, etc., and is brought into close contact with the moving frame 1022. When a user applies a force against the elastic force of the elastic elements 1222 and 1223, the space separated from the lower frame 1021 is widened and the biological tissue 1020 may be withdrawn or inserted.
Here, a separation space expansion mechanism is required for the user to apply a force against the elastic force of the elastic elements 1222 and 1223 to widen the space separated from the lower frame 1021. In order to configure the separation space expansion mechanism, the moving frame 1022 includes a pillar 1022a formed in an inverted “L” shape at a portion thereof. The pillar 1022a passes through a hole 1211 formed in the lower frame 1021, and is integrally coupled to a flat frame 1022b at a lower part of the lower frame 1021 by a screw 1226. As a result, the moving frame 1022 is assembled to receive a downward pressure by the elastic elements 1222 and 1223 between the lower frame 1021 and the upper frame 1023, which are integrally fixed and assembled, and a pillar 1234 serves as a guide for preventing the moving frame 1022 from being separated and inclined when the moving frame 1022 moves.
Since the flat frame 1022b integrally assembled to the lower part of the moving frame 1022 bent in the inverted “L” shape is exposed below the lower frame 1021, when a larger force is applied upward to the flat frame 1022b in a direction opposite to the elastic force of the elastic elements 1222 and 1223, the moving frame 1022 moves toward the upper frame 1023 and expands a separation distance (i.e., the separation space) from the lower frame 1021 to D so that the biological tissue 1020 such as an earlobe or flesh between fingers may be inserted into the separation space. A separation distance D1 between facing surfaces of the lower frame 1021 and the upper frame 1023 has a fixed value. Accordingly, in the moving frame 1022, when a thickness of the plate in contact with the biological tissue 1020 is D2, a maximum value of the separation distance D is designed to satisfy D(max)=D1−D2. Accordingly, a maximum thickness t of the biological tissue 1020 inserted into the probe is determined to satisfy t≤D(max).
Describing an operation sequence for inserting and fastening biological tissue, (1) press the flat frame 1022b with a hand to maximize D, (2) insert the biological tissue 1020 between the lower frame 1021 and the moving frame 1022, and then (3) remove a pressing force, so that the biological tissue 1020 is easily adhered and coupled between the moving frame 1022 and the lower frame 1021 by the elastic force of the elastic elements 1222 and 1223. Here, small protrusions 1221 additionally formed in the moving frame 1022 serve to prevent the biological tissue 1020 from being separated while being fastened to the probe.
In addition, the moving frame 1022 further includes a hole 1220 for a light signal path formed in accordance with a position of a light sending and receiving module 1231 assembled to the upper frame 1023, and a transparent window 1224 assembled to the hole 1220. The transparent window 1224 may be transparent glass or transparent plastic having a small thickness.
In the upper frame 1023, a bottom 1422 of both pillars 1411 and 1412, which are shown in a side view of
The moving frame 1022 and the upper frame 1023 have additional structures such as grooves or holes into which the elastic elements 1222 and 1223 may be inserted and assembled. Alternatively, the upper frame 1023 is assembled by including a circular or polygonal pillar 1234, and the moving frame 1022 further includes a hole 1225 through which the pillar 1234 may move. As a result, the moving frame 1022 is assembled to receive a downward pressure by the elastic elements 1222 and 1223 between the lower frame 1021 and the upper frame 1023, which are integrally fixed and assembled, and the pillar 1234 serves as a guide for preventing the moving frame 1022 from being separated and inclined when the moving frame 1022 moves.
In addition, as shown in
The upper frame 1023 includes the light sending and receiving module 1231 and the upper PBA 1027 connected to the light sending and receiving module 1231, and is fixedly assembled. The light sending and receiving module 1231 may include the light source units 27 and 28, the receiving units 23 and 24, and the sensor units 25 and 26 for measuring a temperature and a thickness, which are described above with reference to
Meanwhile, an ultrasound module 1215 and the lower PBA 1026 connected to the ultrasound module 1215 are assembled to the lower frame 1021. The ultrasound module 1215 may include an ultrasound element 1214 and an impedance matching plate 1213 for assisting smooth transmission of ultrasound to the ultrasound element 1214. At least a portion of the ultrasound signal 1203 generated in the biological tissue 1020 and passing through the biological tissue 1020 passes through the impedance matching plate 1213 and is detected by the ultrasound element 1214.
Unlike the conventional pivot-type probe described with reference to
In addition, the probe of
In addition, the probe of
A rubber boot 1028, which is another component not yet described in
In
A structure viewed from the above of the upper frame 1033 in
The other two of the four light modules assembled to the upper frame 1033 of
In order to help understanding the overall structure of the upper frames 1023 and 1033 and to describe additional functions,
In addition, in the upper frames 1023 and 1033, three circular grooves 1401, 1402, and 1403 are formed with a diameter and a certain depth that can accommodate the above-described elastic elements, and a through hole 1404 is formed to accommodate another elastic element described above. Specifically, the groove 1401 is a position at which the elastic element 1222 of
As shown in the first side view 41 of
As described above, the balanced fastening structure probe for noninvasive blood glucose measurement according to the present invention basically provides a means capable of inserting and fixing biological tissues such as earlobes of various thicknesses between frames in a state in which a transmitting element and a receiving element are always installed in a constant form on the frames of the probe. In addition, although the light sending and receiving elements and the ultrasound element are mainly described in
As an example, in
Hereinafter, an operation of the noninvasive blood glucose measurement apparatus and method, measurement examples of the light reflection and the transmission, and signal processing methods will be described.
First, as a step-wise process for the blood glucose measurement, a transmission signal for a light wavelength λg targeted in a wavelength region (for example, the wavelength region 612 of
Next, at least one transmission signal of an arbitrary comparison wavelength λc of light for relative correction is selected in wavelength regions (for example, 610, 620, 613, and 614 in
The selected multi-channel light signals are sent through the biological tissue to be measured, and an intensity of a reception signal sent at each wavelength is measured, and a wavelength ratio of λc/λg is obtained by dividing an intensity of a reception signal transmitted at the comparison wavelength λc by an intensity of a reception signal transmitted at a target wavelength λg. The wavelength ratio of λc/λg is measured in this way for each of samples having different glucose concentrations, and a relative difference (defined as a relative ratio) for the sample with the glucose concentration of 0 mg/dL is finally obtained. The above description may be more clearly expressed using equations. That is, a ratio R(λgc), at the two wavelengths of λc/λg, of an intensity I(λc) of the reception signal transmitted at the comparison wavelength λc described in
R(λgc)=I(λc)/I(λg) (1)
In addition, a relative difference Drs(λgc) between the ratio Rr(λgc) at the wavelengths of λc/λg in the measurement sample and the ratio Rs(λgc) at the wavelengths of λc/λg in the reference sample in which the glucose concentration is 0 mg/dL is summarized as an equation and is expressed as Equation (2) below.
Next, pieces of data obtained by measuring various relative ratios according to actual glucose concentrations in the biological tissue to be measured are accumulated, and a standard comparison table may be created based on the accumulated data. The actual glucose concentration for the biological tissue may be utilized on the basis of a value measured through a conventional blood drawing or minimally invasive blood glucose meter. A reference comparison table prepared by extracting learning data for noninvasive blood glucose measurement using the above method is input to the bio-recorder 13 or the like.
Now, the biological tissue to be measured in a state in which a blood glucose value is unknown is inserted into the probe, and a relative ratio is measured from the target wavelength kg and the comparison wavelength λc described above, and a blood-glucose concentration value corresponding to the measured relative ratio is found from the reference comparison table and displayed as the evaluated blood glucose level. Since a glucose concentration in the human body may not be 0 mg/dL, a reference value in the reference comparison table having a blood glucose value of a predetermined level extracted from the learning data described above may be used instead of the reference sample having a glucose concentration of 0 mg/dL as described with reference to
Specifically, the target wavelength λg is in the wavelength region 612 of
Meanwhile, the above-described basic signal processing characteristics are maintained to be the same, but the relative ratio Drs(λgc) in Equation (2) is used in a rearranged form as in Equation (3) by adding a natural logarithm and a minus (−) sign according to the convenience of use, thereby increasing the visibility of the characteristic analysis as necessary,
In Equation (3),
is transmittance of the measurement sample relative to the reference sample at the comparison wavelength λc, and −ln( ) for the transmittance means comparative extinction with respect to the reference sample at the comparative wavelength λc, and thus may be expressed as
means comparative extinction of the measurement sample with respect to the reference sample at the target wavelength λg. Physically, extinction indicates a degree by which light energy incident on the biological tissue is absorbed and scattered internally and attenuated, and comparative extinction relative to the reference sample is a term expressing a degree of relative extinction to the reference sample.
Equation (3) may be defined as a difference of the extinction of the measurement sample relative to the reference sample at each of the comparison wavelength λc and the target wavelength χg, that is ΔEc(λgc), and may be named and expressed as a normalized extinction difference (NED) method. The NED method implicitly represents that a difference in extinction appears when the natural logarithm and minus calculations are applied on the result reflecting both the normalization between the reference sample and the measurement sample and the normalization between the comparison wavelength λc and the target wavelength λg.
Such a signal processing method of the present invention provides an efficient means for deriving a correlation with respect to a target material concentration from chaotic measurement signals that are diffusely transmitted through or reflected by an inhomogeneous material such as biological tissue.
Meanwhile, the above-described balanced fastening probe according to an embodiment of the present invention includes a means for measuring a thickness of an inserted biological tissue by effectively using spatial structural characteristics between the moving frames 1022 and 1032 and the lower frames 1021 and 1031. That is, the thickness of the biological tissue may be estimated from an electrical signal such as a resistance or a voltage output from the pressure sensor 1271 through the means 1022, 1023, 1027, 1271, and 1223 related to the thickness measurement based on the pressure applied to the biological tissue described in
The light sending and receiving module 1231 included in the upper frame 1023 of FIG. 11 and the plurality of light modules 1331a, 1331b, 1331c, and 1332 and the temperature sensor 1336 included in the upper frame 1033 of
The process shown in the flowchart of
In the light and/or photoacoustic transmission measurement 91, the output light signals 1201, 1301a, 1301b, and 1301c output from the upper frames 1023 and 1033 described in
In the light reflection measurement 92, the output light signals 1201, 1301a, 1301b, and 1301c output from the upper frames 1023 and 1033, diffused and reflected in the biological tissue, and transmitted to the light sending and receiving module 1231 or the light module 1332 of the upper frame are detected, and the light reflection characteristics are measured using the relative ratio Drs(λgc) or the normalized extinction difference ΔEc(λgc) described in
In the temperature measurement 93, multiple pieces of temperature information are simultaneously measured based on a first temperature sensor (e.g., 1336, or included in 1231) included in the upper frames 1023 and 1033 for monitoring the temperature of the light modules, of, and a second temperature sensor 1212 for monitoring the temperature on the surface of the biological tissue or in the vicinity of a bio-signal receiving module, and a third temperature sensor 1252 for monitoring the temperature of the housing of the probe or ambient air temperature.
In the pressure measurement 94 a pressure signal is detected through an organic interaction of the thickness measurement means (1022, 1223, 1027, 1271, and the like) included in the upper frames 1023 and 1033 to use as information for determining whether biological tissue is inserted into the probe, and produce a measurement result monitored in real time up to a change in the thickness of the inserted biological tissue on the basis of the pressure signal as shown in the method of
A short-term blood glucose value measurement 95 includes (1) a process of deriving an average value by repeating the light and/or photoacoustic transmission measurement 91, the light reflection measurement 92, the temperature measurement 93, and the pressure measurement 94 N times during a certain time interval Δt, (2) a process of correcting the light transmission measurement and light reflection measurement results on the basis of the temperature and pressure measurement values, (3) a process of deriving each expected blood glucose level by comparing and analyzing the reference comparison table obtained in advance through prior learning data, the averaged and derived light and/or photoacoustic transmission measurement result, and the light reflection measurement results, (4) a process of finally determining a short-term blood glucose level on the basis of the blood glucose estimation values derived from the light and/or photoacoustic transmission and light reflection measurements, and 5) a process of recording and outputting the finally determined short-term blood glucose value. As an example, the short-term blood glucose value may be measured through repeated measurement and correction for a period of several seconds to several minutes.
A continuous blood glucose measurement and prediction 96 includes a process of repeatedly performing the short-term blood glucose value measurement 95 for a predetermined period of time (e.g., 5 minutes) and recording and outputting pieces of blood glucose value data (12 pieces of data per hour, 288 pieces of data in 24 hours) accumulated for a long time (e.g., 24 hours). Furthermore, the continuous blood glucose measurement and prediction 96 may further include a process of predicting an expected blood glucose value after predetermined lengths of time on the basis of the data accumulated and measured for the predetermined period of time or more.
The probe for noninvasive blood glucose measurement according to the embodiment described above may equally be used for round-shaped biological tissues including bones, such as fingers and toes, as well as thin biological tissues at the extremities of the human body, such as earlobes and flesh between the fingers. For example, the components constituting the probe of the new structure according to the present invention may be equally applied by manufacturing and applying the part of the probe that is closely applied to biological tissue in a flat or round shape.
According to the present invention, a noninvasive blood glucose measurement apparatus and method using multiple sensors can be provided in which a blood-glucose concentration for a biological tissue part such as an earlobe of the human body can be measured. More stable and accurate signal measurement is possible by always maintaining an interval and directionality of signal measurement components constant although the biological tissue varies in thickness. It is also possible to automatically and simultaneously perform personalized thickness correction in noninvasive measurement of a bio-signal by additionally including a means for measuring a thickness of the biological tissue inserted into a probe.
In addition, since the noninvasive blood glucose measurement apparatus and method according to embodiments of the present invention use a light source in a near-infrared wavelength region, manufacturing costs can be reduced, and miniaturization is possible so that it can be easily carried.
A human body wearable probe can be worn more conveniently even when the measurement is performed continuously for a long time, by applying a uniform force (pressure) to the human body on the basis of a probe platform of a new balanced fastening-type tongs structure to solve the problems of a conventional scissors type or pivotal tongs structure.
In the above, the embodiments specifically implementing the spirit of the present invention have been described. However, the technical scope of the present invention is not limited to the above-described embodiments and drawings, but is determined by reasonable interpretation of the claims.
Number | Date | Country | Kind |
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10-2022-0037822 | Mar 2022 | KR | national |
10-2022-0114890 | Sep 2022 | KR | national |
10-2023-0025690 | Feb 2023 | KR | national |