Phantom set configuration system for infrared non-invasive blood glucose meter

Abstract

The present invention relates to a phantom set configuration system for an infrared-type non-invasive blood glucose meter, comprising a combination of slides with different energy absorption rates for each wavelength, for quality control of the accuracy and precision of a non-blood sampling and non-invasive blood glucose meter that measures blood glucose by emitting infrared rays with multiple frequency wavelengths to a user's finger and detecting scattered light. This project (result) is the result of research conducted under the Phase 3 Leading University Industry-Academic Cooperation Project (LINC 3.0), which was funded by the Ministry of Education and the National Research Foundation of Korea. - NTIS Project Number: 1345370645 - (Institution) R&D Project Number: LINC3.0-2023-26

Description

Technology Field

[0001] The present invention relates to an infrared-type non-invasive blood glucose meter, and more specifically, to a phantom set configuration system for an infrared-type non-invasive blood glucose meter that comprises a combination of slides with different energy absorption rates for each wavelength, for quality control of the accuracy and precision of a non-blood sampling and non-invasive blood glucose meter that measures blood glucose by emitting infrared rays having multiple frequency wavelengths to a user's finger and detecting scattered light.

[0002] This project (result) is the result of the Phase 3 Leading University Industry-Academic Cooperation Project (LINC 3.0), which was funded by the Ministry of Education and the National Research Foundation of Korea.

[0003] - NTIS Project Number: 1345370645

[0004] - (Institution) R&D Project Number: LINC3.0-2023-26 Background Technology

[0005] Near-infrared spectroscopy is a technology widely used for the non-destructive analysis of components in grains, fruits, and dairy products. Because it is safe for the human body and allows for the accurate comparison of water and glucose values, it is also applied in the field of medical devices for non-invasive oxygen saturation (SpO2) measurement.

[0006] Because it is possible to predict blood glucose levels using wavelengths in this near-infrared region (700 to 2500 nm) and to measure various vital signs such as pulse, respiration, and blood pressure by analyzing photoplethysmography (PPG) and pulse waves, its value is recognized in platforms that integrate various vital signs, lifelogs, and dietary information, ranging from digital healthcare to precision medicine. A representative example is the non-invasive blood glucose meter called Pebble G, developed by Tomato Crew in early 2023, which analyzes various bio-information including blood glucose using near-infrared light that passes through the finger.

[0007] Diabetes is a very common disease, affecting one in six adults over the age of 30 as of 2020, and patients are required to measure their blood sugar regularly. Traditional blood glucose meters use a method of measuring blood sugar (glucose) from blood obtained by pricking a needle.

[0008] However, due to pain and inconvenience of use, non-invasive continuous glucose monitoring technology has recently been developed, which measures blood glucose from information transmitted by irradiating the skin with a laser or LED.

[0009] This method utilizes multiple light sources capable of irradiating a wearer's body part with near-infrared light of multiple wavelengths having characteristic absorption peaks for blood glucose, a photodetector that receives light irradiated from the multiple light sources and scattered from the body part and converts it into an electrical signal, and an electrical signal from the photodetector that analyzes the electrical signal to obtain the amount of scattered received signal for each wavelength range, and calculates the blood glucose concentration of the body part through matrix formula analysis using the signal amount and the signal amount of a reference sample, which is a preset standard.

[0010] In this case, conditions such as the patient's age, skin thickness and tissue type, skin color by race, and subcutaneous water, fat, and protein components affect the measurement accuracy and quality of the sensor. Therefore, a dedicated phantom is required for the development and evaluation of such non-invasive blood glucose meters. Prior art literature

[0011] Republic of Korea Published Patent No. 10-2007-0055614 (May 30, 2007) The problem to be solved

[0012] The present invention was created to ensure the reliability and stability of an infrared-type non-invasive blood glucose meter against the background described above. The objective of the present invention is to provide a phantom set configuration system for an infrared-type non-invasive blood glucose meter that helps to QC (Quality Control) the accuracy and precision of the non-invasive blood glucose meter by configuring a phantom set with different attenuations by frequency using slides with different energy absorption rates by wavelength, based on a phantom that schematically represents blood glucose measurement according to the analysis of the light absorption pattern of the user's finger portion. means of solving the problem

[0013] For the above purposes, the present invention provides a phantom set configuration system for a non-invasive blood glucose meter, comprising: a phantom set in which a plurality of artificial skin slides configured to have a set racial pigment content, a composite material slide containing a base material containing glucose to have a set absorption rate for infrared light of a selected wavelength, and a finishing slide composed of a blocking material that blocks scattering are sequentially stacked; a test module having a light-emitting unit that selectively emits light of a plurality of wavelengths and a light-receiving unit located on the side of the light-emitting unit to receive scattered light emitted through the light-emitting unit, wherein a test is performed with the artificial skin slides of the phantom set adjacent to each other; a light analysis module that analyzes the wavelength of light received from the light-receiving unit; and a database in which the analysis results of the light analysis module are stored as first analysis information according to the light wavelength of the light-emitting unit, the pigment content, and the base material content. It is characterized by comprising a data analysis module that derives second analysis information including light wavelength and base material content for calibration based on first analysis information for a plurality of phantom sets with different pigment content and base material content excluding glucose for a fixed glucose concentration.

[0014] At this time, it is preferable that the composite material slide is configured by stacking a plurality of blood glucose slides configured to have a glucose content set in stages; a water slide configured to have a light absorption rate corresponding to a water content set in stages; a protein slide configured to have a light absorption rate corresponding to a protein content set in stages; a fat slide configured to have a light absorption rate corresponding to a fat content set in stages; and a base material slide configured to have a light absorption rate corresponding to a base material content set in stages in a selected order.

[0015] In addition, it is preferable that the above blood glucose slides be configured to have blood glucose values ​​of 50 mg / dL, 100 mg / dL, 150 mg / dL, 200 mg / dL, and 300 mg / dL, respectively.

[0016] In addition, the light-emitting unit preferably comprises a plurality of LEDs that output a selected infrared band in the range of 1400 to 1750 nm. Effects of the invention

[0017] Through the present invention, calibration of non-invasive blood glucose meters purchased by individuals and quality control (QC) at the manufacturer can be easily performed, thereby ensuring the reliability and precision of the non-invasive blood glucose meters. Brief explanation of the drawing

[0018] FIG. 1 is a conceptual diagram of a phantom set configuration system for a non-invasive blood glucose meter according to the present invention. FIG. 2 is a conceptual diagram of a phantom set according to the present invention, FIG. 3 is a block diagram showing the configuration and connection relationships according to the present invention, Figure 4 is a graph showing the absorption rates of various composite materials in the finger according to infrared wavelength. Specific details for implementing the invention

[0019] The configuration of the phantom set configuration system for the infrared non-invasive blood glucose meter of the present invention will be described in detail below with reference to the attached drawings.

[0020] FIG. 1 is a conceptual diagram of a phantom set configuration system for a non-invasive blood glucose meter according to the present invention, FIG. 2 is a conceptual diagram of a phantom set according to the present invention, and FIG. 3 is a block diagram showing the configuration and connection relationship according to the present invention. The present invention is a technology for configuring a combination of slides with different energy absorption rates for each wavelength to control the quality of accuracy and precision of a non-blood sampling and non-invasive blood glucose meter that measures blood glucose by transmitting infrared rays of a set wavelength to a finger and detecting scattered light. The main components include a phantom set (1), a test module (2), a light analysis module (3), a database (4) and a data analysis module (5), as well as an interlocking module (6).

[0021] The above phantom set (1) is basically a phantom that mimics a human finger by combining slides corresponding to various substances, namely water, fat, protein, glucose, and other base substances, inside the finger, and each slide contains a substance corresponding to a human body component, including blood sugar, which constitutes the human body.

[0022] The infrared non-invasive blood glucose meter to which the present invention is applied operates based on the fact that the degree of absorption according to the wavelength of light varies depending on various components in our body. For example, when passing through a substance that absorbs orange light, the output of the spectrophotometer is smallest at 620 nm, which corresponds to orange. In other words, the relative degree of absorption for that wavelength is analyzed differently depending on the degree of absorption, and in this case, the absorbance is expressed by the formula: absorption coefficient * transmission path length (cell length) × concentration.

[0023] Through this, a standard substance with a known concentration (e.g., 0.5 ppm, 1 ppm, 5 ppm, 10 ppm) can be measured using a spectrophotometer, and a calibration curve of concentration and absorbance can be constructed. Then, the concentration of an unknown sample can be determined by measuring its absorbance.

[0024] Similarly, absorbance based on internal substances within the human body can be obtained using infrared (IR). By utilizing a finger, which typically contains internal blood vessels and internal components such as melanin, fat, protein, water, and glucose, glucose concentration can also be calculated by determining the absorbance of LEDs of various wavelengths.

[0025] However, when calibrating or quality-controlling IR-based continuous glucose monitors, scattered signals cannot simply be handled using blood samples; therefore, to simulate IR signals, blood vessels, skin, bones, muscles, nerves, etc., must be considered, and a phantom must be created and used from among these that significantly influences the IR signal.

[0026] In addition, the part that is greatly affected by glucose density among these must be varied to match mg / dL, and the phantom set (1) that performs this role in the present invention consists of an artificial skin slide (11) modeled after human skin, a composite material slide (12) made of a base material that is a body internal component and greatly affects IR signals, and a finishing slide (13) made of a blocking material that blocks reflection and scattering.

[0027] The above artificial skin slide (11) is configured to have a plurality of set pigment contents and is selectively used to represent racial information. That is, since light absorption rates may vary by race / body weight, it is necessary to produce a standardized phantom, and in particular, melanin is used as a pigment component representing racial information, and the artificial skin slide is constructed by adjusting its content in stages.

[0028] Melanin is a black or brown pigment found in tissues such as the skin and eyes of various animals. It exists primarily as melanin protein that forms strong bonds with globulin, and skin color is determined by the amount of melanin.

[0029] Chemical formula C 18 H 10It has the characteristic that it dissolves in alkaline solutions or concentrated sulfuric acid as N2O4, but does not dissolve in water. The artificial skin slide (11) above is manufactured to have skin information specific to different races by gradually increasing the content of this melanin pigment. In this case, even if melanin is not used, Indian ink, molecular dye, or fluoropolymer spectralon can be used as a light medium that absorbs light within a predetermined wavelength range, and carbon is added to control the scattering rate to produce an effect substantially identical to the known absorbance of skin.

[0030] Spectralon, the fluoropolymer mentioned above, is a material that generally has the highest diffuse reflectance (causing scattering in all directions) among known materials or coatings across the ultraviolet, visible, and near-infrared regions of the spectrum, and the scattering rate can be controlled by adding carbon to it. For example, a slide with an absorption rate of 50% can be made by compressing and sintering 50% of spectralon and 50% of carbon powder into a solid.

[0031] As described below, in the present invention, infrared light is emitted through a phantom and light scattered from the side is received. At this time, since the reflection information that occurs between slides or between the blood glucose measuring device and the slide, which is not scattered by the human body-mimicking material, is unnecessary information, an artificial skin slide (11) corresponding to artificial skin is required to reduce this.

[0032] The above composite material slide (12) is a slide corresponding to a composite material containing glucose to have a set absorption rate for infrared light of a selected wavelength. In the present invention, blood sugar, i.e., glucose, which is the main measurement target, as well as water, protein, fat, and other base materials constituting the body including bone that have a significant effect on IR signals are used.

[0033] Specifically, the composite material slide (12) is configured by stacking a plurality of blood glucose slides (121) configured to have a light absorption rate corresponding to a stepwise set glucose content, a water slide (122) configured to have a light absorption rate corresponding to a stepwise set water content, a protein slide (123) configured to have a light absorption rate corresponding to a stepwise set protein content, and a fat slide (124) configured to have a light absorption rate corresponding to a stepwise set fat content in a selected order.

[0034] It is preferable that the above blood glucose slide (121) be configured to have blood glucose values ​​of 50 mg / dL, 100 mg / dL, 150 mg / dL, 200 mg / dL, and 300 mg / dL, respectively.

[0035] The above water slide (122) is configured to have a light absorption rate corresponding to a water content set in stages, the above protein slide (123) is configured to have a light absorption rate corresponding to a protein content set in stages, the above fat slide (124) is configured to have a light absorption rate corresponding to a fat content set in stages, and the above base material slide (125) is configured to have a light absorption rate corresponding to a base material content set in stages.

[0036] Similarly, a method may be used in which substances corresponding to water, proteins and fats, and other base material components are injected into the slide at a predetermined concentration, or, as mentioned, Spectralon, a fluoropolymer having the highest diffuse reflectance (causing scattering in all directions) among known materials or coatings across the ultraviolet, visible, and near-infrared regions of the spectrum, may be used, and carbon may be added to control the scattering rate.

[0037] The above finishing slide (13) is composed of a blocking material that blocks reflection and scattering, and serves to finish the uppermost layer, that is, the last layer on the opposite side to the test module, with a black material so that the light from the light-emitting part is not reflected or scattered after binding the blood glucose slide, water slide, protein slide, and fat slide corresponding to various tissues.

[0038] The above test module (2) is configured to optically analyze the phantom set (1) and is equipped with a light-emitting unit (21) that selectively emits infrared light of a plurality of wavelengths and a light-receiving unit (22) located on the side of the light-emitting unit (21) that receives scattered light emitted through the light-emitting unit (21), and the test is performed by placing the artificial skin slide (11) of the phantom set (1) adjacent to the light-emitting unit (21) and the light-receiving unit (22).

[0039] Considering the scattering rate rather than the reflectance, the light from the light-emitting part enters the finger vertically, and the light scattered obliquely rather than vertically is received by the light-receiving part (22) located on the side of the light-emitting part (21).

[0040] At this time, the light-emitting unit (21) preferably has a plurality of LEDs (211) that output a selected infrared band in the range of 1400 to 1750 nm.

[0041] Figure 4 is a graph showing the absorption rate of various composite materials in the finger according to infrared wavelengths. Since these values ​​vary by race, body weight / height, and blood sugar levels, it is possible to ensure the accuracy and precision of the device with a phantom for a specific race, body weight, and height according to the present invention.

[0042] At this time, it is preferable to select the wavelength of the LED (211) constituting the light-emitting part (21) as the peak value of the scattering rate according to each component of the human body (wavelength at which the most absorption occurs). In the embodiment of the present invention, water: 1450 nm, protein: 1500 nm, fat: 1720 nm, glucose: 1600 nm, and 1650 nm as a base material without a peak value were selected.

[0043] As mentioned earlier, a single phantom set is substantially composed of 7 slides, including 5 material slides, an artificial skin slide, and a finishing slide, and can be made to have respective absorption rates for the wavelengths used as follows.

[0044] Wavelength used protein slide fat slide water slide blood sugar slide 1450㎚ 50% -3% 50% 2% 1500㎚ 60% -9% 18% 40% 1600㎚ 18% -10% -25% 85% 1350㎚ 2% 90% -8% 80% 1720㎚ 65% 90% -27% 78%

[0045] In the table above, the absorption rate for blood glucose is based on a specific value (e.g., absorption rate for 100 mg / dL blood glucose), and this absorption rate changes for other blood glucose values.

[0046] Therefore, as mentioned, multiple blood glucose values ​​of 50 mg / dL, 100 mg / dL, 150 mg / dL, 200 mg / dL, and 300 mg / dL are created and selected to determine the accuracy and linearity of the device for each blood glucose level, and the phantom for 50 mg / dL blood glucose consists of phantoms of 5 wavelengths.

[0047] For example, a bundle of slides with absorption rates for protein, fat, water, blood glucose, and other base substances using a 1450 nm phantom constitutes one phantom, and if made for each of the five wavelengths, it forms one set for one blood glucose level. The phantoms for the five blood glucose levels (glucose levels) consist of 5 sets, that is, 5 × 5 = 25 bundles of slides.

[0048] Generally, non-invasive blood glucose meters using IR (infrared) measure by sequentially irradiating frequencies corresponding to the five wavelengths mentioned above. Calibration can be performed by sequentially measuring all five corresponding phantoms with the non-invasive blood glucose meter, and then by sequentially measuring with a phantom corresponding to another blood glucose level. Calibration can also be performed using a phantom that matches the user's race, height, weight, and the representative value of hyperglycemia, which is 200 mg / dL.

[0049] The light analysis module (3) is configured to analyze the wavelength of light received from the light receiving unit (22), and the absorbance analysis of the phantom set that is tested by contacting the test module (2) is performed, and the test is performed on a plurality of phantom sets and the analysis is performed.

[0050] The above database (4) stores the analysis results of the light analysis module (3) as first analysis information according to the light wavelength of the light-emitting part (21), the pigment content, and the base material content. That is, the analysis results are classified according to the five wavelengths mentioned above, and classified according to the pigment content and base material content and stored as first analysis information.

[0051] In this case, blood glucose measurement is easy if the absorbance analysis results are identical for the same light wavelength and blood glucose level; however, since differences in absorbance actually occur due to different base materials, it is necessary to analyze this aspect additionally.

[0052] The above data analysis module (5) derives second analysis information including light wavelength and base material content for calibration based on first analysis information for a plurality of phantom sets with different pigment content and base material content excluding glucose for a fixed glucose concentration. That is, by deriving second analysis information that summarizes the correlation between changes in other base materials, including pigment, and wavelength for the same glucose concentration, it is possible to confirm changes in light absorbance according to changes in base materials at the same blood glucose level.

[0053] The above-mentioned interlocking module (6) is configured to apply the phantom set according to the present invention to an actual non-invasive blood glucose meter, and supports that the absorbance analysis results obtained through the test module (2) and the light analysis module (3) for the same phantom set are identical to the absorbance analysis results obtained using light of the same wavelength in a known non-invasive blood glucose meter.

[0054] An example of a known non-invasive blood glucose measuring device technology is Korean Registered Patent No. 10-2033914 (registered on October 14, 2019). The present invention is a non-invasive blood glucose measuring device capable of determining blood glucose from a signal obtained by transmitting and receiving multiple infrared rays. From the perspective of a manufacturer, by providing a phantom set for performance evaluation or calibration of this non-invasive blood glucose measuring device, calibration can be performed by confirming that the blood glucose measurement results using a specific phantom set yield the same result for all manufactured products, under the assumption that the product's scattered light analysis algorithm and the algorithm of the light analysis module (3) are substantially identical.

[0055] Using the phantom set (1) according to the present invention, a non-invasive blood glucose meter can be evaluated in conjunction with a relevant standard as follows.

[0056] For example, as an accuracy evaluation, the following rules must be applied to guide the testing process and record and manage the evaluation process for 3 types of phantoms and 10 non-invasive continuous glucose monitors: 1. Intermediate measurement accuracy must be evaluated under normal usage conditions where the user uses the same non-invasive glucose monitor for several days. 2. The test design must include multiple users. 3. The evaluation must be conducted with at least one measurement per phantom per day, using at least 10 non-invasive glucose monitors and three glucose concentrations representing hyperglycemia, normal glucose, and hypoglycemia conditions. The total number of measurements must be at least 300.

[0057] In addition, as an evaluation of measurement repeatability, the following may be applied: 1. Evaluation based on a series of measurements taken by a single user within a short period using the same non-invasive blood glucose meter; 2. The evaluation of measurement repeatability must be conducted using at least 10 non-invasive blood glucose meters and 5 phantoms representing conditions of hyperglycemia, normoglycemia, and hypoglycemia. At least 10 measurements must be performed for each non-invasive continuous glucose meter; 3. A regulation may be applied requiring that measurement repeatability data be collected for a period not exceeding one day using the non-invasive blood glucose meter.

[0058] To this end, five human blood-mimicking phantoms are used, and ten non-invasive blood glucose meters are prepared. One phantom is assigned to each non-invasive glucose meter, and measurements are taken using the phantom. This process is repeated nine more times using the same phantom after five minutes. Additionally, the previous steps are repeated on the remaining nine non-invasive glucose meters. This results in a total of 100 measurements per phantom. (10 devices * 10 times)

[0059] Then, by taking the next phantom and repeating the steps described above, a total of 500 measurements are obtained, and the mean, standard deviation, and coefficient of variation (CV) are calculated for each sugar concentration, and this test process is guided and the evaluation process is recorded and managed.

[0060] The rights of the present invention are not limited to the embodiments described above but are defined by what is stated in the claims, and it is obvious that a person skilled in the art may make various modifications and adaptations within the scope of the rights described in the claims. Explanation of the symbols

[0061] 1: Phantom Set 11: Artificial Skin Slide 12: Complex substance slide 121: Blood glucose slide 122: Water slide 123: Protein slide 124: Fat slide 125: Base material slide 13: Closing Slide 2: Test Module 21: Light-emitting part 211: LED 22: Light receiving unit 3: Optical analysis module 4: Database 5: Data Analysis Module 6: Interfacing Module

Claims

Claim 1 A phantom set configuration system for a non-invasive blood glucose meter comprises: a plurality of artificial skin slides (11) configured to have a set racial pigment content, a composite material slide (12) containing a base material containing glucose to have a set absorption rate for infrared light of a selected wavelength, and a finishing slide (13) composed of a blocking material that blocks scattering, which are sequentially stacked; a test module (2) in which a test is performed adjacent to the artificial skin slides (11) of the phantom set (1), wherein a light emitting part (21) that selectively emits light of a plurality of wavelengths so as to be incident vertically toward the phantom set (1), and a light receiving part (22) positioned on the side of the light emitting part (21) to receive scattered light emitted through the light emitting part (21) at an angle rather than vertically; a light analysis module (3) that analyzes the wavelength of light received from the light receiving part (22); and the light wavelength of the light emitting part (21) and the pigment content and A database (4) in which the analysis results of the optical analysis module (3) are stored as first analysis information according to the content of the base material; a data analysis module (5) that derives second analysis information including optical wavelengths and base material content for calibration based on the first analysis information for a plurality of phantom sets with different pigment content and base material content excluding glucose for a fixed glucose concentration;The composite material slide (12) is composed of a plurality of blood glucose slides (121) configured to have glucose contents set in steps to have blood glucose values ​​of 50 mg / dL, 100 mg / dL, 150 mg / dL, 200 mg / dL, and 300 mg / dL, respectively; a water slide (122) configured to have a light absorption rate corresponding to a water content set in steps; a protein slide (123) configured to have a light absorption rate corresponding to a protein content set in steps; a fat slide (124) configured to have a light absorption rate corresponding to a fat content set in steps; and a base material slide (125) configured to have a light absorption rate corresponding to a base material content set in steps, stacked in a selected order, and the light-emitting part (21) corresponds to a peak value of the scattering rate according to each component of the human body within the range of 1400 to 1750 nm, wherein 1450 nm for water absorption, 1500 nm for protein absorption, and glucose A phantom set configuration system for a non-invasive blood glucose meter, characterized by comprising a plurality of LEDs (211) that selectively output wavelengths of 1600 nm for absorption, 1650 nm for base material absorption, and 1720 nm for fat absorption, wherein each slide constituting the composite material slide (12) is manufactured by adding carbon powder for controlling scattering rate to a fluoropolymer and compressing and sintering it into a solid, wherein the artificial skin slide (11) is configured with a melanin content that is controlled in stages, and the finishing slide (13) is made of a black material so that the light from the light-emitting part (21) is not reflected or scattered. Claim 2 delete Claim 3 delete Claim 4 delete

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