Skin phantom, component concentration measurement device, and measurement method

Abstract

A skin phantom (1) is obtained by laminating a porous film (3) on a hydrogel (2) comprising a gelling agent, glucose, an electrolyte, and water. The porous film (3) is one that is impregnated with a hydrophobic material or one in which a hydrophobic material is formed on the surface of the porous film (3) on the side in contact with the hydrogel (2).

Description

Skin phantom, component concentration measuring device and measuring method

[0001] The present invention relates to a skin phantom that simulates human skin, and a constituent concentration measuring device and measuring method that are capable of estimating the glucose concentration in a measurement target such as a skin phantom.

[0002] Efforts have been made to measure the amount of glucose contained in interstitial fluid in the skin as an index correlated with blood glucose levels, and in recent years, painless measurement techniques using microneedles have been developed. To measure the performance of microneedles, studies have been conducted on skin-simulating environments (skin phantoms). Non-Patent Document 1 proposes the use of a system in which parafilm is attached to a hydrogel.

[0003] On the other hand, in addition to direct measurement using microneedles, etc., methods for non-invasively investigating biological tissues using radio waves are also being considered. Non-Patent Document 2 proposes a skin phantom using hydrogel targeted at the GHz band and measurement of dielectric constant using a coaxial probe method.

[0004] The content proposed in Non-Patent Documents 1 and 2 is a technology that is ultimately aimed at application to humans, and by obtaining knowledge using a phantom equivalent to a human, it will contribute to improving the accuracy of measurements on humans.

[0005] However, the technique disclosed in Non-Patent Document 1 has a problem in that the microneedles penetrate the skin, which may cause damage to the skin tissue. To reduce damage to the skin tissue, it is necessary to estimate the glucose level by a non-invasive method using radio waves or the like, as disclosed in Non-Patent Document 2.

[0006] The skin phantom used in Non-Patent Document 1 is a multi-layered skin phantom made of a combination of parafilm and hydrogel, and is adjusted to have a hardness equivalent to that of skin. However, it is unclear whether this multi-layered skin phantom has a structure equivalent to that of skin with respect to radio waves.

[0007] On the other hand, Non-Patent Document 2 proposes a hydrogel that is equivalent to a living body in terms of radio wave reflection. However, the dielectric loss of this hydrogel below 1 GHz is significantly different from that of actual skin. Furthermore, skin has a multi-layer structure including the stratum corneum, epidermis, and dermis. In contrast, the hydrogel proposed in Non-Patent Document 2 is made of a uniform material, and it is unclear how it will respond to radio waves when substances such as glucose are changed.

[0008] As described above, a multilayered skin phantom that can be applied to noninvasive methods using radio waves, etc. has not been realized until now. Furthermore, because the response of the multilayered skin phantom to radio waves when the glucose level in the multilayered skin phantom is changed is unknown, it has not been possible to estimate the glucose level in the multilayered skin phantom using previous technology.

[0009] Hazhir Teymourian, et al., “Microneedle-Based Detection of Ketone Bodies along with Glucose and Lactate: Toward Real-Time Continuous Interstitial Fluid Monitoring of Diabetic Ketosis and Ketoacidosis”, Analytical Chemistry, 2020, 92, PP.2291-2300Sergio Castello-Palacios, et al., “Gel Phantoms for Body Microwave Propagation in the (2 to 26.5) GHz Frequency Band”, IEEE TRANSACTIONS ON ANTENNAS AND PROPAGATION, VOL.67, NO.10, PP.6564-6573, 2019

[0010] The present invention has been made to solve the above problems, and aims to provide a skin phantom that can obtain dielectric properties similar to those of human skin. Another aim of the present invention is to provide an element concentration measuring device and a measuring method that can non-invasively measure the glucose concentration of a multi-layered measurement target.

[0011] The skin phantom of the present invention is characterized by laminating a porous film on a hydrogel consisting of four components: a gelling agent, glucose, an electrolyte, and water.

[0012] In addition, the constituent concentration measuring device of the present invention is characterized by comprising a measuring unit configured to irradiate an electromagnetic wave onto a measurement object and measure a reflected signal of the electromagnetic wave; a dielectric constant calculation unit configured to calculate the relative dielectric constant and dielectric loss of the measurement object for each frequency based on the measurement results by the measuring unit; a first estimation unit configured to estimate the electrolyte concentration in the measurement object based on the frequency at which the dielectric loss is minimized; a second estimation unit configured to estimate the water content in the measurement object based on the slope of the approximation curve of the relative dielectric constant at a first specific frequency; and a third estimation unit configured to estimate the glucose concentration in the measurement object based on the value of the dielectric loss at a second specific frequency.

[0013] Furthermore, the component concentration measurement method of the present invention is characterized by including a first step of irradiating an electromagnetic wave onto a measurement object and measuring a reflected signal of the electromagnetic wave; a second step of calculating the relative permittivity and dielectric loss of the measurement object for each frequency based on the measurement results of the first step; a third step of estimating the electrolyte concentration in the measurement object based on the frequency at which the dielectric loss is minimized; a fourth step of estimating the water content in the measurement object based on the slope of the approximation curve of the relative permittivity at a first specific frequency; and a fifth step of estimating the glucose concentration in the measurement object based on the value of the dielectric loss at a second specific frequency.

[0014] According to the present invention, a skin phantom with dielectric properties similar to those of human skin can be realized by laminating a porous film onto a hydrogel consisting of four components: a gelling agent, glucose, electrolytes, and water. This invention allows preliminary studies of human testing to be performed using the skin phantom. Furthermore, since the material in the skin phantom can be easily changed, the accuracy of noninvasive measurement methods using radio waves, etc., can be confirmed using the skin phantom. Furthermore, this invention allows the skin phantom to be used in the development of sensing device technology and transdermal drug delivery.

[0015] Furthermore, in the present invention, the glucose concentration of a multilayered object can be measured noninvasively by irradiating the object with electromagnetic waves, measuring the reflected signal of the electromagnetic waves, calculating the dielectric constant and dielectric loss of the object for each frequency, estimating the electrolyte concentration in the object based on the frequency at which the dielectric loss is minimized, estimating the water content in the object based on the slope of the approximation curve of the dielectric constant at a first specific frequency, and estimating the glucose concentration in the object based on the value of the dielectric loss at a second specific frequency. Furthermore, the component concentration measurement method of the present invention can be used in situations requiring glucose quantification and management, such as food testing, beverage testing, cell culture media, and plant factory media.

[0016] FIG. 1 is a cross-sectional view of a skin phantom according to an embodiment of the present invention. FIG. 2 is a block diagram showing the configuration of a constituent concentration measuring device according to an embodiment of the present invention. FIG. 3A is a graph showing the results of measuring the relative permittivity obtained by the constituent concentration measuring device. FIG. 3B is a graph showing the results of measuring the dielectric loss obtained by the constituent concentration measuring device. FIG. 4 is a graph showing the results of comparing the characteristics of a skin phantom according to an embodiment of the present invention with human skin. FIG. 5A is a graph showing the relative permittivity when the composition of the hydrogel in a skin phantom according to an embodiment of the present invention is changed. FIG. 5B is a graph showing the dielectric loss when the composition of the hydrogel in a skin phantom according to an embodiment of the present invention is changed. FIG. 6A is a graph showing the frequency at which the dielectric loss of the hydrogel is minimized. FIG. 6B is a graph showing the slope at 1 GHz of the approximation curve of the relative permittivity of the hydrogel. FIG. 7 is a graph showing the dielectric loss of the hydrogel at 1 GHz. FIG. 8A is a graph showing the frequency at which the dielectric loss of the skin phantom is minimized. FIG. 8B is a graph showing the slope at 1 GHz of the approximation curve of the relative permittivity of the skin phantom. FIG. 9 is a graph showing the dielectric loss of the skin phantom at 1 GHz. Fig. 10 is a flowchart illustrating a constituent concentration measurement method according to an embodiment of the present invention. Fig. 11A is a diagram showing the results of estimating glucose concentration using the constituent concentration measurement method according to an embodiment of the present invention for only hydrogel. Fig. 11B is a diagram showing the results of estimating glucose concentration using the constituent concentration measurement method according to an embodiment of the present invention for a skin phantom. Fig. 12 is a block diagram showing an example of the configuration of a computer that realizes a constituent concentration measurement device according to an embodiment of the present invention.

[0017] An embodiment of the present invention will now be described. Fig. 1 is a cross-sectional view of a skin phantom according to an embodiment of the present invention. In this embodiment, a two-layered skin phantom 1 is proposed, which is a skin phantom with a dielectric constant equivalent to that of human skin, and is formed by laminating a porous film 3 impregnated with a hydrophobic material onto a hydrogel 2 made of four components: gelatin, glucose, electrolytes, and water.

[0018] The hydrogel 2 is composed of, for example, 15% gelatin as a gelling agent, and the remaining 85% is composed of pseudo-interstitial fluid (ISF) that simulates interstitial fluid. The pseudo-interstitial fluid contains, for example, 123 mM NaCl, 3.5 mM KCl, and 1.5 mM CaCl. ２ 2.5 mM, MgSO ４ 0.7 mM, NaH ２ P.O. ４ ・2H ２ The simulated interstitial fluid contained 1.5 mM O, 7.4 mM sucrose, and 5 mM glucose. In this example, a simulated interstitial fluid containing multiple electrolytes was used, but a material containing a single electrolyte, glucose, and water may also be used. Examples of electrolytes include NaCl or KCl. Furthermore, agar or agarose may be used as a gelling agent instead of gelatin.

[0019] The porous film 3 may be placed on top of the hydrogel 2 as described above. Examples of hydrophobic materials that may be impregnated into the porous film 3 include paraffin. Instead of impregnating the porous film 3 with paraffin, a hydrophobic material such as parylene may be formed by vapor deposition on the surface of the porous film 3 that comes into contact with the hydrogel 2. Examples of materials for the porous film 3 include paper. The thickness of the porous film 3 is, for example, 27 μm.

[0020] In this example, dielectric loss characteristics similar to those of human skin appear at frequencies of 1 GHz or less by adding an electrolyte to the hydrogel 2. The reason such characteristics are obtained is that actual skin also contains electrolytes.

[0021] However, a structure consisting only of the hydrogel 2 would have a higher dielectric constant than that of actual skin, so by laminating the porous film 3 on top of the hydrogel 2, the dielectric constant is reduced to the same level as that of human skin.

[0022] By impregnating the porous film 3 with a hydrophobic material or coating the surface of the porous film 3 that comes into contact with the hydrogel 2 with a hydrophobic material, it is possible to prevent the porous film 3 from tearing. It is also possible to prevent the porous film 3 from absorbing excessive moisture. The reason for suppressing moisture absorption is to simulate the keratin that exists in human skin, which has a low moisture content.

[0023] 2 is a block diagram showing the configuration of the constituent concentration measuring device according to this embodiment. The constituent concentration measuring device includes a coaxial probe 10 arranged so that its open end is in contact with a measurement object (skin phantom 1), a measurement unit 11 that irradiates electromagnetic waves onto the skin phantom 1 via the coaxial probe 10 and measures a reflected signal of the electromagnetic waves, a feeder 12 that connects the coaxial probe 10 and the measurement unit 11, a dielectric constant calculation unit 13 that calculates the relative permittivity and dielectric loss of the skin phantom 1 for each frequency based on the measurement results by the measurement unit 11, an electrolyte concentration estimation unit 14 (first estimation unit) that estimates the electrolyte concentration of the skin phantom 1 based on the frequency at which the dielectric loss is minimized, a water content estimation unit 15 (second estimation unit) that estimates the water content in the skin phantom 1 based on the slope of the approximation curve of the relative permittivity at a first specific frequency, and a glucose concentration estimation unit 16 (third estimation unit) that estimates the glucose concentration in the measurement object based on the value of the dielectric loss at a second specific frequency.

[0024] Examples of the measuring unit 11 include a vector network analyzer and an impedance analyzer. The feeder line 12 may be, but is not limited to, a coaxial line, a metal waveguide, a dielectric line, a microstrip line, a coplanar line, or the like.

[0025] The measurement results of the relative permittivity obtained by the constituent concentration measuring device are shown in Fig. 3A, and the measurement results of the dielectric loss are shown in Fig. 3B. The imaginary part of the complex permittivity obtained by the measuring unit 11 corresponds to the dielectric loss. In Fig. 3A, 300 indicates the relative permittivity when the measurement object is water, 301 indicates the relative permittivity when the measurement object is a hydrogel consisting of three components, gelatin, glucose, and water, 302 indicates the relative permittivity when the measurement object is a hydrogel consisting of four components, gelatin, glucose, NaCl, and water, and 303 indicates the relative permittivity when the measurement object is the skin phantom 1 of this example.

[0026] 3B, 304 indicates the dielectric loss when the measurement object is water, 305 indicates the dielectric loss when the measurement object is a hydrogel consisting of three components: gelatin, glucose, and water, 306 indicates the dielectric loss when the measurement object is a hydrogel consisting of four components: gelatin, glucose, NaCl, and water, and 307 indicates the dielectric loss when the measurement object is the skin phantom 1 of this example. In the examples of Figures 3A and 3B, hydrogel 2 of skin phantom 1 is made of four components: gelatin, glucose, NaCl, and water.

[0027] When the measurement object was a skin phantom 1 in which NaCl was added to a hydrogel 2, it was confirmed from Figure 3B that the dielectric loss increased at frequencies below 1 GHz. Furthermore, when the measurement object was a skin phantom 1 in which a porous film 3 was laminated on a hydrogel 2, it was confirmed from Figure 3A that the relative dielectric constant decreased.

[0028] Figure 4 shows the results of comparing the characteristics of skin phantom 1, which was the measurement subject in Figures 3A and 3B, with human skin. As in Figures 3A and 3B, 303 indicates the relative permittivity of skin phantom 1, and 307 indicates the dielectric loss of skin phantom 1. In Figure 4, 308 indicates the relative permittivity of human skin obtained by the constituent concentration measuring device, and 309 indicates the dielectric loss of human skin. It can be seen that skin phantom 1 of this example can obtain dielectric characteristics close to those of actual skin.

[0029] Figure 5A shows the relative permittivity of the skin phantom when the composition of the hydrogel is changed, and Figure 5B shows the dielectric loss of the skin phantom when the composition of the hydrogel is changed. Reference numeral 500 in Figure 5A represents the relative permittivity of the skin phantom using a hydrogel consisting of two components, gelatin and water, and reference numeral 509 in Figure 5B represents the dielectric loss of the skin phantom using a hydrogel consisting of two components, gelatin and water. The gelatin content in the hydrogel is 20%.

[0030] In Figure 5A, 501 and 502 represent the relative permittivity of a skin phantom made of a hydrogel consisting of three components: gelatin, NaCl, and water. In Figure 5B, 510 and 511 represent the dielectric loss of a skin phantom made of a hydrogel consisting of three components: gelatin, NaCl, and water. The gelatin content in the hydrogel is 20%. The NaCl concentration in the cases of 501 and 510 is 500 mM, and the NaCl concentration in the cases of 502 and 511 is 1000 mM.

[0031] In Figure 5A, 503 and 504 are the relative permittivity of a skin phantom made of a hydrogel consisting of three components: gelatin, glucose, and water. In Figure 5B, 512 and 513 are the dielectric loss of a skin phantom made of a hydrogel consisting of three components: gelatin, glucose, and water. The gelatin content in the hydrogel is 20%. The glucose concentration in the cases of 503 and 512 is 500 mM, and the glucose concentration in the cases of 504 and 513 is 1000 mM.

[0032] In Figure 5A, 505 to 508 indicate the relative permittivity of the skin phantom 1 of this example, which uses a hydrogel 2 consisting of four components: gelatin, glucose, NaCl, and water, and in Figure 5B, 514 to 517 indicate the dielectric loss of the skin phantom 1 of this example. The gelatin content in the hydrogel is 20%. In the cases of 505 and 514, the NaCl and glucose concentrations are both 500 mM. In the cases of 506 and 515, the NaCl concentration is 500 mM and the glucose concentration is 1000 mM. In the cases of 507 and 516, the NaCl concentration is 1000 mM and the glucose concentration is 500 mM. In the cases of 508 and 517, the NaCl and glucose concentrations are both 1000 mM. In the cases of 504 and 513, the glucose concentration is 1000 mM.

[0033] Fig. 5B shows that the frequency at which the dielectric loss is minimized depends on the NaCl concentration, even when the water content of the skin phantom is changed. Fig. 5A also shows that the slope of the approximation curve of the relative dielectric constant in the frequency range of 0.2 to 1 GHz depends on the NaCl concentration.

[0034] In the case of a skin phantom that does not contain NaCl in the hydrogel, there is no difference in dielectric loss around 1 GHz. However, around 5 GHz, there is a difference in dielectric loss depending on the glucose concentration. Therefore, it is better to estimate the glucose concentration based on the dielectric loss value around 5 GHz.

[0035] Similarly, in the case of the skin phantom 1 of this example, which contains 500 mM NaCl in the hydrogel, the dielectric loss varies depending on the glucose concentration around 5 GHz, which indicates that it is better to estimate the glucose concentration based on the dielectric loss value at 5 GHz, for example.

[0036] Furthermore, in the case of the skin phantom 1 of this example, which contains 1000 mM NaCl in the hydrogel, the dielectric loss varies depending on the glucose concentration around 1 GHz. Therefore, it is clear that it is better to estimate the glucose concentration based on the dielectric loss value at 1 GHz, for example.

[0037] Characteristic data obtained by varying the NaCl concentration, glucose concentration, and water content of only the hydrogel are shown in Figures 6A, 6B, and 7. Figure 6A shows the frequency at which the dielectric loss of the hydrogel is minimized, Figure 6B shows the slope of the approximation curve of the relative dielectric constant of the hydrogel at 1 GHz, and Figure 7 shows the dielectric loss of the hydrogel at 1 GHz.

[0038] 6A and 6B, 600 to 623 represent the average values ​​of the measurement results for the hydrogel containing no glucose, the hydrogel containing 500 mM glucose, and the hydrogel containing 1000 mM glucose. 600, 603, 606, 609, 612, 615, 618, and 621 represent the results for the hydrogel containing no NaCl, 601, 604, 607, 610, 613, 616, 619, and 622 represent the results for the hydrogel containing 500 mM NaCl, and 602, 605, 608, 611, 614, 617, 620, and 623 represent the results for the hydrogel containing 1000 mM NaCl.

[0039] 6A, regardless of the water content of the hydrogel, the frequency at which the dielectric loss is minimized is almost the same for the same NaCl concentration. Therefore, it is clear that the NaCl concentration can be estimated based on the frequency at which the dielectric loss is minimized.

[0040] 6B, the slope of the approximation curve of the relative dielectric constant at 1 GHz changes depending on the water content of the hydrogel. Therefore, it is clear that the water content can be estimated based on this slope.

[0041] In Figure 7, 700, 709, 718, and 727 are measurement results for hydrogels containing neither NaCl nor glucose. 701, 710, 719, and 728 are measurement results for hydrogels containing neither NaCl nor glucose but with a glucose concentration of 500 mM. 702, 711, 720, and 729 are measurement results for hydrogels containing neither NaCl nor glucose but with a glucose concentration of 1000 mM. 703, 712, 721, and 730 are measurement results for hydrogels containing neither NaCl nor glucose but with a NaCl concentration of 500 mM. 704, 713, 722, and 731 are measurement results for hydrogels containing NaCl and glucose but with a NaCl concentration of 500 mM. 705, 714, 723, and 732 are measurement results for hydrogels containing NaCl and glucose but with a NaCl concentration of 500 mM and glucose concentration of 1000 mM. 706, 715, 724, and 733 are measurement results for hydrogels with a NaCl concentration of 1000 mM and no glucose. 707, 716, 725, and 734 are measurement results for hydrogels with a NaCl concentration of 1000 mM and a glucose concentration of 500 mM. 708, 717, 726, and 735 are measurement results for hydrogels with a NaCl concentration of 1000 mM and a glucose concentration of 1000 mM.

[0042] In Figure 7, the dielectric loss value corresponding to the glucose concentration varies depending on the NaCl concentration and water content. Therefore, it can be seen that the glucose concentration can be estimated based on the dielectric loss value. However, there are cases where the glucose concentration cannot be estimated based on the dielectric loss value alone. The reason why the glucose concentration cannot be estimated is that when the NaCl concentration or water content changes, the dielectric loss value may be the same even though the glucose concentration is different.

[0043] Next, for a skin phantom in which the porous film of this example was laminated to the hydrogel that was the subject of measurement in Figures 6A, 6B, and 7, characteristic data when the NaCl concentration, glucose concentration, and water content were changed are shown in Figures 8A, 8B, and 9. Figure 8A is a graph showing the frequency at which the dielectric loss of the skin phantom is minimized, Figure 8B is a graph showing the slope of the approximation curve of the relative dielectric constant of the skin phantom at 1 GHz, and Figure 9 is a graph showing the dielectric loss of the skin phantom at 1 GHz.

[0044] In Figures 8A, 8B, and 9, the skin phantoms using the same hydrogels as in Figures 6A, 6B, and 7 are assigned the same reference numerals as in Figures 6A, 6B, and 7. Figures 8A, 8B, and 9 show that similar results to those in Figures 6A, 6B, and 7 were obtained. From the above results, it is desirable to first estimate the NaCl concentration and water content, which show characteristic trends in dielectric constant evaluation, and then estimate the glucose concentration last.

[0045] 10 is a flowchart illustrating the component concentration measurement method of this example. As shown in FIG. 2, the coaxial probe 10 is positioned so that its open end is in contact with the surface of the porous film 3 opposite the hydrogel 2. The end of the coaxial probe 10 opposite the open end is connected to the measurement unit 11 via a power supply line 12.

[0046] The measurement unit 11 irradiates the skin phantom 1 with electromagnetic waves via the coaxial probe 10 (step S1 in FIG. 10), and receives the electromagnetic waves reflected by the skin phantom 1 via the coaxial probe 10 (step S2 in FIG. 10).

[0047] The permittivity calculation unit 13 calculates the complex permittivity of the skin phantom 1 based on the reflected signal (S11 parameter) of the electromagnetic wave obtained by the measurement unit 11, and further calculates the relative permittivity and dielectric loss of the skin phantom 1 from the complex permittivity (step S3 in Figure 10).

[0048] The real part of the complex permittivity corresponds to the permittivity of the skin phantom 1, and the imaginary part of the complex permittivity corresponds to the dielectric loss. By performing the measurements and calculations in steps S1 to S3 while changing the frequency of the electromagnetic wave, the relative permittivity and dielectric loss of the skin phantom 1 can be calculated for each frequency.

[0049] In this embodiment, the dielectric constant calculation unit 13 is provided separately from the measurement unit 11 such as a vector network analyzer or an impedance analyzer, but the dielectric constant calculation unit 13 may be provided inside the measurement unit 11.

[0050] Next, the electrolyte concentration estimation unit 14 estimates the electrolyte concentration (NaCl concentration in this embodiment) in the skin phantom 1 based on the frequency at which the dielectric loss calculated by the dielectric constant calculation unit 13 is minimized (step S4 in FIG. 10).

[0051] To investigate in advance the relationship between the frequency at which the dielectric loss is minimized and the NaCl concentration, for example, dielectric loss is measured using a skin phantom 1 whose NaCl concentration, water content, and glucose concentration are known. Then, a first regression equation (first model) can be created in advance by regression analysis using the frequency at which the dielectric loss is minimized as an explanatory variable and the NaCl concentration as an explained variable. The electrolyte concentration estimation unit 14 can estimate the NaCl concentration using the first regression equation prepared in advance.

[0052] Next, the water content estimating unit 15 estimates the water content in the skin phantom 1 based on the slope at 1 GHz of the approximate curve of the relative dielectric constant calculated by the dielectric constant calculating unit 13 (step S5 in FIG. 10).

[0053] To investigate the relationship between the slope of the approximated curve of the relative permittivity and the water content in advance, for example, the relative permittivity is measured using a skin phantom 1 with known NaCl concentrations, water content, and glucose concentrations. Then, a second regression equation (second model) can be created in advance by regression analysis using the slope of the approximated curve of the relative permittivity at 1 GHz as the explanatory variable and the water content as the explained variable. The water content estimation unit 15 can estimate the water content using the second regression equation prepared in advance. Note that, although the first specific frequency for determining the slope of the approximated curve is set to 1 GHz here, the slope can also be determined at a single frequency in the range of 0.2 to 1 GHz.

[0054] Finally, the glucose concentration estimation unit 16 estimates the glucose concentration of the skin phantom 1 based on the value of the dielectric loss at the second specific frequency calculated by the dielectric constant calculation unit 13 (step S6 in FIG. 10). The second specific frequency refers to a frequency at which the glucose concentration is uniquely determined by the value of the dielectric loss. As explained above, there are cases where the dielectric loss value is the same despite different glucose concentrations. Therefore, it is necessary to determine the second specific frequency based on the NaCl concentration and water content estimated in steps S4 and S5. The second specific frequency may be a single frequency or multiple frequencies.

[0055] For example, the dielectric loss is measured using a skin phantom 1 with known NaCl concentrations, water content, and glucose concentrations, and the second specific frequency corresponding to the NaCl concentration and water content is determined in advance. A database associating the NaCl concentration, water content, and second specific frequency with each other may be created in advance. Alternatively, a third regression equation (third model) may be created in advance by performing regression analysis using the NaCl concentration and water content as explanatory variables and the second specific frequency as an explained variable.

[0056] Furthermore, a fourth regression equation (fourth model) may be prepared in advance by performing regression analysis using the dielectric loss value at the second specific frequency as an explanatory variable and the glucose concentration as an explained variable. However, the fourth regression equation needs to be prepared for each second specific frequency (or for each combination of frequencies if there are multiple second specific frequencies).

[0057] The glucose concentration estimation unit 16 can determine a second specific frequency using a database prepared in advance or a third regression equation, and can further estimate the glucose concentration using a fourth regression equation corresponding to the second specific frequency.

[0058] 11A and 11B show the results of a regression equation obtained by regression analysis using the frequency at which the dielectric loss is minimized, the slope of the approximation curve of the relative dielectric constant from 0.2 to 1 GHz, the dielectric loss at 1 GHz, and the dielectric loss at 5 GHz as explanatory variables, and the glucose concentration as the explained variable.

[0059] Figure 11A shows the results of estimating the glucose concentration of samples not used in the regression analysis, using only the hydrogel 2 of this example. Figure 11B shows the results of estimating the glucose concentration of samples not used in the regression analysis, using the skin phantom 1 of this example. Although there is some variability in the estimated values, it is clear that the actual tendency of changes in glucose concentration can be captured. By increasing the amount of data in the future, it is expected that the accuracy of estimating glucose concentration will improve.

[0060] As described above, this example allows for the realization of a two-layer skin phantom with dielectric properties similar to those of human skin. This example allows for preliminary testing of human subjects using the skin phantom. Furthermore, it is difficult to control the variation of substances in the skin of an actual human. In contrast, this example allows for the easy modification of the substances in the skin phantom, making it possible to use the skin phantom to examine whether variations in substances in the skin can be accurately measured using noninvasive measurement methods such as radio waves. Furthermore, this example allows for the development of sensing device technologies such as wearable sensors and implantable sensors, or transdermal drug delivery.

[0061] Furthermore, in this embodiment, the glucose concentration, which is usually quantified by an enzyme reaction such as glucose oxidase and a current response, can be measured in a non-contact manner by the constituent concentration measurement method described in Fig. 10. Furthermore, the constituent concentration measurement method of this embodiment can be used not only in skin phantoms but also in situations requiring glucose quantification and management, such as food testing, beverage testing, cell culture media, and plant factory media.

[0062] In this embodiment, the processing of the estimated NaCl concentration, water content, and glucose concentration is not described, but it goes without saying that appropriate processing can be performed as needed, such as displaying the estimated values, storing them, and transmitting the data.

[0063] The measuring unit 11, the dielectric constant calculation unit 13, the electrolyte concentration estimation unit 14, the water content estimation unit 15, and the glucose concentration estimation unit 16 of the constituent concentration measuring device described in this embodiment can be realized by a computer equipped with a CPU (Central Processing Unit), a storage device, and an interface, and a program that controls these hardware resources. An example of the configuration of this computer is shown in Figure 12.

[0064] The computer includes a CPU 100, a storage device 101, and an interface device (I / F) 102. The I / F 102 is connected to components such as the hardware part of the measurement unit 11. In such a computer, a program for realizing the constituent concentration measurement method of the present invention is stored in the storage device 101. The CPU 100 executes the processing described in this embodiment in accordance with the program stored in the storage device 101.

[0065] Some or all of the above embodiments can be described as, but are not limited to, the following supplementary notes.

[0066] (Note 1) The skin phantom of the present invention is characterized by laminating a porous film on a hydrogel consisting of four components: a gelling agent, glucose, an electrolyte, and water.

[0067] (Appendix 2) In the skin phantom described in Appendix 1, the porous film is impregnated with a hydrophobic material, or a hydrophobic material is formed on the surface of the porous film on the side that comes into contact with the hydrogel.

[0068] (Appendix 3) The constituent concentration measuring device of the present invention comprises a measuring unit configured to irradiate an electromagnetic wave onto a measurement object and measure a reflected signal of the electromagnetic wave; a dielectric constant calculation unit configured to calculate the relative permittivity and dielectric loss of the measurement object for each frequency based on the measurement results by the measuring unit; a first estimation unit configured to estimate the electrolyte concentration in the measurement object based on the frequency at which the dielectric loss is minimized; a second estimation unit configured to estimate the water content in the measurement object based on the slope of the approximation curve of the relative permittivity at a first specific frequency; and a third estimation unit configured to estimate the glucose concentration in the measurement object based on the value of the dielectric loss at a second specific frequency.

[0069] (Supplementary Note 4) In the constituent concentration measuring device according to Supplementary Note 3, the first specific frequency is a frequency in the range of 0.2 to 1 GHz.

[0070] (Supplementary Note 5) In the constituent concentration measuring device according to Supplementary Note 3 or 4, the third estimation unit determines the second specific frequency based on the electrolyte concentration and the water content.

[0071] (Appendix 6) The component concentration measurement method of the present invention includes a first step of irradiating an electromagnetic wave to a measurement object and measuring a reflected signal of the electromagnetic wave; a second step of calculating the relative permittivity and dielectric loss of the measurement object for each frequency based on the measurement results of the first step; a third step of estimating the electrolyte concentration in the measurement object based on the frequency at which the dielectric loss is minimized; a fourth step of estimating the water content in the measurement object based on the slope of the approximation curve of the relative permittivity at a first specific frequency; and a fifth step of estimating the glucose concentration in the measurement object based on the value of the dielectric loss at a second specific frequency.

[0072] (Supplementary Note 7) In the constituent concentration measuring method described in Supplementary Note 6, the first specific frequency is a frequency in the range of 0.2 to 1 GHz.

[0073] (Supplementary Note 8) In the constituent concentration measurement method according to Supplementary Note 6 or 7, the fifth step includes a step of determining the second specific frequency based on the electrolyte concentration and the water content.

[0074] The present invention can be applied to a technique for simulating the characteristics of human skin.

[0075] 1...skin phantom, 2...hydrogel, 3...porous film, 10...coaxial probe, 11...measuring unit, 12...power supply line, 13...dielectric constant calculation unit, 14...electrolyte concentration estimation unit, 15...water content estimation unit, 16...glucose concentration estimation unit

Claims

1. A skin phantom characterized by a porous film laminated onto a hydrogel consisting of four components: gelling agent, glucose, electrolytes, and water.

2. A skin phantom as described in claim 1, characterized in that the porous film is impregnated with a hydrophobic material or has a hydrophobic material formed on the surface of the porous film on the side in contact with the hydrogel.

3. An ingredient concentration measuring device comprising: a measuring unit configured to irradiate an electromagnetic wave to a measurement object and measure a reflected signal of the electromagnetic wave; a dielectric constant calculation unit configured to calculate the relative dielectric constant and dielectric loss of the measurement object for each frequency based on the measurement results by the measuring unit; a first estimation unit configured to estimate an electrolyte concentration in the measurement object based on the frequency at which the dielectric loss is minimized; a second estimation unit configured to estimate a water content in the measurement object based on a slope of an approximation curve of the relative dielectric constant at a first specific frequency; and a third estimation unit configured to estimate a glucose concentration in the measurement object based on the value of the dielectric loss at a second specific frequency.

4. An ingredient concentration measuring device according to claim 3, wherein the first specific frequency is a frequency in the range of 0.2 to 1 GHz.

5. An ingredient concentration measuring device according to claim 3 or 4, characterized in that the third estimation unit determines the second specific frequency based on the electrolyte concentration and the water content.

6. A method for measuring component concentration comprising: a first step of irradiating an electromagnetic wave to a measurement object and measuring a reflected signal of the electromagnetic wave; a second step of calculating the relative dielectric constant and dielectric loss of the measurement object for each frequency based on the measurement results of the first step; a third step of estimating an electrolyte concentration in the measurement object based on the frequency at which the dielectric loss is minimized; a fourth step of estimating the water content in the measurement object based on the slope of an approximation curve of the relative dielectric constant at a first specific frequency; and a fifth step of estimating the glucose concentration in the measurement object based on the value of the dielectric loss at a second specific frequency.

7. A method for measuring the concentration of an ingredient according to claim 6, wherein the first specific frequency is a frequency in the range of 0.2 to 1 GHz.

8. A method for measuring the concentration of a component according to claim 6 or 7, characterized in that the fifth step includes a step of determining the second specific frequency based on the electrolyte concentration and the water content.

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