CN103536275B - Reflectance-detection measuring device for skin autofluorescence - Google Patents

Abstract

The present invention provides a reflection detection type measurement device for skin fluorescence, which is configured to perform light irradiation and light detection on a reference sample and a measurement target.

Description

Reflectance-detection measuring device for skin autofluorescence

technical field

The present invention relates to a skin autofluorescence measurement device for diagnosing various diseases such as diabetes by measuring the autofluorescence of the skin from advanced glycation end products (AGE) accumulated in the skin.

Background technique

Recently, various devices using light for the purpose of diagnosis and treatment of diseases are being developed. In particular, various devices for diagnosing diseases using skin autofluorescence emitted from skin by excitation light irradiated from a light source are being developed and used.

Autofluorescence is the emission of light from the skin after excitation light is absorbed into the skin. With biometric data inside the skin, autofluorescence is used as a biomarker of disease and enables non-invasive methods to examine damage to the physiological state of all body organs.

For example, advanced glycation end products (AGEs) are formed via sugar oxidation of proteins in humans as a result of the Maillard reaction, which impairs the function of many proteins. Typically, AGEs are produced by exposure to cardiac risk factors such as smoking, intake of higher fatty acids with food, hypercholesterolemia, and oxidative stress due to acute illness (eg, sepsis). The AGEs thus produced are slowly broken down in the body and accumulate over a long period of time. Increased AGE production is associated with the progression of chronic diseases such as atherosclerosis. As the aging process progresses, AGEs tend to accumulate in the body throughout a person's lifetime.

During the duration of hyperglycemia, a continuous reaction of nonenzymatic protein glycation and sugar oxidation occurs, thus forming AGEs (ie, irreversible complexes of glycogen and protein). The accumulation of AGEs develops rapidly in patients with diabetes, renal failure and cardiovascular disease. AGEs accumulate in various tissues including skin. AGE has the property of irradiating autofluorescence (AF) in the blue spectral range (peak around 440 nm) by irradiation with excitation light in the UV range (peak around 370 nm).

AGEs are useful as biomarkers for a range of diseases and enable the assessment of physiological damage to organs throughout the body by measuring autofluorescence of the skin using non-invasive methods. That is, AGEs predict long-term complications in age-related diseases. Specifically, the amount of skin autofluorescence is increased in patients with diabetes and renal failure and is associated with the progression of vascular complications and coronary heart disease (CHD). AGE accumulation can be measured by skin autofluorescence with a non-invasive method, a non-invasive clinical tool useful for risk assessment of long-term vascular complications in the context of AGE accumulation and diabetes.

U.S. Patent Application Publication No. 2004-186363 (hereinafter, referred to as reference 1) discloses evaluation by measuring skin fluorescence near a patient's forearm as a method and apparatus proposed for AGE evaluation using skin autofluorescence measurement AGE technology.

In Reference 1, the excitation light source is a backlit fluorescent tube emitting light in the UV wavelength range of about 300 nm to about 420 nm. The collection and recording of light is performed by a fiber optic spectrometer. In order to increase the measurement area, the end face of the optical fiber is arranged at a certain distance (d is about 5 mm to about 9 mm) from the transparent window of the device. In order to reduce the effect of light reflected from the skin and window, the optical fiber is positioned at an approximately 45 degree angle to the surface of the window.

Specifically, in Reference 1, the end face of the optical fiber used to collect light is set as far away from the target as possible. In this case, the area of the target spot to be measured is about 0.4 cm ² .

However, there is a limitation in the above method, that is, as the measurement distance (d) increases to increase the measurement area of the target point of interest, the collected fluorescence signal decreases considerably. Therefore, in Reference 1 according to the related art, the reliability of data detection may decrease due to the limitation in the size of the skin area that can be measured. In particular, such precision limitations manifest considerably in parts that are heterogeneous targets of the skin, such as moles, blood vessels, and wounds.

Meanwhile, US Patent Application Publication No. 2008-103373 (hereinafter, referred to as reference 2) discloses an apparatus for measuring AGE to perform a screening test for diabetic patients. Similar to Ref. 1, the device disclosed in Ref. 2 includes a fiber optic spectrometer that performs fluorescence measurements on the skin of the forearm. However, unlike Reference 1, the fiber optic probe is provided in the form of a bundle including a plurality of branches.

In the device of Reference 2, UV light and blue light emitted from light-emitting diodes are irradiated on the subject's forearm through fiber optic probes, and skin fluorescence and diffuse reflection light emitted from the forearm are collected through these probes. The collected light is wavelength dispersed in a spectrometer and then detected by a linear array detector. Two branches of the fiber optic probe (irradiation fiber; channel 1 and channel 2) are used to irradiate light onto the target of interest, and a third branch (collection fiber) delivers light from the target to the multi-channel spectrometer. The end face of the tissue interface at which the branch bundles of the fiber optic probe are combined comes into contact with the skin to be irradiated.

Light from a white light LED is emitted from one branch of the fiber optic probe for reflected light spectroscopy measurements, and light from a suitable LED among LEDs emitting light in the ultraviolet to blue spectral range is transmitted from the other branch of the fiber optic probe via a switching device. A branch launches. Various wavelengths can be selected to select optimal fluorescence excitation conditions. Reflected light spectroscopy measurements are used to detect autofluorescence due to melanin and hemoglobin and to compensate the measurements. The individual optical fibers are arranged in a certain order in the fiber bundle. The optical fibers from the three branches of the optical fiber bundle are sequentially arranged in a mosaic pattern at intervals of b=0.5 mm.

In Reference 2, since light is irradiated on the subject's forearm through the fiber optic probe, the fiber optic probe is included as an optically transmissive medium. However, fiber optic probes have limitations on transmission loss that occurs according to the small diameter and low numerical aperture of the fiber.

In addition, since both devices disclosed in References 1 and 2 include an optical fiber in a light receiving unit that receives light, there is an inherent limit to the fiber optic probe of the light receiving unit. Because references 1 and 2 were configured to use a fiber optic spectrometer and a line array detector, there was a limitation because the autofluorescence signal wavelength of AGE became relatively small in the detection area occupied by the line array detector. Therefore, the detected fluorescence signal is dispersed, and the light intensity of the wavelength to be detected by the line array detector becomes relatively small. Furthermore, it is difficult to minimize the facility due to fiber optic probes and fiber optic spectrometers.

On the other hand, the diagnostic devices disclosed in References 1 and 2 have limitations because it is impossible to diagnose diseases such as diabetic foot accompanied by diabetes.

Diabetic foot is a serious complication of diabetic foot ulcers and calf amputations caused by the progression of diabetes. Diabetic foot is reported to occur in approximately 15% of all diabetic patients, and approximately 40% to approximately 60% of all lower leg amputee patients are diabetic. Diabetic foot ulcers are the cause of approximately 80% or more of all lower leg amputations. When about 90% or more of patients with diabetic feet are treated properly at an early stage, they can be cured without amputation. Autofluorescence measurement test can be used for early diagnosis of diabetic foot. In the early stages of a diabetic foot, the diabetic foot usually occurs in one foot before it develops in the other. Therefore, early diagnosis of diabetic foot using the fluorescence test can be performed by comparing and evaluating the degree of fluorescence of the skin of the symmetrical foot portion. Therefore, for early diagnosis of diseases such as typical diabetes-accompanied diabetic foot, it is necessary to develop an apparatus enabling selective diagnosis on body parts to be measured.

Specifically, in order to realize a selective diagnostic device, it is first necessary to prepare for the miniaturization and mobility of the device. Therefore, the efficiency of light irradiation and fluorescence detection in the device is required.

Meanwhile, although such selective diagnosis is performed on body parts, the intensity of fluorescence generated from the skin is affected by light scattering and absorption occurring inside the skin and fluorescent substances included in the skin.

Therefore, it is very important to improve the efficiency of light irradiation and fluorescence detection, and to reduce the measurement error due to light scattering and absorption inside the skin, in order to analyze the disease by more clearly distinguishing people with disease from those without disease. The selective diagnostic section enables precise diagnosis.

The above information disclosed in this Background section is only for enhancement of understanding of the background of the invention and therefore it may contain information that does not form the prior art that is already known in this country to a person of ordinary skill in the art.

Contents of the invention

The present invention provides a reflection detection type measurement device for skin fluorescence that can simply correct light due to light scattering and absorption generated in the skin and reflection of irradiated light from the skin surface when measuring skin fluorescence The resulting measurement error of skin fluorescence.

The present invention also provides a reflectance detection measuring device for skin fluorescence, which can improve the diagnostic possibility of a disease by accurately evaluating diagnostic factors such as AGE from corrected skin fluorescence values.

The present invention also provides a reflective detection measuring device for skin fluorescence, which can efficiently concentrate light from a light source onto skin tissue and minimize light from the surface of skin tissue when measuring skin fluorescence. spectral reflectance to improve optical efficiency.

The present invention also provides a reflection detection type measurement device for skin fluorescence, which can improve optical concentration and optical uniformity by uniformly concentrating light irradiated from a light source to a measurement target.

The present invention also provides a reflective detection measuring device for skin fluorescence, in which an optical system and a light source system can be simply configured to conveniently perform a diagnostic procedure.

In one aspect, the present invention provides a reflectance detection measurement device for skin fluorescence, the reflection detection measurement device configured to perform light irradiation and light detection on a reference sample and a measurement target, the device comprising: a first light source, which irradiates excitation light; a second light source which irradiates light of a wavelength different from that of light from the first light source; a first optical detector and a second optical detector which are arranged for the fluorescence signal and the reflected light The signal detects two different wavelengths; the light source switch controller, which is used to control the on/off of the first light source and the second light source; and the arithmetic unit, according to the fluorescence signal detected by the first optical detector and the second optical detector A corrected skin fluorescence signal is calculated from the reflected light signal, wherein the second light source irradiates light in the same wavelength range as the skin fluorescence excited and emitted by the excitation light from the first light source.

In an exemplary embodiment, the present invention provides a reflection detection measurement device for skin fluorescence, the reflection detection measurement device comprising: a light source, which irradiates excitation light; a fluorescence signal caused by the irradiated excitation light; and an optical prism configured to transmit the excitation light irradiated from the light source to the measurement target and to transmit the fluorescence signal to the optical detector, wherein the optical prism has a connection with the measurement target The lower surface and the two or more upper surfaces on which the light source and the optical detector are arranged.

In another exemplary embodiment, the apparatus may further include an optical connector disposed under a lower surface of the optical prism and contacting the measurement target.

In yet another exemplary embodiment, the optical connector may include a connection layer formed of a liquid material or an elastic material between the optical prism and the measurement target.

In yet another exemplary embodiment, the optical prism may include two upper inclined surfaces and a lower surface adjacent to the measurement target, and may be a triangular prism having a triangular cross section.

In yet another exemplary embodiment, the first light source and the second light source may be disposed above one upper inclined surface of the optical prism, and the first optical detector and the second optical detector may be disposed on the other of the optical prism. above the sloping surface.

In another exemplary embodiment, the optical prism may include two upper inclined surfaces, an upper surface connected to the two upper inclined surfaces, and a lower surface connected to the measurement target, and may be a trapezoidal prism having a trapezoidal cross section.

In another exemplary embodiment, the first light source and the second light source can be arranged above one upper inclined surface of the optical prism, and the first optical detector and the second optical detector can be arranged on the other surface of the optical prism. above the sloping surface.

In yet another exemplary embodiment, the first light source and the second light source may be disposed above one upper inclined surface and the other upper inclined surface of the optical prism, respectively, and the first optical detector and the second optical detector may be disposed by disposed above the upper surface of the optical prism.

In yet another exemplary embodiment, the first light source and the second light source may be disposed above one upper inclined surface and the other upper inclined surface of the optical prism, and the first optical detector and the second optical detector may be disposed above the upper surface of the optical prism.

In yet another exemplary embodiment, the optical prism may include four upper inclined surfaces, an upper surface connected to the four upper inclined surfaces, and a lower surface adjacent to the measurement target, and may be a quadrangular pyramid having a trapezoidal section truncated cone.

In yet another exemplary embodiment, the first light source and the second light source may be respectively disposed above the two upper inclined surfaces of the optical prism, and the first optical detector and the second optical detector may be respectively disposed above the optical prism. other upward sloping surfaces.

In yet another exemplary embodiment, the first light source and the second light source may be disposed above two upper inclined surfaces facing each other, and the first optical detector and the second optical detector may be disposed on the other upper slope facing each other. above the sloping surface.

In yet another exemplary embodiment, the apparatus may further include a polarizer and a crossed polarizer disposed between the optical prism and the light source and between the optical prism and the optical detector, respectively.

In an exemplary embodiment, the light source switch controller may control the first light source and the second light source such that on states of the first light source and the second light source are temporally separated from each other.

In another exemplary embodiment, the switch controller may be configured to detect the fluorescence signal and the reflected light signal from the first light source while continuously repeating the process of sequentially turning on and off the first light source and the second light source and Reflected light signal from the second light source.

In yet another exemplary embodiment, the measurement target and the reference sample may be selectively disposed on the light paths of the first light source and the second light source.

In yet another exemplary embodiment, the first light source may irradiate light having a wavelength of 370±20 nm.

In yet another exemplary embodiment, the second light source may irradiate light having a wavelength of 440±20 nm.

In another exemplary embodiment, the switch controller may control all of the first light source and the second light source to be turned off before turning on each light source.

In another exemplary embodiment, when the switch controller turns off all the first light source and the second light source, the first optical detector and the second optical detector can measure the dark signal, and the arithmetic unit can store the measured dark signal signal, and compensate the detected fluorescence signal and reflected light signal according to the stored dark signal.

In yet another exemplary embodiment, the switch controller may control the first light source and the second light source to repeatedly turn on/off at a cycle of about 10 Hz to about 100 Hz.

In yet another exemplary embodiment, the apparatus may further include an optical detector switch controller for controlling on/off of the first optical detector and the second optical detector.

In yet another exemplary embodiment, the apparatus may include: a measurement scanner including a first light source, a second light source, a first optical detector, and a second optical detector; and a main body electrically connected to the measurement scanner. connected, and includes an operator, wherein the optical sensor is detachable from the main body.

In yet another exemplary embodiment, the measurement scanner may be formed in a hand-held form, and may include a first light source, a second light source, a first optical detector, and a second optical detector disposed at one end thereof. .

In yet another exemplary embodiment, the survey scanner may include a memory for storing detected data.

In yet another exemplary embodiment, in the measurement scanner, the first light source, the second light source, the first optical detector, and the second optical detector may be vertically arranged parallel to each other, so that the measurement target is performed vertically Light irradiation and light detection.

In yet another exemplary embodiment, in the measurement scanner, the first light source, the second light source, the first optical detector and the second optical detector may be arranged obliquely at certain angles to each other such that Light irradiation and light detection are performed obliquely to the measurement target.

In yet another exemplary embodiment, the first light source, the second light source, the first optical detector, and the second optical detector may be arranged to perform light irradiation and light detection from the same location.

In yet another exemplary embodiment, the first light source, the second light source, the first optical detector, and the second optical detector may all be arranged to be inclined at an angle of about 45 degrees to each other.

In still another exemplary embodiment, the main body may include a mounting part in which the measurement scanner is mounted, and the measurement scanner may be configured to be removable from the mounting part.

In yet another exemplary embodiment, the first light source, the second light source, the first optical detector, and the second optical detector may be disposed at one end of the measurement scanner, and the mounting part may have an aperture formed therein structure, the aperture structure has a shape matching the shape of one end of the measurement scanner.

In yet another exemplary embodiment, the aperture structure of the mounting part may be configured such that the reference sample is optically connected to the first light source, the second light source, the first optical detector and the second optical detector of the measurement scanner.

In still another exemplary embodiment, when the measurement scanner may be installed in the installation part, the main body may perform measurement on the reference sample, and may receive detection data of the measurement target and the reference sample stored in the measurement scanner, to Allows the calculator to calculate the corrected skin fluorescence signal.

In yet another exemplary embodiment, the mounting part may include a charging terminal for the measuring scanner, and may allow the measuring scanner to be charged when the measuring scanner is mounted in the mounting part.

In yet another exemplary embodiment, a measurement scanner may include two pairs of crossed polarizers disposed thereon.

In yet another exemplary embodiment, the first light source and the second light source may be connected to one end of the measurement target side of the measurement scanner via a light guide.

In yet another exemplary embodiment, the first optical probe and the second optical probe may be connected to one end of the measurement scanner on the measurement target side via a light guide.

In still another exemplary embodiment, the main body may further include a display part that may output the corrected skin fluorescence signal calculated in the arithmetic unit.

In yet another exemplary embodiment, the arithmetic unit may calculate a skin fluorescence value corrected by the following equation:

AF _corr =K[I(λ2,t1)/I ₀ (λ2,t1)]/{[R(λ1)] ^k1 [R(λ2)]} ^k2

(Here, R(λ1)=I(λ1,t1)/I ₀ (λ1,t1): diffuse reflectance in excitation wavelength;

R(λ2)=I(λ2,t2)/I ₀ (λ2,t2): diffuse reflection coefficient in emission wavelength;

I(λ2,t1): intrinsic fluorescence (skin fluorescence) signal value of skin tissue;

I(λ1,t1): the reflected light signal value of the skin tissue in the excitation light wavelength;

I(λ2, t2): the reflected light signal value of the skin tissue in the emitted light wavelength;

k1,k2: exponents of the correction function with respect to the excitation and emission wavelengths;

I ₀ (λ2,t1): the intrinsic fluorescence signal value of the reference sample;

I ₀ (λ1,t1): the reflected light signal value of the reference sample in the excitation light wavelength; and

I ₀ (λ2, t2): the reflected light signal value of the reference sample in the emitted light wavelength. )

K: A ratio factor that takes into account the characteristics of the reference sample used.

Other aspects and exemplary embodiments of the invention are discussed below.

Description of drawings

The above and other features of the present invention will now be described in detail with reference to certain exemplary embodiments of the invention and the accompanying drawings, which are given hereinafter by way of illustration only and therefore do not Limit the invention in which:

1 is a graph showing the intensity of light input from a light source and light detected by an optical detector, which is displayed according to time to explain the reflection detection type measurement device for skin fluorescence according to an embodiment of the present invention. measurement principle;

FIG. 2 is a view showing a reflection detection type measurement device for skin fluorescence according to an embodiment of the present invention;

FIG. 3 is a diagram showing an exemplary arrangement of a light source and an optical detector when there is no gap between the light source and the optical detector and the target skin in the reflection detection measurement device for skin fluorescence according to an embodiment of the present invention. view;

4 is a view showing an exemplary arrangement of a light source and an optical detector when there is a gap between the light source and the optical detector and the target skin in the reflection detection type measurement device for skin fluorescence according to an embodiment of the present invention ;

5 is a view showing an optical prism and an optical connector in a reflective detection type measurement device for skin fluorescence according to an embodiment of the present invention;

6 to 10 are views showing an optical prism and an optical connector in a reflection detection type measurement device for skin fluorescence according to another embodiment of the present invention;

11 is a view showing a reflection detection type measurement device for skin fluorescence according to an embodiment of the present invention, the reflection detection type measurement device is configured to include a housing equipped with two light sources and two optical detectors;

12 is a plan view showing a pyramid holder in which a light source and an optical detector are installed in a reflection detection pyramid measurement device for skin fluorescence according to an embodiment of the present invention;

13 to 15 are exploded views illustrating a pyramid measurement module of a reflection detection pyramid measurement device for skin fluorescence according to an embodiment of the present invention; and

Fig. 16 is a view showing an optical attenuation filter in a reflectance detection pyramid measuring device for skin fluorescence.

Numerals recited in the figures include references to the following elements as discussed further below:

100: Measurement scanner 200: Main body

111: first light source 112: second light source

121: first optical detector 122: second optical detector

130: polarizer 131: crossed polarizer

210: Installation parts 220: Display parts

310: light source 320: optical detector

311: first light source 312: second light source

321: first optical detector 322: second optical detector

330: Optical Prism 340: Optical Connector

351: polarizer 352: crossed polarizer

360: main body

411: first light source 412: second light source

421: first optical detector 422: second optical detector

430: Optical Prism 440: Optical Connector

451: Polarizer 452: Crossed Polarizer

511: first light source 512: second light source

513: first optical detector 514: second optical detector

515,516: Polarizers 517,518: Crossed Polarizers

519,520: Optical filters

521,522,523,524: side panels

525: window 526: bottom plate

527: Bolt 530: Pyramid bracket

531,532,533,534: through holes 535: openings

536,537: Optical attenuation filters

T: measurement target (skin)

It should be understood that the appended drawings are not necessarily to scale, presenting a somewhat simplified representation of various preferred features illustrative of the basic principles of the invention. The specific design features of the present invention as disclosed herein, including, for example, specific dimensions, orientations, locations and shapes will be determined in part by the particular intended application and use environment.

In the figures, reference numbers refer to the same or equivalent parts of the present invention throughout the several figures of the drawings.

detailed description

Various embodiments of the invention will now be discussed in detail hereinafter, examples of which are illustrated in the accompanying drawings and described below. While the invention will be described in conjunction with exemplary embodiments, it will be understood that the description given is not intended to limit the invention to those exemplary embodiments. On the contrary, it is intended that the invention cover not only the exemplary embodiments, but also various alternatives, modifications, equivalents and other embodiments, which may be included within the spirit and scope of the invention as defined by the appended claims.

The above and other features of the invention are discussed below.

The present invention relates to a skin fluorescence measuring device for the purpose of diagnosing a disease such as diabetes, for irradiating excitation light on skin and measuring skin fluorescence generated by the excitation light. Specifically, it provides a reflectance detection measuring device for skin fluorescence that accurately measures, Fluorescence of the skin detected at the location on which the reflected light falls.

To this end, while the light source and the optical detector can be sequentially turned on/off according to certain conditions required in the above process, sequential measurements can be performed on the target to be diagnosed and a reference sample, and the The information of the target is compared with the information obtained by the reference sample to remove the individual bias of the target. Accordingly, a reflectance detection measuring device for skin fluorescence is provided which provides corrected skin fluorescence values.

Hereinafter, an exemplary embodiment of a reflectance detection measuring device for skin fluorescence will be described in detail with reference to the accompanying drawings.

It is necessary to select a skin target for measuring fluorescence generated on the skin and to consider factors affecting the measured fluorescence. The measured fluorescence may depend on light scattering and absorption occurring inside the skin even when specular reflection occurring on the skin surface is removed, and fluorescent substances included in the skin. Specifically, it is necessary to correct the measured fluorescence value in consideration of the influence of light absorption and scattering of fluorescence wavelengths generated in the fluorescent substance and light absorption and scattering of excitation light wavelengths irradiated to excite the fluorescent substance. Therefore, the following empirical equation (1) can be considered to reduce the influence of optical factors on the fluorescence intensity.

${\mathrm{<span\; class="notranslate">\; AF</span>}}_{\mathrm{<span\; class="notranslate">\; corr</span>}}<span\; class="notranslate">\; =</span>\mathrm{<span\; class="notranslate">\; AF</span>}<span\; class="notranslate">\; /</span><span\; class="notranslate">\; (</span>{\mathrm{<span\; class="notranslate">\; R</span>}}_{\mathrm{<span\; class="notranslate">\; 1</span>}}^{\mathrm{<span\; class="notranslate">\; k</span>}\mathrm{<span\; class="notranslate">\; 1</span>}}{\mathrm{<span\; class="notranslate">\; R</span>}}_{\mathrm{<span\; class="notranslate">\; 2</span>}}^{\mathrm{<span\; class="notranslate">\; k</span>}\mathrm{<span\; class="notranslate">\; 2</span>}}<span\; class="notranslate">\; )</span><span\; class="notranslate">\; .</span><span\; class="notranslate">\; .</span><span\; class="notranslate">\; .</span><span\; class="notranslate">\; (</span>\mathrm{<span\; class="notranslate">\; 1</span>}<span\; class="notranslate">\; )</span>$

Here, the corrected fluorescence value AF _corr can be obtained by dividing the measured fluorescence value AF by the emitted excitation diffuse reflection light R1 and diffuse reflection light R2 in the fluorescence wavelength range. The two diffuse light values can be adjusted to any degree using the indices k1 and k2.

Equation (1) can be used to obtain corrected skin fluorescence values, and specific values can be introduced to obtain corrected skin fluorescence values through practical testing.

I(λ2,t1): Intrinsic fluorescence (skin fluorescence) signal value of skin tissue

I(λ1,t1): Reflected light signal value of the excitation light wavelength of skin tissue

I(λ2,t2): Reflected light signal value of the emitted light wavelength of skin tissue

k1,k2: Exponents of the correction function with respect to the excitation and emission wavelengths

The newly generated corrected skin fluorescence value can be expressed as equation (2).

AF _tissue =[I(λ2,t1]/[I(λ1,t1) ^k1 I(λ2,t2) ^k2 ];k1,k2<1...(2)

Among them, AF _tissue is the correction signal of intrinsic fluorescence of skin tissue.

Light measurements may be performed periodically at different time intervals t1 and t2. The average value of the measurement results can be taken to improve the accuracy. Measured values can be recorded as a time series graph to track changes at appropriate times.

At the same time, instrument- and calibration-measure-dependent bias corrections for comparison between results obtained from different samples may be required. Therefore, in the present invention, the same measurement can be performed by introducing a reference sample together with the measurement of the target skin tissue. In order to improve the measurement accuracy, the fluorescence intensity I ₀ (λ2,t1) in the excitation light and the emission light and the reflected light signal values I ₀ (λ1,t1) and I ₀ (λ2,t2) can be similar to the optical properties of the skin.

The signal values generated during the measurement of the introduced reference sample can be expressed similarly to the signal values generated during the measurement of the target skin tissue as follows.

I ₀ (λ2,t1): the intrinsic fluorescence signal value of the reference sample

I ₀ (λ1,t1): The reflected light signal value of the excitation light wavelength of the reference sample

I ₀ (λ2,t2): The reflected light signal value of the emitted light wavelength of the reference sample

The signal from the reference sample can be processed with Equation (3) similarly to Equation (2).

AF _reference =[I ₀ (λ2,t1)]/[I ₀ (λ1,t1) ^k1 I ₀ (λ2,t2) ^k2 ]…(3)

The result obtained by dividing AF _tissue by AF _reference can be normalized, and the final corrected intrinsic fluorescence value can be expressed as equation (4).

AF _corr =K(AF _tissue /AF _reference )…(4)

AF _corr =K[I(λ2,t1)/I ₀ (λ2,t1)]/{[I(λ1,t1)/I ₀ (λ1,t1)] ^k1 [I(λ2,t2)/I ₀ ( λ2,t2)]} ^k2 …(5)

where K is a ratio factor that takes into account the characteristics of the reference samples used.

Equation (5) can be simplified to Equation (6).

AF _corr =K[I(λ2,t1)/I ₀ (λ2,t1)]/{[R(λ1)] ^k1 [R(λ2)]} ^k2 …(6)

R(λ1)=I(λ1,t1)/I ₀ (λ1,t1): Diffuse reflectance of excitation wavelength

R(λ2)=I(λ2,t2)/I ₀ (λ2,t2): Diffuse reflection coefficient of emission wavelength

Therefore, with regard to the reflective detection measuring device of skin fluorescence according to the embodiment of the present invention, the corrected skin fluorescence value can be calculated through the above operation process.

In this regard, the principle proposed for the measurement will be described in detail with reference to FIG. 1 .

1 is a graph showing the intensity of light input from a light source and light detected by an optical detector, which is displayed according to time to explain the reflection detection type measurement device for skin fluorescence according to an embodiment of the present invention. Measuring principle. As shown in FIG. 1 , in the reflectance detection type measurement device for skin fluorescence, measurement may be continuously performed under the first condition and the second condition when the first condition and the second condition are separated in time from each other, at Under one condition, light corresponding to the wavelength range (first wavelength λ1) of the excitation light is irradiated as input, and under the second condition, corresponding to the wavelength range (second wavelength λ2) of skin fluorescence generated by the excitation light light is irradiated. The wavelength range of the irradiated light corresponding to the first condition and the second condition may be selectively configured according to the fluorescence of the skin to be detected. For example, considering that skin fluorescence is detected relative to AGE in the exemplary embodiment, light having a first wavelength of 370 nm ± 20 nm can be used as the excitation light for fluorescence excitation under the first condition, and can be used under the second condition Light having a second wavelength of 440 nm ± 20 nm corresponding to the wavelength of skin fluorescence relative to AGE is selectively used.

Measurements may be performed using a measurement scanner 100 comprising a light source for emitting light of two different wavelengths and an optical detector for detecting light of two different wavelengths. Measurement may be performed by bringing the measurement scanner 100 into contact with skin tissue corresponding to a measurement target during diagnostic observation or a reference sample during calibration.

Regarding the measurement process, FIG. 1A shows an operation timing diagram showing simultaneous operation of respective light sources with respect to two different wavelengths separated in time from each other. In this case, the light Φ(λ1, t1) irradiated from the first light source 111 may be configured to exist at a different time than the light Φ(λ2, t2) from the second light source 112, which is The excitation light source, the second light source 112 is a reference light source with different wavelengths.

Figure 1B shows a timing diagram for the operation of two optical detectors. While the light Φ(λ1, t1) is irradiated from the first light source 111, two signals may be generated for the excited skin fluorescence and the reflected light. The two signals generated in the excitation light wavelength may be a reflected light signal I(λ1,t1) and an excited fluorescence signal I(λ2,t1).

Meanwhile, when the light Φ(λ2, t2) is irradiated from the second light source 112, only a single signal may be generated after a period of time. The signal generated by the second light source 112 may only be the reflected light signal I(λ2, t2) within the wavelength range of the irradiated light.

As shown in FIG. 1 , in the reflective detection measuring device for skin, the light irradiation of the first light source 111 and the light irradiation of the second light source 112 can be sequentially performed on the measurement target T, while the light irradiation of the first light source 111 The light exposure and the light exposure of the second light source 112 are temporally separated from each other. In this case, each time light is irradiated, signals detected from the optical detector can be collected and then calculated using the above equation to output a corrected skin fluorescence value.

FIG. 2 is a view showing a reflection detection measurement device for skin fluorescence according to an embodiment of the present invention, which is realized according to the above-mentioned measurement principle.

As shown in FIG. 2 , the reflective detection measurement device for skin fluorescence may include a measurement scanner 100 and a main body 200. The measurement scanner 100 irradiates excitation light on the skin and detects skin fluorescence. The main body 200 and the measurement scanner 100 is connected, and the data detected by the measurement scanner 100 is analyzed to display the data.

However, it is only an exemplary configuration that the measurement scanner 100 and the main body 200 are configured to be separated from each other. Thus, if necessary, the reflectance detection measuring device for skin fluorescence can be manufactured in the form of a single sensor without a separate body, or can also include other components connected to the sensor.

The reflectance detection type measurement apparatus for skin fluorescence may be configured to include a light source and an optical detector that irradiate light onto a target to be measured and detect skin fluorescence generated by the irradiated light.

Specifically, in order to provide accurate skin fluorescence values by correcting detected skin fluorescence values, reflectance detection measurement devices for skin fluorescence may include two light sources and two optical detectors, the two light sources irradiating different wavelengths , the two optical detectors detect reflected light and skin fluorescence at different wavelengths produced by the two irradiated lights.

Specifically, the two light sources may include a first light source 111 and a second light source 112, the first light source 111 emits light corresponding to the wavelength range (first wavelength λ1) of laser light, and the second light source 112 emits light corresponding to the excitation light The wavelength range (second wavelength λ2) of the generated skin fluorescence corresponds to light. The two optical detectors may include a first optical detector 121 and a second optical detector 122, the first optical detector 121 is used to detect the reflected light λ1 relative to the excitation light from the first light source 111, and the second optical detector is used for For detecting the reflected light λ2 relative to the skin fluorescence λ2 from the second light source 112 and by the excitation light.

Thus, two light sources and optical detectors can be configured to simultaneously detect reflected light and skin fluorescence. Preferably, two light sources and optical detectors may be disposed at one end of the measurement scanner 100 and may be close to each other so as to irradiate light on the measurement target T and detect reflected light.

In an exemplary embodiment of the present invention, to detect skin fluorescence relative to AGE, light with a first wavelength of 370nm±20nm can be used as excitation light for fluorescence excitation, and a second wavelength of 440nm±20nm (corresponding to relative Light at the wavelength of skin fluorescence of AGE) can be used as emitted light.

In this case, the first light source 111 may include a light emitting diode irradiating light in a first wavelength range of 370nm±20nm. The second light source 112 may include a light emitting diode irradiating light in a second wavelength range of 440nm±20nm. In addition, the first optical detector 121 may include a photodiode that detects light in a first wavelength range, and the second optical detector 122 may include a photodiode that detects light in a second wavelength range.

Although not shown in FIG. 2 , the reflection detection type measurement device for skin fluorescence may further include a light source switch control unit for controlling on/off of the first light source 111 and the second light source 112 . More preferably, the reflective detection measurement device for skin fluorescence may further include an optical detector switch control unit for controlling on/off of the first optical detector 121 and the second optical detector 122 .

The light source switch control unit and the optical detector switch control unit can control the switches so that the light source and the optical detector can be accurately operated according to detection conditions of skin fluorescence and reflected light, so as to accurately calculate the skin fluorescence value.

The light source switch control unit may be configured to turn on or off the light source according to light irradiation conditions of the reflection detection measuring device for skin fluorescence. For example, under the first condition that the excitation light λ1 is irradiated on the measurement target, the second light source 112 can be turned off, the first light source 111 can be turned on, and the switch of the light source is controlled so that only the first light source 111 irradiates the first light source. wavelength range of light. On the other hand, under the second condition that the emission light λ2 of a wavelength range different from that of the excitation light is irradiated on the measurement target, the first light source 111 may be turned off, and the second light source 112 may be turned on, so that only the second light source 112 The light source 112 irradiates light of the second wavelength range.

Similarly, the optical detector switch control unit may be configured to control on/off of the optical detector according to measurement conditions. The optical detector switch control unit may be configured to turn on/off the optical detector for detecting light in a wavelength range to be detected under current measurement conditions.

In particular, the second optical detector 122 for detecting light relative to the second wavelength may be kept on since detection of an optical signal relative to the second wavelength may be required under both the first condition and the second condition, wherein at Under the first condition, excitation light in the first wavelength range is irradiated, and under the second condition, emission light in the second wavelength range is irradiated.

In this case, switching control may be sequentially performed on the light source for a certain time during the entire measurement process including the first condition and the second condition. Regarding the cycle of switching for each light source, switching control may be performed at a high frequency of about 10 Hz to about 100 Hz so that changes in diffuse reflection due to blood flow do not affect measurement by considering the pulse rate of the human body.

When the measurement scanner 100 of the reflective detection type measurement device for skin fluorescence is manufactured in a hand-held form, even when the measurement scanner 100 is moved by a scanning method of continuously measuring the skin fluorescence while moving the scanner, such The high-speed switch can also realize the measurement of basically the same target point.

Although not shown in FIG. 2 , the reflectance detection measurement device for skin fluorescence may include optical filters selectively disposed in front of the light source and the optical detector. Preferably, in order to prevent the detection of skin fluorescence with relatively low light intensity from becoming difficult due to specular reflection of irradiated light on the skin surface, a pair of polarizers may be provided between the corresponding light source and the optical detector 130 and a pair of crossed polarizers 131.

Polarizers and crossed polarizers may need to be arranged on the pair of first light source 111 and first optical detector 121 and the pair of second light source 112 and second optical detector 122 at mutually crossing positions, respectively.

Meanwhile, the reflection detection type measuring apparatus for skin fluorescence may be configured to include a main body 200 configured to be connectable to the measurement scanner 100 including two light sources and two optical detectors. The main body 200 may be configured to include an operation part that calculates a corrected value of skin fluorescence from data measured by the measurement scanner 100 .

The main body 200 may be configured to be optically, electrically, and mechanically connected to the measurement scanner 100 .

Specifically, the main body 200 may include a mounting part 210 having a shape matching a shape of a measurement terminal of the measurement scanner 100 so that the measurement scanner 100 may be mechanically mounted to the main body 200 . The measurement scanner 100 may be fixedly installed in the mounting part 210 by mechanical coupling.

In an exemplary embodiment of the present invention, the first light source 111 and the second light source 112 and the first optical detector 121 and the second optical detector 122 may be configured to be disposed on one end of the measurement scanner 100, And the mounting part 210 may be configured to have an aperture structure formed in a shape corresponding to the shape of one end of the measurement scanner 100 , allowing the light source and the optical probe to be fixed in the mounting part 210 while facing each other.

Preferably, when the measurement scanner 100 is installed on the main body 200, the main body 200 can be configured to be electrically connected to the measurement scanner 100, allowing the measurement scanner 100 to irradiate light on the measurement target T and obtain information about the detection Skin fluorescence and reflected light data. More preferably, a reference sample for comparison with the measurement target T may be provided above the installation part 210 of the main body 200, and the light source and the optical detector of the measurement scanner 100 may be configured so that when the measurement scanner 100 sits on The mounting part 210 of the main body is optically connected to the reference sample while on. In this case, the reference sample can be chosen to have similar diffuse reflectance and fluorescence optical properties as the human tissue being measured.

Accordingly, when the measurement scanner 100 is installed into the mounting part 210 of the main body 200 to be electrically and optically connected, the measurement scanner 100 may perform the light irradiation and light detection processes that have been performed on the measurement target T on the reference sample. The measured data of the measurement target and the reference sample may be transmitted to the operation part of the main body 200 .

The arithmetic section may calculate a corrected skin fluorescence value with respect to an actual measurement target using data on received fluorescence signals and reflected light signals. The calculation result can be displayed via the display part 220 on the main body 200 .

The above sequential measurements can be repeated. In order to perform an operation process of performing corrections based on the results of repeated measurements, all measured data may be stored in the measurement scanner 100 via a memory. Preferably, the measurement results can be stored in the form of a timing diagram to track changes in the measurement results.

A charging terminal may be provided in the mounting part 210 of the main body 200 to charge the measurement scanner 100 . The charging terminal may be configured to perform charging when the measurement scanner 100 is mechanically coupled with the mounting part 210 .

If necessary, the measurement scanner 100 may be configured to be connected with the main body 200 through Bluetooth.

Exemplary arrangements of light sources and optical detectors in reflectance detection measuring devices for skin fluorescence are shown in FIGS. 3 and 4 .

FIG. 3 is a view showing an exemplary arrangement of a light source and an optical probe when there is no gap between the light source/optical probe and a measurement target. FIG. 4 is a view showing an exemplary arrangement of a light source and an optical probe when there is a gap between the light source/optical probe and a measurement target.

As shown in FIG. 3 , the light source and the optical detector may be arranged parallel to each other and perpendicular to the measurement target, respectively. In order to form an optimal detection area, the first light source 111 and the second light source 112 can be arranged on the outside respectively, and the first optical detector 121 and the second optical detector 122 can be arranged between the first light source 111 and the second light source 112 between.

As shown in Figure 4, when there is a certain gap between the light source/optical detector and the measurement target, the light source and the optical detector can be obliquely arranged to be inclined at certain angles to each other, and can be configured to form a light An irradiation path and a light detection path so that the light source can irradiate light on the same area of the measurement target, and the optical detector can respectively detect the light generated in the same area. Preferably, the light sources and optical detectors corresponding to each other may be arranged to be inclined at an angle of about 45 degrees to each other. For example, when the light source irradiates light perpendicularly on the skin surface, the optical detector can be positioned at an angle of approximately 45 degrees relative to the light source, thereby reducing the effect of specular reflections. The angle between the first light source 111 and the second light source 112 and the first optical detector 121 and the second optical detector 122 may be minimized according to the structure of the instrument. More preferably, the effect of specular reflection can be minimized by arranging a pair of crossed polarizers 130 with filters in front of the light source and optical detector between the corresponding light source and optical detector to remove specularly reflected light.

In this case, the first light source 111 , the second light source 112 , the first optical probe 121 , and the second optical probe 122 may be configured to be connected to the measurement target side ends of the measurement scanner 100 via light guides, respectively. A transparent protective film (eg, a glass plate) may be provided on the contact surface between the skin and the sensor to protect the measurement scanner 100 from impurities (eg, external moisture).

Hereinafter, a test example of light irradiation, light detection, and operation procedures performed by the reflective detection type measuring apparatus for skin fluorescence configured as above will be described as follows.

Example 1

It is necessary to perform measurements on a measurement target and a reference sample (two targets that are introduced to obtain corrected fluorescence values). Light measurements are performed on human skin, which is the measurement target among these two targets.

For diagnosis, the measurement is performed by a light source and an optical detector in contact with or close to a measurement target on the subject's upper arm. The measurement scanner is moved along the skin surface to scan a target portion of about 5 cm ² to about 19 cm ² .

Before measurement, all light sources are turned off, and then level evaluation of the dark signal is performed to automatically compensate light leaked from the outside.

The optical module sequentially generates the first light source illumination light Φ(λ1, t1) with wavelength λ1 and the second light source illumination light Φ(λ2, t2) with wavelength λ2 respectively at different time intervals t1 and t2.

During the entire measurement process, the light generated by the two light sources was sequentially irradiated at time intervals t1 and t2 while repeating on/off at a cycle of about 50 Hz.

Next, the optical detector detects the light irradiated from the light source to convert it into an electrical signal.

The first light source in the near-ultraviolet spectral range (around 370nm) irradiates the light Ф(λ1, t1) to excite the fluorescence of the target to form a corresponding signal I(λ2, t1) through the optical detector, and form a Diffuse reflection is proportional to the signal I(λ1,t1) of the excitation-reflection light.

The second light source illumination light Ф(λ2,t2) in the blue spectral range (around 440nm) corresponds to the maximum of intrinsic fluorescence generated in AGE and NADH and forms a signal proportional to the emitted light diffusely reflected by the target skin I(λ2,t2).

The above measurement is performed repeatedly and periodically at different time intervals t1 and t2, and the average value of the measurement results is taken and stored.

The same measurement process is carried out on the reference sample, and the data calculated in each process is processed in the arithmetic part to calculate a corrected skin fluorescence value.

A timing diagram regarding the actuation of the light source with two wavelengths in the above test example can be shown in Table 1 below.

Table 1

In this test example, the respective cycle times were designed to be approximately 20 ms. Also, the measurement target scan time is calculated to be about 2 seconds, and 100 measurement cycles are performed.

The data measured in this test example are stored and saved in the internal memory of the measurement scanner. When the measurement scanner is placed on the mounting part of the main body, the detection information is automatically moved to the operation part of the main body to be operated according to the function conversion and processed statistically, and the measurement result is displayed.

Meanwhile, the present invention proposes a structure in which an optical prism and an optical connector are disposed on an optical path so that optical transmittance and detection efficiency can be improved.

Fig. 5 shows a reflective measuring device for skin according to an embodiment of the present invention in comparison to a typical reflective measuring device for skin. Figure 5A shows optical irradiation and optical detection without optical prisms and optical connectors. Figure 5B shows optical irradiation and optical detection with optical prisms and optical connectors.

In the case where optical irradiation and optical detection are performed without an optical prism and an optical connector as described in FIG. fluorescence.

In this case, as shown in FIG. 5A , since a light source 310 such as a light emitting diode (LED) is used as an excitation light source that irradiates light with a wide divergence angle, optical loss may occur on the measurement target, and from Scattering of the fluorescence of the skin on which the light is irradiated may cause a loss in the amount of light detected by the optical detector 320 .

Since the detected skin fluorescence is much smaller than the other excitation light or its reflected light, optical losses can considerably reduce the accuracy of the measurement and the reliability of the diagnosis even when they are small.

On the other hand, in order to prevent optical loss, a reflection detection type measurement device for skin fluorescence including an optical prism as shown in FIG. 5B has been proposed.

Referring to FIG. 5B, the excitation light irradiated from the light source 310 may be concentrated by the optical prism 330, and the optical uniformity of the skin portion which is the measurement target may be improved.

Specifically, the optical prism 330 may have two upper inclined surfaces 331 and 332 adjacent to the light source 310 and the optical detector 320, respectively, and a lower surface 333 adjacent to the skin. The excitation light with a wide divergence angle irradiated from the upper inclined surface 331 adjacent to the light source 310 can all be reflected from the upper inclined surface 332 of the optical prism 330 on the optical detector 320 side, and be concentrated on the skin to the maximum extent, thereby reducing the The inhomogeneity of the light source (ie, the property that the optical intensity becomes smaller outside the optical axis than in the center of the optical axis), resulting in improved optical uniformity.

In addition, the optical prism 330 may be used to focus secondary light generated by the light transmitted to the skin tissue portion on the optical detector 320 . Therefore, in the reflectance detection measuring device for skin fluorescence, the optical signal can be improved, and the measurement error can be reduced. Therefore, it is possible to perform optical measurement on a wide skin portion by a scanning method without an optical sensor.

The reflective detection type measurement device for skin fluorescence according to an embodiment of the present invention may be configured to include an optical connector 340 for reducing a specular reflection component reflected by the surface of the skin as a measurement target, and Allows light to penetrate effectively into the skin.

The optical connector 340 may be configured to be located between the lower surface 333 of the optical prism 330 adjacent to the skin as a measurement target and the skin surface, and may contact the lower surface 333 of the optical prism and the skin surface, respectively.

The optical connector 340 may contact the lower surface 333 of the optical prism and the skin surface to serve as a connecting layer for allowing smooth optical contact at its boundary with a suitable refractive index. The optical connector 340 can prevent specular reflection from the skin surface and can allow light to effectively penetrate into the skin.

The optical connector 340 may have a certain refractive index between the two media to prevent possible light leakage between the two media due to refraction and scattering of excitation light between the optical prism 330 and the skin tissue, and Can be used to fill in uneven areas (eg, small unevenness in skin tissue).

The optical connector 340 may be formed of an elastic material or a liquid material (eg, water or oil immersion). The optical connector 230 may be formed of a material having a refractive index similar to that of the optical prism 330 and the skin.

Due to the optical connector 340, total internal reflection of irradiated light may not occur at the boundary between the prism and the skin tissue, and penetration efficiency of light emitted from the light source into the skin may be significantly improved.

Therefore, the reflective detection measurement device for skin including the optical prism 330 and the optical connector 340 can improve optical concentration and optical uniformity, and can significantly reduce specular reflection in which light irradiated from a light source is reflected by the skin surface portion.

Example 2

A reflectance detection measurement device for skin including an optical prism and an optical connector was manufactured. In addition, as a comparative example, a device constructed so that a light source and an optical detector are arranged similarly to those of a reflective detection type measurement device, and without an optical prism and an optical connector Perform optical irradiation and optical probing below.

In this test example, a UV LED (No33, Nichia) emitting light around 365 nm was used as the light source and a fiber optic spectrometer (AVaspec-2048) was used as the optical detector. In addition, optical photodiodes can also be used as optical detectors. A commercial model (Right Angle Prism, Uncoated, 20mm, Edmund Optics) was used as the optical prism.

In this test example, water was used as an optical connector placed between the optical prism and the skin surface as the measurement target.

The specular reflection component of the light irradiated from the light source in the reflection detection measuring device of the test example was measured, and the specular reflection component was also measured in the device of the comparative example.

In the measurement results of the test example and the comparative example, the specular reflection component of the test example was measured to be reduced by about 10 times or more compared to the specular reflection component of the comparative example.

FIG. 6 shows a reflection detection measurement device for skin fluorescence constructed as shown in Test Examples 1 and 2, comprising two light sources 311 and 312 and two optical detectors 321 and 322 . Like in FIG. 5 , an optical prism 330 and an optical connector 340 may be placed between the two light sources 311 and 312 and the two optical detectors 321 and 322 and the skin T as a measurement target.

In this embodiment, the optical prism 330 may have two upper inclined surfaces 331 and 332 adjacent to the light source and the optical detector, respectively, and a lower surface 333 adjacent to the skin. A triangular prism 330 having a triangular cross-section may be used as in FIG. 5 . Preferably, two light sources 311 and 312 can be arranged on the upper inclined surface 331 of the triangular prism 330, and two optical detectors 321 and 322 can be arranged on the upper inclined surface 332 of the triangular prism, thereby allowing the lowering of the prism 330. Surface 333 is in contact with the skin.

In this case, when two different light sources 311 and 312 are disposed on the upper inclined surface 331 , optical axes of the two light sources 311 and 312 may be different from each other. Accordingly, areas of the skin T on which light is irradiated may differ from each other.

However, since the light source is connected to the measurement target T through the optical prism 330 , uniform light under which a difference between optical axes can be corrected by optical reflection inside the optical prism 330 can be obtained.

In addition, a polarizer 351 may be disposed between the light sources 311 and 312 and the optical prism 330 , and a cross polarizer 352 may be disposed between the optical detectors 321 and 322 and the optical prism 330 . As shown in FIG. 6, the polarizer 351 can be arranged on the upper inclined surface of the optical prism 330 below the first light source 311 and the second light source 312, and the crossed polarizer 352 can be arranged on the optical prism 330 under the first optical detector. 321 and 322 below the other on the sloped surface.

As shown in FIG. 6 , an optical connector 340 may be provided between the skin T as a measurement target and the lower surface 333 of the optical prism 330 . The optical connector 230 may contact the lower surface 333 of the optical prism 330 and the surface of the skin T, respectively, allowing smooth optical contact at the boundary thereof with a suitable refractive index.

Therefore, the specular reflection component generated by the optical connector 340 from the surface of the skin T can be reduced, and the light partially reflected due to the difference in refractive index between the surface of the skin T and the optical connector 340 can be additionally placed on the optical detection surface. Crossed polarizer 352 in front of polarizers 321 and 322 blocks.

The reflective detection measurement device for skin fluorescence can be configured to be connected to the main body 360, the main body 360 includes a light source switch controller and an arithmetic unit, the light source switch controller is used to control the first light source 311 and the second light source 312 to turn on/off , the arithmetic unit is used to calculate the correction value of the skin fluorescence signal from the detected fluorescence signal and the reflected light signal.

As described in FIG. 2, in the reflective detection type measurement device for skin fluorescence according to this embodiment, light sources 311 and 312 and optical detectors 321 and 322 can also be arranged at one end of the measurement scanner, and can be The corrected skin fluorescence value is obtained through an operation procedure similar to that of FIG. 2 except that light irradiation is performed through an optical prism disposed between the light source and the measurement target.

Fig. 7 shows a reflection detection measuring device for skin fluorescence according to another embodiment of the present invention. As shown in Figure 7, the reflective detection measuring device may include an optical prism 430 with a trapezoidal section and an optical connector 440, the optical prism 430 has an upper surface 431, a lower surface 432 and two inclined surfaces 433 and 434, the optical connector 440 is placed Between the lower surface 432 and the skin T. Two light sources 411 and 412 may be disposed above the two inclined surfaces 433 and 434 , respectively, and two optical detectors 421 and 422 may be disposed above the upper surface 431 of the optical prism 430 .

Unlike FIG. 6 , the optical prism 430 may have a trapezoidal section having an upper surface in addition to two upper inclined surfaces and a lower surface.

Specifically, the optical prism 430 may be formed to have a trapezoidal shape, in which, except for the two upper inclined surfaces 433 and 434 adjacent to the light source and the optical detector and the lower surface 432 adjacent to the skin T In addition, an upper surface 431 is also included. In addition, the light sources 411 and 412 and the optical detectors 421 and 422 may be disposed above the two upper inclined surfaces 433 and 434 and the upper surface 431 , respectively.

In this embodiment, the first light source 411 and the second light source 412 irradiating light having a different wavelength from the first light source 411 may be disposed above the upper inclined surfaces 433 and 434 of the optical prism 430 , respectively. In addition, the first optical detector 421 and the second optical detector 422 may be disposed above the upper surface 431 connected with the two upper inclined surfaces 433 and 434 to detect light having different wavelengths with respect to the fluorescence signal and the reflected light signal. .

Similar to FIG. 6 , a polarizer 451 and a crossed polarizer 452 may be respectively disposed between the light sources 411 and 412 or the optical detectors 421 and 422 and the optical prism 430 to remove reflected light. As shown in FIG. 7 , a polarizer 451 can be disposed between the first light source 411 and the second light source 412 and the upper inclined surfaces 433 and 434 of the optical prism 430, and a crossed polarizer 452 can be disposed on the first optical detector 421. and between the second optical detector 422 and the upper inclined surface 431 of the optical prism.

In addition, an optical connector 440 may be provided between the lower surface 432 of the optical prism 430 and the skin T as a measurement target. The optical connector 440 may contact the lower surface 432 of the optical prism 430 and the surface of the skin T, respectively.

Figures 8 and 9 illustrate reflective probe measurement devices for skin fluorescence according to other embodiments of the present invention. In these embodiments, an optical prism having a trapezoidal cross-section may be used similarly to the optical prism of FIG. 7 , but the arrangements of the light source and the optical detector are different from each other.

In FIG. 8, two light sources 411 and 412 may be disposed above an upper surface 431 of an optical prism 430, and two optical detectors 421 and 422 may be disposed above two upper inclined surfaces 433 and 434, respectively.

In FIG. 9 , two light sources 411 and 412 may be disposed above one upper inclined surface 433 of the optical prism 430 , and two optical detectors 421 and 422 may be disposed above the other upper inclined surface 434 of the optical prism 430 .

Fig. 10 shows a reflection detection measuring device for skin fluorescence according to another embodiment of the present invention. In this embodiment, an optical prism 430 of trapezoidal cross-section having four upper inclined surfaces 433, 434, 435, and 436 may be provided. Here, the two light sources 411 and 412 and the two optical detectors 421 and 422 may be disposed above the upper inclined surfaces 433, 434, 435 and 436, respectively, so that the two light sources 411 and 412 and the two optical detectors 421 and 422 facing each other.

As shown in FIG. 10, the first light source 411 and the second light source 412 can be selectively disposed above the two upper inclined surfaces 435 and 436, and the first optical detector 421 and the second optical detector 422 can be selectively Set above the other two upper inclined surfaces 433 and 434 .

The first light sources 411 and 412 may be disposed above the two upper inclined surfaces 435 and 436 opposite to each other, and the first optical detector 421 and the second optical detector 422 may be disposed on the two upper inclined surfaces 433 and 436 opposite to each other. 434 above.

In this case, the light sources 411 and 412 and the optical detectors 421 and 422 may be arranged orthogonally to each other. Such an orthogonal arrangement reduces the specular component.

The reflectance detection pyramid measuring device for skin fluorescence according to an embodiment of the present invention can be configured to have a structure in which two light sources 111 and 112 and two optical detectors 121 and 122 are respectively It is arranged on the four sides of the pyramid-shaped bracket. The measurement principle of the pyramid measuring device for skin fluorescence can be basically similar to the case where the light source and the optical detector are arranged side by side as shown in FIG. 1 .

In this regard, FIG. 11 shows a pyramidal mount equipped with two light sources and two optical detectors to realize the above measurement principle. Fig. 12 is a plan view showing a pyramid bracket.

As shown in FIG. 11 , a reflection detector type measurement device for skin fluorescence according to an embodiment of the present invention may include a measurement scanner 100 and a main body 200. The measurement scanner 100 can irradiate excitation light and detect skin fluorescence. 200 interfaces with the scanner 100 to analyze the information detected from the scanner and display the information.

However, such a configuration in which the measurement scanner 100 and the main body 200 are separately provided is only one of exemplary embodiments of the present invention. Therefore, a separate body may not be provided as desired, but may be manufactured as a single sensor type, and other components may be additionally connected to the sensor.

The light source and the optical detector may be disposed on the pyramid measurement module 500 disposed on one end of the measurement scanner 100 .

That is, two light sources and two optical detectors may be installed in the four sides of the pyramid-shaped bracket to form a pyramid-shaped measurement module disposed on one end of the measurement scanner 100 as shown in FIG. 11 500.

More specifically, as shown in FIG. 12 , the pyramid-shaped bracket constituting the pyramid-shaped measurement module 500 may have four through holes on its four sides, and these four through holes may accommodate the first light sources L1 and L2 respectively. and optical detectors D1 and D2.

In this case, as shown in FIG. 12 , the light sources L1 and L2 can be respectively installed in two sides of the pyramid-shaped bracket opposite to each other, and the optical detectors D1 and D2 can be respectively installed in the sides of the pyramid-shaped bracket. in the other two sides opposite each other.

In this arrangement, direct inflow of reflected light to the optical detector can be reduced when an irradiation angle of light and a main optical path of reflected light according thereto are considered.

In addition, optical filters can be selectively provided at the light source and light source detector in the reflection detection type measurement device for skin fluorescence, and polarizers and crossed polarizers can be provided to interrupt light irradiated from the light source by specular reflection while incident on the optical detector.

Accordingly, polarizers and crossed polarizers may be disposed at positions crossing each other on the first light source and first optical detector pair and the second light source and second optical detector pair, respectively.

However, the purpose of setting polarizers and crossed polarizers is to facilitate the detection of skin fluorescence whose light intensity is relatively low compared to the light due to specular reflection, and the intensity of the light source and the detection of fluorescence can be reduced by polarizers and crossed polarizers . In this case, an appropriate design is required because difficulties in fluorescence measurement may occur.

In this regard, since polarizers and crossed polarizers are not necessary components for reducing specular reflections, and in reflectance-detection measurement devices for skin fluorescence, the light source and optical detector are mutually coupled via a pyramid-shaped measurement module. Arranged at an angle of 90 degrees, so the specular reflection effect can be substantially reduced by the structural arrangement.

13 to 15 show the specific configuration of the pyramid measurement module of the reflection detection pyramid measurement device for skin fluorescence according to an embodiment of the present invention.

13 is an exploded perspective view of a pyramid measurement module according to an embodiment of the present invention. 14 and 15 are side views viewed from arrows "A" and "B" of FIG. 13 .

As shown in FIG. 13 , the pyramid module 500 of the reflection detection pyramid measurement device for skin fluorescence may include two light sources and two optical detectors and a pyramid holder 530 equipped with these light sources and optical detectors. .

The pyramid module 530 may have a pyramid shape having four sides and a bottom. The light source and the optical detector may be installed in sides of the pyramid bracket 530, respectively.

More specifically, four through holes 531, 532, 533, and 534 may be formed in the sides of the pyramid bracket 530 to accommodate light sources and optical detectors. That is to say, as shown in FIG. 12, the first through hole 531 formed in one side of the pyramid-shaped bracket 530 can accommodate the first light source 511, and the second through hole 532 opposite to the first through hole 531 can accommodate the second through hole 532. Two light sources 512 . In addition, the third through hole 533 and the fourth through hole 534 may be formed in both sides between the two sides having the first through hole 531 and the second through hole 532 , respectively. The third through hole 533 can accommodate the first optical detector, and the fourth through hole 534 can accommodate the second optical detector 514 .

In this case, two light sources may be provided to obliquely irradiate light from the side of the pyramid bracket 530 to the measurement target. The two optical detectors can also be arranged obliquely on two sides facing each other.

Furthermore, the optical irradiation path and the optical detection path can be allowed to be formed so that the light source and the optical detector can irradiate light on the same area of the measurement target and detect light generated from the same area. Preferably, the light source and the optical detector opposite to each other can be obliquely arranged at an angle of about 45 degrees with respect to the bottom surface of the pyramid bracket 530 adjacent to the measurement target, thereby significantly reducing the effect of specular reflection.

Additionally, a pair of polarizers 515 and 516 and crossed polarizers 517 and 518 may be disposed in vias 531, 532, 533 and 534 along with filters 519 and 520 to minimize the effect of specular reflection.

Polarizers 515 and 516, crossed polarizers 517 and 517, and filters 519 and 520 may be disposed in through-holes 531, 532, 533, and 534 to meet the bottom surface of pyramid 530 on the inside of the light source and optical detector. adjacent.

Through holes 531 , 532 , 533 , and 534 formed in four sides of the pyramid bracket 530 may communicate with the center, and may be connected with an opening ( 535 ) of the bottom surface of the pyramid bracket 530 .

The window 525 may be formed in the opening 535 to contact the measurement target, and the window 525 may be selected in consideration of a refractive index of light, and may be formed of a transparent material such as glass.

The window 525 can be used to protect the skin-contacting and sensor surfaces from impurities such as external moisture.

In addition, the bottom plate 526 may be coupled with the bottom surface of the pyramid bracket 530 via coupling members (eg, bolts 527 ) to fix the window 525 . Bottom plate 526 may have an opening therein so that window 525 may be provided.

Although not shown, the reflection detection type measurement device for skin fluorescence may further include an optical connector that reduces a specular reflection component reflected from the skin surface as a measurement target and allows light to efficiently penetrate into the skin .

The optical connector may be configured to be located between the skin surface and the window 525 adjacent to the skin as a measurement target and to contact the window 525 and the skin surface.

Preferably, a step may be formed between the bottom surface of the bottom plate 526 and the lower surface of the window 525 . The optical connector may be filled in the portion where the step is formed to form a structure in which the optical connector can come into contact with the measurement target.

Thus, the optical connector can contact the window 525 and the skin surface to serve as a connecting layer for enabling smooth optical contact at its boundary with a suitable refractive index. The optical connector prevents specular reflection from the skin surface and allows light to penetrate efficiently into the skin.

The optical connector may have a certain refractive index between the two media to prevent light leakage that may occur between the two media due to refraction and scattering of excitation light between the window 525 and the skin tissue, and may be used for Fills in uneven areas (for example, small unevenness in skin tissue).

Optical connectors may be formed from elastic materials or liquid materials (eg, water or oil immersion). Additionally, the optical connector may be formed from a material having a refractive index similar to that of the window 525 and the skin.

Meanwhile, mounting grooves may be formed in the through-holes 531, 532, 533, and 534 of the pyramid bracket 530, so that the light source, optical detector, polarizer, crossed polarizer, and optical detector may be seated in appropriate positions, respectively. position.

In Fig. 13, four side plates 521, 522, 523 and 524 can be fixedly installed on the sides of the pyramid bracket 530, and light sources and optical detectors can be installed on the side plates 521, 522, 523 and 524 superior. That is, two light sources may be installed inside two side plates among the four side plates 521, 522, 523, and 524, and two optical detectors may be installed inside the other two side plates. The side plates 521 , 522 , 523 and 524 may be fixed on the pyramid bracket 530 through coupling members (eg, bolts 527 ).

Similar to what was described above, in FIG. 13 , optical detection of optical radiation and fluorescent signals from the light source to the measurement target can be performed through four through holes 531 , 532 , 533 and 534 .

Side views viewed from arrows "A" and "B" of FIG. 13 are shown in FIGS. 14 and 15 . In Figures 14 and 15, arrangements of light sources, optical detectors, polarizers and filters are shown.

Hereinafter, exemplary embodiments of optical irradiation, optical detection, and operation procedures performed by the reflective detection measurement device for skin fluorescence will be described as follows.

Example 3

It is necessary to perform measurements on a measurement target and a reference sample (two targets that are introduced to obtain corrected fluorescence values). Light measurement is performed on human skin as a measurement target.

For diagnosis, the measurement is performed by a light source and an optical detector in contact with or close to a measurement target on the subject's upper arm. The measurement scanner is moved along the skin surface to scan a target area of about 5 cm ² to about 19 cm ² . The diameter of the optically irradiated area of the reflection-detection pyramid measuring device for skin fluorescence can be approximately 15 mm at a time.

Before measurement, all light sources are turned off, and then level evaluation of the dark signal is performed to automatically compensate light leaked from the outside.

The optical module sequentially generates the first light source illumination light Φ(λ1, t1) with wavelength λ1 and the second light source illumination light Φ(λ2, t2) with wavelength λ2 respectively at different time intervals t1 and t2.

During the entire measurement process, the light generated by the two light sources was sequentially irradiated at time intervals t1 and t2 while repeating on/off at a cycle of about 50 Hz.

Next, the optical detector detects the light irradiated from the light source to convert it into an electrical signal.

The first light source in the near-ultraviolet spectral range (near 370nm) irradiates light Ф(λ1, t1) to excite the fluorescence of the target to form a corresponding signal I(λ2, t1) through the optical detector, and forms a diffuse signal that is compatible with the skin that is used as the measurement target. The reflected excitation-reflection light is proportional to the signal I(λ1,t1). For the test, the optical detector 513 for measuring the reflected light signal value of the excitation light wavelength of the target skin tissue used a 370nm±20nm UV bandpass filter as the filter 519, and used EdmundOptics Inc's product #48-630.

The second light source illumination light Ф(λ2,t2) in the blue spectral range (around 440nm) corresponds to the maximum of intrinsic fluorescence generated in AGE and NADH and forms a signal proportional to the emitted light diffusely reflected by the target skin I(λ2,t2). The second optical detector 514 for measuring the intrinsic fluorescence signal value of skin tissue uses a 440nm±20 bandpass filter as the filter 520, and uses a product #86-340 of Edmund Optics Inc. In the second optical detector 514, a bandpass filter 520 as described above is used to transmit the intrinsic fluorescence of the skin tissue and interrupt the wavelength (ie, approximately 370 nm) of the excitation light reflected from the skin tissue.

The above measurement is repeatedly and periodically performed at different time intervals t1 and t2, and the measurement results are averaged and stored.

The same measurement process is carried out on the reference sample, and the data calculated in each process is processed in the arithmetic part to calculate a corrected skin fluorescence value.

Meanwhile, in order to obtain a corrected fluorescence signal value of the skin tissue, it is necessary to detect reflected light from the first light source 511 and the second light source 512 emitting light having a fluorescence wavelength, which is reflected by the target. However, since the intensity of reflected light is relatively greater than the intensity of intrinsic fluorescence emitted from skin tissue, measurement signal saturation may occur in the first optical detector and the second optical detector when reflected light is detected. Therefore, in order for an optical detector to simultaneously detect reflected light and intrinsic fluorescence values without loss, an optical attenuation filter that reduces the amount of light within the irradiance reflection and does not generate fluorescence in the visible range can be placed in a part of the optical path superior.

In this regard, FIG. 16 shows an optical attenuation filter disposed in front of the second light source and the first optical detector. In this embodiment, the optical attenuation filters 536 and 537 may be arranged in front of the second light source 512 and the first optical detector 513, and the optical attenuation filters may not be arranged in front of the first light source 511 and the second optical detector 513. detector 514. That is, as shown in FIG. 16A, an optical attenuation filter 536 can be arranged in front of the first optical detector 513, and as shown in FIG. 16B, another optical attenuation filter 537 can be arranged in the second in front of the light source.

Accordingly, the optical attenuation filters 536 and 537 may prevent signal output from the first optical detector 513 and the second optical detector 514 from being saturated by reducing the intensity of the reflected light of the excitation light and the emission light. On the other hand, since the optical attenuation filter is not disposed in front of the first light source 511 that excites intrinsic fluorescence and the second optical detector 513 that detects the fluorescence signal, the fluorescence signal value can be detected without loss.

As described above, the reflection detection type measurement device for skin fluorescence according to the embodiment of the present invention has the following advantages.

First, since diabetes can be easily diagnosed by evaluating skin autofluorescence, a batch test can be performed to find likely diabetic patients. In addition, the risk of cardiovascular disease and its complications can be predicted.

Second, since the optical concentration and optical uniformity of light irradiated from the light source are improved, more uniform light can be irradiated on the measurement target.

Third, since optical efficiency can be improved by efficiently concentrating light from a light source on skin tissue and minimizing specular reflection on the surface of skin tissue, miniaturization of the device can be achieved.

Fourth, since errors due to specular reflection generated on the skin surface and errors due to light scattering and absorption generated inside the skin can be corrected when measuring skin fluorescence, accurate measurement and use of skin fluorescence can be achieved Skin fluorescence for definitive diagnosis of disease.

Fifth, reflective detection measurement devices for skin fluorescence may include light sources and optical detectors, and may be manufactured in the form of small-sized scanners that can be held in the hand to measure skin fluorescence. Accordingly, since a user can scan a diagnosis target by bringing the scanner into contact with the subject's skin, non-invasive diagnosis can be performed in real time.

Sixth, since selective diagnosis can be performed on certain body parts, and the region of the measurement target can be extended to a certain extent by the scanning method, the reliability of signals and the accuracy of diagnosis can be improved.

The invention has been described in detail with reference to the exemplary embodiments of the invention. However, it will be appreciated by those skilled in the art that changes may be made in these embodiments without departing from the principles and spirit of the invention, the scope of which is defined in the appended claims and their equivalents.

Claims (48)

1. A reflectance detection measurement device for measuring skin fluorescence, the reflection detection measurement device configured to perform light irradiation and light detection on a reference sample and a measurement target, the device comprising: a first light source that irradiates excitation light (λ1); a second light source that irradiates light of a wavelength different from that of light from the first light source (λ2); A first optical detector arranged to detect reflected light produced by the excitation light from the first light source and a second optical detector arranged to detect the reflected light produced by the excitation light from the first light source skin fluorescence produced by excitation light from the first light source and reflected light produced by light from the second light source; a light source switch controller for controlling on/off of the first light source and the second light source; and an arithmetic unit, the arithmetic unit calculates a corrected skin fluorescence signal according to the skin fluorescence and reflected light detected by the first optical detector and the second optical detector, wherein the second light source irradiates light (λ2) in the same wavelength range as skin fluorescence excited and emitted by the excitation light from the first light source, Wherein, the light source switch controller controls the first light source and the second light source so that the on states of the first light source and the second light source are separated from each other in time, When the first light source is turned on and the second light source is turned off, the first optical detector detects the reflected light (λ1) for the excitation light from the first light source, and the second optical detector detects Skin fluorescence (λ2) generated by the above excitation light, when the first light source is off and the second light source is on, the second optical detector detects reflected light (λ2) for emitted light from the second light source, Wherein, the switch controller is configured to detect the fluorescence signal and reflected light signal from the first light source and the reflection from the second light source while continuously repeating the process of sequentially turning on and off the first light source and the second light source. light signal. 2. The reflective detection measuring device according to claim 1, further comprising: an optical prism configured to transmit the excitation light irradiated from the light source to the measurement target and to transmit the fluorescence signal to the optical detector, Wherein, the optical prism has a lower surface connected to the measurement target and two or more upper surfaces on which the light source and the optical detector are disposed. 3. The reflective detection type measurement device according to claim 2, further comprising an optical connector disposed under the lower surface of the optical prism and contacting the measurement target. 4. The reflective detection type measurement device according to claim 3, wherein the optical connector includes a connection layer formed of a liquid material or an elastic material between the optical prism and the measurement target. 5. The reflective detection measuring apparatus according to claim 2, wherein the optical prism includes two inclined surfaces and a lower surface adjacent to the measurement target, and is a triangular prism having a triangular cross section. 6. The reflective detection measurement device according to claim 5, wherein said first light source and second light source are disposed above an upper inclined surface of an optical prism, and said first optical detector and second optical The detector is disposed above the other upper inclined surface of the optical prism. 7. The reflective detection measuring device according to claim 2, wherein the optical prism comprises two upper inclined surfaces, an upper surface connected to the two upper inclined surfaces, and a lower surface connected to the measurement target, And is a trapezoidal prism having a trapezoidal section. 8. The reflective detection measurement device according to claim 7, wherein said first light source and second light source are disposed above an upper inclined surface of an optical prism, and said first optical detector and second optical The detector is disposed above the other upper inclined surface of the optical prism. 9. The reflective detection measuring device according to claim 7, wherein the first light source and the second light source are respectively arranged above one upper inclined surface and the other upper inclined surface of the optical prism, and the first An optical detector and a second optical detector are disposed above the upper surface of the optical prism. 10. The reflective detection measuring device according to claim 7, wherein the first optical detector and the second optical detector are respectively arranged above one upper inclined surface and the other upper inclined surface of the optical prism, and The first light source and the second light source are disposed above the upper surface of the optical prism. 11. The reflective detection measuring device according to claim 2, wherein the optical prism comprises four upper inclined surfaces, an upper surface connected to the four upper inclined surfaces, and a lower surface adjacent to the measurement target , and is a frustum of a quadrangular pyramid with a trapezoidal cross-section. 12. The reflective detection measuring device according to claim 11, wherein the first light source and the second light source are respectively arranged above the two upper inclined surfaces of the optical prism, and the first optical detector and the second optical detector The two optical detectors are respectively arranged above the other upper inclined surfaces of the optical prism. 13. The reflective detection measuring device according to claim 12, wherein the first light source and the second light source are arranged above two upper inclined surfaces facing each other, and the first optical detector and the second Optical detectors are arranged above the other upwardly inclined surfaces facing each other. 14. The reflective detection measurement device of claim 2, further comprising a polarizer and a crossed polarizer disposed between the optical prism and the light source and between the optical prism and the optical detector, respectively. 15. The reflective detection measurement device of claim 1 , further comprising a pyramid-shaped support having four sides and a base, Wherein, the first light source, the second light source, the first optical detector and the second optical detector are respectively arranged in one of the four sides. 16. The reflective detection measuring device according to claim 15, wherein the pyramid bracket has a through hole in the four sides respectively, and the through hole is configured to be connected to the pyramid bracket The openings formed in the bottom surface of the first light source and the second light source and the first optical detector and the second optical detector are communicated with each other through the through holes to perform optical irradiation and optical detection respectively. 17. The reflective detection measuring device according to claim 15, wherein the first light source and the second light source are respectively installed in two sides of the pyramid bracket opposite to each other, and the first The optical detector and the second optical detector are respectively installed in the other two sides of the pyramid bracket opposite to each other. 18. The reflection detection measuring device according to claim 16, wherein said pyramid bracket comprises four side plates covering through holes in said four sides, and said first light source, second light source , a first optical detector and a second optical detector are respectively arranged on the side plate to face the through hole. 19. The reflective probe measurement device of claim 16 , further comprising polarizers inside said through hole, first light source and second light source, and inside said through hole, first light source and second light source, respectively. Crossed polarizers inside the light source. 20. The reflection probing measurement device of claim 19, further comprising an optical filter in the through hole, inboard of the optical detector and crossed polarizers. 21. The reflection detecting type measurement device according to claim 16 , further comprising a bottom plate disposed below the bottom surface of the pyramid support, said bottom plate having an opening at its center and a window. 22. The reflective detection measurement device of claim 21, further comprising an optical connector disposed below the window to be contactable with a measurement target. 23. The reflective probe measurement device of claim 22, wherein the optical connector includes a connection layer formed of a liquid material or an elastic material. 24. The reflection detection measuring apparatus according to any one of claims 1 to 23, wherein the measurement target and the reference sample are selectively arranged on the optical path of the first light source and the second light source. 25. The reflective detection measuring device according to any one of claims 1 to 23, wherein the first light source irradiates light having a wavelength of 370±20 nm. 26. The reflective detection measuring apparatus according to any one of claims 1 to 23, wherein the second light source irradiates light having a wavelength of 440±20 nm. 27. A reflective detection measuring apparatus according to any one of claims 1 to 23, wherein the switch controller controls all of the first light source and the second light source to be turned off before each light source is turned on. 28. The reflective detection measurement device of claim 27, wherein the first and second optical detectors measure dark signals when the switch controller turns off all of the first and second light sources, and The arithmetic unit stores the measured dark signal, and compensates the detected fluorescent signal and reflected light signal according to the stored dark signal. 29. The reflective detection measuring apparatus according to any one of claims 1 to 23, wherein the switch controller controls the first light source and the second light source to repeatedly turn on/off at a cycle of 10 Hz to 100 Hz. 30. The reflective detection measuring device according to any one of claims 1 to 23, further comprising an optical detector switch controller for controlling on/off of the first optical detector and the second optical detector. 31. Reflective detection measuring apparatus according to any one of claims 1 to 23, comprising: a measurement scanner comprising a first light source, a second light source, a first optical detector and a second optical detector; and a main body electrically connected to the measurement scanner and including an arithmetic unit, Wherein, the optical sensor is detachable from the main body. 32. The reflective detection measurement device according to claim 31, wherein the measurement scanner is formed in a hand-held form and includes a first light source, a second light source, a first optical detector and a second optical detector. 33. The reflective detection measurement device of claim 31, wherein the measurement scanner includes a memory for storing detected data. 34. The reflective detection measurement device of claim 1, comprising: a measurement scanner comprising a first light source, a second light source, a first optical detector and a second optical detector; and a main body electrically connected to the measurement scanner and including an arithmetic unit, wherein the optical sensor is detachable from the main body; Among them, in the measurement scanner, the first light source, the second light source, the first optical detector, and the second optical detector are vertically arranged parallel to each other so that light irradiation and light detection are performed vertically to the measurement target. 35. The reflective detection measurement device of claim 1, comprising: a measurement scanner comprising a first light source, a second light source, a first optical detector and a second optical detector; and a main body electrically connected to the measurement scanner and including an arithmetic unit, wherein the optical sensor is detachable from the main body; Wherein, in the measurement scanner, the first light source, the second light source, the first optical detector, and the second optical detector are obliquely arranged to be inclined at certain angles to each other, so that light is obliquely performed on the measurement target. Irradiation and light detection. 36. The reflection detection measurement device of claim 35, wherein the first light source and first optical detector and the second light source and second optical detector are all at 45 degrees with respect to the bottom surface of the pyramid-shaped support Angle set diagonally. 37. The reflectance detection measurement device of claim 31, wherein the first light source, second light source, first optical detector and second optical detector are arranged to perform light irradiation and light detection from the same location . 38. The reflective detection measurement device of claim 31, wherein the body includes a mounting member in which a measurement scanner is mounted, and the measurement scanner is configured to be removable from the mounting member. 39. The reflective detection measurement device of claim 38, wherein the first light source, the second light source, the first optical detector and the second optical detector are arranged at one end of the measurement scanner, and The mounting part has formed therein an aperture structure having a shape matching that of one end of the measurement scanner. 40. The reflective detection measurement device according to claim 39, wherein the aperture structure of the mounting part is configured such that the reference sample is in contact with the first light source, the second light source, the first optical detector and the second light source of the measurement scanner. The two optical detectors are optically connected. 41. The reflective detection type measurement apparatus according to claim 40, wherein when the measurement scanner is installed in the installation part, the main body performs measurement on the reference sample, and receives the measurement target and the reference sample stored in the measurement scanner detection data to allow the calculator to calculate the corrected skin fluorescence signal. 42. The reflective detection measurement device of claim 38, wherein the mounting part includes charging terminals for the measurement scanner and allows the measurement scanner to be charged when the measurement scanner is mounted in the mounting part. 43. The reflective detection measurement device of claim 1, comprising: a measurement scanner comprising a first light source, a second light source, a first optical detector and a second optical detector; and a main body electrically connected to the measurement scanner and including an arithmetic unit, wherein the optical sensor is detachable from the main body; Wherein, the measurement scanner includes a pair of polarizers and a pair of crossed polarizers disposed thereon. 44. The reflective detection measurement device of claim 1, comprising: a measurement scanner comprising a first light source, a second light source, a first optical detector and a second optical detector; and a main body electrically connected to the measurement scanner and including an arithmetic unit, wherein the optical sensor is detachable from the main body; Wherein, the first light source and the second light source are connected to one end of the measurement scanner on the measurement target side via a light guide. 45. The reflective detection measurement device of claim 1, comprising: a measurement scanner comprising a first light source, a second light source, a first optical detector and a second optical detector; and a main body electrically connected to the measurement scanner and including an arithmetic unit, wherein the optical sensor is detachable from the main body; Wherein, the first optical detector and the second optical detector are connected to one end of the measurement scanner on the measurement target side via a light guide. 46. The reflective detection measuring device according to claim 31, wherein the main body further comprises a display part, and the display part outputs the corrected skin fluorescence signal calculated in the arithmetic unit. 47. Reflective detection measuring apparatus according to any one of claims 15 to 23, further comprising optical attenuation filters in front of the second light source and the first optical detector, respectively. 48. The reflectance detection measurement device according to any one of claims 1 to 23, wherein said arithmetic unit calculates a skin fluorescence value corrected by the following equation: AF _corr ＝K[I(λ2,t1)/I ₀ (λ2,t1)]/{[R(λ1)] ^k1 [R(λ2)]} ^k2 Here, R(λ1)=I(λ1,t1)/I ₀ (λ1,t1): diffuse reflectance in the excitation wavelength; R(λ2)=I(λ2,t2)/I ₀ (λ2,t2): the diffuse reflection coefficient in the emission wavelength; I(λ2,t1): intrinsic fluorescence (skin fluorescence) signal value of skin tissue; I(λ1,t1): the reflected light signal value of the skin tissue in the excitation light wavelength; I(λ2, t2): the reflected light signal value of the skin tissue in the emitted light wavelength; k1,k2: exponents of the correction function with respect to the excitation and emission wavelengths; I ₀ (λ2,t1): the intrinsic fluorescence signal value of the reference sample; I ₀ (λ1,t1): the reflected light signal value of the reference sample in the excitation light wavelength; and I ₀ (λ2,t2): the reflected light signal value of the reference sample in the emitted light wavelength; K: A ratio factor that takes into account the characteristics of the reference sample used.