HK1193734B

HK1193734B - Transmitted light detection type measurement apparatus for skin autofluorescence

Info

Publication number: HK1193734B
Application number: HK14107172.9A
Authority: HK
Inventors: 姜旭; G．V．帕帕岩; 申伊炯; 李大善; 培寿振; 金广熏
Original assignee: 韩国电气研究院
Priority date: 2012-07-09
Filing date: 2014-07-14
Publication date: 2017-07-07

Description

Transmitted light detection type measuring apparatus for skin autofluorescence

Technical Field

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

The present invention relates to a skin autofluorescence measuring apparatus for diagnosing various diseases by measuring skin autofluorescence from substances accumulated in the skin.

Background

Autofluorescence is the emission of light from the skin after the excitation light is absorbed into the skin. Since there is biometric data inside the skin, autofluorescence functions as a biomarker for disease and enables the examination of physiological state impairment of systemic organs by non-invasive methods.

For example, advanced glycation end products (age) are formed by sugar oxidation of proteins in the human body as a result of Maillard (Maillard) reactions that impair many protein functions. In general, exposure to heart disease risk factors, such as smoking, ingestion of high fatty acid containing foods, hypercholesterolemia, and oxidative stress due to acute diseases, such as sepsis, leads to the production of AGEs. Thus, the produced AGEs slowly decompose and accumulate in the body for a long period of time. An increase in AGE products is associated with the progression of chronic diseases such as arteriosclerosis. AGE tends to accumulate in the body throughout the lifetime of a person as it AGEs.

During the duration of polysaccharidoses, a sustained reaction of enzyme-free protein glycation and sugar oxidation occurs, whereby AGEs, which are complexes of irreversible glycogen and protein, are formed. AGE accumulation, rapidly progresses in patients suffering from diabetes, renal failure and cardiovascular disease. AGEs are accumulated in various tissues including the skin. AGEs are irradiated with excitation light in the ultraviolet range (with a peak near about 370nm) and are characterized by spontaneous fluorescence (AF) irradiated over the blue spectral range (with a peak near about 440 nm).

AGE can be used as a biomarker associated with a range of diseases and can assess physiological damage throughout body organs by measuring autofluorescence of the skin using a non-invasive method. That is, AGE can predict long-term complications in AGE-related diseases. In particular, the amount of skin autofluorescence is increased in patients with diabetes and renal failure, and is implicated in vascular complications and coronary heart disease (CHD,). AGE accumulation can be measured by skin autofluorescence with a non-invasive method, which is a non-invasive clinical tool useful for assessing the risk of long-term vascular complications and diabetes in the environment associated with AGE accumulation.

U.S. patent application publication No.2004-186363 (hereinafter referred to as reference 1) discloses a technique for evaluating AGEs by measuring skin fluorescence in the vicinity of the forearm of a patient as a method and apparatus for suggesting the use of skin autofluorescence measurements as an AGE evaluation.

In reference 1, the excitation light source is a black light fluorescent tube emitting UV-wavelength light in a range of about 300nm to about 420 nm. The collection and recording of the light is performed by a fiber optic spectrometer. To increase the measurement area, the end face of the optical fiber is arranged at a distance (d is about 5mm to about 9mm) from the transparent window of the device. To reduce the effect of light reflected from the skin and the window, the optical fiber is arranged inclined at about 45 degrees to the surface of the window.

Specifically, in reference 1, the end face of the optical fiber for collecting light is disposed as far as possible from the target spot. In this case, the target spot area to be measured is about 0.4cm²。

However, the above method has a limitation in that as the measurement distance (d) is increased to increase the target spot area, the collected fluorescence signal is also greatly reduced. Therefore, in reference 1 according to the related art, the reliability of data detection can be lowered due to the limitation of the size of the skin area that can be measured. In particular, this accuracy limitation is rather pronounced in parts of nevi, vessels and wounds, such as heterogeneous spots of the skin.

Meanwhile, U.S. patent application publication No.2008- & 103373 (hereinafter referred to as reference 2), discloses an apparatus for measuring AGE for use in performing a screening test for diabetic patients. Similar to reference 1, the apparatus disclosed in reference 2 comprises a fiber optic spectrometer for fluorescence measurement of the forearm skin. But unlike reference 1, the fiber optic probe is provided in the form of a bundle containing multiple branches.

In the apparatus of reference 2, ultraviolet light and blue light emitted from light emitting diodes are irradiated on the forearm of a subject (subject) through a fiber-optic probe, and skin fluorescence and diffuse reflected light emitted therefrom are collected through the fiber-optic probe. The collected light is wavelength dispersed (wavelengh-dispersed) in the spectrometer and then detected by a linear array detector. Two branches of the fiber optic probe (illumination fiber; channel 1 and channel 2) are used to illuminate light on the target spot, while the third branch (collection fiber) carries light from the target to the multi-channel spectrometer. The end face of the tissue interface where the branched bundles of fiber optic probes are combined becomes in contact with the irradiated skin.

The light of the white light LED is emitted from one branch of the fiber optic probe for spectral measurement of the reflected light, and the light of the appropriate LED among the LEDs emitting light in the ultraviolet to blue spectral range is emitted from the other branch of the fiber optic probe via the switching device. Various wavelengths can be selected to select the optimal fluorescence excitation conditions. Reflected light spectroscopy is used to detect autofluorescence produced by melanin and hemoglobin and compensate for the measurements. The respective optical fibers are arranged in the bundle in a certain order. The fibers from the three branches of the bundle are sequentially arranged in a mosaic pattern with a spacing b of 0.5 mm.

In reference 2, since light is irradiated on the forearm of the subject through the fiber-optic probe, the fiber-optic probe is included as a light transmission medium. However, fiber optic probes have a transmission loss limitation that arises from the small diameter and low numerical aperture of the optical fiber.

Further, since both of the apparatuses disclosed in references 1 and 2 include an optical fiber in a light receiving unit that receives light, there is an inherent limitation in the optical fiber probe of the receiving unit. Since references 1 and 2 are configured to use a fiber optic spectrometer and a linear array detector, there is a limitation that the wavelength of the autofluorescence signal of AGE becomes relatively smaller in the detection area occupied by the linear array detector. Therefore, the detected fluorescent signal is dispersed, and the light intensity of the wavelength detected by the linear array detector becomes relatively smaller. Furthermore, it is difficult to minimize facilities due to the fiber optic probe and the fiber optic spectrometer.

Meanwhile, when skin fluorescence is measured to diagnose a disease, in addition to a reflection detection method of detecting reflected light reflected by a light irradiation area on the skin and skin fluorescence, a transmitted light detection method of detecting transmitted light of light irradiated on the skin and skin fluorescence at a position where the transmitted light is measured may be considered.

In the transmitted light detection method, the target skin, which is used to measure the intensity of intrinsic fluorescence generated from the target skin, is transmitted by the irradiation light, so that the light can be detected on the opposite side of the target skin.

In general, each part of the target skin can be considered as follows according to the transmitted light detection method. First, in the case of an earlobe having a thickness of 3mm, the loss of transmitted light is considerable, and the influence of light absorbed by blood is very considerable. Also, in the case of a finger, when the measurement is made between the nail and the skin on both sides of the nail, the influence of fluorescence generated from the nail on the measurement is considerable. On the other hand, when the measurement is made between the nail and the skin on the opposite side in the direction perpendicular to the nail, the optical path-to-loss ratio increases, and the measurement is appreciably affected by the finger skin condition and blood. Meanwhile, when the measurement is performed on the skin between the thumb and the index finger, there are the following benefits. First, since the thickness of the skin is about 1mm, the optical loss is not large. Second, the measurement is less affected by blood. Third, the measurement is less affected by skin pigments and is convenient to perform.

Meanwhile, although selective diagnosis using transmitted light is performed on a body part, the intensity of fluorescence generated from the skin, absorption by light scattering and appearing in the skin, and the influence of fluorescent substances contained in the skin.

Thus, since measurement errors occur due to the influence of light scattering and absorption, it is necessary to correct the measurement errors in order to accurately detect skin fluorescence due to fluorescence excitation. In particular, in the case of diagnosing a disease such as diabetes using skin fluorescence measurement values, since the difference between a person with a disease and a person without a disease is not large enough to offset the measurement error, an apparatus for more accurately detecting skin fluorescence is required even when skin fluorescence is measured by a transmitted light detection method.

Therefore, in order to realize a selective diagnosis apparatus using the transmitted light detection method, miniaturization and mobility of the apparatus must first be prepared. Accordingly, efficiency of light irradiation and fluorescence detection in the device are necessary.

In addition, it is very important to improve the efficiency of light irradiation and fluorescence detection and reduce measurement errors due to light scattering and absorption in the skin in order to more clearly discriminate between a diseased person and a non-diseased person, so as to obtain accurate diagnosis of a selective diagnosis section.

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 to a person skilled in the art of local area.

Disclosure of Invention

The present invention provides a transmitted light detection type measuring device for skin fluorescence, which is capable of detecting skin fluorescence together with transmitted light in measuring advanced glycation end product (AGE) fluorescence of skin, and calculating a corrected skin fluorescence signal with improved accuracy from the detected skin fluorescence and transmitted irradiation light.

The present invention also provides a transmitted light detection type measuring apparatus for skin fluorescence, which can increase the possibility of diagnosis of diseases such as diabetes by accurately assessing diagnostic factors such as AGE from corrected skin fluorescence values.

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

In one aspect, the present invention provides a transmitted light detection-type measuring apparatus for skin fluorescence, which is configured to perform light irradiation and light detection on a reference sample and a measurement target, the apparatus comprising: a first light source that irradiates excitation light; a second light source irradiating light having a wavelength different from that of the light of the first light source; first and second light detectors arranged to detect transmitted light from the first and second light sources and arranged to detect two different wavelengths in respect of the fluorescent and transmitted light signals; a light source switch controller for controlling on/off of the first light source and the second light source; and an arithmetic unit that calculates a corrected skin fluorescence signal from the fluorescence signal and the transmitted light signal detected by the first light detector and the second light detector, wherein the second light source irradiates light that is excited by the excitation light of the first light source and is in the same wavelength range as the emitted skin fluorescence.

In an exemplary embodiment, the light source switching controller may control the first light source and the second light source so 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: the fluorescent signal and the transmitted light signal from the first light source and the transmitted light signal from the second light source are detected while continuously repeating the process of sequentially turning the first light source and the second light source on and off.

In yet another exemplary embodiment, the measurement target and the reference sample may be selectively positioned on the optical 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 yet another exemplary embodiment, the switch controller may control all of the first and second light sources to be turned off before turning on each light source.

In still another exemplary embodiment, when the switching controller turns off all of the first and second light sources, the first and second photodetectors may measure a dark signal, and the operator may store the measured dark signal and compensate the detected fluorescent and transmitted light signals 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 be repeatedly turned on/off at a cycle of about 10Hz to about 100 Hz.

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

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

In still another exemplary embodiment, the light sensor may include a first fixing portion connected to the first light source and the second light source, and a second fixing portion connected to the first light detector and the second light detector, and the first and second fixing portions may face each other to form an insertion space therebetween.

In yet another exemplary embodiment, the light sensor may include a memory for storing the detection data.

In still another exemplary embodiment, the light sensor may include a common light source optical waveguide for transmitting the light irradiated from the first light source and the second light source in a common manner.

In yet another exemplary embodiment, the light sensor may include a common detection light guide for transmitting the transmitted light and the skin fluorescence light to the first light detector and the second light detector in a common manner.

In still another exemplary embodiment, the light sensor may include a first dichroic mirror on a light path to transmit light irradiated from the first light source and the second light source to the common light source optical waveguide.

In yet another exemplary embodiment, the light sensor may include a second dichroic mirror in the light path to separate light from the common detection light waveguide and transmit the separated light to the first and second light detectors.

In yet another exemplary embodiment, the apparatus may include a light source filter between the first light source and the first dichroic mirror to pass light of the first wavelength irradiated from the first light source and to block light of the second wavelength irradiated from the second light source.

In still another exemplary embodiment, the apparatus may include an objective lens between the first and second light sources and the first dichroic mirror to condense the light irradiated from the first and second light sources, respectively.

In yet another exemplary embodiment, the apparatus may include a first detection filter between the second dichroic mirror and the first photodetector, wherein the first detection filter passes light of the first wavelength and blocks light of the second wavelength, and a second detection filter between the second dichroic mirror and the second photodetector, wherein the second detection filter blocks light of the first wavelength and passes light of the second wavelength.

In yet another exemplary embodiment, the apparatus may include an objective lens between the first and second photodetectors and the second dichroic mirror so that light passing through the second dichroic mirror is focused on the first photodetector and the second photodetector, respectively.

In still another exemplary embodiment, the apparatus may include a first light source optical waveguide for transmitting light irradiated from the first light source, and a second light source optical waveguide for transmitting light irradiated from the second light source.

In yet another exemplary embodiment, the light sensor may include a first detection light guide for transmitting the transmitted light of the first light source to the first light detector, and a second detection light guide for transmitting the transmitted light of the second light source or the skin fluorescence to the second light detector.

In yet another exemplary embodiment, the apparatus may include a light source filter between the first light source and the first light source optical waveguide to pass light of the first wavelength irradiated from the first light source and to block light of the second wavelength irradiated from the second light source.

In yet another exemplary embodiment, the apparatus may include a first detection filter between the first light source optical waveguide and the first light detector for passing light of the first wavelength and blocking light of the second wavelength, and a second detection filter between the second light source optical waveguide and the second light detector for blocking light of the first wavelength and passing light of the second wavelength.

In still another exemplary embodiment, the first and second light sources may be disposed at a distal end of the first fixing portion so as to directly irradiate light on the measurement target, and the first and second light detectors may be disposed at a distal end of the second fixing portion so as to directly detect the transmitted light and the skin fluorescence.

In yet another exemplary embodiment, the first and second photodetectors may be configured to form two sectors and may include a band pass filter in front of the two sectors for separating light into a first wavelength (λ 1) and a second wavelength (λ 2), respectively.

In still another exemplary embodiment, the first fixing portion and the second fixing portion may be manufactured in the form of a clip for fixing the measurement target while pressing the measurement target.

In yet another exemplary embodiment, the reference sample may be movably installed in the optical sensor and may be fitted into an insertion space between the first fixing portion and the second fixing portion when the measurement target is removed from the insertion space.

In still another exemplary embodiment, the light sensor may measure the skin as a measurement target when the skin is positioned in the insertion space, and the reference sample may be measured when the measurement target is removed and then the reference sample is positioned in the insertion space.

In still another exemplary embodiment, the light sensor may store the measurement results with respect to the skin and the reference sample as the measurement target T, and may transmit the stored data with respect to the skin and the reference sample to the main body, so as to allow the operator to calculate the corrected skin fluorescence signal.

In still another exemplary embodiment, the main body may further include a display part, and the display part outputs the corrected skin fluorescence signal calculated in the operator.

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

AF_corr＝K[I(λ2，t1)/I₀(λ2，t1)]/{[T(λ1)]^k1[T(λ2)]}^k2

here, T (λ 1) ═ I (λ 1, T1)/I₀(λ 1, t 1): in the excitation wavelengthThe diffuse reflection coefficient of (a);

T(λ2)＝I(λ2，t2)/I₀(λ 2, t 2): diffuse reflectance in the emission wavelength;

i (λ 2, t 1): intrinsic fluorescence (skin fluorescence) signal values of skin tissue;

i (λ 1, t 1): a transmitted light signal value of skin tissue in the excitation light wavelength;

i (λ 2, t 2): a transmitted light signal value of skin tissue in the emitted light wavelength;

k1, k 2: the index of the correction function with respect to the wavelength of the excitation and emission light;

I₀(λ 2, t 1): intrinsic fluorescence signal values of the reference sample;

I₀(λ 1, t 1): the transmitted light signal value of the reference sample in the wavelength of the excitation light; and

I₀(λ 2, t 2): the transmitted light signal value of the reference sample in the wavelength of the emitted light.

K: taking into account the ratio coefficient of the reference sample property used.

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

In yet another exemplary embodiment, the present invention provides a transmitted light detection-type measuring apparatus for skin fluorescence, including: a first light source that irradiates excitation light; a light detector for detecting transmitted light and a fluorescent signal with respect to the excitation signal irradiated from the light source; a pair of light transmitters configured to transmit excitation light irradiated from the light source to the measurement target and transmit transmitted light and the fluorescence signal to the light detector; wherein the optical transmitter has: a mounting surface on which a light source or a light detector is mounted; a reflection surface extending from the mounting surface to the measurement target and reflecting light; and a contact surface connected to cause light to be incident on the measurement target.

In yet another exemplary embodiment, the light source may be configured to include: a first light source that irradiates excitation light; and a second light source irradiating light having a wavelength different from that of the light of the first light source. The light detector may be configured to include a first light detector and a second light detector arranged to detect two different wavelengths for the fluorescent light signal and the reflected light signal.

In yet another exemplary embodiment, the second light source may irradiate light having a wavelength range of skin fluorescence that is excited by the excitation light of the first light source and is emitted.

In still another exemplary embodiment, the apparatus may further include: a light source switch controller for controlling on/off of the first light source and the second light source; and an arithmetic unit for calculating a corrected skin fluorescence signal from the fluorescence signal and the transmitted light signal detected by the first photodetector and the second photodetector.

In still another exemplary embodiment, the pair of optical transmitters may include: a first optical prism connected to the light source; and a second optical prism connected to the light detector.

In still another exemplary embodiment, the first optical prism and the second optical prism may be triangular prisms having a triangular cross section.

In still another exemplary embodiment, the first optical prism may have: a mounting surface on which a first light source is mounted; and a reflective surface mounted with a second light source.

In still another exemplary embodiment, the second optical prism may have: a mounting surface on which the first photodetector is mounted, and a reflective surface on which the second photodetector is mounted.

In still another exemplary embodiment, the pair of optical transmitters may include: a first light pipe connected to the light source; and a second light pipe connected to the light detector.

In yet another exemplary embodiment, the first light pipe and the second light pipe may have an inclined reflective surface and a tapered cylindrical shape in which a mounting surface is larger than a contact surface.

In yet another exemplary embodiment, the first light pipe may have: a mounting surface on which the first light source and the second light source are mounted.

In yet another exemplary embodiment, the second light pipe may have: a mounting surface on which the first photodetector and the second photodetector are mounted.

In still another exemplary embodiment, the apparatus may further include a dichroic prism on a side of the mounting surface of the second light guide for splitting the detected light into two wavelength bands.

In yet another exemplary embodiment, the first light detector may be arranged to detect light reflected from the color separation prism, and the second light detector may be arranged to detect transmitted light from the color separation prism.

In still another exemplary embodiment, the first light guide and the second light guide may be vertical type light guides extending in a vertical direction to a contact surface having a measurement target.

In still another exemplary embodiment, the first light guide and the second light guide may be horizontal type light guides extending in parallel directions to a contact surface having a measurement target.

In yet another exemplary embodiment, the reflective surfaces of the first and second light pipes may be tapered so as to reduce their cross-sectional area from the mounting surface to the contact surface.

In yet another exemplary embodiment, the mounting surfaces of the first and second light pipes may be inclined to their reflective surfaces.

In yet another exemplary embodiment, the reflective surfaces of the first light pipe and the second light pipe may each include a curved reflective surface that is inclined to the contact surface.

In yet another exemplary embodiment, the reflective surfaces of the first and second light pipes may be treated with a specular coating (mirrorcoating).

In still another exemplary embodiment, the apparatus may further include: a transfer section for moving the optical transmitter in a vertical direction; and a thickness indicator for measuring a distance between the two light transmitters and indicating a thickness of a measurement target.

In still another exemplary embodiment, the apparatus may further include an optical connector disposed on the contact surface of the optical transmitter and contacting the measurement target.

In still another exemplary embodiment, the optical connector may function as a connection layer formed of a liquid material or an elastic material between the optical transmitter and the measurement target.

Drawings

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

FIG. 1 is a graph showing intensities of light input from a light source and light detected by a photodetector, plotted in time, to explain a measurement principle of a transmitted light detection type measurement apparatus for skin fluorescence according to an embodiment of the present invention;

FIG. 2 is a view showing a transmitted light detection type measuring apparatus for skin fluorescence according to an embodiment of the present invention;

FIG. 3 is a view illustrating an exemplary arrangement of a light source and a light detector when there is no gap between the light source and the light detector and a target skin in a transmitted light detection type measuring apparatus for skin fluorescence according to an embodiment of the present invention;

FIG. 4 is a view illustrating an exemplary arrangement of a light source and a light detector when there is a gap between the light source and the light detector and a target skin in a transmitted light detection type measuring apparatus for skin fluorescence according to an embodiment of the present invention;

FIG. 5 is a view showing a transmitted light detection type measuring apparatus for skin fluorescence according to an embodiment of the present invention, in which an optical prism is used;

FIGS. 6 to 10 are views showing a transmitted light detection type measuring apparatus for skin fluorescence according to another embodiment of the present invention;

FIG. 11 is a view showing a transmitted light detection type measuring device for skin fluorescence according to still another embodiment of the present invention, in which a modified light guide is used; and

fig. 12 is a view showing a transmitted light detection type measuring device for skin fluorescence according to still another embodiment of the present invention, in which an optical fiber or a fiber bundle may be used instead of the light guide.

Reference numerals, which are set forth in the accompanying drawings, include reference to the following elements, as discussed further below:

100: the optical sensor 200: main unit body

111: first light source 112: second light source

113: first dichroic mirror 114: light source filter

115. 116: objective lens 117: common light source optical waveguide

121: the first light detector 122: second photodetector

123: second dichroic mirror 124: first detection filter

125: second detection filters 126, 127: objective lens

128: common detection optical waveguide 130: electronic control module

131. 132: a/D converter 133: data transfer module

134: the driver module 210: operation part

220: display part

300: the optical sensor 400: main unit body

311: first light source 312: second light source

313: light source filter 314: first light source optical waveguide

315: second light source optical waveguide 321: first photodetector

322: the second photodetector 323: first detection filter

324: second detection filter 325: first detection optical waveguide

326: second detection optical waveguide 330: electronic control module

331. 332: a/D converter 333: data transfer module

334: the driver module 410: operation part

420: display part

511: first light source 512: second light source

521: first light detector 522: second photodetector

530: electronic control modules 531, 532: A/D converter

533: the data transfer module 534: driver module

600: the main body 610: operation part

620: display part

710: first light source 712: second light source

720: first optical prism 730: second optical prism

741: first photodetector 742: second photodetector

750: optical connectors 761, 762: filter with a filter element having a plurality of filter elements

800: optical sensor

811: first light source 812: second light source

820: first light pipe 830: second light pipe

841: first light detector 842: second photodetector

850: optical connector 860: main unit body

870: color separation prism

911: first light source 912: second light source

920: first light pipe 930: second light pipe

941: first photodetector 942: second photodetector

950: optical connector

T: measurement target (skin) R: reference sample

It should be understood that the 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 specific dimensions, orientations, locations, and shapes, for example, will be determined in part by the particular intended application and use environment.

In the drawings, reference numerals refer to the same or equivalent parts throughout the several views of the drawings.

Detailed Description

Reference will now be made in detail to the various embodiments of the invention, examples of which are illustrated in the accompanying drawings and described below. While the invention will be described in conjunction with the exemplary embodiments, it will be understood that they are not intended to limit the invention to those exemplary embodiments. On the contrary, the invention is intended to cover not only these exemplary embodiments, but also various changes, 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 present invention are discussed below.

The present invention relates to a skin fluorescence measuring apparatus for irradiating excitation light on skin and measuring skin fluorescence generated by the excitation light for the purpose of diagnosis of diseases such as diabetes. In particular, it provides a transmitted light detection type measuring apparatus for skin fluorescence, which is capable of accurately measuring corrected skin fluorescence from skin fluorescence data at a position at which: a transmitted light of the irradiation light; and transmitted light of skin fluorescence scattered and emitted from within the skin due to the irradiated light on the skin.

For this purpose, sequential measurements are made of the target to be diagnosed and of a reference sample, and the information obtained from the target can be compared with the information obtained with the reference sample to eliminate the individual deviations that the target has, while the light source and the light detector can be switched on/off sequentially according to certain conditions required by the above-mentioned process. Thus, provided is a transmitted light detection type measuring device for skin fluorescence, which is capable of providing a corrected skin fluorescence value.

Hereinafter, exemplary embodiments of a transmitted light detection type measuring apparatus for skin fluorescence will be described in detail with reference to the accompanying drawings.

For the measurement of fluorescence generated on the skin, it is necessary to select a skin target and consider factors that affect the measured fluorescence. The fluorescence measured may depend on the light scattering and absorption occurring inside the skin, as well as fluorescent substances contained in the skin. In particular, it is necessary to take into account the influence of light absorption and scattering in the wavelength of fluorescence generated in the fluorescent substance and the wavelength of excitation light of irradiation that excites the fluorescent substance to correct the measured fluorescence value. Therefore, the following empirical equation (1) can be considered to reduce the influence of optical factors on the fluorescence intensity.

Here, by dividing the measured fluorescence value AF by the excitation diffuse transmission light T1 and the diffuse transmission light T2 emitted in the fluorescence wavelength range, a corrected fluorescence value AF can be obtained_corr. The two diffuse transmission light values can be adjusted slightly (with) by the indices k1 and k 2.

In an exemplary embodiment of the present invention, equation (1) may be used to obtain corrected skin fluorescence values by the transmitted light detection method, and discrete values may be introduced to obtain corrected skin fluorescence values by actual testing.

k1, k 2: the index of the correction function to the wavelength of the excitation light and the emission light;

the newly resulting corrected skin fluorescence value by the transmission detection method can be expressed as equation (2).

AF_tissue＝[I(λ2，t1]/[I(λ1，t1)^k1I(λ2，t2)^k2]；k1，k2＜1(2)

AF here_tissueIs a correction signal for the intrinsic fluorescence of the skin tissue.

The measurement of light may be performed periodically at different time intervals t1 and t 2. The measurements may be averaged to increase accuracy. The measured values may be recorded in the form of a time map to track changes at the appropriate time.

Also, depending on the equipment and the offset correction of the correction measurements, a comparison between the results obtained for different samples may be required. Thus, in the present invention, the same measurement can be carried out together with the measurement of the target skin tissue by introducing a reference sample. To increase the accuracy of the measurement, the fluorescence intensity 1₀(lambda 2, t1) and the transmitted light signal value I in the excitation light and the emission light₀(lambda 1, t1) and I₀(λ 2, t2) may have optical characteristics similar to skin.

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

I₀(λ 2, t 1): intrinsic fluorescence signal values of the reference sample.

I₀(λ 1, t 1): the transmitted light signal value of the reference sample in the excitation light wavelength.

The signal obtained from the reference sample can be processed using equation (3) similar to equation (2).

AF_reference＝[I₀(λ2，t1)]/[I₀(λ1，t1)^k1I₀(λ2，t2)^k2](3)

By AF_referenceExcept for AF_tissueThe results obtained 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)/I₀(λ2，t1)]/{[I(λ1，t1)/I₀(λ1，t1)]^k1[I(λ2，t2)/I₀(λ2，t2)]}^k2(5)

Where K is a ratio coefficient taking into account the characteristics of the reference sample used.

Equation (5) can be simplified to equation (6),

AF_corr＝K[I(λ2，t1)/I₀(λ2，t1)]/{[T(λ1)]^k1[T(λ2)]}^k2(6)

t (λ 1) ═ I (λ 1, T1)/I0(λ 1, T1): diffuse transmission coefficient in excitation wavelength.

T (λ 2) ═ I (λ 2, T2)/I0(λ 2, T2): diffuse transmission coefficient in the emission wavelength.

Therefore, with the transmitted light detection type measuring apparatus of skin fluorescence according to the embodiment of the present invention, the corrected skin fluorescence value can be calculated by the above-described operation procedure.

In this connection, the principle of the measurement proposal will be described in detail with reference to fig. 1.

Fig. 1 is a graph showing intensities of light input from a light source and light detected by a photodetector, which are plotted in time to explain a measurement principle of a transmitted light detection type measurement apparatus for skin fluorescence according to an embodiment of the present invention. As shown in fig. 1, in the transmitted light detection type measuring apparatus for skin fluorescence, measurement may be performed successively under a first condition in which light corresponding to the wavelength range (first wavelength λ 1) of excitation light is irradiated as input, and a second condition in which light corresponding to the wavelength range (second wavelength λ 2) of skin fluorescence generated by the excitation light is irradiated, while the two conditions are separated from each other in time. The wavelength ranges of the irradiated light corresponding to the first and second conditions may be selectively configured according to the skin fluorescence to be detected. For example, in an exemplary embodiment, light having a first wavelength of 370nm ± 20nm may be used as the excitation light for fluorescence excitation under the first condition, and light having a second wavelength of 440nm ± 20nm corresponding to the wavelength of skin fluorescence with respect to AGE may be selectively used under the second condition, considering that skin fluorescence is detected with respect to AGE.

The measurement may be performed with a light sensor comprising: a light source for emitting light of two different wavelengths, and a light detector for detecting light of two different wavelengths. The measurement can be performed by bringing the optical sensor into contact with skin tissue corresponding to a measurement target during diagnostic observation, or a reference sample during calibration.

With respect to this measurement process, FIG. 1A depicts an operational time diagram illustrating the operation of the respective light sources with respect to two different wavelengths, separated in time from one another. In this case, the light Φ (λ 1, t1) irradiated from the first light source as the excitation light source may be configured to exist at different times from the light Φ (λ 2, t2) from the second light source as the reference light source of different wavelength ranges.

FIG. 1B is a graph of operating time for two photodetectors. In the same time when light Φ (λ 1, t1) is being irradiated from the first light source, two signals can be generated with respect to excited skin fluorescence and transmitted light. The two signals generated in the excitation light wavelength may be a transmitted light signal I (λ 1, t1) and an excited fluorescence signal I (λ 2, t 1).

Meanwhile, when the light Φ (λ 2, t2) is irradiated from the second light source, only a single signal in time can be generated. The signal generated by the second light source may be only the transmitted light signal I (λ 2, t2) in the irradiated light wavelength range.

As shown in fig. 1, in the transmitted light detection type measuring apparatus for skin fluorescence, light irradiation of the first light source and light irradiation of the second light source may be sequentially performed on the measurement target temporally separately from each other. In this case, the signal detected by the photodetector may be collected for each such exposure and then may be calculated using the above equation to output a corrected skin fluorescence value.

Fig. 2 to 4 are views showing a transmitted light detection type measuring apparatus for skin fluorescence according to an exemplary embodiment of the present invention, which is implemented according to the above-described measuring principle.

As shown in fig. 2 to 4, the transmitted light detection type measuring apparatus for skin fluorescence may include: a photosensor irradiating the excitation light on the skin and detecting fluorescence of the skin; and a main body connected to the light sensor and analyzing data detected by the light sensor to display the data.

However, as an exemplary configuration only, the light sensor and the host body are configured to be separated from each other. Therefore, if necessary, the transmitted light detection type measuring device for skin fluorescence may be fabricated in the form of a single sensor without a separate main body, or may further include other components connected thereto.

The transmitted light detection type measuring apparatus for skin fluorescence may be configured to include a light source and a photodetector for irradiating light on an object to be measured and detecting skin fluorescence generated with the irradiated light.

In particular, in order to provide an accurate skin fluorescence value by correcting the detected skin fluorescence value, the transmitted light detection type measuring apparatus for skin fluorescence may include two light sources that irradiate light of different wavelengths, and two light detectors that can detect the transmitted light and the skin fluorescence generated using the two irradiated lights of different wavelengths.

Specifically, the two light sources may include a first light source that emits light corresponding to the wavelength range of the excitation light (first wavelength λ 1), and a second light source that emits light corresponding to the wavelength range of the skin fluorescence generated with the excitation light (second wavelength λ 2). The two light detectors may be arranged at positions capable of detecting the transmitted light of the first light source and the second light source.

The two photodetectors may include a first photodetector for detecting transmitted light λ 1 with respect to the excitation light from the first light source and a second photodetector for detecting transmitted light λ 2 with respect to the emission light from the second light source and skin fluorescence λ 2 generated using the excitation light.

Thus, the two light sources and the light detector may be arranged at positions capable of detecting the transmitted light and the skin fluorescence simultaneously. Preferably, the light source and the light detector may be disposed to face each other so as to form a space into which a measurement target or a sample can be inserted at an end of the light sensor.

In this case, the light source and the light detector do not necessarily face each other. When connecting with an optical signal transmission method such as an optical waveguide, an end portion where light irradiation is performed and another end portion where light detection is performed may be arranged to face each other.

Therefore, in the transmitted light detection type measuring apparatus for skin fluorescence according to the embodiment of the present invention, the optical waveguide may be disposed between insertion spaces where the measurement target is positioned so as to allow light to be transmitted to the skin and the reference sample as the measurement target through the optical waveguide. Furthermore, the optical waveguide may also be arranged between the insertion space and the light detector so as to allow the transmitted light through the skin and the skin fluorescence to be transmitted to the light detector through the optical waveguide.

The light sensor, which includes a light source and a light detector, may be configured to perform light transmission to a measurement target and light signal detection, respectively, and for this, an end portion of the light sensor may be configured to be in contact with skin or a reference sample as a measurement target.

The light sensor may be configured in the form of a clip in which an insertion space is formed between a first fixing portion on a side where the light source irradiates light and a second fixing portion on a side where the light detector detects light, the two portions facing each other.

Therefore, when the measurement target is positioned in the insertion space between the first fixing portion and the second fixing portion, the light irradiation and the light detection are performed on the measurement target.

When no measurement target is in the insertion space, a reference sample may be inserted into the insertion space, and light irradiation and light detection may be performed on the inserted reference sample. The reference sample may be configured to be automatically inserted into the insertion space. In this case, the reference sample may be automatically inserted when the measurement target is removed from the insertion space after the light irradiation and the light detection, and thereafter, the light irradiation and the light detection may be performed on the reference sample.

In this case, the reference sample may be selected so as to have optical characteristics similar to the diffuse transmission and fluorescence of the human body tissue being measured.

Meanwhile, the transmitted light detection type measuring apparatus for skin fluorescence may further include a light source switch control unit for controlling on/off of the first and second light sources. Preferably, the transmitted light detection type measuring apparatus for skin fluorescence may further include a photodetector switch control unit for controlling on/off of the first and second photodetectors.

The light source switch control unit and the photodetector switch control unit may control the switches so that the light source and the photodetector can be accurately operated in accordance with the detection conditions of the skin fluorescence and the transmitted light to accurately calculate the skin fluorescence value.

The light source switch control unit may be configured to turn on or off the light source in accordance with a light irradiation condition of the transmitted light detection type measurement apparatus for skin fluorescence. For example, in the first condition in which the excitation light λ 1 is irradiated on the measurement target, the second light source may be turned off and the first light source may be turned on, the switching of the light sources is controlled so that only the first light source irradiates light of the first wavelength range. On the other hand, in the second condition in which the emission light λ 2 of the different wavelength range of the excitation light is irradiated on the measurement target, the first light source may be turned off and the second light source may be turned on, so that light of the second wavelength range is irradiated only from the second light source.

Similarly, the photodetector switch control unit may be configured to control on/off of the photodetector according to the measurement condition. The light detector switch control unit may be configured to power on/off the light detector in order to detect light of a wavelength range to be detected under current measurement conditions.

In particular, the second light detector for detecting light with respect to the second wavelength may remain on because, with respect to the light signal with the second wavelength, it may be necessary to be detected under both a first condition in which the excitation light of the first wavelength range is irradiated and a second condition in which the emission light of the second wavelength range is irradiated.

In this case, the switch control may be performed on the light source sequentially for a period of time throughout the measurement including the first condition and the second condition. As for the switching period with respect to each light source, the switching control may be performed at a high frequency of about 10Hz to about 100Hz, so that the measurement is not affected by the change in the diffusion transmittance due to the blood flow by taking into account the pulse rate of the human body. In this process, all light sources may be turned off before light irradiation and light detection, and then intensity evaluation of a dark signal may be performed in order to automatically compensate for light leaked from the outside.

Further, the transmitted light detection type measuring apparatus for skin fluorescence may include an optical filter, optionally disposed in front of the light source and the light detector. The optical filter may be arranged in the optical path of the light source so that only light of the desired wavelength range can be irradiated from the light source, or may be arranged in front of the light detector so that only light of the wavelength range intended to be detected can enter the light detector.

Meanwhile, the transmitted light detection type measuring apparatus for skin fluorescence may be configured to include a main body configured to be connectable to a light sensor including two light sources and two light detectors. The main body may be configured to include an operation section for calculating a corrected skin fluorescence value from data measured by the light sensor.

The main body may be configured to be connected to the light sensor, either wired or wirelessly, to receive detected data from the light sensor, and may be configured to calculate a corrected skin fluorescence value by performing an operational procedure as described above in the operational section of the main body.

Further, the main body may include a display part for outputting data on the skin fluorescence signal, and may be configured to output the corrected skin fluorescence signal calculated in the operation part to the outside.

In the transmitted light detection type measuring apparatus for skin fluorescence, when a measurement target is positioned in an insertion space of a photosensor, the photosensor can perform light irradiation and light detection processes on the measurement target. Thereafter, when the measurement target is removed and then the reference sample is inserted into the insertion space, the light irradiation and light measurement processes that have been performed on the measurement target may be similarly performed on the reference sample.

The measured data of the measurement target and the reference sample are transmitted to the operation section of the main body. The operation section may calculate a corrected skin fluorescence value with respect to an actual measurement target using data on the received fluorescence signal and the reflected light signal. The calculation result may be displayed through a display part on the main body.

The measurement of the measurement target and the reference sample may be repeated at a certain period, and the entire repeated measurement results may be stored in the optical sensor through the memory. The stored data may be stored in the operation section to perform operation processing for correction. In this case, the repeated measurements may be averaged for use in operation. Preferably, the measurements may be stored in the form of a time map in order to track changes in the measurements.

In this regard, fig. 2 is a view illustrating a transmitted light detection type measuring apparatus for skin fluorescence according to an exemplary embodiment of the present invention. In fig. 2, the light sensor 100 may include a first light source 111 and a second light source 112. The first and second light sources 111, 112 may be configured to transmit light to a measurement target through a common light source light waveguide 117, and a common detection light waveguide 128 may be disposed on the opposite side of the common light source light waveguide 117. Further, the light sensor 100 may be configured to transmit the transmitted light and the skin fluorescence light to the first light detector 121 and the second light detector 122 through the common detection light waveguide 128.

As shown in fig. 2, light emitted from the first light source 111 and the second light source 112 may enter the common light source light guide 117 through a lens. In this case, the light sources 111 and 112 may comprise LEDs, laser diodes, or other light sources capable of providing sufficient brightness of light in the excitation and emission wavelength ranges. The light source filter 114 may be disposed between the first light source 111 and the common light source light guide 117 to block light of the second wavelength λ 2 generated from the second light source 112. A separate filter may not necessarily be arranged at the second light source 112. The second detection filter 125 may be arranged in front of the second light detector 122. Therefore, the wavelength range of the light emitted from the second light source 112 may be larger than the wavelength range passing through the second detection filter 125. For example, a white LED may be used as the second light source 112.

Light emitted from the first and second light sources 111 and 112 may enter the common light source light guide 117 through the first dichroic mirror 113. In this case, the objective lenses 115 and 116 may be disposed between the dichroic mirror 113 and the respective light sources 111 and 112. When the second wavelength λ 2 is greater than the first wavelength λ 1, the first dichroic mirror 113 may reflect the light of the first wavelength λ 1 as the short wavelength light and may pass the light of the second wavelength λ 2 as the long wavelength light. However, the first dichroic mirror 113 may also be configured to pass the short wavelength light and reflect the long wavelength light. In this case, the positions of the first light source 111 and the second light source 112 need to be exchanged. The power of the first light source 111 and the second light source 112 may be provided through the switches of the light source switch controller. Preferably, as shown in fig. 2, power may be supplied through a relay switch in the driver module 134, and power supply to the first and second light sources 111 and 112 may be alternately performed.

When the measurement target T is positioned in the insertion space of the optical sensor 100, the optical sensor 100 performs light irradiation and light detection processes on the measurement target T. Thereafter, when the reference sample R is automatically inserted into the insertion space after the measurement target T is removed, the light irradiation and light measurement processes that have been performed on the measurement target T can be similarly performed on the reference sample R as well.

The measurement data on the measurement target T and the reference sample R may be transmitted to the operating part 210 of the main body 200. The operation part 210 can calculate a corrected skin fluorescence value with respect to an actual measurement target using data on the received fluorescence signal and transmitted light signal. The calculation result may be displayed through the display part 220 on the main body 200.

Meanwhile, as shown in fig. 2, light that has entered the common detection optical waveguide 128 may enter the first optical detector 121 and the second optical detector 122 through an optical system including objective lenses 128 and 127. The dichroic mirror 123 may be arranged to distribute light into the first light detector 121 and the second light detector 122. Similar to the first dichroic mirror 113, the second dichroic mirror 123 may be configured to reflect the short wavelength light and pass the long wavelength light. Further, as in the case where the positions of the first light source 111 and the second light source 112 are exchanged with respect to the first dichroic mirror 113 when the positions of the first photodetector 121 and the second photodetector 122 are exchanged, the transmittance and reflection characteristics of light can become opposite. In this case, the objective lenses 126 and 127 may function to effectively condense light on the photodetectors 121 and 122, respectively.

Also, filters may be arranged in front of the light detectors 121 and 122, respectively. The filter may comprise a first detection filter 124 and a second detection filter 125. The first detection filter 124 may be disposed in front of the first photodetector 121 and may be configured to pass spectral components of the first wavelength λ 1 while blocking spectral components of the second wavelength λ 2. On the other hand, the second detection filter 125 may be disposed in front of the second photodetector 122 and may be configured to pass the spectral components of the second wavelength λ 2 while blocking the spectral components of the first wavelength λ 1.

Meanwhile, the transmitted light detection-type measuring apparatus for skin fluorescence according to an embodiment of the present invention may include an Electronic Control Module (ECM)130 that controls light irradiation from a light source in the light sensor 100 and processes a detected light signal to transmit the processed light signal to the operating part 210.

The signals from the first and second photodetectors 121 and 122 may enter analog-to-digital converters (ADCs) 131 and 132 belonging to the ECM130, and then may enter an operation part 210 of the main body through a bi-directional bus through a Data Transfer Module (DTM) 133. Here, the DTM133 may function as a multiplexer that performs time division control transmission, and functions to select data. The synchronization function of the DTM133 and the relay switch may be performed by a command from the main body through the bidirectional bus.

The main body 200 may be configured to control the driver module 134 corresponding to the light source switch control unit and control the reference sample R to enter the loading module of the measurement insertion part. In addition, the main body may perform statistical processing of the signals and calculate corrected fluorescence values according to the equations described above. The main body may perform operations related to signal processing and control and data output, and may be configured to output the operation results through the display part 220.

In an exemplary embodiment of the present invention, in order to detect skin fluorescence with respect to AGE, light having a first wavelength of 370nm ± 20nm may be used as excitation light for fluorescence excitation, and light having a second wavelength of 440nm ± 20nm corresponding to the skin fluorescence wavelength with respect to AGE may be used as emission light.

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

Fig. 3 is a view illustrating a transmitted light detection type measuring apparatus for skin fluorescence according to another exemplary embodiment of the present invention. In fig. 3, a pair of optical waveguides may be separately arranged on the light source and light detector sides, respectively.

As shown in fig. 2, the transmitted light detection type measuring apparatus for skin fluorescence may further include: the light source device comprises a first light source, a second light source, a first light detector, a second light detector and an electronic control module. However, unlike fig. 2, the individual optical waveguides, not the common optical waveguide, may be connected to the light source and the light detector in order to transmit light.

Thus, in fig. 3, a first light source optical waveguide 314 and a second light source optical waveguide 315 may be connected to the first light source 311 and the second light source 312, respectively. On the opposite side, a first detection light guide 325 and a second detection light guide 326 may be connected to the first light detector 321 and the second light detector 322, respectively.

In this embodiment, since light transmission for light irradiation and light detection can be performed through the respective optical waveguides 314, 315, 325, and 326, there is no need for a dichroic mirror for acquiring and diffusing light as in fig. 2.

Further, since light is transmitted through an optical waveguide directly connected to the light source and the photodetector, it is not necessary to pass through an optical system such as a dichroic mirror, and an objective lens for condensing light is also not necessary.

Similar to fig. 2 described above, the main body 400 may include a light source filter 313, first and second detection filters 323 and 324, analog-to-digital converters 331 and 332, a data transfer module 333, an operation part 410 connected to the data transfer module 333, and a display part 420.

Fig. 4 is a view illustrating a transmitted light detection type measuring apparatus for skin fluorescence according to still another exemplary embodiment of the present invention. In fig. 4, a light source and a light detector may be disposed at a distal end of the light sensor, and light irradiation and light detection may be directly performed on the measurement target.

In this embodiment, the first light source 511 and the second light source 512 may be disposed on the same substrate (chip) and may generate light of the first wavelength λ 1 and the second wavelength λ 2, respectively. In this case, when the light from the first light source 511 does not contain a spectral component of the second wavelength λ 2, a filter is not necessary.

The light detector may be divided into two sectors containing the first light detector 521 and the second light detector 522, and a band-pass filter may be arranged in front of the two sectors in order to divide the light into the first wavelength λ 1 and the second wavelength λ 2. The electronic control module may be used to turn on/off the first light source 511 and the second light source 512 in sequence, and may control and synchronize the light detection signals received through the two channels in a time-sharing manner.

In this embodiment, as the light sources 511 and 512 and the light detectors 521 and 522 are positioned to face each other, the ends of the light sources 511 and 512 and the ends of the light detectors 521 and 522 may be formed in a clip shape, allowing the measurement target to be fixed while pressing the measurement target. In this case, the measurement target may be formed into a clip shape adapted to fit into the optical sensor, and then, the light irradiation and light detection processes may be performed on the measurement target. Thereafter, when the measurement target is removed and the reference sample is fitted into the clamp, the light irradiation and light detection process, which has been performed on the measurement target, can be automatically performed on the reference sample.

Thereafter, after being converted into corresponding digital signals, data regarding the measured optical signals may be transmitted to the fixed main body 600 through the communication module, and the operation part 610 may calculate corrected skin fluorescence values regarding the actual measurement target using the data regarding the transmitted fluorescence signals and transmitted light signals. The calculation result may be displayed to the outside through the display part 520 on the main body 600.

Meanwhile, a light transmitter, such as an optical prism or a light guide, may be provided to improve light transmission and detection efficiency.

A light transmitter comprising an optical prism or a light guide may be used to intensively irradiate uniform light on a narrow area of a skin portion to be measured and may collect the transmitted light on a light detector.

The optical transmitter included in the optical sensor according to the embodiment of the present invention may have a structure in which light not irradiated on the region to be measured is also transmitted to the measurement region or the optical detector without loss. Thus, the optical transmitter may have: a mounting surface on which a light source or a light detector is mounted; and at least one reflecting surface other than the mounting surface capable of internally reflecting incident light. In addition, the light transmitter may include a contact surface that contacts the measurement target in addition to the mounting surface and the reflection surface.

Thus, the light transmitter, including the mounting surface, the reflecting surface and the contact surface, may be implemented as an optical prism or a light guide as described in detail below. Exemplary light sensors, including the light transmitter, are shown in detail in fig. 5 to 8.

Fig. 5 illustrates an exemplary transmitted light detection type measuring apparatus for skin fluorescence according to an embodiment of the present invention, in which an optical prism is used.

Since a Light Emitting Diode (LED) light source, which is widely used as an excitation light source, irradiates light with wide divergence, optical loss may occur on a measurement target, and scattering of fluorescence from the light-irradiated skin may cause loss of the amount of light detected by the light detector 320.

Because the skin fluorescence to be detected is significantly smaller than the other excitation light or the reflected light of the excitation light, even when the optical loss is not serious, the optical loss greatly reduces the accuracy of measurement and the reliability of diagnosis.

On the other hand, in order to prevent the loss of light, it is suggested that the transmitted light detection type measuring apparatus for skin fluorescence includes optical prisms 720 and 730 as light transmitters, as shown in fig. 5.

In this embodiment, the excitation light irradiated from the light source can be condensed by the optical prism, and the optical uniformity of the skin portion as the measurement target can be improved. In addition, the transmitted light and the fluorescence transmitted through the measurement target may be transmitted to the photodetector through another optical prism.

Referring to fig. 5, the transmitted light detection type measuring apparatus for skin fluorescence may respectively include: an optical prism 720 on the light source side; and a prism 730 on the photodetector side. To distinguish between the two optical prisms 720 and 730, the optical prisms adjacent to the light sources 711 and 712 will be referred to as a first optical prism 720, and the optical prisms adjacent to the light detectors 741 and 742 will be referred to as a second optical prism 730.

The first optical prism 720 may include: a mounting surface in which the light source is mounted; and a reflection surface for reflecting a portion of the incident light passing through the mounting surface that is not transmitted to the measurement target.

In fig. 5, on the basis of the first light source 711, an optical prism surface on which the first light source 711 is disposed may be a mounting surface 721, and an optical prism surface adjacent to the mounting surface 721 and capable of reflecting light irradiated from the first light source 711 may be a reflecting surface 722.

On the other hand, on the basis of the second light source 712, as an optical prism surface with respect to the reflection surface 722 of the first light source 711, a mounting surface 722 of the second light source may be made, and with respect to the mounting surface 721 of the first light source 711, the reflection surface 722 may be made.

In this embodiment comprising a plurality of light sources, the mounting surface and the reflecting surface may be relative concepts, which are determined in accordance with any one of the light sources. The transmitted light detection type measuring apparatus for skin fluorescence only has to include a mounting surface and a reflecting surface depending on a specific light source. Therefore, the light irradiated from the light source can be totally reflected from the inside so as to be maximally condensed on the skin, thereby reducing the nonuniformity of the light source, i.e., a feature in which the light intensity outside the optical axis becomes smaller than in the center of the optical axis, thus obtaining improved optical uniformity.

In this case, the filter may be disposed on a mounting surface (or a reflection surface) of the optical prism so as to transmit only a specific light wavelength.

Further, the first optical prism 720 may include a contact surface 723 on a side of the first optical prism 720 in addition to the mounting surface and the reflection surface. The contact surface 723 may contact or abut against the measurement target T and press the measurement portion during measurement. The contact surface 723 may be a surface of the first optical prism 720 connected to the measurement part. Light can be transmitted to the measurement portion through the contact surface 723.

Meanwhile, light passing through the contact surface 723 of the first optical prism 720 may generate fluorescence in the skin, and then may be emitted to the photodetectors 741 and 742 together with the transmitted light. Therefore, as shown in fig. 5, in this exemplary embodiment, the second optical prism 730 may also be arranged as another light transmitter for efficiently transmitting the transmitted light and the fluorescence to the photodetectors 741 and 742.

Similar to the first optical prism 720, according to the first light detector 741, the second optical prism may be configured to include: a mounting surface 731 on which the photodetector is mounted; a reflection surface 732 as an optical prism surface that abuts the mounting surface and reflects the transmitted light and the fluorescent light; and a contact surface 733 that contacts or abuts against the measuring portion and presses the measuring portion.

The second optical prism 730 may be configured to allow the transmitted light and the fluorescence passing through the skin as a measurement target to directly enter the photodetector, or to enter the photodetectors 741 and 742 by internal reflection.

Meanwhile, the transmitted light detection type measuring apparatus for skin fluorescence according to the embodiment of the present invention may be configured to include the optical connector 750 that prevents light leakage that may occur between two media due to transmitted light and fluorescence from a skin portion as the measurement target T, light diffraction and scattering on the contact surface between the optical prism 720 and the skin portion.

The optical connector 750 may be configured to be positioned between a contact surface of an optical prism abutting the skin as a measurement target and a skin surface, and may contact the contact surface of the optical prism and the skin surface, respectively.

The optical connector 340 may be arranged above the contact surface of the first optical prism 720 and may contact the contact surface and the surface of the skin to function as a connection layer for allowing smooth optical contact at an appropriate refractive index on its boundary.

The optical connector 750 can control a certain refractive index between two media so as to prevent light leakage between the two media due to refraction and scattering of the excitation light between the optical prism and the skin tissue, and can be used to fill uneven portions such as fine unevenness of the skin tissue.

The optical connector 750 may be formed of an elastomeric material or a liquid material, such as water or oil. The optical connector 750 may be formed of a material having refractive indices similar to those of the optical prism and the skin.

Due to the optical connector 750, total internal reflection of the irradiated light may not occur on the boundary between the prism and the skin tissue, and the transmission efficiency of the light emitted from the light source into the skin can be significantly improved.

Therefore, the transmitted light detection type measuring apparatus for skin fluorescence including the optical prism and the optical connector 750 can improve optical concentration and optical uniformity, and can significantly reduce specular reflection components of transmitted light and fluorescence on the contact surface.

Meanwhile, as shown in fig. 5, the transmitted light detection type measuring apparatus for skin fluorescence may be configured to include a light source switch controller (not shown) for calculating a corrected skin fluorescence signal from the fluorescence signal and the transmitted light signal detected by the two photodetectors 741 and 742, in addition to an operator (not shown) for controlling on/off of the two light sources 711 and 712 and the two photodetectors 741 and 742.

In this case, as shown in fig. 5, the first optical prism 720 and the second optical prism 730 may be configured as triangular prisms having a contact surface abutting the skin and two mounting surfaces (or reflecting surfaces).

Further, the mounting surface of the optical prism may be mounted with a light source and a light detector. For example, as shown in fig. 5, two light sources 711 and 712 may be disposed on two mounting surfaces of first optical prism 720, and two light detectors 741 and 742 may be disposed on two mounting surfaces of second optical prism 730. In this case, the filters 761 and 762 may be disposed on both mounting surfaces of the second optical prism 730 to remove noise and pass only a certain wavelength range of light.

Structural characteristics such as the mounting positions of the light source and the photodetector, and the shape of the optical prism can be appropriately modified as needed. For example, the optical prism may be a trapezoidal prism having a trapezoidal cross section. The light source and the light detector may suitably be arranged on the mounting surface instead of the contact surface.

Further, the transmission light detection type measuring apparatus for skin fluorescence can obtain corrected skin fluorescence values through the same operation procedure as described in fig. 2, except that light irradiation and light detection are performed through the optical prism.

Fig. 6 and 7 show a transmitted light detection type measuring device for skin fluorescence according to another embodiment of the present invention, in which a light guide is used as a light transmitter.

Referring to fig. 6, two light pipes 820 and 830, instead of two optical prisms, are used as a light transmitter that transmits light from a light source and secondary light, such as fluorescence and transmitted light through the skin, to a light detector.

In this embodiment, the light pipes 820 and 830 may be formed of glass similar to an optical prism. As shown in fig. 6, the light pipes 820 and 830 may be tapered in a polygonal prism (polyprism) or cylindrical shape. Light pipes 820 and 830 may have two surfaces at their respective ends. The light source or light detector may be positioned on one side of the larger of the two surfaces. The smaller surface is configured to be in contact with the skin tissue to be measured. Therefore, the light guide is formed in a tapered cylindrical shape with inclined side surfaces. In this case, the first light pipe 820 at the side of the light source and the second light pipe 830 at the side of the light detector may be symmetrically arranged with the skin placed therebetween, as shown in fig. 6.

Thus, the light pipes 820 and 830 may have: mounting surfaces 821 and 831 on which light sources 811 and 812 or light detectors 841 and 842 are arranged; a reflecting surface 822 connected to the mounting surfaces 821 and 831 and extending to skin tissue; contact surfaces 823 and 833 are connected to the reflective surfaces 822 and 832, respectively, and are in contact with the skin tissue.

In the transmitted light detection type measuring apparatus for skin fluorescence with the light guide, light irradiated from the light source may be reflected along the inclined reflecting surfaces 822 and 832 and then may be transmitted to the measurement target T. Thereafter, the light may enter the skin tissue through the contact surfaces 823 and 833 of the light conduits 820 and 830, which are in contact with the skin tissue.

Accordingly, since the light guide having a tapered shape in which the cross-sectional area is gradually reduced from the mounting surface to the contact surface is used, the light emitted from the light source can be condensed on the contact area with the skin, increasing the optical concentration of the irradiated light.

The light pipe may even allow light from LED light sources with relatively larger divergence angles to be concentrated over a narrow area. Further, even when a plurality of light sources having different optical axes are used, the light can be made uniform, and the optical axis of the light irradiated on the skin can be aligned while passing through the light guide.

Also, since the optical axis of the light source and the optical axis of the photodetector can be aligned, the accuracy of detection can be improved.

Further, since light is reflected and transmitted along the inclined reflection surface, uniform light can be irradiated over a larger range at a portion in contact with the skin through an increased Numerical Aperture (NA), thereby increasing the occurrence of secondary light.

The second light pipe 830 may be disposed on the opposite side of the first light pipe 820 from the light source side. The transmitted light and the fluorescent light passing through the second light guide 830 may be detected by a photodetector disposed on the mounting surface of the second light guide 830. Fluorescence from the transmitted light and the light transmitted into the skin along the reflective surface 822 of the first light pipe 820 may be emitted from the opposite side of the skin and may be transmitted along the reflective surface 832 of the second light pipe 830 to the light detector.

The optical signal detected by the photodetector may be transmitted to a main body 860 including an operator. As described above, the main body 860 may calculate a corrected skin fluorescence value with respect to an actual measurement target using data on the transmitted fluorescence signal and the transmitted light signal.

In another exemplary embodiment of the present invention, optical fibers may be used instead of light pipes, as shown in FIG. 12. Specifically, the second light pipe 830 may be replaced with an optical fiber or fiber bundle 880, and the optical fiber or fiber bundle 880 may be configured to be connected to the spectrometer 890. In this case, an optical fiber may be disposed on the opposite side of the first light pipe 820, and the spectrometer 890 may be disposed to detect transmitted light and fluorescence light passing through the optical fiber.

Fig. 7 shows a modified example of the transmitted light detection type measuring apparatus for skin fluorescence shown in fig. 6, in which a dichroic prism is disposed on one side of a photodetector.

As shown in fig. 7, the dichroic prism 870 may be disposed between the mounting surface of the second light pipe 830 and the light detector. The dichroic prism 870 may separate the secondary light present in the skin tissue into two wavelength ranges λ₁And λ₂。

The light, which is split into two wavelength ranges, may be detected by photodetectors 841 and 842. The photodetectors 841 and 842 for each wavelength range may be arranged on different surfaces of the light guide. Thus, as described above, the reduced numerical aperture of light compared to light introduced into skin tissue can be improved using the two photodetectors 841 and 842 disposed on different surfaces.

As described above, due to the first light pipe 820 and the second light pipe 830, measurement errors can be reduced by matching the optical axes despite the spatial mismatch between the light source and the light detector.

Similar to the previous embodiment comprising an optical prism, the optical connector 850 may be arranged between the skin portion being the target of the measurement and the contact surface of the first light guide 820. The optical connector 850 may be disposed at the first and second light pipes 820 and 830, and a detailed description of the optical connector 850 will be omitted herein.

Fig. 8 to 10 show practical examples of the transmitted light detection type measuring apparatus for skin fluorescence manufactured as shown in fig. 6, which shows a photosensor as a main component. The light sensor may include a light source, a light detector, and two light pipes. The light sensor may include: a transfer portion for transferring the light guide in a vertical direction so as to press the measurement target T; and a thickness indicator for indicating the thickness of the skin, the thickness varying with the raising and lowering of the light guide through the transition portion. Further, the light sensor may be configured to be connected to the main body for controlling the light source and the light detector and collecting measurement data.

As shown in fig. 8, a space may be provided between the first light pipe 820 and the second fixture 830 in order to insert the measurement target T. As shown in fig. 8, the light source may include two light sources 811 and 812 for emitting light of different wavelength ranges.

A specific measurement process using the transmitted light detection type measurement apparatus for skin fluorescence configured as described above will be described below.

The light sensor 800 may be placed on a portion of the skin between the thumb and forefinger and then the first light pipe 820 may be lowered to allow the light source to irradiate light.

In this case, mixed light may be irradiated from the two light sources through the first light pipe 820, as shown in fig. 10. In particular, the distribution characteristics of the mixed light can be seen from the enlarged view on the right. In this light distribution characteristic, it can be seen that the mixed light has a uniform distribution and is concentrated on the measurement target T.

The light collected on the region to be measured may be divided into transmitted light passing through the skin and skin fluorescence generated by fluorescence excitation, which are detected by the light detector through the second light guide 830.

In this case, in order to improve the reliability of the measurement, a process of maintaining the thickness of the skin portion to be measured may be performed. For example, a transfer portion (not shown) may be provided to press the skin portion as the measurement target T by transferring the first light guide. Furthermore, a thickness indicator (not shown) may be provided to measure the thickness of the skin while the skin portion is being squeezed through the first and second conduits displaced by the displaced portion.

Accordingly, during the measurement, the transfer portion may transfer the first light pipe 820 so as to press the skin portion, and then the thickness indicator may measure the distance between the first light pipe 820 and the second light pipe 830 so as to verify the thickness of the measurement target. The transfer may be stopped when the skin portion is pressed to a predetermined thickness.

Due to the above process, the thickness of the measurement target can be fixedly maintained, and a certain degree of reproducibility can be achieved.

FIG. 11 depicts a modified light pipe according to another embodiment of the present invention.

Fig. 6 shows a vertical type light guide extending in a vertical direction to a contact surface with a measurement target, and fig. 11 shows a horizontal type light guide extending in a substantially parallel direction to the measurement target.

Specifically, the apparatus of FIG. 11 may comprise: a light source; a photodetector; and a horizontal type light guide functioning as a light transmitter for transmitting light from the light source to the light detector. The horizontal type light guide may include: a first light guide 920 and a second light guide 930 which are in contact with the measurement target T in upward and downward directions, respectively. Light pipes 920 and 930 may have: mounting surfaces 921 and 931 to which light sources 911 and 912 or light detectors 941 and 942 are mounted; reflective surfaces 922 and 932 for reflecting light irradiated from a light source, or transmitted light and fluorescence passing through the skin; and contact surfaces 923 and 933 that are respectively in contact with the measurement target T.

In this embodiment, the first light pipe 920 may be arranged so as to tilt the mounting surface 921 of the light source to the reflective surface 922 for effectively allowing uniform light to be incident on the contact surface 923, the contact surface 923 having the measurement target T substantially parallel to the reflective surface 922. Accordingly, the irradiation light from the light source disposed on the mounting surface 921 is reflected along the reflection surface 922, and can enter the measurement target T through the contact surface 923. Similarly, the photodetector-side mounting surface 931 may also be arranged to be inclined with respect to the reflecting surface 932 of the second light pipe 930.

In addition, as shown in fig. 11, the first light guide 920 and the second light guide 930 may have curved reflective surfaces 924 and 934 inclined to the contact surfaces 923 and 933 so as to allow the irradiated light to be efficiently incident to the measurement target T and allow the transmitted light and the fluorescence to be efficiently incident to the photodetectors 941 and 942.

In this embodiment, the mirror coating may be applied to the reflective surface by a separate deposition process to cause light reflection to occur at the reflective surface of the light pipe. The mirror coating may not be applied to the contact surface of the light pipe to enable light transmission to the skin. Thus, the light irradiation and the collection of secondary light can be performed through the contact surface without the mirror plating. In addition, the mirror coating may not be performed on a mounting surface on which the light source and the photodetector are positioned.

Similar to the previous embodiments, an optical connector 950 may be inserted between the contact surfaces 923 and 933 of the optical conduit and the measurement target T. The optical connector 950 can improve light transmission efficiency. Further, a transfer portion similar to those of fig. 6 and a thickness indicator for pressing the measurement target and maintaining the thickness thereof may be provided.

Accordingly, in the embodiment using the horizontal type light guide as shown in fig. 11, since the light sensor can be simply configured in a clip type, the measurement can be easily performed.

As described above, a transmitted light detection type measuring apparatus for skin fluorescence according to an embodiment of the present invention has the following advantages.

First, because diabetic conditions can be easily diagnosed by assessing skin autofluorescence, a large number of examinations can be conducted to discover potential diabetic patients. In addition, the risk of cardiovascular disease and its complications can be predicted.

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

Third, since the light from the light source can be efficiently condensed on the skin tissue, the optical efficiency can be improved, and the specular reflection on the surface of the skin tissue can be minimized, the miniaturization of the apparatus can be achieved.

Fourth, in measuring skin fluorescence, by the transmitted light measuring method, error occurrence factors due to specular reflection at the skin surface, and the influence of external factors such as roughness, scars, and hairs of the skin and internal factors such as pigments and hemoglobin of blood can be substantially eliminated, and thus, a disease can be accurately diagnosed.

Fifth, since skin fluorescence is used, errors due to light scattering and absorption generated inside the skin can be simply corrected, and accurate measurement of skin fluorescence and accurate diagnosis of diseases can be obtained.

Sixth, the transmitted light detection type measuring device for skin fluorescence may contain a light source and a light detector, and may be manufactured in the form of a hand-held small-sized scanner for measuring skin fluorescence. In this way, non-invasive diagnosis can be performed in real time because the user can reach to bring the scanner into contact with the subject's skin to scan the target to be diagnosed.

The present invention has been described in detail with reference to exemplary embodiments thereof. It would 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 claims and their equivalents.

Claims

1. A transmitted light detection type measuring apparatus for skin fluorescence, configured to perform light irradiation and light detection on a reference sample and a measurement target, characterized by comprising:

a first light source that irradiates excitation light;

a second light source irradiating light having a wavelength different from that of the light from the first light source;

first and second light detectors arranged to detect transmitted light from the first and second light sources and arranged to detect two different wavelengths in respect of the fluorescent and transmitted light signals;

a light source switch controller for controlling on/off of the first light source and the second light source; and

an arithmetic unit for calculating a corrected skin fluorescence signal from the fluorescence signal and the transmitted light signal detected by the first photodetector and the second photodetector,

wherein the second light source irradiates light having the same wavelength range as that of skin fluorescence excited by the excitation light from the first light source and emitted.

2. The transmitted light detection-type measurement apparatus of claim 1, further comprising:

a pair of light transmitters configured to transmit excitation light irradiated from the light source to the measurement target and transmit transmitted light and the fluorescence signal to the light detector;

wherein the optical transmitter has: a mounting surface on which a light source or a light detector is mounted; a reflection surface extending from the mounting surface to the measurement target and reflecting light; and a contact surface connected to make light incident on the measurement target.

3. The transmitted light detection-type measuring apparatus of claim 2, wherein the pair of light transmitters comprises: a first optical prism connected to the light source; and a second optical prism connected to the light detector.

4. The transmission light detection type measuring apparatus of claim 3, wherein the first optical prism and the second optical prism are triangular prisms having a triangular cross section.

5. The transmitted light detection-type measuring apparatus according to claim 4, wherein the first optical prism has: a mounting surface on which a first light source is mounted; and a reflective surface mounted with a second light source.

6. The transmitted light detection-type measuring apparatus according to claim 5, wherein the second optical prism has: a mounting surface on which the first photodetector is mounted, and a reflective surface on which the second photodetector is mounted.

7. The transmitted light detection-type measuring apparatus of claim 2, wherein the pair of light transmitters comprises: a first light pipe connected to the light source; and a second light pipe connected to the light detector.

8. The transmission light detection type measuring apparatus of claim 7, wherein the first light guide and the second light guide have inclined reflecting surfaces and have a tapered cylindrical shape in which the mounting surface is larger than the contact surface.

9. The transmission light detection type measuring apparatus of claim 7, wherein the first light guide has: a mounting surface on which the first light source and the second light source are mounted.

10. The transmission light detection type measuring apparatus of claim 7, wherein the second light guide has: a mounting surface on which the first photodetector and the second photodetector are mounted.

11. The transmission light detection type measuring apparatus according to claim 7, further comprising a dichroic prism on a side of the mounting surface of the second light guide for splitting the detected light into two wavelength bands.

12. The transmitted light detection-type measurement apparatus of claim 11, wherein the first light detector is arranged to detect light reflected from the color separation prism and the second light detector is arranged to detect transmitted light from the color separation prism.

13. The transmission light detection type measuring apparatus of claim 7, wherein the first light guide and the second light guide are vertical type light guides extending in a vertical direction to the contact surface having the measurement target.

14. The transmission light detection type measuring apparatus of claim 7, wherein the first light guide and the second light guide are horizontal light guides extending in parallel directions to the contact surface having the measurement target.

15. The transmission light detection measurement apparatus of claim 14, wherein the reflective surfaces of the first light pipe and the second light pipe are tapered such that their cross-sectional areas decrease from the mounting surface to the contact surface.

16. The transmission light detection type measurement apparatus of claim 14, wherein the mounting surfaces of the first light guide and the second light guide are inclined to their reflection surfaces.

17. The transmission light detection type measurement apparatus of claim 14, wherein the reflection surfaces of the first light guide and the second light guide each comprise a curved reflection surface inclined to the contact surface.

18. The transmission light detection type measuring apparatus of claim 14, wherein the reflecting surfaces of the first light guide and the second light guide are treated with a mirror coating.

19. The transmitted light detection-type measuring apparatus of claim 2, further comprising:

a transfer section for moving the optical transmitter in a vertical direction; and

a thickness indicator for measuring a distance between the two light transmitters and for indicating a thickness of a measurement target.

20. The transmitted light detection-type measuring apparatus according to claim 2, further comprising an optical connector disposed on the contact surface of the light transmitter and contacting the measurement target.

21. The transmitted light detection-type measurement apparatus according to claim 20, wherein the optical connector functions as a connection layer formed of a liquid material or an elastic material between the light transmitter and the measurement target.

22. The transmission light detection type measurement apparatus of any one of claims 1 to 21, wherein the light source switch controller controls the first light source and the second light source so that on states of the first light source and the second light source are temporally separated from each other.

23. The transmission light detection-type measurement apparatus of claim 22, wherein the switch controller is configured to detect the fluorescent signal and the transmission light signal from the first light source and the transmission light signal from the second light source while constantly repeating a process in which the first light source and the second light source are sequentially turned on and off.

24. The transmitted light detection-type measurement apparatus of any one of claims 1 to 21, wherein the measurement target and the reference sample are selectively positioned on optical paths of the first light source and the second light source.

25. The transmitted light detection-type measurement apparatus according to any one of claims 1 to 21, wherein the first light source irradiates light having a wavelength of 370 ± 20 nm.

26. The transmitted light detection-type measurement apparatus according to any one of claims 1 to 21, wherein the second light source irradiates light having a wavelength of 440 ± 20 nm.

27. The transmission light detection type measurement apparatus of any one of claims 1 to 21, 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 transmission light detection type measuring apparatus of claim 27, wherein the first photodetector and the second photodetector measure dark signals when the switch controller turns off all of the first light source and the second light source, and the operator stores the measured dark signals and compensates the detected fluorescence signal and the transmission light signal based on the stored dark signals.

29. The transmission light detection type measurement apparatus of any one of claims 1 to 21, wherein the switch controller controls the first light source and the second light source to be repeatedly turned on/off at a cycle of about 10Hz to about 100 Hz.

30. The transmission light detection type measurement apparatus according to any one of claims 1 to 21, further comprising a photodetector switch controller for controlling on/off of the first photodetector and the second photodetector.

31. The transmitted light detection-type measurement apparatus according to any one of claims 1 to 21, comprising:

a light sensor including a first light source, a second light source, a first light detector, and a second light detector; and

a main body electrically connected to the light sensor, and including an operator,

wherein the light sensor is detachable from the main body.

32. The transmitted light detection-type measuring device according to claim 31, wherein the light sensor includes a memory for storing detection data.

33. The transmission light detection type measuring apparatus of claim 1, comprising:

wherein the light sensor is detachable from the main body;

wherein the optical sensor includes a first fixing portion connected to the first light source and the second light source, and a second fixing portion connected to the first light detector and the second light detector, and the first fixing portion and the second fixing portion face each other so as to form an insertion space therebetween.

34. The transmission light detection type measuring apparatus of claim 1, comprising:

wherein the light sensor is detachable from the main body;

wherein the light sensor includes a common light source optical waveguide for transmitting the light irradiated from the first light source and the second light source in a common manner.

35. The transmission light detection type measuring apparatus of claim 34, wherein the optical sensor includes a common detection optical waveguide for transmitting the transmission light and the skin fluorescence to the first photodetector and the second photodetector in a common manner.

36. The transmitted light detection-type measuring apparatus of claim 34, wherein the light sensor includes a first dichroic mirror in a light path so that light irradiated from the first light source and the second light source is transmitted to the common light source optical waveguide.

37. The transmission light detection type measuring apparatus of claim 36, wherein the light sensor comprises a second dichroic mirror on a light path to separate light from the common detection light guide and transmit the separated light to the first light detector and the second light detector.

38. The transmission light detection type measuring apparatus of claim 36, comprising a light source filter between the first light source and the first dichroic mirror so as to pass light of the first wavelength irradiated from the first light source and to block light of the second wavelength irradiated from the second light source.

39. The transmission light detection type measuring apparatus of claim 36, comprising an objective lens between the first and second light sources and the first dichroic mirror so as to condense the light irradiated from the first and second light sources, respectively.

40. The transmitted light detection-type measurement apparatus of claim 37, comprising a first detection filter between the second dichroic mirror and the first photodetector, and a second detection filter between the second dichroic mirror and the second photodetector,

wherein the first detection filter passes light of the first wavelength and blocks light of the second wavelength, and the second detection filter blocks light of the first wavelength and passes light of the second wavelength.

41. The transmitted light detection-type measuring apparatus of claim 37, comprising an objective lens between the first and second photodetectors and the second dichroic mirror so that light passing through the second dichroic mirror is collected on the first photodetector and the second photodetector, respectively.

42. The transmission light detection type measuring apparatus of claim 1, comprising:

a light sensor including a first light source, a second light source, a first light detector, and a second light detector;

wherein the light sensor is detachable from the main body; and

a first light source optical waveguide for transmitting light irradiated from the first light source, and a second light source optical waveguide for transmitting light irradiated from the second light source.

43. The transmitted light detection-type measurement apparatus of claim 42, wherein the light sensor comprises: a first detection optical waveguide for transmitting the transmitted light of the first light source to the first light detector; and a second detection optical waveguide for transmitting the transmitted light or skin fluorescence of the second light source to the second light detector.

44. The transmission light detection type measuring apparatus of claim 42, comprising a light source filter between the first light source and the first light source optical waveguide to pass light of the first wavelength irradiated from the first light source and to block light of the second wavelength irradiated from the second light source.

45. The transmitted light detection-type measurement apparatus of claim 43, comprising: a first detection filter between the first light source optical waveguide and the first photodetector to pass light of the first wavelength and to block light of the second wavelength; and a second detection filter between the second light source optical waveguide and the second light detector to block light of the first wavelength and pass light of the second wavelength.

46. The transmitted light detection-type measuring apparatus of claim 33, wherein the first light source and the second light source are disposed at a distal end of the first fixing portion so as to irradiate light directly on the measurement target, and the first light detector and the second light detector are disposed at a distal end of the second fixing portion so as to detect the transmitted light and the skin fluorescence directly.

47. The transmission light detection type measuring apparatus of claim 46, wherein the first photodetector and the second photodetector are configured to form two sectors, and include a band-pass filter in front of the two sectors to separate light into a first wavelength (λ 1) and a second wavelength (λ 2), respectively.

48. The transmission light detection type measuring apparatus of claim 46, wherein the first fixing portion and the second fixing portion are manufactured in a clip shape so as to fix the measurement target while pressing the measurement target.

49. The transmission light detection type measuring apparatus of claim 33, wherein the reference sample is movably installed in the photosensor, and is fitted into an insertion space between the first fixing portion and the second fixing portion when the measurement target is removed from the insertion space.

50. The transmission light detection type measuring apparatus of claim 49, wherein the light sensor measures the skin as the measurement target when the skin is positioned in the insertion space, and the light sensor measures the reference sample when the measurement target is removed and then the reference sample is positioned in the insertion space.

51. The transmission light detection type measuring apparatus of claim 50, wherein the photosensor stores the measurement results with respect to the skin and the reference sample as the measurement target T and transmits the stored data with respect to the skin and the reference sample to the main body so as to allow the operator to calculate the corrected skin fluorescence signal.

52. The transmission light detection type measuring apparatus of claim 31, wherein the main body further comprises a display part, and the display part outputs the corrected skin fluorescence signal calculated in the operator.

53. The transmission light detection type measuring apparatus of any one of claims 1 to 21, wherein the operator calculates the corrected skin fluorescence value by the following equation:

AF_corr＝K[I(λ2，t1)/I₀(λ2，t1)]/{[T(λ1)]^k1[T(λ2)]}^k2

here, T (λ 1) ═ I (λ 1, T1)/1₀(λ 1, t 1): diffuse transmission coefficient in excitation wavelength;

T(λ2)＝I(λ2，t2)/1₀(λ 2, t 2): a diffuse transmission coefficient in the emission wavelength;

1₀(λ 2, t 1): intrinsic fluorescence signal values of the reference sample;

1₀(λ 1, t 1): the transmitted light signal value of the reference sample in the wavelength of the excitation light; and

1₀(λ 2, t 2): in the wavelength of the emitted lightThe value of the transmitted light signal of the reference sample,

54. A transmitted-light type measuring apparatus for skin fluorescence configured to perform light irradiation and light detection on a reference sample and a measurement target, characterized by comprising:

a first light source that irradiates excitation light;

a light guide configured to transmit light irradiated from the first and second light sources to a measurement target;

a spectrometer arranged to detect transmitted light from the first and second light sources and arranged to detect two different wavelengths for the fluorescence signal and the transmitted light signal;

an optical fiber configured to transfer the transmitted light and the fluorescent signal to a photodetector;