JP2004147706A - Apparatus and method for determining non-invasive biomedical component - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an apparatus and a method for determining non-invasive biomedical components with a smaller size and the saving of power. <P>SOLUTION: An optical apparatus which determines the biomedical components in an invasive fashion comprises an irradiation means which irradiates a subject sequentially with lights with a plurality of different wavelengths in the near infrared wavelength range of 1,000 nm to 2,500 nm, a photodetecting means 12 for receiving the reflected light from the subject or the transmission light through the subject and an arithmetic means 14 for calculating the concentration of the biomedical components by the arithmetic processing from the absorbance per the wavelength obtained by the photodetecting means 12. The subject 8 is irradiated sequentially with the lights with varied wavelengths. <P>COPYRIGHT: (C)2004,JPO

Description

[0001]
TECHNICAL FIELD OF THE INVENTION
The present invention relates to a non-invasive biological component quantification device and method for analyzing the concentration of a humor component of a chemical component in a biological tissue or a body fluid by utilizing light absorption in a near-infrared region. More specifically, the present invention relates to an apparatus and a method for performing a blood glucose level measurement by performing a quantitative analysis of a glucose concentration in skin tissue.
[0002]
[Prior art]
The glucose concentration in the skin tissue has a high correlation with the glucose concentration in the blood (blood sugar level), and is therefore used as a substitute value for quantifying the blood sugar level. Assuming that the glucose concentration is determined non-invasively, the light (near infrared light) of a light source composed of a halogen lamp is focused by a condenser lens and irradiated on the subject 8, and transmitted or diffusely reflected in the subject 8. There is a type in which the light obtained is split by a diffraction grating or the like, then received by a light receiving element unit, and a glucose concentration is calculated based on a biological signal obtained by the light receiving element unit. In this case, the light from the light source is applied to a standard plate such as a ceramic plate, and the light reflected by the standard plate is also received to obtain a reference signal, which is derived from the glucose concentration change based on the reference signal and the biological signal. It analyzes the minute change in absorbance in the spectrum to be calculated and calculates the glucose concentration.
[0003]
For example, in the glucose concentration quantification method and apparatus disclosed in JP-A-2000-131322 (Patent Document 1), as shown in FIG. 27, a light source 61 composed of a halogen lamp and light from the light source 61 are focused. A condenser lens 62, an optical fiber bundle probe 63 for irradiating the object with light passing through the condenser lens 62 and receiving light transmitted or diffusely reflected in the object, and disperses the received light. A diffraction grating unit 64 containing a diffraction grating, an InGaAs array type light receiving element unit 65 for detecting light dispersed by the diffraction grating unit 64, and a glucose concentration based on a signal obtained by the array type light receiving element unit 65. And an operation unit 66 for calculating the following equation.
[0004]
In this apparatus, at the time of spectrum measurement, a light from a light source 61 irradiates a standard plate such as a ceramic plate via the optical fiber bundle probe 63 and receives light (reference signal) reflected by the standard plate. The sensing part of the optical fiber bundle probe 63 is brought into contact with the skin surface at a contact pressure of 100 to 500 gf / cm ² using a positioning jig for stabilizing the light, and the light transmitted or diffused and reflected in the skin tissue Signal), and based on the obtained reference signal and biological signal, the arithmetic unit 66 analyzes a minute change in absorbance in the spectrum derived from the change in glucose concentration to calculate the glucose concentration. At this time, generally, signals of all pixels (eg, 256 pixels) in the analysis wavelength range obtained by the multi-channel detector are used.
[0005]
By the way, since the glucose concentration is as small as several tens to several hundreds mg / dl, in order to quantify the glucose concentration based on the light (biological signal) transmitted or diffusely reflected through the skin tissue, the light is converted to S / N. It is important to capture well, so that the absorbance baseline fluctuation is suppressed as much as possible to increase the stability of the spectrum measurement, and at the same time it has a resolution that can correctly capture the spectrum change according to the glucose concentration change Must be kept. For this reason, in the above configuration, a spectrum of 1000 nm to 2500 nm is used as a wavelength region (actually, the spectrum is assigned to the number of light receiving element arrays (for example, 256 elements)), and a quantitative calculation of glucose concentration is performed by multivariate analysis and estimated. ing.
[0006]
[Patent Document]
JP 2000-131322 A
[Problems to be solved by the invention]
In the above-described method in which the analysis for estimating the glucose concentration is performed after converting all the signals within the analysis wavelength range obtained by the multi-channel detector into absorbances, the system configuration is inevitably large. Further, a light source that must generate continuous near-infrared light requires a halogen lamp or the like, and measures against heat are also difficult. In addition, a spectroscopic unit including a diffraction grating for decomposing continuous light into a spectrum is required. In addition, the multi-channel detector, which is a light receiving element, may be analyzed without correctly reflecting a change in the spectrum corresponding to a change in the concentration of the biological component because the characteristics of each pixel are not necessarily uniform. This is a factor for obtaining good analysis accuracy in estimation.
[0008]
The present invention has been made in view of the above points, and an object of the present invention is to provide a small-sized and power-saving non-invasive quantification apparatus and method for a biological component.
[0009]
[Means for Solving the Problems]
Thus, the present invention is an optical device for non-invasively quantifying a biological component, comprising: an irradiating means for sequentially irradiating a subject with light having a plurality of different wavelengths in a near-infrared wavelength range of 1000 nm to 2500 nm; Light receiving means for receiving reflected light from the specimen or transmitted light transmitted through the subject, and arithmetic means for calculating the biological component concentration by performing arithmetic processing from the absorbance for each wavelength obtained by the light receiving means. have. Light of different wavelengths is sequentially irradiated on the subject.
[0010]
The irradiating means may include a light source having a plurality of light sources that output light of different wavelengths, a light source having a wavelength tunable laser as a light source, a light source covering a near-infrared wavelength range of 1000 nm to 2500 nm, and a plurality of light sources from the light source. And a wavelength selecting means for extracting the specific wavelength.
[0011]
A variable wavelength filter, a gradient film thickness filter, or an optical device can be suitably used as the wavelength selecting means.
[0012]
The irradiating means may include a plurality of light sources that output light of different wavelengths and sequentially emit light, and a light guiding means that guides light from these light sources to a probe for irradiating the subject. . In this case, as the light guiding means, a diffractive optical device or an optical waveguide can be suitably used.
[0013]
Further, the irradiating means includes a light source that outputs light of different wavelengths, and a switching unit that selectively guides light from these light sources to a probe for irradiating the subject. A light source that covers 2500 nm, a wavelength selection unit that extracts a plurality of specific wavelengths from the light source, and a switching unit that selectively guides light passing through the wavelength selection unit to a probe for irradiating an object is used. The switching means in these cases may switch at least one of the light source side and the probe side to switch the opposing position between the light source side and the probe side, or may transmit light of a required wavelength. In addition, a shutter that blocks light of another wavelength and an optical switch that transmits light of a required wavelength and blocks light of another wavelength can be preferably used.
[0014]
And a reference light guiding means for guiding the light of each wavelength to the light receiving device without passing through the subject, and the calculating means calculates a biological component concentration based on the absorbance calculated from the reference light and the light passing through the subject. If it is, the quantification of the biological component can be performed more accurately.
[0015]
When the biological component for the purpose of quantification is glucose, the irradiating means includes a measuring probe that is in contact with the surface of the subject, and the measuring probe includes a light projecting unit that projects light to the subject and the subject. It is preferable that a light-receiving unit that receives reflected light from the object or transmitted light transmitted through the subject is disposed at a center-to-center distance of 0.2 mm to 2.0 mm.
[0016]
The method for quantifying a non-invasive biological component according to the present invention includes sequentially irradiating the subject with light having a plurality of different wavelengths in the near-infrared wavelength range of 1000 nm to 2500 nm, and reflecting light from the subject or the subject. The transmitted light is guided to the light receiving unit, and the light of each wavelength is guided to the light receiving unit without passing through the subject, and the biological component concentration is calculated by performing an arithmetic process from the absorbance for each wavelength obtained by the light receiving unit. It has special features.
[0017]
BEST MODE FOR CARRYING OUT THE INVENTION
Hereinafter, the present invention will be described in detail based on an example of an embodiment. In FIG. 1, reference numeral 3 denotes a light source composed of a plurality of LEDs (four in the illustrated example) 3a, 3b, 3c, and 3d. It is arranged on a concentric circle of a disk rotated and driven by such a drive unit 2. In the figure, reference numeral 1 denotes a power supply.
[0018]
Each of the LEDs 3a, 3b, 3c, and 3d emits light in a specific wavelength band, and includes, for example, LED 3a: 1400 nm, LED 3b: 1550 nm, LED 3c: 1700 nm, and LED 3d: 1850 nm. Note that the number of LEDs and the allocation of wavelength bands are not limited to the above example, and are set according to required accuracy, but can be accommodated at a maximum of ten.
[0019]
On the other hand, a plurality of light projecting optical fibers 6 (cladding diameter 200 μm, core diameter 180 μm) for irradiating the subject 8 with light, and a light receiving optical fiber 9 for receiving light transmitted or diffusely reflected by the subject 8. The optical fiber bundle 11 (also having a clad diameter of 200 μm and a core diameter of 180 μm) has a measurement surface at the distal end surface of the probe 7 which is brought into contact with the surface of the subject 8 as shown in FIG. The light emitting end 16 of the light projecting optical fiber 6 and the light incident end 17 of the light receiving optical fiber 9 are arranged. A plurality of the light emitting ends 16 are arranged on a circle around the incident end 17. The exit end 16 and the entrance end 17 are arranged at an interval L of 0.2 mm to 2.0 mm (0.65 mm in the illustrated example). As shown in FIG. 3, the arrangement of the light receiving optical fiber 9 (17) and the light projecting optical fiber 6 (16) may be interchanged.
[0020]
The light inlet 4 (see FIG. 2 (c)) of the light projecting optical fiber 6 is opposed to the light source 3, and the light emitting port 11 (see FIG. 2 (b)) of the light receiving optical fiber 9 is a single element type light receiving device. It faces the element 12.
[0021]
The output of the light receiving element 12 is digitally converted by the A / D converter 13 and sent to the calculating means 14. In the figure, reference numeral 15 denotes a display device for displaying a biological component concentration, and reference numeral 5 denotes a reflecting mirror for guiding reference light to the light receiving element 12 at the beginning of measurement.
[0022]
In measuring a spectrum for quantifying a biological component, first, the reference light of the light source 3 is measured. That is, the reflecting mirror 5 is directly opposed to the probe 7, and the stepping motor of the driving unit 2 is operated at intervals of about one second to sequentially switch the LED facing the light inlet 5 of the light emitting optical fiber 6. This switching signal is output from the calculating means 14 as described above. The switching signal is also transmitted to the single-element light receiving element 12 at the same time, and resets the single-element light receiving element 12 for each wavelength. The light reflected from the reflecting mirror 5 is converted into an electric signal by the light receiving element 12, is converted into a digital signal by the A / D converter 13, and is stored in the arithmetic means 14 as a reference light electric signal for each wavelength.
[0023]
Next, the probe 7 is brought into contact with a subject 8 which is skin of a living body. At this time, it is preferable that the contact pressure between the probe 7 and the subject 8 be 100 to 500 gf / cm ² by using a positioning jig for fixing the contact position.
[0024]
Then, the drive unit 2 is operated at intervals of about one second to sequentially switch the LEDs 3a, 3b, 3c, and 3d having four specific wavelengths. At this time, the switching signal is also sent to the single-element light-receiving element 12 to reset the single-element light-receiving element 12 for each wavelength.
[0025]
The light emitted from the emission end 16 of the probe 7 through the light projecting optical fiber 6 propagates through the subject 8 (skin tissue), and then is emitted as scattered light from the skin tissue. The light is sent to the single-element light-receiving element 12 by the light-receiving optical fiber 9 and is converted into an electric signal. The bioelectric signal for each wavelength digitally converted by the A / D converter 13 is stored in the arithmetic means 14.
[0026]
Assuming that the measured reference photoelectric signal is Ref and the bioelectric signal is Sig, the absorbance Abs is represented by the following equation (1).
[0027]
Abs = log ₁₀ (Ref / Sig) (1)
In this example, since there are four specific wavelength lights, four absorbance Abs can be measured.
[0028]
Abs 1400 nm = log ₁₀ (Ref / Sig) (2)
Abs 1550 nm = log ₁₀ (Ref / Sig) (3)
Abs 1700 nm = log ₁₀ (Ref / Sig) (4)
Abs 1850 nm = log ₁₀ (Ref / Sig) (5)
Then, based on the four pieces of absorbance Abs information, the calculating means 14 calculates the biological component concentration based on the biological component concentration calculation formula stored in advance, and displays the calculation result on the display device 15. 4 to 6 show flowcharts of the above operation.
[0029]
Although the case of using reflected / diffused light in the subject 8 (living body) has been described, as shown in FIG. 7, light transmitted through a living body may be used. FIG. 8 shows an example of the arrangement of the exit end 16 and the entrance end 17 in this case. Further, the A / D converter 13 and the arithmetic unit 14 have been described separately, but this is for the purpose of explanation. Actually, the arithmetic unit 14 generally includes the A / D converter 13 as well. is there. Furthermore, although the case where the LEDs 3a to 3d of the light source 3 are sequentially switched by rotating the rotary plate has been described, it may be performed by linear movement or the like, or the light inlet 4 side is moved as shown in FIG. Thus, it goes without saying that the LEDs 3a to 3d to which the light inlet 4 faces may be switched.
[0030]
FIG. 10 shows a configuration in which the reference light is received by the light receiving element 12 by the reference light optical fiber 10. In this device, the wavelength of the light source 3 and its light guide path (the path through the subject 8 or the path directly to the light receiving element 12 are determined by a switching signal sent from the calculating means 14 to the driving unit 2 and the light receiving element 12. ).
[0031]
The operation will be described. In the spectrum measurement, the operation is sequentially switched such that LED3a → LED3a → LED3b → LED3b → LED3c → LED3c → LED3d → LED3d → LED3a → LED3a⇒ by operating the drive unit 2 at intervals of about one second. This switching signal output from the calculating means 14 is also sent to the light receiving element 12 and used for identifying the light receiving wavelength of the light receiving element 12 and the light receiving path.
[0032]
11 to 13 show flowcharts of the operation in this case. Here, after sequentially measuring the biological component light and the reference light at a certain wavelength, the biological component light and the reference light at the next wavelength are measured. After receiving the reference light, the biological component light for each wavelength may be received. Also in this case, it is needless to say that the transmitted light transmitted through the subject 8 may be used as shown in FIG.
[0033]
FIG. 15 shows a light source using a tunable laser as the light source 3. Since the light source 3 and the light introduction port 4 can be fixed in a state where they are always opposed to each other, problems such as misalignment do not occur.
[0034]
FIG. 16 shows another example. Here, a broad light emitting light source (monochromatic light) is used as the light source 3 and the light source 3 and the wavelength selecting means 22 are interposed between the light introduction port 4 so that light of a plurality of different wavelengths is sequentially applied to the subject 8. Irradiation is possible. As the light source 3 in this case, a semiconductor LED, a white laser, a halogen lamp, or the like can be used. As the wavelength selecting means 22, a plurality of band-pass filters 22a, 22b, 22c, and 22c having different transmission wavelength bands shown in FIG. 22d, a wavelength tunable filter 22e shown in FIG. 18, a prism 22f as an optical device (see FIG. 19), a gradient film thickness filter 22g (see FIG. 20), a diffraction grating (not shown), or the like. it can. Further, as shown in FIG. 21 (a), a plurality of transmission type band-pass filters 22h are combined to demultiplex into a plurality of wavelengths λ1, λ2, λ3, λ4, or as shown in FIG. The light may be split using the light reflection type multilayer filter 22i. In FIG. 20, reference numeral 23 denotes a condenser lens. Here, the wavelength of light entering the light entrance 4 by moving the light source 3, the condenser lens 23, and the light entrance 4 along the inclined film thickness filter 22g. Is switched.
[0035]
When a plurality of light sources (for example, the LEDs 3a to 3d described above) that output light of different wavelengths are used as the light source 3, the light source or the light introduction port 4 is moved to introduce the light of these light sources into the light introduction port 4. Instead, light introducing means such as a diffraction grating device 30 shown in FIGS. 22 and 23, an optical fiber 31, a combination of an optical fiber 31 and an optical coupler 32, an optical waveguide 33 for photosynthesis, and optical lenses 34 and 35 are provided. May be used. When an ultra-small light source 3 can be used, each light source may be directly opposed to the light inlet 4 as shown in FIG. However, when these devices are used, a plurality of light sources that output light of different wavelengths are sequentially emitted as the light source 3 so that only light of a required wavelength reaches the light inlet 4.
[0036]
When a plurality of light sources that output light of different wavelengths are used as the light source 3 and it is desired to continuously light these light sources to stabilize the output (including the case where the demultiplexing shown in FIG. 21 is performed), As shown in FIG. 25, a shutter 35 that transmits light of a required wavelength and blocks light of other wavelengths is used, or as shown in FIG. 26, an optical switch that operates by switching the angle of a fine reflecting mirror. It is sufficient that only light having a necessary wavelength is sent to the light inlet 4 using the light emitting device 36. Of course, the light emission of the light source 3 may be sequentially switched in accordance with the operation of the shutter 35 and the optical switch 36.
[0037]
By the way, at present, it is necessary to use an expensive InGaAs-type element requiring cooling as the light receiving element 12 in view of the amount of received light. However, if an ultra-high brightness light source is developed, a general-purpose red light source is required. An inexpensive and small-sized electronic circuit using an external photodiode or an infrared phototransistor can be realized. In addition, the use of an optical waveguide, an optical switch, and the like due to the improvement of the microfabrication technology enables further miniaturization and power saving.
[0038]
【The invention's effect】
As described above, in the present invention, instead of spectrally analyzing the light received by irradiating the whole light of the near-infrared light, instead of sequentially irradiating light of a plurality of different wavelengths and receiving light, the light source Along with miniaturization and low power consumption, there is no need for a spectroscopic device on the light-receiving side, and a single-element light-receiving element may be used for light reception, and no multi-channel light-receiving means is required. It can be ultra-compact, lightweight and low power.
[Brief description of the drawings]
FIG. 1 is a block diagram illustrating an example of an embodiment of the present invention.
FIGS. 2A and 2B show an example of the above optical fiber bundle, wherein FIG. 2A is an end view of a probe tip, FIG. 2B is an end view of a light exit port, and FIG.
FIG. 3 is an end view of a probe tip in another example of the same optical fiber bundle.
FIG. 4 is a flowchart of the above operation.
FIG. 5 is a flowchart of the above operation.
FIG. 6 is a flowchart of the above operation.
FIG. 7 is a block diagram of another example.
FIGS. 8A and 8B are end views of the same optical fiber.
FIG. 9 is a block diagram of still another example.
FIG. 10 is a block diagram of another example.
FIG. 11 is a flowchart of the above operation.
FIG. 12 is a flowchart of the above operation.
FIG. 13 is a flowchart of the above operation.
FIG. 14 is a block diagram of still another example.
FIG. 15 is a block diagram of an example in which a wavelength variable laser is used as a light source.
FIG. 16 is a block diagram of an example using a light source and wavelength selection means.
FIG. 17 is a front view of an example of a wavelength selection unit.
FIG. 18 is a perspective view of another example of the wavelength selection means.
FIG. 19 is a perspective view of another example of the wavelength selection means.
FIG. 20 is a perspective view of still another example of the wavelength selection means.
FIGS. 21A and 21B are cross-sectional views of another example of a light source.
FIGS. 22A to 22C are cross-sectional views showing examples of light introducing means.
FIGS. 23A and 23B are cross-sectional views each showing an example of light introducing means.
24A and 24B are a side view and a front view showing another example of the light source.
FIG. 25 is a cross-sectional view of an example including a shutter.
FIGS. 26A and 26B are cross-sectional views of examples provided with optical switches, respectively.
FIG. 27 is a block diagram of a conventional example.
[Explanation of symbols]
3 light source 7 probe 8 subject 12 light receiving element 14 calculation means

Claims (18)

An optical device for non-invasively quantifying a biological component, comprising: an irradiation unit that sequentially irradiates a subject with light having a plurality of different wavelengths in a near-infrared wavelength range of 1000 nm to 2500 nm; A non-invasive living body, comprising: light receiving means for receiving transmitted light transmitted through a subject; and arithmetic means for calculating a biological component concentration by performing arithmetic processing on the absorbance for each wavelength obtained by the light receiving means. Component quantification device. The non-invasive biological component quantification device according to claim 1, wherein the irradiation means includes a plurality of light sources that output light of different wavelengths. 2. A non-invasive biological component quantifying apparatus according to claim 1, wherein the irradiating means includes a variable wavelength laser as a light source. 2. The non-invasive biological component according to claim 1, wherein the irradiating means includes a light source covering a near infrared wavelength range of 1,000 nm to 2500 nm, and a wavelength selecting means for extracting a plurality of specific wavelengths from the light source. Quantitative device. 5. The non-invasive biological component quantitative device according to claim 4, wherein the wavelength selecting means is a variable wavelength filter. 6. The non-invasive biological component quantification device according to claim 5, wherein the wavelength variable filter is a gradient film thickness filter. 5. The apparatus according to claim 4, wherein the wavelength selecting means is an optical device. 2. The light emitting device according to claim 1, wherein the irradiating means includes a plurality of light sources that output light of different wavelengths and emit light sequentially, and a light guiding unit that guides light from these light sources to a probe for irradiating an object. 3. The non-invasive biological component quantification device according to 2. 9. The non-invasive apparatus for quantifying a biological component according to claim 8, wherein the light guiding means is a diffractive optical device. 9. The non-invasive apparatus for quantifying a biological component according to claim 8, wherein the light guiding means is an optical waveguide. 3. The non-illuminating device according to claim 1, wherein said irradiating means comprises a light source for outputting light of different wavelengths, and a switching means for selectively guiding light from these light sources to a probe for irradiating an object. Quantitative device for invasive biological components. The irradiating means is a light source covering a near-infrared wavelength range of 1000 nm to 2500 nm, a wavelength selecting means for extracting a plurality of specific wavelengths from the light source, and a probe for irradiating the object with light passing through the wavelength selecting means. 5. The non-invasive biological component quantification device according to claim 1, further comprising switching means for guiding the flow. 13. The noninvasive biological component quantification device according to claim 11, wherein the switching means switches at least one of the light source side and the probe side to switch the opposing position between the light source side and the probe side. 13. The non-invasive apparatus for quantifying a biological component according to claim 11, wherein the switching means is a shutter that transmits light of a required wavelength and blocks light of another wavelength. 13. The noninvasive biological component quantifying device according to claim 11, wherein the switching means is an optical switch that transmits light of a required wavelength and blocks light of another wavelength. Reference light guiding means for guiding the light of each wavelength to the light receiving device without passing through the subject is provided, and the calculating means calculates a biological component concentration based on the absorbance calculated from the reference light and the light passing through the subject. The non-invasive biological component quantification device according to any one of claims 1 to 15, wherein: The biological component for the purpose of quantification is glucose, and the irradiating means includes a measuring probe that is in contact with the surface of the subject, and the measuring probe is configured to emit light to the subject and reflect light from the subject. The non-light-receiving device according to any one of claims 1 to 16, wherein the light or a light-receiving portion that receives light transmitted through the subject is arranged at a center-to-center distance of 0.2 mm to 2.0 mm. Quantitative device for invasive biological components. An optically non-invasive method for quantifying a biological component in a non-invasive manner, comprising sequentially irradiating a subject with light having a plurality of different wavelengths in a near-infrared wavelength range of 1,000 nm to 2500 nm. The reflected light or transmitted light transmitted through the subject is guided to the light receiving means, and light of each wavelength is guided to the light receiving means without passing through the subject, and arithmetic processing is performed from the absorbance for each wavelength obtained by the light receiving means. A method for quantifying a non-invasive biological component, comprising:

Images