JP6775660B2 - Multiposition diffusion spectrum data processing, modeling, prediction methods and processing equipment - Google Patents

Description

The present disclosure relates generally to the field of spectrum detection, and more specifically to spectrum detection methods, component concentration modeling and prediction methods, and processing devices used for spectrum detection.

The spectral detection method is pollution-free, does not destroy the sample, has a high detection rate, can realize simultaneous quantitative analysis of multiple components, does not require the use of any reagent or test strip, and is continuous. It has advantages such as real-time monitoring, and is a truly non-invasive detection technology. In the field of biochemistry, the adoption of near-infrared absorption spectroscopy has already successfully realized rapid and non-invasive detection of biochemical indicators such as biological tissue blood oxygen saturation, and near-red. Infrared spectroscopy is recognized as one of the most promising non-invasive detection techniques for chemical components in the human body.
When detecting the component concentration of an object to be measured using the spectral method, the object to be measured, usually a complex sample without pretreatment such as purification, or a component to be measured in the human body. is there. When the concentration change of the component to be measured has a clear wavelength characteristic, a calibration model can be constructed by adopting the method of multivariate regression to measure the concentration of the component to be measured. However, in complex samples and individuals, except for the components to be measured, many unpredictable interference components are contained. For example, changes in the concentration of certain components in the human body are affected by changes in human body temperature, feelings, etc., and wavelength characteristics are clear. is not. Therefore, it is necessary to remove the influence of these unpredictable backgrounds on the concentration analysis of the object to be measured, and then perform the concentration measurement analysis again. For near-infrared spectral analysis, the calibration sample set used to build the mathematical model should include various backgrounds of the sample under test.
Taking non-invasive blood glucose concentration detection as an example, the blood glucose content in human tissues is low and the change within the physiological range is very small, so that the signal due to the blood glucose change is extremely faint. On the other hand, the optical properties of the tissue itself are also very complicated, and when light passes through dynamically changing human tissue, some light is absorbed and sugar signals are extracted due to the presence of non-linear scattering. Things get very difficult. All near-infrared regions such as water, fat, and protein in tissues may be absorbed, and the signal intensity due to these interfering factors is larger than the light intensity due to the change in glucose concentration. And since the same radical can have absorption peaks in different multiple frequency regions in this spectral region, a complex sample or individual can have spectral peaks of different molecules and multiple types of radicals in the same near-infrared spectral region. Are well overlapped. In addition to this, factors such as metabolism, menstrual cycle, mood swings and environmental impacts of the living body all directly or indirectly affect the content of various substance components in human tissues and are effectively measured. Blood glucose concentration information in the sample cannot be extracted. Due to the large number and complexity of these factors, it is difficult to monitor changes in these factors in real time at current scientific research levels. Therefore, the method of obtaining one kind of reference measurement is also a feasible route to solve the above problem. Human blood oxygen saturation measurement is a classic example of successful taking relative measurements.
In vitro experiments typically employ dual optical reference measurements and adjacent background subtraction to eliminate common-mode interference due to instrument drift, that is, to background the spectrum of a reference sample whose spectral properties are close to those of the object under test. The difference calculation is performed by measuring as a spectrum. Experimental results show that this method can effectively eliminate the effects of common mode changes on the measurements.
However, in some applications, for example, in the measurement of human blood glucose concentration, it is difficult to obtain a reference material having the same optical properties as the object to be measured and to include background fluctuation information of the object to be measured, and to realize the reference measurement. In the clinical setting of near-infrared non-invasive blood glucose detection, it is difficult to obtain a reference whose optical properties are similar to those of the human body, and it is not possible for a part of the human body to contain no glucose or to fix the glucose concentration unchanged. Therefore, the spectral processing method for subtracting the background reference material that can be adopted in such an in vitro experiment cannot be directly applied to biodetection. Introducing a standard reflector or replica as a background reference into the measurement system, whose reflectance order is close to the diffuse reflectance of the human skin, also eliminates the effects of some hardware system reference signals, but the reflector. Because the light propagation method in the model and the model is different from that of the human skin, factors such as metabolism, physiological cycle, mood unevenness and environmental effects of the human body are not shown in the spectrum of the reflector and the model. No change signal is available, which is also currently the biggest obstacle to extracting the blood glucose concentration of the human body using the near-infrared spectral method.
Therefore, when using the near-infrared spectral method to detect the concentration of certain components in human tissue, the practical measurement process is summarized so as to extract faint concentration change specificity information from a complex overlapping background. The process of extracting useful information is restricted and influenced by various physiological factors of the human body.
For this reason, Xu Kakin et al. Have invented the principle and method for realizing concentration measurement using the floating reference position (Chinese patent application, publication number CN1699973A), and as shown in FIG. 1, the information contained in the measurement spectrum itself. Of these, I was looking for a reference standard that could be used as the "background". When the concentration of a component under test, such as the human body, such as glucose, changes, it causes changes in optical properties such as the absorption coefficient and scattering coefficient of the object to be measured. A predetermined radially directed position r _k away from the light source, the diffuse reflection light energy was changed by absorption and scattering effects in the tissue can be offset essentially each other, varies essentially with a change in glucose concentration it does not have, call this position r _k and the floating reference position. The light energy measured at this position reflects the elimination of the effects of all basic interfering factors other than changes in glucose concentration during detection. Therefore, it is possible to extract glucose specificity information using the spectrum at this position as the "background" in the non-invasive detection process of human blood glucose, and realize something similar to the reference measurement in the in vitro experiment. The existence characteristics of the position floating reference have been verified by Monte Carlo simulation methods and in vitro experiments. However, since the change in light energy due to the change in blood glucose concentration is related to the optical characteristics of human tissue, this "background" reference standard is used for different objects to be measured, different positions of the same object to be measured, and different wavelengths of probe light. They are different, that is, the positions of the floating reference positions are different.
In the calculation of the Monte Carlo simulation, the skin of the palm was selected as the target tissue layer for measuring the human blood glucose concentration, and the three-dimensional skin model was targeted for measurement, that is, the skin was divided into three, epidermis, dermis, and subcutaneous tissue. Divide. The number of photons of which is provided on a Monte Carlo simulation program is 10 ^9. Based on the optical parameters of each layer given by Maruo et al. (Maruo K., Tsurugi M., Chin J., et al., Noninvasive blood glucose assay using a newly developed near-infrared system, IEEE Journal of Selected Topics in Quantum Electronics , 2003. 9 (2): p. 322-330; Maruo K., Oota T., Tsurugi M., et al., New methodology to obtain a calibration model for noninvasive near-infrared blood glucose monitoring, Applied Spectroscopy, 2006 60 (4): p. 441-449), when the glucose concentration increased from 0 to 500, 1000 and 1500 mg / dL, respectively, the optical parameters of the dermal layer of the skin model also changed accordingly, and of the other skin layers. Optical parameters do not change. When the epidermis, dermis and subcutaneous tissue of the three-dimensional skin model are set to 0.5 mm, 3.5 mm and ∞, respectively, a typical diffuse reflection spectrum in which the detector is radially distributed from the light source at wavelengths of 1200 to 1700 nm. As shown in FIG. 2, the distribution becomes close to a negative exponential distribution, and the diffuse reflected light intensity rapidly decreases as the radial distance increases. 2.0mm weak diffuse reflection light intensity later, smaller from 10 ^-1 to ^{10 -8} order.
The radial distributions obtained by subtracting the diffuse reflection intensity of 0 mg / dL from the diffuse reflection intensity of different glucose concentrations obtained are wavelengths of 1200 nm, 1300 nm, and 1400 nm, respectively, as shown in FIGS. 3 (a1) to 3 (a4). Corresponds to the overall diagram at each wavelength. With the same skin layer thickness, it is considered that there is one radial position where the diffuse reflection light intensity is not sensitive to changes in glucose concentration at different wavelengths at the same measurement position of the same object to be measured. , This position is the floating reference position. However, as can be seen from the figure, this floating reference position has a clear wavelength characteristic, and the change in the position floating reference position is gradual from 1200 nm to 1300 nm. In particular, in the first half region, the reference position due to the change in wavelength Does not change much. In the range of 1300 nm to 1400 nm, the fluctuation of the reference position is large, and the reference position tends to approach the light source. And when the wavelength is larger than 1400 nm, the floating reference position does not exist.
Even if the wavelength is the same, there are differences in the tissue components of different measurement targets, and the same measurement targets are not all the same at different times, that is, there are differences in the optical characteristics of the tissue, so 1300 nm. Using the normal human blood glucose concentration (100 mg / dL) as a model environment at the wavelength of, the absorption coefficient μ _a and the scattering coefficient μ _s of the dermis layer were changed and changed with a gradient of 20%, respectively, in FIG. 3 (b). As shown in, we obtain a distribution map in which the floating reference position in the three-dimensional skin model changes according to the optical characteristics of the dermis layer. As can be seen from the figure, different measurement targets or the same measurement target have different scattering specificities of the skin tissue at different time zones, which significantly affects the positioning of the floating reference position.
Similarly, for different measurement objects or different physiological sites of the same measurement object, the physiological structure and tissue thickness of the skin are not all the same, and the floating reference position changes correspondingly at the same wavelength. Similar to the case of the above simulation, at a wavelength of 1300 nm, using a normal human blood glucose concentration (100 mg / dL) as a model environment, the epidermis thickness is 0 according to the typical value of the skin thickness of the palm. The distribution of the floating reference position in the three-dimensional skin model when changing to the range of 1 to 1.0 mm and the dermis thickness to the range of 2.0 to 4.0 mm is as shown in FIG. 3 (c). become. The influence of the change in the epidermis layer thickness on the extended reflected light is large, and the floating reference position moves away from the light source as the epidermis layer thickness increases.
As described above, when one fixed radial position is selected as a reference point and measured, it becomes impossible to cover different measurement objects, different states of the same measurement object, and multiple wavelengths, which in turn causes a measurement error. become. It is desirable to develop a measurement method that can achieve general applicability for different objects and wavelengths to be measured.

Publication of Chinese patent application CN1699973A Gazette

Maruo K., Tsurugi M., Chin J., et al., Noninvasive blood glucose assay using a newly developed near-infrared system, IEEE Journal of Selected Topics in Quantum Electronics, 2003. 9 (2): p. 322-330 ; Maruo K., Oota T., Tsurugi M., et al., New methodology to obtain a calibration model for noninvasive near-infrared blood glucose monitoring, Applied Spectroscopy, 2006. 60 (4): p. 441-449

An object of the present disclosure is, at least in part, to provide a more universal spectrum measurement technique.

According to one aspect of the present disclosure, the probe light is used to irradiate the measurement medium containing a specific component, and the first spectral data and the second spectral data at the first radial position of the measurement medium. The second spectral data at the radial position is acquired, the first radial position and the second radial position are arbitrarily selected, and the first spectral data and the second spectral data are obtained. It provides a spectrum data processing method including performing difference processing.
According to another aspect of the present disclosure, the first optical fiber bundle for guiding the incident light, the first optical fiber bundle whose emission end face is located substantially at the center of the detection end face of the optical fiber probe, and the first. A second optical fiber bundle and a third optical fiber bundle are provided, and in the detection end face, the end face of the optical fiber in the second optical fiber bundle and the end face of the optical fiber in the third optical fiber bundle are the first. We provide optical fiber probes that are separated from the exit end face of the optical fiber bundle of.
According to another aspect of the present disclosure, a background medium or a reference medium and a series of media to be measured containing specific components having different known concentrations contained in the background medium or the reference medium are provided, and the reference medium is the background medium. And the prediction model is acquired based on the inclusion of the specific component of the initial concentration, the processing of the series of media to be measured according to the above method, and the respective known concentrations and the corresponding processed spectrum data. It provides a way to do and build a predictive model that includes.
According to another aspect of the present disclosure, the measurement medium including the background medium or the reference medium is processed according to the above method, the reference medium contains the background medium and the specific component of the initial concentration, and the concentration of the characteristic component changes. Concentration prediction including the fact that the concentration of the specific component in the measurement medium becomes unknown and that the concentration of the specific component is predicted based on the processed spectrum data and the prediction model for the measurement medium. Provides a method.
According to another aspect of the present disclosure, an probe for detecting spectral data of diffuse reflection and / or diffuse scattered light of a medium to be measured containing a specific component, and an probe are optionally used. Provided is a processing apparatus including a processor arranged to detect spectral data at a selected first radial position and a second radial position and perform difference processing on them.

According to the embodiments of the present disclosure, it is not necessary to determine the floating reference position, which is usually complicated.

The above and other objectives, features and advantages of the present disclosure will be further clarified by the description of the embodiments of the present disclosure with reference to the drawings below. In the drawing
The measurement principle of the position floating reference is schematically shown. The radial distribution of a typical diffuse reflection spectrum is schematically shown. Examples of the position floating reference variation are schematically shown, and FIGS. 3 (a1) to 3 (a2) show the position floating reference variation due to different wavelengths. An example of the position floating reference fluctuation is schematically shown. Examples of the position-floating reference variation are schematically shown, of which FIG. 3 (b) shows the position-floating reference variation due to skin optical characteristics, and FIG. 3 (c) shows the position-floating reference variation due to skin structural characteristics. A schematic comparison of spectral changes in the inner and outer regions of the floating reference position is shown. A flowchart of the spectrum data processing method according to the embodiment of the present disclosure is schematically shown. The rate of change of the scattering coefficient with wavelength is shown in the skin model. Jensen et al. Show the difference between the molar extinction coefficient of water at different temperatures and the molar extinction coefficient at 30 ° C. obtained in the experiment. Chen Rin et al. Show the absorbance change curve between water at different temperatures and water at 30 ° C obtained in the experiment. The stepwise reception policy according to the embodiment of the present disclosure is shown. The optical fiber probe according to the embodiment of the present disclosure is shown, in which FIG. 10 (a) is a side view and 10 (b) (c) is a cross-sectional view. The optical fiber probes according to the examples of the present disclosure are shown, of which 10 (d) to 10 (e) are sectional views. It is a schematic diagram which shows the general principle of constructing a concentration prediction model, and performing concentration prediction. It is a flowchart which shows the prediction model construction and concentration prediction method by an Example of this disclosure. The floating reference position calculation result of the Monte Carlo simulation of the 5% intralipid solution is shown. The amount of change in the number of diffusely reflected photons when the glucose in the 5% intralipid solution changes from 50 mM to 100 mM is shown. The curve of the number of diffusely reflected photons at different radial positions away from the light source is shown before the light source drift is corrected. The change curve of the number of diffuse reflected photons at different radial positions after correcting the light source drift is shown. Each radial position at different temperatures shows the amount of change in the number of diffusely reflected photons obtained with the change in glucose concentration. The curve of change in the number of diffuse reflected photons depending on the density is shown before and after correcting the light source drift. It is shown that the comparison before and after the signal correction is performed with 0 mg / dL glucose as the initialized state. It is shown that the comparison before and after the signal correction is performed with 3000 mg / dL glucose as the initialized state. It is shown that the comparison before and after the signal correction is performed with 6000 mg / dL glucose as the initialized state. An example of arrangement of the measurement system according to the embodiment of the present disclosure is shown. The change in the amount of relative change in diffused light depending on the radial position due to the action of element X is schematically shown. After changing the light source power, the amount of relative change in light intensity inside, itself, and outside the floating reference position is shown. It shows the existence of a single temperature line of action and a temperature reference point.

又はｓ＝（Ｉ_２−Ｉ_１）／Ｉ_１）を取得してもよいことを留意すべきである。
本開示の多くの実施例において、初期スペクトルを測定する必要であり可能である。背景媒体に特定成分を含まない場合のスペクトルを初期スペクトルとして採用しても良く、背景媒体に任意な固定の初期濃度の特定成分（すなわち、基準媒体）を含む場合のスペクトルを初期スペクトルとして採用しても良い。例えば、いくつかの媒体（特に、特定成分を含まない背景媒体）に対して、初期スペクトルのデータベースを構築して、重複に使用する（例えば、予め実験に使用し、実際な測定に使用するなど）ことによって、作業の負担を低下してもよい。
第一の径方向位置と第二の径方向位置のところで、プローブ光に対する被測定媒体の拡散反射光及び／又は拡散散乱光の光強度が当該特定成分の濃度変化に伴って異なる変化率を有するように、この第一の径方向位置と第二の径方向位置を選択することができる。このほか、この二つ位置でのコモンモード干渉が一般に特定の関係があるため、実際の測定においては、データ処理によってこの両位置の間のコモンモード干渉を除去して、被測定成分の濃度変化に関する情報を残すことができる。
具体的に、第一の径方向位置と第二の径方向位置のところで、プローブ光に対する被測定媒体の拡散反射光及び／又は拡散散乱光の光強度が当該特定成分の濃度変化に伴って異なる符号の変化率を有するように、この第一の径方向位置と第二の径方向位置を選択することができる。ここで、「異なる符号」とは、正（＋）と負（−）、正（＋）と零（０）、又は負（−）と零（０）を含むことができる。即ち、本願において、零（０）値を正（＋）および負（−）と異なる符号を有するものと見なすようにする。変化率が零値の径方向位置は、例えば、上記の浮動基準位置である。実際な測定において、絶対値が一定閾値より小さい変化率を「零」変化率と見なすことができ、この閾値は実際な応用環境に応じて設定されて良い。
下記のとおり、このようにして選択される第一の径方向位置と第二の径方向位置は、コモンモード干渉を除去することに寄与する。例えば、第一の径方向位置と第二の径方向位置は、これらの変化率が１つの正と負（例えば、第一の径方向位置の変化率が負、第二の径方向位置の変化率が正）になるように選択することができる。このとき、第一の径方向位置が浮動基準位置（例えば、図４に示すＢエリア内）の内側（例えば、図４に示すＡエリア）にあり、第二の径方向位置が浮動基準位置の外側（例えば、図４に示すＣエリア）にある。そのため、実際な応用において、第一の径方向位置を光源位置に近いように選択し、かつ第二の径方向位置を光源位置から離れるように選択することができる。そして、大多数の場合に対して、第一の径方向位置が浮動基準位置の内側にあり、第二の径方向位置が浮動基準位置の外側にあることができる。それによって、固定の第一の径方向位置と第二の径方向位置のところでスペクトルデータを測定することができており、それぞれ浮動基準位置の精確な位置のあるところを確定する必要がない。また、以下にさらに説明するように、複数の測定環境に適する検知器配置を提供することができる。
径方向位置の選択はスペクトル測定と同時に行うことができる。例えば、いくつかの径方向位置を初期選択して、これらの径方向位置のところで初期スペクトル、例えば光強度（或は上記のように、初期スペクトルデータベースから取得）を測定することができる。そして、被測定媒体における特定成分濃度が変化した後（或は、特定成分濃度が初期スペクトルデータベースからデータを取得するために用いられる特定成分濃度に対して異なり）、これらの径方向位置のところで変化スペクトル、例えば光強度を測定する。初期スペクトルと変化スペクトルによって、各径方向位置での光強度変化（率）の方向（正又は負）を確定することができる。補間によってその他の径方向位置での光強度変化（率）を取得することもできる。そのうち変化が正の１つ径方向位置および変化が負の１つ径方向位置をそれぞれ第一の径方向位置および第二の径方向位置として選択することができ、あるいは、そのうち変化が正又は負の１つ径方向位置及び変化が一定閾値（或は「零」）より小さい１つ径方向位置（上記のように、この径方向位置は実際に浮動基準位置と見なすことができる）をそれぞれ第一の径方向位置および第二の径方向位置として選択することができ、かつこのとき第一の径方向位置および第二の径方向位置でのスペクトルデータも上記のように得られている。
このように、予め浮動基準位置を確定する必要がなく、このような確定は手間のかかる（複数回測定して光強度変化の最小の位置を確定する必要あり）ことである。もし初期選択された径方向位置にちょうど浮動基準位置を含めば、もちろんこの位置を利用することもできる。ただし、これはあらかじめ浮動基準位置を確定してからこの位置でのスペクトルデータを用いることと異なっており、浮動基準位置を確定する不便を解消したためである。
他の実施例によれば、浮動基準点の位置を確定することもできる。例えば、光強度絶対変化の最小の径方向位置を浮動基準点として選択する。光強度変化が零に近い径方向位置の近いところで複数測定して、浮動基準点の位置精度を改善することができる。それ以外に、浮動基準点でのスペクトルデータを取得することができる。
上記のように第一と第二の径方向位置でのスペクトルデータを取得した後に、当該方法は、操作Ｓ５０３において、スペクトルデータに対して差分処理を行うことも含む。
例えば、このような差分処理は以下のように行うことができる。
第一の径方向位置がρ_mと記され、第二の径方向位置がρ_nと記される。特に、径方向位置が浮動基準点の内側にあると、ρ_Iと（変化率が負であることができる）記述される；径方向位置が浮動基準点の外側にあると、ρ_Oと（変化率が正であることができる）記述される。なお、もしあらかじめ浮動基準点を確定していれば、あるいは、選択された径方向位置にちょうど浮動基準点を含めば、浮動基準点がρ_Rと記される。
本開示の実施例によれば、重み付け係数η例えば以下のように確定することができる。数値計算を採用し或は特定成分濃度Cを一定に保って、異なる径方向位置での拡散反射光を繰り返し測定して、任意の２つ径方向位置での干渉要因ΔNの影響下での拡散反射光の変化量の比率ΔI(ρ_m, C, ΔN)/ ΔI(ρ_n, C, ΔN)を得ており、ηと記し、即ち：

ただし、ρ_mとρ_nは任意の異なる径方向位置、例えばρ_I、ρ_Oとρ_Rのうち任意の２つを示す；ΔI(ρ_m, C, ΔN)は特定成分濃度Cが固定の場合にρ_mでの干渉要因ΔNによる光強度の変化を示し、ΔI(ρ_n, C, ΔN)は特定成分濃度Cが固定の場合にρ_nでのΔNによる光強度の変化を示す。
実際の測定過程では、測定する成分の濃度変化以外、拡散反射光の変化を引き起こす干渉要因の変化もある。測定する成分の濃度がΔC変化し、干渉要因がΔN変化するとき、以下のようになる。

ただし、ρ_iは任意の径方向位置、例えばρ_I、ρ_Oおよびρ_Rのいずれか一つを示す；ΔI(ρ_i, ΔC, ΔN)はρ_iでの濃度変化ΔCおよび干渉要因ΔNによる光強度変化を示し、ΔI(ρ_i, C, ΔN)はρ_iでの干渉要因ΔNによる光強度変化を示し、ΔI(ρ_i, ΔC, N)はρ_iでの濃度変化ΔCによる光強度変化を示す。
式（１）によって、任意の二つ径方向位置（例えば、ρ_I、ρ_Oおよびρ_Rのいずれか二つ）でのスペクトルデータを以下の差分処理を行うことができる。

式（３）から分かるように、このような差分処理によって、コモンモード干渉によるノイズ信号を効果的に減少又は差し引くことができ、測定する成分濃度（ΔC）だけに関する有用な信号（ΔI(ΔC)）を得る。
以下の説明においては主としてρ_I、ρ_Oおよびρ_Rのいずれか二つに対して説明するが、ここで、式（３）から分かるように、このような差分処理は任意の二つ径方向位置ρ_mおよびρ_nに適用できることを留意すべきである。
また、任意の二つ径方向位置ρ_mおよびρ_nで、コモンモード干渉によるノイズ信号の間の比例定数ηはあらかじめ推定できるものである。実際の測定では、この比例定数を直接に採用して両位置での光強度絶対変化量に対して差分処理を行うことができ、即ち、測定する成分の濃度（ΔC）だけに関する有用な信号（ΔI(ΔC)）を得ることができる。
以下、無限媒体における拡散方程式の定常解でηの表現式を推定し、この理論に基づいて比例定数ηのサンプル推定方法を与える。
無限媒体において一つ点光源の場合に対する光束Φの解は下記である。 ・

ただし、ρは検出器と光源との間の径方向距離である；λは光源から発されるプローブ光の波長である；μ_aは吸収係数である；μ_s'は等価散乱係数であり、 (1-g)μ_sと定義され、gは異方性因子である；μ_sは散乱係数である；Dは光子の拡散係数であり、

；μ_effは有効減衰係数であり、

したがって、式（４）は下記のように記述することができる。

入射光が媒体に入った後に、光子が媒体における粒子と相互作用を発生した後に出射されて拡散反射光を得ており、一般に拡散反射エネルギー変化を引き起こす要因は主で下記の三種類に分けることができる：（１）被測定媒体の光学特性の変化；（２）入射光源のドリフト；（３）検出器状態のドリフトなど。そのうち、入射光が媒体に入った後に、光子が媒体における粒子と衝突し、一部の光子が粒子に吸収されて損失し、他の部分の光子が散乱され、被測定媒体の光学特性の変化は吸収効果と散乱効果の総合的な作用の結果である。被測定媒体の吸収係数及び散乱係数などの光学特性の変化を引き起こす要因は、主で被測定媒体における測定する成分の濃度変化、干渉成分濃度の変化及び温度の変化などを含む。上記の拡散反射エネルギーの変化を引き起こす要因に、被測定媒体における測定する成分の濃度変化の測定だけが希望されるものであり、他の影響要因による拡散反射光エネルギー変化は減少又は差し引きすべきである。
人体組織中のブドウ糖濃度変化を例として、無限媒体における拡散方程式の定常解によって、血糖濃度が変化ΔC_gするの場合に、同一径方向位置で血糖濃度変化による光束Φ(ρ)の変化量ΔΦ(ρ, ΔC_g)は以下である：

ただし、

式（６）から分かるように、ある一つの波長で、光束の変化量ΔΦ(ρ, ΔC_g)は径方向距離ρの関数である。
浮動基準位置の定義によって、被測定物による被測定媒体における光源から離れた異なる位置の光強度の変化率が最も小さい受光点、即ち特定成分例えば血糖の濃度変化に対して敏感ではない径方向位置が、浮動基準位置である。そのために、理想的な場合に、血糖の濃度変化ΔC_gだけがあっていかなる干渉要因がないとき、ある一つの波長で、無限媒体における拡散方程式の定常解によって、血糖濃度変化の浮動基準位置ρ_Rに下記の感度Sen_g(ρ_R)がある：

式（７）と式（８）を（９）に代入して得られる浮動基準位置は以下である：

この位置で、血糖濃度変化による光束Φ(ρ_R)の変化量ΔΦ(ρ_R, ΔC_g)は０（ゼロ）である。そして、実際の測定過程では、浮動基準位置ρ_Rでの拡散反射光の変化が背景干渉変化によるものであり、血糖濃度変化に関連しない、つまり、

通常∂μ_a/∂C_gは∂μ_s'/∂C_gに比べて１〜２オーダー低くなるため、式（８）を式（６）に代入して近似的に得ることができる：

これによって得られる拡散反射光の変化率は下記である：

式において、∂μ_s'/∂C_gはブドウ糖濃度変化による等価散乱係数の変化率である。通常、ある一つの固定の母液モデルに対して、等価散乱係数に対するブドウ糖濃度の変化の影響が定数である。例えば、異なる濃度のIntralipid溶液モデルに対して、∂μ_s'/∂C_gは下記のように表すことができる：

皮膚（水＋ポリスチレン）モデルに対して、∂μ_s'/∂C_gは下記のように表すことができる：

ただし、ｍ値は、図６に示すように（Matthias Kohl, Matthias Essenpreis and Mark Cope, The influence of glucose concentration upon the transport of light in tissue-simulating phantoms）、Mie理論によって計算された波長変化による散乱係数の変化率である。図中の２つ実線曲線はそれぞれ皮膚（水＋ポリスチレン）モデルにおいて、ブドウ糖濃度が85mM/Lと144mM/Lときの散乱係数μ_s変化の曲線を示しており、それを直線にフィッティングする傾きがそれぞれ-1.569*10^-7及び-1.5*10^-7であり、後のシミュレーションは50、100、150mMの三つの異なる勾配を採用して行われるものであるため、それぞれ近似的な傾きを選択して計算を行う。
これによって、図２３に示すように、ブドウ糖濃度変化による拡散反射光の変化率dΦ/Φは径方向距離ρの（略線形）関数であると近似的に考えられる。
実際の測定では、光強度Iと光のエネルギー束密度Φの関係は固定倍数の関係であり、光のエネルギー束密度の相対変化量は光強度の相対変化量に近似的に等価し、即ち、

。そのために、測定位置の変化によるΔＩ／Ｉの変化も線形に近似される。
したがって、以下のように異なる位置間の比例定数ηを推定することができる。
同一影響要因ΔXで、ΔI(ρ)/I(ρ)がρの線形関数を利用し、先に第一の径方向位置における光強度相対変化量ΔI(ρ_m, ΔX)/I(ρ_m)によって、第二の径方向位置における光強度相対変化量ΔI(ρ_n, ΔX)/I(ρ_n)を推定するようにして、両者の比率をξと記し、それが径方向位置の選択に関するものであり、下記の式（Ｓ−１）で示される。

(S-1)

式（Ｓ−１）において、

はこの要因作用の非敏感位置である。例えばブドウ糖が変化する場合、この位置がブドウ糖測定の浮動基準位置である。特定の被測定物および特定の被測定媒体に対して、

が相対的な固定の位置であることが証明されている。そのために、二つの測定位置

及び

が固定された後、ξの値が１つの固定定数値である。これから分かるように、ξの値はあらかじめ実験によって推定することができる。
式（Ｓ−１）を変形した後、下記の式（Ｓ−２）を得ることができる。

(S-2)
そして、

(S-3)
式（Ｓ−２）及び（Ｓ−３）から分かるように、あらかじめξの値を推定した後に、式（Ｓ−３）に代入した後、比例定数ηの値を得ることができ、ηを式（３）に代入して測定する成分濃度（ΔC）に関する有用な信号（ΔI(ΔC)）を得ることができる。
実際の測定過程に拡散反射光エネルギーの変化を引き起こす影響要因ΔNを大きく２種類に分けて討論を行う：一種類は、被測定媒体において干渉成分濃度又は測定温度による光学特性の変化である；もう一種類は、測定システムにおいて光源ドリフト又は検出器状態ドリフトなどである。
（１）被測定媒体において干渉成分濃度又は測定温度による光学特性の変化
干渉成分濃度又は測定温度が変化する場合、被測定媒体の光学特性の変化を引き起こすことになる。温度変化を例として、温度の変化が分子の振動・回転状態及びエネルギー遷移確率を変化させるため、異なる温度下で物質のモル吸光係数が若干異なることになる。同時に、温度の変化は、吸収物質の濃度がそれに伴って変化することを引き起こすことになり、これは以下のためである：温度上昇が分子間の化学結合の結合程度を増加することになって、同一分子の隣接分子数が増加するようになり、物質の密度が大きくなる；しかしながら、温度の上昇も分子間の距離を大きく増加させ、物質の密度を小さくすることになる。両者の総合効果は、温度による物質濃度の変化規則を決めている。血糖濃度を相対的に一定C_gに保持し、温度変化ΔTだけある場合、同一径方向位置で引き起こされる光束Φ(ρ)の変化量ΔΦ(ρ, C_g, ΔT)は、下記の通りである。

式（７）及び式（８）を式（１６）に代入して下記の式（１７）を得ることができる。

ただし、

と記される。
光源から離れた径方向距離がρ_I及びρ_Oの二つの位置をそれぞれ浮動基準内側測定位置及び外側測定位置として取得し、式（１７）によって、浮動基準内側測定位置ρ_Iと浮動基準位置ρ_Rでの温度変化による光束変化量の比率、及び浮動基準外側測定位置ρ_Oと浮動基準位置ρ_Rでの温度変化による光束変化量の比率は、それぞれ下記の通りである。

生体組織中に７０％程度の水を含むため、生体組織近赤外スペクトルに対する温度はかなりの程度水のスペクトルの温度特性に関連する。図７に示すのは、Jensenたちが実験によって得られた３２℃〜４２℃下での水モル吸光係数ε_w(λ)と３０℃下でのε_w(λ)の間の差曲線図（Peter Snor Jensen, Jimmy Bak, Stenfan Andersson-Engels, Influence of temperature on water and aqueous glucose absorption spectra in the near- and mid-infrared regions at physiologically relevant temperatures, Applied Spectroscopy, 2003, 57(1):28-36）である。１４４０ｎｍ、１７８０ｎｍ、２１８０ｎｍ、２７５０ｎｍ、４９００ｎｍ、５３００ｎｍ、および６３００ｎｍで温度の変化に敏感ではないこと以外、他の波長でε_w(λ)が温度の変化に伴って規則的に変化する。そのために、人体体温変化の範囲内（約３５℃〜４０℃）の各波長下で、温度によるモル吸光係数の変化率∂ε_w(λ)/ ∂Tは定数であるが、異なる波長に対してこの定数が異なる値を取ると近似的に考えられる。これによって、各波長下での温度による吸光係数の変化率∂μ_a(λ)/ ∂Tも定数に近似される。類似的に、陳韻たちは、２℃を間隔にして、温度範囲が３０℃〜４０℃の水サンプルをスペクトル測定実験を行うことによって、図８に示す異なる温度下での水と３０℃下での水の間の吸光度変化値曲線を得ており、１５２５、１８３２、および２０６０ｎｍでの吸光度変化量と温度の間の線形関係式（陳韻,近赤外非侵襲的血糖測定−基準波長浮動基準法の研究：「博士学位論文」,天津,天津大学,２００９）を得ている。図からも分かるように、各波長下で、吸光度の変化量と温度の間は線形関係に近似する。水は純粋な吸収媒体であるため、同じ結論、即ち各波長下での温度による吸光係数の変化率∂μ_a(λ)/ ∂Tが定数に近似すると考えることを得ることができる。
Lauferたちは、インビトロ皮膚サンプル実験を採用し、２５℃〜４０℃の範囲内に人体真皮層及び皮下組織と温度影響の関係を研究していた（Jan Laufer, et al., Effect of temperature on the optical properties of ex vivo human dermis and subdermis, Phys. Med. Biol.,1998, 43: 2479-2489）。実験結果は、温度変化による真皮層の等価散乱係数の変化率が(4.7±0.5)×10^-3℃^-1であり、温度変化による皮下組織の等価散乱係数の変化が(-1.4±0.28) ×10^-3℃^-1であることを示している。そのために、人体体温変化の範囲内（約３５℃〜４０℃）で、温度変化による等価散乱係数の変化率∂μ_s'/ ∂Tが定数に近似する。
従って、式（１８）及び式（１９）から分かるように、浮動基準内側測定位置ρ_I、
浮動基準位置ρ_R及び浮動基準外側測定位置ρ_Oが確定した場合、同一波長下で温度変化による光束の変化量の比率ΔΦ(ρ_I, C_g, ΔT)/ΔΦ(ρ_R, C_g, ΔT)及びΔΦ(ρ_O, C_g, ΔT)/ΔΦ(ρ_R, C_g, ΔT)はいずれも定数であり、それぞれη₁とη₂を記述する。即ち：

そのために温度変化による拡散反射光強度の変化量はコモンモード干渉とすることができる。そのうち、光学パラメータが既知の被測定媒体に対して、式（１８）及び式（１９）によって定数η₁とη₂を計算することができる；光学パラメータが未知の被測定媒体に対して、測定して得られる拡散反射スペクトルを採用して、光学パラメータを再構成する方法によって、被測定媒体の光学パラメータを算出することができ、さらに式（１８）及び式（１９）によって定数η₁とη₂を計算し、或は血糖濃度が相対的に一定に保持される場合で、温度変化時の拡散反射光の変化量を繰り返し測定し、式（２０）及び式（２１）によって定数η₁とη₂の値を計算する（例えば、複数回の測定の平均値を取る）。
実際の測定過程では、ブドウ糖濃度がΔC_g変化する同時に測定温度がΔT変化する場合、同一の径方向位置でこの二つ要因による光束Φ(ρ)の変化量ΔΦ(ρ, ΔC_g, ΔT)は下記の通りである。

ただし、ΔΦ(ρ, ΔC_g, T)は関心のある測定待ちの有用な信号であり、ΔΦ(ρ, C_g, ΔT)は径方向位置に関するコモンモード干渉信号である。
次に式（１１）及び（２２）によって、浮動基準内側測定位置ρ_I、浮動基準位置ρ_R及び浮動基準外側測定位置ρ_OでΔC_gとΔTとによる光束Φ(ρ)の変化量ΔΦ(ρ_I, ΔC_g, ΔT)、ΔΦ(ρ_R, ΔC_g, ΔT)及びΔΦ(ρ_O, ΔC_g, ΔT)は、それぞれ下記の通りである。

式（２０）で式（２３）と（２４）を重み付け差分演算して下記の式を得ることができる。

式（26）から分かるように、温度変化による拡散反射光変化のコモンモード干渉量は、浮動基準内側測定位置ρ_I及び浮動基準位置ρ_Rでの拡散反射光変化量の差分演算によって除去され、血糖濃度の変化のみに関する有用な信号を得ることができる。
類似的に、式（２１）、（２４）及び（２５）によって、浮動基準外側測定位置ρ_O及び浮動基準位置ρ_Rでの拡散反射光変化量の差分演算で同様に温度変化による拡散反射光変化のコモンモード干渉量を除去することができる：

式（２６）及び（２７）は、それぞれ浮動基準内側測定位置ρ_Iでの信号と浮動基準外側測定位置ρ_Oでの信号を採用して浮動基準位置ρ_Rでの信号を結合し、血糖濃度の変化情報のみに関する有用な信号を効果的に得ており、コモンモードノイズの干渉を差し引いている。
式（２０）及び（２１）から分かるように、浮動基準内側測定位置ρ_Iと浮動基準外側測定位置ρ_Oが確定した場合、同一波長下で温度変化による二つの測定位置での光束の変化量の比率ΔΦ(ρ_I, C_g, ΔT)/ΔΦ(ρ_O, C_g, ΔT)も定数であり、η₃と記する。

即ち：

そして、式（２３）、（２５）及び（２９）によって、浮動基準内側測定位置と外側測定位置での測定信号を差分演算して下記の式を得る。

式（３０）から分かるように、浮動基準内側測定位置ρ_Iと外側測定位置ρ_Oでの拡散反射光変化量の差分演算によって、同様に温度変化による拡散反射光変化のコモンモード干渉量を除去し、血糖濃度変化のみに関する有用な信号を得るという目的を達成することができる。なお、図４から分かるように、血糖濃度変化による浮動基準内側測定位置ρ_Iと外側測定位置ρ_Oでの拡散反射光の変化量の方向は反対になり、式（３０）における差分演算方法を採用することは、微弱な有用な信号の絶対値も増加して、測定待ち信号の特異性を向上し、より正確な測定結果を得ている。
被測定媒体に干渉成分濃度変化によるコモンモード干渉信号は、類似的な方法を採用して差し引くことができる。
（２）測定システムにおいて光源ドリフト又は検出器状態ドリフト
入射光源の光強度がドリフトする、または拡散反射光を検出するための検出器状態がドリフトする場合は、いずれも拡散反射光強度値の変化を引き起こすことになる。入射光源の光強度がドリフトすることを例として、血糖濃度を相対的に一定C_gに保持し、入射光源の光強度がΔF倍変化する場合、同一径方向位置に対して引き起こされる光束Φ(ρ)の変化量ΔΦ(ρ, C_g, ΔF)は下記の通りである。

ただし、Φ₀(ρ)はこの測定位置での拡散反射光強度の初期値を示す。光源から離れた径方向距離がρ_Iとρ_Oの二つの位置をそれぞれ浮動基準内側測定位置及び外側測定位置として取り、式（３１）によって、浮動基準内側測定位置ρ_Iと浮動基準位置ρ_Rで入射光源の光強度のドリフトによる光束変化量の比率、及び浮動基準外側測定位置ρ_Oと浮動基準位置ρ_Rで入射光源の光強度のドリフトによる光束変化量の比率は、それぞれ下記の通りである。

式（３２）と式（３３）も任意の二つの測定位置に拡張することができる。式を変形し

て分かるように、任意の測定位置での光強度相対変化量

は全部同じであり、１つの固定値と見なすことができ、即ち図２３において、光源ドリフト干渉だけある場合、その作用線は１つ横軸に平行な直線であり、このとき式（Ｓ−３）における
の値は約１になって、式（Ｓ−３）を式（Ｓ−４）に簡略化する。即ち、

(S-4)
図２４は、ｉｎｔｒａｌｉｐｉｄ ３％溶液に対して拡散反射光を測定する結果である。拡散光の出力電力を変更して光源のドリフトをシミュレーションし、五回連続して変更した後に、三つの異なる測定位置を見つけることができ、その拡散反射光強度の相対変化量が一貫性のある現象を呈し、即ちこのときξの値は約１と記することができる。
浮動基準内側測定位置ρ_I、浮動基準位置ρ_R及び浮動基準外側測定位置ρ_Oが確定した場合、各測定位置での拡散反射光強度の初期値が既知で確定であるため、同一波長下で入射光源の光強度のドリフトによる光束の変化量の比率ΔΦ(ρ_I, C_g, ΔF)/ΔΦ(ρ_R, C_g, ΔF)及びΔΦ(ρ_O, C_g, ΔF)/ΔΦ(ρ_R, C_g, ΔF)は、いずれも定数であり、それぞれη₄とη₅を記し、即ち下記の式がある。

そのために、入射光源の光強度のドリフトによる拡散反射光強度の変化量は、コモンモード干渉とすることができる。ただし、η₄およびη₅の値は、血糖濃度が相対的に一定に保持されるときに、温度が変化するときの拡散反射光の変化量を繰り返し測定し、式（３４）と（３５）によって計算して得られる。
実際の測定過程においては、ブドウ糖濃度がΔC_g変化すると同時に入射光源の光強度値がΔF倍ドリフトする場合、同一の径方向位置でこの二つ要因による光束Φ(ρ)の変化量ΔΦ(ρ, ΔC_g, ΔF)が下記の通りである。

実際の測定過程では、ΔFが10^-3〜10^-2オーダーであり、乗積

は無視可能である。式（３６）は下記のように記することができる。

ただし、ΔΦ(ρ, C_g, ΔF)は径方向測定位置に関するコモンモード干渉信号であり、ΔΦ(ρ, ΔC_g, F)は関心のある測定待ちの有用な信号である。
そして式（１１）及び（３７）によって、浮動基準内側測定位置ρ_I、浮動基準位置ρ_R及び浮動基準外側測定位置ρ_OでΔC_gとΔFとによる光束Φ(ρ)の変化量ΔΦ(ρ_I, ΔC_g, ΔF)、ΔΦ(ρ_R, ΔC_g, ΔF)及びΔΦ(ρ_O, ΔC_g, ΔF)は、それぞれ下記の通りである。

式（３４）で式（３８）と（３９）を差分演算して、下記の式を得ることができる。

式（３８）から分かるように、入射光源の光強度のドリフトによる拡散反射光変化のコモンモード干渉量は、浮動基準内側測定位置ρ_Iと浮動基準位置ρ_Rでの拡散反射光変化量の差分演算によって除去され、血糖濃度変化のみに関する有用な信号を得ることができる。
類似的に、式（３５）、（３９）及び（４０）によって、浮動基準外側測定位置ρ_O和と浮動基準位置ρ_Rでの拡散反射光変化量の差分演算で同様に入射光源の光強度のドリフトによる拡散反射光変化のコモンモード干渉量を除去することができる。

式（４１）及び（４２）は、それぞれ浮動基準内側測定位置ρ_Iでの信号と浮動基準外側測定位置ρ_Oでの信号を採用して浮動基準位置ρ_Rでの信号を結合して、血糖濃度変化情報のみに関する有用な除法を効果的に得ており、コモンモードノイズの干渉を差し引いている。
式（３４）及び（３５）から分かるように、浮動基準内側測定位置ρ_Iと浮動基準外側測定位置ρ_Oが確定した場合、同一波長下で入射光源の光強度のドリフトによる二つの測定位置での光束の変化量の比率ΔΦ(ρ_I, C_g, ΔF)/ΔΦ(ρ_O, C_g, ΔF)も定数であり、η₆と記する。

即ち：

そして、式（３８）、（４０）及び（４４）によって、浮動基準内側測定位置と外側測定位置での測定信号を差分演算して下記の式を得る。

式（４５）から分かるように、浮動基準内側測定位置ρ_Iと外側測定位置ρ_Oでの拡散反射光変化量の差分演算によって、入射光源の光強度のドリフトによる拡散反射光の変化のコモンモード干渉量を除去し、血糖濃度変化のみに関する有用な信号を得るという目的を同様に達成することができ、かつ、浮動基準測定方法の普遍性を向上し、微弱な有用な信号の絶対値を増加している。
拡散反射光強度を検出するための検出器状態ドリフトによるコモンモード干渉信号は、類似的な方法を採用して差し引くことができる。
これから分かるように、操作５０３においては、第一と第二の径方向位置でのスペクトルデータを差分処理しており、２種類の異なる干渉要因が式（３）に示すような重み付け差分によってコモンモード干渉信号を除去することができる。ほかの異なる波長下で測定された拡散反射光信号を類似的な方法で修正して、重み付け差分処理された各波長下での有効信号ΔΦ(λ_i, C_g)を得ることができる。
本開示の実施例によれば、異なる受信方式を採用して異なる位置でのスペクトル信号を検出することができる。
同一被測定媒体の異なる被測定部位、異なる測定波長または異なる被測定媒体の変化に伴って浮動基準位置のオフセットがあまり大きくない場合、以下のように異なる位置での拡散反射スペクトルを抽出することができる。
１）図９（ａ）に示すように、光源からの浮動基準内側の位置（図４中のエリアＡ）でのスペクトル信号を測定点として受信し、浮動基準位置（図４中のエリアＢ）でのスペクトル信号を参考点として受信する；
２）図９（ｂ）に示すように、絶対変化率が最も小さい受光点、即ちＢ点を浮動基準位置として選択し、変化率の局部的な極大値の受光点、即ちＣ点を測定点として選択する；
３）図９（ｃ）に示すように、光源からの浮動基準内側の位置（図４中のエリアＡ）、浮動基準位置（図４中のエリアＢ）及び光源からの浮動基準外側の位置（図４中のエリアＣ）でのスペクトル信号を同時に受信し、浮動基準内側と外側のスペクトル信号を重み付け差分処理する。
同一被測定媒体の異なる被測定部位、異なる測定波長または異なる被測定媒体の変化に伴って浮動基準位置のオフセットが大きくて浮動基準位置を確定しにくい場合、以下のように異なる位置での拡散反射スペクトルを抽出することができる。具体的に，同一測定個体の異なる測定部位、異なる波長又は異なる測定個体に対して、光学パラメータの相違が浮動基準位置の確定に大きく影響するため、図３に示すように、測定部位、測定波長の変化に伴って，浮動基準位置が相応的に変化する。これによって、図 ９（ｄ）に示すように、光源からの浮動基準内側と外側とが同じノイズ情報を含む特征を利用して，浮動基準内側の受信半径を適当に縮小し、浮動基準外側の受信半径を増大して、各波長或は各部位での浮動基準位置がいずれも含まれないことを保証して、径向半径が浮動基準位置より小さい（図 4におけるエリアA）及び浮動基準位置より大きい（図 4におけるエリアC）拡散反射光をそれぞれ受信することによって，浮動基準位置の内外両側のスペクトルに対して重み付け差分分析計算をする。
図１０(ａ)には本開示の実施例による光ファイバプローブ構造を模式的に示している。図１０に示すように、この光ファイバプローブ１０００はクラッドに被覆された複数の光ファイバ束１００１、１００３、１００５及び１００７を含むことができる。光ファイバ束毎に1本又は複数本のファイバを含むことができる。その中、光ファイバ束１００１が光源からの入射光を案内するために用いられ、光ファイバ束１００３、１００５及び１００７が被測定媒体からの拡散反射光を案内するために用いられる。より具体的に、光ファイバ束１００３が浮動基準位置内側の径向位置からの拡散反射光を案内するために用いられ、光ファイバ束１００５が浮動基準位置からの拡散反射光を案内するために用いられ、光ファイバ束１００７が浮動基準位置外側の径向位置からの拡散反射光を案内するために用いられ、これらの光ファイバ束はN端から集束する。光ファイバ束１００１に案内された入射光はM端から出射することができ、かつ、光ファイバ束１００３、１００５及び１００７はM端から拡散反射光を受信することができる。これによって，M端は光ファイバプローブ１０００の検知端面と呼ぶことができる。
ここで留意されたいことは、ここに記載の”光ファイバ束”はこれらの機能による論理的な区画である。物理的には、すべてのファイバが混在して、明確なグループ分けがない可能性がある。
なお，図１０（ａ）には四つの光ファイバ束が示されているが，本開示がこれに限定されない。例えば、より多い、又はより少ない光ファイバ束を含んでもいい。そして，これらの光ファイバ束の配列も図１０（ａ）に示すレイアウトに限定されない。例えば、各光ファイバ束中の光学がクラッド内に絡み合うことまでできる。
図１０（ｂ）−１０（ｅ）は本開示の異なる実施例の光ファイバプローブのM端での断面図をそれぞれ模式的に示している。図の中、各円形パターンは光ファイバ束におけるファイバの端面を示すことができる。
図１０（ｂ）に示すように、入射光を案内するための光ファイバ束１００１は、ほぼ中心に位置することができる。光ファイバ束１００３は光ファイバ束１００１を回ってその周囲に設置することができ、光ファイバ束１００７は光ファイバ束１００１を回って、相対的に光ファイバ束１００１から離れるように設置することができる。また、光ファイバ束１００５は光ファイバ束１００１を回って、光ファイバ束１００３と１００７との間に設置することができる。異なる被測定物の浮動基準位置の差異によって、異なるサイズの光ファイバプローブを設計することができる。
実際に測定する場合には、光ファイバ束１００５の端面が浮動基準位置（もし存在し且つ確定する、或はそのおおよその範囲を分かる）にほぼ合わせ、光ファイバ束１００３、１００５和１００７における拡散反射光信号（即ち、浮動基準位置及び浮動基準位置内側と外側位置でのスペクトル信号）を抽出することができるように、光ファイバプローブ１０００を放置する。或は、光ファイバ束１００３及び１００７における拡散反射光信号（即ち、浮動基準内側と外側のスペクトル信号；例えば、浮動基準位置が正確に確定されていない場合或は光ファイバ束１００５の端面が浮動基準位置のおおよそのエリアに大略に合わせられて浮動基準位置に正確に合わせられていない場合）、又は光ファイバ束１００３及び１００５における拡散反射光信号（即ち、浮動基準内側と浮動基準位置でのスペクトル信号）、又は光ファイバ束１００５及び１００７における拡散反射光信号（即ち、浮動基準位置と浮動基準外側のスペクトル信号）だけを抽出しても良い。
図１０（Ｃ）は光ファイバ束１００７を含めず、光ファイバ束１００１、１００３及び１００５を含む配置を示している。このような配置で、浮動基準位置内側と浮動基準位置のスペクトル信号を受信することができる。
図１０（ｄ）は光ファイバ束１００５を含めず、光ファイバ束１００１、１００３及び１００７を含む配置を示している。このような配置で、浮動基準位置内側と浮動基準位置外側のスペクトル信号を受信することができる。
図１０（ｅ）は光ファイバ束１００３を含めず、光ファイバ束１００１、１００５及び１００７を含む配置を示している。このような配置で、浮動基準位置と浮動基準位置外側のスペクトル信号を受信することができる。
通常、浮動基準位置に対する光ファイバ束１００５の端面と光ファイバ束１００１の端面の間の距離は大体確定的な数値（上記の配置に、光ファイバ束１００５の端面は光ファイバ束１００１の端面を回る所定半径の円形状に現れる）である；ほかの光ファイバ束１００３／１００７の端面と光ファイバ束１００１の端面の間の距離は一定の範囲（上記の配置に、光ファイバ束１００３／１００７の端面は光ファイバ束１００１の端面を回るリング形状に現れる）を覆うことができる。
ここで留意されたいことは、図１０（ｂ）〜１０（ｅ）において、光ファイバ束１００３、１００５及び１００７における各光ファイバの端面を、光ファイバ束１００１を回って略円形状又はリング形状に緊密に配列するように示しているが、本開示はこれに限られない。例えば、これらは緊密に配列されなく、まばらに配列されても良い；或はこれらは完全な円形状又はリング形状パターンを構成しなく、このようなパターンの一部だけ構成しても良い。
実際の測定環境において、測定位置及び基準位置は物理的に実現可能な点からなる可能であるが、入射や出射にかかわらず、点以外、同じ特性の複数の点の集合からなる幾何図形であっても良く、円形状、リング形状、矩形状などを含む。
本開示の実施例によれば、光強度の相対変化量をスペクトルデータとして採用して差分して、濃度変化に関する測定情報のみを保留する。
発明者は、径方向位置ρに沿って光強度の相対変化量も線形又は線形近似を呈することを既に発見していた。以上の論述を参照し、例えば図２３の説明を結合して分かるように、上記の差分処理は同様に光強度相対変化量に適用する。例えば、二つの径方向位置での光強度相対変化量を直接差分処理することによって、乗法性ノイズを除去することができる；二つの径方向位置での光強度相対変化量を上記のように因数ηを利用して重み付け差分処理することで、加法性ノイズを除去することができる。
図１１はスペクトルデータを利用して濃度予測を行う一般的な原理を示している。図１１に示すように、背景媒体又は基準媒体（背景媒体及び初期濃度の特定成分を含み）に一連の既知濃度{C_i}の特定成分を入れ、それに応じたスペクトルデータ{I(ρ)}をそれぞれ取得する。これらの既知濃度のデータ集合
と相応的なスペクトルデータの集合
によって、予測モデルを構築することができる。そして、背景媒体又は基準媒体に特定成分の未知濃度（或は濃度変化）C'_iに対して、それに応じたスペクトルデータI'(ρ)（“Y”）を取得することができる。I'(ρ)と予測モデルＭによって、濃度（“X”）を予測することができる。
上記のように、スペクトルデータは、各種の適合なデータ、例えば拡散反射及び／又は拡散散乱光の光強度変化や相対変化を含むことができる。
モデリングするときには、背景媒体又は基準媒体のスペクトルを初期スペクトルとして測定することができ、既知濃度{C_i}の特性成分が入れられた後のスペクトルを測定スペクトルとして測定することができ、これで光強度変化情報を取得することができる。予測するときには、同様に背景媒体又は基準媒体（基準媒体に特定成分の初期濃度がモデリングするとき基準媒体に特定成分の初期濃度と同じでも異なっても良く）のスペクトルを初期スペクトルとして測定することができ、特定成分濃度変化後のスペクトルを測定スペクトルとして測定することができ、これで光強度変化情報を取得することができる。予測されたものは濃度相対値（即ち、濃度変化量）であってもよく、初期値（背景媒体の場合は０；基準媒体の場合は上記初期濃度）を加えて濃度予測値を得ても良い。
本開示の実施例によれば、これらのスペクトルデータに対して上記の差分処理を行って、干渉要因の影響を効果的に除去することができる。例えば、計量化学方法を採用して予測モデルＭを構築する。具体的に、差分処理が行われた後のデータに対して最小二乗法を採用してモデリングすることができ、さらに正味信号モデルを構築することができる。
予測モデルＭは背景媒体／基準媒体と特定成分に対して予め構築され、例えばデータベース又はサーバに保存されることができる。必要の場合にデータベース又はサーバから予測モデルＭを取得することができる。
ここで、このようなモデリング及び／又は濃度予測方法を提出している。図１２を参照して、操作Ｓ１２０１において、スペクトルデータを取得することができる。例えば、モデリングするときには、既知濃度{C_i}の特定成分が入れられた後の背景媒体又は基準媒体に対して、スペクトルデータ（例えば、特定成分を入れる前に対しての光強度変化情報）を取得することができる；予測するときには、そのうち特定成分濃度が変化した背景媒体又は基準媒体に対して、スペクトルデータ（例えば、特定成分濃度変化前に対しての光強度変化情報）を取得することができる。続いて、操作Ｓ１２０３において、スペクトルデータに対して差分処理を行うことができ、例えば、光強度変化率の符号が異なる二つの位置でのスペクトルデータに対して差分処理を行う。そして、操作Ｓ１２０５において、処理された後の差分信号を利用してモデリング又は予測することができる。図１２の処理は、モデリングに応用されると予測に応用されるときに基本的に同じであり、その区別は以下にある：モデリングするときには、特定成分の濃度が既知であり、濃度（
）とスペクトルデータ（
）によって予測モデル（Ｍ）を得ることである；予測するときには、特定成分の濃度（或は濃度変化）が未知であり、スペクトルデータ（Ｙ）と予測モデル（Ｍ）によって予測濃度（或は濃度変化）（Ｘ）を得ることである。
本開示の実施例によれば、このようなモデリング／予測方法は人体非侵襲的血糖濃度測定に応用することができる。この場合、プローブ光の波長は約１．０〜２．４μmの範囲内にあって良い。
一例によれば、モンテカルロシミュレーションの方法によって５％ ｉｎｔｒａｌｉｐｉｄ溶液の浮動基準位置を確定することができ、入射光子数の変化によって光源のドリフトをシミュレーションすることができる。
図１３は濃度が５％であるｉｎｔｒａｌｉｐｉｄ溶液に対するモンテカルロシミュレーションの浮動基準位置計算結果である。シミュレーションに用いられる、吸収係数、散乱係数、各異方性因子及び散乱係数を含む光学パラメータは、Tamara L. Troy & Suresh N. Thennadil, Optical properties of human skin in the near infrared wavelength range of 1000 to 2200 nm, Journal of Biomedical Optical, 2001, 6(2):167-176.からのものであり、シミュレーションの波長範囲は１１００〜１６００ｎｍである。ブドウ糖濃度はそれぞれ０〜１００ｍＭであり、間隔が１０ｍＭであり、光子数が１０^９である。異なるブドウ糖濃度下でのｉｎｔｒａｌｉｐｉｄ溶液による拡散反射光とブドウ糖が含まれない純粋なｉｎｔｒａｌｉｐｉｄ溶液による拡散反射光の差を算出して、波長範囲が１１００〜１６００ｎｍで、浮動基準位置が約０．９〜２ｍｍの範囲内に変化することを分かることができる。同一被測定個体又はサンプルの基準位置は異なる波長下で大きな差があることを示している。
したがって、図９（ｄ）に示す拡散反射光受信方案を採用することができる。具体的に、光源からの浮動基準内側、外側の両位置でのスペクトルを同時に受信する。図１４は入射光子数が１０^９の場合に、１３００ｎｍ波長下でブドウ糖濃度が５０ｍＭと１００ｍＭ変化するときの拡散反射光光子数変化量の図。
通常、測定された信号をブドウ糖濃度変化による有用な信号I_S及び人体生理背景又は外部環境変化に関するノイズ信号I_Nに分ける、即ち、

ただし、I_Sはブドウ糖濃度C_gに関連しており、I_Nは主に光源ドリフト、温度、圧力、変位などの物理的要因によって影響される。ここで、光源ドリフトによるノイズ干渉のみを考えるようにする。これによって、光源ドリフトと血糖濃度変化とによる光強度測定値Iの変化は下記の通りである。

ただし、ρは検出器と光源の径方向距離（モンテカルロシミュレーションに球座標の径方向半径位置）であり、ΔC_gは血糖濃度の変化量であり、ΔNは背景の変化量である。ΔI_S(ρ, ΔC_g, N)は有効なブドウ糖濃度情報であり、この部分の情報が必要である。背景干渉信号であるΔI_N(ρ, C_g, ΔN)はブドウ糖濃度情報に関連しなく、かつ、通常不規則に変化して、ΔI(ρ, ΔC_g, ΔN)からブドウ糖濃度変化情報を抽出し難しいことに至る主な理由である。
基準位置ρ_Rで、拡散反射光強度はブドウ糖濃度変化に敏感でなく又はブドウ糖濃度変化に関連しなくて、下記がある：

基準位置での光強度変化は完全に背景干渉によって引き起こされて、下記がある：

相応的に、浮動基準内側と外側測定位置での拡散反射光強度変化は、それぞれ下記の通りである。

基準位置ρ_Rでの背景干渉変化ΔI_N(ρ_R, C_g, ΔN)、と測定位置での背景干渉変化との間の内因性関係は、固定的なものであるので、

ただし、η₁及びη₂は比例係数である。留意されたいことは、異なる径方向位置又は異なる測定半径を測定位置として選択する場合、得られる倍数関係が異なり、即ち適当な重み付け係数を選択すべきである。実際の測定過程においては、ブドウ糖濃度が相対的に一定に保持されるときに繰り返し測定することによって得られることができる。式（４９）〜（５３）によって差分演算で下記の有効なブドウ糖信号表現式を求めることができる。

式（５４）によって、浮動基準内側及び浮動基準測定位置の情報だけを採用して、さらに計量化学モデリング分析を行うことができる；式（５５）によって、浮動基準外側及び浮動基準位置の情報だけを採用して計量化学モデリング分析を行うことができる。浮動基準位置の情報を完全に採用しない場合、式（５２）と（５３）を除算して下記の式を得ている。

これによって、浮動基準内−外側受信方案を採用して、有効な測定信号ΔI_I-O(ΔC_g)を得ることができる。

浮動基準位置に基づく拡散反射信号を差分処理して得られた血糖情報は、直接測定して得られた拡散反射光強度変化情報に比べて、より高い特異性を有しており、実際の測定における背景干渉を効果的に差し引いている。
本実施例は、入射光子数を変更することによって光源のドリフトをシミュレーションしており、変化範囲が±２０％である。図１３から分かるように、波長１３００ｎｍで、ブドウ糖の浮動基準位置が約１．３ｍｍ付近であるので、図１４中のエリアＡのように、径方向位置が０．７〜０．９ｍｍの位置を浮動基準内側測定位置として選択することができて、測定されたスペクトルがI(ρ_I)である；図１４中のエリアＢのように、径方向位置が１．３ｍｍの位置を浮動基準位置として選択して、測定されたスペクトルがI(ρ_R)である；図１４中のエリアＣのように、径方向位置が１．８ｍｍ〜２．０ｍｍの位置を浮動基準外側測定位置として選択して、測定されたスペクトルがI(ρ_O)である。
溶液中にブドウ糖が含まれず、即ち光源ドリフトのノイズ信号のみが含まれる場合には、同一測定位置が光源ドリフトで相応的なノイズ信号を発することになる。モンテカルロシミュレーションの結果によって得られる、異なる入射光子数で異なる測定位置での拡散反射光子数を表１に示す。入射光子数が１０^９から±２０％変化する場合には、相応的な測定位置で拡散反射光子数の変化量を表２に示す。なお、拡散反射光子数の相対変化量は表２−１に示される。これから分かるように、三つの測定位置で、拡散反射光子数の相対変化量は基本的に一致している。したがって、任意の二つ位置の拡散光子数の相対変化量の比率ξは約１である。

このときブドウ糖濃度が変わらないため，測定された信号変化量は完全に光源ドリフトの変化によって引き起こされるものであり、即ち、このとき測定された信号変化量はノイズ信号であると考えられる。したがって、表３に示すように、異なる測定位置でのノイズ干渉の比率を計算することができる。


表3

表３における任意の二つの位置でのノイズ干渉の絶対変化量の比率も、以下の方法によって直接取得される。
ξはもう１と確定されるため，表３−１に示すように、式（Ｓ−３）を利用して直接に
ηの値を取得することができる。

表３と表３−１とを比較して、実際に得られたηの値は式（Ｓ−３）を採用して推定されたηの値と基本的に一致している。
表３と３−１から分かるように、ブドウ糖濃度が変化せず、光源のみドリフトする場合には、下記の通りである：
浮動基準内側測定位置信号の変化量ΔI_N(ρ_I, ΔC_g, ΔN)は、浮動基準測定位置信号の変化量ΔI_N(ρ_R, ΔC_g, ΔN)の約７．０倍であり、即ち、ΔI_N(ρ_I, ΔC_g, ΔN)＝７．０ΔI_N(ρ_R, ΔC_g, ΔN)；
浮動基準外側測定位置信号の変化量ΔI_N(ρ_O, ΔC_g, ΔN)は、浮動基準測定位置信号の変化量の約１．０６倍であり、即ち、ΔI_N(ρ_o, ΔC_g, ΔN)＝１．０６ΔI_N(ρ_R, ΔC_g, ΔN)；
浮動基準内側測定位置信号の変化量ΔI_N(ρ_I, ΔC_g, ΔN)は、浮動基準外側測定位置信号の変化量ΔI_N(ρ_O, ΔC_g, ΔN)の６．６倍であり、即ち、ΔI_N(ρ_I, ΔC_g, ΔN)＝６．６ΔI_N(ρ_O, ΔC_g, ΔN)。
ブドウ糖濃度と光源は何れも変化する場合には、浮動基準位置での光強度変化がブドウ糖濃度変化に関連せず、即ち、この位置での光強度変化が完全に光源ドリフトによって引き起こされるものであるため、式（５４）と式（５５）によって得られる浮動基準内側と外側のブドウ糖濃度変化による有用な信号はそれぞれ下記の通りである。

それぞれ六つの異なる濃度のブドウ糖拡散反射スペクトルを選択して、対応するブドウ糖濃度と入射光子数を表４に示す。

光源ドリフトに対して修正しない場合に、図１５に示すように、ブドウ糖濃度がそれぞれ２０、４０、６０、８０及び１００ｍＭ変化する場合、光源から離れた異なる径方向位置での拡散反射光子数変化曲線が得られており、即ち、拡散反射光強度を測定する曲線は、ブドウ糖濃度によって規則的な逓増又は逓減変化を呈することがない。つまり、光源ドリフトによる信号変化はブドウ糖濃度変化の特徴信号を覆っている。
同様に浮動基準内側測定位置を０．７〜０．９ｍｍに、基準位置を１．３ｍｍ、外側測定位置を１．８〜２ｍｍに取る。光源ドリフトに対して修正する前に、表５に示すように、ブドウ糖濃度変化下で各測定位置での拡散反射光子数変化値が得られる。

式（５８）と（５９）を採用して浮動基準位置の情報を結合して浮動基準内側と外側測定位置拡散反射光子数変化量に対してそれぞれ光源ドリフトの修正を行っており、計算結果を表６に示す。

図１６から分かるように、浮動基準内側測定位置で、ブドウ糖濃度変化の増大に伴い、拡散反射光子数は順に逓減するように変化し、変化量が負値である；浮動基準外側測定位置で、ブドウ糖濃度変化の増大に伴い、拡散反射光子数は順に逓増するように変化し、変化量が正値である。すなわち、光源ドリフトの影響を効果的に除去している。
完全に浮動基準位置での測定情報を採用しないと、上記の計算から分かるように、浮動基準内側測定位置信号の変化量ΔI_N(ρ_I, ΔC_g, ΔN)が浮動基準外側測定位置信号の変化量ΔI_N(ρ_O, ΔC_g, ΔN)の約６．６倍であり、即ち、ΔI_N(ρ_I, ΔC_g, ΔN)＝６．６ΔI_N(ρ_O, ΔC_g, ΔN)、式（５７）によって測定された浮動基準内側と外側測定信号に対して重み付け差分演算を行って下記になる。

即ち、得られた信号は浮動基準内側と外側有効信号の加重和であり、完全に光源ドリフトによるノイズを除去している。
式（６０）を採用し、完全に浮動基準位置情報を採用せず、浮動基準位置内側と外側測定信号のみを採用して上記のブドウ糖濃度変化だけでなく光源ドリフトも存在する情況に対して修正して、算出された異なるブドウ糖濃度変化でのΔI_I-O(ΔC_g)結果を表７に示す。結果に表われることは、ブドウ糖濃度変化量の逓増に伴い、浮動基準内側と外側測定信号に対する重み付け差分処理によって得られた有効信号ΔI_I-O(ΔC_g)が順に逓増する傾向を呈し、光源ドリフトによるコモンモード干渉の影響を効果的に除去していることである。

その他の異なる波長下で測定されたスペクトル信号に対して類似的な方法を採用して光源ドリフトの修正を行い、さらに重み付け差分処理を行って得られた各波長下での有効信号ΔI_S(λ_i)をそれに対応する一系列の参考濃度パラメタと結合して、部分最小二乗数理モデルを構築し、未知濃度スペクトル濃度の予測を行うことができる。
別の一例によれば、モンテカルロシミュレーションの方法によって、光源からの浮動基準内側−外側を受信方案として測定待ち対象温度が変化するときの情況を分析することができる。
２％のｉｎｔｒａｌｉｐｉｄ溶液に対して、波長が１４００ｎｍより大きいの場合、浮動基準位置がなくなり、つまり、波長が１４００より大きいの場合、浮動基準測定方法の理論が適用されなくなることを発見した。そのために、ここで濃度が２％のｉｎｔｒａｌｉｐｉｄ溶液をモデルとして、波長１６００ｎｍ下でのブドウ糖濃度と温度とによる拡散反射光の変化情況に対してモンテカルロシミュレーションを行う。ブドウ糖濃度変化範囲が０〜１００ｍＭであり、間隔が２０ｍＭである；温度変化範囲が３２℃〜４０℃であり、間隔が０．５℃である；入射光子数が10¹¹であり、サンプルを経過して拡散反射された絶対光子数を出射光とする。温度変化する場合には、吸収係数と散乱係数の変化量がそれぞれ下記の通りである。

１６００ｎｍを例として、温度のみを変化させて、３２度の出射光を基準として、得られる温度による拡散光の相対変化量を図２５に示す。
これから分かるように、光源−探触子距離が２ｍｍの付近に、温度変化に敏感でない位置があり、それを「温度基準位置」と呼ぶすることができる。それに、光源から一定の距離を離れた後、一定の範囲に、異なる位置の間の光強度相対変化量が線形に近似した変化規則を呈する。注意されることは、光源からあまり離れすぎた後、出射光が急に下がるため、ノイズ影響が大きくなり、このとき測定が大きな影響を受けることになる。ここで、ノイズが大きすぎるの情況を考えないようにする。二つの測定位置を固定すると、図２５によって、ξの値を推定することができる。また式（Ｓ−３）を利用して、ηの値を直接取得することができる。ηの値を精確に取得するために、以下、温度変化した後で実際に生じられたノイズ量によって計算する。
温度が３２℃、３５℃、３８℃及び４０℃でブドウ糖濃度が６０ｍＭ及び１００ｍＭ変化するとき異なる位置での拡散反射光変化量をそれぞれ取って、図１７に示す分布図が得られる。図から分かるように、この波長で、私たちは浮動基準位置がないと考えることは、ブドウ糖濃度の変化による感度がほぼゼロに常に保持されるある一つの径方向位置が実際にないことである。しかしながら、いかなる一つの温度で、ブドウ糖濃度の変化による拡散反射光の変化量が常に負値になる径方向位置があり、それにこのエリア内の拡散反射光の変化量はより高い絶対値と安定性を有する。そのため、このエリアで二つの径方向位置を二つの測定位置として選択し、浮動基準位置がない場合のコモンモード干渉ノイズを除去するために用いることができる。
径方向位置０．６〜１ｍｍを測定位置１として、径方向位置１〜２ｍｍを測定位置２として選択する。溶液にブドウ糖が含まれない場合、即ち温度による変化しかない場合、異なる径方向位置は温度の変化に伴って相応的なノイズ信号を生じることになる。モンテカルロシミュレーションによって、異なる温度で異なる径方向測定位置での拡散反射光子数を得ることができる。３６℃を基準として、温度が３２℃から４０℃まで変化する場合、即ち、温度が±４℃変化する場合、二つの測定位置で検出された拡散反射光子数の変化量を表８に示す。

このときブドウ糖濃度が変わらないため、測定された信号変化量が完全に温度変化によって引き起こされるものであり、即ち、このとき測定された信号変化量がノイズ信号と考えられる。そのため、二つの測定位置でノイズ干渉の比率を計算することができ、温度変化で、測定位置２の拡散反射光子数変化量と測定位置１の拡散反射光子数変化量の比率が約０．１７である。即ち、下記のように記することができる。

したがって、ブドウ糖濃度と温度が全部変化する場合、式（６３）によってρ₁とρ₂での拡散反射光の変化量に対して差分演算を行って、得られるブドウ糖濃度変化による、温度によるコモンモード干渉を除去する有効信号は、下記の通りである。

ランダムで六つの異なる温度で異なる濃度のブドウ糖拡散反射光を選択して、ブドウ糖濃度と温度の間の相関係数が−０．０１９１８であるため、両者の間に関係がないと考えられ、これで実際の測定過程においてブドウ糖濃度が変化すると同時に温度が不規則的なドリフトを発生する情況をシミュレーションしており、対応するブドウ糖濃度及び温度の情況は表９に示すとおりである。

第一グループのデータを測定開始時刻の状態として、温度変化による干渉信号に対して修正しない場合に、図１８に示すように、ブドウ糖濃度がそれぞれ２０、４０、６０、８０及び１００ｍＭ変化する場合、同じの二つの測定位置での拡散反射光子数の変化曲線が得られる。図の中で拡散反射光強度変化量を測定する曲線は、ブドウ糖濃度の変化によって規則的な逓増又は逓減変化を呈することがなく、温度変化による信号変化はブドウ糖濃度変化の特徴信号を覆っている。
式（６４）を採用して二つの測定位置での拡散反射光子数変化量に対して温度変化の修正を行って、計算結果は図１８における曲線に示す通りである。図から分かるように、二つの測定位置での信号の重み付けと修正後の信号を採用して、その絶対値が修正前の二つの測定位置での信号値より小さくなるが、曲線の絶対値がブドウ糖濃度の変化に伴って規則的な逓増変化を呈して、温度ドリフトによるコモンモード干渉を除去するという目的を達成している。
別の一例によれば、ＳＬＤ光源に基づく多環式光ファイバ測定システムを採用して、濃度が３％のｉｎｔｒａｌｉｐｉｄ溶液を測定待ち対象として、光源がドリフトする場合の情況を分析する。
実験分析によって測定されることは、波長が１２１９ｎｍである場合、濃度が３％のｉｎｔｒａｌｉｐｉｄ溶液のブドウ糖の浮動基準位置がおよそ３．０〜３．２ｍｍのところにあることである。これによって、この位置を多環式光ファイバプローブに浮動基準位置信号検出リングとして選択する。加工工程に対する考慮から、径方向位置が０．２４〜０．９６ｍｍの位置を内側測定位置信号検出リングとし、３．２〜４．１ｍｍの位置を外側測定位置信号検出リングとして、図１０（ａ）に示すような構造の多環式光ファイバプローブが作製された。
実験過程では、ランダムでＳＬＤの電力を変更して光源の不規則的なドリフト現象をシミュレーションして、波長が１２１９ｎｍになるときに、異なる時刻での三つの径方向位置での拡散反射光強度を測定し、一回目の測定値を測定の初期状態と仮定して、光源がドリフトを発生する場合、拡散反射光の変化量は当時状態の光強度測定値と初期状態ときの光強度値で差分計算を行って得られる。これによって、光源ドリフトによる三つの測定位置での拡散反射光信号値の変化量の比率を算出することができる。計算によって得られることは、浮動基準外側測定位置での光源ドリフトによる拡散反射光信号値の変化量が浮動基準位置での信号変化量の約０．８４場合であり、浮動基準位置での信号の変化量が浮動基準内側測定位置での信号変化量の約０．７倍であり、浮動基準外側測定位置での信号の変化量が内側測定位置での信号の変化量の約０．５８倍である。これらを光源状態とブドウ糖濃度が同時に変化するときの差分比例係数として信号の修正を行うために用いており、即ち、下記のように近似的に考えられる。

次いで、濃度が３％のｉｎｔｒａｌｉｐｉｄ溶液を母液として、ブドウ糖濃度範囲が１０００〜６０００ｍｇ／ｄＬ、間隔が１０００ｍｇ／ｄＬの六つのサンプルを配置して、ランダム順に六つのブドウ糖ｉｎｔｒａｌｉｐｉｄ溶液を測定し、測定過程中に同時にＳＬＤの電力を変更して光源の不規則的なドリフト現象をシミュレーションして、異なる時刻での三つの径方向位置での拡散反射光強度を測定し、サンプル溶液の拡散反射光強度と初期状態時の拡散反射光強度に対して差演算を行って、光源ドリフトとブドウ糖濃度が同時に変化するときに三つの測定位置での拡散反射光の変化量を算出しており、結果は図１９に示すとおりである。結果から分かるように、光源ドリフトがブドウ糖濃度の検出に大きな影響を与え、光源ドリフトのランダム性によって、三つの位置で測定された信号はいずれもブドウ糖変化との間の線形関係を失ってしまい、即ち、光源ドリフトによる拡散反射光強度信号の変化量はもう完全にブドウ糖濃度変化の有効情報を覆っているため、測定された光強度信号を修正する必要がある。
式（６５）、（６６）及び（６７）の比例関係によって、式（５４）、（５５）及び（５７）を採用してブドウ糖濃度変化と光源ドリフトとによって共同で引き起こされた拡散反射光強度信号を修正しており、結果は図１９に示すとおりである。結果から分かるように、任意の二つの位置の信号を採用して重み付け差分処理を行い、修正後の光強度信号はいずれもブドウ糖濃度変化と明らかな線形関係を呈し、ブドウ糖濃度検出に対する光源ドリフトの影響が減少又は除去され、さらにブドウ糖濃度変化の有効情報を効果的に抽出することができる。なお、結果からも分かるように、内リングと基準リング測定位置での信号、および外リングと内リング測定位置での信号を採用して修正された有効信号は、外リングと基準リング測定位置での信号を採用して修正された有効信号より明らかに大きくなっており、これは、光源からの径方向距離の増大に伴い、拡散反射光強度値は式指数的に減衰する。それに内リング及び外リングを採用する修正効果と内リング及び基準リングを採用する効果が伯仲しているが、内リング及び外リングを採用して信号検出と修正を行う場合、基準リングでの測定信号を採用しなくなり、浮動基準位置に対する測定波長、被測定対象自身状態などの変化の影響を受けなくても良く、当該信号修正方法の普遍性を効果的に強めている。
上記の分析において、濃度が３％の純粋なｉｎｔｒａｌｉｐｉｄ溶液で光源ドリフトによる比例係数を算出し、それを測定の初期状態として後続の信号処理を行う。同様に、類似的なステップに従って、異なる濃度を含むブドウ糖溶液サンプルで、最初に光源のランダムのドリフト下で相応的な比例係数を計算して、さらにこの濃度サンプルを測定の初期状態として後続の信号処理を行うことができる。ブドウ糖濃度が３０００と６０００ｍｇ／ｄＬのサンプルをそれぞれ採用してスペクトル修正に用いられる比例係数を算出し、それを測定の初期状態としてスペクトル信号の修正を行い、図２０と図２１に示すようなブドウ糖濃度が３０００と６０００ｍｇ／ｄＬのサンプルをそれぞれ初期状態として信号修正を行った結果を得ており、図から分かるように、異なる濃度のブドウ糖溶液を初期状態として、光源ドリフトによるコモンモード干渉を減少又は除去するという目的を同様に達成することができ、それに内側と外側測定位置での信号、及び内側と浮動基準位置での信号を採用して修正された効果が、外側と浮動基準位置での信号を採用して修正された効果より優れるように同様に現れており、得られた結論は純粋なｉｎｔｒａｌｉｐｉｄ溶液を初期サンプルとして信号修正を行う場合と一致している。また注意されたいことは、どのようなブドウ糖濃度のサンプルを初期状態として信号修正を行う場合でも、得られた修正後の結果は全部初期状態でのブドウ糖濃度情報に対する変化量であるため、異なる測定時刻でのブドウ糖濃度測定値がこの変化量と初期状態でのブドウ糖濃度値の和になるべきである。
図２２は本開示実施例による測定システムの配置例を示している。
図２２に示すように、当該測定システムは、光源２２０１、光源２２０１からの光を光ファイバに結合されるように適合するための結合システム２２０３、光ファイバプローブ２２０５、及び処理装置２２０９を含むことができる。
光源２２０１は、必要な波長の光を発射可能な各種の適切な光源を含むことができる。例えば、近赤外範囲で、ハロゲンランプを連続光源として使用することができる。或は、光源２２０１はスーパーコンティニウムパルスレーザ光源も含むことができる。
結合システム２２０３は、光源２２０１からの光を直線偏光に変換するためのグランプリズム２２０３−１、グランプリズム２２０３−１からの直線偏光を偏光状態が０次光と直交する＋１次光（或は−１次光）に分光（回折）するための音響光学チューナブルフィルタ（ＡＯＴＦ）２２０３−２、グランプリズム２２０３−１と直交して設けられて０次光を除去するためのグランプリズム２２０３−３、およびグランプリズム２２０３−３からの＋１次光（或は−１次光）を後継デバイスに結合するためのカプラ２２０３−４を含むことができる。
ここで留意されたいことは、図２２は結合システムの１つ具体的な例を示しているが、本開示がこれに限らない。業業者は、複数の結合システムを知っており、光源からの光を光ファイバシステムに結合することができる。
光ファイバプローブ２２０５は例えば前に図１０を参照して説明した構造を含むことができる。具体的に、結合システム２２０３は光源からの光を光ファイバプローブ２２０５の入射光ファイバ束（例えば、図１０中の１００１）に結合することができ、入射光ファイバ束は、光を被測定媒体２２０７に案内することができる。そして、光ファイバプローブ２２０５中のプローブ光ファイバ束（例えば、図１０中の１００３、１００５及び１００７の二つ以上）は被測定媒体２００７の拡散反射光を処理装置２２０９に案内することができる。
処理装置２２０９は、探触子２２０９−１（例えば、光電探触子）を含むことができ、光ファイバプローブからの光信号を探知するために用いられ、それを電信号に変換してさらなる処理に供することができる。光ファイバプローブの配置によって、探触子２２０９−１は、複数の径方向位置（例えば、浮動基準位置内側、浮動基準位置及び／又は浮動基準外側）でのスペクトルデータを探知することができる。
処理装置２２０９はプロセッサ２２０９−２を更に含める。プロセッサ２２０９−２は、探触子２４０１に探知されたスペクトルデータに対して上記のような差分処理を行うように配置されることができる。具体的に、プロセッサ２２０９−２は、被測定媒体における特定成分の濃度変化の伴って拡散反射光の光強度が異なる符号の変化率を有する二つの径方向位置を選択し、この二つの径方向位置でのスペクトルデータに対して重み付け差分処理を行うことができる。
プロセッサ２２０９−２は、例えば汎用コンピューター、専用集積回路（ＡＳＩＣ）、ＦＰＧＡなどの各形式の計算設備を含むことができる。プロセッサ２４０３は、記憶装置に記憶されるプログラム、コードセグメントなどをロードすることによって、上記のような各方法、プロセスに従って動作して、スペクトルデータ差分処理、モデルの構築及び濃度予測を実現することができる。
該処理装置２２０９は、例えばマウス、キーボードなどの、ユーザの命令、データなどを入力するための入力装置２２０９−３と、例えばディスプレイなどの、プロセッサ２４０３の処理結果（例えば、分離した散乱信号／吸収信号、予測結果など）を出力するための出力装置２２０９−４と、をさらに含める。入力装置２２０９−３及び出力装置２２０９−４は組み合ってタッチパネルとして実現されることができる。
本開示の技術は、データ処理装置で実行できるアルゴリズムのプログラムを含むように実現でき、あるいは、非一時的なコンピューター読み取り可能な媒体に記憶されて提供されることができる。
本開示の技術はコンピューターの読み取り可能な媒体におけるコンピューター読み取り可能なコードとして実現されることができる。コンピューター読み取り可能な媒体は、コンピューターの読み取り可能な記録媒体及びコンピューター読み取り可能な伝送媒体を含む。コンピューター読み取り可能な記録媒体は、データをその後コンピューターシステムにより読み取る可能なプログラムとして記憶する任意のデータ記憶装置である。コンピューター読み取り可能な記録媒体の例示は、リードオンリーメモリ（ＲＯＭ）、ランダムアクセスメモリ（ＲＡＭ）、シーディーＲＯＭ（ＣＤ-ＲＯＭ）、テープ、ディスク及び光データの記憶装置を含む。コンピューター読み取り可能な記録媒体はインターネットに接続されるコンピューターシステムにおいて分布されてもよく、これにより、分散的な形式によってコンピューター読み取り可能なコードを記憶して実行する。コンピューター読み取り可能な伝送媒体は、搬送波又は信号によって伝送されることができる（例えば、インターネットを介する有線又は無線データ伝送）。また、本開示技術を実現する機能プログラム、コード及びコードセグメントは、本発明の全体構想の本分野のプログラマーにより容易に解釈されることができる。
以上、複数の実施例に本開示の複数の特徴をそれぞれ説明している。しかしながら、これは、これらの特徴が有利に結合されて使用できないことを意味しない。
以上、本開示の実施例を説明している。しかしながら、これらの実施例は説明するためものであり、本開示の範囲を限定しない。本開示の範囲は権利請求項及びその等価物により限定される。本開示の範囲を逸脱しない限り、当業者は複数の置換及び補正を行え、これらの置換及び補正は全て本開示の範囲に含まれるべきである。

Hereinafter, examples of the present disclosure will be described with reference to the drawings. However, it should be understood that these explanations are merely exemplary and do not limit the scope of this disclosure. In addition, in the following description, in order to avoid unnecessarily confusing the concepts of the present disclosure, the description of the known structure and technology may be omitted.
According to the embodiment of the present disclosure, the first radial position and the second radial position at different positions away from the light source can be arbitrarily selected, and spectral data of these two radial positions are acquired and these are obtained. Is subjected to difference processing. The inventor has found that such delta processing can achieve similarly effective removal of multiple types of interference (particularly common mode interference). Compared with the technique disclosed in Chinese patent application CN1699973A, the trouble of determining the floating reference point can be avoided.
In order to realize better processing effects (for example, suppression of interference and improvement of effective signal), such a first radial position and a second radial position can be selected as follows. For example, it is necessary for the measurement according to the rate of change of diffuse reflection and / or diffusion scattering at different positions away from the light source of the measurement medium depending on the concentration of a specific component (component of interest, for example, blood glucose) in the measurement medium. The radial position (selectable, floating reference position can also be determined) can be acquired. Specifically, the floating reference position can be defined as the light receiving point with the smallest absolute rate of change (eg, near zero), that is, the radial position that is basically insensitive to changes in the concentration of this particular component. it can. For example, as can be seen from the Monte Carlo simulation results of a typical three-layer structure model of human skin, the floating reference position for blood glucose concentration measurement is approximately 1.7 to 3.2 mm away from the light source, and the range of change is large. At the same probe light wavelength, with the floating reference position as the critical point, the glucose concentration increases, the diffuse reflection and / or diffuse scattered light intensity gradually decreases toward the radial position inside the floating reference, and the diameter outside the floating reference. The diffuse reflection and / or diffuse scattered light intensity gradually increases in the directional position, so that the diffuse reflection and / or diffuse scattered light intensity is a negative value inside the floating reference and floats as shown in FIG. It is a positive value outside the reference. Furthermore, the order of diffuse reflection and / or diffuse scattered light intensity is in the middle of the floating reference at a position close to the floating reference position, and it is considered that the sensitivity of these two positions to the change of glucose concentration is in the middle. As the radial distance decreases, that is, the closer to the light source position, the absolute value of the diffuse reflection and / or diffuse scattered light intensity change increases, and the diffuse reflection and / or diffuse scattered light intensity change outside the floating reference. The closer to the light source, the more diffuse reflection and / or the absolute value of the change in diffuse scattered light intensity is about 100 times the outside, and the diffuse reflection and / or diffusion emitted from the epidermis, as compared to the largest. The scattered light intensity value also increases.
According to the above characteristics, the present disclosure submits a spectrum detection method. As shown in FIG. 5, this method measures the first spectral data at the first radial position and the second spectral data at the second radial position of the medium to be measured in operation S501. including. As described above, the first radial position and the second radial position can be arbitrarily selected. That is, the first radial position and the second radial position can be randomly determined. The medium to be measured can include various media such as human skin. For convenience of explanation, the medium to be measured is considered to contain a background medium and certain components in the background medium (ie, the background medium may be other components other than the specific components in the medium to be measured). Such specific components may be of interest, such as blood glucose.
Those skilled in the art are aware of multiple methods of performing spectral measurements and acquiring spectral data. For example, the light source irradiates the measurement medium with probe light having a constant wavelength, and the detector detects the diffuse reflection and / or the diffuse transmission light of the measurement medium, and measures the light intensity thereof, for example. In the following description, diffusely reflected light will be taken as an example, but the present disclosure is not limited to this. Alternatively, both the light source and the detector can penetrate the inside of the medium to be measured and measure the spectral data, which is similar to the case of the infinite medium. The position of the detector can be adjusted to realize measurement of multiple radial positions. Alternatively, the detector can simultaneously detect the light intensity at two or more suitable positions including the two or more light receiving units provided at different positions. This will be described in more detail below.
Further, depending on the characteristics of the medium to be measured and / or a specific component thereof, probe light having one or more wavelengths, for example, ultraviolet, visible light and infrared bands can be selected and measured. For example, a wavelength sensitive to the scattering and / or absorption characteristics of the specific component and / or a wavelength insensitive to the scattering and / or absorption characteristics of the background medium can be selected.
Advantageously, the amount of change in light intensity (absolute and / or relative) (for example, due to the change in the concentration of a specific component in the medium to be measured) can be measured as spectral data. For example, in the case where the background medium does not contain the specific component, or the specific component has a fixed initial concentration value (hereinafter, the background medium + the specific component of the initial concentration is referred to as a "reference medium"). Measure the spectrum in one radial position, and use I as the initial spectrum.₁
Can be described in. Then, when the concentration of the specific component changes with respect to the initial concentration in the background medium, the spectrum of the medium to be measured at this time at this radial position is measured, and I₂
Describe in. For example, for the measurement of blood glucose, first, the blood spectrum on an empty stomach (at this time, the blood glucose is at a stable low level) is measured and used as the initial spectrum; and after meals (at this time, blood glucose). (Changes and gradually stabilizes up to 2 hours after meals) can be measured to obtain information on changes in blood glucose. The amount of (absolute) change in light intensity s = (I) according to these two spectra.₂-I₁) Can be obtained as the above spectral data. However, the spectral data is not limited to the above-mentioned absolute change in light intensity, and other types of data (for example, relative change in light intensity) as described below.

Or s = (I₂-I₁) / I₁) May be obtained.
In many examples of the present disclosure, it is necessary and possible to measure the initial spectrum. The spectrum when the background medium does not contain a specific component may be adopted as the initial spectrum, and the spectrum when the background medium contains a specific component (that is, a reference medium) having an arbitrary fixed initial concentration is adopted as the initial spectrum. You may. For example, for some media (particularly background media that do not contain specific components), a database of initial spectra is constructed and used for duplication (for example, used in advance for experiments and used for actual measurements). ) By doing so, the work load may be reduced.
At the first radial position and the second radial position, the light intensity of the diffuse reflected light and / or the diffuse scattered light of the measurement medium with respect to the probe light has a different rate of change with the change in the concentration of the specific component. As described above, the first radial position and the second radial position can be selected. In addition, since the common mode interference at these two positions generally has a specific relationship, in actual measurement, the common mode interference between these two positions is removed by data processing to change the concentration of the component to be measured. You can leave information about.
Specifically, at the first radial position and the second radial position, the light intensity of the diffuse reflected light and / or the diffuse scattered light of the measurement medium with respect to the probe light differs with the change in the concentration of the specific component. The first radial position and the second radial position can be selected so as to have a sign change rate. Here, the "different sign" can include positive (+) and negative (−), positive (+) and zero (0), or negative (−) and zero (0). That is, in the present application, the zero (0) value is regarded as having a sign different from the positive (+) and negative (−) values. The radial position where the rate of change is zero is, for example, the above-mentioned floating reference position. In actual measurement, a rate of change whose absolute value is smaller than a certain threshold value can be regarded as a "zero" rate of change, and this threshold value may be set according to the actual application environment.
As described below, the first radial position and the second radial position selected in this way contribute to eliminating common mode interference. For example, the first radial position and the second radial position have one positive and negative rate of change (for example, the rate of change of the first radial position is negative and the change of the second radial position). The rate can be selected to be positive). At this time, the first radial position is inside the floating reference position (for example, in the B area shown in FIG. 4) (for example, the A area shown in FIG. 4), and the second radial position is the floating reference position. It is on the outside (for example, area C shown in FIG. 4). Therefore, in a practical application, the first radial position can be selected to be close to the light source position and the second radial position can be selected to be away from the light source position. And, for the majority of cases, the first radial position can be inside the floating reference position and the second radial position can be outside the floating reference position. As a result, the spectral data can be measured at the fixed first radial position and the second radial position, and it is not necessary to determine the exact position of the floating reference position. Further, as will be further described below, it is possible to provide a detector arrangement suitable for a plurality of measurement environments.
The radial position can be selected at the same time as the spectral measurement. For example, some radial positions can be initially selected and the initial spectrum, eg, light intensity (or obtained from the initial spectrum database, as described above), can be measured at these radial positions. Then, after the specific component concentration in the measurement medium changes (or the specific component concentration differs from the specific component concentration used to acquire data from the initial spectrum database), the change occurs at these radial positions. Measure the spectrum, eg light intensity. The direction (positive or negative) of the light intensity change (rate) at each radial position can be determined by the initial spectrum and the change spectrum. It is also possible to acquire the light intensity change (rate) at other radial positions by interpolation. One radial position with a positive change and one radial position with a negative change can be selected as the first radial position and the second radial position, respectively, or the change is positive or negative, respectively. One radial position and one radial position whose change is smaller than a certain threshold (or "zero") (as described above, this radial position can actually be considered a floating reference position). It can be selected as one radial position and a second radial position, and at this time, spectral data at the first radial position and the second radial position are also obtained as described above.
As described above, it is not necessary to determine the floating reference position in advance, and such determination is troublesome (it is necessary to measure a plurality of times to determine the minimum position of the change in light intensity). Of course, this position can also be used if the initially selected radial position includes just the floating reference position. However, this is different from using the spectrum data at this position after determining the floating reference position in advance, and this is because the inconvenience of determining the floating reference position has been eliminated.
According to other embodiments, the position of the floating reference point can also be determined. For example, the smallest radial position of absolute change in light intensity is selected as the floating reference point. It is possible to improve the position accuracy of the floating reference point by making a plurality of measurements near the radial position where the light intensity change is close to zero. Besides that, spectral data at the floating reference point can be acquired.
After acquiring the spectral data at the first and second radial positions as described above, the method also includes performing a difference process on the spectral data in operation S503.
For example, such a difference process can be performed as follows.
The first radial position is ρ_mThe second radial position is ρ_nIs written. Especially when the radial position is inside the floating reference point, ρ_I(The rate of change can be negative); if the radial position is outside the floating reference point, ρ_O(The rate of change can be positive). If the floating reference point is determined in advance, or if the floating reference point is included in the selected radial position, the floating reference point is ρ._RIs written.
According to the embodiment of the present disclosure, the weighting coefficient η can be determined as follows, for example. Diffuse under the influence of the interference factor ΔN at any two radial positions by repeatedly measuring the diffuse reflection light at different radial positions by adopting numerical calculation or keeping the specific component concentration C constant. Ratio of change in reflected light ΔI (ρ_m, C, ΔN) / ΔI (ρ_n, C, ΔN) is obtained and is written as η, that is:

However, ρ_mAnd ρ_nIs any different radial position, eg ρ_I, Ρ_OAnd ρ_RIndicates any two of; ΔI (ρ)_m, C, ΔN) is ρ when the specific component concentration C is fixed_mThe change in light intensity due to the interference factor ΔN is shown in ΔI (ρ)._n, C, ΔN) is ρ when the specific component concentration C is fixed_nThe change in light intensity due to ΔN is shown in.
In the actual measurement process, in addition to the change in the concentration of the component to be measured, there is also a change in the interference factor that causes the change in the diffuse reflected light. When the concentration of the component to be measured changes by ΔC and the interference factor changes by ΔN, it becomes as follows.

However, ρ_iIs any radial position, eg ρ_I, Ρ_OAnd ρ_RIndicates any one of; ΔI (ρ)_i, ΔC, ΔN) is ρ_iThe light intensity change due to the density change ΔC and the interference factor ΔN is shown in ΔI (ρ)._i, C, ΔN) is ρ_iThe change in light intensity due to the interference factor ΔN is shown in ΔI (ρ)._i, ΔC, N) is ρ_iThe change in light intensity due to the change in density ΔC is shown.
According to equation (1), any two radial positions (eg, ρ)_I, Ρ_OAnd ρ_RThe following difference processing can be performed on the spectrum data in any two of the above.

As can be seen from equation (3), such difference processing can effectively reduce or subtract the noise signal due to common mode interference, and is a useful signal (ΔI (ΔC)) only for the component concentration (ΔC) to be measured. ).
In the following explanation, mainly ρ_I, Ρ_OAnd ρ_RAs can be seen from the equation (3), such a difference processing is performed at any two radial positions ρ._mAnd ρ_nIt should be noted that it can be applied to.
Also, any two radial positions ρ_mAnd ρ_nTherefore, the proportionality constant η between the noise signals due to common mode interference can be estimated in advance. In the actual measurement, this proportionality constant can be directly adopted to perform the difference processing on the absolute change in light intensity at both positions, that is, a useful signal regarding only the concentration (ΔC) of the component to be measured (ΔC). ΔI (ΔC)) can be obtained.
Hereinafter, the expression of η is estimated from the stationary solution of the diffusion equation in an infinite medium, and a sample estimation method of the proportionality constant η is given based on this theory.
The solution of the luminous flux Φ for the case of a single point light source in an infinite medium is as follows.・

Where ρ is the radial distance between the detector and the light source; λ is the wavelength of the probe light emitted by the light source; μ_aIs the absorption coefficient; μ_s'Is the equivalent scattering factor, (1-g) μ_sDefined as, g is an anisotropic factor; μ_sIs the scattering coefficient; D is the diffusion coefficient of photons,

Μ_effIs the effective damping coefficient,

Therefore, equation (4) can be described as follows.

After the incident light enters the medium, the photons interact with the particles in the medium and then are emitted to obtain diffuse reflection light. Generally, the factors that cause the diffuse reflection energy change are mainly divided into the following three types. (1) Changes in the optical characteristics of the medium to be measured; (2) Drift of the incident light source; (3) Drift of the detector state, etc. After the incident light enters the medium, the photons collide with the particles in the medium, some photons are absorbed by the particles and lost, the photons in other parts are scattered, and the optical characteristics of the medium to be measured change. Is the result of the combined action of absorption and scattering effects. Factors that cause changes in optical characteristics such as the absorption coefficient and scattering coefficient of the measurement medium mainly include changes in the concentration of the component to be measured, changes in the concentration of interference components, and changes in temperature in the measurement medium. Only the measurement of the concentration change of the component to be measured in the measurement medium is desired as the factor causing the above-mentioned change in diffuse reflection energy, and the change in diffuse reflection light energy due to other influential factors should be reduced or subtracted. is there.
Taking the change in glucose concentration in human tissue as an example, the blood glucose concentration changes due to the steady solution of the diffusion equation in an infinite medium ΔC_gIn the case of, the amount of change in the luminous flux Φ (ρ) due to the change in blood glucose concentration at the same radial position ΔΦ (ρ, ΔC)_g) Is:

However,

As can be seen from equation (6), the amount of change in luminous flux ΔΦ (ρ, ΔC) at a certain wavelength._g) Is a function of the radial distance ρ.
By the definition of the floating reference position, the light receiving point where the rate of change in light intensity at different positions away from the light source in the medium to be measured by the object to be measured is the smallest, that is, the radial position that is not sensitive to changes in the concentration of specific components such as blood glucose. Is the floating reference position. Therefore, in the ideal case, the blood glucose concentration change ΔC_gFloating reference position ρ of blood glucose concentration change by steady solution of diffusion equation in infinite medium at a certain wavelength when there is only and no interference factor_RTo the following sensitivity Sen_g(ρ_R) Is:

The floating reference positions obtained by substituting equations (7) and (8) into (9) are as follows:

At this position, the luminous flux Φ (ρ) due to the change in blood glucose concentration_R) Change amount ΔΦ (ρ)_R, ΔC_g) Is 0 (zero). Then, in the actual measurement process, the floating reference position ρ_RThe change in diffuse reflection light in is due to the change in background interference and is not related to the change in blood glucose concentration, that is,

Usually ∂μ_a/ ∂C_gIs ∂μ_s'/ ∂C_gSince it is 1 to 2 orders lower than that of Eq. (8), it can be obtained approximately by substituting Eq. (8) into Eq. (6):

The rate of change of diffusely reflected light obtained by this is as follows:

In the equation, ∂μ_s'/ ∂C_gIs the rate of change of the equivalent scattering coefficient due to the change in glucose concentration. Usually, for one fixed mother liquor model, the effect of changes in glucose concentration on the equivalent scattering coefficient is constant. For example, for different concentration Intralipid solution models, ∂μ_s'/ ∂C_gCan be expressed as:

∂μ for skin (water + polystyrene) model_s'/ ∂C_gCan be expressed as:

However, as shown in FIG. 6 (Matthias Kohl, Matthias Essenpreis and Mark Cope, The influence of glucose concentration upon the transport of light in tissue-simulating phantoms), the m value is the scattering coefficient due to the wavelength change calculated by the Mie theory. The rate of change of. The two solid curves in the figure are the scattering coefficients μ when the glucose concentration is 85 mM / L and 144 mM / L in the skin (water + polystyrene) model, respectively._sIt shows a curve of change, and the slope that fits it in a straight line is -1.569 * 10 respectively.^-7And -1.5 * 10^-7Since the later simulation is performed by adopting three different slopes of 50, 100, and 150 mM, the calculation is performed by selecting an approximate slope for each.
As a result, as shown in FIG. 23, the rate of change of diffuse reflected light due to the change in glucose concentration dΦ / Φ is approximately considered to be a (substantially linear) function of the radial distance ρ.
In the actual measurement, the relationship between the light intensity I and the energy flux density Φ of light is a fixed multiple relationship, and the relative change in the energy flux density of light is approximately equivalent to the relative change in light intensity, that is,

.. Therefore, the change in ΔI / I due to the change in the measurement position is also linearly approximated.
Therefore, the proportionality constant η between different positions can be estimated as follows.
Using the linear function of ΔI (ρ) / I (ρ) of ρ with the same influencing factor ΔX, the amount of relative change in light intensity at the first radial position ΔI (ρ)_m, ΔX) / I (ρ_m) Causes a relative change in light intensity ΔI (ρ) at the second radial position._n, ΔX) / I (ρ_n) Is estimated, and the ratio of the two is written as ξ, which is related to the selection of the radial position, and is expressed by the following equation (S-1).

(S-1)

In formula (S-1)

Is the insensitive position of this factor action. For example, when glucose changes, this position is the floating reference position for glucose measurement. For a specific object to be measured and a specific medium to be measured

Has been proven to be a relative fixed position. Therefore, two measurement positions

as well as

After is fixed, the value of ξ is one fixed constant value. As can be seen, the value of ξ can be estimated in advance by experiment.
After transforming the formula (S-1), the following formula (S-2) can be obtained.

(S-2)
And

(S-3)
As can be seen from the equations (S-2) and (S-3), after estimating the value of ξ in advance and substituting it into the equation (S-3), the value of the proportionality constant η can be obtained, and η can be obtained. A useful signal (ΔI (ΔC)) regarding the component concentration (ΔC) to be measured by substituting into the equation (3) can be obtained.
The influential factor ΔN that causes the change in diffuse reflected light energy in the actual measurement process is roughly divided into two types for discussion: one type is the change in optical characteristics due to the interference component concentration or the measurement temperature in the measurement medium; One type is light source drift or detector state drift in the measurement system.
(1) Changes in optical characteristics due to interference component concentration or measurement temperature in the medium to be measured
Changes in the concentration of interfering components or the measurement temperature will cause changes in the optical characteristics of the medium to be measured. Taking temperature change as an example, the change in temperature changes the vibration / rotation state and energy transition probability of the molecule, so that the molar extinction coefficient of the substance is slightly different under different temperatures. At the same time, changes in temperature will cause the concentration of the absorbing material to change accordingly, for the following: Increased temperature will increase the degree of chemical bonds between the molecules. However, the number of adjacent molecules of the same molecule increases and the density of the substance increases; however, the increase in temperature also greatly increases the distance between the molecules and reduces the density of the substance. The combined effect of both determines the rule of change in substance concentration with temperature. Blood glucose concentration is relatively constant C_gWhen there is only a temperature change ΔT, the amount of change ΔΦ (ρ, C) of the luminous flux Φ (ρ) caused at the same radial position_g, ΔT) is as follows.

The following equation (17) can be obtained by substituting the equations (7) and (8) into the equation (16).

However,

Is written.
The radial distance away from the light source is ρ_IAnd ρ_OAre obtained as the floating reference inner measurement position and the outer measurement position, respectively, and the floating reference inner measurement position ρ is calculated by Eq. (17)._IAnd floating reference position ρ_RRatio of luminous flux change due to temperature change in, and floating reference outside measurement position ρ_OAnd floating reference position ρ_RThe ratio of the amount of change in luminous flux due to the temperature change in is as follows.

Since the living tissue contains about 70% water, the temperature relative to the living tissue near-infrared spectrum is related to the temperature characteristics of the water spectrum to a large extent. Figure 7 shows the water molar extinction coefficient ε obtained by Jensen et al. At 32 ° C to 42 ° C._w(λ) and ε at 30 ° C_wDifference curve diagram between (λ) (Peter Snor Jensen, Jimmy Bak, Stenfan Andersson-Engels, Influence of temperature on water and aqueous glucose absorption spectra in the near- and mid-infrared regions at physiologically relevant temperatures, Applied Spectroscopy, 2003 , 57 (1): 28-36). Ε at other wavelengths, except that it is not sensitive to temperature changes at 1440 nm, 1780 nm, 2180 nm, 2750 nm, 4900 nm, 5300 nm, and 6300 nm._w(λ) changes regularly as the temperature changes. Therefore, the rate of change in the molar extinction coefficient with temperature ∂ε under each wavelength within the range of changes in human body temperature (about 35 ° C to 40 ° C)._w(λ) / ∂T is a constant, but it is approximately considered that this constant takes different values for different wavelengths. As a result, the rate of change in the extinction coefficient with temperature under each wavelength ∂μ_a(λ) / ∂T is also approximated to a constant. Similarly, Chen Lin et al. Performed a spectrum measurement experiment on a water sample having a temperature range of 30 ° C. to 40 ° C. at intervals of 2 ° C. to obtain water at different temperatures and 30 ° C. below as shown in FIG. We have obtained the absorbance change curve between water in 1525, 1832, and 2060 nm, and the linear relational expression between the amount of change in absorbance and temperature (Chen, near-infrared non-invasive blood glucose measurement-reference wavelength floating). Standard method research: "Doctoral degree thesis", Tianjin, Tianjin University, 2009). As can be seen from the figure, under each wavelength, the amount of change in absorbance and the temperature approximate a linear relationship. Since water is a pure absorption medium, the same conclusion is that the rate of change of the absorption coefficient with temperature under each wavelength ∂μ_aIt can be obtained that (λ) / ∂T is considered to be close to a constant.
Laufer et al. Adopted an in vitro skin sample experiment to study the relationship between temperature effects on the human dermis layer and subcutaneous tissue within the range of 25 ° C to 40 ° C (Jan Laufer, et al., Effect of temperature on the). optical properties of ex vivo human dermis and subdermis, Phys. Med. Biol., 1998, 43: 2479-2489). The experimental results show that the rate of change in the equivalent scattering coefficient of the dermis layer due to temperature changes is (4.7 ± 0.5) × 10.^-3℃^-1The change in the equivalent scattering coefficient of the subcutaneous tissue due to the temperature change is (-1.4 ± 0.28) × 10^-3℃^-1It shows that. Therefore, within the range of changes in human body temperature (about 35 ° C to 40 ° C), the rate of change in the equivalent scattering coefficient due to temperature changes ∂μ_s'/ ∂T approximates a constant.
Therefore, as can be seen from Eqs. (18) and (19), the floating reference inner measurement position ρ_I,
Floating reference position ρ_RAnd floating reference outside measurement position ρ_OWhen is determined, the ratio of the amount of change in luminous flux due to temperature change under the same wavelength ΔΦ (ρ)_I, C_g, ΔT) / ΔΦ (ρ)_R, C_g, ΔT) and ΔΦ (ρ)_O, C_g, ΔT) / ΔΦ (ρ)_R, C_g, ΔT) are all constants, respectively η₁And η₂To describe. That is:

Therefore, the amount of change in diffuse reflected light intensity due to temperature change can be regarded as common mode interference. Among them, for the medium to be measured whose optical parameters are known, the constant η according to the equations (18) and (19).₁And η₂Can be calculated; for a medium to be measured whose optical parameters are unknown, the optical parameters of the medium to be measured are calculated by a method of reconstructing the optical parameters by adopting the diffuse reflection spectrum obtained by measurement. And further by equations (18) and (19) the constant η₁And η₂Or when the blood glucose concentration is kept relatively constant, the amount of change in diffusely reflected light at the time of temperature change is repeatedly measured, and the constant η is calculated by equations (20) and (21).₁And η₂Calculate the value of (for example, take the average of multiple measurements).
In the actual measurement process, the glucose concentration is ΔC_gWhen the measured temperature changes by ΔT at the same time, the amount of change in the luminous flux Φ (ρ) due to these two factors at the same radial position ΔΦ (ρ, ΔC)_g, ΔT) is as follows.

However, ΔΦ (ρ, ΔC_g, T) are useful signals awaiting measurement of interest, ΔΦ (ρ, C)_g, ΔT) is a common mode interference signal with respect to the radial position.
Next, according to equations (11) and (22), the floating reference inner measurement position ρ_I, Floating reference position ρ_RAnd floating reference outside measurement position ρ_OWith ΔC_gAmount of change in luminous flux Φ (ρ) due to and ΔT ΔΦ (ρ)_I, ΔC_g, ΔT), ΔΦ (ρ)_R, ΔC_g, ΔT) and ΔΦ (ρ)_O, ΔC_g, ΔT) are as follows.

The following equation can be obtained by weighting the difference between equations (23) and (24) in equation (20).

As can be seen from Eq. (26), the common mode interference amount of the diffuse reflection light change due to the temperature change is the floating reference inside measurement position ρ._IAnd floating reference position ρ_RIt is removed by the difference calculation of the amount of change in diffusely reflected light in, and a useful signal regarding only the change in blood glucose concentration can be obtained.
Similarly, according to equations (21), (24) and (25), the floating reference outer measurement position ρ_OAnd floating reference position ρ_RSimilarly, the common mode interference amount of the diffuse reflection light change due to the temperature change can be removed by the difference calculation of the diffuse reflection light change amount in.

Equations (26) and (27) are the floating reference inner measurement positions ρ, respectively._ISignal and floating reference outside measurement position ρ_OFloating reference position ρ by adopting the signal at_RBy combining the signals in the above, a useful signal regarding only the change information of the blood glucose concentration is effectively obtained, and the interference of the common mode noise is subtracted.
As can be seen from equations (20) and (21), the floating reference inner measurement position ρ_IAnd floating reference outside measurement position ρ_OWhen is determined, the ratio of the amount of change in luminous flux at the two measurement positions due to temperature changes under the same wavelength ΔΦ (ρ)_I, C_g, ΔT) / ΔΦ (ρ)_O, C_g, ΔT) is also a constant, η₃Write.

That is:

Then, according to the equations (23), (25) and (29), the measurement signals at the floating reference inner measurement position and the outer measurement position are differentially calculated to obtain the following equation.

As can be seen from equation (30), the floating reference inner measurement position ρ_IAnd outer measurement position ρ_OBy the difference calculation of the amount of change in diffusely reflected light in, the purpose of similarly removing the amount of common mode interference of the change in diffusely reflected light due to temperature change and obtaining a useful signal regarding only the change in blood glucose concentration can be achieved. As can be seen from FIG. 4, the floating reference inner measurement position ρ due to the change in blood glucose concentration._IAnd outer measurement position ρ_OThe direction of the amount of change in the diffusely reflected light is opposite, and adopting the difference calculation method in Eq. (30) also increases the absolute value of the weak and useful signal and improves the specificity of the signal waiting for measurement. However, more accurate measurement results have been obtained.
The common mode interference signal due to the change in the concentration of the interference component on the medium to be measured can be subtracted by adopting a similar method.
(2) Light source drift or detector state drift in the measurement system
When the light intensity of the incident light source drifts or the detector state for detecting the diffuse reflected light drifts, it causes a change in the diffuse reflected light intensity value. Taking the example of drifting the light intensity of an incident light source, the blood glucose concentration is relatively constant C_gWhen the light intensity of the incident light source changes by ΔF times, the amount of change in the luminous flux Φ (ρ) caused by the same radial position ΔΦ (ρ, C)_g, ΔF) is as follows.

However, Φ₀(ρ) indicates the initial value of the diffuse reflected light intensity at this measurement position. The radial distance away from the light source is ρ_IAnd ρ_OThe two positions are taken as the floating reference inner measurement position and the outer measurement position, respectively, and according to equation (31), the floating reference inner measurement position ρ_IAnd floating reference position ρ_RThe ratio of the amount of change in luminous flux due to the drift of the light intensity of the incident light source, and the floating reference outside measurement position ρ_OAnd floating reference position ρ_RThe ratio of the amount of change in luminous flux due to the drift of the light intensity of the incident light source is as follows.

Equations (32) and (33) can also be extended to any two measurement positions. Transform the formula

As you can see, the amount of relative change in light intensity at any measurement position

Are all the same and can be regarded as one fixed value, that is, in FIG. 23, when there is only light source drift interference, the line of action is one straight line parallel to the horizontal axis, and then the equation (S-3). )
The value of is about 1, and the equation (S-3) is simplified to the equation (S-4). That is,

(S-4)
FIG. 24 shows the results of measuring the diffuse reflected light with respect to the intralipid 3% solution. After changing the output power of the diffused light to simulate the drift of the light source and changing it five times in a row, three different measurement positions can be found, and the relative change in the diffuse reflected light intensity is consistent. The phenomenon is exhibited, that is, the value of ξ can be described as about 1.
Floating reference inside measurement position ρ_I, Floating reference position ρ_RAnd floating reference outside measurement position ρ_OWhen is confirmed, since the initial value of the diffuse reflected light intensity at each measurement position is known and confirmed, the ratio of the amount of change in the luminous flux due to the drift of the light intensity of the incident light source under the same wavelength ΔΦ (ρ)._I, C_g, ΔF) / ΔΦ (ρ_R, C_g, ΔF) and ΔΦ (ρ)_O, C_g, ΔF) / ΔΦ (ρ_R, C_g, ΔF) are all constants, respectively η_FourAnd η_FiveThat is, there is the following formula.

Therefore, the amount of change in the diffuse reflected light intensity due to the drift of the light intensity of the incident light source can be regarded as common mode interference. However, η_FourAnd η_FiveThe value of is obtained by repeatedly measuring the amount of change in diffusely reflected light when the temperature changes while the blood glucose concentration is kept relatively constant, and calculating by equations (34) and (35).
In the actual measurement process, the glucose concentration is ΔC_gWhen the light intensity value of the incident light source drifts ΔF times at the same time as the change, the amount of change ΔΦ (ρ, ΔC) of the luminous flux Φ (ρ) due to these two factors at the same radial position_g, ΔF) is as follows.

In the actual measurement process, ΔF is 10.^-3~Ten^-2It is an order and a product

Can be ignored. Equation (36) can be written as follows.

However, ΔΦ (ρ, C_g, ΔF) is a common mode interference signal related to the radial measurement position, and ΔΦ (ρ, ΔC)._g, F) are useful signals awaiting measurement of interest.
Then, according to the equations (11) and (37), the floating reference inner measurement position ρ_I, Floating reference position ρ_RAnd floating reference outside measurement position ρ_OWith ΔC_gAmount of change in luminous flux Φ (ρ) due to and ΔF ΔΦ (ρ)_I, ΔC_g, ΔF), ΔΦ (ρ_R, ΔC_g, ΔF) and ΔΦ (ρ)_O, ΔC_g, ΔF) are as follows.

The following equation can be obtained by performing a difference calculation between equations (38) and (39) with equation (34).

As can be seen from the equation (38), the common mode interference amount of the diffuse reflection light change due to the drift of the light intensity of the incident light source is the floating reference inner measurement position ρ._IAnd floating reference position ρ_RIt is removed by the difference calculation of the amount of change in diffusely reflected light in, and a useful signal regarding only the change in blood glucose concentration can be obtained.
Similarly, according to equations (35), (39) and (40), the floating reference outer measurement position ρ_OSum and floating reference position ρ_RSimilarly, the common mode interference amount of the diffuse reflection light change due to the drift of the light intensity of the incident light source can be removed by the difference calculation of the diffuse reflection light change amount in.

Equations (41) and (42) are the floating reference inner measurement positions ρ, respectively._ISignal and floating reference outside measurement position ρ_OFloating reference position ρ by adopting the signal at_RBy combining the signals in, we have effectively obtained a useful division only for blood glucose concentration change information, subtracting the interference of common mode noise.
As can be seen from equations (34) and (35), the floating reference inner measurement position ρ_IAnd floating reference outside measurement position ρ_OWhen is determined, the ratio of the amount of change in the luminous flux at the two measurement positions due to the drift of the light intensity of the incident light source under the same wavelength ΔΦ (ρ)_I, C_g, ΔF) / ΔΦ (ρ_O, C_g, ΔF) is also a constant, η₆Write.

That is:

Then, according to the equations (38), (40) and (44), the measurement signals at the floating reference inner measurement position and the outer measurement position are differentially calculated to obtain the following equation.

As can be seen from equation (45), the floating reference inner measurement position ρ_IAnd outer measurement position ρ_OBy calculating the difference in the amount of change in diffusely reflected light in, the common mode interference amount of the change in diffusely reflected light due to the drift of the light intensity of the incident light source is removed, and the purpose of obtaining a useful signal only for the change in blood glucose concentration is similarly achieved. It is possible to improve the universality of the floating reference measurement method and increase the absolute value of weak and useful signals.
Common mode interference signals due to detector state drift to detect diffuse intensity can be subtracted using a similar method.
As can be seen from this, in the operation 503, the spectral data at the first and second radial positions are subjected to the difference processing, and the two different interference factors are subjected to the common mode by the weighted difference as shown in the equation (3). The interference signal can be removed. Diffuse signals measured under other different wavelengths are modified in a similar manner and the weighted difference processed effective signal ΔΦ (λ) under each wavelength._i, C_g) Can be obtained.
According to the embodiments of the present disclosure, different reception methods can be adopted to detect spectral signals at different positions.
If the offset of the floating reference position is not so large due to changes in different measurement sites, different measurement wavelengths, or different measurement media on the same measurement medium, the diffuse reflection spectra at different positions can be extracted as follows. it can.
1) As shown in FIG. 9A, the spectral signal at the position inside the floating reference (area A in FIG. 4) from the light source is received as a measurement point, and the floating reference position (area B in FIG. 4) is received. Receives the spectral signal at as a reference point;
2) As shown in FIG. 9B, the light receiving point having the smallest absolute rate of change, that is, point B is selected as the floating reference position, and the light receiving point having the local maximum value of the rate of change, that is, point C is the measurement point. Select as;
3) As shown in FIG. 9 (c), the position inside the floating reference from the light source (area A in FIG. 4), the floating reference position (area B in FIG. 4), and the position outside the floating reference from the light source (area B in FIG. 4). The spectral signals in the area C) in FIG. 4 are simultaneously received, and the spectral signals inside and outside the floating reference are weighted and differentially processed.
When the offset of the floating reference position is large and it is difficult to determine the floating reference position due to changes in different measurement parts, different measurement wavelengths, or different measurement media of the same measurement medium, diffuse reflection at different positions is performed as follows. The spectrum can be extracted. Specifically, for different measurement sites, different wavelengths, or different measurement individuals of the same measurement individual, the difference in optical parameters greatly affects the determination of the floating reference position. Therefore, as shown in FIG. 3, the measurement site and measurement wavelength The floating reference position changes accordingly with the change of. As a result, as shown in Fig. 9 (d), the reception radius inside the floating reference is appropriately reduced by utilizing the special conquest that contains the same noise information inside and outside the floating reference from the light source, and the outside of the floating reference is outside. The radial radius is smaller than the floating reference position (Area A in Figure 4) and the floating reference position by increasing the receiving radius to ensure that none of the floating reference positions at each wavelength or location is included. By receiving each of the larger diffusely reflected light (area C in Fig. 4), the weighted difference analysis calculation is performed for the spectra on both the inside and outside of the floating reference position.
FIG. 10A schematically shows an optical fiber probe structure according to an embodiment of the present disclosure. As shown in FIG. 10, the fiber optic probe 1000 can include a plurality of fiber optic bundles 1001, 1003, 1005 and 1007 coated in a cladding. Each optical fiber bundle may include one or more fibers. Among them, the optical fiber bundle 1001 is used to guide the incident light from the light source, and the optical fiber bundles 1003, 1005 and 1007 are used to guide the diffuse reflected light from the measurement medium. More specifically, the optical fiber bundle 1003 is used to guide the diffusely reflected light from the radial position inside the floating reference position, and the optical fiber bundle 1005 is used to guide the diffusely reflected light from the floating reference position. The optical fiber bundle 1007 is used to guide diffusely reflected light from a radial position outside the floating reference position, and these optical fiber bundles are focused from the N end. The incident light guided to the optical fiber bundle 1001 can be emitted from the M end, and the optical fiber bundles 1003, 1005 and 1007 can receive diffuse reflected light from the M end. As a result, the M end can be called the detection end face of the optical fiber probe 1000.
It should be noted here that the "optical fiber bundle" described here is a logical partition due to these functions. Physically, all fibers may be mixed and there may be no clear grouping.
Although FIG. 10A shows four optical fiber bundles, the present disclosure is not limited to this. For example, it may contain more or less fiber optic bundles. The arrangement of these optical fiber bundles is also not limited to the layout shown in FIG. 10 (a). For example, the optics in each optical fiber bundle can even be entangled in the clad.
10 (b) -10 (e) schematically show cross-sectional views at the M end of the optical fiber probes of different embodiments of the present disclosure. In the figure, each circular pattern can indicate the end face of the fiber in the optical fiber bundle.
As shown in FIG. 10B, the optical fiber bundle 1001 for guiding the incident light can be located substantially at the center. The optical fiber bundle 1003 can be installed around the optical fiber bundle 1001 and the optical fiber bundle 1007 can be installed so as to rotate around the optical fiber bundle 1001 and relatively away from the optical fiber bundle 1001. .. Further, the optical fiber bundle 1005 can be installed between the optical fiber bundles 1003 and 1007 by rotating around the optical fiber bundle 1001. Different sized fiber optic probes can be designed due to the difference in the floating reference position of different objects to be measured.
In the actual measurement, the end face of the optical fiber bundle 1005 is approximately aligned with the floating reference position (if it exists and is determined, or its approximate range is known), and the diffuse reflection in the optical fiber bundles 1003 and 1005 is 1007. The fiber optic probe 1000 is left unattended so that optical signals (ie, spectral signals at the floating reference position and inside and outside the floating reference position) can be extracted. Alternatively, the diffusely reflected light signals in the optical fiber bundles 1003 and 1007 (that is, the spectral signals inside and outside the floating reference; for example, when the floating reference position is not accurately determined, or the end face of the optical fiber bundle 1005 is a floating reference. Roughly aligned to the approximate area of the position and not exactly aligned to the floating reference position), or the diffuse signal at the fiber bundles 1003 and 1005 (ie, the spectral signal inside the floating reference and at the floating reference position). ), Or only the diffusely reflected light signals in the optical fiber bundles 1005 and 1007 (that is, the floating reference position and the spectral signal outside the floating reference) may be extracted.
FIG. 10C shows an arrangement that does not include the optical fiber bundle 1007 but includes the optical fiber bundles 1001, 1003, and 1005. With such an arrangement, spectral signals inside the floating reference position and at the floating reference position can be received.
FIG. 10D shows an arrangement that does not include the optical fiber bundle 1005 but includes the optical fiber bundles 1001, 1003, and 1007. With such an arrangement, spectral signals inside the floating reference position and outside the floating reference position can be received.
FIG. 10E shows an arrangement that does not include the optical fiber bundle 1003 but includes the optical fiber bundles 1001, 1005, and 1007. With such an arrangement, it is possible to receive spectral signals at the floating reference position and outside the floating reference position.
Normally, the distance between the end face of the optical fiber bundle 1005 and the end face of the optical fiber bundle 1001 with respect to the floating reference position is a roughly definite numerical value (in the above arrangement, the end face of the optical fiber bundle 1005 orbits the end face of the optical fiber bundle 1001. (Appears in a circular shape with a predetermined radius); the distance between the end face of another optical fiber bundle 1003/1007 and the end face of the optical fiber bundle 1001 is within a certain range (in the above arrangement, the end face of the optical fiber bundle 1003/1007). Appears in a ring shape around the end face of the optical fiber bundle 1001).
It should be noted here that in FIGS. 10 (b) to 10 (e), the end faces of the respective optical fibers in the optical fiber bundles 1003, 1005 and 1007 are formed into a substantially circular shape or a ring shape around the optical fiber bundle 1001. Although shown to be closely aligned, the present disclosure is not limited to this. For example, they may not be closely arranged and may be sparsely arranged; or they may not form a perfect circular or ring-shaped pattern, but only a portion of such a pattern.
In an actual measurement environment, the measurement position and the reference position can consist of physically feasible points, but they are geometric figures consisting of a set of multiple points with the same characteristics other than points, regardless of whether they are incident or emitted. It may have a circular shape, a ring shape, a rectangular shape, and the like.
According to the embodiment of the present disclosure, the relative change amount of the light intensity is adopted as the spectral data and differentiated, and only the measurement information regarding the density change is reserved.
The inventor has already discovered that the relative change in light intensity along the radial position ρ also exhibits a linear or linear approximation. With reference to the above discussion, for example, as can be seen by combining the explanations in FIG. 23, the above difference processing is similarly applied to the amount of relative change in light intensity. For example, multiplicative noise can be removed by directly differentiating the relative changes in light intensity at the two radial positions; the relative changes in light intensity at the two radial positions are factored as described above. Additive noise can be removed by performing weighted difference processing using η.
FIG. 11 shows a general principle of concentration prediction using spectral data. As shown in FIG. 11, a series of known concentrations {C on the background medium or reference medium (including the background medium and specific components of the initial concentration)._i} Is inserted, and the spectrum data {I (ρ)} corresponding to it is acquired respectively. Data set of these known concentrations
And a set of appropriate spectral data
Allows you to build a predictive model. Then, the unknown concentration (or concentration change) C'of the specific component on the background medium or the reference medium_iHowever, the spectrum data I'(ρ) (“Y”) corresponding to the spectrum data can be acquired. The concentration (“X”) can be predicted by I'(ρ) and the prediction model M.
As mentioned above, the spectral data can include various compatible data such as light intensity changes and relative changes of diffuse reflection and / or diffuse scattered light.
When modeling, the spectrum of the background medium or reference medium can be measured as the initial spectrum and the known concentration {C_iThe spectrum after the characteristic component of} is added can be measured as a measurement spectrum, and light intensity change information can be obtained from this. When predicting, the spectrum of the background medium or the reference medium (when the initial concentration of the specific component is modeled on the reference medium, it may be the same as or different from the initial concentration of the specific component on the reference medium) can be measured as the initial spectrum. It is possible to measure the spectrum after the change in the concentration of the specific component as the measurement spectrum, and it is possible to acquire the light intensity change information. The predicted value may be a relative concentration value (that is, the amount of change in concentration), or an initial value (0 in the case of the background medium; the above initial concentration in the case of the reference medium) may be added to obtain the predicted concentration value. good.
According to the examples of the present disclosure, the influence of the interference factor can be effectively removed by performing the above-mentioned difference processing on these spectral data. For example, a chemometric method is used to build a prediction model M. Specifically, the data after the difference processing can be modeled by adopting the least squares method, and a net signal model can be further constructed.
The prediction model M can be pre-built for the background / reference medium and specific components and stored in, for example, a database or server. The prediction model M can be obtained from the database or server if necessary.
Here, such a modeling and / or concentration prediction method is submitted. With reference to FIG. 12, spectrum data can be acquired in operation S1201. For example, when modeling, the known concentration {C_iIt is possible to obtain spectral data (for example, light intensity change information before the specific component is added) to the background medium or the reference medium after the specific component is added; Spectral data (for example, light intensity change information before the change in the specific component concentration) can be acquired for the background medium or the reference medium in which the specific component concentration has changed. Subsequently, in operation S1203, the difference processing can be performed on the spectrum data. For example, the difference processing is performed on the spectrum data at two positions where the signs of the light intensity change rates are different. Then, in operation S1205, modeling or prediction can be performed using the difference signal after processing. The process of FIG. 12 is basically the same when applied to modeling and when applied to prediction, the distinction is as follows: When modeling, the concentration of a particular component is known and the concentration (
) And spectral data (
) To obtain the predicted model (M); when predicting, the concentration (or concentration change) of the specific component is unknown, and the predicted concentration (or concentration) is obtained by the spectral data (Y) and the predicted model (M). Change) (X) is to be obtained.
According to the examples of the present disclosure, such a modeling / prediction method can be applied to non-invasive blood glucose concentration measurement in the human body. In this case, the wavelength of the probe light may be in the range of about 1.0 to 2.4 μm.
According to one example, the floating reference position of the 5% intralipid solution can be determined by the Monte Carlo simulation method, and the drift of the light source can be simulated by the change in the number of incident photons.
FIG. 13 shows the floating reference position calculation result of the Monte Carlo simulation for the intralipid solution having a concentration of 5%. The optical parameters used in the simulation, including absorption coefficient, scattering coefficient, each anisotropy factor and scattering coefficient, are Tamara L. Troy & Suresh N. Thennadil, Optical properties of human skin in the near infrared wavelength range of 1000 to 2200. From nm, Journal of Biomedical Optical, 2001, 6 (2): 167-176., The simulation wavelength range is 1100 to 1600 nm. Each glucose concentration is 0-100 mM, the interval is 10 mM, and the number of photons is 10.⁹Is. The difference between the diffuse reflected light from the intralipid solution under different glucose concentrations and the diffuse reflected light from the pure intralipid solution containing no glucose was calculated, and the wavelength range was 1,100 to 1600 nm, and the floating reference position was about 0.9 to. It can be seen that it changes within a range of 2 mm. It shows that there is a large difference in the reference position of the same individual or sample under different wavelengths.
Therefore, the diffuse reflection light reception plan shown in FIG. 9D can be adopted. Specifically, the spectra at both the inside and outside of the floating reference from the light source are received at the same time. In FIG. 14, the number of incident photons is 10.⁹In this case, the amount of change in the number of diffuse reflected photons when the glucose concentration changes between 50 mM and 100 mM under a wavelength of 1300 nm.
Usually, the measured signal is a useful signal due to changes in glucose concentration I_SAnd noise signals related to human physiology background or changes in the external environment I_NDivide into, that is,

However, I_SIs glucose concentration C_gRelated to I_NIs mainly affected by physical factors such as light source drift, temperature, pressure and displacement. Here, only noise interference due to light source drift is considered. As a result, the change in the measured light intensity I due to the drift of the light source and the change in blood glucose concentration is as follows.

However, ρ is the radial distance between the detector and the light source (the radial radial position of the spherical coordinates in the Monte Carlo simulation), and ΔC._gIs the amount of change in blood glucose concentration, and ΔN is the amount of change in the background. ΔI_S(ρ, ΔC_g, N) is valid glucose concentration information, and this part of the information is needed. Background interference signal ΔI_N(ρ, C_g, ΔN) is not related to glucose concentration information and usually changes irregularly, ΔI (ρ, ΔC)_g, ΔN) is the main reason why it is difficult to extract glucose concentration change information.
Reference position ρ_RSo, the diffuse reflected light intensity is not sensitive to changes in glucose concentration or is not related to changes in glucose concentration, and there are the following:

The change in light intensity at the reference position is entirely caused by background interference and includes:

Correspondingly, the changes in diffuse reflection light intensity at the measurement positions inside and outside the floating reference are as follows, respectively.

Reference position ρ_RBackground interference change ΔI_N(ρ_R, C_g, ΔN), and the background interference change at the measurement position are fixed because they are fixed.

However, η₁And η₂Is a proportional coefficient. It should be noted that when selecting different radial positions or different measurement radii as measurement positions, the resulting multiple relationships are different, i.e., appropriate weighting factors should be selected. In the actual measurement process, it can be obtained by repeated measurement when the glucose concentration is kept relatively constant. The following effective glucose signal expression can be obtained by the difference calculation by the equations (49) to (53).

Equation (54) allows only information on the inside of the floating reference and the floating reference measurement position to be used for further cheometric modeling analysis; equation (55) provides only information on the outside of the floating reference and the floating reference position It can be adopted to perform cheometric modeling analysis. When the information on the floating reference position is not completely adopted, the following equation is obtained by dividing equations (52) and (53).

This allows a valid measurement signal ΔI by adopting a floating reference inner-outer reception strategy._IO(ΔC_g) Can be obtained.

The blood glucose information obtained by differentially processing the diffuse reflection signal based on the floating reference position has higher specificity than the diffuse reflection light intensity change information obtained by direct measurement, and is actually measured. The background interference in is effectively subtracted.
In this embodiment, the drift of the light source is simulated by changing the number of incident photons, and the change range is ± 20%. As can be seen from FIG. 13, at a wavelength of 1300 nm, the floating reference position of glucose is around 1.3 mm, so that the position in the radial direction is 0.7 to 0.9 mm as in area A in FIG. Can be selected as the floating reference inner measurement position and the measured spectrum is I (ρ)_I); As shown in area B in FIG. 14, the position where the radial position is 1.3 mm is selected as the floating reference position, and the measured spectrum is I (ρ)._R); As shown in area C in FIG. 14, a position having a radial position of 1.8 mm to 2.0 mm is selected as the floating reference outer measurement position, and the measured spectrum is I (ρ)._O).
When glucose is not contained in the solution, that is, only the noise signal of the light source drift is contained, the same measurement position emits a noise signal corresponding to the light source drift. Table 1 shows the number of diffusely reflected photons at different measurement positions with different numbers of incident photons obtained from the results of the Monte Carlo simulation. The number of incident photons is 10⁹Table 2 shows the amount of change in the number of diffusely reflected photons at the appropriate measurement position when the change is ± 20%. The relative change in the number of diffusely reflected photons is shown in Table 2-1. As can be seen, the relative changes in the number of diffusely reflected photons are basically the same at the three measurement positions. Therefore, the ratio ξ of the relative change in the number of diffused photons at any two positions is about 1.

Since the glucose concentration does not change at this time, the measured signal change amount is considered to be completely caused by the change in the light source drift, that is, the signal change amount measured at this time is considered to be a noise signal. Therefore, as shown in Table 3, the ratio of noise interference at different measurement positions can be calculated.


Table 3

The ratio of the absolute change in noise interference at any two positions in Table 3 is also directly obtained by the following method.
Since ξ is determined to be 1, as shown in Table 3-1 directly, the equation (S-3) is used.
The value of η can be obtained.

Comparing Table 3 and Table 3-1 the actually obtained η value is basically in agreement with the η value estimated by adopting the equation (S-3).
As can be seen from Tables 3 and 3-1 when the glucose concentration does not change and only the light source drifts, it is as follows:
Floating reference inner measurement Position signal change amount ΔI_N(ρ_I, ΔC_g, ΔN) is the amount of change ΔI of the floating reference measurement position signal_N(ρ_R, ΔC_g, ΔN) is about 7.0 times, that is, ΔI_N(ρ_I, ΔC_g, ΔN) = 7.0ΔI_N(ρ_R, ΔC_g, ΔN) ；
Floating reference outer measurement Position signal change amount ΔI_N(ρ_O, ΔC_g, ΔN) is about 1.06 times the amount of change in the floating reference measurement position signal, that is, ΔI._N(ρ_{o o}, ΔC_g, ΔN) = 1.06ΔI_N(ρ_R, ΔC_g, ΔN) ；
Floating reference inner measurement Position signal change amount ΔI_N(ρ_I, ΔC_g, ΔN) is the amount of change ΔI of the floating reference outside measurement position signal_N(ρ_O, ΔC_g, ΔN) 6.6 times, that is, ΔI_N(ρ_I, ΔC_g, ΔN) = 6.6ΔI_N(ρ_O, ΔC_g, ΔN).
When both the glucose concentration and the light source change, the change in light intensity at the floating reference position is not related to the change in glucose concentration, that is, the change in light intensity at this position is entirely caused by the light source drift. Therefore, the useful signals due to the changes in glucose concentration inside and outside the floating reference obtained by the formulas (54) and (55) are as follows, respectively.

Table 4 shows the corresponding glucose concentrations and the number of incident photons, each with six different glucose diffuse reflection spectra selected.

As shown in FIG. 15, when the glucose concentration changes by 20, 40, 60, 80 and 100 mM, respectively, when not corrected for the light source drift, the diffuse reflection photon number change curve at different radial positions away from the light source. That is, the curve for measuring the diffuse reflected light intensity does not show a regular increasing or decreasing change depending on the glucose concentration. That is, the signal change due to the light source drift covers the characteristic signal of the glucose concentration change.
Similarly, the floating reference inner measurement position is set to 0.7 to 0.9 mm, the reference position is set to 1.3 mm, and the outer measurement position is set to 1.8 to 2 mm. As shown in Table 5, the change in the number of diffusely reflected photons at each measurement position is obtained under the change in glucose concentration before the correction for the light source drift.

Equations (58) and (59) are used to combine the information of the floating reference position to correct the light source drift for the amount of change in the number of diffuse reflected photons at the measurement position inside and outside the floating reference. It is shown in Table 6.

As can be seen from FIG. 16, at the floating reference inner measurement position, as the glucose concentration change increases, the number of diffusely reflected photons gradually decreases, and the amount of change is negative; at the floating reference outer measurement position. As the change in glucose concentration increases, the number of diffusely reflected photons changes in order, and the amount of change is a positive value. That is, the influence of the light source drift is effectively removed.
If the measurement information at the floating reference position is not completely adopted, as can be seen from the above calculation, the amount of change of the floating reference inner measurement position signal ΔI_N(ρ_I, ΔC_g, ΔN) is the amount of change in the floating reference outside measurement position signal ΔI_N(ρ_O, ΔC_g, ΔN) is about 6.6 times, that is, ΔI_N(ρ_I, ΔC_g, ΔN) = 6.6ΔI_N(ρ_O, ΔC_g, ΔN), weighting difference calculation is performed on the floating reference inner and outer measurement signals measured by the equation (57) to obtain the following.

That is, the obtained signal is the weighted sum of the floating reference inner and outer effective signals, and the noise due to the light source drift is completely removed.
Formula (60) is adopted, the floating reference position information is not completely adopted, and only the measurement signals inside and outside the floating reference position are adopted to correct the situation where not only the above glucose concentration change but also the light source drift exists. And ΔI at the calculated different glucose concentration changes_IO(ΔC_g) The results are shown in Table 7. The result shows the valid signal ΔI obtained by the weighting difference processing for the floating reference inner and outer measurement signals as the amount of change in glucose concentration gradually increases._IO(ΔC_g) Tends to increase in order, effectively eliminating the effect of common mode interference due to light source drift.

The effective signal ΔI under each wavelength obtained by correcting the light source drift by adopting a similar method for other spectral signals measured under different wavelengths and further performing weighting difference processing._S(λ_i) Can be combined with the corresponding series of reference concentration parameters to construct a partial least squares mathematical model and predict the unknown concentration spectral concentration.
According to another example, the Monte Carlo simulation method can analyze the situation when the temperature to be measured changes with the inside-outside of the floating reference from the light source as the reception plan.
It has been discovered that for a 2% intralipid solution, if the wavelength is greater than 1400 nm, there is no floating reference position, that is, if the wavelength is greater than 1400, the theory of floating reference measurement methods is no longer applicable. For this purpose, a Monte Carlo simulation is performed here using an intralipid solution having a concentration of 2% as a model for the state of change in diffused reflected light due to the glucose concentration and temperature at a wavelength of 1600 nm. The glucose concentration change range is 0 to 100 mM and the interval is 20 mM; the temperature change range is 32 ° C to 40 ° C and the interval is 0.5 ° C; the number of incident photons is 10.¹¹The absolute number of photons diffusely reflected after passing through the sample is used as the emitted light. When the temperature changes, the amounts of change in the absorption coefficient and the scattering coefficient are as follows.

Taking 1600 nm as an example, the relative change amount of the diffused light due to the obtained temperature is shown in FIG. 25 with reference to the emitted light of 32 degrees by changing only the temperature.
As can be seen, there is a position in the vicinity of the light source-probe probe distance of 2 mm that is not sensitive to temperature changes, and this can be called a "temperature reference position". In addition, after a certain distance from the light source, a change rule is exhibited in which the relative change in light intensity between different positions is linearly approximated in a certain range. It should be noted that after being too far from the light source, the emitted light drops sharply, which increases the noise effect, which greatly affects the measurement. Now, don't think about the situation where the noise is too loud. When the two measurement positions are fixed, the value of ξ can be estimated by FIG. 25. Further, the value of η can be directly obtained by using the equation (S-3). In order to accurately obtain the value of η, the following calculation is made based on the amount of noise actually generated after the temperature changes.
When the glucose concentration changes by 60 mM and 100 mM at temperatures of 32 ° C., 35 ° C., 38 ° C. and 40 ° C., the amount of diffuse reflected light change at different positions is taken, and the distribution map shown in FIG. 17 is obtained. As can be seen from the figure, at this wavelength we consider that there is no floating reference position is that there is actually no one radial position where the sensitivity to changes in glucose concentration is always kept at near zero. .. However, at any single temperature, there is a radial position where the amount of change in diffuse due to changes in glucose concentration is always negative, and the amount of change in diffuse within this area is higher absolute and stable. Has. Therefore, two radial positions can be selected as the two measurement positions in this area and used to remove common mode interference noise when there is no floating reference position.
The radial position of 0.6 to 1 mm is selected as the measurement position 1, and the radial position of 1 to 2 mm is selected as the measurement position 2. If the solution does not contain glucose, i.e. only changes with temperature, the different radial positions will produce a corresponding noise signal with the change in temperature. Monte Carlo simulations allow the number of diffuse photons to be obtained at different temperatures and at different radial measurement positions. Table 8 shows the amount of change in the number of diffuse reflected photons detected at the two measurement positions when the temperature changes from 32 ° C. to 40 ° C., that is, when the temperature changes by ± 4 ° C. with reference to 36 ° C.

Since the glucose concentration does not change at this time, the measured signal change amount is completely caused by the temperature change, that is, the signal change amount measured at this time is considered to be a noise signal. Therefore, the ratio of noise interference can be calculated at the two measurement positions, and the ratio of the change in the number of diffuse reflected photons at the measurement position 2 to the change in the number of diffuse reflected photons at the measurement position 1 is about 0.17 due to the temperature change. Is. That is, it can be described as follows.

Therefore, when the glucose concentration and temperature all change, ρ according to equation (63).₁And ρ₂The effective signal for removing the common mode interference due to temperature due to the change in glucose concentration obtained by performing the difference calculation on the amount of change in the diffuse reflected light in the above is as follows.

Randomly selecting glucose diffusely reflected light at six different temperatures and different concentrations, the correlation coefficient between glucose concentration and temperature is -0.01918, so it is considered that there is no relationship between the two. In the actual measurement process, the situation where the glucose concentration changes and the temperature drifts irregularly is simulated, and the corresponding glucose concentration and temperature conditions are shown in Table 9.

When the glucose concentration changes by 20, 40, 60, 80 and 100 mM, respectively, as shown in FIG. 18, when the data of the first group is set as the state of the measurement start time and is not corrected for the interference signal due to the temperature change. A change curve of the number of diffusely reflected photons at the same two measurement positions can be obtained. The curve for measuring the amount of change in diffuse reflected light intensity in the figure does not show a regular gradual increase or decrease due to a change in glucose concentration, and the signal change due to temperature change covers the characteristic signal of the glucose concentration change. ..
Equation (64) was adopted to correct the temperature change with respect to the amount of change in the number of diffusely reflected photons at the two measurement positions, and the calculation result is as shown in the curve in FIG. As can be seen from the figure, the signal weighting at the two measurement positions and the corrected signal are adopted, and the absolute value is smaller than the signal value at the two measurement positions before the correction, but the absolute value of the curve is It exhibits regular increasing changes with changes in glucose concentration, achieving the purpose of eliminating common-mode interference due to temperature drift.
According to another example, a polycyclic optical fiber measurement system based on an SLD light source is adopted to analyze the situation when the light source drifts with an intralipid solution having a concentration of 3% as a measurement waiting target.
What is measured by experimental analysis is that when the wavelength is 1219 nm, the floating reference position of glucose in the intralipid solution at a concentration of 3% is approximately 3.0-3.2 mm. This selects this position for the polycyclic fiber optic probe as a floating reference position signal detection ring. In consideration of the processing process, the position where the radial position is 0.24 to 0.96 mm is the inner measurement position signal detection ring, and the position where the radial position is 3.2 to 4.1 mm is the outer measurement position signal detection ring. ), A polycyclic optical fiber probe having a structure as shown in) was produced.
In the experimental process, the power of the SLD is randomly changed to simulate the irregular drift phenomenon of the light source, and when the wavelength reaches 1219 nm, the diffuse reflected light intensity at three radial positions at different times is obtained. When the light source drifts, assuming that the first measurement value is the initial state of the measurement, the amount of change in the diffuse reflection light is the difference between the light intensity measurement value in the state at that time and the light intensity value in the initial state. Obtained by performing a calculation. This makes it possible to calculate the ratio of the amount of change in the diffusely reflected light signal value at the three measurement positions due to the light source drift. What can be obtained by calculation is that the amount of change in the diffused reflected light signal value due to the light source drift at the measurement position outside the floating reference position is about 0.84 of the amount of signal change at the floating reference position, and the signal at the floating reference position The amount of change is about 0.7 times the amount of signal change at the floating reference inner measurement position, and the amount of signal change at the floating reference outer measurement position is about 0.58 times the amount of signal change at the inner measurement position. is there. These are used to correct the signal as the difference proportional coefficient when the light source state and the glucose concentration change at the same time, that is, they can be considered approximately as follows.

Next, using an intralipid solution having a concentration of 3% as a mother liquor, six samples having a glucose concentration range of 1000 to 6000 mg / dL and an interval of 1000 mg / dL were arranged, and six glucose intralipid solutions were measured in random order. Simultaneously change the power of the SLD to simulate the irregular drift phenomenon of the light source, measure the diffuse intensity at three radial positions at different times, and determine the diffuse intensity of the sample solution. A difference calculation is performed on the diffuse reflected light intensity in the initial state, and the amount of change in the diffuse reflected light at the three measurement positions is calculated when the light source drift and the glucose concentration change at the same time. The result is shown in FIG. As shown in. As can be seen from the results, the light source drift has a great influence on the detection of glucose concentration, and due to the randomness of the light source drift, all the signals measured at the three positions lose their linear relationship with the glucose change. That is, since the amount of change in the diffuse reflected light intensity signal due to the light source drift completely covers the effective information of the change in glucose concentration, it is necessary to correct the measured light intensity signal.
Due to the proportional relationship of equations (65), (66) and (67), the diffuse reflected light intensity is jointly caused by the change in glucose concentration and the light source drift by adopting the equations (54), (55) and (57). The signal has been modified and the results are shown in FIG. As can be seen from the results, the signals at arbitrary two positions are used for weighting difference processing, and the corrected light intensity signals both show a clear linear relationship with the change in glucose concentration, and the light source drift for glucose concentration detection. The effect is reduced or eliminated, and effective information on changes in glucose concentration can be effectively extracted. As can be seen from the results, the signal at the inner ring and the reference ring measurement position, and the effective signal corrected by adopting the signal at the outer ring and the inner ring measurement position are at the outer ring and the reference ring measurement position. It is clearly larger than the effective signal modified by adopting the signal of, which means that the diffuse reflected light intensity value is attenuated in an expression exponential manner as the radial distance from the light source increases. The correction effect of adopting the inner ring and the outer ring and the effect of adopting the inner ring and the reference ring are in conflict with each other. However, when the signal detection and correction are performed by adopting the inner ring and the outer ring, the measurement with the reference ring is performed. The signal is no longer adopted, and it is not necessary to be affected by changes in the measurement wavelength, the state of the object to be measured, etc. with respect to the floating reference position, and the universality of the signal correction method is effectively strengthened.
In the above analysis, a proportional coefficient due to light source drift is calculated in a pure intralipid solution having a concentration of 3%, and the subsequent signal processing is performed with this as the initial state of measurement. Similarly, according to similar steps, with glucose solution samples containing different concentrations, first calculate the appropriate proportionality factor under a random drift of the light source, and then use this concentration sample as the initial state of measurement for subsequent signals. Processing can be performed. Using samples with glucose concentrations of 3000 and 6000 mg / dL, respectively, the proportionality coefficient used for spectrum correction was calculated, and the spectrum signal was corrected using this as the initial state of measurement, and glucose as shown in FIGS. 20 and 21. The results of signal correction were obtained with samples with concentrations of 3000 and 6000 mg / dL as the initial states, respectively. As can be seen from the figure, common mode interference due to light source drift was reduced or with glucose solutions of different concentrations as the initial states. The purpose of elimination can be achieved as well, and the effect modified by adopting the signal at the inner and outer measurement positions and the signal at the inner and floating reference positions is the signal at the outer and floating reference positions. It also appears to be superior to the modified effect by adopting, and the conclusions obtained are consistent with the signal modification using pure intralipid solution as the initial sample. It should also be noted that no matter what glucose concentration sample is used as the initial state for signal correction, all the corrected results obtained are changes in the glucose concentration information in the initial state, so different measurements are taken. The measured glucose concentration at time should be the sum of this change and the glucose concentration in the initial state.
FIG. 22 shows an arrangement example of the measurement system according to the present disclosure embodiment.
As shown in FIG. 22, the measurement system may include a light source 2201, a coupling system 2203 for adapting light from the light source 2201 to be coupled to an optical fiber, an optical fiber probe 2205, and a processing device 2209. it can.
Light source 2201 may include a variety of suitable light sources capable of emitting light of the required wavelength. For example, in the near infrared range, a halogen lamp can be used as a continuous light source. Alternatively, the light source 2201 can also include a supercontinuum pulsed laser light source.
The coupling system 2203 uses the Gran prism 2203-1 for converting the light from the light source 2201 into linear polarization, and the +1st order light (or-) whose polarization state is orthogonal to the 0th order light for the linear polarization from the Gran prism 2203-1. Acoustic and optical tunable filter (AOTF) 2203-2 for spectroscopic (diffraction) to primary light), Gran prism 2203-3 for removing 0th order light provided orthogonal to Gran prism 2203-1, And a coupler 2203-4 for coupling the +1st order light (or -1st order light) from the Gran prism 2203-3 to the successor device can be included.
It should be noted here that FIG. 22 shows one specific example of the coupling system, but the present disclosure is not limited to this. The trader knows multiple coupling systems and can couple the light from the light source to the fiber optic system.
The fiber optic probe 2205 may include, for example, the structure previously described with reference to FIG. Specifically, the coupling system 2203 can couple the light from the light source to the incident optical fiber bundle of the optical fiber probe 2205 (for example, 1001 in FIG. 10), and the incident optical fiber bundle transfers the light to the medium 2207 to be measured. Can guide you to. Then, the probe optical fiber bundle in the optical fiber probe 2205 (for example, two or more of 1003, 1005 and 1007 in FIG. 10) can guide the diffuse reflected light of the medium to be measured 2007 to the processing device 2209.
The processing device 2209 can include a probe 2209-1 (eg, a photoelectric probe), which is used to detect an optical signal from an optical fiber probe, which is converted into a telegraph for further processing. Can be offered to. The placement of the fiber optic probe allows the probe 2209-1 to detect spectral data at multiple radial positions (eg, inside the floating reference position, inside the floating reference position and / or outside the floating reference position).
The processing device 2209 further includes a processor 2209-2. The processor 2209-2 can be arranged so as to perform the above-mentioned difference processing on the spectrum data detected by the probe 2401. Specifically, the processor 2209-2 selects two radial positions having different sign changes in the light intensity of the diffusely reflected light with the change in the concentration of the specific component in the measurement medium, and these two radial positions. Weighted difference processing can be performed on the spectral data at the position.
The processor 2209-2 can include various types of computing equipment such as a general-purpose computer, an application specific integrated circuit (ASIC), and an FPGA. The processor 2403 can operate according to each method and process as described above by loading a program, a code segment, etc. stored in the storage device to realize spectral data difference processing, model construction, and concentration prediction. it can.
The processing device 2209 includes an input device 2209-3 for inputting user commands, data, etc., such as a mouse and keyboard, and a processing result (for example, separated scattered signal / absorption) of the processor 2403, such as a display. An output device 2209-4 for outputting signals, prediction results, etc.) is further included. The input device 2209-3 and the output device 2209-4 can be combined to be realized as a touch panel.
The techniques of the present disclosure can be implemented to include a program of algorithms that can be executed by a data processor, or can be stored and provided on a non-transitory computer-readable medium.
The techniques of the present disclosure can be implemented as computer-readable code on a computer-readable medium. Computer-readable media include computer-readable recording media and computer-readable transmission media. A computer-readable recording medium is any data storage device that stores data as a program that can then be read by a computer system. Examples of computer-readable recording media include read-only memory (ROM), random access memory (RAM), CD-ROM, tapes, disks and optical data storage devices. Computer-readable recording media may be distributed in computer systems connected to the Internet, thereby storing and executing computer-readable code in a decentralized format. Computer-readable transmission media can be transmitted by carrier waves or signals (eg, wired or wireless data transmission over the Internet). In addition, the functional programs, codes and code segments that realize the disclosed technology can be easily interpreted by programmers in this field of the overall concept of the present invention.
In the above, the plurality of features of the present disclosure will be described in each of the plurality of examples. However, this does not mean that these features are advantageously combined and cannot be used.
The examples of the present disclosure have been described above. However, these examples are for illustration purposes only and do not limit the scope of this disclosure. The scope of this disclosure is limited by claims and their equivalents. As long as it does not deviate from the scope of the present disclosure, those skilled in the art may make multiple substitutions and amendments, all of which should be included in the scope of the present disclosure.

Claims (23)

A method of predicting a change in the concentration of a specific component detected in a measurement medium with respect to a reference based on spectral data.
The process of irradiating the medium to be measured with light from a probe, etc.
The process of selecting the first radial position and the second radial position based on the reference position, and
Further, a step of acquiring the first spectral data regarding the medium at the first radial position and the second spectral data regarding the medium at the second radial position due to the change in density with respect to the reference.
It comprises a step of calculating the difference between the first spectral data and the second spectral data and a step of predicting the concentration change of a specific component based on the calculated difference , wherein the first one is provided. The radial position, the second radial position, and the reference position are the radial positions on the path of the light passing through the medium, respectively, and the reference position is the intensity of the diffused reflected light and / or the diffused transmitted light. A method characterized in that, with a change in the concentration of a particular component, it indicates a radial position that changes at a rate of change with substantially the smallest absolute value. The intensities of the diffuse reflected light and the diffuse transmitted light detected at the first radial position change at the first rate of change with the change of the concentration of the special component in the medium, and the second one. The intensity of the diffuse reflected light and / or the diffuse transmitted light detected at the radial position of the above changes at a second rate of change with a change in the concentration of a specific component in the medium, and the intensity of the diffuse reflected light and / or the diffuse transmitted light changes at the second rate of change. The method according to claim 1, wherein the position and the second radial position are selected so that the first rate of change and the second rate of change have different symbols. The first rate of change has a positive sign, while the second rate of change has a negative sign, or the first rate of change has a positive or negative sign, while the second. The method according to claim 2, wherein the rate of change is substantially zero. The method of claim 1, wherein the rate of change at the reference position is substantially zero. In the step of selecting the first radial position and the second radial position,
(A) A position closer to the light source than the reference position is selected as the first radial position, while a position farther from the light source than the reference position is selected as the second radial position, or (b) the first. While selecting the reference position as the radial position, select a position closer to the light source than the reference position as the second radial position, or (c) select the reference position as the first radial position. The method according to claim 1, wherein a position farther from the light source than the reference position is selected as the second radial position. The method according to claim 5, wherein the case (a) further includes a step of acquiring a third spectral data at a reference position caused by a change in concentration with respect to the reference. The method of claim 1, wherein the first spectral data and the second spectral data each include a change in light intensity measured for the medium relative to the reference. 7. The step of calculating the difference includes a step of subtracting a light intensity change in the second radial position weighted by a factor η which is a coefficient or a factor from the light intensity change in the first radial position. The method described in.
Here, the factor η is a ratio of the light intensity change in the second radial position caused by the same interference factor as the light intensity change of the diffuse reflected light and / or the diffuse transmitted light in the first radial position. , The concentration of the specific component remains substantially unchanged. The method of claim 8, wherein the factor η is calculated from the optical parameters of the medium. The method according to claim 9, wherein the optical parameters of the medium are obtained by the optical parameter inverse configuration method. The method of claim 8, wherein the factor η is obtained by a plurality of measurements. The factor η is estimated by multiplying the ratio between the light intensity at the first radial position and the light intensity at the second radial position above with respect to the reference by a fixed factor. The method according to claim 8. 12. The method of claim 12, wherein the fixation factor is estimated based on the first radial position and the second radial position. The method of claim 1, wherein the first spectral data and the second spectral data each include a relative change in light intensity measured for the medium relative to the reference. The method of claim 1, wherein the prediction is performed based on a prediction model, the prediction model being established by the following steps.
Here, for each medium of the series of media, the medium includes a background medium or a reference medium in which a specific component is added to the background medium or the reference medium at known concentrations, and the reference medium is the background medium and the initial concentration. Consisting of specific components, the light irradiation step and the first spectral data of the medium at the first radial position due to the density change with respect to the background medium or reference medium and the density change with respect to the background medium or reference medium. Including the step of acquiring the second spectral data of the medium in the second radial position due to the above , where the first radial position and the second radial position are arbitrarily selected and also again. It includes the step of calculating the difference between the first spectral data and the second spectral data, and the step of establishing a prediction model based on the respective known concentration and the corresponding calculated difference. 15. The method of claim 15, wherein the method is used for non-invasive detection of blood glucose levels. 16. The method of claim 16, wherein the irradiated light has a wavelength in the range of about 1.0 to 2.4 μm. An apparatus for carrying out the method according to claim 1, wherein the probe is configured to detect spectral data of diffused reflected light and / or diffuse transmitted light from a medium to detect a specific component inside. Etc., means for selecting a first radial position and a second radial position based on a reference position, and by using the detector, due to a change in the concentration of a particular component relative to the reference. Obtain spectral data at the triggered first radial position and second radial position, and calculate the difference between the spectral data detected at the first radial position and the second radial position. A processing device comprising a processor configured in. The intensity of the diffuse reflected light and the diffuse transmitted light detected at the first radial position changes at the first rate of change with the change in the concentration of the specific component in the medium, and is detected at the second radial position. The intensity of the diffuse reflected light and the diffuse transmitted light is changed at a second rate of change with a change in the concentration of a specific component in the medium, and the first radial position and the second radial position are described above. The processing apparatus according to claim 18, wherein the first rate of change and the second rate of change are selected to have different reference numerals. A method of predicting a change in the concentration of a specific component detected in a measurement medium with respect to a reference based on spectral data.
The process of irradiating the medium to be measured with light from a probe, etc.
The process of selecting the first radial position and the second radial position based on the reference position, and
Further, a step of acquiring the first spectral data regarding the medium at the first radial position and the second spectral data regarding the medium at the second radial position due to the change in density with respect to the reference.
The process of calculating the difference between the first spectral data and the second spectral data,
Then, it includes a step of predicting a change in the concentration of a specific component based on the calculated difference .
Here, the first radial position, the second radial position, and the reference position are radial positions on the path of light passing through the medium, respectively, and are the first radial position and the second diameter. The directional position is such that the intensity of the diffuse reflected light and / or the diffuse transmitted light changes with the first change rate and the second change rate together with the change in the concentration of a specific component in the medium, and the direction position is the same as the first radial position. A method characterized in that a second radial position is selected such that the first rate of change and the second rate of change have different signs. In the method of claim 20, the first rate of change has a positive sign, while the second rate of change has a negative sign, or the first rate of change has a positive sign or a negative sign. The method is characterized in that the second fluctuation rate is substantially zero. An apparatus for carrying out the method according to claim 20, wherein the probe is configured to detect spectral data of diffuse reflected light and / or diffuse transmitted light from a medium to detect a specific component inside. Etc. and each of the first radial position and the second radial position is a radial position on the path of light passing through the medium, where diffuse reflected light and / or diffuse transmitted light. At the first radial position and the second radial position, the intensity of the light changes at the first rate of change and the second rate of change according to the change in the concentration of a specific component in the medium, respectively, and the first radius. The position and the second radial position are selected so that the first and second volatility have different signs and are subtracted by the change in the concentration of a particular component relative to the reference by using the detector. The spectral data at the first radial position and the second radial position that are raised are acquired, and the difference between the spectral data detected at the first radial position and the second radial position is calculated. A processing device comprising a processor configured as described above. The first rate of change has a positive sign while the second rate of change has a negative sign, or the first rate of change has a positive or negative sign, while the second. 22. The processing apparatus according to claim 22, wherein the rate of change of the above is substantially zero.

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