JP2017181211A - Optical transcutaneous oxygen sensor and transcutaneous oxygen concentration measurement device having the same - Google Patents

Optical transcutaneous oxygen sensor and transcutaneous oxygen concentration measurement device having the same Download PDF

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JP2017181211A
JP2017181211A JP2016066847A JP2016066847A JP2017181211A JP 2017181211 A JP2017181211 A JP 2017181211A JP 2016066847 A JP2016066847 A JP 2016066847A JP 2016066847 A JP2016066847 A JP 2016066847A JP 2017181211 A JP2017181211 A JP 2017181211A
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oxygen sensor
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transcutaneous oxygen
transcutaneous
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岡田　浩孝
Hirotaka Okada
浩孝 岡田
健治 田畠
Kenji Tabata
健治 田畠
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KATERA CO Ltd
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PROBLEM TO BE SOLVED: To provide an optical transcutaneous oxygen sensor that can be tightly fixed on skin easily, and a transcutaneous oxygen concentration measurement device having the same.SOLUTION: An optical transcutaneous oxygen sensor 11 is configured to measure oxygen diffusing from blood through body tissue on a surface of the skin, and comprises a gas-impermeable transparent resin film 13, and a transparent polymer material 15 containing a pigment compound 17 that emits light when excited and varies emission intensity in accordance with oxygen concentration. The polymer material 15 is adhered to one surface of resin film 13, and the surface is coated with an adhesive 19 in an area surrounding the polymer material 15.SELECTED DRAWING: Figure 1

Description

本発明は、血液中から生体組織を経て拡散する酸素を皮膚表面で測定する光学的経皮酸素センサ及びこれを用いた経皮酸素濃度測定装置に関する。   The present invention relates to an optical transcutaneous oxygen sensor for measuring oxygen diffused from blood through living tissue on the skin surface and a transcutaneous oxygen concentration measuring apparatus using the same.

血液中の酸素濃度は、患者の健康状態を判断する重要な指標の一つとなる。血液中の酸素濃度を測定する方法の一つとして、患者から血液を採取して酸素濃度を測定する方法があるが、連続的に測定することができず、また、患者に採血の苦痛を伴う。この問題を解決するために、血液中の酸素や二酸化炭素が毛細血管から皮膚組織を経て拡散されることを利用して経皮的に血液中の酸素濃度を測定する様々なタイプの経皮酸素センサが提案されている。   The oxygen concentration in the blood is one of the important indicators for judging the health condition of the patient. One method of measuring oxygen concentration in blood is to collect blood from a patient and measure the oxygen concentration, but it cannot be measured continuously, and the patient suffers from blood sampling pain . To solve this problem, various types of transcutaneous oxygen are used to measure the oxygen concentration in the blood transcutaneously using the diffusion of oxygen and carbon dioxide in the blood from the capillaries through the skin tissue. Sensors have been proposed.

このような経皮酸素センサの一つとして、特許文献１は、皮膚に付着させて電気化学的にガス分圧を測定する経皮ガス分圧測定器用センサを提案している。特許文献１に記載のようなタイプの電気化学的経皮酸素センサでは、皮膚に当接するガス透過性のメンブレンと電極との間に電解液が充満されており、皮膚から発散されメンブレンを透過した酸素を電解液に溶け込ませ、溶け込んだ酸素による電極での電解還元により発生した電流を検出して酸素の分圧を測定する。   As one such transcutaneous oxygen sensor, Patent Document 1 proposes a sensor for a transcutaneous gas partial pressure measuring instrument that is attached to the skin and electrochemically measures the gas partial pressure. In the electrochemical transcutaneous oxygen sensor of the type described in Patent Document 1, the electrolyte is filled between the gas-permeable membrane that contacts the skin and the electrode, and the membrane is emitted from the skin and penetrates the membrane. Oxygen is dissolved in the electrolyte, and the partial pressure of oxygen is measured by detecting the current generated by the electrolytic reduction at the electrode by the dissolved oxygen.

特開平７−２３９３６号公報Japanese Patent Laid-Open No. 7-23936 特開平５−２９６９０号公報JP-A-5-29690

しかしながら、このように電極と電解液を使用するタイプの電気化学的経皮酸素センサは、構造上小型化が困難であるという問題や電気分解により測定の過程で酸素を消費してしまうという問題がある。   However, the type of electrochemical transcutaneous oxygen sensor that uses an electrode and an electrolyte as described above has a problem that it is difficult to downsize due to its structure and a problem that oxygen is consumed in the measurement process due to electrolysis. is there.

このため、近年、光励起物質の発光強度が光励起物質と酸素との消光反応により変化することを利用して酸素分圧を測定するタイプの光学的経皮酸素センサが注目されている。例えば、特許文献２は、透明板に蛍光物質を塗布して形成した蛍光層を基体の前面に着脱自在に取り付けた経皮酸素センサを提案している。特許文献２に記載の経皮酸素センサは、蛍光物質を塗布した側を皮膚へ向けて装着され、透明板側から蛍光物質に励起光を照射したときの蛍光強度が、酸素と蛍光物質との消光反応により変化することを利用して、酸素分圧を測定する。   Therefore, in recent years, attention has been paid to an optical transcutaneous oxygen sensor that measures the partial pressure of oxygen by utilizing the fact that the emission intensity of the photoexcited substance changes due to the quenching reaction between the photoexcited substance and oxygen. For example, Patent Document 2 proposes a transcutaneous oxygen sensor in which a fluorescent layer formed by applying a fluorescent material to a transparent plate is detachably attached to the front surface of a substrate. The transcutaneous oxygen sensor described in Patent Document 2 is mounted with the fluorescent material-coated side facing the skin, and the fluorescence intensity when the fluorescent material is irradiated with excitation light from the transparent plate side is determined by the relationship between oxygen and the fluorescent material. The oxygen partial pressure is measured by utilizing the change caused by the quenching reaction.

しかしながら、基体や透明板が硬いために、経皮酸素センサを皮膚に密着して固定することが難しく、皮膚から拡散される酸素が外部に漏れ出てしまい、正確に酸素分圧を測定できない恐れがある。   However, since the substrate and the transparent plate are hard, it is difficult to fix the percutaneous oxygen sensor in close contact with the skin, and oxygen diffused from the skin may leak out and the oxygen partial pressure may not be measured accurately. There is.

よって、本発明の目的は、従来技術に存する課題を解決して、皮膚への密着固定が容易な光学的経皮酸素センサ及びこれを用いた経皮酸素濃度測定装置を提供することにある。   Accordingly, an object of the present invention is to solve the problems existing in the prior art and provide an optical transcutaneous oxygen sensor that can be easily adhered and fixed to the skin, and a transdermal oxygen concentration measuring apparatus using the same.

上記目的に鑑み、本発明は、第１の態様として、血液中から生体組織を経て拡散する酸素を皮膚表面で測定する光学的経皮酸素センサであって、ガス不透過性の透明な樹脂フィルムと、励起状態下で発光し酸素濃度に応じて発光強度を変化させる色素化合物を含有する透明なポリマ体とを備え、前記樹脂フィルムの一方の表面に前記ポリマ体が固着され、前記表面における前記ポリマ体の周囲に粘着剤が塗布されているようにした光学的経皮酸素センサを提供する。   In view of the above object, the present invention provides, as a first aspect, an optical transcutaneous oxygen sensor for measuring oxygen diffused from blood through biological tissue on the skin surface, which is a gas-impermeable transparent resin film. And a transparent polymer body containing a dye compound that emits light in an excited state and changes emission intensity according to the oxygen concentration, the polymer body is fixed to one surface of the resin film, Provided is an optical transcutaneous oxygen sensor in which an adhesive is applied around a polymer body.

上記光学的経皮酸素センサでは、皮膚表面の形状に追従することが容易な透明樹脂フィルム上に、色素化合物を含有するポリマ体が固着されており、ポリマ体が固着された側の樹脂フィルムの面に粘着剤が塗布されているので、ポリマ体を皮膚側へ向けた状態で皮膚表面に密着して樹脂フィルムを貼り付けることができる。また、樹脂フィルムがガス不透過性であるので、樹脂フィルムが皮膚に密着した状態では皮膚から拡散される酸素が外部に漏れだすこととが防止され、皮膚と樹脂フィルムとの間の空間中の酸素分圧が血管中の酸素分圧と平衡状態になる。したがって、血管中の酸素と平衡状態になった皮膚と樹脂フィルムとの間の空間内に存在する酸素による消光反応が起きて、励起光が色素化合物に照射されたときの色素化合物の発光強度（例えばリン光の強度）が血管中の酸素分圧に応じて変化し、発光強度に基づいて血管中の酸素分圧を正確に測定することが可能となる。   In the optical transcutaneous oxygen sensor, a polymer body containing a pigment compound is fixed on a transparent resin film that can easily follow the shape of the skin surface, and the resin film on the side on which the polymer body is fixed is fixed. Since the adhesive is applied to the surface, the resin film can be adhered to the skin surface in a state where the polymer body is directed to the skin side. In addition, since the resin film is gas-impermeable, oxygen diffused from the skin is prevented from leaking to the outside when the resin film is in close contact with the skin, and in the space between the skin and the resin film. The oxygen partial pressure is in equilibrium with the oxygen partial pressure in the blood vessel. Therefore, the quenching reaction due to oxygen existing in the space between the skin and the resin film in equilibrium with oxygen in the blood vessel occurs, and the emission intensity of the dye compound when the excitation light is irradiated to the dye compound ( For example, the intensity of phosphorescence changes according to the oxygen partial pressure in the blood vessel, and the oxygen partial pressure in the blood vessel can be accurately measured based on the emission intensity.

上記光学的経皮酸素センサでは、前記ポリマ体がフィルム形状であることが好ましい。ポリマ体がフィルム形状であれば、経皮酸素センサを皮膚に貼り付けたときの違和感が軽減される。   In the optical transcutaneous oxygen sensor, the polymer body is preferably in the form of a film. If the polymer body is a film shape, the uncomfortable feeling when the transcutaneous oxygen sensor is attached to the skin is reduced.

また、前記ポリマ体が前記樹脂フィルムよりも酸素透過度が高い樹脂材料から形成されていることが好ましい。ポリマ体の酸素透過度が高ければ、ポリマ体に含有される色素化合物が酸素による消光反応を起こしやすくなり、酸素分圧の検出感度が向上する。   Moreover, it is preferable that the said polymer body is formed from the resin material whose oxygen permeability is higher than the said resin film. If the oxygen permeability of the polymer body is high, the dye compound contained in the polymer body tends to cause a quenching reaction due to oxygen, and the detection sensitivity of the oxygen partial pressure is improved.

一つの実施形態では、前記色素化合物が白金（ＩＩ）−オクタエチルポルフィリン、白金（ＩＩ）−テトラキスカルボキシフェニルポルフィリン又は白金（ＩＩ）−テトラキスペンタフルオロフェニルポルフィリンである。   In one embodiment, the dye compound is platinum (II) -octaethylporphyrin, platinum (II) -tetrakiscarboxyphenylporphyrin, or platinum (II) -tetrakispentafluorophenylporphyrin.

さらに、前記色素化合物が励起状態でリン光を発するリン光化合物であり、前記ポリマ体が、励起状態下で蛍光を発する蛍光化合物をさらに含有することが好ましい。蛍光化合物の蛍光強度は酸素の消光作用の影響を受けにくく、酸素濃度によりほとんど変化しないことから、蛍光化合物からの蛍光強度とリン光化合物からのリン光強度との比を測定することにより、測定光学系の影響を受けることなく、正確な酸素分圧の測定が可能となる。   Furthermore, it is preferable that the dye compound is a phosphorescent compound that emits phosphorescence in an excited state, and the polymer body further contains a fluorescent compound that emits fluorescence in the excited state. The fluorescence intensity of a fluorescent compound is not easily affected by the quenching action of oxygen, and hardly changes depending on the oxygen concentration. Therefore, it is measured by measuring the ratio of the fluorescence intensity from the fluorescent compound to the phosphorescence intensity from the phosphorescent compound. Accurate oxygen partial pressure can be measured without being affected by the optical system.

前記蛍光化合物は、例えばクマリンとすることができる。   The fluorescent compound can be, for example, coumarin.

また、前記樹脂フィルムは、延伸高密度ポリエチレンから形成することができる。   The resin film can be formed from stretched high-density polyethylene.

また、本発明は、第２の態様として、患者の皮膚に貼り付けられる上記経皮酸素センサと、前記経皮酸素センサに励起光を照射する励起光源と、前記励起光源によって照射された前記光学的経皮酸素センサからの発光強度を測定する発光強度測定器とを備え、前記発光強度測定器によって測定された発光強度に基づいて、血管中の酸素の濃度が求められる経皮酸素濃度測定装置を提供する。   Further, the present invention provides, as a second aspect, the transdermal oxygen sensor attached to the skin of a patient, an excitation light source that irradiates the transdermal oxygen sensor with excitation light, and the optical that is irradiated by the excitation light source. A transcutaneous oxygen concentration measuring device for measuring the oxygen concentration in a blood vessel based on the light emission intensity measured by the light emission intensity measuring device I will provide a.

前記色素化合物が励起状態でリン光を発するリン光化合物であり、前記光学的経皮酸素センサの前記ポリマ体が、励起状態下で蛍光を発する蛍光化合物をさらに含有し、前記発光強度測定器がリン光と同時に蛍光も測定し、前記経皮酸素濃度測定装置が、測定された蛍光の強度に対するリン光の強度の比に基づいて、血管中の酸素濃度が求められることが好ましい。   The dye compound is a phosphorescent compound that emits phosphorescence in an excited state, and the polymer body of the optical transcutaneous oxygen sensor further contains a fluorescent compound that emits fluorescence in the excited state, and the emission intensity measuring device includes It is preferable that fluorescence is measured simultaneously with phosphorescence, and the transcutaneous oxygen concentration measuring device determines the oxygen concentration in the blood vessel based on the ratio of the phosphorescence intensity to the measured fluorescence intensity.

さらに、前記発光強度測定器が分光計及び光計測プローブによって構成されており、前記光計測プローブを通して前記励起光源から前記光学的経皮酸素センサに励起光を照射し、前記光計測プローブを通して、前記光学的経皮酸素センサから発せられた蛍光及びリン光を前記分光計に導くようにすることが好ましい。   Further, the emission intensity measuring device is constituted by a spectrometer and an optical measurement probe, irradiates the optical transdermal oxygen sensor from the excitation light source through the optical measurement probe, passes through the optical measurement probe, and Preferably, fluorescence and phosphorescence emitted from an optical transcutaneous oxygen sensor are directed to the spectrometer.

本発明の光学的経皮酸素センサ及びこれを用いた経皮酸素濃度測定装置によれば、光学的経皮酸素センサを皮膚に密着して貼り付けることが容易で、血管中の酸素分圧又は酸素濃度を正確に測定することが可能となる。また、光学的経皮酸素センサを皮膚に貼り付けている間も皮膚への違和感が少なく、患者の負担も少なくなる。   According to the optical transcutaneous oxygen sensor and the transcutaneous oxygen concentration measuring apparatus using the same according to the present invention, it is easy to attach the optical transcutaneous oxygen sensor in close contact with the skin. It becomes possible to accurately measure the oxygen concentration. In addition, while the optical transcutaneous oxygen sensor is attached to the skin, there is less discomfort to the skin, and the burden on the patient is reduced.

本発明による光学的経皮酸素センサの全体構成を示す断面図である。It is sectional drawing which shows the whole structure of the optical transcutaneous oxygen sensor by this invention. 図１に示されている光学的経皮酸素センサを備える経皮酸素濃度測定装置の全体構成を示す概略図である。It is the schematic which shows the whole structure of the transdermal oxygen concentration measuring apparatus provided with the optical transcutaneous oxygen sensor shown by FIG. 本発明による光学的経皮酸素センサの原理を示す説明図である。It is explanatory drawing which shows the principle of the optical transcutaneous oxygen sensor by this invention. 酸素分圧と光学的経皮酸素センサから発せられるリン光強度との相関関係を示すグラフである。It is a graph which shows correlation with oxygen partial pressure and the phosphorescence intensity emitted from an optical transcutaneous oxygen sensor. 光学的経皮酸素センサのＳｔｅｒｎ−Ｖｏｌｍｅｒプロットを示すグラフである。It is a graph which shows the Stern-Volmer plot of an optical transcutaneous oxygen sensor. 酸素分圧と光学的経皮酸素センサからのリン光の強度に対する蛍光の強度の比との相関関係を示すグラフである。It is a graph which shows the correlation with the ratio of the fluorescence intensity with respect to the intensity | strength of the phosphorescence from the oxygen partial pressure and the optical transcutaneous oxygen sensor. 図２に示されている経皮酸素濃度測定装置の光学的経皮酸素センサからの発光のスペクトルを示すグラフである。It is a graph which shows the spectrum of the light emission from the optical transcutaneous oxygen sensor of the transcutaneous oxygen concentration measuring apparatus shown by FIG.

以下、図面を参照して、本発明による光学的経皮酸素センサ及びこれを用いた経皮酸素濃度測定装置の実施の形態を説明する。   Hereinafter, embodiments of an optical transcutaneous oxygen sensor and a transcutaneous oxygen concentration measuring apparatus using the same according to the present invention will be described with reference to the drawings.

最初に、図１を参照して、光学的経皮酸素センサ（以下、単に経皮酸素センサと記載する。）１１の全体構成を説明する。経皮酸素センサ１１は、樹脂フィルム１３と、ポリマ体１５とを備え、ポリマ体１５が、励起状態下で発光する測定用色素化合物１７を含有している。   First, the overall configuration of an optical transcutaneous oxygen sensor (hereinafter simply referred to as a transcutaneous oxygen sensor) 11 will be described with reference to FIG. The transcutaneous oxygen sensor 11 includes a resin film 13 and a polymer body 15, and the polymer body 15 contains a measurement dye compound 17 that emits light in an excited state.

樹脂フィルム１３は、ガス不透過性で且つ励起光を透過できる透明な樹脂フィルムであり、特に酸素不透過性であることが好ましい。樹脂フィルム１３は、例えば、延伸高密度ポリエチレンやポリビニールフルオライド、ポリエチレンテレフタレート、延伸高密度ポリエチレンなどから形成することができる。樹脂フィルム１３の厚さは、ガス不透過性を確保できれば材質に応じて適宜の厚さとすることができるが、体表の形状に追従しやすくするべく柔軟性を確保するために薄いことが好ましい。また、樹脂フィルム１３の形状は皮膚に貼り付けることができれば適宜に選択することができる。   The resin film 13 is a gas-impermeable and transparent resin film that can transmit excitation light, and is particularly preferably oxygen-impermeable. The resin film 13 can be formed from, for example, stretched high-density polyethylene, polyvinyl fluoride, polyethylene terephthalate, stretched high-density polyethylene, or the like. The thickness of the resin film 13 can be set to an appropriate thickness depending on the material as long as the gas impermeability can be ensured, but it is preferably thin in order to ensure flexibility so as to easily follow the shape of the body surface. . In addition, the shape of the resin film 13 can be appropriately selected as long as it can be attached to the skin.

ポリマ体１５は、樹脂フィルム１３の一方の表面に固着されており、その表面における少なくともポリマ体１５の周囲には粘着剤１９が塗布されている。このように樹脂フィルム１３の表面に粘着剤１９を塗布することによって、ポリマ体１５を患者の皮膚へ向けた状態で樹脂フィルム１３を患者の皮膚に貼り付けることが可能となる。樹脂フィルム１３へのポリマ体１５の固着は適宜の方法で行うことができ、例えば、接着剤（図示せず）を用いてポリマ体１５を樹脂フィルム１３の表面に固着させることができる。   The polymer body 15 is fixed to one surface of the resin film 13, and an adhesive 19 is applied around at least the polymer body 15 on the surface. Thus, by applying the adhesive 19 to the surface of the resin film 13, the resin film 13 can be attached to the patient's skin with the polymer body 15 facing the patient's skin. The polymer body 15 can be fixed to the resin film 13 by an appropriate method. For example, the polymer body 15 can be fixed to the surface of the resin film 13 using an adhesive (not shown).

ポリマ体１５は、酸素透過性を有し且つ励起光を透過できる透明な樹脂材料から形成されており、少なくとも樹脂フィルム１３よりも酸素透過度が高い樹脂材料から形成されていることが好ましい。ポリマ体１５は、例えば、ポリスチレン、低密度ポリエチレン、ポリ酢酸ビニル、ポリメチルメタクリレートなどから形成することができる。ポリマ体１５は、測定用色素化合物１７を担持する機能を果たすものであり、ポリマ体１５の材質は、測定用色素化合物１７の発光強度が酸素分圧比２０％付近で大きく変化するように測定用色素化合物１７の種類に合せて選択されることが好ましい。ポリマ体１５は、任意の形状とすることができるが、皮膚に貼り付けたときの違和感を軽減させるために、図１に示されているように、フィルム形状とすることが好ましい。   The polymer body 15 is formed of a transparent resin material that has oxygen permeability and can transmit excitation light, and is preferably formed of a resin material that has at least an oxygen permeability higher than that of the resin film 13. The polymer body 15 can be formed from, for example, polystyrene, low density polyethylene, polyvinyl acetate, polymethyl methacrylate, or the like. The polymer body 15 functions to carry the measurement dye compound 17, and the material of the polymer body 15 is used for the measurement so that the emission intensity of the measurement dye compound 17 changes greatly in the vicinity of the oxygen partial pressure ratio of 20%. It is preferable to select according to the type of the dye compound 17. The polymer body 15 can have any shape, but in order to reduce the uncomfortable feeling when pasted on the skin, the polymer body 15 is preferably a film shape as shown in FIG.

ポリマ体１５に含有される測定用色素化合物１７は、励起光を照射されて光励起状態になると発光し周囲の酸素濃度に応じて発光強度を変化させる酸素応答性の発光化合物であり、特に励起状態になったときにリン光を発するリン光化合物であることが好ましい。測定用色素化合物１７としては、ポルフィリン及びポルフィリン類縁体を用いることができ、特に、リン光の量子収率が高く、リン光寿命が長くて酸素による消光作用の影響を受けやすいことから白金（ＩＩ）−オクタエチルポルフィリン（Ｐｔ−ＯＥＰ）、白金（ＩＩ）−テトラキスカルボキシフェニルポルフィリン（Ｐｔ−ＴＣＰＰ）、又は白金（ＩＩ）−テトラキスペンタフルオロフェニルポルフィリン（Ｐｔ−ＴＦＰＰ）が好ましい。   The measurement dye compound 17 contained in the polymer body 15 is an oxygen-responsive light-emitting compound that emits light when irradiated with excitation light and enters a photo-excited state, and changes the light emission intensity according to the surrounding oxygen concentration. It is preferable that the phosphorescent compound emits phosphorescence. Porphyrins and porphyrin analogs can be used as the measurement dye compound 17, and platinum (II) is particularly preferable because of its high phosphorescence quantum yield, long phosphorescence lifetime, and being susceptible to the quenching action of oxygen. ) -Octaethylporphyrin (Pt-OEP), platinum (II) -tetrakiscarboxyphenylporphyrin (Pt-TCPP), or platinum (II) -tetrakispentafluorophenylporphyrin (Pt-TFPP) is preferred.

ポリマ体１５は、補正用色素化合物２１として、励起光を照射されて光励起状態になったときに蛍光を発する蛍光化合物をさらに含有していてもよい。補正用色素化合物２１は、特に限定されるものではなく、クマリン類、フルオレセイン類、ローダミン類、シアニン類、ピレン類などの蛍光化合物から、励起波長と蛍光波長とに基づいて選択され得る。使用される測定用色素化合物１７からの発光と異なる波長の蛍光を発する蛍光化合物を使用することが好ましい。例えば、測定用色素化合物１７として白金（ＩＩ）−オクタエチルポルフィリン、白金（ＩＩ）−テトラキスカルボキシフェニルポルフィリン、又は白金（ＩＩ）−テトラキスペンタフルオロフェニルポルフィリンを用い、波長４０５ｎｎｍの青色の励起光を発する励起光源を用いる場合、測定用色素化合物１７から発せられるリン光の極大発光波長は６５０ｎｍ付近で赤色となることから、青色など赤色以外の蛍光を発する蛍光化合物を補正用色素化合物２１として使用することが好ましい。   The polymer body 15 may further contain, as the correction dye compound 21, a fluorescent compound that emits fluorescence when irradiated with excitation light and enters a photoexcited state. The correcting dye compound 21 is not particularly limited, and can be selected from fluorescent compounds such as coumarins, fluoresceins, rhodamines, cyanines, and pyrenes based on the excitation wavelength and the fluorescence wavelength. It is preferable to use a fluorescent compound that emits fluorescence having a wavelength different from that of light emitted from the measurement dye compound 17 used. For example, platinum (II) -octaethylporphyrin, platinum (II) -tetrakiscarboxyphenylporphyrin, or platinum (II) -tetrakispentafluorophenylporphyrin is used as the measurement dye compound 17, and blue excitation light having a wavelength of 405 nm is emitted. When an excitation light source is used, the maximum emission wavelength of phosphorescence emitted from the measurement dye compound 17 is red near 650 nm, and therefore a fluorescent compound that emits fluorescence other than red, such as blue, should be used as the correction dye compound 21. Is preferred.

次に、図２を参照して、図１に示される経皮酸素センサ１１を用いて測定した経皮酸素分圧から血管中の酸素濃度を測定するための経皮酸素濃度測定装置３１の全体構成を説明する。経皮酸素濃度測定装置３１は、図１に示されている経皮酸素センサ１１と、励起光源３３と、発光強度測定器３５と、演算装置３７とを備え、粘着剤を塗布された樹脂フィルム１３の面を患者の皮膚側へ向けて患者の皮膚３９に貼り付けられた経皮酸素センサ１１からの発光の強度に基づいて、酸素分圧を測定し、血管中の酸素濃度を求める。   Next, referring to FIG. 2, the entire transcutaneous oxygen concentration measuring device 31 for measuring the oxygen concentration in the blood vessel from the transcutaneous oxygen partial pressure measured using the transcutaneous oxygen sensor 11 shown in FIG. The configuration will be described. The transdermal oxygen concentration measuring device 31 includes the transdermal oxygen sensor 11 shown in FIG. 1, an excitation light source 33, a light emission intensity measuring device 35, and a computing device 37, and a resin film coated with an adhesive. The partial pressure of oxygen is measured based on the intensity of light emitted from the transcutaneous oxygen sensor 11 attached to the patient's skin 39 with the surface 13 facing the patient's skin 39, and the oxygen concentration in the blood vessel is obtained.

励起光源３３は、経皮酸素センサ１１の測定用色素化合物１７を励起状態にさせる波長の励起光を発し、経皮酸素センサ１１に照射する。励起光源３３としては、市販されるＬＥＤ光源を使用することができる。色素化合物１７として、白金（ＩＩ）−オクタエチルポルフィリン、白金（ＩＩ）−テトラキスカルボキシフェニルポルフィリン、又は白金（ＩＩ）−テトラキスペンタフルオロフェニルポルフィリンを用いる場合、励起光源３３として、例えば発光波長４０５ｎｍのＬＥＤ光源を用いることができる。   The excitation light source 33 emits excitation light having a wavelength that causes the measurement dye compound 17 of the transcutaneous oxygen sensor 11 to be in an excited state, and irradiates the transcutaneous oxygen sensor 11. As the excitation light source 33, a commercially available LED light source can be used. When platinum (II) -octaethylporphyrin, platinum (II) -tetrakiscarboxyphenylporphyrin, or platinum (II) -tetrakispentafluorophenylporphyrin is used as the dye compound 17, for example, an LED having an emission wavelength of 405 nm is used as the excitation light source 33. A light source can be used.

発光強度測定器３５は、励起光源３３から経皮酸素センサ１１に励起光を照射したときに経皮酸素センサ１１の測定用色素化合物１７から発せられる光の強度から酸素分圧又は酸素濃度を測定し、測定された酸素分圧又は酸素濃度に基づいてさらに血管中の酸素濃度を求める。図１に示されている実施形態では、発光強度測定器３５は、光計測プローブ４１と、分光計４３とによって構成されており、経皮酸素センサ１１からのリン光強度を測定できるようになっている。経皮酸素センサ１１のポリマ体１５に補正用色素化合物２１が含まれているときには、発光強度測定器３５は、測定用色素化合物１７からのリン光と共に補正用色素化合物２１からの蛍光も測定する。光計測プローブ４１は、励起光源３３からの励起光を通す光源用ファイバ４１ａと反射光を通すための測定用ファイバ４１ｂとを備えており、励起光源３３からの励起光を光源用ファイバ４１ａを通して経皮酸素センサ１１に照射し、経皮酸素センサ１１からの発光を測定用ファイバ４１ｂを通して分光計４３に導くことができる。分光計４３は、光計測プローブ４１を通して導かれた測定光のスペクトル分析を行い、測定用色素化合物１７からのリン光に相当する波長付近の極大ピーク波長の強度をリン光強度として測定する。また、経皮酸素センサ１１のポリマ体１５に補正用色素化合物２１が含まれているときには、分光計４３は、リン光強度と共に、補正用色素化合物２１からの蛍光に相当する波長付近の極大ピーク波長の強度を蛍光強度として測定する。   The emission intensity measuring device 35 measures the partial pressure of oxygen or the oxygen concentration from the intensity of light emitted from the measurement dye compound 17 of the transdermal oxygen sensor 11 when the excitation light source 33 irradiates the transcutaneous oxygen sensor 11 with excitation light. Then, the oxygen concentration in the blood vessel is further determined based on the measured oxygen partial pressure or oxygen concentration. In the embodiment shown in FIG. 1, the emission intensity measuring device 35 includes an optical measurement probe 41 and a spectrometer 43, and can measure the phosphorescence intensity from the transcutaneous oxygen sensor 11. ing. When the correction dye compound 21 is included in the polymer body 15 of the transcutaneous oxygen sensor 11, the emission intensity measuring device 35 measures the fluorescence from the correction dye compound 21 together with the phosphorescence from the measurement dye compound 17. . The optical measurement probe 41 includes a light source fiber 41a for passing excitation light from the excitation light source 33 and a measurement fiber 41b for allowing reflected light to pass, and passes the excitation light from the excitation light source 33 through the light source fiber 41a. The skin oxygen sensor 11 can be irradiated to emit light from the transcutaneous oxygen sensor 11 to the spectrometer 43 through the measurement fiber 41b. The spectrometer 43 performs spectrum analysis of the measurement light guided through the optical measurement probe 41 and measures the intensity of the maximum peak wavelength near the wavelength corresponding to the phosphorescence from the measurement dye compound 17 as the phosphorescence intensity. Further, when the correction pigment compound 21 is included in the polymer body 15 of the transcutaneous oxygen sensor 11, the spectrometer 43 has a maximum peak around the wavelength corresponding to the fluorescence from the correction pigment compound 21 together with the phosphorescence intensity. The intensity of the wavelength is measured as the fluorescence intensity.

なお、本実施形態では、経皮酸素センサ１１の測定用色素化合物１７からリン光が生じる場合を説明しているが、測定用色素化合物１７からリン光以外の光が発せられる場合でも、励起光や蛍光に相当する波長以外の極大波長ピークの発光強度を測定すればよい。   In this embodiment, the case where phosphorescence is generated from the measurement dye compound 17 of the transcutaneous oxygen sensor 11 is described. However, even when light other than phosphorescence is emitted from the measurement dye compound 17, excitation light is emitted. And the emission intensity at the maximum wavelength peak other than the wavelength corresponding to the fluorescence may be measured.

演算装置３７は、発光強度測定装置３５によって測定された測定用色素化合物１７からの発光の強度から酸素分圧を求め、求められた酸素分圧から血管中の酸素濃度を推測する。経皮酸素センサ１１のポリマ体１５に補正用色素化合物２１が含まれている場合には、演算装置３７は、測定用色素化合物１７からの発光の強度と補正用色素化合物２１からの発光の強度との比から、酸素分圧を求め、血管中の酸素濃度を推測する。本実施形態では、演算装置３７は、測定用色素化合物１７からのリン光の強度と補正用色素化合物２１からの蛍光の強度との比から、酸素分圧を求め、求められた酸素分圧から血管中の酸素濃度を推測する。   The arithmetic unit 37 obtains the oxygen partial pressure from the intensity of light emitted from the measuring dye compound 17 measured by the light emission intensity measuring device 35, and estimates the oxygen concentration in the blood vessel from the obtained oxygen partial pressure. When the correction dye compound 21 is included in the polymer body 15 of the transcutaneous oxygen sensor 11, the arithmetic unit 37 calculates the intensity of light emission from the measurement dye compound 17 and the intensity of light emission from the correction dye compound 21. From this ratio, the oxygen partial pressure is obtained, and the oxygen concentration in the blood vessel is estimated. In the present embodiment, the arithmetic unit 37 obtains the oxygen partial pressure from the ratio of the phosphorescence intensity from the measurement dye compound 17 and the fluorescence intensity from the correction dye compound 21, and from the obtained oxygen partial pressure. Estimate the oxygen concentration in the blood vessels.

ここで、図３を参照して、本発明の経皮酸素濃度測定測定装置３１の測定原理を説明する。基底状態にある測定用色素化合物１７や補正用色素化合物２１が励起光によって光励起されると、励起一重項状態に遷移する。励起一重項状態の測定用色素化合物１７や補正用色素化合物２１は、熱の放出による無放射遷移又は光の放出による放射遷移で基底状態に戻り、この放射遷移の際に放出される光が蛍光であり、その寿命は１０−７〜１０−１０秒と、非常に短い。一般的に励起一重項状態の色素化合物は酸素分子と反応しないため、消光されない場合が多い。また、励起一重項状態にある色素化合物の一部は系間交差により励起三重項状態となり、励起三重項状態から基底状態へ放射遷移するときに放出される光がリン光である。このときの放射遷移は禁制遷移であるため、その確率は低く、リン光寿命は１０−５〜１０秒と、蛍光寿命よりも長い。励起三重項状態の色素化合物から酸素分子へはエネルギ移動が起こりやすいため、リン光は酸素分子との反応（消光反応）により容易に消光され、リン光強度は酸素分子の存在により減少する。このときのリン光強度は以下のＳｔｅｒｎ−Ｖｏｌｍｅｒの式（１）に従うことが知られている。
Ｉ０／Ｉ＝１＋ＫＳＶ［Ｏ２］ （１）
ここで、Ｉ０とＩはそれぞれ酸素非存在時と酸素存在時におけるリン光強度、ＫＳＶはＳｔｅｒｎ−Ｖｏｌｍｅｒ定数、［Ｏ２］は酸素濃度である。したがって、リン光強度を測定することによって酸素濃度すなわち大気圧下での酸素分圧を求めることができる。一方、血管中の酸素は、毛細血管の血液中から皮膚組織を含む生体組織を経て体外へ拡散する。したがって、皮膚表面で生体組織を経て拡散する酸素の濃度すなわち大気圧下での酸素分圧を測定すれば、血管壁の酸素透過率や生体組織による酸素消費を考慮して、測定した酸素濃度又は酸素分圧から血管中の酸素濃度が求められる。 Here, with reference to FIG. 3, the measurement principle of the transdermal oxygen concentration measurement and measurement apparatus 31 of the present invention will be described. When the measurement dye compound 17 or the correction dye compound 21 in the ground state is photoexcited by excitation light, the state transitions to the excited singlet state. The excited singlet state measurement dye compound 17 and the correction dye compound 21 return to the ground state by a non-radiative transition due to heat emission or a radiative transition due to light emission, and light emitted at the time of this radiative transition is fluorescent. The lifetime is as short as 10 −7 to 10 −10 seconds. In general, a dye compound in an excited singlet state does not react with oxygen molecules and thus is often not quenched. In addition, a part of the dye compound in the excited singlet state becomes an excited triplet state due to intersystem crossing, and light emitted when the radiation transition from the excited triplet state to the ground state is phosphorescence. Since the radiation transition at this time is a forbidden transition, the probability is low, and the phosphorescence lifetime is 10 −5 to 10 seconds, which is longer than the fluorescence lifetime. Since energy transfer easily occurs from the excited triplet state dye compound to the oxygen molecule, phosphorescence is easily quenched by reaction with the oxygen molecule (quenching reaction), and the phosphorescence intensity decreases due to the presence of the oxygen molecule. It is known that the phosphorescence intensity at this time follows the following Stern-Volmer equation (1).
I 0 / I = 1 + K SV [O 2 ] (1)
Here, I 0 and I are phosphorescence intensities in the absence and presence of oxygen, K SV is the Stern-Volmer constant, and [O 2 ] is the oxygen concentration. Therefore, by measuring the phosphorescence intensity, the oxygen concentration, that is, the oxygen partial pressure under atmospheric pressure can be obtained. On the other hand, oxygen in blood vessels diffuses from the blood of capillaries through living tissues including skin tissues to the outside of the body. Therefore, if the concentration of oxygen diffused through the biological tissue on the skin surface, that is, the partial pressure of oxygen under atmospheric pressure is measured, the measured oxygen concentration or The oxygen concentration in the blood vessel is obtained from the oxygen partial pressure.

本発明による経皮酸素センサ１１を利用した経皮酸素濃度測定装置３１では、患者の皮膚に経皮酸素センサ１１を貼り付けて酸素濃度すなわち大気圧下での酸素分圧を測定するとき、ガス不透過性の樹脂フィルム１３と皮膚表面との間の空間では酸素分圧が毛細血管中の酸素分圧と平衡に達することを利用して、大気圧と等しくなっている樹脂フィルム１３と皮膚表面との間の空間における酸素分圧を経皮酸素センサ１１からのリン光の強度から上記原理に従って測定し、測定された酸素分圧から血管中の酸素濃度を求める。   In the transcutaneous oxygen concentration measuring device 31 using the transcutaneous oxygen sensor 11 according to the present invention, when the transcutaneous oxygen sensor 11 is attached to the skin of a patient and the oxygen concentration, that is, the partial pressure of oxygen under atmospheric pressure, is measured, In the space between the impermeable resin film 13 and the skin surface, the oxygen partial pressure reaches equilibrium with the oxygen partial pressure in the capillaries, and the resin film 13 and the skin surface are equal to the atmospheric pressure. Is measured from the intensity of phosphorescence from the transcutaneous oxygen sensor 11 according to the above principle, and the oxygen concentration in the blood vessel is obtained from the measured oxygen partial pressure.

次に、酸素濃度測定装置３１を用いた経皮酸素分圧及び血管中の酸素濃度の測定手順を説明する。以下、ガス不透過性の透明樹脂フィルム１３として延伸ポリエチレンフィルムを、ポリマ体１５としてポリ酢酸ビニルを、測定用色素化合物１７として白金（ＩＩ）−テトラキスカルボキシフェニルポルフィリン（Ｐｔ−ＴＣＰＰ）を、補正用色素化合物２１としてクマリンを採用した経皮酸素センサ１１と、波長４０５ｎｍの励起光を生ずる励起光源３３とを備える酸素濃度測定装置３１を用いた実施例を参照して説明する。なお、測定用色素化合物１７及び補正用色素化合物２１を含有するポリマー体１５のフィルムは、メタノールに溶解した５．７×１０−４ｍｏｌ／ＬのＰｔ−ＴＣＰＰ８μＬと５．９×１０−４ｍｏｌ／Ｌのクマリン３μＬをポリ酢酸ビニルの重量濃度１０％のアセトン溶液６０μＬに混合したものを１０μＬずつポリプロピレンフィルム上に滴下し、乾燥させたものをポリプロピレンフィルムから剥がすことにより作製した。 Next, a procedure for measuring the transdermal oxygen partial pressure and the oxygen concentration in the blood vessel using the oxygen concentration measuring device 31 will be described. Hereinafter, a stretched polyethylene film is used as the gas-impermeable transparent resin film 13, polyvinyl acetate is used as the polymer body 15, and platinum (II) -tetrakiscarboxyphenylporphyrin (Pt-TCPP) is used as the measurement dye compound 17. A description will be given with reference to an embodiment using an oxygen concentration measuring apparatus 31 including a transdermal oxygen sensor 11 employing coumarin as the dye compound 21 and an excitation light source 33 that generates excitation light having a wavelength of 405 nm. In addition, the film of the polymer body 15 containing the pigment compound for measurement 17 and the pigment compound for correction 21 is 5.7 × 10 −4 mol / L Pt-TCPP 8 μL and 5.9 × 10 −4 mol dissolved in methanol. 10 μL of a mixture of 3 μL of / L coumarin in 60 μL of a 10% weight concentration acetone solution of polyvinyl acetate was dropped onto the polypropylene film, and the dried product was peeled off from the polypropylene film.

まず、測定に先立ち、酸素分圧を変えながら、発光強度測定器３５を用いて経皮酸素センサ１１から発せられるリン光の強度を測定し、酸素分圧と経皮酸素センサ１１から発せられるリン光の強度との相関関係を予め求めておく。   First, prior to the measurement, the intensity of phosphorescence emitted from the transcutaneous oxygen sensor 11 is measured using the luminescence intensity measuring device 35 while changing the oxygen partial pressure, and the oxygen partial pressure and phosphorus emitted from the transcutaneous oxygen sensor 11 are measured. A correlation with light intensity is obtained in advance.

図４は、本実施例の経皮酸素センサ１１について、波長４０５ｎｍの励起光を用いたときの酸素分圧とリン光強度との相関関係を示すグラフである。また、図５は、図４の結果に基づいたＳｔｅｒｎ−Ｖｏｌｍｅｒプロットを示すグラフである。さらに、図６は、経皮酸素センサ１１について、波長４０５ｎｍの励起光を用いたときの酸素分圧とリン光強度に対する蛍光強度との相関関係を示すグラフである。測定は、サンプルチャンバ内に経皮酸素センサ１１を配置して、サンプルチャンバ内の酸素分圧を変化させ、励起光源３３（ＬＥＤ光源）から経皮酸素センサ１１に波長４０５ｎｍ励起光を照射したときの経皮酸素センサ１１からの反射光を光計測プローブ４１を用いて分光計４３に導き、測定用色素化合物１７からのリン光に相当する波長付近における極大ピーク波長の強度と補正用色素化合物２１からの蛍光に相当する波長付近における極大ピーク波長の強度を求めることにより行った。図５から、Ｓｔｅｒｎ−Ｖｏｌｍｅｒプロット曲線に沿った相関関係を有しており、経皮酸素センサ１１が酸素を消光剤として反応していることが分かる。   FIG. 4 is a graph showing the correlation between oxygen partial pressure and phosphorescence intensity when using excitation light with a wavelength of 405 nm for the transcutaneous oxygen sensor 11 of this example. FIG. 5 is a graph showing a Stern-Volmer plot based on the result of FIG. Further, FIG. 6 is a graph showing the correlation between the oxygen partial pressure and the fluorescence intensity with respect to the phosphorescence intensity when the excitation light having a wavelength of 405 nm is used for the transdermal oxygen sensor 11. The measurement is performed when the transcutaneous oxygen sensor 11 is arranged in the sample chamber, the oxygen partial pressure in the sample chamber is changed, and the transcutaneous oxygen sensor 11 is irradiated with excitation light having a wavelength of 405 nm from the excitation light source 33 (LED light source). The reflected light from the percutaneous oxygen sensor 11 is guided to the spectrometer 43 using the optical measurement probe 41, the intensity of the maximum peak wavelength in the vicinity of the wavelength corresponding to the phosphorescence from the measurement dye compound 17, and the correction dye compound 21. The maximum peak wavelength intensity in the vicinity of the wavelength corresponding to the fluorescence from was obtained. FIG. 5 shows that there is a correlation along the Stern-Volmer plot curve, and that the transdermal oxygen sensor 11 is reacting with oxygen as a quencher.

測定の際には、最初に、粘着剤１９が塗布され且つポリマ体１５が固着された樹脂フィルム１３の面を患者の皮膚３９側へ向けて経皮酸素センサ１１を患者の皮膚３９へ貼り付ける。このとき、経皮酸素センサ１１を貼り付けた部分の皮膚を加温して所定温度に到達させることが好ましい。測定用色素化合物１７及び補正用色素化合物２１が含有されるポリマ体１５はガス不透過性の樹脂フィルム１３に固着されており、樹脂フィルム１３は患者の体表面の形状に容易に追従して変形し、皮膚に密着して貼り付けられる。したがって、ガス不透過性の樹脂フィルム１３と皮膚との間に密閉された空間を形成することができ、当該空間中の酸素分圧が血管中の酸素分圧と平衡状態になる。   In measurement, first, the transcutaneous oxygen sensor 11 is attached to the patient's skin 39 with the surface of the resin film 13 to which the adhesive 19 is applied and the polymer body 15 is fixed facing the patient's skin 39 side. . At this time, it is preferable to heat the skin where the transcutaneous oxygen sensor 11 is attached to reach a predetermined temperature. The polymer body 15 containing the dye compound 17 for measurement and the dye compound 21 for correction is fixed to a gas-impermeable resin film 13, and the resin film 13 easily follows the shape of the patient's body surface and deforms. And sticks to the skin. Therefore, a sealed space can be formed between the gas-impermeable resin film 13 and the skin, and the oxygen partial pressure in the space is in equilibrium with the oxygen partial pressure in the blood vessel.

次に、励起光源３３から光計測プローブ４１の光源用ファイバ４１ａを通して励起光を経皮酸素センサ１１のポリマ体１５に照射し、ポリマ体１５からの光（以下、反射光と記載する。）を発光強度測定装置３５の光計測プローブ４１の測定用ファイバ４１ｂを通して発光強度測定装置３５の分光計４３に導く。励起光により励起状態になった測定用色素化合物１７はリン光を発し、励起光により励起状態になった補正用色素化合物２１からは蛍光を発する。したがって、反射光中には、励起光の反射成分とポリマ体１５中の測定用色素１７からのリン光と補正用色素化合物２１からの蛍光とが含まれる。   Next, the excitation light is irradiated onto the polymer body 15 of the transcutaneous oxygen sensor 11 from the excitation light source 33 through the light source fiber 41a of the optical measurement probe 41, and light from the polymer body 15 (hereinafter referred to as reflected light). The light is guided to the spectrometer 43 of the light emission intensity measuring device 35 through the measurement fiber 41 b of the optical measurement probe 41 of the light emission intensity measuring device 35. The measurement dye compound 17 that has been excited by excitation light emits phosphorescence, and the correction dye compound 21 that has been excited by excitation light emits fluorescence. Therefore, the reflected light includes a reflection component of excitation light, phosphorescence from the measurement dye 17 in the polymer body 15, and fluorescence from the correction dye compound 21.

分光計４３は、反射光のスペクトル分析を行い、測定用色素化合物１７からのリン光に相当する波長付近の極大ピーク波長の強度をリン光強度として測定すると共に、補正用色素化合物２１からの蛍光に相当する波長付近の極大ピーク波長の強度を蛍光強度として測定する。   The spectrometer 43 performs spectral analysis of the reflected light, measures the intensity of the maximum peak wavelength near the wavelength corresponding to the phosphorescence from the measurement dye compound 17 as the phosphorescence intensity, and emits the fluorescence from the correction dye compound 21. The intensity of the maximum peak wavelength near the wavelength corresponding to is measured as the fluorescence intensity.

図７は、実施例の経皮酸素センサ１１を使用し且つ波長４０５ｎｍの励起光を用いたときの経皮酸素センサ１１からの発光スペクトルを示すグラフである。図７中矢印Ａで示されているピークは励起光の波長、矢印Ｂで示されているピークは補正用色素化合物２１からの蛍光の波長、矢印Ｃで示されているピークは測定用色素化合物１７からのリン光の波長であり、矢印Ｂで示されているピークの波長の強度が蛍光強度として、矢印Ｃで示されているピークの波長の強度がリン光強度として測定される。   FIG. 7 is a graph showing an emission spectrum from the transcutaneous oxygen sensor 11 when the transcutaneous oxygen sensor 11 of the example is used and excitation light having a wavelength of 405 nm is used. In FIG. 7, the peak indicated by arrow A is the wavelength of the excitation light, the peak indicated by arrow B is the wavelength of the fluorescence from the correction dye compound 21, and the peak indicated by arrow C is the measurement dye compound. 17 is the wavelength of phosphorescence from 17, the intensity of the peak wavelength indicated by arrow B is measured as fluorescence intensity, and the intensity of the peak wavelength indicated by arrow C is measured as phosphorescence intensity.

次に、演算装置３７は、予め求められている、酸素分圧と経皮酸素センサ１１から発せられるリン光の強度との相関関係（図４参照）又はＳｔｅｒｎ−Ｖｏｌｍｅｒプロット曲線（図５参照）を用いて、発光強度測定装置３５の分光計４３によって測定されたリン光強度から酸素分圧を求め、求められた酸素分圧から血管中の酸素濃度を推定する。   Next, the arithmetic unit 37 obtains a correlation between the oxygen partial pressure and the intensity of phosphorescence emitted from the transcutaneous oxygen sensor 11 (see FIG. 4) or a Stern-Volmer plot curve (see FIG. 5). The oxygen partial pressure is obtained from the phosphorescence intensity measured by the spectrometer 43 of the emission intensity measuring device 35, and the oxygen concentration in the blood vessel is estimated from the obtained oxygen partial pressure.

演算装置３７は、図６に示されている、酸素分圧と経皮酸素センサからのリン光の強度に対する蛍光の強度の比との相関関係を用いて、発光強度測定装置３５の分光計４３によって測定された蛍光強度とリン光強度の比から酸素分圧を求め、求められた酸素分圧から血管中の酸素濃度を推定してもよい。発光強度測定装置３５によって測定されるリン光強度は、励起光の照射角度などによって変化する励起光の強度や光計測プローブ４１の向きなどによって変化するリン光の検出効率の影響を受ける。リン光強度が酸素の存在の影響を受けるのに対して蛍光強度は酸素の存在の影響をほとんど受けないことを利用して、リン光強度と同じように測定条件の影響を受ける蛍光強度によりリン光強度を補正し、酸素分圧と経皮酸素センサからのリン光の強度に対する蛍光の強度の比に基づいて酸素分圧を求めることにより、上述した励起光の強度やリン光の検出効率などの影響を抑制し、より正確な酸素分圧を求めることが可能となる。   The computing device 37 uses the correlation between the partial pressure of oxygen and the ratio of the fluorescence intensity to the phosphorescence intensity from the transcutaneous oxygen sensor shown in FIG. The oxygen partial pressure may be obtained from the ratio of the fluorescence intensity and the phosphorescence intensity measured by the above, and the oxygen concentration in the blood vessel may be estimated from the obtained oxygen partial pressure. The phosphorescence intensity measured by the emission intensity measuring device 35 is affected by the detection efficiency of phosphorescence that varies depending on the intensity of excitation light that varies depending on the irradiation angle of the excitation light, the direction of the optical measurement probe 41, and the like. Utilizing the fact that the fluorescence intensity is hardly affected by the presence of oxygen while the phosphorescence intensity is affected by the presence of oxygen, phosphorescence is affected by the fluorescence intensity affected by the measurement conditions in the same way as the phosphorescence intensity. By correcting the light intensity and calculating the oxygen partial pressure based on the ratio of the fluorescence intensity to the oxygen partial pressure and the phosphorescence intensity from the transcutaneous oxygen sensor, the above-described excitation light intensity, phosphorescence detection efficiency, etc. Thus, it is possible to obtain a more accurate oxygen partial pressure.

経皮酸素センサ１１では、測定に利用される測定用色素化合物１７や補正用色素化合物２１を含有するポリマ体１５が樹脂フィルム１３に固着され、固着されている樹脂フィルム１３の面におけるポリマ体１５の周囲に粘着剤が塗布されている。したがって、経皮酸素センサ１１によれば、樹脂フィルム１３は体表の形状に追従して柔軟に変形し、皮膚に密着固定されると共に、皮膚と樹脂フィルム１３との間に血管の酸素分圧と平衡させるための密閉された空間を形成することができる。また、経皮酸素センサ１１を用いた経皮酸素濃度測定装置３１によれば、経皮酸素センサ１１を用いて血管中の酸素分圧と相関する皮膚表面の酸素分圧を光学的に測定でき、皮膚表面の酸素分圧から血管中の酸素濃度を求めることができるので、血管中の血液を採取することなく、血管中の酸素濃度を測定することができる。   In the transcutaneous oxygen sensor 11, a polymer body 15 containing the measurement dye compound 17 and the correction dye compound 21 used for measurement is fixed to the resin film 13, and the polymer body 15 on the surface of the fixed resin film 13. An adhesive is applied around the. Therefore, according to the transcutaneous oxygen sensor 11, the resin film 13 flexibly deforms following the shape of the body surface, is closely fixed to the skin, and the oxygen partial pressure of the blood vessel between the skin and the resin film 13. It is possible to form a sealed space for equilibrating with. Further, according to the transcutaneous oxygen concentration measuring device 31 using the transcutaneous oxygen sensor 11, the oxygen partial pressure on the skin surface correlated with the oxygen partial pressure in the blood vessel can be optically measured using the transcutaneous oxygen sensor 11. Since the oxygen concentration in the blood vessel can be obtained from the oxygen partial pressure on the skin surface, the oxygen concentration in the blood vessel can be measured without collecting blood in the blood vessel.

以上、図示されている実施形態を参照して、本発明による経皮酸素センサ１１及びこれを用いた経皮酸素濃度測定装置３１を説明したが、本発明は図示されている実施形態に限定されるものではない。例えば、図示されている実施形態では、スペクトル分析によりリン光強度を測定しているが、励起光の波長が測定用色素化合物からのリン光の波長と大きく異なるように励起光源が選択されていれば、波長による色の差を利用して、反射光をＣＣＤカメラ等で撮影し、画像解析で反射光の色の変化を検出して視覚的にリン光強度を測定することも可能である。図示されている実施形態と同様に、波長４０５ｎｍの励起光を用い、経皮酸素センサ１１の測定用色素化合物１７として白金（ＩＩ）−テトラキスカルボキシフェニルポルフィリンを用いる場合、励起光は青色となり、測定用色素化合物１７からのリン光は赤色となるので、画像解析などによりリン光強度を視覚的に測定することが可能である。   As described above, the transcutaneous oxygen sensor 11 and the transcutaneous oxygen concentration measuring device 31 using the same according to the present invention have been described with reference to the illustrated embodiment. However, the present invention is limited to the illustrated embodiment. It is not something. For example, in the illustrated embodiment, the phosphorescence intensity is measured by spectral analysis, but the excitation light source is selected so that the wavelength of the excitation light is significantly different from the wavelength of the phosphorescence from the measurement dye compound. For example, the reflected light can be photographed with a CCD camera or the like using the color difference depending on the wavelength, and the phosphorescence intensity can be measured visually by detecting the color change of the reflected light by image analysis. Similarly to the illustrated embodiment, when excitation light having a wavelength of 405 nm is used and platinum (II) -tetrakiscarboxyphenylporphyrin is used as the measurement dye compound 17 of the transcutaneous oxygen sensor 11, the excitation light becomes blue, and measurement is performed. Since phosphorescence from the dye compound 17 for use becomes red, it is possible to visually measure the phosphorescence intensity by image analysis or the like.

１１ 光学的経皮酸素センサ
１３ 樹脂フィルム
１５ ポリマ体
１７ 測定用色素化合物
１９ 粘着剤
２１ 補正用色素化合物
３１ 経皮酸素濃度測定装置
３３ 励起光源
３５ 発光強度測定装置
４１ 光計測プローブ
４３ 分光計 DESCRIPTION OF SYMBOLS 11 Optical transcutaneous oxygen sensor 13 Resin film 15 Polymer body 17 Dye compound for measurement 19 Adhesive 21 Dye compound for correction 31 Transcutaneous oxygen concentration measuring device 33 Excitation light source 35 Luminous intensity measuring device 41 Optical measurement probe 43 Spectrometer

Claims (10)

血液中から生体組織を経て拡散する酸素を皮膚表面で測定する光学的経皮酸素センサであって、
ガス不透過性の透明な樹脂フィルムと、
励起状態下で発光し酸素濃度に応じて発光強度を変化させる色素化合物を含有する透明なポリマ体と、
を備え、前記樹脂フィルムの一方の表面に前記ポリマ体が固着され、前記表面における前記ポリマ体の周囲に粘着剤が塗布されていることを特徴とする光学的経皮酸素センサ。 An optical transcutaneous oxygen sensor that measures oxygen diffused from blood through living tissue on the skin surface,
A gas impermeable transparent resin film,
A transparent polymer body containing a dye compound that emits light in an excited state and changes emission intensity according to the oxygen concentration;
An optical transcutaneous oxygen sensor, wherein the polymer body is fixed to one surface of the resin film, and an adhesive is applied around the polymer body on the surface. 前記ポリマ体がフィルム形状である、請求項１に記載の光学的経皮酸素センサ。   The optical transcutaneous oxygen sensor according to claim 1, wherein the polymer body has a film shape. 前記ポリマ体が前記樹脂フィルムよりも酸素透過度が高い樹脂材料から形成されている、請求項２に記載の光学的経皮酸素センサ。   The optical transcutaneous oxygen sensor according to claim 2, wherein the polymer body is formed of a resin material having a higher oxygen permeability than that of the resin film. 前記色素化合物が白金（ＩＩ）−オクタエチルポルフィリン、白金（ＩＩ）−テトラキスカルボキシフェニルポルフィリン又は白金（ＩＩ）−テトラキスペンタフルオロフェニルポルフィリンである、請求項１から請求項３の何れか一項に記載の光学的経皮酸素センサ。   The said pigment | dye compound is platinum (II) -octaethyl porphyrin, platinum (II) -tetrakis carboxyphenyl porphyrin, or platinum (II) -tetrakis pentafluorophenyl porphyrin, It is any one of Claims 1-3. Optical transcutaneous oxygen sensor. 前記色素化合物が励起状態でリン光を発するリン光化合物であり、前記ポリマ体が、励起状態下で蛍光を発する蛍光化合物をさらに含有する、請求項１から請求項４の何れか一項に記載の光学的経皮酸素センサ。   The said pigment | dye compound is a phosphorescence compound which emits a phosphorescence in an excited state, The said polymer body further contains the fluorescent compound which emits a fluorescence in an excited state, The method as described in any one of Claims 1-4. Optical transcutaneous oxygen sensor. 前記蛍光化合物がクマリンである、請求項５に記載の光学的経皮酸素センサ。   The optical transdermal oxygen sensor according to claim 5, wherein the fluorescent compound is coumarin. 前記樹脂フィルムが延伸高密度ポリエチレンから形成されている、請求項１から請求項６の何れか一項に記載の光学的経皮酸素センサ。   The optical transcutaneous oxygen sensor according to any one of claims 1 to 6, wherein the resin film is formed of stretched high-density polyethylene. 患者の皮膚に貼り付けられる請求項１から請求項４の何れか一項に記載の光学的経皮酸素センサと、
前記光学的経皮酸素センサに励起光を照射する励起光源と、
前記励起光源によって照射された前記光学的経皮酸素センサからの発光強度を測定する発光強度測定器と、
を備え、前記発光強度測定器によって測定された発光強度に基づいて、血管中の酸素の濃度が求められることを特徴とする経皮酸素濃度測定装置。 The optical transcutaneous oxygen sensor according to any one of claims 1 to 4, which is attached to a patient's skin;
An excitation light source for irradiating the optical transcutaneous oxygen sensor with excitation light;
A light emission intensity measuring device for measuring light emission intensity from the optical transcutaneous oxygen sensor irradiated by the excitation light source;
A transcutaneous oxygen concentration measuring device, characterized in that the oxygen concentration in the blood vessel is obtained based on the luminescence intensity measured by the luminescence intensity measuring device. 前記色素化合物が励起状態でリン光を発するリン光化合物であり、前記光学的経皮酸素センサの前記ポリマ体が、励起状態下で蛍光を発する蛍光化合物をさらに含有し、前記発光強度測定器がリン光の強度と同時に蛍光の強度も測定し、測定された蛍光の強度に対するリン光の強度の比に基づいて、血管中の酸素濃度が求められる、請求項８に記載の経皮酸素濃度測定装置。   The dye compound is a phosphorescent compound that emits phosphorescence in an excited state, and the polymer body of the optical transcutaneous oxygen sensor further contains a fluorescent compound that emits fluorescence in the excited state, and the emission intensity measuring device includes The transcutaneous oxygen concentration measurement according to claim 8, wherein the fluorescence intensity is measured simultaneously with the phosphorescence intensity, and the oxygen concentration in the blood vessel is determined based on the ratio of the phosphorescence intensity to the measured fluorescence intensity. apparatus. 前記発光強度測定器が分光計及び光計測プローブによって構成されており、前記光計測プローブを通して前記励起光源から前記光学的経皮酸素センサに励起光を照射し、前記光計測プローブを通して、前記光学的経皮酸素センサから発せられた蛍光及びリン光を前記分光計に導く、請求項９に記載の経皮酸素濃度測定装置。   The emission intensity measuring device is constituted by a spectrometer and an optical measurement probe, irradiates excitation light from the excitation light source to the optical transcutaneous oxygen sensor through the optical measurement probe, and passes the optical measurement probe through the optical measurement probe. The transcutaneous oxygen concentration measuring apparatus according to claim 9, wherein fluorescence and phosphorescence emitted from a transcutaneous oxygen sensor are guided to the spectrometer.
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