JP7754735B2 - Dialysis effluent component measuring device and method - Google Patents
Dialysis effluent component measuring device and methodInfo
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Description
本発明は、透析排液用成分測定装置及び方法に関する。 The present invention relates to a device and method for measuring components in dialysis effluent.
血液浄化装置では、血液浄化器(ダイアライザとも呼称される)において、血液浄化膜を介して血液と透析液とを接触させることで、血液を浄化する。この際、血液中の特定の成分が透析液へと漏出し過ぎると、合併症等の不具合が発生するおそれがある。よって、このような不具合を避けるため、血液浄化器から排出された透析排液中の特定の成分の濃度を監視することが望まれる。 In blood purification devices, the blood is purified by bringing the blood into contact with the dialysate via a blood purification membrane in a blood purifier (also called a dialyzer). If excessive leakage of certain components from the blood into the dialysate occurs, complications and other problems may occur. Therefore, to avoid such problems, it is desirable to monitor the concentrations of certain components in the dialysis effluent discharged from the blood purifier.
透析排液で監視が望まれる成分(被測定成分という)として、例えばアルブミンがある。特許文献1では、液中のアルブミンに対して光励起を行い、発生する蛍光を測定することで、アルブミンの濃度を測定する方法が開示されている。 One example of a component (referred to as a measured component) that may be desired to be monitored in dialysis effluent is albumin. Patent Document 1 discloses a method for measuring albumin concentration by optically exciting albumin in the fluid and measuring the resulting fluorescence.
しかしながら、蛍光は光強度が小さく、特に、被測定成分の濃度が低いときには、測定精度が低下してしまうおそれがある。例えば、被測定成分がアルブミンである場合、このアルブミンは血液から漏出し過ぎてはならない成分であるため、通常はアルブミンの濃度はそれほど高くならないと考えられる。そのため、被測定成分の濃度が低い状態でも精度よく濃度を測定することが望まれる。 However, fluorescence has a low light intensity, and measurement accuracy may decrease, especially when the concentration of the component being measured is low. For example, if the component being measured is albumin, this is a component that should not leak too much from the blood, so it is thought that the concentration of albumin would not normally be very high. For this reason, it is desirable to be able to measure the concentration of the component being measured accurately even when its concentration is low.
そこで、本発明は、透析排液中の被測定成分の濃度を精度よく測定可能な透析排液用成分測定装置及び方法を提供することを目的とする。 The present invention aims to provide a dialysis effluent component measuring device and method that can accurately measure the concentration of a target component in dialysis effluent.
本発明の一実施の形態に係る透析排液用成分測定装置は、血液浄化器から排出された透析排液中に含まれる被測定成分の濃度を測定する装置であって、前記被測定成分は、第1波長の光を吸収し、かつ前記第1波長の光で励起され前記第1波長と異なる第2波長の蛍光を発する成分であり、前記透析排液中には、前記第1波長の光を吸収し、かつ、前記第1波長の光で励起され前記第1及び第2波長と異なる第3波長の蛍光を発する測定阻害成分が含まれており、前記透析排液に前記第1波長の光を照射する光源と、前記光源からの光が前記透析排液を透過した透過光の光強度を測定し、当該透過光の光強度と前記光源の光強度とから前記第1波長における吸光度を求める吸光度測定部と、前記光源からの光により励起され前記被測定成分が放出する前記第2波長の蛍光の光強度を測定する第1蛍光測定部と、前記光源からの光により励起され前記測定阻害成分が放出する前記第3波長の蛍光の光強度を測定する第2蛍光測定部と、前記第1及び第2蛍光測定部の測定結果を基に、前記透析排液中に含まれる前記被測定成分の濃度と前記測定阻害成分との濃度の比率を演算する比率演算部と、前記比率演算部が演算した濃度の比率と、前記吸光度測定部が測定した前記第1波長における吸光度とを基に、前記透析排液中の前記被測定成分の濃度を演算する被測定成分濃度演算部と、を備えた。 A dialysis effluent component measuring device according to one embodiment of the present invention is a device for measuring the concentration of a metered component contained in dialysis effluent discharged from a blood purifier, wherein the metered component is a component that absorbs light of a first wavelength and is excited by light of the first wavelength to emit fluorescence at a second wavelength different from the first wavelength, and the dialysis effluent contains a measurement-inhibiting component that absorbs light of the first wavelength and is excited by light of the first wavelength to emit fluorescence at a third wavelength different from the first and second wavelengths, and the device includes a light source that irradiates the dialysis effluent with light of the first wavelength, and measures the light intensity of the transmitted light from the light source that has passed through the dialysis effluent, and determines the concentration of the metered component contained in the dialysis effluent discharged from a blood purifier. a first fluorescence measurement unit that measures the intensity of fluorescence at the second wavelength emitted by the analyte component upon excitation by light from the light source; a second fluorescence measurement unit that measures the intensity of fluorescence at the third wavelength emitted by the measurement-inhibiting component upon excitation by light from the light source; a ratio calculation unit that calculates the ratio of the concentration of the analyte component to the concentration of the measurement-inhibiting component contained in the dialysis effluent based on the measurement results of the first and second fluorescence measurement units; and a analyte component concentration calculation unit that calculates the concentration of the analyte component in the dialysis effluent based on the ratio of the concentrations calculated by the ratio calculation unit and the absorbance at the first wavelength measured by the absorbance measurement unit.
本発明の一実施の形態に係る透析排液用成分測定方法は、血液浄化器から排出された透析排液中に含まれる被測定成分の濃度を測定する方法であって、前記被測定成分は、第1波長の光を吸収し、かつ前記第1波長の光で励起され前記第1波長と異なる第2波長の蛍光を発する成分であり、前記透析排液中には、前記第1波長の光を吸収し、かつ、前記第1の光で励起され前記第1及び第2波長と異なる第3波長の蛍光を発する測定阻害成分が含まれており、光源から前記透析排液に前記第1波長の光を照射し、前記光源からの光が前記透析排液を透過した透過光の光強度を測定し、当該透過光の光強度と前記光源の光強度とから前記第1波長における吸光度を求め、前記光源からの光により励起され前記被測定成分が放出する前記第2波長の蛍光の光強度を測定し、前記光源からの光により励起され前記測定阻害成分が放出する前記第3波長の蛍光の光強度を測定し、前記第2及び第3波長の蛍光の測定結果を基に、前記透析排液中に含まれる前記被測定成分の濃度と前記測定阻害成分との濃度の比率を演算し、演算した濃度の比率と、測定した前記第1波長における吸光度とを基に、前記透析排液中の前記被測定成分の濃度を演算する。 A dialysis effluent component measurement method according to one embodiment of the present invention is a method for measuring the concentration of a metered component contained in dialysis effluent discharged from a blood purifier, wherein the metered component is a component that absorbs light of a first wavelength and is excited by light of the first wavelength to emit fluorescence of a second wavelength different from the first wavelength, and the dialysis effluent contains a measurement-inhibiting component that absorbs light of the first wavelength and is excited by the first light to emit fluorescence of a third wavelength different from the first and second wavelengths, and the dialysis effluent is irradiated with light of the first wavelength from a light source, and the intensity of the transmitted light from the light source that has passed through the dialysis effluent is measured. The intensity of the fluorescence at the second wavelength emitted by the component to be measured upon excitation with light from the light source is measured, the intensity of the fluorescence at the third wavelength emitted by the component to be measured upon excitation with light from the light source is measured, and the ratio of the concentration of the component to be measured to the concentration of the component to be measured contained in the dialysis effluent is calculated based on the measurement results of the fluorescence at the second and third wavelengths, and the concentration of the component to be measured in the dialysis effluent is calculated based on the calculated concentration ratio and the measured absorbance at the first wavelength.
本発明によれば、透析排液中の被測定成分の濃度を精度よく測定可能な透析排液用成分測定装置及び方法を提供できる。 The present invention provides a dialysis effluent component measuring device and method that can accurately measure the concentration of a target component in dialysis effluent.
[実施の形態]
以下、本発明の実施の形態を添付図面にしたがって説明する。
[Embodiment]
Hereinafter, an embodiment of the present invention will be described with reference to the accompanying drawings.
(血液浄化装置)
まず、本実施の形態に係る透析排液用成分測定装置を適用する血液浄化装置について説明する。図1は、本実施の形態に係る透析排液用成分測定装置を用いた血液浄化装置の概略構成図である。
(blood purification device)
First, a blood purification apparatus using the dialysis effluent component measuring device according to the present embodiment will be described. Fig. 1 is a schematic diagram of a blood purification apparatus using the dialysis effluent component measuring device according to the present embodiment.
図1に示すように、血液浄化装置10は、患者の血液を体外循環させる血液回路11と、血液回路11に設けられた血液浄化器12に供給液を供給する液供給流路13と、血液浄化器12からの排液を排出する排液流路14と、を備えている。図1の例では、液供給流路13が、血液浄化器12に透析液を供給する透析液流路13aである場合を示している。ただし、これに限らず、液供給流路13は、補充液を血液回路11に直接供給する補充液流路であってもよいし、透析液流路13aと補充液流路の両方を有していてもよい。 As shown in FIG. 1, the blood purification device 10 includes a blood circuit 11 for extracorporeally circulating the patient's blood, a liquid supply flow path 13 for supplying supply liquid to a blood purifier 12 provided in the blood circuit 11, and a drainage flow path 14 for discharging drainage liquid from the blood purifier 12. In the example of FIG. 1, the liquid supply flow path 13 is shown as a dialysate flow path 13a for supplying dialysate to the blood purifier 12. However, this is not limited to this, and the liquid supply flow path 13 may be a replenishment flow path that directly supplies replenishment liquid to the blood circuit 11, or may have both a dialysate flow path 13a and a replenishment flow path.
血液回路11は、例えば可撓性を有するチューブ等から構成される。血液回路11には、血液の流れにおける上流側から下流側にかけて、血液ポンプ111、血液浄化器12、エアトラップチャンバ112が順次設けられている。血液ポンプ111は、血液を送液する送液ポンプである。エアトラップチャンバ112は、血液から気泡を除去するためのものである。 The blood circuit 11 is composed of, for example, flexible tubing. The blood circuit 11 is sequentially equipped with a blood pump 111, a blood purifier 12, and an air trap chamber 112, arranged from upstream to downstream in the blood flow. The blood pump 111 is a pump that pumps blood. The air trap chamber 112 is used to remove air bubbles from the blood.
透析液流路13aには、逆浸透膜(RO(Reverse Osmosis)膜)を用いて清浄な透析用水を製造するRO装置(不図示)から、透析用水が供給される。また、透析液流路13aには、A原液及びB原液の2種類の透析液原液が供給される。両原液は、それぞれ原液貯留タンク151に貯留されており、原液流路152を介して原液貯留タンク151から透析液流路13aにそれぞれA原液とB原液とが供給される。両原液流路152には、A原液またはB原液を送液する送液ポンプである原液注入ポンプ153がそれぞれ設けられている。透析液流路13aにて透析用水にA原液及びB原液が混合されることで、透析液が調製される。調製された透析液は、複式ポンプ16を介して血液浄化器12に導入される。なお、これに限らず、例えば、既にA原液とB原液とが混合された調整済みの透析液原液が供給されるように構成してもよい。また、透析用水と透析液原液とから透析液を調製する機構を省略し、外部から透析液が供給されるよう構成してもよい。つまり、血液浄化装置10は、透析用水と透析液原液とから透析液を調製する機構を有する個人用透析装置であってもよいし、多人数用透析液供給装置から透析液が供給される透析用監視装置であってもよい。 Dialysis water is supplied to the dialysate flow path 13a from an RO device (not shown), which produces clean dialysis water using a reverse osmosis (RO) membrane. Two types of dialysis solution stock solutions, stock solution A and stock solution B, are also supplied to the dialysate flow path 13a. Both stock solutions are stored in stock solution storage tanks 151, and stock solution A and stock solution B are supplied from the stock solution storage tanks 151 to the dialysate flow path 13a via stock solution flow paths 152. Each stock solution flow path 152 is provided with a stock solution injection pump 153, which is a liquid delivery pump that delivers stock solution A or stock solution B. Dialysis water is prepared by mixing stock solution A and stock solution B with the dialysis water in the dialysate flow path 13a. The prepared dialysis solution is introduced into the blood purifier 12 via the duplex pump 16. However, the present invention is not limited to this, and may be configured to supply a prepared dialysis solution stock solution prepared by mixing stock solutions A and B. Alternatively, the mechanism for preparing dialysis solution from dialysis water and dialysis solution stock solution may be omitted, and dialysis solution may be supplied from an external source. In other words, the blood purification device 10 may be a personal dialysis device having a mechanism for preparing dialysis solution from dialysis water and dialysis solution stock solution, or a dialysis monitoring device supplied with dialysis solution from a multi-person dialysis solution supply device.
血液浄化器12から排出された透析排液は、排液流路14を通り排出される。複式ポンプ16は、透析液流路13aと排液流路14とにわたって設けられており、血液浄化器12に導入される透析液の量と、血液浄化器12から排出される排液の量が等しくなるように、ポンプ動作を行う。また、排液流路14には、複式ポンプ16をバイパスするように除水流路14aが設けられており、この除水流路14aに、除水ポンプ17が設けられている。除水ポンプ17を駆動すると、血液浄化器12に導入される透析液の量よりも、血液浄化器12から排出される排液の量が多くなり、血液からの除水が行われる。除水ポンプ17の送液量を調整することにより、血液からの除水量を調整することができる。 The dialysis effluent discharged from the blood purifier 12 is discharged through the drainage flow path 14. The duplex pump 16 is provided across the dialysate flow path 13a and the drainage flow path 14, and performs pumping operation so that the amount of dialysate introduced into the blood purifier 12 is equal to the amount of effluent discharged from the blood purifier 12. The drainage flow path 14 is also provided with a water removal flow path 14a that bypasses the duplex pump 16, and this water removal flow path 14a is provided with a water removal pump 17. When the water removal pump 17 is driven, the amount of effluent discharged from the blood purifier 12 becomes greater than the amount of dialysate introduced into the blood purifier 12, thereby removing water from the blood. The amount of water removed from the blood can be adjusted by adjusting the amount of fluid delivered by the water removal pump 17.
血液浄化装置10の排液流路14には、本実施の形態に係る透析排液用成分測定装置1が設けられている。透析排液用成分測定装置1は、除水流路14aが排液流路14に合流する位置よりも下流側の排液流路14に設けられている。なお、図1の構成はあくまで一例であり、血液浄化装置10の具体的な構成は適宜変更可能である。 A dialysis effluent component measuring device 1 according to this embodiment is provided in the drainage flow path 14 of the blood purification device 10. The dialysis effluent component measuring device 1 is provided in the drainage flow path 14 downstream of the position where the water removal flow path 14a joins the drainage flow path 14. Note that the configuration in Figure 1 is merely an example, and the specific configuration of the blood purification device 10 can be modified as appropriate.
(透析排液用成分測定装置1)
透析排液用成分測定装置1は、血液浄化器12から排出された透析排液中に含まれる特定の被測定成分の濃度を測定する装置である。被測定成分は、第1波長の光を吸収し、かつ第1波長の光で励起され第1波長と異なる第2波長の蛍光を発する成分である。本実施の形態では、被測定成分がアルブミンである場合を説明する。つまり、透析排液用成分測定装置1は、例えば、透析排液中のアルブミンの濃度を測定する装置である。被測定成分がアルブミンである場合、励起光の波長である第1波長は、250nm以上330nm以下、より好ましくは275nm以上285nm以下となる。そして、アルブミンが発する蛍光の波長である第2波長は、300nm以上400nm以下となる。
(Dialysis effluent component measuring device 1)
The dialysis effluent component measuring device 1 is a device that measures the concentration of a specific analyte component contained in the dialysis effluent discharged from the blood purifier 12. The analyte component is a component that absorbs light of a first wavelength and, upon being excited by light of the first wavelength, emits fluorescence of a second wavelength different from the first wavelength. In this embodiment, a case will be described in which the analyte component is albumin. That is, the dialysis effluent component measuring device 1 is a device that measures the concentration of albumin in the dialysis effluent, for example. When the analyte component is albumin, the first wavelength, which is the wavelength of the excitation light, is 250 nm or more and 330 nm or less, more preferably 275 nm or more and 285 nm or less. The second wavelength, which is the wavelength of the fluorescence emitted by albumin, is 300 nm or more and 400 nm or less.
ところで、蛍光の光強度は小さく、特に被測定成分の濃度が低い場合には、十分な検知精度を確保することが困難になる場合がある。これに対して、本発明者らは、吸光度を用いることを考えた。吸光度を用いる場合、透過光を測定することになるため、被測定成分の濃度が低い状態でも十分な光強度で測定可能である。しかし、吸光度のみでは、透析排液中の他の成分の影響を受けて十分な測定精度が得られない場合があった。 However, the light intensity of fluorescent light is low, and it can be difficult to ensure sufficient detection accuracy, especially when the concentration of the component to be measured is low. In response to this, the inventors considered using absorbance. When using absorbance, transmitted light is measured, making it possible to measure with sufficient light intensity even when the concentration of the component to be measured is low. However, with absorbance alone, sufficient measurement accuracy may not be achieved due to the influence of other components in the dialysis effluent.
図2(a)は、透析排液中に含まれる主なろ過毒素物質の吸収スペクトルを示す図であり、図2(b)はその蛍光スペクトルを示す図である。図2(a)に示すように、被測定成分であるアルブミンは、クレアチニンや尿素とは吸収スペクトルがほぼ重なっていないが、尿酸と吸収スペクトルが重なっている。尿酸は、第1波長(波長250nm以上330nm以下)の光を吸収するため、第1波長の光の吸光度を測定するのみでは、尿酸の影響により被測定成分であるアルブミンの濃度を精度よく測定することはできないといえる。 Figure 2(a) shows the absorption spectra of the main filtered toxins contained in dialysis effluent, and Figure 2(b) shows their fluorescence spectra. As shown in Figure 2(a), the absorption spectrum of the measured component, albumin, does not overlap with that of creatinine or urea, but does overlap with that of uric acid. Because uric acid absorbs light of the first wavelength (wavelength 250 nm or greater and 330 nm or less), it can be said that the concentration of the measured component, albumin, cannot be accurately measured simply by measuring the absorbance of light of the first wavelength due to the influence of uric acid.
他方で、図2(b)に示すように、アルブミンによる蛍光の波長(第2波長)は、尿酸による蛍光の波長と異なっていることが分かる。このように、透析排液中には、第1波長の光を吸収し、かつ、第1波長の光で励起され第1及び第2波長と異なる第3波長の蛍光を発する測定阻害成分が含まれている。被測定成分がアルブミンである場合は、尿酸が測定阻害成分に相当する。この場合、尿酸の蛍光の波長である第3波長は、380nm以上480nm以下である。なお、ここでは、一例として、測定阻害成分が尿酸である場合を説明するが、測定阻害成分は被測定成分に対応したものであればよく、尿酸に限定されない。また、2成分以上の測定阻害成分が透析排液中に含まれていてもよい。 On the other hand, as shown in Figure 2(b), the wavelength of fluorescence (second wavelength) due to albumin is different from the wavelength of fluorescence due to uric acid. Thus, the dialysis effluent contains a measurement-inhibiting component that absorbs light of the first wavelength and, upon being excited by light of the first wavelength, emits fluorescence of a third wavelength different from the first and second wavelengths. When the component to be measured is albumin, uric acid corresponds to the measurement-inhibiting component. In this case, the third wavelength, which is the wavelength of the fluorescence of uric acid, is 380 nm or more and 480 nm or less. Here, we will explain the case where the measurement-inhibiting component is uric acid as an example, but the measurement-inhibiting component may be any component that corresponds to the component to be measured and is not limited to uric acid. Furthermore, two or more measurement-inhibiting components may be contained in the dialysis effluent.
このように、被測定成分の濃度を測定するにあたって、蛍光のみを用いる場合は蛍光の光強度が小さいことに起因して測定精度が低下するおそれがあり、吸光度のみを用いる場合は測定阻害成分の影響で測定精度が低下するおそれがある。本発明者らは、これらの知見に基づき検討を重ね、本発明に至った。 As such, when measuring the concentration of a component to be measured, if only fluorescence is used, there is a risk of measurement accuracy being reduced due to the low light intensity of the fluorescence, and if only absorbance is used, there is a risk of measurement accuracy being reduced due to the influence of components that inhibit measurement. Based on these findings, the inventors conducted extensive research and arrived at the present invention.
図3は、本実施の形態に係る透析排液用成分測定装置1の模式図である。図3に示すように、透析排液用成分測定装置1は、光源2と、吸光度測定部3と、第1蛍光測定部4と、第2蛍光測定部6と、演算装置5と、を主に備えている。光源2は、被測定成分であるアルブミンを励起可能な第1波長の光を透析排液に照射する。ここでは、光源2として、波長280nmの紫外光を照射する発光ダイオードを用いた。本実施の形態では、光源2を、発光と非発光を所定の周期で繰り返すようにパルス駆動した。これにより、消費電力を低減し光源2として用いる発光ダイオードの寿命を延ばすことができ、さらに、ノイズの影響を抑制することも可能になる(ノイズの影響抑制については後述する)。 Figure 3 is a schematic diagram of a dialysis effluent component measuring device 1 according to this embodiment. As shown in Figure 3, the dialysis effluent component measuring device 1 mainly comprises a light source 2, an absorbance measurement unit 3, a first fluorescence measurement unit 4, a second fluorescence measurement unit 6, and a calculation unit 5. The light source 2 irradiates the dialysis effluent with light of a first wavelength capable of exciting albumin, the component to be measured. In this example, a light-emitting diode that irradiates ultraviolet light with a wavelength of 280 nm is used as the light source 2. In this embodiment, the light source 2 is pulse-driven so that light emission and non-emission are repeated at a predetermined cycle. This reduces power consumption and extends the life of the light-emitting diode used as the light source 2, and also makes it possible to suppress the effects of noise (the suppression of noise effects will be described later).
排液流路14には、流路が略一定の厚さとなるように薄く形成した平板状の測定部14bが設けられている。ここでは、光源2側から見て略楕円形状の測定部14bを形成した。光源2は、測定部14bの厚さ方向において測定部14bの中心部分と対向するように設けられている。測定部14bは、少なくとも第1波長及び第2波長の光を透過する(第1波長及び第2波長の透過率が十分に高い)材質で構成されている。また、光源2と測定部14bとの間には、レンズ7が設けられている。光源2から照射された光は、レンズ7により集光されて測定部14bへと入射する。ここでは、レンズ7により光源2からの光を平行光に変換して測定部14bへと入射するように構成した。 The drainage flow path 14 is provided with a thin, flat measuring section 14b that is formed to ensure that the flow path has a substantially uniform thickness. Here, the measuring section 14b is formed to have a substantially elliptical shape when viewed from the light source 2 side. The light source 2 is provided facing the center of the measuring section 14b in the thickness direction. The measuring section 14b is made of a material that transmits light of at least the first and second wavelengths (having sufficiently high transmittance for the first and second wavelengths). A lens 7 is provided between the light source 2 and the measuring section 14b. Light emitted from the light source 2 is focused by the lens 7 and enters the measuring section 14b. Here, the light from the light source 2 is converted by the lens 7 into parallel light that enters the measuring section 14b.
吸光度測定部3は、光源2からの光が透析排液を透過した透過光の光強度を測定し、当該透過光の光強度と光源2の光強度とから第1波長における吸光度を求める。吸光度測定部3は、透過光を受光する透過光用受光素子(PD)31と、透過光を集光して透過光用受光素子31に導くレンズ32と、を有している。また、図示していないが、吸光度測定部3は、透過光用受光素子31で受光した透過光の光強度と、光源2の光強度とを基に、吸光度を演算する吸光度演算部を有している。吸光度演算部は、例えば、演算装置5に搭載されていてもよいし、演算装置5とは別の制御基板等に搭載されていてもよく、演算素子、メモリ、ソフトウェア、インターフェイス等を適宜組み合わせて実現されている。光源2の光強度については、例えば、光源2の光強度を測定するための光源用測定部を設けておき、その光源用測定部の測定結果を用いてもよいし、予め設定された設定値(予め測定した光源2の光強度)を用いてもよい。 The absorbance measurement unit 3 measures the light intensity of transmitted light from the light source 2 that has passed through the dialysis effluent, and calculates the absorbance at the first wavelength from the light intensity of the transmitted light and the light intensity of the light source 2. The absorbance measurement unit 3 includes a transmitted light receiving element (PD) 31 that receives the transmitted light, and a lens 32 that focuses the transmitted light and directs it to the transmitted light receiving element 31. Furthermore, although not shown, the absorbance measurement unit 3 includes an absorbance calculation unit that calculates absorbance based on the light intensity of the transmitted light received by the transmitted light receiving element 31 and the light intensity of the light source 2. The absorbance calculation unit may be mounted on the calculation unit 5, for example, or on a control board or the like separate from the calculation unit 5, and is realized by an appropriate combination of calculation elements, memory, software, interfaces, etc. Regarding the light intensity of the light source 2, for example, a light source measurement unit for measuring the light intensity of the light source 2 may be provided, and the measurement results of the light source measurement unit may be used, or a preset value (previously measured light intensity of the light source 2) may be used.
透過光用受光素子31としては、微弱な光信号も検出可能で、入射光に対する応答速度が速いフォトダイオードを用いるとよく、より好ましくは、アバランシェ・フォトダイオードを用いるとよい。これにより、透過光の経時的な変化をとらえることができ、また微小な光量でも増倍率が高いため、受光感度を向上することができる。透過光用受光素子31は、測定部14bを挟んで、光源2と対向して配置されている。 The transmitted light receiving element 31 is preferably a photodiode that can detect even weak optical signals and has a fast response speed to incident light, and more preferably an avalanche photodiode. This allows it to capture changes in transmitted light over time and improves light receiving sensitivity due to its high multiplication factor even for small amounts of light. The transmitted light receiving element 31 is positioned opposite the light source 2, with the measuring unit 14b in between.
レンズ32は、透過光用受光素子31と測定部14bとの間に配置されている。図示していないが、吸光度測定部3は、レンズ32で集光された光を、第2及び第3波長の光を遮断して第1波長の光を通過させるフィルタを通して透過光用受光素子31に導くように構成されていてもよい。この場合、フィルタとしては、光源2の発光波長の光を通過させるバンドパスフィルタを用いるとよく、波長が250nm以上330nm以下、より好ましくは275nm以上285nm以下の光を通過させるように構成されているとよい。これにより、レンズ32で集光された光から、アルブミンや尿酸による蛍光(及びノイズとなる光)を除くことができ、より精度の高い測定を行うことが可能になる。 The lens 32 is disposed between the transmitted light receiving element 31 and the measurement unit 14b. Although not shown, the absorbance measurement unit 3 may be configured to direct the light focused by the lens 32 to the transmitted light receiving element 31 through a filter that blocks light of the second and third wavelengths and passes light of the first wavelength. In this case, the filter may be a bandpass filter that passes light of the emission wavelength of the light source 2, and is preferably configured to pass light with a wavelength of 250 nm to 330 nm, more preferably 275 nm to 285 nm. This makes it possible to remove fluorescence (and light that becomes noise) due to albumin and uric acid from the light focused by the lens 32, enabling more accurate measurements.
また、本実施の形態では、光源2を発光と非発光を所定の周期で繰り返すパルス駆動としているが、吸光度測定部3は、光源2の発光時と非発光時との受光強度の差を、透過光による光強度として測定するよう構成されているとよい。信号処理部(演算装置5)にて所定周期の受光成分のみを取り出すことで、ノイズの影響を抑制し、より精度の高い測定を行うことが可能になる。 In addition, in this embodiment, the light source 2 is pulse-driven, repeatedly emitting and not emitting light at a predetermined cycle. The absorbance measurement unit 3 is preferably configured to measure the difference in the light intensity received when the light source 2 is emitting and not emitting light as the light intensity of transmitted light. By extracting only the light-receiving component at a predetermined cycle in the signal processing unit (arithmetic unit 5), the effects of noise can be suppressed, enabling more accurate measurements.
第1蛍光測定部4は、被測定成分であるアルブミンによる蛍光の光強度を測定するためのものであり、光源2からの光により励起されアルブミンが放出する第2波長の蛍光の光強度を測定する。第1蛍光測定部4は、第1蛍光用受光素子(PD)41と、第1フィルタ42と、透析排液で生じた(すなわち、測定部14bで生じた)蛍光を第1蛍光用受光素子41に導く第1導光部材としての第1レンズ43と、を有している。第1フィルタ42は、測定部14bと第1蛍光用受光素子41との間に設けられ、第1波長の光(透過光や散乱光)及び第3波長の光(尿酸による蛍光)が第1蛍光用受光素子41に入射されないよう遮断して、アルブミンの蛍光による第2波長の光のみを通過させる。第1フィルタ42としては、第2波長と同じ300nm以上400nm以下の波長の光を通過させるバンドパスフィルタを用いるとよく、より好ましくはアルブミンの蛍光波長である340nm近傍の波長範囲(例えば、330nm以上350nm以下)の波長の光を通過させるバンドパスフィルタであるとよい。蛍光は光強度が比較的小さいため、本実施の形態では、第1レンズ43により集光した光を第1蛍光用受光素子41で受光するように構成している。第1レンズ43は、測定部14bと第1フィルタ42との間に設けられる。 The first fluorescence measurement unit 4 measures the intensity of fluorescence emitted by albumin, the component to be measured, by measuring the intensity of fluorescence at a second wavelength emitted by albumin upon excitation by light from the light source 2. The first fluorescence measurement unit 4 includes a first fluorescence photodetector (PD) 41, a first filter 42, and a first lens 43 as a first light-guiding member that guides fluorescence generated in the dialysis effluent (i.e., generated in the measurement unit 14b) to the first fluorescence photodetector 41. The first filter 42 is disposed between the measurement unit 14b and the first fluorescence photodetector 41, and blocks light of the first wavelength (transmitted light and scattered light) and light of the third wavelength (fluorescence due to uric acid) from entering the first fluorescence photodetector 41, while allowing only light of the second wavelength due to the fluorescence of albumin to pass through. The first filter 42 may be a bandpass filter that passes light with a wavelength of 300 nm or more and 400 nm or less, the same as the second wavelength, and more preferably a bandpass filter that passes light with a wavelength in the wavelength range around 340 nm, the fluorescence wavelength of albumin (e.g., 330 nm or more and 350 nm or less). Because the light intensity of fluorescence is relatively low, in this embodiment, the light collected by the first lens 43 is received by the first fluorescence light receiving element 41. The first lens 43 is disposed between the measurement unit 14b and the first filter 42.
第2蛍光測定部6は、測定阻害成分である尿酸による蛍光の光強度を測定するためのものであり、光源2からの光により励起され尿酸が放出する第3波長の蛍光の光強度を測定する。第2蛍光測定部6は、第2蛍光用受光素子(PD)61と、第2フィルタ62と、透析排液で生じた(すなわち、測定部14bで生じた)蛍光を第2蛍光用受光素子61に導く第2導光部材としての第2レンズ63と、を有している。第2フィルタ62は、測定部14bと第2蛍光用受光素子61との間に設けられ、第1波長の光(透過光や散乱光)及び第2波長の光(アルブミンによる蛍光)が第2蛍光用受光素子61に入射されないよう遮断して、尿酸の蛍光による第3波長の光のみを通過させる。第2フィルタ62としては、第3波長と同じ380nm以上480nm以下の波長の光を通過させるバンドパスフィルタを用いるとよく、より好ましくは尿酸の蛍光波長である430nm近傍の波長範囲(例えば、420nm以上440nm以下)の波長の光を通過させるバンドパスフィルタであるとよい。蛍光は光強度が比較的小さいため、本実施の形態では、第2レンズ63により集光した光を第2蛍光用受光素子61で受光するように構成している。第2レンズ63は、測定部14bと第2フィルタ62との間に設けられる。 The second fluorescence measurement unit 6 measures the light intensity of fluorescence due to uric acid, a measurement-inhibiting component, and measures the light intensity of fluorescence at a third wavelength emitted by uric acid upon excitation by light from the light source 2. The second fluorescence measurement unit 6 includes a second fluorescence photodetector (PD) 61, a second filter 62, and a second lens 63 as a second light-guiding member that guides fluorescence generated in the dialysis effluent (i.e., generated in the measurement unit 14b) to the second fluorescence photodetector 61. The second filter 62 is disposed between the measurement unit 14b and the second fluorescence photodetector 61 and blocks light of the first wavelength (transmitted light and scattered light) and light of the second wavelength (fluorescence due to albumin) from entering the second fluorescence photodetector 61, allowing only light of the third wavelength due to the fluorescence of uric acid to pass through. The second filter 62 may be a bandpass filter that passes light with a wavelength of 380 nm or more and 480 nm or less, the same as the third wavelength, and more preferably a bandpass filter that passes light with a wavelength in the wavelength range around 430 nm, the fluorescent wavelength of uric acid (e.g., 420 nm or more and 440 nm or less). Because fluorescent light has a relatively low light intensity, in this embodiment, the light collected by the second lens 63 is received by the second fluorescent light receiving element 61. The second lens 63 is disposed between the measurement unit 14b and the second filter 62.
第1蛍光用受光素子41及び第2蛍光用受光素子61としては、上記の透過光用受光素子31と同様に、微弱な光信号も検出可能で、入射光に対する応答速度が速いフォトダイオードを用いるとよく、より好ましくは、アバランシェ・フォトダイオードを用いるとよい。これにより、蛍光の経時的な変化をとらえることができ、また微小な光量でも増倍率が高いため、受光感度を向上することができる。 As with the transmitted light light receiving element 31 described above, the first fluorescent light receiving element 41 and the second fluorescent light receiving element 61 should preferably be photodiodes that can detect weak optical signals and have a fast response speed to incident light, and more preferably, avalanche photodiodes. This makes it possible to capture changes in the fluorescent light over time, and the high multiplication factor even for small amounts of light improves light receiving sensitivity.
また、本実施の形態では、光源2を発光と非発光を所定の周期で繰り返すパルス駆動としているが、第1蛍光測定部4及び第2蛍光測定部6は、光源2の発光時と非発光時との受光強度の差を、蛍光による光強度として測定するよう構成されているとよい。信号処理部(演算装置5)にて所定周期の受光成分のみを取り出すことで、ノイズの影響を抑制し、より精度の高い測定を行うことが可能になる。 In addition, in this embodiment, the light source 2 is pulse-driven, repeatedly emitting and not emitting light at a predetermined cycle, but the first fluorescence measurement unit 4 and second fluorescence measurement unit 6 can be configured to measure the difference in light intensity received when the light source 2 is emitting and not emitting light as the light intensity due to fluorescence. By extracting only the light-receiving component at a predetermined cycle in the signal processing unit (arithmetic device 5), the effects of noise can be suppressed, enabling more accurate measurements.
演算装置5には、比率演算部51、被測定成分濃度演算部52、被測定成分漏出量演算部53、警報部54、及び記憶部55が搭載されている。比率演算部51、被測定成分濃度演算部52、被測定成分漏出量演算部53、及び警報部54は、演算素子、メモリ、ソフトウェア、インターフェイス、ハードディスク等の記憶装置等を適宜組み合わせて実現されている。記憶部55は、メモリや、ハードディスク等の記憶装置における所定の記憶領域を用いて実現される。演算装置5は、例えば、血液浄化装置10の制御装置であってもよい。 The calculation device 5 is equipped with a ratio calculation unit 51, a measured component concentration calculation unit 52, a measured component leakage amount calculation unit 53, an alarm unit 54, and a memory unit 55. The ratio calculation unit 51, the measured component concentration calculation unit 52, the measured component leakage amount calculation unit 53, and the alarm unit 54 are realized by appropriately combining calculation elements, memory, software, interfaces, storage devices such as hard disks, etc. The memory unit 55 is realized using a specified storage area in a memory or storage device such as a hard disk. The calculation device 5 may be, for example, a control device for the blood purification device 10.
比率演算部51は、第1蛍光測定部4及び第2蛍光測定部6の測定結果を基に、透析排液中に含まれる被測定成分(ここでは、アルブミン)の濃度と測定阻害成分(ここでは、尿酸)との濃度の比率を演算する。つまり、比率演算部51は、アルブミンによる蛍光の光強度と、尿酸による蛍光の光強度とを比較する(例えば、光強度の比を演算する)ことで、アルブミンと尿酸の濃度の比率を演算する。 The ratio calculation unit 51 calculates the ratio between the concentration of the measurement target component (here, albumin) contained in the dialysis effluent and the concentration of the measurement-inhibiting component (here, uric acid) based on the measurement results of the first fluorescence measurement unit 4 and the second fluorescence measurement unit 6. In other words, the ratio calculation unit 51 calculates the ratio between the concentrations of albumin and uric acid by comparing the light intensity of the fluorescence due to albumin with the light intensity of the fluorescence due to uric acid (for example, by calculating the ratio of the light intensities).
被測定成分濃度演算部52は、比率演算部51が演算したアルブミンと尿酸の濃度の比率と、吸光度測定部3が測定した第1波長における吸光度とを基に、透析排液中の被測定成分(ここでは、アルブミン)の濃度を演算する。吸光度測定部3が測定した吸光度は、アルブミンと尿酸の両方の影響を受けている(図2(a)参照)。よって、アルブミンと尿酸の濃度の比率を考慮することで、アルブミンの影響のみを分離してアルブミンの濃度を演算することが可能になる。 The analyte concentration calculation unit 52 calculates the concentration of the analyte (here, albumin) in the dialysis effluent based on the ratio of albumin to uric acid concentrations calculated by the ratio calculation unit 51 and the absorbance at the first wavelength measured by the absorbance measurement unit 3. The absorbance measured by the absorbance measurement unit 3 is affected by both albumin and uric acid (see Figure 2(a)). Therefore, by taking into account the ratio of albumin to uric acid concentrations, it is possible to calculate the albumin concentration while isolating only the effect of albumin.
被測定成分漏出量演算部53は、被測定成分濃度演算部52で求めた被測定成分(ここでは、アルブミン)の濃度と、透析排液の流量とを基に、治療開始からの被測定成分の漏出量を演算する。透析排液の流量は、複式ポンプ16及び除水ポンプ17の駆動量から求めてもよいし、排液流路14に流量センサを設けて測定してもよい。 The analyte leakage amount calculation unit 53 calculates the leakage amount of the analyte component since the start of treatment based on the concentration of the analyte component (here, albumin) calculated by the analyte concentration calculation unit 52 and the flow rate of the dialysis effluent. The flow rate of the dialysis effluent may be calculated from the drive amount of the duplex pump 16 and the ultrafiltration pump 17, or may be measured by installing a flow sensor in the drainage flow path 14.
より具体的には、被測定成分漏出量演算部53は、1分間の平均アルブミン濃度を演算し、その平均アルブミン濃度に透析排液の流量を掛け合わせることで、1分間当りのアルブミン漏出量を演算し、記憶部55に1分間毎に記憶する。そして、記憶部55に記憶した1分間当りのアルブミン漏出量を治療経過時間分全て足し合わせることで、治療開始からの被測定成分の漏出量を演算する。 More specifically, the measurement component leakage calculation unit 53 calculates the average albumin concentration for one minute, and multiplies this average albumin concentration by the flow rate of the dialysis effluent to calculate the albumin leakage per minute, which is stored in the memory unit 55 for each minute. The albumin leakage per minute stored in the memory unit 55 is then added together over the entire elapsed treatment time to calculate the leakage amount of the measurement component since the start of treatment.
警報部54は、被測定成分濃度演算部52が求めたアルブミンの濃度が、予め設定した閾値以上であるとき、光や音、あるいはディスプレイの表示等の適宜な手段により警報を発する。また、本実施の形態では、警報部54は、被測定成分漏出量演算部53が求めたアルブミンの漏出量が、予め設定した閾値以上であるとき、光や音、あるいはディスプレイの表示等の適宜な手段により警報を発する。 The alarm unit 54 issues an alarm by appropriate means such as light, sound, or display when the albumin concentration calculated by the analyte concentration calculation unit 52 is equal to or greater than a preset threshold. In this embodiment, the alarm unit 54 also issues an alarm by appropriate means such as light, sound, or display when the amount of albumin leakage calculated by the analyte leakage amount calculation unit 53 is equal to or greater than a preset threshold.
(透析排液用成分測定方法)
図4は、本実施の形態に係る透析排液用成分測定方法のフロー図である。例えば、血液浄化治療の開始時に、図4のフローが開始される。
(Method for measuring components in dialysis effluent)
4 is a flow diagram of the method for measuring components in a dialysis effluent according to the present embodiment. For example, the flow of FIG. 4 starts at the start of blood purification treatment.
図4に示すように、本実施の形態に係る透析排液用成分測定方法では、まず、ステップS1にて、光源2から透析排液に第1波長(ここでは波長280nm)の光を照射し、ステップS2にて、吸光度測定部3の透過光用受光素子31で透過光を受光し光強度を測定し第1波長における吸光度を求める。また、第1蛍光測定部4の第1蛍光用受光素子41で被測定成分(ここでは、アルブミン)による第2波長の蛍光の光強度を測定すると共に、第2蛍光測定部6の第2蛍光用受光素子61で測定阻害成分(ここでは、尿酸)による第3波長の蛍光の光強度を測定する。 As shown in FIG. 4, in this embodiment of the dialysis effluent component measurement method, first, in step S1, light of a first wavelength (here, 280 nm) is irradiated onto the dialysis effluent from the light source 2. In step S2, the transmitted light is received by the transmitted light receiving element 31 of the absorbance measurement unit 3, and the light intensity is measured to determine the absorbance at the first wavelength. Furthermore, the first fluorescent light receiving element 41 of the first fluorescent measurement unit 4 measures the light intensity of fluorescence at a second wavelength due to the component to be measured (here, albumin), and the second fluorescent light receiving element 61 of the second fluorescent measurement unit 6 measures the light intensity of fluorescence at a third wavelength due to a measurement-inhibiting component (here, uric acid).
その後、ステップS3にて、比率演算部51は、第1及び第2蛍光測定部4,6の測定結果を基に、透析排液中に含まれる被測定成分(ここでは、アルブミン)の濃度と測定阻害成分(ここでは、尿酸)との濃度の比率を演算する。本実施の形態では、アルブミンによる第2波長(340nm)の蛍光の光強度と、尿酸による第3波長(430nm)の蛍光の光強度とを比較することで、アルブミンと尿酸の濃度の比率を演算する。 Then, in step S3, the ratio calculation unit 51 calculates the ratio between the concentration of the measured component (here, albumin) contained in the dialysis effluent and the concentration of the measurement-inhibiting component (here, uric acid) based on the measurement results of the first and second fluorescence measurement units 4 and 6. In this embodiment, the ratio between the concentrations of albumin and uric acid is calculated by comparing the light intensity of the fluorescence at the second wavelength (340 nm) due to albumin with the light intensity of the fluorescence at the third wavelength (430 nm) due to uric acid.
その後、ステップS4にて、被測定成分濃度演算部52は、ステップS3で演算した濃度の比率と、ステップS2で吸光度測定部3により測定した吸光度とを基に、透析排液中の被測定成分(ここでは、アルブミン)の濃度を演算する。演算により求めたアルブミンの濃度は、記憶部55に記憶される。 Then, in step S4, the analyte concentration calculation unit 52 calculates the concentration of the analyte (here, albumin) in the dialysis effluent based on the ratio of the concentrations calculated in step S3 and the absorbance measured by the absorbance measurement unit 3 in step S2. The calculated albumin concentration is stored in the memory unit 55.
その後、ステップS5にて、警報部54が、ステップS4で求めたアルブミンの濃度が、予め設定した閾値以上かを判定する。ステップS5にてYES(Y)と判定された場合、ステップS6にて光や音等により警報を発し、ステップS7に進む。ステップS5でNO(N)と判定された場合、警報を発することなくステップS7に進む。 Then, in step S5, the alarm unit 54 determines whether the albumin concentration determined in step S4 is equal to or greater than a preset threshold. If step S5 returns YES (Y), an alarm is issued using light, sound, etc. in step S6, and the process proceeds to step S7. If step S5 returns NO (N), the process proceeds to step S7 without issuing an alarm.
ステップS7では、被測定成分漏出量演算部53が、ステップS4で求めたアルブミンの濃度と、透析排液の流量とを基に、治療開始からの被測定成分の漏出量を演算する。より具体的には、上述のように、被測定成分漏出量演算部53は、1分間の平均アルブミン濃度を演算し、その平均アルブミン濃度に透析排液の流量を掛け合わせることで、1分間当りのアルブミン漏出量を演算して1分間毎に記憶部55に記憶する。そして、記憶部55に記憶した1分間当りのアルブミン漏出量を治療経過時間分全て足し合わせることで、治療開始からのアルブミンの漏出量を演算する。 In step S7, the measurement component leakage calculation unit 53 calculates the leakage amount of the measurement component since the start of treatment based on the albumin concentration determined in step S4 and the flow rate of the dialysis effluent. More specifically, as described above, the measurement component leakage calculation unit 53 calculates the average albumin concentration for one minute, and multiplies this average albumin concentration by the flow rate of the dialysis effluent to calculate the albumin leakage amount per minute, which is stored in the memory unit 55 for each minute. The albumin leakage amount per minute stored in the memory unit 55 is then added together over the entire elapsed treatment time to calculate the albumin leakage amount since the start of treatment.
その後、ステップS8にて、警報部54が、ステップS7で求めたアルブミンの漏出量が、予め設定した閾値以上かを判定する。ステップS8にてYES(Y)と判定された場合、ステップS9にて光や音等により警報を発し、ステップS10に進む。ステップS8でNO(N)と判定された場合、警報を発することなくステップS10に進む。 Then, in step S8, the alarm unit 54 determines whether the amount of albumin leakage determined in step S7 is equal to or greater than a preset threshold. If step S8 returns YES (Y), an alarm is issued using light, sound, etc. in step S9, and the process proceeds to step S10. If step S8 returns NO (N), the process proceeds to step S10 without issuing an alarm.
ステップS10では、演算装置5が、治療が終了したかを判定する。治療が終了したか否かは、例えば、透析用の制御装置からの信号により判定することができる。ステップS10でNO(N)と判定された場合、ステップS1に戻り、透析排液のアルブミン濃度の監視を継続する。ステップS10でYES(Y)と判定された場合、処理を終了する。 In step S10, the calculation device 5 determines whether the treatment has ended. Whether the treatment has ended can be determined, for example, by a signal from the dialysis control device. If the determination in step S10 is NO (N), the process returns to step S1 and continues monitoring the albumin concentration in the dialysis effluent. If the determination in step S10 is YES (Y), the process ends.
(実施の形態の作用及び効果)
以上説明したように、本実施の形態に係る透析排液用成分測定装置1では、被測定成分は、第1波長の光を吸収し、かつ第1波長の光で励起され第1波長と異なる第2波長の蛍光を発する成分であり、透析排液中には、第1波長の光を吸収し、かつ、第1波長の光で励起され第1及び第2波長と異なる第3波長の蛍光を発する測定阻害成分が含まれており、透析排液に第1波長の光を照射する光源2と、光源2からの光が透析排液を透過した透過光の光強度を測定し、当該透過光の光強度と光源2の光強度とから第1波長における吸光度を求める吸光度測定部3と、光源2からの光により励起され被測定成分が放出する第2波長の蛍光の光強度を測定する第1蛍光測定部4と、光源2からの光により励起され測定阻害成分が放出する第3波長の蛍光の光強度を測定する第2蛍光測定部6と、第1及び第2蛍光測定部4,6の測定結果を基に、透析排液中に含まれる被測定成分の濃度と測定阻害成分との濃度の比率を演算する比率演算部51と、比率演算部51が演算した濃度の比率と、吸光度測定部3が測定した第1波長における吸光度とを基に、透析排液中の被測定成分の濃度を演算する被測定成分濃度演算部52と、を備えている。
(Functions and Effects of the Embodiments)
As described above, in the dialysis effluent component measuring device 1 according to this embodiment, the component to be measured is a component that absorbs light of a first wavelength and is excited by light of the first wavelength to emit fluorescence of a second wavelength different from the first wavelength, and the dialysis effluent contains a measurement-inhibiting component that absorbs light of the first wavelength and is excited by light of the first wavelength to emit fluorescence of a third wavelength different from the first and second wavelengths, and the device comprises a light source 2 that irradiates the dialysis effluent with light of the first wavelength, an absorbance measuring unit 3 that measures the light intensity of transmitted light from the light source 2 that has passed through the dialysis effluent and determines the absorbance at the first wavelength from the light intensity of the transmitted light and the light intensity of the light source 2, and a light source 4 that measures the light intensity of the transmitted light and the light intensity of the light source 2. The device is equipped with a first fluorescence measurement unit 4 that measures the light intensity of fluorescence at a second wavelength emitted by a measurement component excited by light from the light source 2; a second fluorescence measurement unit 6 that measures the light intensity of fluorescence at a third wavelength emitted by a measurement-inhibiting component excited by light from the light source 2; a ratio calculation unit 51 that calculates the ratio of the concentration of the measurement component to the concentration of the measurement-inhibiting component contained in the dialysis effluent based on the measurement results of the first and second fluorescence measurement units 4 and 6; and a measurement component concentration calculation unit 52 that calculates the concentration of the measurement component in the dialysis effluent based on the concentration ratio calculated by the ratio calculation unit 51 and the absorbance at the first wavelength measured by the absorbance measurement unit 3.
これにより、被測定成分の濃度が低く蛍光の光強度が小さくなるような場合であっても、十分な光強度を確保可能な透過光の光強度を基に(より詳細には、透過光の光強度から求めた吸光度を基に)被測定成分の濃度を測定することができ、被測定成分の濃度の測定精度を向上できる。さらに、被測定成分と測定阻害成分との識別が容易な蛍光によって両者の濃度の比率を求め、得られたこの比率を考慮した上で、吸光度を基に被測定成分の濃度を求めることで、測定阻害成分の影響を排除して精度よく被測定成分の濃度を測定することが可能になる。 As a result, even when the concentration of the component to be measured is low and the intensity of the fluorescence is low, the concentration of the component to be measured can be measured based on the intensity of the transmitted light that ensures sufficient light intensity (more specifically, based on the absorbance calculated from the intensity of the transmitted light), thereby improving the accuracy of measuring the concentration of the component to be measured. Furthermore, by calculating the concentration ratio of the component to be measured and measurement-inhibiting components using fluorescence, which makes it easy to distinguish between them, and then taking this ratio into consideration, the concentration of the component to be measured can be calculated based on absorbance, eliminating the influence of measurement-inhibiting components and allowing for accurate measurement of the concentration of the component to be measured.
(実施の形態のまとめ)
次に、以上説明した実施の形態から把握される技術思想について、実施の形態における符号等を援用して記載する。ただし、以下の記載における各符号等は、特許請求の範囲における構成要素を実施の形態に具体的に示した部材等に限定するものではない。
(Summary of the embodiment)
Next, the technical ideas grasped from the above-described embodiments will be described by using the reference numerals and the like in the embodiments. However, the reference numerals and the like in the following description do not limit the components in the claims to the members and the like specifically shown in the embodiments.
[1]血液浄化器(12)から排出された透析排液中に含まれる被測定成分の濃度を測定する装置であって、前記被測定成分は、第1波長の光を吸収し、かつ前記第1波長の光で励起され前記第1波長と異なる第2波長の蛍光を発する成分であり、前記透析排液中には、前記第1波長の光を吸収し、かつ、前記第1波長の光で励起され前記第1及び第2波長と異なる第3波長の蛍光を発する測定阻害成分が含まれており、前記透析排液に前記第1波長の光を照射する光源(2)と、前記光源(2)からの光が前記透析排液を透過した透過光の光強度を測定し、当該透過光の光強度と前記光源の光強度とから前記第1波長における吸光度を求める吸光度測定部(3)と、前記光源(2)からの光により励起され前記被測定成分が放出する前記第2波長の蛍光の光強度を測定する第1蛍光測定部(4)と、前記光源(2)からの光により励起され前記測定阻害成分が放出する前記第3波長の蛍光の光強度を測定する第2蛍光測定部(6)と、前記第1及び第2蛍光測定部(4,6)の測定結果を基に、前記透析排液中に含まれる前記被測定成分の濃度と前記測定阻害成分との濃度の比率を演算する比率演算部(51)と、前記比率演算部(51)が演算した濃度の比率と、前記吸光度測定部(3)が測定した前記第1波長における吸光度とを基に、前記透析排液中の前記被測定成分の濃度を演算する被測定成分濃度演算部(52)と、を備えた、透析排液用成分測定装置(1)。 [1] An apparatus for measuring the concentration of a component to be measured contained in a dialysis effluent discharged from a blood purifier (12), wherein the component to be measured is a component that absorbs light of a first wavelength and, upon being excited by light of the first wavelength, emits fluorescence at a second wavelength different from the first wavelength; the dialysis effluent contains a measurement-inhibiting component that absorbs light of the first wavelength and, upon being excited by light of the first wavelength, emits fluorescence at a third wavelength different from the first and second wavelengths; the apparatus comprises: a light source (2) that irradiates the dialysis effluent with light of the first wavelength; an absorbance measurement unit (3) that measures the light intensity of the transmitted light from the light source (2) that has passed through the dialysis effluent and determines the absorbance at the first wavelength from the light intensity of the transmitted light and the light intensity of the light source; a first fluorescence measurement unit (4) that measures the light intensity of the fluorescence of the second wavelength emitted by the analyte component when excited by light from the light source (2); a second fluorescence measurement unit (6) that measures the light intensity of the fluorescence of the third wavelength emitted by the measurement-inhibiting component when excited by light from the light source (2); a ratio calculation unit (51) that calculates the ratio of the concentration of the analyte component to the concentration of the measurement-inhibiting component contained in the dialysis effluent based on the measurement results of the first and second fluorescence measurement units (4, 6); and a analyte component concentration calculation unit (52) that calculates the concentration of the analyte component in the dialysis effluent based on the concentration ratio calculated by the ratio calculation unit (51) and the absorbance at the first wavelength measured by the absorbance measurement unit (3).
[2]前記被測定成分がアルブミンであり、前記測定阻害成分が尿酸である、[1]に記載の透析排液用成分測定装置(1)。 [2] The dialysis effluent component measuring device (1) described in [1], wherein the component to be measured is albumin and the measurement-inhibiting component is uric acid.
[3]前記第1波長が、250nm以上330nm以下であり、前記第2波長が、300nm以上400nm以下であり、前記第3波長が、380nm以上480nm以下である、[2]に記載の透析排液用成分測定装置(1)。 [3] The dialysis effluent component measuring device (1) described in [2], wherein the first wavelength is 250 nm or more and 330 nm or less, the second wavelength is 300 nm or more and 400 nm or less, and the third wavelength is 380 nm or more and 480 nm or less.
[4]前記第1蛍光測定部(4)は、第1蛍光用受光素子(41)と、前記第1波長及び前記第3波長の光が前記第1蛍光用受光素子(41)に入射されないよう遮断し、かつ前記第2波長の光を透過する第1フィルタ(42)と、を有し、前記第2蛍光測定部(6)は、第2蛍光用受光素子(61)と、前記第1波長及び前記第2波長の光が前記第2蛍光用受光素子(61)に入射されないよう遮断し、かつ前記第3波長の光を透過する第2フィルタ(62)と、を有する、[1]乃至[3]の何れか1項に記載の透析排液用成分測定装置(1)。 [4] The dialysis effluent component measuring device (1) described in any one of [1] to [3], wherein the first fluorescence measurement unit (4) has a first fluorescence light receiving element (41) and a first filter (42) that blocks light of the first wavelength and the third wavelength from entering the first fluorescence light receiving element (41) and transmits light of the second wavelength, and the second fluorescence measurement unit (6) has a second fluorescence light receiving element (61) and a second filter (62) that blocks light of the first wavelength and the second wavelength from entering the second fluorescence light receiving element (61) and transmits light of the third wavelength.
[5]前記第1蛍光測定部(4)は、前記透析排液で生じた蛍光を前記第1蛍光用受光素子(41)に導く第1導光部材(43)を有し、前記第2蛍光測定部(6)は、前記透析排液で生じた蛍光を前記第2蛍光用受光素子(61)に導く第2導光部材(63)を有する、[4]に記載の透析排液用成分測定装置(1)。 [5] The dialysis effluent component measuring device (1) described in [4], wherein the first fluorescence measurement unit (4) has a first light-guiding member (43) that guides the fluorescence generated in the dialysis effluent to the first fluorescence light-receiving element (41), and the second fluorescence measurement unit (6) has a second light-guiding member (63) that guides the fluorescence generated in the dialysis effluent to the second fluorescence light-receiving element (61).
[6]前記光源(2)は、発光と非発光を所定の周期で繰り返し、前記吸光度測定部(3)は、前記光源の発光時と非発光時の受光強度の差を、前記透過光による光強度として測定し、前記第1及び第2蛍光測定部(4,6)は、前記光源の発光時と非発光時の受光強度の差を、前記蛍光による光強度として測定する、[1]乃至[5]の何れか1項に記載の透析排液用成分測定装置(1)。 [6] The dialysis effluent component measuring device (1) described in any one of [1] to [5], wherein the light source (2) repeatedly emits and does not emit light at a predetermined cycle, the absorbance measuring unit (3) measures the difference in the intensity of light received when the light source emits and does not emit light as the light intensity of the transmitted light, and the first and second fluorescence measuring units (4, 6) measure the difference in the intensity of light received when the light source emits and does not emit light as the light intensity of the fluorescent light.
[7]血液浄化器(12)から排出された透析排液中に含まれる被測定成分の濃度を測定する方法であって、前記被測定成分は、第1波長の光を吸収し、かつ前記第1波長の光で励起され前記第1波長と異なる第2波長の蛍光を発する成分であり、前記透析排液中には、前記第1波長の光を吸収し、かつ、前記第1の光で励起され前記第1及び第2波長と異なる第3波長の蛍光を発する測定阻害成分が含まれており、光源(2)から前記透析排液に前記第1波長の光を照射し、前記光源(2)からの光が前記透析排液を透過した透過光の光強度を測定し、当該透過光の光強度と前記光源(2)の光強度とから前記第1波長における吸光度を求め、前記光源(2)からの光により励起され前記被測定成分が放出する前記第2波長の蛍光の光強度を測定し、前記光源(2)からの光により励起され前記測定阻害成分が放出する前記第3波長の蛍光の光強度を測定し、前記第2及び第3波長の蛍光の測定結果を基に、前記透析排液中に含まれる前記被測定成分の濃度と前記測定阻害成分との濃度の比率を演算し、演算した濃度の比率と、測定した前記第1波長における吸光度とを基に、前記透析排液中の前記被測定成分の濃度を演算する、透析排液用成分測定方法。 [7] A method for measuring the concentration of a component to be measured contained in a dialysis effluent discharged from a blood purifier (12), wherein the component to be measured is a component that absorbs light of a first wavelength and is excited by light of the first wavelength to emit fluorescence of a second wavelength different from the first wavelength, and the dialysis effluent contains a measurement-inhibiting component that absorbs light of the first wavelength and is excited by the first light to emit fluorescence of a third wavelength different from the first and second wavelengths, and wherein the dialysis effluent is irradiated with light of the first wavelength from a light source (2), the light intensity of the transmitted light from the light source (2) that has passed through the dialysis effluent is measured, and the light intensity of the transmitted light is compared with the light intensity of the previous measurement. A dialysis effluent component measurement method comprising: determining the absorbance at the first wavelength from the light intensity of the light source (2); measuring the light intensity of the fluorescence at the second wavelength emitted by the analyte component excited by the light from the light source (2); measuring the light intensity of the fluorescence at the third wavelength emitted by the measurement-inhibiting component excited by the light from the light source (2); calculating the ratio of the concentration of the analyte component to the concentration of the measurement-inhibiting component contained in the dialysis effluent based on the measurement results of the fluorescence at the second and third wavelengths; and calculating the concentration of the analyte component in the dialysis effluent based on the calculated concentration ratio and the measured absorbance at the first wavelength.
以上、本発明の実施の形態を説明したが、上記に記載した実施の形態は特許請求の範囲に係る発明を限定するものではない。また、実施の形態の中で説明した特徴の組合せの全てが発明の課題を解決するための手段に必須であるとは限らない点に留意すべきである。また、本発明は、その趣旨を逸脱しない範囲で適宜変形して実施することが可能である。 The above describes embodiments of the present invention, but the above-described embodiments do not limit the scope of the invention as claimed. It should also be noted that not all of the combinations of features described in the embodiments are necessarily essential to solving the problems of the invention. Furthermore, the present invention can be modified and implemented as appropriate within the scope of its spirit.
1…透析排液用成分測定装置
2…光源
3…吸光度測定部
31…透過光用受光素子
4…第1蛍光測定部
41…第1蛍光用受光素子
42…第1フィルタ
43…第1レンズ(第1導光部材)
5…演算装置
51…比率演算部
52…被測定成分濃度演算部
53…被測定成分漏出量演算部
54…警報部
6…第2蛍光測定部
61…第2蛍光用受光素子
62…第2フィルタ
63…第2レンズ(第2導光部材)
10…血液浄化装置
12…血液浄化器
REFERENCE SIGNS LIST 1...dialysis effluent component measuring device 2...light source 3...absorbance measuring unit 31...transmitted light receiving element 4...first fluorescence measuring unit 41...first fluorescence receiving element 42...first filter 43...first lens (first light guiding member)
5...Calculation device 51...Ratio calculation section 52...Measured component concentration calculation section 53...Measured component leakage amount calculation section 54...Alarm section 6...Second fluorescence measurement section 61...Second fluorescence light receiving element 62...Second filter 63...Second lens (second light guiding member)
10...blood purification device 12...blood purifier
Claims (7)
前記被測定成分は、第1波長の光を吸収し、かつ前記第1波長の光で励起され前記第1波長と異なる第2波長の蛍光を発する成分であり、
前記透析排液中には、前記第1波長の光を吸収し、かつ、前記第1波長の光で励起され前記第1及び第2波長と異なる第3波長の蛍光を発する測定阻害成分が含まれており、
前記透析排液に前記第1波長の光を照射する光源と、
前記光源からの光が前記透析排液を透過した透過光の光強度を測定し、当該透過光の光強度と前記光源の光強度とから前記第1波長における吸光度を求める吸光度測定部と、
前記光源からの光により励起され前記被測定成分が放出する前記第2波長の蛍光の光強度を測定する第1蛍光測定部と、
前記光源からの光により励起され前記測定阻害成分が放出する前記第3波長の蛍光の光強度を測定する第2蛍光測定部と、
前記第1及び第2蛍光測定部の測定結果を基に、前記透析排液中に含まれる前記被測定成分の濃度と前記測定阻害成分との濃度の比率を演算する比率演算部と、
前記比率演算部が演算した濃度の比率と、前記吸光度測定部が測定した前記第1波長における吸光度とを基に、前記透析排液中の前記被測定成分の濃度を演算する被測定成分濃度演算部と、を備えた、
透析排液用成分測定装置。 An apparatus for measuring the concentration of a target component contained in dialysis wastewater discharged from a blood purifier,
the component to be measured is a component that absorbs light of a first wavelength and is excited by the light of the first wavelength to emit fluorescence of a second wavelength different from the first wavelength,
the dialysis effluent contains a measurement-inhibiting component that absorbs light of the first wavelength and is excited by light of the first wavelength to emit fluorescence of a third wavelength different from the first and second wavelengths;
a light source that irradiates the dialysis effluent with light of the first wavelength;
an absorbance measurement unit that measures the light intensity of transmitted light from the light source that has passed through the dialysis effluent, and calculates the absorbance at the first wavelength from the light intensity of the transmitted light and the light intensity of the light source;
a first fluorescence measurement unit that measures the light intensity of the fluorescence of the second wavelength emitted by the component to be measured upon excitation by the light from the light source;
a second fluorescence measurement unit that measures the light intensity of the fluorescence of the third wavelength emitted by the measurement-inhibiting component upon excitation by light from the light source;
a ratio calculation unit that calculates a ratio between the concentration of the measurement target component and the concentration of the measurement inhibiting component contained in the dialysis effluent based on the measurement results of the first and second fluorescence measurement units;
and a measurement component concentration calculation unit that calculates the concentration of the measurement component in the dialysis effluent based on the concentration ratio calculated by the ratio calculation unit and the absorbance at the first wavelength measured by the absorbance measurement unit.
Dialysis effluent component measuring device.
前記測定阻害成分が尿酸である、
請求項1に記載の透析排液用成分測定装置。 the component to be measured is albumin,
The measurement-inhibiting component is uric acid.
The dialysis effluent component measuring device according to claim 1.
前記第2波長が、300nm以上400nm以下であり、
前記第3波長が、380nm以上480nm以下である、
請求項2に記載の透析排液用成分測定装置。 the first wavelength is equal to or greater than 250 nm and equal to or less than 330 nm,
the second wavelength is 300 nm or more and 400 nm or less,
the third wavelength is 380 nm or more and 480 nm or less;
The dialysis effluent component measuring device according to claim 2.
前記第2蛍光測定部は、第2蛍光用受光素子と、前記第1波長及び前記第2波長の光が前記第2蛍光用受光素子に入射されないよう遮断し、かつ前記第3波長の光を透過する第2フィルタと、を有する、
請求項1乃至3の何れか1項に記載の透析排液用成分測定装置。 the first fluorescence measurement unit includes a first fluorescence light-receiving element and a first filter that blocks light of the first wavelength and the third wavelength from being incident on the first fluorescence light-receiving element and transmits light of the second wavelength;
the second fluorescence measurement unit includes a second fluorescence light-receiving element and a second filter that blocks light of the first wavelength and the second wavelength from being incident on the second fluorescence light-receiving element and transmits light of the third wavelength.
The dialysis effluent component measuring device according to any one of claims 1 to 3.
前記第2蛍光測定部は、前記透析排液で生じた蛍光を前記第2蛍光用受光素子に導く第2導光部材を有する、
請求項4に記載の透析排液用成分測定装置。 the first fluorescence measurement unit has a first light guiding member that guides the fluorescence generated in the dialysis effluent to the first fluorescence light receiving element,
the second fluorescence measurement unit has a second light guiding member that guides the fluorescence generated in the dialysis effluent to the second fluorescence light receiving element.
The dialysis effluent component measuring device according to claim 4.
前記吸光度測定部は、前記光源の発光時と非発光時の受光強度の差を、前記透過光による光強度として測定し、
前記第1及び第2蛍光測定部は、前記光源の発光時と非発光時の受光強度の差を、前記蛍光による光強度として測定する、
請求項1乃至5の何れか1項に記載の透析排液用成分測定装置。 the light source repeats light emission and non-light emission at a predetermined cycle;
the absorbance measurement unit measures a difference between the received light intensity when the light source emits light and when it does not emit light as the light intensity of the transmitted light;
The first and second fluorescence measurement units measure a difference in received light intensity between when the light source emits light and when it does not emit light as the light intensity due to the fluorescence.
The dialysis effluent component measuring device according to any one of claims 1 to 5.
前記被測定成分は、第1波長の光を吸収し、かつ前記第1波長の光で励起され前記第1波長と異なる第2波長の蛍光を発する成分であり、
前記透析排液中には、前記第1波長の光を吸収し、かつ、前記第1の光で励起され前記第1及び第2波長と異なる第3波長の蛍光を発する測定阻害成分が含まれており、
前記装置が、
光源から前記透析排液に前記第1波長の光を照射し、
前記光源からの光が前記透析排液を透過した透過光の光強度を測定し、当該透過光の光強度と前記光源の光強度とから前記第1波長における吸光度を求め、
前記光源からの光により励起され前記被測定成分が放出する前記第2波長の蛍光の光強度を測定し、
前記光源からの光により励起され前記測定阻害成分が放出する前記第3波長の蛍光の光強度を測定し、
前記第2及び第3波長の蛍光の測定結果を基に、前記透析排液中に含まれる前記被測定成分の濃度と前記測定阻害成分との濃度の比率を演算し、
演算した濃度の比率と、測定した前記第1波長における吸光度とを基に、前記透析排液中の前記被測定成分の濃度を演算する、
透析排液用成分測定方法。 A method for measuring the concentration of a target component contained in a dialysis effluent discharged from a blood purifier using a dialysis effluent component measuring device , comprising:
the component to be measured is a component that absorbs light of a first wavelength and is excited by the light of the first wavelength to emit fluorescence of a second wavelength different from the first wavelength,
the dialysis effluent contains a measurement-inhibiting component that absorbs light of the first wavelength and is excited by the first light to emit fluorescence of a third wavelength different from the first and second wavelengths;
The device,
irradiating the dialysis effluent with light of the first wavelength from a light source;
measuring the intensity of light transmitted from the light source through the dialysis effluent, and calculating the absorbance at the first wavelength from the intensity of the transmitted light and the intensity of the light source;
measuring the light intensity of the fluorescence of the second wavelength emitted by the component to be measured upon excitation by the light from the light source;
measuring the light intensity of the fluorescence of the third wavelength emitted by the measurement-inhibiting component upon excitation by the light from the light source;
calculating a ratio of the concentration of the measurement target component contained in the dialysis effluent to the concentration of the measurement inhibiting component based on the measurement results of the fluorescence of the second and third wavelengths;
calculating a concentration of the measured component in the dialysis effluent based on the ratio of the calculated concentrations and the measured absorbance at the first wavelength;
Method for measuring components in dialysis effluent.
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| US20070292963A1 (en) | 2006-06-02 | 2007-12-20 | Dickerson Bryan D | Optical determination of serum components for cancer screening |
| JP2015521492A (en) | 2012-06-15 | 2015-07-30 | フレゼニウス メディカル ケアー ドイチュラント ゲゼルシャフト ミット ベシュレンクテル ハフツングFresenius Medical Care Deutschland GmbH | Method and apparatus for monitoring a patient's extracorporeal blood treatment |
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