JP2011047767A - Method and device for measuring urea concentration - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a device and method for measuring urea concentration having high time resolution without requiring any large-scale remodeling of devices in artificial dialysis equipment. <P>SOLUTION: An infrared light source 12 is provided on a side of a channel 11 of a solution to be measured. A first infrared sensor 14b and a second infrared sensor 15b are provided at positions facing the infrared light source 12 via the channel 11. The first infrared sensor 14b detects a first infrared transmission amount at a wavelength band absorbed by urea within the solution to be measured, and the second infrared sensor 15b detects a second infrared transmission amount at a wavelength band not absorbed by urea. Then, the urea concentration is measured, based on a difference between the first infrared transmission amount and the second infrared transmission amount. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

  The present invention relates to a urea concentration measuring method for quantifying a urea concentration in a sample solution, and a urea concentration measuring apparatus using the same.

  When kidney function is impaired, waste products that should be excreted from the body remain in the body. Artificial dialysis treatment has been conventionally performed as a means for artificially discharging waste products. In the artificial dialysis treatment, blood is passed through a tubular hollow fiber assembly called a dialyzer made of a semipermeable membrane having an inner diameter of about 100 μm. At this time, low-molecular solutes such as nitrogen compounds derived from urea existing in the blood are removed from the body by permeating into the dialysate side while passing through the dialyzer. As a result, waste products in the blood can be removed.

  One item to be monitored in the artificial dialysis treatment is the amount of urea in the blood. The amount of urea in the blood is analyzed by collecting blood and evaluated as a blood urea nitrogen (hereinafter sometimes abbreviated as “BUN”) value.

  As a method for measuring the urea concentration in a sample solution containing urea, a colorimetric method that measures the urea concentration by using a reagent that develops color by reacting with urea and comparing it with the standard color of the reagent, specific to urea An enzyme thermistor method that measures urea concentration by immobilizing urease, which is a working enzyme, around glass beads and measuring the heat of reaction accompanying the hydrolysis reaction of urea, an oxidizing agent that reacts with urea to produce chemiluminescence, for example A chemiluminescence method for measuring urea concentration from the intensity of chemiluminescence using hypohalite is known.

  Among these, the chemiluminescence method can measure the urea concentration in real time, and therefore can be used as a means for knowing the timing at which dialysis treatment should be terminated, particularly in artificial dialysis medical treatment. However, in the luminescent reaction between urea and hypohalite ions, the stability of an oxidizing agent such as sodium hypobromite is not good, and the concentration is likely to change, so an improvement has been demanded. As a countermeasure, a proposal shown in Patent Document 1 has been made.

  In Patent Document 1, hypohalite ions are generated in the system by electrolysis, and further, by using a stirring tank having a piston and a cylinder as a tank for performing electrolysis, a uniform luminescence reaction is accurately performed. A real-time urea quantification method to be measured is described.

  In addition, leakage of blood components from the dialyzer is an item to be monitored in the artificial dialysis treatment. For example, during dialysis medical treatment, pressure is applied to the dialyzer, but when the dialyzer is cracked by the pressure, blood components leak into the dialysate. In such a case, there is a proposal shown in Patent Document 2 as means for quickly detecting leakage.

  In Patent Document 2, a glass plate is disposed in parallel so as to sandwich a dialysate flow path, light is incident on the dialysate from the outside of one glass, and a light receiving element is received from the outside of the other glass plate. In the configuration, incident light from the light source is received and the intensity is processed by a computer. When blood components are mixed in the dialysate, the light transmittance of the dialysate decreases because the blood components are absorbed by incident light. Therefore, by monitoring the intensity of the light receiving element, the presence or absence of leakage of blood components is determined, and dialysis medical care is controlled.

JP 2009-069024 A No. 05-22180

  However, when the urea concentration measurement method described in Patent Document 1 is applied to an artificial dialysis treatment, an electrolysis electrode for generating a hypohalite ion and a stirring layer composed of a piston and a cylinder for measuring the urea concentration A good solution is required and a major modification of the artificial dialysis machine is required. Furthermore, since a chemical reaction is required, a measurement time lag corresponding to at least the reaction time occurs. The method described in Patent Document 2 only monitors the leakage of blood components into the dialysate, and cannot determine and identify the leakage components. The present invention has been made in view of the problems as described above, and an object thereof is to provide a urea concentration measuring method and a urea concentration measuring apparatus which do not require a large-scale modification of an artificial dialysis apparatus and have high time resolution. Is to provide.

  The present invention has been made to achieve such an object, and the invention according to claim 1 is characterized in that an infrared light source is disposed on a side surface of a flow path of a solution to be measured, and the infrared light source of the flow path is provided. The first infrared sensor and the second infrared sensor are disposed on the side opposite to the first infrared sensor, and the first infrared sensor detects the first infrared transmission amount in the wavelength band absorbed by urea, and the second infrared sensor. A second infrared transmission amount in a wavelength band that is not absorbed by urea is detected by an infrared sensor, and a urea concentration is measured based on a difference between the first infrared transmission amount and the second infrared transmission amount. Is a method for measuring urea concentration.

  According to a second aspect of the present invention, the first infrared sensor includes a first optical filter that selectively transmits infrared light in a wavelength band absorbed by urea, and a first quantum infrared sensor, The second infrared sensor is a urea concentration measuring method comprising a second optical filter that selectively transmits infrared light in a wavelength band that is not absorbed by urea and a second quantum infrared sensor.

  The invention according to claim 3 includes an infrared light source on a side surface of the flow path of the solution to be measured, and includes a first infrared sensor and a second infrared sensor on the side surface of the flow channel facing the infrared light source, The first infrared sensor detects a first infrared transmission amount in a wavelength band absorbed by urea, and the second infrared sensor detects a second infrared transmission amount in a wavelength band not absorbed by urea. A urea concentration measuring apparatus that measures urea concentration based on a difference between the first infrared transmission amount and the second infrared transmission amount.

  According to a fourth aspect of the present invention, the first infrared sensor includes a first optical filter and a first quantum infrared sensor that selectively transmit infrared light in a wavelength band absorbed by urea. The second infrared sensor is a urea concentration measuring device including a second optical filter that selectively transmits infrared light in a wavelength band that is not absorbed by urea and a second quantum infrared sensor.

  According to a fifth aspect of the present invention, the quantum infrared sensor has a sensor element portion, and the sensor element portion is provided on the first contact layer provided on the substrate and on the first contact layer. An absorption layer formed thereon, a barrier layer provided on the absorption layer, a second contact layer provided on the barrier layer, a second electrode provided on the second contact layer, A passivation layer provided adjacent to the first contact layer, the absorption layer, the barrier layer, and the second contact layer; and a first electrode provided on the substrate via the passivation layer; The urea concentration measuring device according to claim 3, wherein the urea concentration measuring device is provided.

  According to a sixth aspect of the present invention, the first contact layer is made of n-type InSb, the absorption layer is made of π-type InSb, the barrier layer is made of p-type AlInSb, and the second contact 6. The urea concentration measuring apparatus according to claim 5, wherein the layer is made of p-type InSb.

  The invention according to claim 7 is the urea concentration measuring apparatus according to any one of claims 3 to 6, wherein the quantum well infrared sensor has a plurality of sensor element portions connected in series. .

  According to the present invention, a plurality of quantum infrared sensor elements and a plurality of optical elements provided on the infrared light source side with respect to the quantum infrared sensor elements and selectively transmitting infrared light in different specific wavelength bands. By providing the filter in a shape that sandwiches the flow path of the measurement target solution, the filter has a small and simple element shape, and can perform high time resolution urea concentration determination in the measurement target solution.

It is a block diagram of the quantum type infrared sensor in this invention. It is sectional drawing of the quantum type infrared sensor which consists of a some sensor element in this invention. Is a diagram showing the transmittance in the infrared region of the H ₂ O. It is a figure which shows the transmittance | permeability in the infrared region of urea.

  Embodiments of the present invention will be described below with reference to the drawings.

  (FIG. 1) A quantum infrared sensor according to the present invention is provided adjacent to a plurality of quantum infrared sensors 14b and 15b and the infrared sensors 14b and 15b. A plurality of optical filters 14a and 15a that transmit light and a holding member 17 that holds at least the quantum infrared sensor elements 14b and 15b and the optical filters 14a and 15a. The optical filters 14a and 15a face the measurement target solution flow path end through the window member 13, and the other measurement target solution flow path end includes the window material 13 and the infrared light source 12 outside thereof. The outputs of the quantum infrared sensor elements 14b and 15b are input to an arithmetic unit 16 that processes an input signal through an amplifier and a filter for removing noise.

  As shown in FIG. 1, the pair of optical filters 14 a and 15 a is a pair of a reference light transmission optical filter from an infrared light source and a wavelength band transmission optical filter different from the reference light. The optical filter that selectively transmits infrared light in a specific wavelength band used in the present invention is an optical member that transmits electromagnetic waves such as infrared rays, and selectively transmits infrared light in a specific wavelength band. It is designed to be transparent. As long as the optical member has a function of selectively transmitting infrared light in a specific wavelength band, an optical member alone can be used. In addition, a dielectric multilayer filter in which dielectrics having different refractive indexes are deposited in layers on an optical member is also used.

  An example of this optical filter is shown below, but the optical filter in this embodiment is not limited to this example, and any optical filter having a function of selectively transmitting infrared light can be used. It can be used without limitation. As an example of the optical filter, an optical member and a thin film formed in a multilayer on the optical member have a function of not transmitting infrared rays having a long wavelength, a short wavelength, or both wavelengths. By combining these transmission functions, the optical filter consequently transmits only infrared rays having a specific wavelength.

This optical filter may perform a function of transmitting only infrared rays having a specific wavelength, or may use a plurality of sheets depending on circumstances. In addition, as a material of the optical member, a material that transmits predetermined infrared rays such as silicon (Si), glass (SiO ₂ ), sapphire (Al ₂ O ₃ ), Ge, ZnS, ZnSe, CaF ₂ , and BaF ₂ is used. be able to. The thin film material deposited on this is silicon (Si), glass (SiO ₂ ), sapphire (Al ₂ O ₃ ), Ge, ZnS, TiO ₂ , MgF ₂ , SiO ₂ , ZrO ₂ , Ta ₂ O. ₅ etc. In addition, the dielectric multilayer filter in which dielectrics having different refractive indexes are laminated in layers on the optical member may be formed on both sides with a configuration having different predetermined thicknesses on the front and back surfaces, or only on one side. It may be formed. Further, for the purpose of preventing unnecessary reflection, an antireflection film may be formed only on the front surface, both surfaces of the back surface, or only one outermost layer.

  The window material used in the present invention may be any material that does not dissolve in the solution to be measured and has a sufficiently small absorption of the reference light wavelength and the wavelength light for wavelength band transmission. Specifically, alumina (Al2O3), calcium fluoride (CaF2), barium fluoride (BaF2), zinc selenide (ZnSe) magnesium fluoride (MgF2), thallium bromoiodide (TlBr + TlI), lithium fluoride (LiF) And optical quartz (SiO2).

  Further, it is desirable that the portion corresponding to the infrared optical path has a configuration in which the non-measurement solution does not stagnate and the infrared optical path length is sufficiently long. Specifically, as shown in FIGS. 1A and 1B, the measurement target solution flow path 11 has a tapered portion 18 or a curve portion 19 in the vicinity of the infrared light path, thereby allowing a non-measurement solution in the infrared light path. It is desirable to have a structure that eliminates the stagnation of the non-measurement solution in the infrared optical path. In addition, the structure shown in FIG. 1C can eliminate the stagnation of the non-measuring solution and sufficiently take the infrared optical path length. That is, by changing a part of the measurement target solution flow path 11 into a crank shape and using the crank portion 20 as an infrared optical path, a change in the width of the measurement target solution flow path 11 that causes a stagnation of the non-measurement solution can be eliminated. Therefore, the stagnation of the non-measurement solution can be minimized. Further, by making the length of the crank portion 20 sufficiently long, a desired infrared optical path length can be obtained.

  (FIG. 2) A quantum infrared sensor operating at room temperature according to the present invention has a light receiving portion having a photodiode structure that generates a photovoltaic effect by infrared rays on a substrate. As this substrate, a single crystal Si substrate, a glass substrate, a GaAs substrate, or the like can be used. Here, a semi-insulating GaAs substrate is used as an example.

  The light receiving unit is a quantum type light receiving unit in which the light receiving surface is excited by infrared photons (photons), and the electrical properties of the light receiving surface are changed by this excitation. In the light receiving unit, infrared energy is converted into electric energy by photoelectric conversion on the light receiving surface. Since it is a quantum type, the infrared detection sensitivity of the light receiving unit is hardly affected by the heat capacity of the light receiving unit and its periphery.

  In addition, the light receiving surface of the light receiving unit is made of InAsxSb1-x (0 ≦ x ≦ 1), for example, and can efficiently photoelectrically convert infrared rays having a wavelength of about 1 to 11 μm. The light receiving unit is composed of, for example, an InSb quantum PIN photodiode formed on a semi-insulating GaAs substrate.

  The InSb-based quantum PIN photodiode is doped with a substrate, an n-type InSb layer (contact layer) formed on the substrate, and a p-type doped layer formed on the n-type InSb layer. An InSb layer (absorption layer), a p-type AlInSb layer (barrier layer) formed on the p-type doped InSb layer, and a p-type InSb layer (contact) formed on the p-type AlInSb layer Layer).

  In the sensor element (light receiving unit), the PIN photodiodes are connected in series by connection wiring. When infrared light is incident from the back side of the substrate (that is, opposite to the surface on which the PIN photodiode is formed), a photoelectromotive force corresponding to the amount of infrared radiation is generated in the PIN photodiode and passes through the connection wiring to receive the light receiving unit. It is designed to be output outside of.

  A quantum infrared sensor operating at room temperature has higher sensitivity than a thermoelectromotive force type element such as a thermopile generally used in the past, and a noise amount per signal, that is, an SN ratio is also better than them. In addition, this quantum infrared sensor can be formed into a shape that can be surface-mounted during assembly.

  Further, the sensor element 29 will be described in more detail. For example, an n-type InSb contact layer 22, a π-type InSb absorption layer 23, a p-type AlInSb barrier layer 24, and a p-type InSb contact layer 25 are formed on a semi-insulating GaAs substrate 21. The InSb contact layer 22 is electrically connected to the first element part electrode 26a, and the p-type InSb contact layer 25 is electrically connected to the second element part electrode 27a.

  The material of the semiconductor thin film constituting the sensor element 29 is not limited to the above-described example. A passivation layer 28 such as SiN is formed at a predetermined position so that the first element portion electrode 26a and the second element portion electrode 27a do not contact the semiconductor layer. Furthermore, since the back surface of the semi-insulating GaAs substrate serves as a window for capturing infrared rays, a protective layer 30 is formed. The protective film 30 is provided for preventing reflection of incident infrared rays and protecting the sensor portion, and a material that transmits as much infrared rays as possible of a wavelength to be measured is preferably selected. For example, silicon oxide or silicon nitride is preferably used.

  With such a configuration, the infrared light transmitted through the optical filters 14a and 15a enters the semi-insulating GaAs substrate 21 from the protective layer 30 of the first and second quantum infrared sensors 14b and 15b. The infrared light transmitted through the optical filters 14a and 15a has a wavelength such as 5.0 μm and 5.7 μm, the semi-insulating GaAs substrate 21 has a wide energy band gap, and the infrared light transmitted through the optical filters 14a and 15a is The light is transmitted without being absorbed by the GaAs substrate 21. The infrared light transmitted through the GaAs substrate 21 is absorbed by the π-type InSb absorption layer 23 of the first and second quantum infrared sensors, and a photocurrent is generated in the π-type InSb absorption layer 23 by photoexcited electrons. . The output voltage can be taken out from the first and second element part electrodes 26a and 27a and the first and second pad electrodes 26b and 27b according to the generation amount of the photocurrent.

  As shown in FIG. 2, the quantum infrared sensor elements can be connected in series. Thereby, a large output signal can be obtained. As the number of sensor elements 29 is increased in series on a substrate having the same area, the sensitivity of the quantum infrared sensor is improved. Therefore, as many sensor elements 29 as possible can be formed using a fine processing technique. preferable.

In the practice of the present invention in actual artificial dialysis, the dialysate flow path is the measurement target solution flow path 11 shown in FIG. When measuring the concentration of urea contained in the dialysate, as shown in FIG. 3, a band-pass filter with a wavelength of 5.0 μm having high transmittance of H ₂ O and urea is used as the optical filter 14a, while FIG. As shown, a band-pass filter with a wavelength of 5.7 μm having a high transmittance of H ₂ O and a low transmittance of urea is used for the optical filter 15a. When infrared light is incident on the measurement target solution (dialysate) flow path 11 from the infrared light source 12, output voltages are generated in the first and second quantum infrared sensors 14b and 15b, respectively, and these are compared. The urea concentration can be measured. For example, when the urea concentration in the solution to be measured increases, the light intensity at a wavelength of 5.0 μm where the transmittance of urea is high does not change, but the light intensity at a wavelength of 5.7 μm where the transmittance of urea is low is the urea concentration. Depending on the light intensity decreases. Since the output voltages of the first and second quantum infrared sensors 14b and 15b increase or decrease depending on the light intensity, the concentration change of urea can be calculated based on the outputs from the sensors 14b and 15b, and the measurement target solution It is possible to measure the urea concentration.

11 Measurement target solution flow path 12 Infrared light source 13 Window member 14a First optical filter 14b First quantum infrared sensor 15a Second optical filter 15b Second quantum infrared sensor 16 Arithmetic device 17 Holding member 18 Tapered portion 19 Curve part 20 Crank part 21 Substrate 22 First contact layer 23 Absorbing layer 24 Barrier layer 25 Second contact layer 26a First element part electrode 26b First pad electrode 27a Second element part electrode 27a Second Pad electrode 28 Passivation layer 29 Quantum infrared sensor element 30 Protective layer

Claims (7)

An infrared light source is placed on the side of the flow path of the solution to be measured,
A first infrared sensor and a second infrared sensor are disposed on a side surface of the flow channel facing the infrared light source;
The first infrared sensor detects a first infrared transmission amount in a wavelength band absorbed by urea,
By the second infrared sensor, a second infrared transmission amount in a wavelength band that is not absorbed by urea is detected,
A urea concentration measurement method, wherein a urea concentration is measured based on a difference between the first infrared transmission amount and the second infrared transmission amount. The first infrared sensor includes a first optical filter that selectively transmits infrared light in a wavelength band absorbed by urea and a first quantum infrared sensor, and the second infrared sensor includes urea. The urea concentration measuring method according to claim 1, comprising: a second optical filter that selectively transmits infrared light in a wavelength band that is not absorbed; and a second quantum infrared sensor. An infrared light source is provided on the side of the flow path of the solution to be measured,
A first infrared sensor and a second infrared sensor are provided on a side surface of the flow channel facing the infrared light source,
The first infrared sensor detects a first infrared transmission amount in a wavelength band absorbed by urea, and the second infrared sensor detects a second infrared transmission amount in a wavelength band not absorbed by urea. A urea concentration measuring device that measures urea concentration based on a difference between the first infrared transmission amount and the second infrared transmission amount. The first infrared sensor includes a first optical filter that selectively transmits infrared light in a wavelength band absorbed by urea and a first quantum infrared sensor, and the second infrared sensor includes urea. The urea concentration measuring apparatus according to claim 3, comprising: a second optical filter that selectively transmits infrared light in a wavelength band that is not absorbed; and a second quantum infrared sensor. The quantum infrared sensor has a sensor element part, and the sensor element part is
A first contact layer provided on the substrate; an absorption layer provided on the first contact layer; a barrier layer provided on the absorption layer; and a second layer provided on the barrier layer. A contact layer, a second electrode provided on the second contact layer, the first contact layer, the absorption layer, the barrier layer, and the second contact layer. The urea concentration measuring apparatus according to claim 3, further comprising: a passivation layer; and a first electrode provided on the substrate via the passivation layer. The first contact layer is made of n-type InSb, the absorption layer is made of π-type InSb, the barrier layer is made of p-type AlInSb, and the second contact layer is made of p-type InSb. The urea concentration measuring apparatus according to claim 5.   The urea concentration measuring apparatus according to any one of claims 3 to 6, wherein the quantum well infrared sensor has a plurality of sensor element units connected in series.

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