JPH0747000B2 - Trace component measuring method and trace component measuring device - Google Patents

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for measuring a trace ingredient and a device for measuring a trace ingredient, and more specifically, a method for measuring a trace ingredient which allows a simple and continuous measurement with little variation in the measurement result due to measurement conditions. And its measuring method, which is excellent in accuracy with little output fluctuation due to measuring conditions such as temperature, lightweight, small size, convenient to handle, and capable of continuously measuring a trace amount component measuring device. Regarding

[0002]

2. Description of the Related Art In recent years, in the field of bioelectronics, development of biosensors including enzyme sensors, microbial sensors, etc. for measuring a specific substance by utilizing an enzymatic reaction has been actively pursued. is there. Furthermore, development of analytical instruments, measuring instruments, medical instruments, etc. equipped with biosensors has been actively conducted. Among these, one of the notable ones is a blood glucose measuring device that measures the glucose concentration in blood. Blood glucose level is an important factor that must be controlled for diabetics. Conventionally, for example, the following blood glucose measuring device has been proposed.

First, a physiological saline solution is first sent to a hollow fiber for dialysis, which is placed in a solution to be measured, such as a biological fluid, using a syringe pump. Next, in the dialysis hollow fiber, glucose contained in the liquid to be measured is dialyzed by utilizing the difference in concentration between the inside and the outside. Then, this dialysate is sent to a measuring unit, and the amount of glucose in the dialysate is measured by the glucose sensor in the measuring unit {Hashiguchi et al., Artificial organ, 21 (3); 1094 (1992), Hashiguchi et al.
Medical Electronics and Biotechnology, Vol. 30, Special Issue (1992)}.

In other cases, first, a physiological saline solution and glucose oxidase are sent to a hollow fiber for dialysis, which is left in a solution to be measured such as a biological fluid by using a syringe pump or a peristaltic pump. Next, in the dialysis hollow fiber, the glucose contained in the liquid to be measured is dialyzed by utilizing the difference in concentration between the inside and outside thereof, and the glucose and glucose oxidase are reacted. Then, the amount of oxygen consumed in the reaction, by measuring with an oxygen sensor in the measurement unit and converted into glucose concentration, is a device for indirectly measuring the glucose concentration {AJMSchoone et al., Biosensors and Bioelectroni
cs 5; 37 (1990), ALAalders et al., Intern.J.Artif.O
rgans 14 (2); 102 (1991)}. In addition to the glucose concentration, a device for measuring the concentration of the drug in the dialysate obtained in the same manner by a mass spectrometer has been proposed {RMCa
prioli, see WO9014791}.

However, in these devices, a mechanically driven syringe pump or the like is used to send physiological saline for dialysis of trace components in the liquid to be measured to the dialysis hollow fiber. However, there is a problem that the entire device is large and heavy, inconvenient to handle, and expensive.

By the way, since the enzyme has an optimum temperature at which its reaction activity is maximized, the enzyme reaction has temperature dependence. Therefore, when using a biosensor that utilizes an enzymatic reaction, it is generally necessary to use it under a constant temperature condition or to have a temperature compensation mechanism itself. However, in the above conventional device,
None of them has a temperature compensation mechanism. Moreover, since the use conditions are often in an environment where the temperature is not always controlled to a constant temperature, there is a problem that the influence of temperature is directly exerted and a measurement error is large. It is very dangerous for a patient to perform treatment / treatment such as insulin administration based on a measurement result having such a large error, for example, a blood glucose level.

In the present age where adult diseases such as diabetes are rapidly increasing and aging society is advancing, trace components such as blood glucose can be measured continuously and safely and accurately with little influence of measurement conditions. There is a particular need in the medical field for a compact and convenient device to handle. The present invention solves the above-mentioned problems, and in response to such a demand, by reducing the output fluctuation due to temperature dependence and the like, it is possible to measure trace components simply and continuously, and with a small measurement error and high accuracy. An object of the present invention is to provide a trace amount measuring device which is small in size and convenient to handle, and a trace amount measuring method.

[0008]

In order to solve the above-mentioned problems, the inventor of the present invention has made earnest studies. As a result, instead of a mechanically driven syringe pump in a conventional measuring device, a gas generated by a chemical reaction It has been found that the use of an injection pump driven by gas pressure makes it possible to reduce the size of the entire apparatus and improve the handleability. Even more surprisingly, the temperature dependence of dialysis glucose concentration and glucose sensor output by a gas pressure driven infusion pump is opposite to each other,
The inventors have found that the temperature dependences of the respective devices are counteracted by the opposite effects, and as a result, the temperature dependence of the entire device can be lowered, and the present invention has been reached.

That is, claim 1 for solving the above problems
The invention described in (1), the perfusion solution is discharged by an injection pump that uses the gas pressure of the gas generated by a chemical reaction as a driving source, the discharged perfusion solution is stored in a dialysis probe, and further trace components to be measured are dialyzed. A method for measuring a trace amount of a component, characterized in that a perfusion liquid containing a trace component is taken into the perfusion liquid and is sent out, and the trace component contained in the sent out perfusion liquid is measured by an enzyme sensor flow cell. The invention according to claim 2 is the method for measuring a trace component according to claim 1, wherein the trace component is glucose, and the invention according to claim 3 drives the gas pressure of a gas generated by a chemical reaction. An infusion pump that discharges a perfusate as a source, and a trace component by containing the discharged perfusate and incorporating a trace component to be measured into the perfusion liquid by dialysis. 5. A trace component measuring device comprising: a dialysis probe for producing a perfusate and delivering the same, and an enzyme sensor flow cell for measuring a trace component contained in the delivered perfusate. The invention of (3) is the trace component measuring apparatus according to claim 3, wherein the trace component is glucose.

[0010]

In the method for measuring trace constituents of the present invention, the perfusate is discharged by the injection pump using the gas pressure of the gas generated by the chemical reaction as the driving source. The discharged perfusate is stored in the dialysis probe. Next, in the dialysis probe, the trace components to be measured are incorporated into the perfusion solution by dialysis. Then, a perfusate containing trace components is generated inside the dialysis probe. It is then sent to the enzyme sensor flow cell. In the enzyme sensor flow cell, trace components contained in the sent perfusate are measured.

In the trace component measuring device of the present invention,
The injection pump discharges the perfusion liquid by using the gas pressure of the gas generated by the chemical reaction as a driving source. The dialysis probe accommodates the perfusate and takes in trace components to be measured into the perfusate by dialysis. Then, in the dialysis probe, a perfusate containing trace components is generated. Further, the dialysis probe delivers the perfusate containing the trace components. The perfusate containing trace components is subjected to an enzymatic reaction in an enzyme sensor flow cell. With this, a trace component is measured.
Since the injection pump is of a gas pressure drive type, a driving member such as a motor and a power source are not necessary in this trace component measuring apparatus, and therefore the entire apparatus is extremely small and convenient to handle.

[0012]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS A method for measuring a trace component as an embodiment of the present invention will be described below together with a trace component measuring apparatus with reference to the drawings. The present invention is not limited to the following embodiments. FIG. 1 is a schematic explanatory view showing one embodiment of the trace component measuring apparatus of the present invention.
The trace component measuring device shown in FIG. 1 includes an infusion pump 1, a dialysis probe 20, and an enzyme sensor flow cell 30.

The infusion pump 1 and the dialysis probe 20
Are connected to each other by a vinyl chloride tube 40a. The dialysis probe 20 and the enzyme sensor flow cell 30 are connected by a vinyl chloride tube 40b. The infusion pump 1 discharges the perfusate and injects it into the dialysis probe.

The infusion pump 1 is provided inside the perfusion solution supply container 3 with a moving member 4 which is in close contact with the inner wall of the perfusion solution supply container 3 and is slidable forward and backward, and a spout 2 in the perfusion solution supply container 3. And a stator 7 fixed by closing the opening on the opposite side to the perfusion fluid chamber 5 defined by the spout 2 and the mover 4, and the mover 4 and the stator 7. The gas generating chamber 6 is formed.

The perfusion solution chamber 5 is filled with a perfusion solution 5a which is physiological saline. In the gas generation chamber 6,
Contains iodine compounds. In the injection pump 1, when the hydrogen peroxide solution is injected into the gas generating chamber 6 from the side of the stator 7 using a syringe or the like, the hydrogen peroxide solution is decomposed by the catalytic effect of the iodine compound to generate oxygen gas. Then, the volume of the gas generation chamber increases due to the generated oxygen gas, so that the mover 4 is pushed toward the spout 2 side. Then, the perfusate 5 a that cannot be stored in the perfusate chamber 5 is discharged from the spout 2. Discharged perfusate 5
a passes through the inside of the tube 40a and passes through the dialysis probe 20.
Is injected into.

The dialysis probe 20 contains the perfusate 5a discharged from the infusion pump 1, and incorporates the trace component to be measured into the perfusate 5a by dialysis to form the trace component-containing perfusate 5b. Send to the enzyme sensor flow cell 30. The trace component measured in this example is glucose contained in blood.

The dialysis probe 20 comprises an inlet 23, a needle shaft 21, a dialysis membrane 22, an outlet 24 and a reinforcing material 25. The shape of the dialysis probe 20 is
It is needle-shaped. The inlet 23 is a hollow fine hole, and one end thereof is connected to the tube 40a. The inlet 23 is housed inside the hollow needle shaft 21. There is a space between the inlet 23 and the needle shaft 21 inside the needle shaft 21. This space is the outlet 24. The outlet 24 and the enzyme sensor flow cell 30 are connected by a tube 40b.

The tip of the dialysis probe 20, that is, the tip of the needle shaft 21 is a dialysis membrane 22. On the other hand, the branching portion of the inlet 23 and the outlet 24 on the opposite side is fixed by the reinforcing material 25. The dialysis membrane 22 is a hollow fiber, which is a hollow fiber dialysis membrane. The length of the dialysis membrane 22 is 15 mm.

In the dialysis probe 20, the dialysis membrane 22
Other than is a closed system, there is no transfer of substances to or from the outside. The dialysis probe 20 is left in the blood to be measured containing glucose. In the dialysis probe 20, the perfusate 5a discharged from the infusion pump 1 is guided to the inlet 23 via the tube 40a. Further, the perfusate 5a is guided to the dialysis membrane 22 through the inlet 23. In the dialysis membrane 22, due to the difference in concentration between the perfusate 5a, which is physiological saline inside the dialysis membrane 22, and the blood, which contains glucose outside, in the dialysis membrane 22, glucose is adsorbed on the dialysis membrane 2
It passes through 2 and moves into the dialysis probe 20, and is taken in. As a result, glucose is dialyzed. Then, the perfusate 5a becomes the glucose-containing perfusate 5b, passes through the outlet 24, and passes through the tube 40b.
And is sent to the enzyme sensor flow cell 30. The enzyme sensor flow cell 30 includes a trace component-containing perfusion solution 5b sent from the dialysis probe 20 through a tube 40b.
While passing through, the trace components contained therein are measured.

The enzyme sensor flow cell 30 comprises an enzyme sensor 31 and a flow cell 32. The enzyme sensor 31 is a glucose sensor. Enzyme sensor 31
Has an enzyme film 33 on which glucose oxidase, which is an enzyme that catalyzes an oxidation reaction of glucose, is immobilized in order to measure glucose to be measured. This enzyme membrane 33
In the enzymatic reaction is carried out.

The principle of measuring glucose is as follows: In the following oxidation reaction of glucose catalyzed by glucose oxidase, glucose + O ₂ → gluconolactone + H ₂ O ₂ generated hydrogen peroxide is measured by a current method using a platinum electrode as a working electrode. By detecting by.

The flow cell 32 is designed so that the perfusate 5b containing a trace component can pass while contacting the enzyme membrane 33 of the enzyme sensor 31. The trace component-containing perfusion liquid 5b that has passed through the enzyme sensor flow cell 30 is guided to a waste liquid bottle by a tube 40c and disposed of as a waste liquid. In the enzyme sensor flow cell 30, the trace component-containing perfusion solution 5b sent from the dialysis probe 20 via the tube 40b is introduced into the enzyme sensor flow cell 30. Perfusion solution containing trace components 5b
Passes through the inside of the enzyme sensor flow cell 30 while being in contact with the enzyme film 33 of the enzyme sensor 31. At this time, the oxidation reaction by glucose oxidase is performed in the enzyme film 33. Hydrogen peroxide generated by this enzymatic reaction is subjected to a redox reaction at a platinum electrode (not shown) in the enzyme sensor 31. Then, a limiting diffusion current is obtained by the redox reaction.
This current is guided by a lead wire 34 to a measuring device (not shown) and is measured. The measurement result is converted into a glucose concentration by a calibration line created in advance. In this way, the amount of glucose can be measured.

<< Characteristics of Trace Component Measuring Device >> The following characteristics of the trace component measuring device in this example were tested. <Relationship Between Discharge Amount of Injection Pump and Temperature> FIG. 4 shows the relationship between the discharge amount of the injection pump and temperature. Here, in the gas generation chamber 6 containing 1 μg of sodium iodide, 17.
The injection pump shown in FIG. 1 into which 0.2 ml of a 5% aqueous hydrogen peroxide solution was injected was used. As can be seen from the graph of FIG. 4, in the infusion pump used in the present invention, the change rate of the discharge amount with respect to the temperature change is much larger than that of the conventional syringe pump. That is, the infusion pump used in the present invention has a greater temperature dependency than the conventional syringe pump. The temperature dependence of the discharge amount in the injection pump is usually +3 to 6 (% / ° C). In this case, 2
The temperature dependence of the discharge amount in the infusion pump is +5.3 (% / ° C.) based on 5 ° C., while the temperature dependence of the discharge amount in the conventional syringe pump is +0.6.
(% / ° C.).

<Relationship between the concentration of glucose dialyzed by the dialysis probe and the temperature> The dialysis probe (caprophane membrane hollow fiber, membrane length 15 mm) in the trace component measuring apparatus of the present invention has a glucose concentration of 100 (mg / dl physiological). The concentration of glucose dialyzed by a dialysis probe was measured by the GOD colorimetric method, and the temperature dependence of the glucose concentration was investigated. At this time, an infusion pump having the characteristics shown in FIG. 4 was used, and a perfusion solution was physiological saline.

[0025] As a result, as shown in FIG. 5, a large temperature dependence of the infusion pump in the present invention, as the temperature rises, in response to the discharge amount increases, glucose
Concentration was found you to decrease. The temperature dependence of the dialysis glucose concentration in the infusion pump is −2.8 (% / ° C.) based on 25 ° C., while the temperature dependence of the dialysis glucose concentration in the conventional syringe pump is −
It was 0.4 (% / ° C.).

<Relationship between the output of the enzyme sensor and the temperature> In order to investigate the temperature dependence of the output of the enzyme sensor,
Using a syringe pump, the glucose concentration is 100 (m
An aqueous solution (g / dl physiological saline) was sent to the enzyme sensor flow cell at a discharge rate of 100 (μl / hr).
For the enzyme sensor, the anode is platinum and the cathode is silver /
A glucose sensor prepared by immobilizing glucose oxidase on a silver chloride hydrogen peroxide electrode was used.
The output current of the enzyme sensor in the enzyme sensor flow cell was measured with a potentiostat (applied voltage 0.65
V), the temperature dependence of the enzyme sensor output was investigated. As a result, the relationship between the enzyme sensor output and the temperature was obtained as shown in FIG. The temperature dependency of the enzyme sensor output was +3.1 (% / ° C.) based on 25 ° C.

<Temperature Dependence of Trace Component Measuring Device According to the Present Invention> The trace component measuring device according to the present invention, that is, a trace component measuring device comprising an infusion pump, a dialysis probe and an enzyme sensor flow cell, and a conventional device, ie, The temperature dependency with a measuring device consisting of a syringe pump, a dialysis probe and an enzyme sensor was investigated. As the infusion pump, the dialysis probe and the enzyme sensor, those having the characteristics shown in FIGS. 4 to 6 were used. It should be noted that physiological saline is used as the perfusate, the dialysis probe is immersed in an aqueous solution having a glucose concentration of 100 (mg / dl physiological saline), and the output current of the enzyme sensor is measured with a potentiostat. did.

As a result, as shown in FIG. 7, the change rate of the enzyme sensor output with respect to the temperature change is smaller in the trace component measuring device according to the present invention than in the conventional measuring device. That is, the temperature dependence was small. The temperature dependency of the trace component measuring device according to the present invention is +0.5 (% / ° C.) based on 25 ° C., while the temperature dependency of the conventional measuring device is +3.5 (% / ° C.). ℃).

The reason for the above results is that in the trace component measuring device according to the present invention, the temperature dependence of the dialysis glucose concentration by the infusion pump and the output of the enzyme sensor are opposite to each other. are respective temperature dependency offset, because it was possible to reduce the temperature dependence of the result. According to trace component measuring apparatus in this invention, when the measurement of trace components, it is possible to reduce the influence of temperature.

As another embodiment of the present invention, instead of the infusion pump 1, the dialysis probe 20 or the enzyme sensor flow cell 30 in the above embodiment, the following infusion pump, dialysis probe or enzyme sensor flow cell is used to measure a trace amount of components. A device can be mentioned. The trace component measured in the above examples was glucose, but in the present invention, there is no particular limitation as long as it is a substance that can be dialyzed with a dialysis probe and can be measured by an enzymatic reaction. For example, neurotransmitters such as acetylcholine, amines, amino acids, aldehydes, uric acid,
In-vivo components such as lactic acid, pyruvic acid, cholesterol, and glucose can be mentioned.

The tube for connecting the dialysis probe and the infusion pump, or the tube for connecting the dialysis probe and the enzyme sensor flow cell is a coil when the dialysis probe 20 is left in a living body such as a human being or an animal. It is preferably in the form of a shape. This is because the coiled shape prevents the dialysis probe 20 from coming off even if the animal or the like moves. In the present invention, instead of the infusion pump 1 in the above-described embodiment, for example, a device using an infusion pump having a gas generating chamber of a variable volume envelope shown in FIG. 2 can be used.

The infusion pump 1 shown in FIG. 2 has the same function as the infusion pump 1, but does not include the mover 4, and the gas generating chamber is composed of a variable-volume rubber envelope, for example. It is different in that it is done. That is, in the infusion pump 1 of FIG. 2, the perfusate chamber 5 and the gas generating chamber 6 are directly defined by the volume-variable enclosure forming the gas generating chamber.

In the injection pump 1, when the gas 6a is generated in the gas generating chamber 6, the gas 6a presses the wall surface of the envelope forming the gas generating chamber 6. Then,
As the volume of the gas generation chamber 6 increases, the volume of the perfusion liquid chamber 5 decreases, and the perfusion liquid 5a that cannot be accommodated inside is discharged from the spout 2. This discharged perfusate 5a
Are delivered to the dialysis probe by a tube connected to the spout 2. Thus, the perfusate can be injected into the dialysis probe.

Another example is an infusion pump having a perfusate 5 formed of a variable volume envelope shown in FIG. The principle of this infusion pump is the same as the infusion pump shown in FIG. However, in that the volume-variable envelope forms the perfusion liquid chamber 5 instead of the gas generation chamber 6, FIG.
Infusion pump. Further, as another example of the infusion pump 1, there are JP-A-63-109873 and JP-A-62-28.
The pumps described in each publication of No. 4653 can be mentioned.

The volume of the perfusate chamber in these infusion pumps 1 is usually 2 to 50 ml. The perfusate can be appropriately selected according to the purpose. For example, when a trace component in blood is to be measured, physiological saline that is isotonic with blood is usually used. The physiological saline may be prepared or commercially available. The discharge amount of the infusion pump is 50 to 400 μl / hr. The discharge speed of the injection pump can be adjusted by changing the diameter of the spout, the amount of reagent filled in the gas generating chamber, such as the amount of iodine compound or the amount of aqueous peroxide solution, so as to suit the purpose.

The injection pump 1 in the present invention may be any pump as long as it can discharge the perfusate without generating a pulsating flow by the gas pressure of the gas generated by the chemical reaction, and its size, shape and structure. There are no particular restrictions,
It can be appropriately selected according to the purpose. The infusion pump may be provided at any position in the trace component measuring device. The number of infusion pumps used may be one, or two or more.

In the present invention, instead of the dialysis probe 20 in the above-mentioned embodiment, for example, a linear dialysis probe in which one end of a hollow fiber having open ends is connected to the inlet and the other end is connected to the outlet. Can be used. In this case, since the dialysis probe has a straight and simple shape, the flow of the perfusate is smooth.

Each part of these dialysis probes can be variously selected. The inlet, outlet, and needle shaft are usually linear shapes made of appropriately selected materials in consideration of the generation of retention of the perfusate flowing through the inside thereof. The dialysis membrane is usually hollow fiber which is a hollow fiber dialysis membrane. Examples of the hollow fiber include caprophane, an ethylene vinyl alcohol copolymer (EVAL), etc., which are excellent in compatibility with a measurement object and diffusion characteristics. In the present invention, they are appropriately selected according to the purpose. be able to.

The length of the dialysis membrane is usually 1 to 30 mm. This length can be appropriately selected depending on the measurement target. The outer diameter of the dialysis membrane is usually 200 to 300 μm. The thickness of the dialysis membrane is usually 5 to 50 μm.
The outer diameter of the dialysis membrane portion of the dialysis probe is usually 200 to 30.
It is 0 μm. The trace components that can be incorporated by this dialysis probe have a molecular weight of about 20000 to 600.
It is a relatively low molecular weight trace component of 00 or less.

Therefore, since proteins such as albumin are rarely dialyzed, there is no need to operate deproteinization or the like when measuring trace components in the enzyme sensor flow cell, and the measurement operation is simple and , High accuracy because there is little loss of trace components to be measured. Further, since the enzyme sensor flow cell is not contaminated with protein or the like, deterioration of the enzyme sensor can be extremely reduced.

As the dialysis probe in the present invention,
As long as it has a function of containing the perfusate discharged from the infusion pump and incorporating the trace component to be measured into the perfusate by dialysis to form the trace component-containing perfusate, and sending it to the enzyme sensor flow cell. There are no particular restrictions,
A commercially available product can also be used. The size, shape, and structure are not particularly limited, but needle-shaped ones can be preferably used.

As a place where the dialysis probe is placed,
Not only in the solution to be measured collected in a container such as a beaker or a test tube, but also in a living body such as a brain of a human or an animal, a tissue or a blood vessel, it can be appropriately selected according to the purpose. One dialysis probe may be used, or two or more dialysis probes may be used. In the present invention, instead of the enzyme sensor flow cell 30 in the above embodiment, various enzyme sensor flow cells selected according to the purpose can be used.

The enzyme sensor flow cell may be provided at any position of the trace component measuring device. One or two or more enzyme sensor flow cells may be used. The enzyme sensor in the enzyme sensor flow cell is not particularly limited as long as it can measure a trace amount of component by utilizing an enzyme reaction, and a sensor having an enzyme membrane on which an enzyme is immobilized can be used. A commercial item can be used for an enzyme sensor.

One enzyme sensor flow cell may be used, or two or more enzyme sensors may be used. At that time, even if only one kind of enzyme sensor is used,
Alternatively, two or more kinds may be used. The enzyme reaction used in the enzyme sensor can be selected according to the measurement target. For example, when the trace component to be measured is glucose, it is an oxidation reaction of glucose, and in the case of lactic acid, it is an oxidation reaction of lactic acid. is there. The enzyme sensors in this case are a glucose sensor and a lactate sensor, respectively.

Any principle may be adopted for the measurement of trace components in the enzyme sensor. For example, when the trace component is glucose, hydrogen peroxide produced in the oxidation reaction of glucose catalyzed by glucose oxidase or oxygen consumed is detected by a current method using a platinum electrode or the like as a working electrode to give glucose. The principle of measuring the concentration can be adopted. Further, for example, the pH change when the gluconolactone produced by the above reaction reacts with water to form gluconic acid is
The principle of measurement by the potential method using the H electrode can be adopted.

Further, as the enzyme sensor 31, it is also possible to use a mediator type enzyme sensor in which an electron mediator such as ferrocene is immobilized together with an enzyme. The size, shape, structure, etc. of the flow cell are not particularly limited, and can be formed of an appropriately selected material. Also in the other embodiments described above,
Since the discharge characteristics of the infusion pump, the dialysis characteristics of the dialysis probe, and the output characteristics of the enzyme sensor are as described in the above embodiments, the temperature dependence of the trace component measuring device can be reduced. In this case, the action described in the above-described embodiment can be realized except that the trace components to be measured are different.

[0047]

According to the present invention, output fluctuations due to temperature dependence and the like can be reduced, and since a driving member, a power source, and the like in the pump are unnecessary, it is simple and continuous, and measurement error is reduced. It is possible to provide a small amount of a trace amount measuring device which can be measured with a small amount of accuracy and is convenient to handle, and a trace amount measuring method.

Since the trace component measuring apparatus and trace component measuring method of the present invention can continuously measure trace components by a safe and simple operation, they are suitable for measuring trace components contained in a biological fluid. Yes, especially in the medical field.

In addition, since proteins such as albumin are not dialyzed at the time of measurement, it is not necessary to perform operations such as deproteinization, so that the measurement operation is simple and
High accuracy because there is little loss of trace components to be measured. Further, since the enzyme sensor flow cell is not contaminated with protein or the like, deterioration of the enzyme sensor can be extremely reduced. Since the structure of the device is simple, maintenance, inspection, replacement, etc. are easy, and therefore handling is convenient. Moreover, because it is small, it can be made portable.
It does not require a lot of space for use.

[Brief description of drawings]

FIG. 1 is a schematic explanatory view showing an embodiment of a trace component measuring device of the present invention.

FIG. 2 is a schematic explanatory view showing an example of an infusion pump in which the gas generation chamber is a variable volume envelope.

FIG. 3 is a schematic explanatory view showing an example of an infusion pump in which the perfusate chamber is a variable volume envelope.

FIG. 4 is a graph showing the relationship between the discharge amount of the infusion pump and the temperature.

FIG. 5 is a graph showing the relationship between glucose concentration taken in by dialysis and temperature.

FIG. 6 is a graph showing the relationship between the output of an enzyme sensor and temperature.

FIG. 7 is a graph showing the relationship between the output of the enzyme sensor and the temperature in the conventional device and the trace component measuring device of the present invention.

[Explanation of sign]

 DESCRIPTION OF SYMBOLS 1 Injection pump 2 Injection port 3 Perfusion solution supply container 4 Mover 5 Perfusion solution chamber 5a Perfusion solution 5b Perfusion solution containing trace components 6 Gas generation chamber 6a Gas 7 Stator 20 Dialysis probe 21 Needle shaft 22 Dialysis membrane 23 Inlet 24 Outlet 25 Reinforcing Material 30 Enzyme Sensor Flow Cell 31 Enzyme Sensor 32 Flow Cell 33 Enzyme Membrane 34 Lead Wire 40a, 40b, 40c Tube

Claims (4)

[Claims] 1. A perfusion solution is discharged by an injection pump using a gas pressure of a gas generated by a chemical reaction as a driving source, the discharged perfusion solution is stored in a dialysis probe, and a trace amount of component to be measured is dialyzed. A method for measuring a trace component, which comprises incorporating a trace component-containing perfusate into the perfusate and sending it out, and measuring the trace component contained in the sent-out perfusate by an enzyme sensor flow cell. 2. The trace component measuring method according to claim 1, wherein the trace component is glucose. 3. An infusion pump that discharges a perfusate using a gas pressure of a gas generated by a chemical reaction as a driving source, and the discharged perfusate is stored therein, and trace components to be measured are taken into the perfusate by dialysis. Thus, a trace component measuring device comprising a dialysis probe for producing a trace component-containing perfusate and delivering the same, and an enzyme sensor flow cell for measuring the trace component contained in the delivered perfusate. 4. The trace component measuring device according to claim 3, wherein the trace component is glucose.