JPH06100575B2 - Inspection device using electrochemical sensor - Google Patents

Description

TECHNICAL FIELD The present invention relates to an inspection apparatus using an electrochemical sensor capable of converting a quantification of a test substance in a sample into an electric signal.

[Conventional technology]

In a conventional electrochemical sensor, a thin film through which a test substance in a sample passes on the electrode surface (for example, a gas permeable membrane when measuring a gas component in a sample, an ion permeable membrane when measuring an ionic component, an enzyme as a base component). When measured by reaction, it is called an enzyme membrane), a boundary phase (mainly an electrolyte solution) in contact with this thin film, and an electrode (transducer) in contact with this liquid phase and the opposite side of the thin film. Has been done,
In addition, there are a gas sensor (also referred to as a gas electrode) for measuring the gas concentration in the sample and an ion sensor (or also referred to as an ion electrode) for measuring the ion concentration in the sample.
, An enzyme sensor (also referred to as an enzyme electrode) that measures the concentration of a special substrate by an enzymatic reaction, a biosensor that measures the amount of microorganisms in the sample, and an antigen-antibody sensor that measures the special antigen in the sample with an antibody It is known to be (for example, blood gas, P150 to P188, published by Shinko Trading Co., Ltd. Medical Book Publishing Department, published in 1981, ion electrode and enzyme electrode, published in 1981, published by Kodansha Scientific Publishing Co., Ltd. ).

In such an electrochemical sensor, the electrode emits a predetermined electric signal depending on the kind and amount of the chemical substance existing through the thin film in the boundary phase existing between the thin film and the electrode,
We are quantifying chemical substances.

As an example of the electrochemical sensor as described above, the glucose in the blood is converted into hydrogen peroxide by an enzymatic reaction in a gas electrode or a blood sample for detecting the gas concentration of CO ₂ or the like in the sample to measure glucose, etc. There is an enzyme electrode.

[Problems to be Solved by the Invention]

In the electrochemical sensor as described above, it is necessary to accurately correspond the amount of chemical substance and the electric signal output from the electrode in order to perform accurate measurement.

Therefore, as the electrochemical sensor is used, the composition of the boundary phase existing between the thin film and the electrode changes, and the amount of the chemical substance in the sample and the electrical signal do not correspond to each other, so that the lifetime of the electrochemical sensor is generally limited. Has been.

Further, the thin film is made thin to improve the responsiveness, and when using the electrochemical sensor, the thin film is deformed when the sensor is in a negative pressure or positive pressure state, and the thickness of the boundary phase depends on the thin film. Change. Therefore, the change in the electrical signal in the boundary phase with the chemical substance in the sample does not correspond accurately. The deformation of the thin film also damages the thin film.

Therefore, in an inspection device that measures the amount of chemical substances in a sample while flowing the sample using the electrochemical sensor as described above, the thin film of the electrochemical sensor is not exposed to positive pressure or negative pressure under atmospheric pressure conditions. The chemical substance in the sample was measured. However, in such an inspection apparatus, the sample must be flown to the position where the chemical electrode is present in the flow channel, and therefore the sample is pulled to the measurement site by the pump. Further, when a part of the flow path is clogged with a highly viscous sample, the pump must apply pressure to the sample in the flow path to remove it.

Therefore, it has been unavoidable that the thin film of the electrochemical sensor is in a pressurized or negative pressure state.

Since this brings about a further shortening of the life of the electrochemical sensor, there is a problem in the accuracy of the inspection device using this electrochemical sensor.

Japanese Unexamined Patent Publication (Kokai) No. 58-55749 discloses a blood analyzer in which a pump is arranged downstream, but does not describe the relationship between driving or stopping the pump and the pressure in the flow path.

Further, JP-A-56-170188 describes a clogging detection mechanism for knowing a pressure abnormality due to clogging at the tip of the nozzle, but it does not quantitatively measure the pressure in the flow passage, Further, the mechanism is complicated because the clogging mechanism is operated by the movement of the liquid to detect the pressure.

It is an object of the present invention to provide an inspection device that enables continuous measurement while allowing a sample to flow in a channel and protects a thin film of an electrochemical sensor from excessive negative pressure or positive pressure. .

[Means for Solving the Problems]

In order to achieve the above-mentioned object, the present invention provides an electrochemical sensor having a polymer thin film in a sample flow passage, and arranges a pump for introducing a sample in a flow passage downstream of the electrochemical sensor, In an inspection device using an electrochemical sensor for measuring a test substance in a sample by a chemical sensor, a pressure sensor for detecting the pressure in a flow path is provided between the electrochemical sensor and the pump, and the pressure sensor By performing pressure correction on the measured value based on the signal of, the electrochemical sensor enables measurement in a pressurized or negative pressure state, and when the pressure in the flow path is abnormal, the operation of the pump is stopped. In addition, the electrochemical sensor is characterized in that a protective member made of a porous woven cloth or a metallic net is provided outside the polymer thin film.

[Action]

According to the above configuration, the pressure sensor detects the pressure change in the sample flow passage, and by associating this detection signal with the operation of the pump, an excessive pressure is not applied to the thin film of the electrochemical sensor. It is possible to accurately measure the amount of chemical substances in a sample. In addition, it is possible to quickly detect clogging in the flow path.

In addition, according to the pressure detected by the pressure sensor, by performing pressure correction on the measurement value, the electric sensor is in a pressurized or negative pressure state, not under atmospheric conditions, that is, while the sample is flowing in the flow channel. It becomes possible to measure.

The protective film used in the electrochemical sensor of the present invention is generally a woven fabric and has a thickness of 300 μm or less made of polymer fibers such as polyester, nylon, polypropylene and carbon fibers,
A net-like metal thin film having a pore diameter of 10 to 300 μm and a net-like metal thin film made of a chemically inert substance such as platinum having the above-mentioned thickness and pore diameter are preferably used. The net-shaped plastic or metal thin film has a wire diameter of 10 to 150 μm.
It is preferable to be woven in a cross shape from the filament fiber of
Further, the pore size of the woven cloth is preferably 60 to 300 mesh and 1 inch as mesh NO. In addition to the above, polyethylene, Teflon (registered trademark), or the like can be used as the polymer resin that is the material of the fiber.

Further, it is desirable that the above-mentioned protective film is one that is not affected by the chemical components in the sample or has no possibility of affecting the sample. For example, when the sample is blood, any chemically inert substance that does not cause blood coagulation can be basically used. In this sense, a chemically inert metal such as platinum can also be used.

〔Example〕

Next, preferred embodiments of the present invention will be described in detail with reference to the accompanying drawings.

FIG. 1 is a configuration diagram showing an example of an electrochemical sensor used in the embodiment of FIG. 2 described later.

In the figure, in the electrode body 56 of the electrochemical sensor, there is a boundary liquid phase 57 in which an electrolyte liquid having conductivity is fixed, and inside the body 56 of this liquid phase 57, the electrode mainly Pt is in contact with the liquid phase 57. An electrode 52 is provided.

The electrochemical sensor is provided with a conducting wire 51 for conducting an electric signal from the electrode 52, and the conducting wire 51 is connected to an amplifier although not shown in the drawing. A thin film 53 that allows the test substance in the sample to pass through to the opposite side of the electrode 52 of the boundary liquid phase 57.
Are provided in contact with the boundary liquid phase 57.

On the surface of the thin film 53, a porous protective film (net-shaped plastic woven cloth) 54 is provided to protect the thin film from the pressure directly applied to the thin film 53. The porous protective film 54 is fixed to the body 56 by an O-ring 55.

Since the sensor of FIG. 1 is provided with the porous protective film 54, the pressure generated on the specimen is not directly applied to the thin thin film 53.

As the thin film 53, a gas permeable film is used when measuring the gas in the sample, and an enzyme film is used when the special substance in the sample is detected by an enzymatic reaction.

In the sensor shown in FIG. 1, the boundary liquid phase is a liquid phase having conductivity. Besides, a solid phase can also be used.
The composition of the liquid phase is determined according to the type of chemical substance to be detected. For example, in an enzyme sensor for measuring the amount of glucose in blood, it is a 1 mol solution of KCl.

FIG. 2 is a block diagram showing an embodiment of the present invention.

In this embodiment, a case where blood is used as a sample will be described.

The blood test apparatus according to this embodiment is roughly divided into three flow path types. One of them is a flow path system 22 composed of a gas electrode part for measuring blood gas such as pH, PO ₂ and PCO ₂ , and two of them are ions for measuring ion concentration of Na, K, Cl, Ca, etc. The flow channel system 23 is composed of electrode portions, three of which are flow channel systems 24 composed of an enzyme electrode portion whose concentration is to be measured by utilizing an enzymatic reaction of glucose, urea nitrogen and the like.

Each of the flow path systems is provided with a squeeze pump 1, 28, 29 so that waste liquid is discharged from the flow path outlet 2. Further, each flow path is provided so as to be connectable to the sampling nozzle 20.

A cut valve 17 to which a standard solution suction valve 18 is connected is provided in the middle of the flow path 22, and further the solution sensor 3,
A reference electrode 9, a PH electrode 4, a PO ₂ electrode 5, a PCO ₂ electrode 7 and a pressure sensor 30 are provided.

A cut valve 25 to which a standard solution ion intake valve 19 and a buffer solution intake valve 21 are connected is provided in the middle of the flow path 23, and a liquid sensor 8, a comparison electrode 26, and a Na are provided in the middle of the flow path 23.
Electrode 10, K electrode 11, Cl electrode 12, Ca electrode 13 and pressure sensor
A liquid sensor 16, a comparison electrode 27, a glucose electrode 14, a urea nitrogen electrode 15, and a pressure sensor 32 are provided in the flow path 24.

Here, the ion electrode of the flow path 23 has a role of 2 to 0.5 kg generated by the squeeze pump 28 when the flow path is clogged because the ion permeable membrane of a general ion electrode is generally thick with a thickness of about 0.2 to 0.4 mm. Can easily withstand positive and negative pressure of / cm ² . However, the gas electrode of the flow channel 22 and the enzyme electrode of the flow channel 24 have an extremely thin polymer membrane of 10 to 30 μm because the gas permeable membrane or the enzyme holding membrane has a response time within 1 to 2 minutes. Is used. Therefore, it is difficult for such a thin film to maintain a stable state under the positive pressure or negative pressure generated by the Shigoki pumps 1, 29 described above, and the gas permeable membrane or the sensitive membrane should be in close contact especially under negative pressure. In some cases, the measurement becomes impossible due to the distance from the electrochemical device.

Next, the operation of this embodiment will be described.

Shigoki pumps 1, 28, 29 provided in the respective flow paths 22, 23, 24
The blood sample is sampled from the sampling nozzle 20 by driving the. At this time, the cut valves 17 and 25 are controlled so that the blood sample flows through the flow paths 22, 23 and 24.

When the blood sample reaches the various electrodes provided in the respective channels 22, 23, 24, the sigmoid pumps 1, 28, 29 are stopped. This is because if the electrodes provided in each flow path system 22, 23, 24 are measured under pressure or negative pressure, it is not possible to carry out a measurement that accurately corresponds to the amount of the test substance in the sample. is there. Next, the gas concentration in the blood, the electrolyte concentration, and the substrate concentration of glycolurea or the like are measured according to the characteristics of the electrodes provided in each flow path system. This measurement is performed by calculating the potential difference between the reference electrodes 9, 26, 27 provided in each flow path system 22, 23, 24 and each electrode, and converting to the concentration of each component according to this difference. Do it.

When the above measurement is completed, the cut valves 17 and 25 are
2 is controlled so that the standard solution gas flows from the standard solution gas valve 18, the standard solution ion flows from the standard solution ion valve 19 to the flow path 23, and the buffer solution flows from the buffer solution valve 21 to the flow path 24. , Shigoki pumps 1, 28, 29 are driven.

Then, by driving the Shigoki pumps 1, 28, 29, the blood existing in the respective flow paths 22, 23, 24 is discharged as waste liquid,
Instead, each standard solution is filled in each channel 22, 23, 24, and the amount of chemical substance in the standard solution is measured at the electrode section in each channel. The reason why the amount of the chemical substance in the standard solution is measured in this way is to obtain an accurate measurement even if the influence of the instability of the output that may occur in each electrode on the measurement is eliminated.

When the measurement of the above standard solution is completed, Shigo pump 1,28,29
Driven by and controlling the cut valves 17, 25
3,24 is replaced with the next blood sample.

By the way, in the case of a thin channel such as blood that is likely to be clogged and clogged, it is necessary to find the clog for accurate measurement. The clogging can be found by the abnormal measurement value at each electrode, but it can be quickly found by providing a pressure sensor for detecting the pressure in each channel 22, 23, 24. . And when a blockage is found, Shigoki pump 1, 2
Clear the block by driving 8,29.

Next, the function when the pressure sensor is provided will be described. By providing a pressure sensor in the inspection device, it is possible to quickly detect clogging in the flow path, and by applying pressure correction to the measured value according to the pressure detected by the pressure sensor, the electric sensor can be operated under atmospheric pressure conditions. Without applying pressure or negative pressure, that is, while allowing the sample to flow in the flow channel, continuous measurement is possible. That is, when blood is clogged in the flow channel or when the sample or standard solution in the flow channel is replaced with another sample or standard solution, the squeeze pump needs to be driven. At this time, a larger pressure than necessary is applied to the gas permeable membrane or ion permeable membrane of the electrochemical sensor,
When it is applied to the surface of the enzyme membrane or the like, the pressure in the flow path is detected by the pressure sensor, and the pump is stopped based on the pressure detection signal. Therefore, it is possible to obtain an inspection apparatus with high measurement accuracy by preventing deterioration of the electrochemical sensor more than expected. Further, since the pressure sensors 30, 31, 32 are provided, the continuous measurement of the sample can be performed while flowing the sample into the flow channel as in the embodiment shown in FIG. Further, the pressure sensor constantly detects the pressure in each flow path, and if the pressure in the flow path becomes a negative pressure, an alarm is generated and the squeeze pump 1 is immediately stopped based on the pressure detection signal. These operations can prevent damage to the membranes of the gas electrode and the enzyme electrode.

FIG. 3 is a block diagram of the pressure sensor used in the embodiment of FIG.

When the sample is blood, a semiconductor pressure sensor typified by a strain cage or the like is preferable as the pressure sensor for measuring the pressure change in the flow channel caused by the change in viscosity and the like. In addition, a glass tube formed by winding a capillary-shaped glass tube in a U shape or a spiral shape can detect the fluctuation of the pressure in the flow path by detecting the fluctuation of the position of the liquid surface. Specifically, as shown in FIG. 3, a capillary-shaped glass tube or a plastic tube 44 is connected to the sample flow channel 45, and at this time, the liquid surface position coming into the capillary tube 44 is determined by the photocouplers 42, 43, etc. If it is detected by, it is possible to know the pressure in the flow path.

In addition, 41 indicates a sampling flow path outlet and 46 indicates a sampling flow path inlet.

The pressure sensor is required to detect the fluctuation of the fluid pressure before the separation phenomenon of the gas permeable membrane or the enzyme membrane from the electrochemical device such as Pt or hydrogen peroxide electrode, and the rotation of the Shiki pump is detected. Since it is necessary to stop the alarm and give an alarm to the operator, the responsiveness to the pressure fluctuation is the most important. As a suitable pressure sensor, not only a semiconductor strain gauge but also a liquid column type can be used very preferably.

〔The invention's effect〕

As described above, according to the present invention, the pressure sensor installed in the sample flow channel allows the continuous measurement of the sample by performing the measurement while quantitatively monitoring the pressure of the flow channel,
When the pressure change in the flow channel is too large, the polymer thin film can be protected by stopping the pump operation to prevent the pressure change in the flow channel, and when the pressure change is relatively small. Since the polymer thin film can be made to work stably by the protective member, the measurement efficiency and measurement accuracy of the electrochemical sensor can be kept high.

[Brief description of drawings]

FIG. 1 is a diagram showing a configuration example of an electrochemical sensor used in the embodiment of FIG. 2, and FIG. 2 is a schematic configuration diagram showing an embodiment of an inspection apparatus using the electrochemical sensor according to the present invention. Three
The figure is a figure for demonstrating the structure of a pressure sensor. 1,28,29 …… Shigoki pump, 22 …… Gas electrode channel, 23
...... Ion electrode part flow path, 24 …… Enzyme electrode part flow path, 30,31,
32 …… pressure sensor, 52 …… electrode, 53 …… thin film, 54 …… protective film, 56 …… body.

Continuation of front page (51) Int.Cl. ⁵ Identification number Reference number within the agency FI Technical display location 7363-2J // G01N 27/30 341 C (72) Inventor Junji Mori 882 Ichige, Ichige, Katsuta, Ibaraki Co., Ltd. Hitachi Factory Naka Factory (72) Inventor Hiroshi Mimaki 882 Imo, Katsuta City, Ibaraki Prefecture Hitachi Factory Naka Factory (56) References JP-A-60-131450 (JP, A) JP-A-58-55749 (JP, A) JP-A-56-43554 (JP, A) JP-A-57-203945 (JP, A) JP-A-54-98699 (JP, A) Actual development Sho-58-76162 (JP, U)

Claims (3)

[Claims] 1. An electrochemical sensor having a polymer thin film is provided in a flow path for sample circulation, a pump for introducing a sample is arranged in a flow path downstream of the electrochemical sensor, and a sample in the sample is detected by the electrochemical sensor. In an inspection device using an electrochemical sensor for measuring a test substance, a pressure sensor for detecting the pressure in the flow path is provided between the electrochemical sensor and the pump, and based on a signal from the pressure sensor, the measurement is performed. By performing pressure correction on the value, the electrochemical sensor enables measurement in a pressurized or negative pressure state, and when the pressure in the flow path is abnormal, the operation of the pump is stopped and the electrochemical sensor Is provided with a protective member made of a porous woven cloth or a metallic net on the outer side of the polymer thin film, which is an inspection apparatus using an electrochemical sensor. 2. An inspection apparatus using an electrochemical sensor according to claim 1, wherein the polymer thin film has a thickness of 30 μm or less. 3. The apparatus according to claim 1, wherein the electrochemical sensor is a gas measuring electrode or an oxygen electrode, and the polymer thin film is a gas permeable film or an oxygen retaining film. Inspection device using the characteristic electrochemical sensor.