JP6750997B2 - Automatic analyzer - Google Patents

Description

Embodiments of the present invention relate to an automatic medical analyzer.

The automatic analyzer analyzes the sample solution by various methods. As an analysis method used in an automatic analyzer, for example, a method of optically measuring a change in color tone of a mixed liquid of a sample and a reagent is well known. Further, as another method, measuring the electric resistance of the sample solution is also one of the effective methods (electrical resistance method), and this method is mainly used for inspecting blood coagulation reaction. In the electric resistance method, the electric resistance of the sample solution changes as the fibrinogen that causes coagulation is deposited. Therefore, by tracking this change, the state of the sample can be quantitatively evaluated.

The blood of a healthy person coagulates in about 10 seconds. On the other hand, the blood of a person who has some kind of disease or is administered with an anticoagulant for the treatment of blood clots takes about a few minutes to coagulate. In extreme cases, it may not coagulate even when mixed with a coagulation reagent.

Japanese Patent No. 2677467 Japanese Patent No. 2845248 Japanese Patent No. 3092361

Since the electric resistance method is simple in principle, it may be widely applied clinically. An existing automatic analyzer measures the electric resistance between electrodes by immersing an electrode probe in a sample solution, applying a voltage, and monitoring the value of the flowing electric current. Therefore, the electrode probe is inevitably soiled, and the electrode probe must be washed after each measurement. Insufficient cleaning causes carryover (contamination) between samples, which adversely affects the test results.

However, the coagulated blood becomes a gel and cannot be easily removed once attached. This is also the reason why the reaction container for coagulation test is disposable. Disposal of the electrode probe is also extremely disadvantageous in terms of cost and device configuration, and it is difficult to remove stains due to the gelled sample. A technique capable of solving such a problem is demanded.

It is an object of the present invention to provide an automatic analyzer which eliminates the harmful effects of stains on the electrode probe.

According to the embodiment, the automatic analysis device includes the first electrode and the second electrode, the measurement unit, the calculation unit, and the analysis unit. The first electrode and the second electrode are in contact with a non-insulating reaction container that contains a solution containing a sample and fix the position of the reaction container. The measurement unit applies a voltage to a closed circuit including the first electrode, the reaction container, and the second electrode, and measures the value of the current flowing therethrough. The calculator calculates the electrical characteristics of the solution in the reaction container based on the measured current value. The analysis unit analyzes the chemical properties of the sample based on the calculated electrical properties.

FIG. 1 is a diagram showing an example of the automatic analyzer according to the embodiment. FIG. 2 is a schematic diagram showing an example of the measuring unit 3. FIG. 3 is a diagram showing a state immediately after the reaction container 100 is set in the measuring unit 3. FIG. 4 is a diagram showing a state where the switch 60 is turned on from the state shown in FIG. FIG. 5 is a diagram showing a state where the sample solution is dispensed into the reaction container 100 from the state shown in FIG. FIG. 6 is a diagram for explaining that the fixing plates 31 and 32 and the sample solution 50 are always separated by the wall surface of the reaction container 100. FIG. 7 is a diagram showing a state in which the probe is immersed in the sample solution in the existing automatic analyzer.

Next, an embodiment of the present invention will be described.

Most blood coagulation tests are performed for the purpose of, for example, the following (1) to (4).

(1) Examination of hemostasis function before surgery This is an examination performed before surgery because it is troublesome if bleeding does not stop during surgery.

(2) Test for measuring coagulation factor This is a test for measuring a health barometer showing the condition of the liver and the like.

(3) Test for measuring thrombus This is a test for measuring the fibrinolytic function that contributes to the ease of clogging of blood vessels.

(4) Confirmation of efficacy of thrombosis therapeutic agent This is a test for measuring the effect of a thrombosis therapeutic agent administered to a patient having a history of cerebral infarction, for example.

To measure the coagulation time, the blood and the coagulation reagent are mixed in a reaction tube in which the metal spheres have been put in advance, and the metal spheres are vibrated by an electromagnet or the like so that the movement of the metal spheres becomes slow as the blood coagulates There is a method to detect (viscosity measurement). In addition, there is a method of detecting a state where light scattering or transmittance changes (measurement of optical characteristics). Furthermore, there is a method of detecting a change in electric conductivity of a solution (measurement of electric characteristics). In short, the principle of the blood coagulation test is to trace the temporal change of some physical quantity that changes with the coagulation of blood. The embodiment discloses a technique for detecting a change in electric conductivity of a solution.

By the way, in addition to the "bleeding time", "prothrombin time (PT)" in which the hemostasis time changes depending on the liver function is known as an index showing the blood coagulation time. Prothrombin is one of the blood coagulation factors and is produced in the liver. By mixing tissue thromboplastin and calcium chloride mixed solution (calcium ion) into the plasma of a patient and measuring the time until prothrombin is produced (blood coagulation time), it is possible to detect disorders or abnormal liver functions it can.

The prothrombin time is used as an index related to the screening test for determining the coagulation mechanism of the extrinsic system/common system, and its normal reference value is about 10 to 12 seconds. If it takes more than 15 seconds to produce prothrombin, it is possible that some kind of liver dysfunction (acute hepatitis/cirrhosis) occurs. Impaired blood coagulation, such as heart failure and vitamin K deficiency, also prolongs prothrombin time. Furthermore, since anticoagulants, which are therapeutic agents for cerebral infarction, heart disease, and hypertension, inhibit the synthesis of vitamin K, patients taking this tend to have a longer prothrombin time.

FIG. 1 is a diagram showing an example of the automatic analyzer according to the embodiment. This automatic analyzer includes a measuring unit 3, a sample disk 8 and a reagent rack 10. In addition, a plurality of reaction vessels (cuvettes) 100 capable of containing a sample solution are arranged in advance in the reaction vessel loading box 1 in an empty state.

Here, the reaction container 100 is a non-insulator. That is, it is not an insulator such as glass. However, it does not need to be as conductive as metal. That is, the reaction container 100 may be made of any material that is as conductive as the sample solution it contains. It is preferably a conductive resin. For example, it is easy to give conductivity to the resin material by mixing carbon powder. If carbon powder is mixed in the manufacturing process of the disposable reaction container 100, a non-insulating reaction container can be easily obtained. Most of the conductive resins are opaque, but the transparency of the reaction container 100 is not particularly limited when measuring by the electric resistance method.

The measuring unit 3 holds the reaction containers 100 transferred from the reaction container loading box 1 by a mechanism arm or the like one by one, and stably fixes the position.

The sample disk 8 is adjacent to the measuring unit 3 and is rotationally driven by the rotating mechanism. The sample disk 8 includes a plurality of holders 5 each capable of holding a sample container. The sample dispensing unit 6 is arranged at a position substantially equidistant from the measuring unit 3 and the sample disk 8. The sample dispensing unit 6 has a sample probe 7 that can be swung. The sample probe 7 is connected to the sample dispensing pump 15. The sample probe 7 sucks the specimen sample from the sample container by the pump action of the sample dispensing pump 15 and dispenses it into the reaction container.

The reagent rack 10 is adjacent to the measuring unit 3 and has a reagent disk 22 and a rotation mechanism that rotationally drives the reagent disk 22. The reagent disc 22 includes a plurality of bottle holders 11 capable of holding reagent containers (reagent bottles). The reagent is prepared for each item in order to cause a chemical reaction specific to the item to be measured. Reagents are placed in dedicated reagent bottles and are kept cold by a cold keeping mechanism (not shown) as needed.

The reagent dispensing unit 12 is arranged at a position substantially equidistant from the measuring unit 3 and the reagent disc 22. The reagent dispensing section 12 has a swivelable reagent probe 23. The reagent probe 23 is connected to the reagent dispensing pump 17. The reagent probe 23 sucks the reagent from the reagent bottle by the pump action of the reagent dispensing pump 17 and dispenses it into the reaction container 100. The mixture of the specimen sample and the reagent is stirred in the reaction container by the stirring unit 14 as necessary to form a sample solution.

The controller 18 controls the measuring unit 3, the rotating mechanism of the sample disk 8, the rotating mechanism of the reagent rack 10, the sample dispensing pump 15, the reagent dispensing pump 17, and the stirring unit 14 to perform a series of procedures relating to automatic analysis. Execute. The display unit 20 displays various numerical data and message data. The operation unit 21 is provided to input various commands such as the setting of the inspection mode.

FIG. 2 is a schematic diagram showing an example of the measuring unit 3. In FIG. 2, a pair of fixed plates 31 and 32 are arranged so as to face each other at an interval wider than the width of the reaction container 100. The fixed plate 31 is connected to the positive electrode of the power supply 300 and functions as a first electrode. The fixed plate 32 is connected to the negative electrode of the power supply 300 and functions as a second electrode. Further, the switch 60 and the ampere meter 200 are directly connected between the negative electrode of the power source 300 and the fixed plate 32.

Each of the fixing plates 31 and 32 is made of a highly conductive material such as metal, and a part of the fixing plates is inserted into a coil around which an electric wire extending from the power supply 300 is wound. When the switch 60 is turned on, the circuit is closed, and the fixed plates 31 and 32 function as electromagnets and move toward each other. When the switch 60 is turned off, the fixed plates 31 and 32 return to their original positions by a reaction force of a spring mechanism (not shown) or the like.

Further, the fixed plates 31, 32 are connected via a load resistor 40 for limiting overcurrent. The resistance value of the load resistor 40 is R1. The resistance value R1 may be a combined value of the resistance value of the load resistor 40 and the resistance value of the electric wire including the coil.

3 to 5 are diagrams showing the state after the reaction container 100 is set in the measuring unit 3 in time series. The reaction vessels 100 are taken out one by one from the reaction vessel loading box 1 by a mechanism arm or the like, and are carried between the fixed plates 31 and 32 in the open state as shown in FIG. When the reaction container 100 is set between the fixed plates 31 and 32, the switch 60 is turned on.

As shown in FIG. 4, when the switch 60 is turned on, the fixed plates 31 and 32 serve as electromagnets to attract each other and come into contact with the reaction container 100 therebetween. When the reaction container 100 is set normally, the reaction container 100 is sandwiched between the fixed plates 31 and 32 which are closed, and the position is firmly fixed. At this time, the fixed plates 31 and 32 and the reaction container 100 are in contact with each other in a constant area for each inspection.

Since the reaction container 100 is conductive, a closed circuit including the fixed plate 31, the reaction container 100 and the fixed plate 32 is formed. The electric current flows to R1 as an electromagnet circuit, to the fixed plates 31 and 32, and further to the bottom and side surfaces (wall surfaces) of the reaction container 100. If the bottom surface of the reaction vessel 100 is sufficiently thicker than the side surface, the conductivity of the bottom surface is sufficiently higher than that of the side surface in contact with the fixing plates 31 and 32, so that most of the current flows through the bottom surface.

When the resistance value of the empty reaction container 100 is R2, a parallel combined resistance with the resistance value R1 of the load resistance 40 is formed. When the voltage of the power supply 300 is E [V], the ampere meter 200 measures a current value I of I=E·(R1·R2)/(R1+R2)[A]. This current value I is notified to the controller 18 (FIG. 1).

The controller 18 also functions as a determination unit that determines the fixed state of the reaction container 100 based on the current value notified from the ampere meter 200.

The current value I when the reaction container 100 is empty is expected to become a constant value each time the reaction container 100 is set. This is because it is expected that the contact area between the fixing plates 31 and 32 and the reaction container 100 will be constant when the reaction container 100 is correctly set and fixed. If the current value is smaller than expected, it is possible that the fixed plates 31 and 32 and the reaction container 100 are not in proper contact with each other, causing a positional shift or a foreign substance being caught. If the current itself is not detected, it can be known that an abnormality has occurred in the circuit itself, so that it is possible to prevent the measurement from being started with the failure.

In this way, the controller 18 determines the fixed state of the reaction container 100 based on the current value I in the state shown in FIG. When it is determined that there is no abnormality in the circuit and the reaction container 100 is set correctly, the test sample is put into the reaction container 100.

As shown in FIG. 5, following the state of FIG. 4, the test sample and the reagent are dispensed into the reaction container 100, and the mixed sample solution 50 is generated. When this state is reached, the resistance value R3 of the sample solution 50 is newly added to the closed circuit, and the parallel combined resistance of R1, R2 and R3 is applied to the voltage E as a whole. In FIG. 5, the resistance value is lower than that in the state of FIG. 4, and the current value I of I=E·(R1·R2·R3)/(R1+R2+R3) [A] is measured.

The controller 18 catches the change in the current value I acquired from the ampere meter 200 and knows the existence of the sample solution 50. Since the resistance value R3 changes as the coagulation reaction progresses, the current value I also changes. The ampere meter 200 repeatedly monitors the current value I with the lapse of time from the start of the reaction, and outputs the value to the controller 18.

The controller 18 as a calculator calculates the resistance value R3 of the sample solution 50 in the reaction container 100 based on the current value I. Further, the controller 18 as an analysis unit analyzes the coagulation characteristic of the sample solution based on the calculated resistance value R3. That is, the controller 18 determines the change state and change point of the monitored current value I, and obtains the analysis result based on the determination logic corresponding to the measurement content. For example, it is possible to determine the time when the current changes suddenly and warms as the blood coagulation time.

When the switch 60 is turned off, the fixed plates 31 and 32 are separated from the reaction vessel wall.

For the presence or absence of the reaction container 100, a dedicated position detection sensor may be provided, but the number of parts increases and the sensor installation location must be secured. Wiring and circuits are also required separately. On the other hand, with the above configuration, the number of newly added components can be reduced by originally diverting the function of the unit required for measurement and fixing of the reaction container 100, which is advantageous for cost reduction and securing of space. Become. If a sensor is provided, the advantage of improving the accuracy of check determination can be obtained. Which one is selected may be appropriately determined according to the specifications of the device.

As described above, in this embodiment, the reaction container 100 of the conductive resin is used in the automatic analyzer that analyzes the sample solution to be inspected by the electric resistance method. The reaction container 100 is fixed by sandwiching it between the fixing plates 31 and 32, and the current flowing in that state is measured to obtain the electric resistance value. The side wall thickness and the bottom wall thickness of the reaction container 100 contacting the fixed plates 31 and 32 have a specific relationship so that a constant resistance value can be obtained under normal conditions. Based on the measured resistance value, the fixed state of the reaction container 100, the state of the measuring unit 3, and the presence or absence of the sample solution 50 are determined. Further, from this state, the sample solution 50 was dispensed into the reaction container 100, and the reaction state of the coagulation reaction was determined by monitoring the change in the resistance value as a whole.

With such a structure, the fixing plates 31 and 32 serve both as a fixing device and an electrode probe. As a result, the number of constituent elements can be markedly reduced as compared with the case where both are provided separately, and it is possible to promote size reduction and simplification of the configuration.

As shown in FIG. 6, the electrode probe (fixing plates 31, 32) does not come into contact with the sample solution 50 in the course of a series of inspections. This is because, as shown in FIGS. 6A and 6B, the fixed plates 31 and 32 and the sample solution 50 are always separated by the wall surface of the reaction container 100. Therefore, the electrode probe is not contaminated and it is not necessary to wash it, so that not only the structure is further simplified, but also various immeasurable advantages such as prevention of contamination can be obtained.

Moreover, since the reaction container 100 has conductivity and is exchanged, the accuracy of measurement of current value and resistance value does not deteriorate. As described above, the operation check of the measurement unit 3, the set state of the reaction container 100, the presence/absence of the sample solution, and the measurement/analysis of the coagulation state are collectively performed by a common measurement circuit using the ampere meter 200. It becomes possible to do.

As shown in FIG. 7, in the existing automatic analyzer, it was necessary to immerse the electrode probe in the sample solution in the container 400. For this reason, when the coagulation reaction test is performed, the gelled sample adheres to the electrode probe, and it is very difficult to remove the stain on the contaminated electrode probe.

On the other hand, according to the embodiment, the electrode probe does not become dirty. Since the electrodes never enter the sample solution in the first place, cleaning is not necessary and there is no risk of carryover between samples. The arm that moves the probe up, down, left and right is also unnecessary. Furthermore, it becomes easy to start monitoring the current value immediately after the reagent is dispensed, and it becomes possible to sufficiently follow a reaction that proceeds rapidly.

From these things, according to the embodiment, it is possible to eliminate the harmful effects due to the contamination of the electrode probe. Not only that, but also many advantages such as the simplification of the device configuration can be obtained at the same time.

The present invention is not limited to the above embodiment. For example, in order to simplify the description, a DC power source is assumed as the power source 300 in the embodiment. Instead of this, it is also possible to use an AC power supply. In this way, the possibility of electrolysis of the sample solution can be eliminated. However, a separate mechanism for preventing the disappearance of the magnetic field of the electromagnet is required. Moreover, it is necessary to measure impedance as a resistance value.

It is possible to convert the AC voltage applied to the reaction container 100 into vibration and stir the sample solution 50, for example. In this way, it is possible to omit the stirring section 14 and promote simplification of the configuration.

Further, the reaction container 100 is sandwiched between the fixing plates 31 and 32 so as to be fixed. Instead of this, the reaction container 100 may be fixed by moving only one of the fixing plates 31 and 32 and pressing the reaction container 100 against the fixed wall.

Although the embodiment of the present invention has been described, the embodiment is presented as an example and is not intended to limit the scope of the invention. The novel embodiment can be implemented in various other forms, and various omissions, replacements, and changes can be made without departing from the spirit of the invention. This embodiment and its modifications are included in the scope and gist of the invention, and are also included in the invention described in the claims and an equivalent range thereof.

DESCRIPTION OF SYMBOLS 1... Reaction container loading box, 3... Measuring part, 5... Holder, 6... Sample dispensing part, 7... Sample probe, 8... Sample disk, 10... Reagent rack, 11... Bottle holder, 12... Reagent dispensing part, 14... Stirring unit, 15... Sample dispensing pump, 17... Reagent dispensing pump, 18... Controller, 20... Display unit, 21... Operating unit, 22... Reagent disk, 23... Reagent probe, 31... Fixed plate, 32... Fixed plate, 40... Load resistance, 50... Sample solution, 60... Switch, 100... Reaction container, 200... Ampere meter, 300... Power supply, 400... Container.

Claims (9)

A first electrode and a second electrode that contact a non-insulating reaction container containing a solution containing a sample to fix the position of the reaction container;
A measurement unit that applies a voltage to a closed circuit including the first electrode, the reaction container, and the second electrode to measure a value of a flowing current;
A calculator that calculates the electrical characteristics of the solution in the reaction vessel based on the measured current value;
An automatic analyzer, comprising: an analysis unit that analyzes the chemical properties of the sample based on the calculated electrical properties. The calculation unit calculates the resistance value of the solution,
The automatic analyzer according to claim 1, wherein the analysis unit analyzes the reaction state of the sample and the reagent based on the calculated resistance value. The automatic analyzer according to claim 2, wherein the analysis unit analyzes the coagulation state of the sample based on the calculated resistance value. The automatic analyzer according to claim 1, further comprising a determination unit that determines a fixed state of the reaction container based on the current value. The automatic analyzer according to claim 1, further comprising a determination unit that determines the presence or absence of the solution in the reaction container based on the current value. The automatic analyzer according to claim 1, further comprising an electromagnet that is provided in the closed circuit and that moves at least one of the first electrode and the second electrode so as to sandwich the reaction container. The automatic analyzer according to claim 1, wherein the reaction container is a conductive resin. The reaction container has a first side surface that contacts the first electrode, a second side surface that contacts the second electrode, and a bottom surface,
The automatic analyzer according to claim 1, wherein the conductivity of the bottom surface is higher than that of the first and second side surfaces. The automatic analyzer according to claim 1, wherein the measuring unit applies an AC voltage to the closed circuit.