JP2007040843A - Autoanalyzer - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an autoanalyzer which changes a sound wave irradiation position without complicating remarkably control or structure, and allows efficient stirring. <P>SOLUTION: A stirring mechanism 112 is attached to a vertically movable shaft. The stirring mechanism 112 is provided with a sound source 207, and the sound source 207 emits an ultrasonic wave 202. When the ultrasonic wave 202 is emitted to the vicinity of a liquid face in a reaction liquid 203 with a reagent 111 added to a specimen 107, the liquid face is inclined with an action of acoustic radiation pressure acting on a gas-liquid interface, and a vortex flow 205 is generated thereby while catching a bubble 204 into the reaction liquid 203. The stirring for the reaction liquid 203 is promoted further by irradiating the bubble 204 with the ultrasonic wave 202, because the action of the acoustic radiation pressure acts on the bubble 204 under the vortex flow 205. An intensity, a frequency and an irradiation position of the ultrasonic wave 202 are controlled by a control part 206, and the sound source 207 is driven by a driver 208. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to an automatic analyzer, and more particularly to an automatic analyzer that uses an ultrasonic wave generation source as a sound source and stirs a reagent or the like with a sample using vibration, acoustic flow, acoustic radiation pressure, or the like.

  In a stirrer of an automatic analyzer, a method is generally used in which a spatula stir bar or the like is directly placed in a reaction vessel, and a sample and a reagent are mixed and stirred by rotating or reciprocating.

  However, when stirring is performed using a stirring bar, the reagent or specimen attached to the stirring bar may affect other analysis results due to carry-over. For this reason, sufficient cleaning is required, and a large amount of water is consumed. Then, ultrasonic stirring which implement | achieves non-contact stirring as described in patent document 1 is proposed.

  While stirring using ultrasonic waves has the advantage that the problem of carry-over does not occur, it is difficult to adjust the irradiation conditions for the object to be stirred, and various methods for adjusting the irradiation conditions have been proposed.

  For example, in Patent Document 2, a sensor for measuring the intensity of generated ultrasonic waves is installed, and an ultrasonic output with a constant intensity is obtained by changing the frequency generated by the ultrasonic wave generation source according to the sensor output. As described above, a technique is disclosed in which uniform stirring can always be performed.

JP 2003-035715 A JP 2001-124784 A

  When ultrasonic stirring is used in the stirring section of the automatic analyzer, non-contact stirring can be realized, so that carry-over does not occur and stirring rod washing water is unnecessary, improving analysis reliability and reducing running costs. There are advantages.

  However, in an automatic analyzer equipped with a large number of reaction containers on a disk-shaped reaction table, a sound source cannot be directly attached to each reaction container, and sound waves are indirectly introduced. When a sound wave is indirectly introduced, in order to obtain a good stirring state, a stirring method using an acoustic radiation pressure acting by an acoustic impedance difference at the gas-liquid interface is excellent.

  When this acoustic radiation pressure is used, the amount of the reaction liquid varies depending on the analysis item, so the height of the gas-liquid interface is not constant, and it is necessary to change the sonication position according to the liquid volume. In order to change the sonication position, means such as changing the construction height of the reaction container, arranging a plurality of sound sources in an array, and selecting a sound source to be driven can be considered.

  In order to control the height of the reaction vessel, when the reaction table is moved up and down, interference with other mechanisms occurs, and the control becomes complicated.

  Even when the height of the specific reaction container is changed, a movable part for moving the specific container up and down independently is required, which complicates the structure.

  In addition, when a piezoelectric element is used as a sound source, a method of arranging a plurality of sound sources in an array is suitable for easily changing the irradiation position, but the electrode structure is limited by the piezoelectric element used, and depending on the system, Sufficient resolution cannot be obtained. Moreover, in order to switch according to the sound source position which drives the energized part of high electric power which implement | achieves ultrasonic stirring, the semiconductor switch which has a long life but insufficiency for safety cannot be used. For this reason, a mechanical contact having a relatively short life must be used, which is not suitable when it is desired to frequently change the irradiation height during stirring.

  An object of the present invention is to realize an automatic analyzer capable of changing an ultrasonic irradiation position and capable of performing efficient stirring without greatly complicating control and structure.

  The present invention includes an automatic stirring unit that stirs a reagent or the like and a test liquid by ultrasonic waves generated from a sound source, an analysis unit that performs component analysis of the test liquid, and a control unit that controls the operation of the stirring unit. In the analyzer, the stirring unit has a mechanism in which the sound source can move back and forth, left and right, and up and down, and the control unit controls the stirring unit, and the position and angle of the sound source, The sound wave intensity and the sound source driving frequency are changed.

  According to the present invention, the ultrasonic irradiation position can be changed without greatly complicating the control and the structure.

  Furthermore, if the movable range is increased by moving the sound source up and down, left and right, the same sound source is shared when performing the stirring operation at multiple locations on the apparatus or when washing the reaction vessel, Since stirring and washing can be performed, the number of stirring mechanisms can be reduced, and costs can be reduced.

  In addition, by adding a sound source measurement unit that measures sound source impedance, it is possible to know information such as the state of the sound source, the positional deviation of the target of sound wave irradiation, the amount of reaction liquid, the presence or absence of bubbles, etc. The display and the position and angle of the sound source, the selection of the array electrode, the sound wave intensity, the control of the driving frequency, and the like can be performed, and efficient stirring can be performed.

  Hereinafter, embodiments of the present invention will be described with reference to the drawings.

  A first embodiment of the present invention will be described with reference to FIGS.

  FIG. 1 is a schematic configuration diagram of an automatic analyzer according to the first embodiment of the present invention.

  In FIG. 1, the automatic analyzer includes a sample storage unit 101, a reagent storage unit 102, a reaction unit 103, a stirring unit 104, an analysis unit 105, and a cleaning unit 106, and is configured by an electronic circuit or a storage device. The detailed operation of each unit is controlled by a control unit (described later).

  The sample liquid 107 placed in a sample container such as a test tube and stored in the sample storage unit 101 is dispensed by the sample dispensing mechanism 108 for a required amount to be used for analysis, and is maintained at a constant temperature by the reaction unit 103. It is discharged into a reaction vessel 109 filled with a constant temperature medium. An amount of reagent 111 required for analysis is dispensed and added to the specimen 107 discharged into the reaction container 109 by the reagent dispensing mechanism 110.

  The sample 107 and the reagent 111 are sufficiently mixed and stirred by the stirring mechanism 112 provided in the stirring unit 104, and component analysis is performed in the analysis unit 105. After completion of the analysis, the reaction vessel 109 is cleaned by the cleaning unit 106 and prepared for the analysis of another analysis target again.

  Here, the agitation mechanism 112 is a mechanism that realizes agitation of the specimen 107 and the reagent 111 in a non-contact manner using ultrasonic vibration, acoustic flow, acoustic radiation pressure, and the like. Can be moved to. The sound source 207 can control the angle with respect to each axis, that is, can be rotated, and can control the sound wave irradiation position, the sound wave intensity, the driving frequency, and the like even during the stirring operation.

  FIG. 2 is a schematic configuration diagram of the stirring mechanism 112 capable of moving up and down of the automatic analyzer according to the first embodiment of the present invention.

  In FIG. 2, the stirring mechanism 112 is attached to a shaft that can move in the front, rear, left, right, and up directions, and is connected to the motor 201 so as to be movable with respect to each shaft.

  The stirring mechanism 112 includes a sound source 207, and the sound source 207 emits an ultrasonic wave 202. When the ultrasonic wave 202 is irradiated in the vicinity of the liquid surface of the reaction liquid 203 in which the reagent 107 is added to the specimen 107, the liquid surface is inclined by the action of acoustic radiation pressure acting on the gas-liquid interface, and bubbles 204 are formed in the reaction liquid 203. A swirl flow 205 is generated while being entrained.

  The acoustic radiation pressure also acts on the bubbles 204 in the swirling flow 205, so that the stirring of the reaction solution 203 is further promoted by irradiating the bubbles 204 with the ultrasonic waves 202. The intensity, frequency, and irradiation position of the ultrasonic wave 202 are controlled by the control unit 206, and the sound source 207 is driven by the driver 208.

  Here, implementation of efficient stirring will be described. Efficient agitation can be realized by repeating ON / OFF or intensity of ultrasonic irradiation at a frequency that is twice the natural frequency of the reaction vessel 109. Moreover, in order to bring about the same effect without turning on / off the ultrasonic wave irradiation or changing the strength, it is sufficient to repeat the sound wave irradiation to the gas-liquid interface and the sound wave irradiation to other than the interface. What is necessary is just to raise / lower the stirring mechanism 112 near liquid level during implementation. Further, by combining ON / OFF of sound wave irradiation and strength change, further improvement of stirring efficiency can be expected.

  Further, in the above method, the direction of the swirl flow 205 is constant, but if the sound wave irradiation position is made to follow the movement time of the bubbles 204, the reverse swirl flow 209 can be induced, and the turbulent flow The improvement of the stirring efficiency by can be expected.

  Here, the following two points can be cited as advantages of allowing the stirring mechanism 112 to move up and down.

  The first point is that the height of the gas-liquid interface changes for different reaction volumes depending on the analysis item, so it is necessary to change the sonication position according to the volume of the liquid, so multiple sound sources 207 are arranged in an array Alternatively, a means such as producing a plurality of electrodes on the same sound source 207 can be considered. For example, when the sound source 207 utilizing vibration in the thickness direction is used, if the electrode dimensions are equal to or smaller than the thickness of the sound source 207, vibration components other than in the thickness direction increase, so that the expected sound wave intensity cannot be obtained. For this reason, the electrode structure is limited, and sufficient resolution cannot be obtained depending on the system. On the other hand, if the stirring mechanism 112 can be moved up and down, the sound wave irradiation position can be freely changed without being limited by the resolution depending on the electrode of the sound source 207, and the resolution of the sound wave irradiation position suitable for the system can be obtained. Can do.

  Secondly, when control that expects the reverse swirl flow 209 is to be realized by an array electrode sound source, a semiconductor that is insufficiently insulated for safety in order to switch the energized location of high power to realize ultrasonic stirring The switch cannot be used. Therefore, a mechanical contact element having a short life must be used. However, when it is desired to frequently change the irradiation height during stirring, it is necessary to frequently perform a switching operation, and the mechanical contact element is not suitable.

  On the other hand, when the stirring mechanism 112 can be moved up and down, even in the above situation, the change of the sound wave irradiation position is not accompanied by the switching of the array electrode, and thus the above-described problem does not occur.

  Next, a second embodiment of the present invention will be described with reference to FIG.

  FIG. 3 is a schematic explanatory diagram of a stirring mechanism capable of changing the sound wave irradiation angle in the automatic analyzer according to the second embodiment of the present invention.

  In the automatic analyzer according to the first embodiment of the present invention, the configuration in which the stirring mechanism 112 can be moved up and down is shown. However, the automatic analyzer according to the second embodiment of the present invention changes the sound wave irradiation angle. It is. That is, as shown in FIGS. 3A and 3B, the stirring mechanism 112 is moved up and down during the stirring as a means for performing the sound wave irradiation on the gas-liquid interface of the reaction liquid 203 and the sound wave irradiation on the interface other than the interface. By providing a mechanism for tilting in the direction, it is possible to obtain the same effect as that of the first embodiment of the present invention in which the sound wave irradiation position is raised and lowered near the liquid surface.

  Next, a third embodiment of the present invention will be described with reference to FIG.

  FIG. 4 is an explanatory diagram when the same sound source is shared by a plurality of agitation positions in the third embodiment of the present invention.

  In FIG. 4, the automatic analyzer according to the third embodiment of the present invention allows the stirring mechanism 104 installed in the reaction unit 103 to slide in the left and right directions at a plurality of stirring positions. The common stirring mechanism 112 can be shared.

  For example, in the case of an analysis item in which three types of reagents are added and reacted, the first reagent is added to the reaction vessel 109 from which the specimen 107 has been discharged if the stirring sequence in the analysis is not simultaneously stirred at a plurality of locations. In this case, the stirring mechanism 112 is moved to the first reagent stirring position 401, and stirring is performed by irradiating the ultrasonic wave 202. When the second reagent is added, the second reagent stirring position 402 and the third reagent are added. In this case, stirring may be performed by moving the stirring mechanism 112 to the third reagent stirring position 403, respectively.

  If the stirring mechanism 112 is slidable to the left and right in this way, even when the reaction vessel 109 is moving, the stirring mechanism 112 is moved to follow the movement of the reaction vessel 109 to perform stirring. Therefore, the time for stopping the movement of the reaction vessel 109 can be saved, and the throughput can be improved.

  Furthermore, when a mechanism for tilting the stirring mechanism 112 in the left-right direction is provided, the sound wave irradiation time can be further increased.

  Also, when cleaning the reaction vessel 109, since the cleaning effect due to the influence of the ultrasonic wave 202 and the improvement of the cleaning effect by applying a swirling flow to the in-container cleaning liquid can be expected, the reaction container 109 filled with the cleaning liquid can be used. Then, the ultrasonic wave 202 can be irradiated by moving the stirring mechanism 112 to the cleaning stirring position 404 where the analysis sequence stops.

  Next, a fourth embodiment of the present invention will be described with reference to FIG.

  FIG. 5 is a schematic configuration diagram of a stirring mechanism 112 that can move up and down by an array sound source in an automatic analyzer according to the fourth embodiment of the present invention. In the example of FIG. 5, a plurality of electrodes are arranged in an array on the sound source 207 in the example shown in FIG.

  In FIG. 5, when a plurality of electrodes are arranged in an array on the sound source 207, an electrode arranged at a position where a sound wave is desired to be irradiated is selected from the plurality of electrodes arranged in an array by the sound source electrode selection unit 501. By selecting, it becomes possible to change the irradiation position of the ultrasonic wave 202 without taking a large movable region by the motor 201.

  Even when the movement of the bubble 204 is faster than the vertical movement of the stirring mechanism 112 by the motor 201, even when a mechanical contact element having a long contact switching time is used, the sound wave irradiation position can be changed in about several milliseconds.

  According to this method, by intermittently moving the sound wave irradiation position up and down, the swirl flow 205 and the reverse swirl flow 209 are alternately generated, and it becomes possible to induce stronger turbulence than the method of FIG. .

  Here, since the mechanical contact element is not used for moving the sound wave irradiation position up and down to generate a swirling flow or the like, it does not involve frequent switching operations.

  Also, when using a mechanical contact element as the sound source electrode selection means 501, in consideration of its life, control such as temporarily stopping sound wave irradiation at the time of contact switching and not performing contact switching in a live state. It can also be implemented.

  Next, a fifth embodiment of the present invention will be described with reference to FIG.

  FIG. 6 is an explanatory diagram of the impedance measurement function of the automatic analyzer according to the fifth embodiment of the present invention.

  In FIG. 6A, since the ultrasonic wave 202 has a characteristic of being reflected at a portion where the difference in acoustic impedance is large, when a piezoelectric element is used as the sound source 207, the ultrasonic wave is superposed by a structure in the sound wave irradiation path. The sound wave 202 is reflected, and an electromotive force is generated by applying pressure by reflected ultrasonic waves to the piezoelectric element. Here, when the piezoelectric element is driven at a constant voltage, the inflow current to the piezoelectric element changes due to the electromotive force generated by the reflected ultrasonic wave, so that the electrical impedance also changes.

  Although the reaction vessel 109 is composed of an organic compound or glass, the difference in acoustic impedance between air and water is larger than that, so that the sound source electrode X602 positioned above the liquid level of the reaction solution 203 in the reaction vessel 109 In the sound source electrode Y604 positioned below the liquid surface of the reaction solution 203, a difference in impedance is caused by the reflection of the ultrasonic wave 202.

  Using the above characteristics, the liquid level position of the reaction solution 203 can be estimated by moving the sound source 207 up and down with the motor 201 and measuring the electrode impedance of the sound source 207 with the impedance measuring means 601. In this case, when the sound source 207 is composed of array electrodes, the electrode to be measured may be selected by the sound source electrode selecting unit 501 and the electrode impedance may be measured by the impedance measuring unit 601.

  In the impedance measurement, if the measurement sensitivity of the impedance measuring means 601 is high, the irradiation of the weak ultrasonic wave 202 is sufficient, and if the driver 208 that can change the driving frequency and the sound wave intensity is used, the impedance measurement unit 601 specializes in impedance measurement. There is no need to prepare another driver. By controlling the controller 206 to drive at a constant voltage while changing the frequency with a weak sound wave intensity, the frequency characteristic of the impedance can be obtained.

  Looking at the frequency characteristics of the impedance, a large impedance change with a low frequency is observed when the sound source and the sound wave reflector are close, and a fine impedance change with a high frequency is obtained when the sound source is far away.

  For example, since the sound source electrode X602 that faces the reaction vessel 109 and is higher than the liquid level of the reaction solution 203 has a sound wave reflection object nearby and strong reflection of sound waves, the sound source electrode X shown in FIG. In the impedance 603, a small number of poles having a large impedance height difference are observed.

  Further, since the sound source electrode Y604 that faces the reaction vessel 109 and is lower than the liquid surface of the reaction solution 203 has a sound wave reflection object nearby and weakly reflects sound waves, the sound source electrode Y shown in FIG. In the impedance 605, the impedance level difference and the number of poles are observed to be moderate.

  Further, in the sound source electrode Z606 at a position lower than the reaction vessel 109, since the sound wave reflector is far away and the reflection of the sound wave is weak, the sound source electrode Z impedance 607 shown in FIG. A large number of poles will be observed.

  From the above, it is possible to obtain information on the perspective of the reaction vessel 109 and the amount of liquid, automatic control of the position and intensity of the sound wave irradiation, the optimum drive frequency, warning of lack of the reaction liquid 203, and sound wave irradiation such as not performing sound wave irradiation. It can be used to control irradiation.

  Further, by providing storage means in the impedance measuring means 601, impedance characteristics in the initial state of the sound source 207 can be stored, and impedance changes can be measured as needed, so that changes over time such as deterioration of the sound source 207 can be known.

  The electrode impedance is measured by applying a constant voltage to the sound source and changing the drive frequency and measuring the inflow current to the sound source, or by applying a constant current and changing the drive frequency to obtain the voltage applied to the sound source. Measure and do.

1 is a schematic configuration diagram of an automatic analyzer to which the present invention is applied. It is a schematic block diagram of the stirring mechanism which can be operated up and down of the automatic analyzer in the 1st Embodiment of this invention. It is a schematic explanatory drawing of the stirring mechanism which can change the sound wave irradiation angle of the automatic analyzer in the 2nd Embodiment of this invention. It is explanatory drawing in the case of sharing the same sound source in the several stirring position of the automatic analyzer in the 3rd Embodiment of this invention. It is a schematic block diagram of the stirring mechanism which can be moved up and down by the array sound source of the automatic analyzer in the 4th Embodiment of this invention. It is explanatory drawing of the impedance measurement function of the automatic analyzer in the 5th Embodiment of this invention.

Explanation of symbols

DESCRIPTION OF SYMBOLS 101 Specimen storage part 102 Reagent storage part 103 Reaction part 104 Stirring part 105 Analysis part 106 Washing part 107 Sample 108 Sample dispensing mechanism 109 Reaction container 110 Reagent dispensing mechanism 111 Reagent 112 Stirring mechanism 201 Motor 202 Ultrasound 203 Reaction liquid 204 Bubble 205 Swirling Flow 206 Control Unit 207 Sound Source 208 Driver 209 Reverse Direction Swirling Flow 401 First Reagent Stirring Position 402 Second Reagent Stirring Position 403 Third Reagent Stirring Position 404 Washing Stirring Position 501 Sound Source Electrode Selection Unit 601 Impedance Measuring Unit 602 Sound Source Electrode X
603 Sound source electrode X impedance 604 Sound source electrode Y
605 Sound source electrode Y impedance 606 Sound source electrode Z
607 Sound source electrode Z impedance

Claims (5)

A stirrer that stirs the reagent or the like and the test liquid by ultrasonic waves generated from a sound source, an analysis unit that performs a component analysis of the test liquid by reacting the reagent or the like with the test liquid to be analyzed, and the above analysis In an automatic analyzer having a control unit for controlling the operation of the unit and the stirring unit,
The stirring unit has a mechanism in which the sound source can move back and forth, left and right, up and down, and can be rotated.
The control unit controls the stirring unit to change the position and angle of the sound source, the sound intensity, and the sound source driving frequency. The automatic analyzer according to claim 1, wherein
The said control part moves a stirring part to the several places on the said automatic analyzer, and performs the stirring operation | movement, The automatic analyzer characterized by the above-mentioned. The automatic analyzer according to claim 1,
The sound source generates an ultrasonic wave by applying a voltage to the electrode, a plurality of the electrodes are arranged, and the control unit switches the electrode to which the voltage is applied in addition to controlling the position of the sound source itself, thereby generating a sound wave. An automatic analyzer characterized by changing an irradiation position. The automatic analyzer according to claim 3,
The sound source is an element that generates an electromotive force when irradiated with an ultrasonic wave. The control unit detects the reflected wave of the ultrasonic wave generated from the sound source by the electromotive force detected by the plurality of electrodes. An automatic analyzer for detecting a liquid surface position of a mixed liquid of the reagent or the like and a subject. The automatic analyzer according to claim 4,
The control unit detects the position of the liquid surface by measuring the sound source electrode impedance, and this electrode impedance is measured by applying a constant voltage to the sound source, changing the drive frequency, and measuring the inflow current to the sound source. Alternatively, an automatic analyzer is characterized in that a constant current is applied and the driving frequency is changed to measure the voltage applied to the sound source.

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