JP5919364B2 - Automatic analyzer - Google Patents

Description

  The present invention relates to an automatic analyzer that performs qualitative and quantitative analysis of biological samples such as blood and urine, and more particularly to an automatic analyzer that includes a stirring means for stirring biological samples and reagents.

  The automatic analyzer mixes and stirs a reagent that reacts with the analyte to be analyzed, reacts for a certain period of time, then measures the change in absorbance of the reaction solution with a photometer in biochemical analysis, and in immunity and gene analysis, Analysis is performed by measuring the number of labeled bodies bound to the analysis target component with a photometer such as a photomultiplier tube. Stirring means include a contact-type stirring method in which a spatula stirrer is immersed in a liquid to be stirred, and the object to be stirred is mixed by rotating or reciprocating, and the object to be stirred is irradiated with sound waves. There is a non-contact stirring method that mixes.

  In Patent Document 1, the rotation speed of the stirrer, the stirring time, and the amount of entry of the rotating stirrer into the liquid to be stirred are changed according to the analysis conditions such as the type of reagent, liquid volume, type of diluent, liquid volume, and dilution factor. And the technique which raises stirring efficiency is disclosed. Patent Document 2 also enables effective stirring by taking into account the liquid level height of the object to be stirred in different reaction vessels and the mechanical properties of the object to be stirred such as viscosity, density, and surface tension. Techniques to do this are disclosed.

JP-A-9-145718 JP-A-2005-99046

  By the way, in recent years, in the field of automatic analyzers, as the number of analysis items increases, the types of analysis reagents having different properties such as liquid viscosity and contact angle increase, and further increases are expected in the future. In addition, the reagent forms are diversified, such as diluting the concentrated reagent with water in the apparatus, and the types of diluted water are also diversifying. In order to sufficiently stir all of the reagents used in such a wide variety of forms, it is impossible to stir sufficiently with a stirring method that has only one stirring condition corresponding to one conventional reagent. Is concerned.

  An object of the present invention is to provide an automatic analyzer capable of performing sufficient stirring for any items when stirring a sample and a reagent in a reaction vessel.

  The above object is achieved by changing the stirring conditions after a lapse of a certain time during a series of stirring operations in the same reagent.

  In other words, it has multiple spatula stirrers that stir the agitated material by immersing it in the agitated material and rotating or repeatedly moving it, and independently change the rotation speed and angle of the stirrer according to the analysis item. In the automatic analyzer characterized by having a drive means that can perform the stirring, the number of rotations and the angle of the stirring bar are changed during a series of stirring operations for the same reagent, and stirring is performed under two or more types of stirring conditions Is solved.

  In addition, in an automatic analyzer characterized in that stirring is performed by irradiating an object to be stirred with a sound wave, the selection of electrodes on the piezoelectric element and the intensity of sound wave irradiation during the series of stirring operations with the same reagent It can be solved by changing.

  According to the present invention described above, an automatic analyzer comprising control means for controlling a means for stirring a mixed solution of a specimen and a reagent so that the same reagent is driven under two or more different stirring conditions In the apparatus having the stirrer, the rotation speed and the stirring time are changed, and in the apparatus having the sound wave generating means, the selection of the electrode on the piezoelectric element and the change of the sound wave irradiation intensity are executed. It is possible to provide an automatic analyzer that can perform sufficient stirring even if it is a simple item.

The perspective view which shows the structure of the automatic analyzer concerning embodiment of this invention. Sectional drawing of the stirring mechanism periphery equipped with the automatic analyzer concerning embodiment of this invention. An example of the drive pattern of the stirring mechanism with which the automatic analyzer concerning embodiment of this invention is equipped. An example of the liquid property and stirring parameter of the reagent concerning embodiment of this invention. An example of the liquid property of the reagent concerning the embodiment of the present invention, and the setting conditions of the stirring mechanism. An example of the drive pattern of the stirring mechanism with which the automatic analyzer concerning embodiment of this invention is equipped. The expansion example of the stirring mechanism with which the automatic analyzer concerning embodiment of this invention is equipped. The expansion example of the stirring mechanism with which the automatic analyzer concerning embodiment of this invention is equipped. Sectional drawing of the stirring mechanism periphery equipped with the automatic analyzer concerning embodiment of this invention.

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

  FIG. 1 is a schematic diagram of a typical automatic analyzer to which the present invention is applied, and is an automatic analyzer equipped with a piezoelectric element as a stirring mechanism. FIG. 2 is a schematic configuration diagram around the stirring mechanism 7 provided in the automatic analyzer shown in FIG.

  As shown in FIG. 1, the automatic analyzer according to this embodiment mainly includes a sample disk 1, a reagent disk 2, a reaction disk 3, a reaction tank 4, a sampling mechanism 5, a pipetting mechanism 6, a stirring mechanism 7, and a photometric mechanism. 8, a cleaning mechanism 9, a display unit 10, an input unit 11, a storage unit 12, and a control unit 13. In the sample disk 1, a plurality of sample containers 16 in which collected samples are placed are fixed and arranged on the circumference of a circular disk 17, and the circular disk 17 includes a motor, a rotating shaft, etc. (not shown). The drive mechanism rotates in the circumferential direction so that positioning is possible. In the reagent disk 2, a plurality of reagent bottles 18 containing reagents for mixing and reacting with the sample are fixedly arranged on the circumference of the circular disk 19, and the periphery thereof is temperature-controlled. It is a cold storage 20. The circular disk 19 is rotated in the circumferential direction so as to be positioned by a drive mechanism including a motor, a rotating shaft, and the like (not shown). A plurality of reaction vessel holders 22 holding reaction vessels 21 for holding samples and reagents are attached to the reaction disk 3, and the circumferential rotation and stop are repeated by a driving mechanism 23 in a certain cycle, and the reaction is performed. The container 21 is intermittently transferred. The reaction tank 4 is installed along the movement trajectory of the reaction vessel 21, and in order to promote the chemical reaction between the sample and the reagent, for example, the reaction solution in the reaction vessel 21 is kept at a constant temperature with temperature-controlled constant temperature water. It is a thermostatic chamber to be controlled. The reaction vessel 21 moves in the reaction tank 4. The sampling mechanism 5 includes a probe 24, an arm 26 attached to the support shaft 25, and a drive mechanism that enables reciprocation between the sample disk 1 and the reaction disk 3 about the support shaft 25. According to a predetermined sequence, the sample in the sample container 16 that is transferred to a fixed position along with the rotation of the sample disk 1 is supplied to the reaction container 21. Similarly, the pipetting mechanism 6 includes a probe 27, an arm 29 attached to the support shaft 28, and a drive mechanism that enables reciprocation between the reagent disk 2 and the reaction disk 3 about the support shaft 28. The reagent in the reagent bottle 18 that is configured and is transferred to a fixed position along with the rotation of the reagent disk 2 is supplied to the reaction container 21 in accordance with a predetermined sequence. Each of the sample container 16 and the reagent bottle 18 contains different types of samples and reagents, and a necessary amount is supplied to the reaction container 21. The stirring mechanism 7 is a stirring mechanism that stirs and mixes the sample and the reagent in the reaction vessel 21 that have been transferred to that position (stirring position). The method of the stirring mechanism in the present invention can exhibit the same effect in any of the contact type stirring method using a stirrer and the non-contact type stirring method using ultrasonic waves.

  An example of a non-contact stirring type stirring mechanism will be described with reference to FIG. 2 as an example. The stirring mechanism 7 includes a fixed portion 31 fixed at a position where the sound wave can be irradiated from the side surface of the reaction vessel 21 at the stirring position, a piezoelectric element driver 14 for driving a piezoelectric element (30 in FIG. 2), and a stirring mechanism controller 15. And comprising. The stirring mechanism controller 15 is connected to the control unit 13 and drives the piezoelectric element driver 14 and controls the entire stirring mechanism 7. The fixed portion 31 is provided with a piezoelectric element 30 serving as a sound source so that one surface thereof is immersed in the constant temperature water of the reaction tank 4. The piezoelectric element 30 has a plurality of electrodes 32 and is configured to be vibrated at a predetermined frequency by the piezoelectric element driver 14 and to change the irradiation position of the sound wave by the vibrated electrode 32. Although not shown, the photometric mechanism 8 includes a light source, a photometer, a lens, and a photometric signal processing unit, and measures the physical properties of the sample, such as measuring the absorbance of the reaction solution in the reaction vessel 21. Measure with light. The cleaning mechanism 9 includes a plurality of nozzles 33 and a vertical drive mechanism 34, and sucks the reaction liquid in the reaction vessel 21, discharges the cleaning liquid, and the reaction that has been transferred to that position (cleaning position). The container 21 is washed. The display unit 10 displays various screens such as analysis items and analysis results, and the input unit 11 inputs various information such as analysis items. The storage unit 12 stores various information such as a predetermined sequence (program) and analysis items for controlling each mechanism.

  In FIG. 2, a reaction vessel 21 into which a sample and a reagent have been injected is fixed to the reaction disk 3 by a reaction vessel holder 22, and is immersed in a reaction tank 4 containing constant temperature water as the reaction disk 3 rotates in the circumferential direction. Move with. When the piezoelectric element 30 is transferred to the stirring position and stopped, the piezoelectric element 30 is vibrated at a predetermined frequency by the piezoelectric element driver 14. The vibration generated by exciting the piezoelectric element 30 propagates as a sound wave in the constant temperature water of the reaction tank 4 and reaches the side surface of the reaction vessel 21. This sound wave passes through the wall surface of the reaction vessel 21 and reaches the sample and reagent, which are the objects to be stirred inside. The transmitted vibration wave acts on the gas-liquid interface of the object to be stirred, causing a swirling flow. The sample and reagent are agitated by this swirl flow.

  The operation of the automatic analyzer configured as described above will be described below.

  First, when the reaction container 21 cleaned by the cleaning mechanism 9 is transferred to the sample injection position by driving the reaction disk 3, the sample disk 1 rotates and the sample container 16 containing the sample is transferred to the sampling position. . Similarly, the reagent disk 2 also transfers the desired reagent bottle 18 to the pipetting position.

  Subsequently, the sampling mechanism 5 operates, and the sample is injected from the sample container 16 transferred to the sampling position into the reaction container 21 transferred to the sample injection position using the probe 24. The reaction container 21 into which the sample has been injected is transferred to the reagent injection position, and is transferred to the reagent injection position from the reagent bottle 18 that has been transferred to the pipetting position on the reagent disk 2 by the operation of the pipetting mechanism 6. The reagent is injected into the reaction container 21.

  Thereafter, the reaction vessel 21 is transferred to the stirring position, and the sample and the reagent are stirred by the stirring mechanism 7.

  When the reaction vessel 21 passes between the light source and the photometer, the absorbance of the reaction solution after the stirring is completed is measured by the photometric mechanism 8. This measurement is performed for several cycles, and the reaction vessel 21 that has been measured is washed by the washing mechanism 9.

  Such a series of operations is executed for each reaction vessel 21, and analysis is performed by the automatic analyzer according to the present embodiment.

  Now, the points that characterize the present embodiment in the stirring by the stirring mechanism 7 will be described in detail.

  In the present embodiment, the stirring mechanism 7 determines the irradiation position of the sound wave and the irradiation intensity of the sound wave according to the instruction of the control unit 13 until the reaction vessel 21 is transferred to the stirring position. At this time, the selection of the electrode and the intensity of sonication are determined in accordance with the liquid amount and liquidity. This is executed by searching for each analysis item from the table stored in the storage unit 12 as the stirring parameter. Furthermore, at the time of stirring, after a certain period of time, the selection of electrodes and the intensity of sound wave irradiation are changed so that stepwise stirring can be performed.

  In an apparatus having a low processing capacity, a sufficient stirring time is ensured by a single stirring, and therefore stirring can be performed using two or more stirring parameters for the same element. FIG. 3 shows an example in which two stirring parameters are applied to one stirring element. When the reaction vessel 21 rotates and the cell containing the mixed liquid of the specimen and the reagent is transferred before the stirring mechanism 7a, the reaction vessel 21 stops and the stirring mechanism 7a is driven. The parameter at this time is the first stirring parameter 301 after the addition of the first reagent. After a certain period of time, the parameter 302 is changed from 301, and stirring is performed. Further, after a few minutes, the second reagent is added, and the reaction vessel 21 rotates as in the case of the first reagent, and the cell containing the mixed liquid of the sample and the reagent is transferred in front of the stirring mechanism 7a. And the reaction vessel 21 is stopped, and the stirring mechanism 7a is driven. The parameter at this time is the first stirring parameter 303 after the addition of the second reagent. Thereafter, switching to the parameter 304 is performed, and stirring is performed. An example of changing the stirring parameter will be described with reference to FIGS. For example, in an analysis using a concentrated reagent, consider a case where the contact angle of the reagent is significantly smaller than that of diluted water. Here, FIG. 4 shows a liquid property example of the virtual reagent, and FIG. 5 shows the stirring parameters at that time. Here, it is assumed that the piezoelectric element 30 can be divided into 10 segments, with the uppermost portion being 1 and the highest voltage being 1 and switching to 10 stages. In the conventional setting, an agitation parameter 501 was adopted in accordance with the liquid volume and liquidity of the diluted water / reagent mixed liquid. The intensity of sound wave irradiation at this time is 5 and medium. However, in this case, the dilution water / reagent ratio is overwhelmingly large as 13: 2. In such a case, in a state where mixing of the dilution water and the reagent is not progressing immediately after the reagent is discharged, it is preferable to employ the stirring parameter 502 along the liquid property of the dilution water. Therefore, the degree of sound wave irradiation is 3, which is relatively strong. Since the diluted water and the reagent are in a mixed state after the first acoustic wave irradiation, the stirring parameter 501 in accordance with the liquid property of the mixed solution is adopted. This is the same as that used in the conventional setting. Moreover, the position of the segment to be used may be changed even with the same liquid amount due to the difference in viscosity.

  Furthermore, when using two or more types of reagents, if the liquid properties of the first reagent and the second reagent are significantly different, select the electrode to be used and change the sonication intensity after a certain period of time. By carrying out, effective stirring can be realized.

  By the way, for a device having a high processing capacity, a sufficient sonication time cannot be secured by a single stirring, and thus a plurality of stirring elements may be used. FIG. 6 shows an example in which different stirring parameters are set for the two stirring elements. When the reaction vessel 21 rotates and the cell containing the mixed liquid of the specimen and the reagent moves in front of the stirring mechanism 7b-1, the reaction vessel 21 is stopped and the stirring mechanism 7b-1 is set at the stirring parameter 601. To drive. Subsequently, when the cell containing the mixed liquid of the specimen and the reagent again moves before the stirring mechanism 7b-2, the reaction vessel 21 stops and the stirring mechanism 7b-2 is driven with the stirring parameter 602. Further, after a few minutes, the second reagent is added, and the reaction vessel 21 rotates as in the case of the first reagent, and the cell containing the mixed liquid of the sample and the reagent is 603 in front of the stirring mechanism 7b-1. The agitation parameter of 604 is driven with an agitation parameter of 604 in front of the agitation mechanism 7b-2.

  Thus, sufficient stirring effect can be obtained by applying a stirring mechanism employing two different stirring parameters to one reagent.

  If the processing capacity is further increased, the number of stirring mechanisms can be further increased. For example, in the analysis using two reagents, it is conceivable to use different stirring mechanisms for the first reagent and the second reagent. The structure in that case can be expanded as shown in FIG. After the first reagent is added, the stirring mechanism 7c-1 executes the stirring parameter 701, and the stirring mechanism 7c-2 executes the stirring parameter 702. Further, after the second reagent is added, the stirring mechanism 7d-1 executes the stirring parameter 703, and the stirring mechanism 7d-2 executes the stirring parameter 704.

  Furthermore, as another embodiment, there is a method in which photometry is performed after repeating the rotation / stop cycle of the reaction vessel a plurality of times. An example is shown in FIG. When downsizing is advanced in an apparatus having a high processing capability, it may be impossible to provide a plurality of stirring elements. In this case, even one stirring mechanism can be solved by starting photometry after sufficiently stirring by irradiating a sound wave every time it passes in front of the stirring mechanism. That is, after the first reagent is added, the stirring mechanism 7e executes the stirring parameter 801. Since there is not enough time to switch the stirring parameters in one stirring, the rotation / stop cycle of the reaction vessel 21 is repeated several times as it is until the reaction vessel 21 makes one round. When the cell containing the mixed liquid of the specimen and the reagent moves again before the stirring mechanism 7e, the stirring mechanism 7e executes the stirring parameter 802. Further, after the addition of the second reagent, the stirring mechanism 7e executes the stirring parameter 803, and executes the stirring parameter 804 after the reaction vessel 21 has made a round.

  FIG. 9 shows a schematic diagram of the stirring bar for the contact type stirring system using the stirring bar. Even in this case, as in the case of the non-contact type stirring mechanism, effective stirring can be realized by changing the stirring conditions after the elapse of a fixed time according to the reagent to be added. For example, when the hypothetical reagent shown in FIG. 4 is considered as an example of changing the stirring parameter, the example of changing the stirring parameter can be replaced with the same concept as in FIG. That is, in the virtual reagent of FIG. 4, in the conventional setting, the agitation parameter 501 along the liquid amount and liquidity of the mixed solution of the dilution water and the reagent was adopted. The stirring parameter at this time sets a stirrer as a moderate stirring speed. However, as in this case, when the dilution water / reagent ratio is 13: 2 and there is an excessive amount of dilution water, in the state where mixing of the dilution water and the reagent immediately after the reagent discharge has not progressed, the dilution water solution It is preferable to employ a stirring parameter 502 in line with the characteristics. In this case, compared with the stirring parameter 501, the stirring speed of the stirring bar is increased. After stirring for a certain time with the parameter 502, the diluted water and the reagent are in a mixed state. Therefore, the stirring parameter 501 that rotates at a medium speed along the liquid property of the mixed solution is adopted. This is the same as that used in the conventional setting. Such a parameter change can be realized not only by changing the rotation speed but also by changing the stirring time, the amount of the stir bar entering the liquid to be stirred, and the like.

  In this way, by changing the parameters after a certain period of time, sufficient stirring can be performed for any device in any item.

DESCRIPTION OF SYMBOLS 1 Sample disk 2 Reagent disk 3 Reaction disk 4 Reaction tank 5 Sampling mechanism 6 Pipetting mechanism 7 Stirring mechanism 8 Photometric mechanism 9 Washing mechanism 10 Display part 11 Input part 12 Storage part 13 Control part 14 Piezoelectric element driver 15 Stirring mechanism controller 16 Sample Containers 17 and 19 Circular disk 18 Reagent bottle 20 Cold storage chamber 21 Reaction container 22 Reaction container holder 23 Drive mechanism 24 and 27 Probes 25 and 28 Bearing shafts 26 and 29 Arm 30 Piezoelectric element 31 Fixing part 32 Electrode 33 Nozzle 34 Vertical drive mechanism 35 Stirring element 301 In the case of one stirring element, the first stirring parameter 302 after the first reagent addition 302 In the case of one stirring element, the second stirring parameter 303 after the first reagent addition The second stirring parameter 303 in the case of one stirring element After the addition of the reagent, the first stirring parameter 304 In this case, after the addition of the second reagent, the second stirring parameter 501 Conventional stirring parameter 502 After the reagent addition, the stirring parameter 601 for the first stirring is performed. Stirring parameter 602 In the case of two stirring elements, after the first reagent addition, the second stirring parameter 603 In the case of two stirring elements, after the second reagent addition, the first stirring parameter 604 The second stirring parameter in the case of two stirring elements After the addition of the reagent, the second stirring parameter 701 In the case of four stirring elements After the first reagent addition, the first stirring parameter 702 In the case of four stirring elements, after the first reagent addition, the second stirring parameter 703 The stirring element In the four cases, after the second reagent addition, the first stirring parameter 704 In the case of four stirring elements, after the second reagent addition, the second time Stirring parameter 801 The processing capacity is high, but when there is only one stirring element, after the first reagent addition, the first stirring parameter 802 Same as above, after the first reagent addition, the second stirring parameter 803 Same as above, second First stirring parameter 804 after reagent addition Same as above, second stirring parameter after second reagent addition

Claims (6)

A reaction container into which a sample and a reagent are injected;
A reaction disc holding the reaction vessel;
First and second stirring means for stirring the mixed solution of the specimen and the reagent in the reaction container;
A control unit for controlling the operation of the reaction disk and the stirring condition of the stirring means;
In an automatic analyzer equipped with
The first stirring means and the second stirring means are respectively arranged at different positions along the circumference of the reaction disk,
The reagent includes a first reagent and a second reagent having different liquidity,
The controller is
The first and second stirring conditions set according to the mixed state of the liquid mixture are stored in the storage unit, the stored first stirring condition is applied, and the first stirring means applies the sample. And stirring the mixed solution of the first reagent and the second reagent, and then rotating the reaction disk holding the reaction vessel to remove the reaction vessel containing the mixed solution from the second stirring means. Move forward,
Applying the stored second stirring condition different from the first stirring condition , the mixed liquid in the reaction vessel after being stirred by the first stirring means is transferred by the second stirring means. Stir ,
The first stirring condition is a condition along the liquidity in a state where the mixing of the first reagent and the second reagent is not progressing, and the second stirring condition is that the first reagent and the second reagent are automatic analyzer according to claim condition der Rukoto along the liquid of the mixed state. The automatic analyzer according to claim 1,
Further, an automatic analyzer comprising photometric means for performing photometry of a mixed liquid containing the same specimen and the same reagent which are stirred by applying the first stirring condition and the second stirring condition. The automatic analyzer according to claim 1 or 2,
The first and second stirring means are piezoelectric elements including a plurality of electrodes as sound wave generation sources,
The automatic analyzer according to claim 1, wherein the controller is configured to select different electrodes to be used depending on the first and second stirring conditions. A reaction container into which a sample and a reagent are injected;
A reaction disc holding the reaction vessel;
First and second stirring means for stirring the mixed solution of the specimen and the reagent in the reaction container;
In the stirring method of the mixed solution in the automatic analyzer comprising the operation of the reaction disk and the control unit for controlling the stirring condition of the clear counter means
The first stirring means and the second stirring means are respectively arranged at different positions along the circumference of the reaction disk,
The reagent includes a first reagent and a second reagent having different liquidity,
The controller is
The first and second stirring conditions set according to the mixed state of the liquid mixture are stored in the storage unit, the stored first stirring condition is applied, and the first stirring means applies the sample. And stirring the mixed solution of the first reagent and the second reagent, and then rotating the reaction disk holding the reaction vessel to remove the reaction vessel containing the mixed solution from the second stirring means. Move forward,
Applying the stored second stirring condition different from the first stirring condition , the mixed liquid in the reaction vessel after being stirred by the first stirring means is transferred by the second stirring means. Stir ,
The first stirring condition is a condition along the liquidity in a state where the mixing of the first reagent and the second reagent is not progressing, and the second stirring condition is that the first reagent and the second reagent are stirring method of the mixture to be mixed with said liquid condition der Rukoto along of the condition. In the stirring method of the liquid mixture of Claim 4 ,
The automatic analyzer further includes photometric means for performing photometry of a mixed solution containing the same specimen and the same reagent that are stirred by applying the first stirring condition and the second stirring condition. A method of stirring the mixed solution. In the stirring method of the liquid mixture of Claim 4 or 5,
The first and second stirring means are piezoelectric elements including a plurality of electrodes as sound wave generation sources,
The said control part makes the selection of the electrode to be used differ between said 1st and said 2nd stirring conditions, The stirring method of the liquid mixture characterized by the above-mentioned.