JP2007303963A - Analyzer, and method for controlling temperature of liquid sample in analyzer - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an analyzer capable of simply holding a liquid sample to a predetermined temperature in the case where the liquid sample held to a reaction container is stirred using a surface elastic wave element, and to provide a method of controlling a temperature of the liquid sample. <P>SOLUTION: The analyzer 1 includes a thermostatic tank 6 which houses a plurality of reaction containers 9 for holding the liquid sample containing a specimen and a reagent, and constituted so as to stirr the liquid sample by the sonic wave emitted from the surface elastic wave element to analyze a reaction liquid. The temperature control method of the liquid sample is also disclosed. The analyzer 1 is provided with a temperature control circuit 16c for holding the liquid sample to a predetermined temperature by controlling the temperature of the thermostatic tank 6 to a temperature lower than a target temperature by the estimated value of the temperature rise of the liquid sample estimated from the drive signal of the surface elastic wave element. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to an analyzer and a temperature control method for a liquid sample in the analyzer.

  2. Description of the Related Art Conventionally, an analyzer, for example, an automatic analyzer that analyzes a biological sample such as blood, includes a reaction wheel that accommodates a plurality of reaction containers holding a specimen and a reagent, and optically reacts a reaction solution obtained by reacting the specimen and the reagent. The component concentration of the specimen is analyzed by measuring it automatically. At this time, the automatic analyzer monitors the temperature in the thermostatic chamber with a temperature sensor, and controls the heater on and off based on the monitored temperature to keep the temperature in the bath, and thus the liquid sample, at a predetermined temperature. ing. Further, as an agitating device for agitating a liquid sample, an apparatus that generates an acoustic stream with a sharp sound field using sound waves and agitates the liquid by the acoustic stream is known (for example, see Patent Document 1).

German Patent Invention No. 10325307

  Incidentally, the stirring device disclosed in Patent Document 1 uses a surface acoustic wave (SAW) element in which a comb electrode (IDT) is formed on a piezoelectric substrate, and drives the surface acoustic wave element by a drive control circuit. For this reason, in the stirring apparatus of Patent Document 1, the energy of the surface acoustic wave (sound wave) used for stirring is finally changed to thermal energy to increase the temperature of the liquid sample. Therefore, when the stirrer disclosed in Patent Document 1 is used in an automatic analyzer, the temperature of the liquid sample held in the reaction vessel rises to a predetermined temperature or higher due to stirring, resulting in a decrease in analysis accuracy, and in some cases, the specimen is altered. There were problems such as. In this case, there is a problem that it is technically difficult to directly measure the temperature of the liquid sample held in the reaction vessel from the viewpoints of a small amount of specimen, prevention of contamination, sensitivity of the temperature sensor, and the like.

  The present invention has been made in view of the above, and in the case of stirring a liquid sample held in a reaction vessel using a surface acoustic wave element, an analyzer capable of easily holding the liquid sample at a predetermined temperature Another object of the present invention is to provide a temperature control method for a liquid sample in an analyzer.

  In order to solve the above-described problems and achieve the object, an analyzer according to claim 1 houses a plurality of reaction containers holding a liquid sample containing a specimen and a reagent, and keeps the liquid sample at a predetermined temperature. An analysis apparatus comprising a thermostatic chamber, wherein the liquid sample is stirred by a sound wave generated by a surface acoustic wave element, and a reaction liquid is analyzed, wherein the temperature of the thermostatic chamber is predicted from a driving signal of the surface acoustic wave element A temperature control means is provided for keeping the liquid sample at a predetermined temperature by controlling the temperature of the liquid sample to be lower than the target temperature by a predicted value of the temperature rise of the liquid sample.

  In order to solve the above-described problems and achieve the object, the temperature control method for a liquid sample in the analyzer according to claim 2 contains a plurality of reaction containers holding a liquid sample containing a specimen and a reagent, A temperature control method for a liquid sample in an analyzer that comprises a thermostatic chamber for keeping the liquid sample at a predetermined temperature, and stirs the liquid sample with sound waves generated by a surface acoustic wave element to analyze a reaction liquid, the thermostat The temperature of the liquid sample is controlled to be lower than the target temperature by the predicted value of the temperature rise of the liquid sample predicted from the driving signal of the surface acoustic wave element, thereby keeping the liquid sample at a predetermined temperature. .

  The analyzer of the present invention controls the temperature of the thermostat to a predetermined temperature by controlling the temperature of the liquid sample to be lower than the target temperature by the predicted value of the temperature rise of the liquid sample predicted from the driving signal of the surface acoustic wave device. A temperature control means for keeping the temperature is provided, and the temperature control method for the liquid sample in the analyzer of the present invention is the target temperature corresponding to the predicted value of the temperature rise of the liquid sample predicted from the driving signal of the surface acoustic wave device. The temperature of the liquid sample is kept at a predetermined temperature by controlling the temperature to a lower level. Therefore, the temperature control method for the liquid sample in the analyzer and the analyzer according to the present invention is such that, even if heat is generated by agitating the liquid sample by driving the surface acoustic wave element, the temperature of the thermostatic chamber is set higher than the target temperature. Since it is controlled to be low, the liquid sample can be easily held at a predetermined temperature.

(Embodiment 1)
Hereinafter, an analysis apparatus and a liquid sample temperature control method according to a first embodiment of the present invention will be described in detail with reference to the drawings. FIG. 1 is a schematic configuration diagram illustrating the automatic analyzer according to the first embodiment. FIG. 2 is an enlarged view of the reaction wheel of the automatic analyzer shown in FIG. 1 together with schematic configurations of a dispensing device and a stirring device.

  As shown in FIGS. 1 and 2, the automatic analyzer 1 includes a sample table 3, a reaction wheel 6 and a reagent table 13 which are spaced apart from each other on a work table 2 and can be rotated and positioned in the circumferential direction. A stirrer 20 is provided. In the automatic analyzer 1, a sample dispensing mechanism 5 is provided between the sample table 3 and the reaction wheel 6, and a reagent dispensing mechanism 12 is provided between the reaction wheel 6 and the reagent table 13. .

  As shown in FIG. 1, the sample table 3 is rotated in the direction indicated by the arrow by the driving means, and a plurality of storage chambers 3 a are provided on the outer periphery at regular intervals along the circumferential direction. In each storage chamber 3a, a sample container 4 storing a sample is detachably stored.

  The sample dispensing mechanism 5 is a means for dispensing a sample such as urine and blood smaller than the reagent into the reaction container 9, and as shown in FIGS. 1 and 2, a plurality of sample tables 3 are provided by a dispensing nozzle 5a. Samples are sequentially dispensed from the sample container 4 to the reaction container 9 accommodated in the holder 6 b of the reaction wheel 6. As shown in FIG. 2, the sample dispensing mechanism 5 includes a dispensing control unit 5b that controls the dispensing timing for dispensing the sample to the reaction container 9 by the dispensing nozzle 5a.

  As shown in FIG. 1, the reaction wheel 6 is rotated in a direction indicated by an arrow by a driving means different from the sample table 3, and a plurality of holders 6 b that are partitioned at equal intervals along the circumferential direction by a partition wall 6 a are provided. Yes. The lower part of the partition wall 6a is opened, and the adjacent holder 6b communicates in the circumferential direction. As shown in FIG. 1, a temperature sensor 7 for detecting the temperature in the plurality of holders 6b is provided in one of the plurality of holders 6b communicating in the circumferential direction at the lower portion in this way. In each holder 6b, a reaction vessel 9 for reacting a specimen with a reagent as a stirring vessel is detachably accommodated, and openings through which light is transmitted are formed on both sides in the radial direction. In the reaction wheel 6, a terminal substrate 22 provided with a surface heater 8 that holds a plurality of holders 6 b communicating in the circumferential direction at a predetermined temperature (for example, 37 ° C.) is disposed in the lower part (FIG. 2). reference). Accordingly, the reaction wheel 6 also serves as a thermostatic chamber that holds the liquid sample held in the reaction vessel 9 accommodated in the plurality of holders 6b at the predetermined temperature. As shown in FIGS. 2 and 3, each holder 6b is provided with an extraction electrode 6d extending vertically through the bottom wall 6c of the reaction wheel 6 in the radial direction. The reaction wheel 6 rotates clockwise (1 turn-1 reaction vessel) / 4 minutes in one cycle and rotates one reaction vessel 9 counterclockwise in four cycles. The reaction wheel 6 is provided with a measurement optical system 10 and a discharge device 11.

  The reaction container 9 is a very small container having a capacity of several nL to several tens of μL, and is a material that transmits 80% or more of the light contained in the analysis light (340 to 800 nm) emitted from the light source 10a, such as heat resistant glass. Synthetic resins such as glass, cyclic olefin and polystyrene are used. As shown in FIGS. 4 and 5, the reaction vessel 9 is formed into a rectangular tube shape having an opening 9c in the upper part by a side wall 9a and a bottom wall 9b, and an inner surface for holding a liquid such as a specimen or a reagent is provided with respect to the liquid. Affinity treatment is applied. The reaction vessel 9 is used as a window through which a part of the pair of side walls 9a facing in parallel transmits the analysis light. As shown in FIG. 5, the reaction vessel 9 has a surface acoustic wave element 21 attached to the lower surface of the bottom wall 9b via an acoustic matching layer.

  The measurement optical system 10 emits analysis light (340 to 800 nm) for analyzing the liquid in the reaction container 9 in which the reagent and the sample have reacted from the light source 10a. The light beam for analysis emitted from the light source 10a passes through the liquid in the reaction vessel 9, and is received by the light receiving element 10b provided at a position facing the light source 10a. On the other hand, the discharge device 11 includes a discharge nozzle, and sucks the liquid after completion of the reaction from the reaction container 9 by the discharge nozzle and discharges it to a discharge container (not shown). Here, the reaction container 9 that has passed through the discharge device 11 is transferred to a cleaning device (not shown) and washed, and then used again for analysis of a new specimen.

  The reagent dispensing mechanism 12 is a means for dispensing a reagent. As shown in FIG. 1, the reagent dispensing mechanism 12 dispenses the reagent from a predetermined reagent container 14 of the reagent table 13 into the reaction container 9 sequentially accommodated in the holder 6b of the reaction wheel 6. Note.

  As shown in FIG. 1, the reagent table 13 is rotated in a direction indicated by an arrow by a driving means different from the sample table 3 and the reaction wheel 6, and a plurality of fan-shaped storage chambers 13 a are provided along the circumferential direction. ing. In each storage chamber 13a, the reagent container 14 is detachably stored. Each of the plurality of reagent containers 14 is filled with a predetermined reagent corresponding to the inspection item, and a barcode label (not shown) for displaying information on the stored reagent is attached to the outer surface.

  Here, a reading device 15 is installed on the outer periphery of the reagent table 13. The reading device 15 reads information such as the reagent type, lot, and expiration date recorded on the barcode label attached to the reagent container 14 and outputs the information to the control unit 16.

  The control unit 16 controls the operation of the surface heater 8, the device control unit 16 a that controls the operation of each unit of the automatic analyzer 1, the linkage unit 16 b that links the control operations of the dispensing control unit 5 b and the drive control circuit 24. For example, a microcomputer or the like having a storage function for storing the analysis result is used. The control unit 16 is connected to the sample dispensing mechanism 5, the light receiving element 10b, the discharge device 11, the reading device 15, the analysis unit 17, the input unit 18, the display unit 19, the stirring device 20, and the like. In addition to controlling the operation, based on the information read from the record of the bar code label, if the reagent lot or expiration date is outside the installation range, the automatic analyzer 1 is controlled so as to regulate the analysis work, or the operator A warning is issued.

  At this time, the temperature control circuit 16c receives a control signal for controlling the operation of the signal generator 23 output from the drive control circuit 24 via the linkage unit 16b (see FIG. 6). 21 drive signals are obtained. The temperature control circuit 16c then lowers the temperature of the reaction wheel 6 below the target temperature of the reaction wheel 6 by the predicted value of the temperature rise of the liquid sample in the reaction vessel 9 predicted from the drive signal of the surface acoustic wave element 21. The surface heater 8 is controlled so that the liquid sample is kept at a predetermined temperature. For example, the temperature control circuit 16 c obtains the amount of electric power applied to the surface acoustic wave element 21 from the drive signal of the surface acoustic wave element 21, and shows the relationship between this electric energy and the temperature rise of the liquid sample in the reaction vessel 9. Find in advance. The temperature control circuit 16c obtains a predicted value of the temperature rise of the liquid sample based on this relationship and the drive signal of the surface acoustic wave element 21 input from the drive control circuit 24 via the linkage unit 16b. Further, temperature information in the plurality of holders 6b in the reaction wheel 6 detected by the temperature sensor 7 is input to the temperature control circuit 16c (see FIG. 6).

  The analysis unit 17 is connected to the light receiving element 10b via the control unit 16, and analyzes the component concentration of the specimen from the absorbance of the liquid in the reaction container 9 based on the amount of light received by the light receiving element 10b, and the analysis result is controlled by the control unit. 16 is output. The input unit 18 is a part that performs an operation of inputting inspection items and the like to the control unit 16, and for example, a keyboard, a mouse, or the like is used. The display unit 19 displays analysis contents, alarms, and the like, and a display panel or the like is used.

  The stirring device 20 is a device for stirring the liquid held in the reaction vessel 9 by sound waves. In addition to the surface acoustic wave element 21 attached to the reaction vessel 9, as shown in FIG. 23 and a drive control circuit 24 are provided.

  As shown in FIG. 5, the surface acoustic wave element 21 has a vibrator (sound generator) 21b made of a comb-shaped electrode (IDT) formed on a piezoelectric substrate 21a made of a piezoelectric material such as lithium niobate (LiNbO3). Yes.

  As shown in FIG. 2, the terminal substrate 22 is a ring-shaped insulating plate disposed below the reaction wheel 6 and does not rotate. The terminal substrate 22 has a position PN, where PN is the position of the holder 6b in the rotation direction of the reaction wheel 6 in which the dispensing nozzle 5a of the sample dispensing mechanism 5 in the plurality of holders 6b dispenses the sample S into the reaction vessel 9. Contact electrodes 22a and 22b that contact the extraction electrode 6d and dispense power to the vibrator 21b are provided in the stirring region corresponding to the range of the positions PN-1 to PN + 2 from the previous one to the second position. Yes. Here, the agitation region is not limited to the range of four positions PN-1 to PN + 2, and if necessary, at least the position PN at which the dispensing nozzle 5a dispenses the sample S is included. You may set to the wide range of 4 or more places, or you may set to the narrow range of less than 4 places.

  As shown in FIG. 2, the signal generator 23 is connected to the contact electrodes 22a and 22b by a wiring 23a, and a high-frequency signal of about several tens to several hundreds of MHz based on a control signal from the drive control circuit 24. Is output to the surface acoustic wave element 21, and the sound wave is oscillated by the vibrator 21b. The drive control circuit 24 uses electronic control means (ECU) incorporating a memory and a timer, and controls the drive signal of the surface acoustic wave element 21.

  As shown in FIG. 2, the drive control circuit 24 is connected to the dispensing control unit 5b via the linkage unit 16b, and controls the operation of the signal generator 23, and the control operation with the dispensing control unit 5b is linked. Has been. The drive control circuit 24 outputs a control signal for controlling the operation of the signal generator 23 to the signal generator 23 and also outputs it to the temperature control circuit 16c via the linkage unit 16b (see FIG. 6). The drive control circuit 24 is, for example, a characteristic (frequency, intensity, phase, wave characteristic), a waveform (sine wave, triangular wave, rectangular wave, burst wave, etc.) or modulation (amplitude modulation, Frequency modulation) and the like. Further, the drive control circuit 24 can switch the frequency of the oscillation signal oscillated by the signal generator 23 according to a built-in timer.

  In the automatic analyzer 1 configured as described above, the reagent dispensing mechanism 12 sequentially dispenses a reagent from a predetermined reagent container 14 to the reaction container 9 conveyed along the circumferential direction by the rotating reaction wheel 6. . The reaction container 9 into which the reagent has been dispensed is transported to the vicinity of the sample dispensing mechanism 5 by the rotation of the reaction wheel 6, and samples are dispensed sequentially from the plurality of sample containers 4 on the sample table 3. The reaction container 9 into which the specimen has been dispensed reacts while the reagent and specimen are stirred by the stirring device 20 while being transported along the circumferential direction by the reaction wheel 6, and the reaction between the light source 10 a and the light receiving element 10 b. Pass between. At this time, the reaction liquid in which the reagent in the reaction container 9 has reacted with the sample is measured by the light receiving element 10b, and the component concentration and the like are analyzed by the analysis unit 17. Then, after the analysis is completed, the reaction vessel 9 is discharged by the discharge device 11 and washed by a washing device (not shown), and then used again for analyzing the specimen.

  At this time, the automatic analyzer 1 controls the liquid sample held in the reaction vessel 9 to a predetermined temperature by a temperature control method described below. Under the control of the temperature control circuit 16c, the automatic analyzer 1 controls the reaction wheel 6 so as to reach the target temperature TH based on the temperature information in the holder 6b of the reaction wheel 6 input from the temperature sensor 7. . In FIG. 7, the dotted line indicates the target temperature TH of the reaction wheel 6, and the solid line indicates the measured temperature of the reaction wheel 6 detected by the temperature sensor 7.

  At this time, when the analysis of the sample is started in the automatic analyzer 1, the temperature control circuit 16c turns off the surface heater 8 for at least the driving time tw of the surface acoustic wave element 21, as shown in FIG. The temperature of the reaction wheel 6 is controlled to be lower than the target temperature TH of the reaction wheel 6 by the predicted value of the temperature rise of the liquid sample predicted based on the relationship obtained in advance from the drive signal of the surface acoustic wave element 21. As a result, the automatic analyzer 1 uses the temperature control circuit 16c to control the liquid sample held in the reaction vessel 9 to the target temperature TL even if heat is generated by stirring the liquid sample by the surface acoustic wave element 21. The sample is kept warm (see FIG. 8) to prevent deterioration of the specimen. Here, the driving time tw of the surface acoustic wave element 21 is expressed as the sum of the driving times of the surface acoustic wave element 21 at the four positions PN-1 to PN + 2 in the stirring region.

  At this time, unless the temperature control circuit 16c is provided, the automatic analyzer 1 controls the inside of the reaction wheel 6 to be the target temperature TH by turning the surface heater 8 on and off as in the conventional automatic analyzer. As shown by the solid line in FIG. 9, the temperature in the reaction wheel 6 varies between the high temperature side and the low temperature side across the target temperature TH indicated by the dotted line. For this reason, when the liquid sample in the reaction vessel 9 is stirred by the surface acoustic wave element 21, the heat generated by the heating by the surface heater 8 and the stirring by the surface acoustic wave element 21 causes the reaction vessel 9 to be stirred as shown in FIG. The temperature of the held liquid sample easily exceeds the target temperature TL. Moreover, since the reaction wheel 6 also serves as a constant temperature bath, the reaction wheel 6 has a large heat capacity. Therefore, even if the surface heater 8 is turned off, the temperature is hardly lowered. For this reason, as shown in FIG. 10, the liquid sample held in the reaction vessel 9 has a very slow temperature drop after the drive time tw, and it is difficult to maintain the target temperature TL.

  Here, in the automatic analyzer 1, since the reaction wheel 6 has a large heat capacity as described above, the time for turning off the surface heater 8 needs to be longer than the drive time tw of the surface acoustic wave element 21. In addition, the surface heater 8 may be divided as necessary, so that the temperature drop in the plurality of holders 6b in the reaction wheel 6 is significantly arranged in a portion that requires significant heating. On the other hand, as described above, the reaction container 9 has a very small capacity of several nL to several tens of μL. For this reason, the temperature control circuit 16c may control the temperature of the reaction wheel 6 to be lower than the target temperature by the predicted value of the temperature rise of the liquid sample. The amount of heat related to the product of numbers is not considered.

(Embodiment 2)
Next, a second embodiment of the analyzer and the temperature control method for a liquid sample in the analyzer according to the present invention will be described in detail with reference to the drawings. In the automatic analyzer of the first embodiment, the drive control circuit is provided independently of the reaction wheel, whereas in the automatic analyzer of the second embodiment, the drive control circuit is provided in the reaction wheel. . FIG. 11 is a schematic diagram illustrating a main part of the automatic analyzer according to the second embodiment. Here, the automatic analyzer according to the second embodiment has the same configuration as the automatic analyzer according to the first embodiment except for the arrangement of the drive control circuit. is doing.

  In the automatic analyzer 1 according to the second embodiment, the drive control circuit 24 is provided in the reaction wheel 6, so that the heat generated by the drive control circuit 24 when the surface acoustic wave element 21 is driven is used to heat the reaction wheel 6. Use. As a result, the automatic analyzer 1 according to the second embodiment has a surface heater 8 that uses the heat generated by the drive control circuit 24 in addition to the effect of controlling the liquid sample held in the reaction vessel 9 to the target temperature TL. Power saving has been achieved by suppressing the use of.

1 is a schematic configuration diagram illustrating an automatic analyzer according to a first embodiment. It is a figure which expands the reaction wheel of the automatic analyzer shown in FIG. 1, and shows with schematic structure of a dispensing apparatus and a stirring apparatus. It is sectional drawing which expands the A section of a reaction wheel and shows an extraction electrode. 2 is a perspective view of a reaction container used in the automatic analyzer according to Embodiment 1. FIG. It is a bottom view of the reaction container of FIG. FIG. 3 is a schematic diagram illustrating a main part of the automatic analyzer according to the first embodiment. FIG. 3 is a temperature control diagram showing a target temperature of a reaction wheel and an actually measured temperature in the automatic analyzer according to the first embodiment. FIG. 3 is a temperature control diagram showing a target temperature and an actually measured temperature of a liquid sample held in a reaction container in the automatic analyzer according to the first embodiment. It is a temperature control figure which shows the target temperature and the actual temperature of the reaction wheel in the conventional automatic analyzer. It is a temperature control figure which shows the target temperature and measured temperature of the liquid sample hold | maintained at the reaction container in the conventional automatic analyzer. FIG. 6 is a schematic diagram showing a main part of an automatic analyzer according to a second embodiment.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Automatic analyzer 2 Work table 3 Specimen table 4 Specimen container 5 Specimen dispensing mechanism 6 Reaction wheel 6b Holder 7 Temperature sensor 8 Surface heater 9 Reaction container 10 Measurement optical system 11 Discharge device 12 Reagent dispensing mechanism 13 Reagent table 14 Reagent container DESCRIPTION OF SYMBOLS 15 Reader 16 Control part 16a Apparatus control part 16b Cooperation part 16c Temperature control circuit 17 Analysis part 18 Input part 19 Display part 20 Stirring device 21 Surface acoustic wave element 22 Terminal board 23 Signal generator 24 Drive control circuit

Claims (2)

A plurality of reaction containers holding a liquid sample containing a specimen and a reagent are accommodated, and a thermostatic bath for keeping the liquid sample at a predetermined temperature is provided. The liquid sample is stirred by a sound wave generated by a surface acoustic wave element, and a reaction solution is prepared. An analysis device for analyzing,
Temperature control for keeping the liquid sample at a predetermined temperature by controlling the temperature of the thermostatic chamber to be lower than the target temperature by the predicted value of the temperature rise of the liquid sample predicted from the driving signal of the surface acoustic wave device An analyzer characterized by providing means. A plurality of reaction containers holding a liquid sample containing a specimen and a reagent are accommodated, and a thermostatic bath for keeping the liquid sample at a predetermined temperature is provided. The liquid sample is stirred by a sound wave generated by a surface acoustic wave element, and a reaction solution is prepared. A temperature control method for a liquid sample in an analyzer for analysis,
Maintaining the temperature of the liquid sample at a predetermined temperature by controlling the temperature of the thermostatic chamber to be lower than the target temperature by the predicted value of the temperature increase of the liquid sample predicted from the driving signal of the surface acoustic wave device. A temperature control method for a liquid sample in a featured analyzer.

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