Automatic analysis device

Abstract

The objective of the present invention is to provide a highly reliable automated analyzing device capable of determining an agitation state with a high degree of accuracy, regardless of differences in physical properties attributable to the materials or construction of an ultrasonic wave generating source. To this end, the automated analyzing device of the present invention comprises an agitating unit for agitating a specimen and a reagent, an analyzing unit for using a reaction solution of the specimen and the reagent to perform a component analysis of the specimen, and a control unit for controlling the agitating unit and the analyzing unit, the agitating unit comprising an ultrasonic wave generating source for generating ultrasonic waves, a drive circuit for driving the ultrasonic wave generating source, and a waveform detecting unit for detecting an electric waveform output from the ultrasonic wave generating source in conjunction with the driving thereof, wherein: the agitating unit additionally includes a harmonic component extracting unit for extracting a harmonic component from the electric waveform detected by the waveform detecting unit; and the control unit determines the acceptability of an agitation state of the agitating unit on the basis of a signal strength of the harmonic component extracted by the harmonic component extracting unit.

Description

[Technical Field]

[0001] The present invention relates to an automatic analyzer. [Background technology]

[0002] Automated analyzers perform qualitative and quantitative analysis by adding, stirring, and reacting reagents that react specifically with specific components contained in biological samples such as blood and urine, and measuring the absorbance and luminescence of the reaction solution.In the stirring section of an automated analyzer, ultrasonic stirring has been proposed to prevent carryover, a phenomenon in which continuous stirring affects the results of the next analysis.

[0003] While stirring using ultrasound has the advantage of not causing carryover, there is a risk that the solution may not be stirred sufficiently if the irradiation conditions for the solution to be stirred are not properly adjusted, so automatic analyzers that determine whether the stirring state is good or bad and adjust the irradiation conditions are known. For example, Patent Document 1 discloses an automatic analyzer that detects the waveform of the voltage generated by an ultrasound source, normalizes the amplitude from the maximum and minimum values ​​of the detected waveform, and determines whether the stirring state caused by the ultrasound source is good or bad by comparing it with the normal state. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Application Laid-Open No. 2003-254979 Summary of the Invention [Problem to be solved by the invention]

[0005] However, it was found that depending on the material and structure of the ultrasonic wave source, a stirred flow may not be obtained even when the detected waveform intensity is high.

[0006] The present invention solves these problems, and its purpose is to provide a highly reliable automatic analyzer that can determine the stirring state with high accuracy regardless of differences in physical properties caused by the material or structure of the ultrasonic source. [Means for solving the problem]

[0007] In order to solve the above-mentioned problems, the present invention provides an automatic analyzer comprising an agitation unit that agitates a sample and a reagent, an analysis unit that performs component analysis of the sample using a reaction solution of the sample and the reagent, and a control unit that controls the agitation unit and the analysis unit, wherein the agitation unit has an ultrasonic wave generating source that generates ultrasonic waves, a drive circuit that drives the ultrasonic wave generating source, and a waveform detection unit that detects the electrical waveform output from the ultrasonic wave generating source as it is driven, and the agitation unit further has a harmonic component extraction unit that extracts harmonic components from the electrical waveform detected by the waveform detection unit, and the control unit determines whether the agitation state of the agitation unit is good or bad based on the signal strength of the harmonic components extracted by the harmonic component extraction unit. [Effects of the Invention]

[0008] According to the present invention, it is possible to provide a highly reliable automatic analyzer that can determine the stirring state with high accuracy regardless of differences in physical properties caused by the material or structure of the ultrasonic wave generating source. [Brief explanation of the drawings]

[0009] [Figure 1] 1 is a schematic diagram illustrating the overall configuration of an automatic analyzer according to an embodiment of the present invention. [Figure 2] FIG. 3 is a configuration diagram showing details of a portion related to a stirring unit. [Figure 3A] A conceptual diagram showing the stirring state when a piezoelectric element performs expansion and contraction motion using only the fundamental wave. [Figure 3B] FIG. 10 is a conceptual diagram showing the stirring state when a piezoelectric element undergoes expansion and contraction motion including harmonics. [Figure 4A] 2 is a graph showing a time change A in the amount of polarization and a frequency distribution A' of the amount of polarization when a sinusoidal voltage a is applied to a piezoelectric element. [Figure 4B]2 is a graph showing a time change B in the amount of polarization and a frequency distribution B' of the amount of polarization when a sinusoidal voltage b is applied to a piezoelectric element. [Figure 5A] 5 is a graph showing a voltage waveform 501 detected by a waveform detection unit and frequency components resolved by a harmonic component extraction unit when the stirring flow is weak. [Figure 5B] 10 is a graph showing a voltage waveform 504 detected by a waveform detection unit and frequency components resolved by a harmonic component extraction unit when the stirring flow is sufficient. [Figure 6] 10 is an example of a screen displayed on the output unit, showing the result of determining whether the stirring state is good or bad. [Figure 7] 10 is a flowchart showing the operation when a mode for determining whether the stirring state is good or bad and an automatic adjustment mode is executed. DETAILED DESCRIPTION OF THE INVENTION

[0010] The embodiments of the present invention will be described in detail with reference to the drawings. In the following embodiments, it goes without saying that the components (including element steps, etc.) are not necessarily essential unless otherwise specified or considered to be obviously essential in principle.

[0011] 1 is a schematic diagram of the overall configuration of an automatic analyzer 101 according to this embodiment. The automatic analyzer 101 reacts a sample 102 with a reagent 103 to analyze a specific component in the sample, and as shown in FIG. 1, includes an analysis unit 104, a stirring unit 105, a control unit 106, an output unit 109, an input unit 130, and an interface 107.

[0012] The analysis unit 104 includes a specimen dispensing mechanism 114 that dispenses specimen 102 from specimen container 113 into reaction container 110, a reagent disk 116 that stores reagent container 115 containing reagent 103, a reagent dispensing mechanism 117 that dispenses reagent 103 into reaction container 110, a light source 118 that irradiates light onto the reaction solution formed by the reaction of specimen 102 and reagent 103 in reaction container 110, a photometer 119 that measures the absorbance of the reaction solution, and a cleaning mechanism 120 that cleans reaction container 110 after measurement is completed.

[0013] The stirring unit 105 stirs the specimen 102 and reagent 103 dispensed into the reaction vessel 110 using ultrasound 108. The control unit 106 controls the operation of each unit, and also performs a quality judgment and automatic adjustment of the stirring state of the stirring unit 105, as described below. The output unit 109 displays the quality judgment and automatic adjustment results, alarms for automatic adjustment errors, etc., and is, for example, a display. The input unit 130 is used when the user inputs operation information, etc., and is, for example, a keyboard. The interface 107 connects each mechanism of the analysis unit 104 to the control unit 106, output unit 109, and input unit 130, and exchanges signals.

[0014] In this embodiment, an automatic biochemical analyzer that determines the concentration of a predetermined component using a photometer 119 that measures absorbance will be described as an example, but the technology disclosed in the embodiments described below may also be used in automatic immunoanalyzers or automatic coagulation analyzers that measure samples using other photometers.

[0015] The component analysis of the specimen 102 in the automatic analyzer 101 is mainly carried out in the following procedure.

[0016] To start an analysis, the user uses the input unit 130 to input information such as the analysis items and the amounts of the specimen 102 and reagent 103. The control unit 106 then automatically creates an analysis program and controls each unit based on the program as follows:

[0017] First, a belt or a motor carries a sample container 113 containing a sample 102 to a sample dispensing position. Next, a sample dispensing mechanism 114 aspirates the sample 102 from the sample container 113 and dispenses the sample 102 into a reaction container 110 placed on a reaction disk 111. Then, as the reaction disk 111 rotates, the reaction container 110 into which the sample 102 has been dispensed moves to the reagent dispensing position. Thereafter, a reagent dispensing mechanism 117 aspirates a reagent 103 from a reagent container 115 and dispenses the reagent 103 into the reaction container 110 into which the sample 102 has been dispensed. As the reaction disk 111 rotates, the reaction container 110 into which the sample 102 and reagent 103 have been dispensed moves to a mixing position.

[0018] Thereafter, the stirring unit 105 stirs the specimen 102 and the reagent 103 in the reaction vessel 110. When stirring is complete, the reaction disk 111 rotates further, and the reaction vessel 110 moves to the absorbance measurement position. Next, the photometer 119 measures the absorbance during or after the reaction between the specimen 102 and the reagent 103. When the absorbance measurement is complete, the reaction disk 111 rotates further, and the reaction vessel 110 moves to the cleaning position. Then, the cleaning mechanism 120 aspirates the reaction liquid in the reaction vessel 110 and cleans the reaction vessel 110.

[0019] The above-described series of operations is used to perform component analysis of one specimen, but similar component analysis is also performed in parallel on multiple other specimens, like batch processing.

[0020] Next, the structure of the stirring unit 105 according to this embodiment will be described.

[0021] 2 is a configuration diagram showing details of the parts related to the agitation unit 105. In addition to the ultrasonic wave generating source 202, the agitation unit 105 is composed of a reflector 207, a selection unit 205, a drive circuit 204, a waveform detection unit 203, and a harmonic component extraction unit 201.

[0022] The ultrasonic wave generating source 202 is installed in a reaction vessel 112 filled with a heat-retaining medium 208, and generates ultrasonic waves 108. The ultrasonic waves 108 propagate through the heat-retaining medium 208, enter the reaction vessel 110 from the side of the reaction vessel 110, which is placed so as to be immersed in the heat-retaining medium 208, and reach the liquid containing the specimen and the reagent (hereinafter referred to as "liquid to be stirred 206"), thereby stirring the liquid to be stirred 206.

[0023] The ultrasonic wave generator 202 is made of a piezoelectric element that utilizes the piezoelectric effect. Among piezoelectric elements, piezoelectric ceramic elements primarily made of lead zirconate titanate (PZT) are preferred because of their simple structure, high sensitivity, and the ability to improve their characteristics through the addition of various additives. Here, the piezoelectric effect refers to the phenomenon in which, when a voltage is applied to a piezoelectric element, polarization occurs, causing the surface charge to shift due to changes in the internal crystal structure. Depending on the state of this polarization, the piezoelectric element mechanically expands or contracts. Because the polarization and mechanical expansion / contraction of the piezoelectric element follow the applied voltage, ultrasonic waves propagate through the medium in contact with the piezoelectric element by applying a voltage with a frequency of approximately 20 kHz or higher.

[0024] The ultrasonic wave generator 202 may be made of a material that utilizes the magnetostrictive effect, in addition to the piezoelectric element that utilizes the piezoelectric effect described above. The magnetostrictive effect is a phenomenon in which a magnetic material expands and contracts due to a magnetic field generated by passing a current through a coil wound around the magnetic material. Compared to the piezoelectric effect, the method that utilizes the magnetostrictive effect has the advantage of not requiring a high voltage because it is current-driven, but the disadvantage is that it requires a large space because of the magnetic material and coil.

[0025] Furthermore, in this embodiment, a plurality of ultrasonic wave generating sources 202 are arranged in an array in the height direction, and each is provided with an electrode. In consideration of the risk of electric leakage to the heat-retaining medium 208, the surface of each electrode that comes into contact with the heat-retaining medium 208 is grounded as a GND electrode or provided with an insulating layer.

[0026] The reflecting plate 207 is provided so as to extend to the opposite side of the ultrasonic wave generating source 202 with respect to the reaction vessel 110, and reflects the ultrasonic waves 108 that have passed through the reaction vessel 110 etc., and irradiates them again toward the reaction vessel 110. The ultrasonic waves 108 reflected by the reflecting plate 207 enter the reaction vessel 110 from the side surface of the reaction vessel 110, and reach the liquid 206 to be stirred, thereby stirring the liquid 206.

[0027] Here, the reflector 207 has an upper slope and a lower slope for refraction. The upper slope serves to reflect the transmitted ultrasonic wave 108 downward and irradiate it again toward the reaction vessel 110. On the other hand, the lower slope serves to allow air bubbles unintentionally generated by stirring the liquid to escape toward the liquid surface of the liquid to be stirred 206. Removing air bubbles from the absorbance measurement area improves the reliability of the analysis.

[0028] As described above, the selection unit 205 switches which electrodes to drive among the electrodes provided in the plurality of ultrasonic wave generating sources 202. Therefore, even if the liquid volume of the liquid to be stirred 206 differs for each analysis item, the selection unit 205 selects and drives one or more electrodes corresponding to the liquid volume, thereby making it possible to irradiate the ultrasonic waves 108 to an appropriate height region. Note that the selection unit 205 may be, for example, a relay or a multiplexer.

[0029] The driving circuit 204 is controlled under the driving conditions set by the control unit 106, and applies a voltage to the electrode selected by the selection unit 205 to drive the corresponding ultrasonic wave generating source 202.

[0030] The waveform detection unit 203 detects the electrical waveform output from the electrodes of the ultrasonic generator 202 as it is driven. The electrical waveform detected by the waveform detection unit 203 may be a current waveform, an output waveform, or an instantaneous power waveform. For example, a current waveform is detected using a coil or a Hall element as a current flowing in response to a magnetic field generated in an electrical circuit. When the waveform detection unit 203 detects a current waveform, it has the advantage of being electrically isolated from the drive circuit 204 compared to when it detects a voltage waveform, but it has the disadvantage of lower accuracy. Furthermore, the instantaneous power waveform can be detected by providing a circuit with a digital or analog multiplier function in addition to detecting the current and voltage waveforms. When the waveform detection unit 203 detects an instantaneous power waveform, it has the advantage of being able to detect power that takes both voltage and current into account, but it has the disadvantage of requiring more time than detecting only voltage or current. The output waveform generated by the ultrasonic generator 202 as it is driven may also be detected using a sound pressure detection sensor or an acceleration sensor.

[0031] The harmonic component extraction unit 201 resolves the electrical waveform detected by the waveform detection unit 203 into frequency components and extracts the harmonic components. Here, harmonics refer to waves that have frequency components that are integer multiples of the frequency of the fundamental wave of the electrical waveform. Means for realizing the function of resolving the electrical waveform into frequency components include, for example, an FFT (Fast Fourier Transform) analyzer and a lock-in amplifier using phase-sensitive detection. Information regarding the signal strength of the harmonic components extracted by the harmonic component extraction unit 201 is fed back to the control unit 106, which determines whether the stirring state of the stirring unit 105 is good or bad based on this information.

[0032] Next, the relationship between the ultrasonic waves 108 output from ultrasonic wave source 202 and the quality of the stirring state will be described with reference to Figures 3A and 3B. In the following description, it is assumed that ultrasonic wave source 202 is a piezoelectric element. Figure 3A is a conceptual diagram showing the stirring state when the piezoelectric element performs an expansion and contraction motion using only the fundamental wave, and Figure 3B is a conceptual diagram showing the stirring state when the piezoelectric element performs an expansion and contraction motion including harmonics.

[0033] First, as shown in Figure 3A, when the piezoelectric element performs periodic expansion and contraction motion using only the fundamental wave cos(x), the ultrasonic wave 108 also becomes a wave of only the fundamental wave. At this time, the displacement information of the ultrasonic wave 108 propagates through the liquid to be stirred 206, which is the medium, but the water molecules 303 themselves in the reaction vessel 110 only perform a small reciprocating motion, as shown by arrow G, which is about the wavelength of the longitudinal wave. In other words, when the expansion and contraction motion of the piezoelectric element is only the fundamental wave, a sufficient stirring flow is not generated in the reaction vessel 110.

[0034] On the other hand, as shown in FIG. 3B, when the piezoelectric element undergoes an expansion / contraction motion that includes harmonics, the ultrasonic waves 108 also contain harmonics. Focusing on the frequency components of the harmonics, odd-order harmonics are expressed as the sum of periodic functions, while even-order harmonics contain DC components. Therefore, when the displacement information of the ultrasonic waves 108 propagates, water molecules 303 in the reaction vessel 110 move in a certain direction, as indicated by arrow H. In other words, the harmonic components contained in the expansion / contraction motion of the piezoelectric element contribute to the generation of an agitated flow in the reaction vessel 110. The agitator 105 can agitate the agitated liquid 206 without contact by intermittently irradiating bursts of ultrasonic waves 108 with this DC component. Here, the duty ratio and irradiation frequency of the ultrasonic waves are preferably set based on the dimensions of the reaction vessel 110.

[0035] Next, we will explain the relationship between the voltage applied to the piezoelectric element and the amount of expansion and contraction (amount of polarization) of the piezoelectric element. i The relationship of the polarization amount P to the polarization characteristic 405 is determined for each physical property of the piezoelectric element. Since the polarization characteristic 405 of a general piezoelectric element has hysteresis, the hysteresis characteristic will be specifically described.

[0036] When no voltage is applied to a piezoelectric element, the polarization is oriented in various directions to stabilize the state within the crystal. On the other hand, when voltage is applied to the piezoelectric element, this polarization becomes biased. As the voltage is further applied, the polarization aligns beyond the energy barrier, and reaches a point where it can no longer align, resulting in a saturation of the polarization amount. When the applied voltage is subsequently reduced, the polarization that has aligned beyond the energy barrier is more energetically stable if it remains in that state than if it were to cross the energy barrier again, making it more difficult to eliminate the polarization bias than when the applied voltage is increased. In other words, the polarization characteristics of a piezoelectric element exhibit hysteresis, with the amount of polarization differing when the applied voltage is increased and decreased.

[0037] FIG. 4A shows the applied voltage V i 4A is a graph showing the time change A of the polarization amount P and the frequency distribution A' of the polarization amount P when a sinusoidal voltage a is applied as a function of frequency. As shown in FIG. 4A, when a sinusoidal voltage a is applied to a piezoelectric element, the time change A of the polarization amount P becomes close to a sine wave, and when this is decomposed into frequency components, it can be seen that the signal strength of the harmonic components is weak, as shown in frequency distribution A'.

[0038] Here, the larger the polarization amount P, the larger the expansion and contraction amount of the piezoelectric element. Also, if the piezoelectric element contracts in response to a positive increase in the polarization amount P, the piezoelectric element expands in response to a negative increase in the polarization amount P. The relationship between the positive and negative increase in the polarization amount P and the expansion and contraction of the piezoelectric element is as follows: i It depends on the orientation of the crystal and the state of polarization within the crystal.

[0039] Therefore, as shown in Figure 4A, the applied voltage V i When the voltage is a sinusoidal wave a, the harmonic components contained in the polarization amount P are small, and the harmonic components contained in the expansion and contraction motion of the piezoelectric element are also small, so a sufficient stirring flow is not generated.

[0040] FIG. 4B shows the applied voltage V i4B is a graph showing the time change B of the polarization amount P and the frequency distribution B' of the polarization amount P when a sine wave voltage b is applied as a voltage V. As shown in FIG. 4B, when a sine wave voltage b is applied to a piezoelectric element, the time change B of the polarization amount P contains distortion, and when this is resolved into frequency components, it can be seen that the signal strength of the harmonic components is strong, as shown in frequency distribution B'. Therefore, as shown in FIG. 4B, when the voltage V applied to the piezoelectric element is i When the voltage is a sinusoidal wave b, the harmonic components contained in the polarization amount P are large, and the harmonic components contained in the expansion and contraction motion of the piezoelectric element are also large, so a sufficient stirring flow is generated.

[0041] In this way, even if the piezoelectric element has the same polarization characteristic 405, the applied voltage V i If the applied voltage V is different, the polarization amount P and the expansion / contraction movement may or may not contain harmonic components. This is because the polarization characteristic 405, which indicates how easily the piezoelectric element is polarized, and the applied voltage V i This means that even if the voltage (amplitude) applied to the piezoelectric element is increased, depending on the polarization characteristics 405 of the piezoelectric element, the expansion and contraction motion of the piezoelectric element may not contain harmonics, and ultrasonic waves that do not generate an agitating flow may be irradiated.

[0042] Next, we will explain how to determine whether the stirring state of the stirring unit 105 in the automatic analyzer 101 is good or bad. As mentioned above, a voltage is applied to the piezoelectric element, which is the ultrasonic wave generating source 202, and the piezoelectric element generates ultrasonic waves by polarization (expansion and contraction), but the waveform detecting unit 203 of this embodiment detects, via electrodes, electric waveforms such as voltage and current generated in the piezoelectric element due to polarization (expansion and contraction).

[0043] 5A is a graph showing a voltage waveform 501 (time change of voltage Vm) detected by waveform detection unit 203 and frequency components (frequency distribution of voltage Vm) resolved by harmonic component extraction unit 201 when the agitation flow is weak. As shown in FIG. 5A, when the voltage waveform 501 detected when the agitation flow is weak is resolved into orders of integer multiples of the fundamental wave, the fundamental wave (f Vi ) and the signal strength of the second harmonic (2f Vi) component signal strength 502 is less than threshold value 503. This confirms that ultrasonic waves that generate a stirring flow could not be output. Note that threshold value 503 corresponds to the signal strength of the second-order harmonic component, which is the minimum condition required for a good stirring state.

[0044] On the other hand, Figure 5B is a graph showing the voltage waveform 504 (time change of voltage Vm) detected by waveform detection unit 203 and the frequency components (frequency distribution of voltage Vm) resolved by harmonic component extraction unit 201 when the agitation flow is sufficient. As shown in Figure 5B, when the voltage waveform 504 detected when the agitation flow is sufficient is resolved into orders of integer multiples of the fundamental wave, it contains a second-order harmonic (2f Vi The signal intensity 505 of the ) component is equal to or greater than the threshold value 503. This confirms that ultrasonic waves that generate a stirring flow have been output.

[0045] Here, the reason why the electrical waveform output from the piezoelectric element contains many high-frequency components is thought to be because the piezoelectric element undergoes expansion and contraction movements that include distortion, as described above. Whether or not the piezoelectric element undergoes expansion and contraction movements that include distortion is determined by a combination of the material and structure of the piezoelectric element and the drive conditions (the voltage and frequency settings of the drive circuit 204). In other words, when the piezoelectric element is regarded as a load, even if the voltage that the drive circuit 204 intends to apply to the piezoelectric element does not contain harmonics, the entire system including the piezoelectric element may operate in a manner that includes harmonic components, depending on the physical properties of the piezoelectric element and the settings of the drive circuit 204.

[0046] Therefore, in this embodiment, the electrical waveform output from the piezoelectric element is broken down into frequency components, and the signal strength of the harmonic components is compared with a threshold value to determine whether the stirring state is good or bad. Furthermore, since only the second harmonic is compared with the threshold value during the determination, highly accurate determination is possible with a small computational load. However, the determination method is not limited to comparing the absolute values ​​of the signal strength of the harmonic components. For example, if the ratio of the signal strength of the second harmonic component to the signal strength of the fundamental wave is equal to or greater than a reference value, the stirring state may be determined to be good. In this way, by normalizing the magnitude of the electrical waveform output from the piezoelectric element and comparing it with a reference value, it becomes possible to make an appropriate pass / fail judgment according to the driving conditions. Furthermore, the harmonics used for pass / fail judgment may be not only the second order but also other even orders to further improve the judgment accuracy.

[0047] Fig. 6 is an example of a screen showing the result of determining whether the stirring state is good or bad, displayed on the output unit 109. When determining whether the stirring state is good or bad when each sample and reagent are stirred during an analysis sequence, the reliability of the analysis results is increased if the sample analysis results and the stirring state at the time of that analysis are output side by side on the output unit 109, as shown in Fig. 6. Furthermore, even if the stirring state is determined to be bad for some analyses, the user can determine that the results of the other analyses are valid if the stirring state for other analyses is determined to be good.

[0048] The above explanation has been given on determining whether the stirring state is good or bad. Next, we will describe how the control unit 106 automatically changes (automatically adjusts) the settings of the drive circuit 204 when it is determined that the stirring state is not good.

[0049] First, the drive conditions of the drive circuit 204 that can be changed by the control unit 106 include the frequency of the waveform applied to the piezoelectric element and the magnitude (waveform amplitude) of the electrical signal applied to the piezoelectric element. For example, as mentioned above, the frequency at which polarization (expansion / contraction) is most likely to occur varies depending on the structure (shape, dimensions, etc.) and material (elastic modulus, density, etc.) of the piezoelectric element. Therefore, if a satisfactory stirring state is not being achieved, changing the frequency of the applied voltage waveform can change the polarization response to the applied waveform and potentially add harmonic components to the expansion / contraction motion of the piezoelectric element. Similarly, changing the magnitude of the applied electrical signal can change the polarization response and cause the expansion / contraction motion of the piezoelectric element to include harmonic components. However, if the expansion / contraction motion of the piezoelectric element includes harmonic components, the drive conditions that can be changed are not limited to frequency and amplitude. For example, methods such as applying an offset to the applied waveform or intentionally distorting the applied waveform can also be used.

[0050] Here, piezoelectric elements, primarily PZT, which have been commonly used as ultrasonic source 202, are thought to have physical properties that generate high harmonic component intensity over a wide frequency range and are prone to distortion with time-dependent changes in expansion and contraction. Therefore, in an automatic analyzer 101 using such an ultrasonic source 202, it is possible to determine the quality of the stirring state by monitoring the intensity, such as the amplitude, of the waveform output from ultrasonic source 202 or by monitoring the resonance frequency through impedance measurement. However, if ultrasonic source 202 is made of a material other than PZT, a stirring flow may not be generated even if the output waveform from ultrasonic source 202 is strong, or a clear frequency resonance point may not be detected by impedance measurement of ultrasonic source 202.

[0051] Therefore, in the automatic analyzer 101 of this embodiment, the harmonic components that contribute to the generation of an agitated flow are monitored, so that the quality of the agitation state can be determined with high accuracy regardless of the material or structure of the ultrasonic source 202, improving the reliability of the automatic analyzer. As a result, a material that is less likely to generate distortion can be used as the ultrasonic source 202, and even if the ultrasonic source 202 is replaced, for example, from a lead-containing material to a lead-free material, a highly reliable automatic analyzer can be provided. Note that by monitoring not only the harmonic components output from the ultrasonic source 202 but also the active power consumed by the ultrasonic source 202, the agitation state can be determined with higher accuracy.

[0052] Next, the overall operation from determining whether the stirring state is good or bad to adjusting the drive conditions will be described. FIG. 7 is a flowchart showing the operation when the stirring state determination and automatic adjustment modes are executed. In this embodiment, the parameters that the control unit 106 can change are the magnitude (voltage setting value) and frequency (frequency setting value) of the voltage that the drive circuit 204 applies to the piezoelectric element. The voltage setting value and frequency setting value are selected from a plurality of discrete values, including initial values. The initial values ​​of the voltage setting value and frequency setting value are stored in advance in the control unit 106 based on the drive conditions under which generation of a stirring flow was confirmed during the development stage of the automatic analyzer 101.

[0053] 7, when the mode for determining whether the stirring state is good or bad is started, the specimen dispensing mechanism 114 dispenses water into the reaction vessel 110, and the reaction vessel 110 moves to the stirring position by the rotation of the reaction disk 111 (step S1). Note that, as long as a liquid necessary for determining the stirring state is dispensed into the reaction vessel 110, it may be something other than water.

[0054] Thereafter, control unit 106 applies a voltage to the piezoelectric element via drive circuit 204, and causes waveform detection unit 203 to detect the electrical waveform output from the piezoelectric element in response to the applied voltage (step S2). Next, harmonic component extraction unit 201 resolves the electrical waveform detected by waveform detection unit 203 into frequency components to extract second-order harmonic components (step S3). Control unit 106 then determines whether the signal strength of the second-order harmonic components extracted by harmonic component extraction unit 201 is equal to or greater than a threshold (step S4).

[0055] If it is determined in step S4 that the value is less than the threshold value, control unit 106 further determines whether the number of times it has been determined to be less than the threshold value is one (step S5). If the number of times is two or more, automatic adjustment is not possible, so control unit 106 outputs an alarm to output unit 109 and the pass / fail determination mode ends (step S6).

[0056] On the other hand, if it is determined in step S5 that the number of times is one, the control unit 106 changes the voltage setting value of the drive circuit 204 to the maximum value (step S7). Furthermore, the control unit 106 executes steps S2 and S3 for all settable frequencies and acquires the harmonic components extracted at each frequency (step S8). The control unit 106 then sets the frequency at which the signal strength of the harmonic components is maximum as the new set frequency after adjustment (step S9), and returns to step S2.

[0057] Next, if it is determined in step S4 that the voltage setting is equal to or greater than the threshold value, the control unit 106 further determines whether the voltage setting is at the maximum value (step S10). If the voltage setting is not the maximum value, the voltage setting remains at the initial value or the current value and automatic adjustment is not required, so the control unit 106 outputs the stirring state determination result and a message indicating that automatic adjustment has ended (not required) to the output unit 109 (step S11).

[0058] On the other hand, if it is determined in step S10 that the voltage setting value is the maximum value, the control unit 106 changes the voltage setting value of the drive circuit 204 from the maximum value to the initial value (step S12). Furthermore, the control unit 106 uses the value changed in step S9 as the frequency setting value, executes steps S2 and S3 again, and acquires the second-order high-frequency component extracted at that time (step S13). Then, the control unit 106 determines whether the second-order high-frequency component acquired in step S13 is equal to or greater than a threshold value (step S14).

[0059] If it is determined in step S14 that the voltage is less than the threshold, the control unit 106 increases the voltage setting value of the drive circuit 204 by one step from the initial value (step S15) and executes step S13 again, and the same operation is repeated until it is determined in step S14 that the voltage is greater than or equal to the threshold.

[0060] If it is determined in step S14 that the voltage setting value is equal to or greater than the threshold value, the control unit 106 sets the voltage setting value at that time and the frequency setting value changed in step S9 as new setting values ​​after automatic adjustment. At this time, the control unit 106 outputs the determination result of the stirring state and a message that the automatic adjustment has been completed to the output unit 109 (step S11).

[0061] As described above, if the stirring state is determined to be poor, i.e., if the harmonic components do not satisfy the predetermined conditions, the control unit 106 automatically changes the voltage and frequency settings of the drive circuit 204 to enable good stirring, thereby eliminating the need for a maintenance person to adjust the stirring unit 105. Furthermore, during automatic adjustment, the voltage setting is changed to the smallest possible value, thereby preventing increases in power consumption and deterioration of the piezoelectric element. Furthermore, if changing the settings of the drive circuit 204 is not sufficient to resolve the issue, i.e., if the harmonic components do not satisfy the predetermined conditions even when the voltage of the drive circuit 204 is set to the maximum and the frequency is set to a frequency that provides high output, the control unit 106 outputs an alarm to the output unit 109, thereby prompting a maintenance person to take action.

[0062] As mentioned above, the initial voltage and frequency settings are determined based on the drive conditions that confirmed satisfactory mixing during the development phase of the automated analyzer 101. In other words, the automatic adjustment of the drive conditions described with reference to FIG. 7 is intended to minimize the impact on mixing due to individual differences in the piezoelectric elements and changes over time. Therefore, it is desirable to perform the automatic adjustment mode not for each mixing operation during an analysis sequence, but rather when initializing the automated analyzer 101 or before the start of an analysis sequence. Performing automatic adjustment for each mixing operation during analysis not only reduces the overall throughput of the automated analyzer 101, but also requires reconfiguring the program used in the sequence processing in order to interrupt and perform automatic adjustment if the mixing status is determined to be poor. However, the mode for determining whether the mixing status is satisfactory may be performed for each mixing operation during an analysis sequence to ensure the reliability of the analysis results.

[0063] As described above, the selector 205 can select one or more piezoelectric elements to drive from among the multiple piezoelectric elements constituting the ultrasonic wave generating source 202. If the physical properties of each piezoelectric element vary, the drive conditions of the drive circuit 204 for distorting the expansion and contraction motion will differ for each piezoelectric element. Furthermore, when multiple piezoelectric elements are driven simultaneously, the characteristics of the entire system will also change. However, as in this embodiment, the stirring state is determined and the drive conditions are adjusted based on the signal strength of the high-frequency component extracted from the electrical waveform actually output when the selected piezoelectric element is driven, so that a stirring flow can be reliably generated. As a result, the sample and reagent can be reliably stirred by ultrasound, improving the reliability of the automated analyzer 101. [Explanation of symbols]

[0064] 101...automatic analyzer, 102...sample, 103...reagent, 104...analysis unit, 105...stirring unit, 106...control unit, 107...interface, 108...ultrasound, 109...output unit, 110...reaction vessel, 111...reaction disk, 112...reaction tank, 113...sample vessel, 114...sample dispensing mechanism, 115...reagent vessel, 116...reagent disk, 117...reagent dispensing mechanism, 118...light source, 119...photometer, 120...cleaning mechanism, 130...input unit, 201...harmonic component extraction unit, 202...ultrasonic wave generation source, 203...waveform detection unit, 204...drive circuit, 205...selection unit, 206...liquid to be stirred, 207...reflector, 208...heat retention medium, 303...water molecules, 405...polarization characteristics, 501, 504...voltage waveform, 502, 505...signal intensity, 503...threshold

Claims

1. a stirring unit for stirring the sample and the reagent; an analysis unit that performs component analysis of the specimen using a reaction solution of the specimen and the reagent; a control unit that controls the stirring unit and the analysis unit, In an automatic analyzer, the stirring unit includes an ultrasonic wave generating source that generates ultrasonic waves, a drive circuit that drives the ultrasonic wave generating source, and a waveform detection unit that detects an electric waveform output from the ultrasonic wave generating source in response to the drive, the stirring unit further includes a harmonic component extracting unit that extracts harmonic components of a fundamental wave that drives the ultrasonic wave generating source from the electrical waveform detected by the waveform detecting unit, The automatic analyzer is characterized in that the control unit determines whether the stirring state of the stirring unit is good or bad based on the signal intensity of the harmonic components extracted by the harmonic component extraction unit.

2. The automatic analyzer according to claim 1, The automatic analyzer is characterized in that the control unit automatically changes the set value of the frequency of the drive circuit when the harmonic components extracted by the harmonic component extraction unit do not satisfy predetermined conditions.

3. The automatic analyzer according to claim 2, An output unit that outputs a result of determining whether the stirring state is good or bad is further provided, The automatic analyzer is characterized in that the control unit outputs an alarm to the output unit if the harmonic components do not satisfy a predetermined condition even when the set value of the voltage of the drive circuit is changed to the maximum.

4. The automatic analyzer according to claim 1, the harmonic component extraction unit decomposes the electrical waveform detected by the waveform detection unit into frequency components and extracts second-order harmonic components; The automatic analyzer is characterized in that the control unit determines whether the stirring state of the stirring unit is good or bad based on the signal intensity of the second-order harmonic component extracted by the harmonic component extraction unit.

5. The automatic analyzer according to claim 4, The control unit determines that the stirring condition of the stirring unit is good when the ratio of the signal strength of the second harmonic to the signal strength of the fundamental wave of the electrical waveform is equal to or greater than a reference value.

6. The automatic analyzer according to claim 1, The automatic analyzer is characterized in that the ultrasonic wave generating source is a piezoelectric element made of a material that does not contain lead.

Images