JP3746239B2 - Automatic analyzer - Google Patents

Description

[0001]
BACKGROUND OF THE INVENTION
The present invention includes an analysis unit that analyzes a component of a sample to be analyzed using a reagent, a stirring unit that stirs the sample and the reagent, a control unit that comprehensively controls the analysis unit, the stirring unit, and the like. BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an automatic analyzer having a function of stirring a reagent and a sample by using an ultrasonic wave generation source as a sound source and utilizing ultrasonic vibration, acoustic flow, acoustic radiation pressure, and the like.
[0002]
[Prior art]
In a conventional agitation unit of an automatic analyzer, a method of mixing and agitating a specimen and a reagent by generally putting a spatula-like agitation rod in a reaction vessel and rotating or reciprocating the reaction vessel is common. However, if the stir bar cannot be washed sufficiently, the reagent or sample attached to the stir bar may cause a phenomenon called carry-over that affects the next analysis result. Agitation has been proposed.
[0003]
While stirring using ultrasonic waves has the advantage of not causing a carry-over problem, there is a risk that sufficient stirring cannot be achieved unless the irradiation conditions for the object to be stirred are adjusted well. Various methods have been proposed. For example, in Japanese Patent Laid-Open No. 2001-124784, a sensor for measuring the intensity of generated ultrasonic waves is installed, and the frequency generated by the ultrasonic wave generation source is changed according to the sensor output, thereby providing a supersonic wave having a constant intensity. A technique is disclosed in which uniform stirring can always be performed in such a manner as to obtain a sonic wave output.
[0004]
[Problems to be solved by the invention]
Providing the ultrasonic sensor separately from the ultrasonic wave generation source may cause a decrease in reliability and an increase in cost due to a complicated mechanism.
[0005]
When stirring with ultrasonic waves is to be performed efficiently, a reflective material may be installed in a region irradiated with ultrasonic waves, which may make it impossible to install an external sensor.
[0006]
In addition, an external sensor that measures the radiation pressure of ultrasonic waves and the flow velocity induced by the ultrasonic waves is easily influenced by physical conditions such as an effective measurement region, an angle, and a distance from a sound source, and requires high positional accuracy.
[0007]
A temperature sensor or the like is also effective in measuring ultrasonic irradiation energy, but is insufficient as a stirring state monitor because of a slow response speed.
[0008]
Furthermore, in a system in which a plurality of electrodes are used and the irradiation position of the ultrasonic wave is changed, the cost increases because it is necessary to change the sensor position or to provide a sensor for each electrode.
[0009]
An object of the present invention is to provide an automatic analyzer including a stirring mechanism that can obtain an ultrasonic output having a constant intensity with a simple configuration.
[0010]
[Means for Solving the Problems]
The configuration of the present invention for achieving the above object is as follows.
[0011]
An analysis unit that performs a component analysis of a sample by reacting a reagent with a sample to be analyzed, an ultrasonic source that generates ultrasonic waves using the ultrasonic source as a sound source, and a drive circuit that drives the ultrasonic source An automatic analyzer including a stirring unit, a waveform detection unit that detects a waveform of an ultrasonic wave generated from an ultrasonic wave generation source, and the drive circuit based on a detection waveform from the waveform detection unit The automatic analysis apparatus is provided with a control unit for controlling the waveform, and the waveform detection unit is formed integrally with the ultrasonic wave generation source or the drive circuit.
[0012]
That is, the waveform detection unit is separate from the ultrasonic wave generation source or drive circuit as in the past, for example, the surface of the reaction container in which the object to be stirred is accommodated, or the irradiated ultrasonic wave reaches the object to be stirred through. It is not installed at the site, but is provided integrally with the ultrasonic wave generation source or the drive circuit. This simplifies the configuration and simplifies the adjustment of the driving frequency and driving voltage required for each ultrasonic wave generation source. A function that changes the drive waveform that drives the ultrasonic wave source, changes the intensity of the generated ultrasonic wave, and changes the stirring state based on the signal obtained from the waveform detector that detects the waveform generated from the ultrasonic wave source The stirring part which added was added.
[0013]
DETAILED DESCRIPTION OF THE INVENTION
The use of ultrasonic waves in the stirrer of the automatic analyzer can stir samples and reagents without contact, and does not contaminate other samples or reagents, and does not require a stirrer, reducing the size of the reaction vessel There is an advantage that the amount of the sample and the reagent can be reduced, but when the ultrasonic wave is generated in the ultrasonic wave generation source and stirring is performed by the ultrasonic wave, the ultrasonic wave sufficient for stirring the sample and the reagent. In order to generate the sound pressure, it is necessary to supply the piezoelectric element electrode, which is a component of the sound source, with electric power having a voltage amplitude that generates a sufficient amount of displacement at the mechanical resonance frequency at which the displacement is maximum. Considering that the resonance frequency differs due to variations in the characteristics of the ultrasonic source, even if the ultrasonic source is driven by supplying power with the same amplitude and frequency, the sound pressure intensity of the generated ultrasonic wave differs. , There is a difference in the stirring state Door can be considered.
[0014]
The variation of the resonance frequency can be absorbed by sweeping the frequency within the range where the resonance frequency is estimated to exist. However, regarding the voltage, if multiple ultrasonic sources are to be driven simultaneously, A drive waveform may change due to a decrease in impedance and interaction with adjacent electrodes as a load, and the intensity of the generated ultrasonic waves may change.
[0015]
In addition, it is conceivable that the characteristics of the ultrasonic wave source change due to scratches, depolarization, deposits on the surface of the sound source, etc. that are acquired after the ultrasonic wave source has been mounted.
[0016]
Furthermore, even during ultrasonic stirring, bubbles stick to the container containing the target to be stirred, and the driving waveform may change and the stirring state may change by inhibiting the swirling flow caused by the acoustic radiation pressure. .
[0017]
The purpose of the present invention is to increase the reliability of analysis results regardless of the difference in the ultrasonic generation source used for ultrasonic stirring, to reduce complicated adjustment work, and to change the stirring state when performing ultrasonic stirring. It is to detect and increase the reliability of the automatic analyzer.
[0018]
Hereinafter, the present invention will be described in detail with reference to examples.
[0019]
Example 1
FIG. 1 is a schematic configuration diagram of an embodiment of an automatic analyzer according to the present invention.
[0020]
In FIG. 1, the automatic analyzer 101 includes a control unit 102, a storage unit 103, an analysis unit 104, and a stirring unit 105.
[0021]
The control unit 102 controls the operation of each unit by an electronic circuit or a storage device that performs detailed operation control of each unit.
[0022]
The storage unit 103 includes a sample storage unit 107 that stores a sample 106 and a reagent storage unit 114 that stores a reagent 109.
[0023]
The analysis unit 104 transmits light from the light source 117 to the reaction of the sample 106 and the reagent 109 in the reaction container 108 of the analysis unit, and performs composition analysis with the spectroscope 118.
[0024]
The agitation unit 105 agitates the sample discharged from the sample storage unit 107 into the reaction container 108 and the reagent 109 discharged from the reagent storage unit 114 into the reaction container 108 using the ultrasonic wave 111 generated by the piezoelectric element 110.
[0025]
The reaction vessel 108 in the stirring unit 105 and the analysis unit 104 is immersed in a heat retaining medium 113 typified by water stored in the reaction tank 112 and is maintained at a constant temperature.
[0026]
The plurality of reaction vessels 108 are arranged on the reaction disk 115, and are rotated or moved together with the reaction disk 115 by controlling the reaction disk motor 116 with the control unit 102. Go back and forth.
[0027]
FIG. 2 is a schematic configuration diagram of the stirring unit.
[0028]
An electrode provided in the same piezoelectric element is used as the applied waveform detecting unit 119 that can detect the applied waveform to the piezoelectric element 110 of the stirring unit 105.
[0029]
The stirring unit 105 controls the driving circuit 120 under the driving conditions set by the control unit 102 to drive the piezoelectric element 110 and irradiate the ultrasonic wave 111.
[0030]
The piezoelectric element 110 is attached to the reaction vessel 112 and uses water as the heat retaining medium 113 as a transmission medium for the ultrasonic wave 111. Considering the risk of leakage to the heat retaining medium 113 when a failure occurs, the surface of the piezoelectric element 110 on the side in contact with the heat retaining medium 113 is a GND electrode, and an insulating layer is provided to contact the heat retaining medium 113. Structure.
[0031]
In order to obtain a good stirring state under the use conditions in the automatic analyzer 101 in which the amount of liquid to be stirred changes for each analysis, it is necessary to change the position where the ultrasonic wave 111 is irradiated depending on the amount of liquid. The element 110 includes a plurality of electrodes on a single piezoelectric material, and simultaneously includes a water leakage detection electrode 203 and an applied waveform detection electrode 202. In the water leakage detection and the applied waveform detection, any electrode can be selected by the piezoelectric element selection unit 201 configured by a switch or the like.
[0032]
The piezoelectric element 110 is mechanically expanded and contracted by the voltage applied to the electrode, thereby generating an ultrasonic wave 111. At the same time, a voltage is also generated in the applied waveform detection electrode 202 provided in the piezoelectric element 110 by the piezoelectric action. The voltage generated by the applied waveform detector 119 is measured and fed back to the controller 102.
[0033]
The control unit 102 compares the comparison waveform set from the output waveform of the applied waveform detection unit 119 when the necessary stirring state is obtained in advance with the current output waveform, and enters the range in which the similarity between both waveforms is set. Until then, the voltage applied to the piezoelectric element 110 is adjusted based on the command of the control unit 102.
[0034]
The piezoelectric element selection unit 201 selects an electrode that is at a height to be irradiated with the ultrasonic wave 111 according to a command from the control unit 102 according to the liquid amount. Further, the connection with the drive circuit 120 is cut off when the irradiation with the ultrasonic wave 111 is unnecessary so that the stirring in the reaction vessel 108 that does not require stirring is not performed. Furthermore, before performing the next irradiation, the leak detection electrode 203 and the leak detection unit 204 for checking whether there is any leak in the piezoelectric element 110 are connected.
[0035]
FIG. 3 is a schematic diagram of the relationship between the frequency and electrical impedance of the piezoelectric element.
[0036]
The frequency characteristic of the ultrasonic intensity possessed by the piezoelectric element has a mechanical resonance frequency that becomes maximum at a certain frequency. In the case of a piezoelectric element, the mechanical resonance frequency exists in the vicinity of the resonance point 303 of the electrical impedance, but is slightly different depending on each piezoelectric element 110, and in particular, has a sharp peak in the frequency characteristic of ultrasonic intensity, When using a piezoelectric material having a large variation in the resonance point 303 of the piezoelectric element 110, even if a sound pressure sufficient to mix and stir the specimen 106 and the reagent 109 is obtained with a certain piezoelectric element, the same production process is used. Even when the same frequency is applied to another piezoelectric element obtained, a sound pressure sufficient to stir the specimen 106 and the reagent 109 may not be obtained.
[0037]
In addition, even between electrodes configured on the same piezoelectric material, an electrode near the center of the piezoelectric material arranged at a position where it can easily move mechanically and an electrode configured around the piezoelectric material that is easily restrained mechanically The same impedance is not obtained even when the same voltage is applied.
[0038]
Furthermore, when simultaneously driving a plurality of electrodes on the same piezoelectric material, the impedance characteristic 305 with a plurality of electrodes has a lower electrical impedance than the impedance characteristic 304 with a single electrode, and the resonance point 303 Tend to be lower.
[0039]
When the drive circuit 120 is configured by a separately-excited oscillation type power amplifier, it is also possible to provide the agitation unit 105 at a plurality of locations and simultaneously drive the plurality of electrodes of the plurality of piezoelectric elements 110 with one drive circuit 120. However, both the resonance point and the output voltage change depending on the number of loads to be driven.
[0040]
FIG. 4 is a schematic diagram of a method for changing the oscillation frequency applied to the piezoelectric element.
[0041]
As means for absorbing the change of the resonance point 303, when the change width of the resonance point 303 is known in advance, a frequency modulation waveform such as a linear sweep using a triangular wave so as to cover from the lowest frequency fmin to the highest frequency fmax. By giving 402, it is possible to forcibly change the oscillation frequency, but there is a time during which the piezoelectric element 110 is driven at a frequency other than the mechanical resonance frequency capable of generating the strongest ultrasonic wave 111. That is, the time-averaged ultrasonic intensity is reduced.
[0042]
It is possible to improve the stirring efficiency by generating liquid pulsation in the reaction vessel 108 by lowering the modulation frequency for applying frequency modulation, changing the applied voltage ON / OFF, or changing the amplitude to large or small. In addition, it is necessary to take into consideration that the case where stirring is not sufficient even with assistance due to the pulsation effect, and the output intensity of the ultrasonic wave 111 is monitored directly or indirectly, and feedback is applied to adjust the output intensity. This is the fundamental solution for creating stable agitation.
[0043]
FIG. 5 is a schematic diagram of an example of a detection waveform during stirring.
[0044]
The piezoelectric element 110 expands and contracts due to a piezoelectric action when a voltage is applied, and generates an ultrasonic wave 111, but simultaneously generates a voltage due to an external force. Since the ultrasonic wave 111 is reflected at a portion where there is a difference in acoustic impedance, bubbles are present in the reaction vessel 108 and the ultrasonic waves reflected from the bubbles are inhibited in a state where the swirl flow caused by the acoustic radiation pressure is inhibited. Since the sound wave 111 returns to the piezoelectric element 110, the applied waveform changes due to the influence of the reflected wave. When the bubble starts to rotate in the reaction vessel 108, the influence of the reflected wave disappears, and the applied waveform becomes equal to the waveform intended to be applied to the piezoelectric element 110.
[0045]
In order to obtain a stable stirring state, control may be performed so that the applied waveform is observed when the swirling flow generated by the acoustic radiation pressure is stably generated, the applied voltage is weak, or the system If the characteristics of the waveform when the overall impedance is high and the swirl flow caused by the acoustic radiation pressure is not generated are shown, the applied voltage is increased to approach the applied waveform 503 in a good stirring state.
[0046]
Further, by monitoring the applied waveform, if the applied waveform 503 in a good stirring state is not observed, it can be known that a stirring failure has occurred.
[0047]
FIG. 6 is an example of a procedure for performing output control based on the detected waveform.
[0048]
When the sampling frequency and the processing capability are sufficient as compared with the frequency of the ultrasonic drive signal, a stable stirring state can be obtained by performing output control according to the following procedure.
Step 1 (S1)
The applied waveform detector 119 for one cycle samples the detected waveform.
Step 2 (S2)
Normalizes the amplitude and frequency from the maximum and minimum values of the detected waveform.
Step 3 (S3)
A detection waveform obtained when the known stirring state is good is set in advance as a reference, and is compared with the detected waveform.
Step 4 (S4)
Extract differences from the reference.
Step 5 (S5)
A feature point is searched from the extracted difference. If the agitation state is good, there is almost no difference from the reference, and when bubbles are blocking the swirling flow, there are often local maximum and minimum points other than the peak within one cycle of the waveform. A big change appears in the difference.
[0049]
When the element loses piezoelectricity due to thermal destruction or the like, it does not take the shape of a sine wave, and the difference is seen from the reference other than the peak point.
Step 6 (S6)
When the detected waveform indicates a good stirring state, the current driving state is maintained.
Step 7 (S7)
In the case where the feature that the bubbles hinder the swirling flow is observed, it is necessary to eliminate the bubbles that hinder the swirling flow, it is necessary to temporarily increase the output, and the applied voltage amplitude is increased.
[0050]
Even after the amplitude of the applied voltage is increased, the process returns to step 1 (S1), and the current state is grasped from the detected waveform, and the control is advanced.
Step 8 (S8)
When a waveform showing the characteristics of the destruction of the element is seen, the stirring state does not change even if the applied voltage amplitude is increased, resulting in uniform stirring failure.
[0051]
If the element is destroyed, the element is stopped and an element destruction error is displayed.
[0052]
(Example 2)
FIG. 7 is a schematic diagram of a configuration for performing ultrasonic output adjustment in a circuit manner.
[0053]
When the drive circuit is composed of SEPP, the drive circuit 120 includes an oscillation unit 701, a preamplifier 702, a bias circuit 703, and the like.
[0054]
The oscillation unit 701 is a part that oscillates a basic waveform that is the basis of a voltage waveform that is finally applied to the piezoelectric element 110, and has a function of outputting various oscillation waveforms.
[0055]
The preamplifier 702 is a part that performs voltage amplification, and is configured by a plurality of amplification stages in some cases.
[0056]
The bias circuit 703 is a circuit for matching the voltage waveform amplified by the preamplifier 702 with the operating point of the subsequent FET in order to perform current amplification by push-pull operation.
[0057]
The electric power applied to the piezoelectric element 110 may be directly supplied to the piezoelectric element 110 from the current amplification stage, but a transformer 704 is used to obtain a large voltage amplitude and to perform impedance matching with the piezoelectric element 110. It is also possible.
[0058]
In order to adjust the ultrasonic output in a circuit, the applied waveform detection electrode 202 may be provided in the piezoelectric element 110 as in the first embodiment. However, when the transformer 704 is used, another transformer 704 is provided. It is possible to detect a current waveform to the piezoelectric element 110 by providing a winding.
[0059]
FIG. 8 is a schematic diagram of a configuration for adjusting the ultrasonic output by detecting the drive current.
[0060]
If the transformer 704 in FIG. 7 is regarded as a current detection unit 805 in a broad sense, when the current detection unit 805 supplies power from the drive circuit 120 to the piezoelectric element 110, the current detection unit 805 is an electromagnetic wave when a closed magnetic circuit is configured with metal or ferrite. It is possible to detect a current by utilizing the fact that a current flows through a conductor that intersects the same closed magnetic circuit by induction.
[0061]
When the driving frequency of the piezoelectric element 110 is fast and the digital processing is not in time, it is possible to perform an averaging process by hardware and evaluate the stirring force using the power supplied to the piezoelectric element 110.
[0062]
A current detection unit 805 detects a supply current to the piezoelectric element 110, and a current / voltage conversion unit 801 converts the current into a voltage. The converted voltage is rectified by the rectification unit 802, shaped by the filter unit 803, and then integrated by the integration unit 804 to detect the average current.
[0063]
If the voltage applied to the piezoelectric element 110 is determined in advance, the average power can be calculated by multiplying the average voltage and the average current.
[0064]
It is possible to perform control such as estimating the stirring force from the average power and increasing the applied voltage if the average power is insufficient.
[0065]
In addition, when sufficient electric power cannot be supplied to the agitation without performing the control, a usage method of issuing a warning that the agitation is insufficient may be considered.
[0066]
Although there is a correlation between the actual stirring force and the average power, if it is considered to evaluate the stirring force more strictly, it is necessary to detect the effective power.
[0067]
FIG. 9 is a schematic diagram of a detected current waveform depending on the state.
[0068]
When the ultrasonic output intensity is large, the detected current amplitude is large, and when the ultrasonic output intensity is small, the detected current amplitude is small. Even if the current waveform at the lowest strength that can be stirred is compared with the detected current waveform when the element is destroyed, the amplitude of the detected current waveform when the element is destroyed is smaller. It is possible to sufficiently monitor the state of the element even by monitoring only the amplitude.
[0069]
When the state of an element is monitored with a voltage waveform, the difference in voltage amplitude between a normal state and a breakdown is extremely small, so that detection of the current waveform is effective for monitoring the state of the element.
[0070]
【The invention's effect】
According to the present invention, in the automatic analyzer, the stirrer that stirs the sample and the reagent by the ultrasonic wave is provided with the applied waveform detection unit that detects the applied waveform of the ultrasonic source, and the output control is performed using the applied waveform. This reduces the effects of changes in electrical characteristics due to the effects of the combined load when there are variations in the electrical characteristics of individual ultrasonic sources or when multiple ultrasonic sources are driven simultaneously. In addition, it is possible to simplify the adjustment operation of the stirring unit and to stabilize the stirring state by stabilizing the output of the ultrasonic wave, thereby improving the reliability of the analysis.
[0071]
In addition, by providing an applied waveform detector, it is possible to detect the intensity of the generated ultrasound due to deterioration of the ultrasound generation source, etc., detect the presence or absence of ultrasound output when not needed, and detect whether the stirring state is good or not. The reliability of the apparatus can be increased.
[Brief description of the drawings]
FIG. 1 is a schematic configuration diagram of an embodiment of an automatic analyzer.
FIG. 2 is a schematic configuration diagram of a stirring unit.
FIG. 3 is a schematic diagram showing the relationship between the frequency and electrical impedance of a piezoelectric element.
FIG. 4 is a schematic view of a method for changing an oscillation frequency applied to a piezoelectric element.
FIG. 5 is a schematic diagram illustrating an example of a detection waveform during stirring.
FIG. 6 shows an example of a procedure for performing output control based on a detected waveform.
FIG. 7 is a schematic diagram of a configuration for performing ultrasonic output adjustment in a circuit manner.
FIG. 8 is a schematic diagram of a configuration for detecting a drive current and adjusting an ultrasonic output.
FIG. 9 is a schematic diagram of a detected current waveform according to a state.
[Explanation of symbols]
DESCRIPTION OF SYMBOLS 101 ... Automatic analyzer, 102 ... Control part, 103 ... Storage part, 104 ... Analysis part, 105 ... Stirring part, 106 ... Sample, 107 ... Sample storage part, 108 ... Reaction container, 109 ... Reagent, 110 ... Piezoelectric element, DESCRIPTION OF SYMBOLS 111 ... Ultrasonic wave, 112 ... Reaction tank, 113 ... Insulation medium, 114 ... Reagent storage part, 115 ... Reaction disk, 116 ... Reaction disk motor, 117 ... Light source, 118 ... Spectroscope, 119 ... Applied waveform detection part, 120 ... Drive circuit 201 ... piezoelectric element selection unit 202 ... applied waveform detection electrode 203 ... leakage detection electrode 204 ... leakage detection unit 301 ... impedance axis 302 ... frequency axis 303 ... resonance point 304 ... single electrode Impedance characteristics of a plurality of electrodes, 401, 501, 904, time axis, 402, frequency modulation waveform, 502, voltage axis, 50 ... Applied waveform in a good stirring state, 504 ... Applied waveform in a state where stirring is inhibited by bubbles, 701 ... Oscillator, 702 ... Preamplifier, 703 ... Bias circuit, 704 ... Transformer, 801 ... Current-voltage converter, 802: Rectification unit, 803: Filter unit, 804 ... Integration unit, 805 ... Current detection unit, 901 ... Current detection current waveform, 902 ... Output low detection current waveform, 903 ... Element disclosed disclosure current waveform, 905 ... Current Axis, fmax... Highest frequency, fc... Center frequency, fmin... Lowest frequency, S1 to S8.

Claims (7)

An agitation unit including an ultrasonic wave generation source that generates ultrasonic waves, and a drive circuit that drives the ultrasonic wave generation source;
A waveform detection unit for detecting a drive current supplied from the drive circuit to the ultrasonic wave generation source by being electrically insulated from the drive current by electromagnetic induction;
A control unit for controlling the drive circuit based on a detection waveform from the waveform detection unit;
An automatic analyzer characterized by comprising: The automatic analyzer according to claim 1, wherein
The ultrasonic generator is supplied with driving power through a transformer, and the waveform detector is magnetically coupled to the transformer. The automatic analyzer according to claim 1 or 2,
The control unit compares the signal waveform detected by the waveform detection unit with a signal waveform obtained when a necessary stirring state prepared in advance is obtained, and controls the drive circuit based on the comparison result. Automatic analyzer. The automatic analyzer according to claim 3,
The automatic analysis apparatus characterized in that the comparison in the control unit performs pattern matching and adjusts the voltage applied to the ultrasonic wave generation source so that the similarity between both waveforms to be compared falls within a preset range. . In the automatic analyzer in any one of Claims 1-4,
An automatic analyzer that estimates a stirring state using a signal waveform of the waveform detector. The automatic analyzer according to claim 1, wherein
The ultrasonic wave generation source is a piezoelectric element including a plurality of electrodes for applying driving power, and the number of electrodes to which the driving power of the piezoelectric element is applied is determined based on the signal waveform detected by the waveform detection unit. An automatic analyzer characterized by changing. In the automatic analyzer in any one of Claims 1-6,
An automatic analyzer characterized in that the waveform detection unit measures the output waveform from the ultrasonic wave generation source even during the time when no ultrasonic irradiation is required, and detects the presence or absence of the generation of ultrasonic waves.

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