WO2001077691A1 - Chemical analyzer - Google Patents
Chemical analyzer Download PDFInfo
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- WO2001077691A1 WO2001077691A1 PCT/JP2000/002320 JP0002320W WO0177691A1 WO 2001077691 A1 WO2001077691 A1 WO 2001077691A1 JP 0002320 W JP0002320 W JP 0002320W WO 0177691 A1 WO0177691 A1 WO 0177691A1
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- WIPO (PCT)
- Prior art keywords
- sound wave
- reaction vessel
- liquid
- reagent
- sound
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- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Classifications
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/02—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F31/00—Mixers with shaking, oscillating, or vibrating mechanisms
- B01F31/80—Mixing by means of high-frequency vibrations above one kHz, e.g. ultrasonic vibrations
- B01F31/87—Mixing by means of high-frequency vibrations above one kHz, e.g. ultrasonic vibrations transmitting the vibratory energy by means of a fluid, e.g. by means of air shock waves
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F2101/00—Mixing characterised by the nature of the mixed materials or by the application field
- B01F2101/23—Mixing of laboratory samples e.g. in preparation of analysing or testing properties of materials
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N2035/00465—Separating and mixing arrangements
- G01N2035/00524—Mixing by agitating sample carrier
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N2035/00465—Separating and mixing arrangements
- G01N2035/00534—Mixing by a special element, e.g. stirrer
- G01N2035/00554—Mixing by a special element, e.g. stirrer using ultrasound
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/02—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
- G01N35/025—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations having a carousel or turntable for reaction cells or cuvettes
Definitions
- the present invention relates to a chemical analyzer, and more particularly to stirring for mixing a reagent and a sample in a reaction vessel.
- an automatic sample dispensing mechanism for supplying a sample to be analyzed and a reagent to a reaction vessel, an automatic reagent dispensing mechanism, Sample in reaction vessel 'Automatic stirring mechanism for stirring reagents, measuring instrument for measuring physical properties of sample during or after reaction, Suction of sample after measurement, discharge and washing of reaction vessel It is composed of an automatic cleaning mechanism to perform these operations, and a control mechanism to control these operations.
- the above automatic stirring mechanism automatically lowers the spatula or screw below the liquid level to stir the sample and reagent, and drives the motor connected to the bottom of the spatula to rotate the spatula and stir.
- 8-146007 discloses that a sample and a reagent are separated from each other by using an acoustic stream generated by irradiating ultrasonic waves to a liquid to be stirred without using a spatula or a screw. Is described in a non-contact manner with stirring.
- a sample and a reagent are automatically dispensed to each reaction vessel housed on the circumference of the turntable by a pipe equipped with a robot arm, and the robot arm is similarly operated.
- the spatula is automatically immersed in the liquid to be measured (sample and reagent dispensed into the reaction vessel) by a spatula stirring mechanism equipped with a stirrer to mix and mix the rain. Then, the reaction is measured and output as an inspection result. After the measurement is completed, the liquid to be measured is suctioned and the reaction container is washed, and the inspection of one item for the sample is completed.
- multiple tests are processed in batches according to a sequence programmed by the user in advance.
- the time allocated to each operation (sample, dispensing of reagents, stirring, and washing) must be shortened.
- the one that is particularly problematic is the operation of stirring the liquid to be measured. If the stirring time is reduced, the desired reaction cannot be achieved due to insufficient mixing, and accurate test results cannot be obtained.
- a part of the liquid to be measured adhered to the spatula scatters outside the reaction vessel so that the spatula can be taken in and out of the reaction vessel in a short time.
- the liquid to be measured adheres to the spatula, it is carried over to the reaction vessel for the next inspection (carry over) even though the washing is performed at each stirring operation, causing contamination.
- the liquid to be measured reacts It will be taken out of the container. For this reason, when testing with a small amount of liquid, the ratio of the amount of reaction liquid to the amount removed is large, which is an error factor that cannot be ignored in the analysis.
- the non-contact stirring method using ultrasonic waves of the second prior art solves the problem of contamination between test samples.
- this stirring method since the object to be stirred is stirred without contact, the liquid does not adhere and the problem of the above-mentioned adhesion to the spatula is solved.
- the basic principle of this stirring method is to irradiate sound waves from the outside of the reaction vessel to give an appropriate sound field intensity distribution to the object to be stirred in the reaction vessel to induce sound flow.
- the volume of the reaction solution is further reduced, the size of the reaction vessel itself is reduced, and the surface area of the reaction vessel is reduced. For this reason, it becomes difficult to provide the acoustic energy necessary for generating acoustic streaming.
- a second object of the present invention is to make it possible to agitate a carry-overless and a very small amount of liquid in a chemical analyzer and to further reduce the size of the apparatus.
- a sound wave generating means is provided outside the reaction vessel, and the sound wave generating means transmits the sound wave in a direction from the liquid phase to the gas phase obliquely or parallel to the liquid surface of the liquid to be measured in the reaction vessel. Irradiate the reagent with the same location where the reagent supply means supplies the reagent to the reaction vessel. This can be achieved by performing stirring.
- FIG. 1 is a perspective view showing an entire configuration of a chemical analyzer according to an embodiment of the present invention.
- FIG. 2 is a longitudinal sectional view showing details of a portion of the embodiment shown in FIG.
- FIG. 3 is an explanatory view in the case where stirring is performed simultaneously with the ejection of the reagent
- FIG. 4 is an explanatory view of a specific embodiment of the array sound source
- FIG. 6 is a vertical cross-sectional view of a thermostat including a stirring mechanism of a chemical analyzer according to an embodiment of the present invention
- FIG. 7 is another view of the present invention.
- FIG. 8 is a longitudinal sectional view showing details of a part of a chemical analyzer according to an embodiment.
- FIG. 8 is a longitudinal sectional view showing details of a part of a chemical analyzer according to another embodiment using the acoustic coupler of the present invention.
- FIG. 9 is a view for explaining a chemical analyzer according to another embodiment of the present invention in which the auxiliary stirring of the present invention is introduced.BEST MODE FOR CARRYING OUT THE INVENTION
- FIG. 1 is a perspective view showing a collar of the chemical analyzer of the present embodiment.
- FIG. 2 is a longitudinal sectional view showing a configuration of a non-invasive (non-contact) stirrer provided in the chemical analyzer shown in FIG. 1 and performing non-contact stirring and mixing on an object to be stirred.
- This chemical analyzer is used to keep the temperature of the reaction disk 101 storing the reaction vessel 102 and the liquid to be detected in the reaction vessel 102 stored in the reaction disk 101 constant.
- a stirring mechanism 109 for stirring in the reaction vessel, a photometric mechanism 110 for measuring the reaction process of the mixed substance in the reaction vessel, and an absorbance after the reaction, and a reaction vessel after the inspection (photometry) is completed. It is composed of a cleaning mechanism 1 1 1 for cleaning. In this embodiment, the respective mechanisms are arranged so that the dispensing and stirring of the reagent can be simultaneously performed at the same position.
- the components described above are automatically set to the main controller 1 1 2 based on the information (analysis items and liquid volume to be analyzed) set by the user in advance from the console 113. It operates according to the sequence program created by.
- the stirring mechanism 109 comprises two sound sources, a lower sound source 205 and a side sound source 206, which are provided on the inner wall side of the thermostat housing the reaction vessel. Have been.
- Each sound source has a structure in which the segments are arranged in an array so that they can be driven independently.
- the drive driver 207 selects an appropriate segment and 'drives it, so that a target position can be irradiated with a sound wave'.
- the liquid to be measured 202 is stirred by sound waves, and the stirring mechanism is constituted by sound wave generating means.
- the sound emitted from the sound source is transmitted to the reaction vessel via a constant temperature chamber.
- FIG. 5 (a) shows the sample dispensing position 501, the reagent dispensing position and the stirring position 502, and the photometry 503 for the 32 reaction vessels stored on the reaction disk in this embodiment.
- FIG. 4 is a diagram showing positions where cleaning 504 is performed. First, the sample sucked by the sampling mechanism 107 from the sample cup 104 is dispensed into the reaction vessel stopped at the sample dispensing position 501. Next, it rotates 9 pitches as indicated by an arrow 505 until the reagent dispensing and stirring is performed at position 50 and stops (hereinafter, the rotation angle for one reaction vessel is referred to as one pitch). ).
- the reagent aspirated by the reagent dispensing mechanism 108 is dispensed from the reagent bottle into the reaction container.
- stirring is performed by a stirring mechanism described in detail later.
- the reaction disk rotates 24 pitches as indicated by an arrow 506 while traversing the photometric mechanism 503, and stops at a position 509 one pitch ahead of the dispensed position. The rotation and stop operation from the sample dispensing to this point is one cycle.
- the next reaction vessel has stopped at the sample dispensing position, and the same operation is repeated.
- the absorbance of the liquid to be measured in the reaction vessel is measured at a position crossing the photometric mechanism at position 507, and the change in absorbance (reaction process) in each cycle is measured.
- the reaction container rotates counterclockwise by one pitch every cycle, but the reaction container into which the reagent is dispensed first is installed with the washing mechanism 504. At that point, the measurement of the absorbance change is stopped, the liquid to be measured (hereinafter called waste liquid) is aspirated, and washing of the reaction vessel is started.
- FIG. 3 is an explanatory diagram of a state of a test subject fluid when stirring is performed simultaneously with ejection of a reagent.
- the drive driver 207 of the side sound source 205 and the lower sound source 206 connected to the main controller 112 that controls the entire apparatus is dispensed with the amount of liquid to be stirred, that is, the sample being dispensed.
- the drive driver 2007 fills the reaction vessel with information belonging to the liquid volume.
- the rise of the liquid level of the liquid to be measured, 304, is calculated, and the optimal sound wave irradiation area including the liquid surface position is determined for the lateral and lower sound sources.
- the segment of the sound source corresponding to the irradiation area on the side is selected and driven as shown by an arrow 303 so as to follow the rise 30 of the liquid level.
- the lower sound wave is driven so that the intensity of the lower sound wave is low enough to lift the liquid surface on one side as shown in the liquid surface 209 in FIG. That is, it is possible to increase the liquid level on one side by driving so that the sound wave intensity on one side of the lower array sound source is increased.
- the sound intensity on the side is set to be higher than the sound intensity on the lower side, and irradiation is performed so that the liquid surface flows toward the opposing reaction vessel wall.
- a swirling flow as indicated by an arrow 210 or 306 is generated in the liquid to be measured in the reaction vessel. This flow mixes the sample with the reagent.
- the electrode 401 on one side is divided as shown in Fig. 4 (a), and the opposing electrodes 4, 05 on the opposite side are all over the opposite side. It is composed of single electrodes.
- a part of the counter electrode 405 is configured to be bent toward one electrode surface side. By bending the electrodes in this way, the connection with the power supply line is concentrated on one side, and wiring is facilitated.
- the principle of stirring and mixing in the present embodiment is based on the conventional method that a sound wave is irradiated from the outside of a reaction vessel to give an appropriate sound field intensity distribution inside a liquid to be measured in the reaction vessel to induce acoustic streaming. It is different from the method of making. That is, in this embodiment, the sound source is operated so that the sound is concentrated near the gas-liquid interface in order to utilize the flow due to the acoustic radiation pressure near the gas-liquid interface, which is not affected by the wall friction at all. . For this reason, it is possible to stir and mix the liquid to be measured with smaller sound intensity than the method using acoustic streaming.
- the nozzles 301 of the reagent dispensing mechanism are arranged as shown in FIG. 3, and the ultrasonic waves are generated simultaneously with the reagent dispensing 302. Therefore, a liquid flow occurs in the direction of arrow 350. Thereby, the swirling flow 303 is promoted, and more efficient mixing is performed as compared with the case of the swirling flow of the ultrasonic wave alone. As a result, it becomes possible to reduce the allocation time in the sequence due to the increase in the speed of the apparatus, that is, to cope with the reduction of the mixing time without lowering the mixing performance.
- both the reagent pitter and the stirring spatula are provided on the robot arm. Interference occurred and it was impossible to do these at the same time. Therefore, in the conventional chemical analyzer, another stop period was inevitably provided in one cycle as shown in Fig. 5 (b). That is, it was stopped at the reagent dispensing position 502, and then moved to a position rotated by one pitch as shown by an arrow 508 and stopped there, and stirring was performed there.
- the stirring mechanism uses the sound wave generating means provided outside the reaction vessel, it is possible to perform the dispensing and stirring rain operations at the same time. This increases the efficiency of mixing and shortens the time of one cycle in the device.
- the analysis processing speed is the same If the time of the cycle is set to be the same as that of the conventional chemical analyzer, the time of stirring (and dispensing of reagents) can be longer, so that sufficient mixing can be performed.
- FIG. 6 is a longitudinal sectional view of a reaction disk containing a thermostat and a reaction vessel at a position provided with a stirring mechanism.
- the reaction disk 101 is connected to a motor 602 via a rotating shaft 601. Then, the reaction disk 101 is rotated and stopped in the above-described sequence.
- the space 60 3 inside (between the thermostatic bath rotational shaft) of the thermostatic chamber is easier to take a relatively space.
- a sound wave generating means is provided on the inner wall of the constant temperature bath, and the wiring drawn out so as to prevent hot water in the constant temperature layer from leaking is resin-molded.
- a feature of the present invention is that a sound wave generating means is provided outside the reaction vessel, and stirring is performed simultaneously with dispensing of the reagent. As a result, the processing speed of the chemical analyzer can be increased. It should be noted that sufficient advantages can be obtained simply by replacing the sound wave stirring mechanism shown in FIG. 2 with a conventional spatula type stirring mechanism. As described above, since the stirring mechanism according to the present invention is completely non-contact with the liquid to be measured to be mixed, the above-mentioned problems associated with the attachment of the spatula are completely eliminated. Therefore, in chemical analyzers that do not require much speed-up, a contamination-less chemical analyzer can be realized by using this stirring mechanism instead of the conventional spatula stirring mechanism. It is possible to In addition, since the stirring mechanism itself is simple as described above, it is more reliable than conventional chemical analyzers, and the size of the entire chemical device can be reduced.
- FIG. 7 shows a configuration in which the sound source is moved and stirred.
- the sound sources 703 and 706 are provided with position adjustment mechanisms 720 and 705, respectively.
- the main controller 112 sends information 204 concerning the amount of liquid to be stirred and the timing of stirring to the drive dryer 701.
- the drive driver 701 determines the irradiation position of the sound wave in accordance with the height of the liquid surface 209, and controls the position adjustment mechanism 702, 705 to move the sound source section to the irradiation position. Moving. Then, a sound wave 70 is applied according to the information on the stirring timing. As a result, a swirling flow 708 is generated and mixing is performed.
- the position adjustment mechanism 705 for the lower sound source is moved in the vertical direction, but cannot move in the left and right directions. It is provided.
- the side sound source position adjusting mechanism 720 is provided so as to be movable in the up-down direction and the front-back direction.
- the frequency of the sound wave generating means in the present invention is a sound wave of several MHz, which can be propagated well in water. Therefore, even if the sound wave generating means provided outside the reaction vessel makes the sound wave reach the inside of the reaction vessel. Was possible.
- a chemical analyzer using an air thermostat that controls the temperature with air instead of using a thermostat, if a sound wave generating mechanism is provided outside the reaction vessel, the sound wave generating mechanism and the reaction vessel There is an air layer between them This makes it difficult to propagate sound waves.
- sound waves can be propagated by coupling the sound impedance between the sound wave generating means and the reaction vessel with a sound wave transmission mechanism (such as a sound coupler) whose material is similar to water. it can.
- a sound wave transmission mechanism such as a sound coupler
- FIG. 8 shows a cross-sectional view of the stirring section of the air-temperature-chamber type chemical analyzer.
- a sound source 802, 805 provided with an acoustic coupler 803, 810 is provided with a position adjustment mechanism 801, 8 of two axes (the direction of sound wave propagation and the direction perpendicular thereto). 0 4 is provided.
- Other configurations are the same as those in the embodiment of FIG. 7.
- the drive driver moves the acoustic force pullers 803 and 810 to contact the reaction vessel. Since the lower sound source section can be moved only in the vertical direction, the lower sound source section is preliminarily offset from the center of the reaction vessel.
- the acoustic coupler is retracted so as not to contact the reaction vessel. In this way, the position of the sound source is adjusted to secure an acoustic transmission path between the sound source and the reaction vessel.
- the swirling flow 706 similar to that in the previous embodiments can be mixed and mixed even in the case of the air-type constant temperature bath.
- FIG. 9 shows the configuration when an auxiliary stirring mechanism is provided.
- FIG. 9 (a) is an example in which two stirring mechanisms 901, 902 are provided in addition to the position of simultaneous stirring with reagent dispensing in the embodiment shown in FIG. 6 (a).
- the operation in one cycle is the same as that of the embodiment shown in Fig. 6 (a).
- the next reaction vessel and the next reaction vessel are dispensed with reagents. While stirring, additional stirring is performed by the auxiliary stirring mechanism.
- FIG. 9 (b) shows a single piezoelectric element that matches the curvature of the thermostat to be installed, and divided electrodes corresponding to the reaction vessel positions 502, 901, and 902, respectively. Things.
- the piezoelectric element as shown in FIG. 9 (b) can be manufactured by almost the same process as the piezoelectric element of FIG. With the sound generator of this configuration, it is possible to easily add a stirring mechanism.
- Fig. 9 (b) shows an example of a sound source on the side. Similarly, a single piezoelectric element is processed at the position corresponding to the position of each reaction vessel to produce a lower sound source.
- auxiliary stirring mechanism as in this configuration, sufficient stirring can be easily performed even when a high-viscosity sample or a highly viscous reagent that is difficult to mix is used.
- a two-stage stirring mechanism is added as an auxiliary, but it is easy to add more as needed.
- the carryoverless method enables the stirring of a very small amount of liquid, thereby further reducing the size of the entire apparatus.
- the present invention relates to a mechanism for mixing and mixing liquids in a non-contact manner, and particularly to a case where the present invention is applied to an apparatus for chemical analysis. It is possible.
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Abstract
Description
化学分析装置 Chemical analyzer
技術分野 Technical field
本発明は化学分析装置に係り、 特に、 反応容器内の試薬とサンプルとを混 合するための攪拌に関する。 The present invention relates to a chemical analyzer, and more particularly to stirring for mixing a reagent and a sample in a reaction vessel.
明 田 Akita
背景技術 書 Background art
米国特許第 4, 4 5 1 , 4 3 3号公報に記載されている化学分析装置では 分析対象となるサンプル、 試薬を反応容器に供給するための自動サンプル分 注機構、 自動試薬分注機構、 反応容器内のサンプル '試薬を攪拌するための 自動攪拌機構、 反応中あるいは反応が終了したサンプルの物性を計測するた めの計測器、 計測が終了したサンプルを吸引 '排出し、 反応容器を洗浄する ための自動洗浄機構、 これらの動作をコントロールする制御機構などから構 成されている。 特に上記自動攪拌機構ではサンプルと試薬を攪拌するために ヘラあるいは、 スクリューを液面下まで自動的に下降させ、 ヘラの根元に接. 続されているモータを駆動し、 ヘラを回転して攪拌する方式を用いている。 また、 特開平 8— 1 4 6 0 0 7号公報にはヘラやスクリューを用いずに、 液状の被攙拌物に超音波を照射することによって発生する音響流を用いて、 サンプルと試薬とを非接触で攪拌し混合する方法が記載されている。 In the chemical analyzer described in U.S. Pat. No. 4,451,433, an automatic sample dispensing mechanism for supplying a sample to be analyzed and a reagent to a reaction vessel, an automatic reagent dispensing mechanism, Sample in reaction vessel 'Automatic stirring mechanism for stirring reagents, measuring instrument for measuring physical properties of sample during or after reaction, Suction of sample after measurement, discharge and washing of reaction vessel It is composed of an automatic cleaning mechanism to perform these operations, and a control mechanism to control these operations. In particular, the above automatic stirring mechanism automatically lowers the spatula or screw below the liquid level to stir the sample and reagent, and drives the motor connected to the bottom of the spatula to rotate the spatula and stir. Is used. Japanese Patent Application Laid-Open No. 8-146007 discloses that a sample and a reagent are separated from each other by using an acoustic stream generated by irradiating ultrasonic waves to a liquid to be stirred without using a spatula or a screw. Is described in a non-contact manner with stirring.
近年、 医療検査センタ ^"などでは、 集められた多数のサンプルを一括して より短時間で分析する高精度な高速処理能力型の化学分析装置が望まれてい る。 これによつて、 検査を行なってから検査結果が得られるまでの時間が短 縮され、 医師はその患者に対してタイムリーかつ適切な治療を施す事が可能 となる。 また、 患者から採取するサンプル量を減らして患者の負担を低減したり、 検査後に処理すべき廃液を低減するために、 従来に比軟して少ない液量で検 査を行う機能も、 今後開発される化学分析装置には必須の課題である。 また、 前述の課題を克服することによって、 使用する試薬の液量も少なくなるので、 検査のランニングコストも低減されるという副次的なメリットも得られる。 また、 このような化学分析装置が設置される医療施設には、 この他にも 様々な機器が導入されつつあり、 装置を設置するスペースの事情から、 上記 課題を克服するにあたり装置が大型化しないことも重要な課題である。 In recent years, medical examination centers ^ "and the like have demanded high-precision, high-throughput chemical analyzers that collectively analyze a large number of collected samples in a shorter time. The time between when the test is performed and when the test results are obtained is reduced, and the physician can give the patient timely and appropriate treatment. To reduce the burden on patients by reducing the amount of samples collected from patients, and to reduce the amount of waste liquid that must be treated after inspections, a function to perform inspections with a relatively small amount of liquids will be developed in the future. This is an indispensable subject for the chemical analyzer to be used. In addition, by overcoming the above-mentioned problems, the amount of reagent used is reduced, so that there is a secondary advantage that the running cost of the test is reduced. In addition, various other devices are being introduced into medical facilities where such chemical analyzers are installed. Due to the space for installing the devices, the devices do not increase in size to overcome the above-mentioned problems. This is also an important issue.
上記の第一の従来技術では、 ターンテーブルの円周上に収納した各反応容 器に対し、 ロボッ トアームを備えたピぺッ夕でサンプルと試薬を自動的に分 注し、 同様にロボットアームを備えたヘラ攪拌機構によって被測定液 (反応 容器に分注されたサンプルと試薬) へ自動的にヘラを浸けて雨者の攪拌 ·混 合する。 そして、 その生ィ匕学反応を計測し検査結果として出力し、 計測終了 後は被測定液の吸引 '反応容器洗浄を行ない、 そのサンプルに対する一項目 の検査が完了する。 実際の使用状況では、 予めユーザによってプログラミン グされたシーケンスに従つて複数の検査をバッチ的に処理して行く。 現在主 流であるこのような化学分析装置において高速ィヒを求める場合、 各操作 (サ ンプル .試薬の分注, 攪拌, 洗浄) に割り当てる時間を短くせざるを得なく なる。 時間を短縮する操作のうち、 特に問題となるの'は、 被測定液の攪拌操 作である。 攪 操作の時間を短縮すると、 混合不足により所望の反応が達成 されず、 正確な検査結果が得られなくなる。 また、 短時間にヘラを反応容器 の中に出し入れするために、 ヘラに付着した被測定液の一部が反応容器外に 飛散する。 また、 被測定液のヘラへ 付着は、 攪拌操作毎に洗浄を行なって いるにも関わらず、 次の検査の反応容器に持ち越され (キャリ^ "オーバー) 、 コンタミネーシヨンを引き起こす。 また、 ヘラへの付着は、 被測定液が反応 容器外に持ち去されることになる。 このため、 少ない液量での検査を行なう 場合には、 この持ち去り量に対する反応液量の比が大きくなり、 分析上無視 し難い誤差要因となる。 In the first prior art described above, a sample and a reagent are automatically dispensed to each reaction vessel housed on the circumference of the turntable by a pipe equipped with a robot arm, and the robot arm is similarly operated. The spatula is automatically immersed in the liquid to be measured (sample and reagent dispensed into the reaction vessel) by a spatula stirring mechanism equipped with a stirrer to mix and mix the rain. Then, the reaction is measured and output as an inspection result. After the measurement is completed, the liquid to be measured is suctioned and the reaction container is washed, and the inspection of one item for the sample is completed. In actual usage, multiple tests are processed in batches according to a sequence programmed by the user in advance. When high-speed data is required in such a chemical analyzer that is currently mainstream, the time allocated to each operation (sample, dispensing of reagents, stirring, and washing) must be shortened. Of the operations to reduce the time, the one that is particularly problematic is the operation of stirring the liquid to be measured. If the stirring time is reduced, the desired reaction cannot be achieved due to insufficient mixing, and accurate test results cannot be obtained. In addition, a part of the liquid to be measured adhered to the spatula scatters outside the reaction vessel so that the spatula can be taken in and out of the reaction vessel in a short time. In addition, although the liquid to be measured adheres to the spatula, it is carried over to the reaction vessel for the next inspection (carry over) even though the washing is performed at each stirring operation, causing contamination. The liquid to be measured reacts It will be taken out of the container. For this reason, when testing with a small amount of liquid, the ratio of the amount of reaction liquid to the amount removed is large, which is an error factor that cannot be ignored in the analysis.
上記第二の従来技術の超音波による非接触での攪拌方法では、 各検査試料 間のコンタミネーシヨンの問題は解決されている。 この攪拌方法は、 被攪拌 物に対し完全に非接触で攪拌するため、 液の付着も発生せず上述したヘラへ の付着に関する問題点は解決される。. この攪拌方法では、 反応容器の外部か ら音波を照射し、 反応容器内の被攪拌物に適当な音場強度分布を与えて、 音 響流動を誘起させる事が基本的な原理である。 ところで、 より反応液量を微 量化していくと、 反応容器そのものも小型化され、 反応容器の表面積も小さ くなつていく。 このため、 音響流動の発生に必要な音響エネルギーを与える 事が困難となってくる。 また、 音響流によって攪拌に有効な循環流れを発生 させるためには、 内部に音場の先鋭的な強度の分布を形成させる必要がある が、 容器がより小型化すると、 容器内の音場の相対的な強度差が小さくなる といった問題から、 短時間での効率のよい攪拌が困難となる。 発明の開示 The non-contact stirring method using ultrasonic waves of the second prior art solves the problem of contamination between test samples. In this stirring method, since the object to be stirred is stirred without contact, the liquid does not adhere and the problem of the above-mentioned adhesion to the spatula is solved. The basic principle of this stirring method is to irradiate sound waves from the outside of the reaction vessel to give an appropriate sound field intensity distribution to the object to be stirred in the reaction vessel to induce sound flow. By the way, when the volume of the reaction solution is further reduced, the size of the reaction vessel itself is reduced, and the surface area of the reaction vessel is reduced. For this reason, it becomes difficult to provide the acoustic energy necessary for generating acoustic streaming. Also, in order to generate a circulating flow that is effective for agitation by acoustic flow, it is necessary to form a sharp distribution of the intensity of the sound field inside, but as the size of the container becomes smaller, the sound field inside the container becomes smaller. The problem that the relative intensity difference is small makes it difficult to perform efficient stirring in a short time. Disclosure of the invention
本発明第一の目的は、 化学分析装置において、 キャリーオーバーレス -微 小液量の攪拌を可能とし、 より高速な分析処理能力を実現するにある。 本発明第二の目的は、 化学分析装置において、 キャリーオーバーレス '微 小液量の攪拌を可能とし、 より装置を小型化することにある。 It is a first object of the present invention to provide a chemical analyzer capable of carrying over a small amount of liquid and agitating a small amount of liquid, thereby realizing higher-speed analytical processing capability. A second object of the present invention is to make it possible to agitate a carry-overless and a very small amount of liquid in a chemical analyzer and to further reduce the size of the apparatus.
上記の各目的は、 反応容器の外部に音波発生手段を設け、 音波発生手段が 反応容器内部の被測定液の液面に対して平行に、 または斜めに液相から気相 に向かう方向へ音波を照射するように設置し、 その設置場所が、 試薬供給手 段が反応容器に試薬を供給する位置と同じ場所として、 試薬供給と同時に攪 拌を実行する様にする事で達成できる。 図面の簡単な説明 For each of the above purposes, a sound wave generating means is provided outside the reaction vessel, and the sound wave generating means transmits the sound wave in a direction from the liquid phase to the gas phase obliquely or parallel to the liquid surface of the liquid to be measured in the reaction vessel. Irradiate the reagent with the same location where the reagent supply means supplies the reagent to the reaction vessel. This can be achieved by performing stirring. BRIEF DESCRIPTION OF THE FIGURES
第 1図は、 本発明の実施例である化学分析装置全体構成を示す斜視図であ り、 第 2図は、 第 1図に示す実施例の部分の詳細を示す縦断面図であり、 第 3図は、 試薬吐出と同時に攪拌を行なう場合の説明図であり、 第 4図は、 ァ レイ音源の具体的な実施例の説明図であり、 第 5図は、 本実施例および従来 の 1サイクルの動作を説明ずる図であり、 第.6図は、 本発明の実施例である 化学分析装置の攪拌機構を含む恒温槽の縦断面図であり、 第 7図は、 本発明 の他の実施例である化学分析装置の部分の詳細を示す縦断面図であり、 第 8 図は、 本発明の音響カップラを用いた他の実施例である化学分析装置の部分 の詳細を示す縦断面図であり、 第 9図は、 本発明の補助攪拌を導入したを他 の実施例である化学分析装置のを説明する図である。 発明を実施するための最良の形態 FIG. 1 is a perspective view showing an entire configuration of a chemical analyzer according to an embodiment of the present invention. FIG. 2 is a longitudinal sectional view showing details of a portion of the embodiment shown in FIG. FIG. 3 is an explanatory view in the case where stirring is performed simultaneously with the ejection of the reagent, FIG. 4 is an explanatory view of a specific embodiment of the array sound source, and FIG. FIG. 6 is a vertical cross-sectional view of a thermostat including a stirring mechanism of a chemical analyzer according to an embodiment of the present invention, and FIG. 7 is another view of the present invention. FIG. 8 is a longitudinal sectional view showing details of a part of a chemical analyzer according to an embodiment. FIG. 8 is a longitudinal sectional view showing details of a part of a chemical analyzer according to another embodiment using the acoustic coupler of the present invention. FIG. 9 is a view for explaining a chemical analyzer according to another embodiment of the present invention in which the auxiliary stirring of the present invention is introduced.BEST MODE FOR CARRYING OUT THE INVENTION
本発明の一実施例を第 1図及び第 2図を用いて説明する。 第 1図は、 本実 施例の化学分析装置の襟成を示す斜視図である。 第 2図は、 第 1図に示す化 学分析装置に装備されている被攪拌物に対して非接触で攪拌混合を行なう非 侵襲 (非接触) 攪拌装置の構成を示す縦断面図である。 One embodiment of the present invention will be described with reference to FIGS. FIG. 1 is a perspective view showing a collar of the chemical analyzer of the present embodiment. FIG. 2 is a longitudinal sectional view showing a configuration of a non-invasive (non-contact) stirrer provided in the chemical analyzer shown in FIG. 1 and performing non-contact stirring and mixing on an object to be stirred.
本化学分析装置は、 反応容器 1 0 2を格納する反応ディスク 1 0 1と、 反 応ディスク 1 0 1に格納されている反応容器 1 0 2内の被検出液等を一定の 温度に保つ為の恒温槽 1 1 4と、 サンプルカップ 1 0 4を収納するサンプル 用ターンテーブル 1 0 3と、 試薬ボトル 1 0 5を格納する試薬用ターンテー ブル 1 0 6と、 サンプルと試薬をそれぞれ反応容器に分注するサンプリング 分注機構 1 0 7と、 試薬分注機構 1 0 8と、 分注されたサンプルと試薬を反 応容器内で攪拌する攪拌機構 1 0 9と、 反応容器内の混合物質の反応過程、 及び反応後の吸光度を測定する測光機構 1 1 0と、 検査 (測光)が終了した後 に反応容器を洗浄する洗浄機構 1 1 1とより構成される。 なお、 本実施例に おいては試薬の分注と攪拌は、 同じ位置で同時に動作できるようそれぞれの 機構は配置されている。 This chemical analyzer is used to keep the temperature of the reaction disk 101 storing the reaction vessel 102 and the liquid to be detected in the reaction vessel 102 stored in the reaction disk 101 constant. A thermostatic bath 1 1 4, a sample turntable 10 3 for storing the sample cup 10 4, a reagent turntable 10 6 for storing the reagent bottle 10 5, Dispensing sampling dispensing mechanism 107, reagent dispensing mechanism 108, and dispensing dispensed sample and reagent A stirring mechanism 109 for stirring in the reaction vessel, a photometric mechanism 110 for measuring the reaction process of the mixed substance in the reaction vessel, and an absorbance after the reaction, and a reaction vessel after the inspection (photometry) is completed. It is composed of a cleaning mechanism 1 1 1 for cleaning. In this embodiment, the respective mechanisms are arranged so that the dispensing and stirring of the reagent can be simultaneously performed at the same position.
以上の各構成要素は、 検査を開始する前に、 予めユーザーがコンソ^ "ル 1 1 3から設定した情報 (分析項目、 分析を行なう液量) に基づいて、 自動的 にメインコントローラ 1 1 2により作成されるシーケンスプログラムに従つ て動作する。 Before starting the inspection, the components described above are automatically set to the main controller 1 1 2 based on the information (analysis items and liquid volume to be analyzed) set by the user in advance from the console 113. It operates according to the sequence program created by.
攪拌機構 1 0 9は、 第 2図に示すように、 反応容器を収納する恒温槽の内 壁面側に設けられた、 下方音源 2 0 5と側方音源 2 0 6の二つの音源から構 成されている。 各音源は、 それぞれ独立に駆動できるように、 セグメントが アレイ状に配置された構造になっている。 駆動ドライバ 2 0 7が適切なセグ メントを選択して'駆動することによって、 目標とする位置に音波を照射する 事が可能と'なっている。 本発明では、 被測定液 2 0 2の攪拌は音波で行われ、 攪拌機構は音波発生手段で構成されている。 なお、 本実施例では、 音源から 出射された音は恒温槽内の恒 ¾ を介して反応容器に伝達する構成となって いる。 As shown in FIG. 2, the stirring mechanism 109 comprises two sound sources, a lower sound source 205 and a side sound source 206, which are provided on the inner wall side of the thermostat housing the reaction vessel. Have been. Each sound source has a structure in which the segments are arranged in an array so that they can be driven independently. The drive driver 207 selects an appropriate segment and 'drives it, so that a target position can be irradiated with a sound wave'. In the present invention, the liquid to be measured 202 is stirred by sound waves, and the stirring mechanism is constituted by sound wave generating means. In this embodiment, the sound emitted from the sound source is transmitted to the reaction vessel via a constant temperature chamber.
次に、 以上の構成に基づく装啬全体の動作の概要を説明し、 次いで本実施 例における攪拌機構の動作の詳細について述べる。 なお、 以下の説明では、 動作の説明を具体化するため、 一例として、 反応ディスク上に 3 2個の反応 容器を有する化学分析装置の例で動作を説明して行く。 Next, an outline of the operation of the entire device based on the above configuration will be described, and then details of the operation of the stirring mechanism in the present embodiment will be described. In the following description, the operation will be described using an example of a chemical analyzer having 32 reaction vessels on a reaction disk as an example in order to embody the description of the operation.
第 5図(a)は、 本実施例における反応ディスク上に収納された 3 2個の反 応容器に対するサンプル分注位置 5 0 1、 試薬分注位置および攪拌位置 5 0 2、 測光 5 0 3及び洗浄 5 0 4が行なわれる位置を示した図である。 まず、 サンプル分注位置 5 0 1で停止している反応容器内に、 サンプル' カップ 1 0 4からサンプリング機構 1 0 7によって吸引されたサンプルが分 注される。 次に、 試薬分注及び攪拌が行なわれる位置 5 0 まで、 矢印 5 0 5のように 9ピッチ回転してー且停止する(以下、 反応容器一個分の回転角 を 1 ピッチと呼ぶことにする)。 この停止期間中に、 反応容器内へ試薬ポト ルから試薬分注機構 1 0 8によって吸引された試薬が分注される。 分注と同 時に後に詳説する攪拌機構によって攪拌が行なわれる。 さらに、 反応ディス クは、 測光機構 5 0 3を横切りながら矢印 5 0 6のように 2 4ピッチ回転し、 先程分注された位置より 1ピッチ先の位置 5 0 9で停止する。 以上、.サンプ ル分注からこの時点までの、 回転及び停止動作を 1サイクルとする。 FIG. 5 (a) shows the sample dispensing position 501, the reagent dispensing position and the stirring position 502, and the photometry 503 for the 32 reaction vessels stored on the reaction disk in this embodiment. FIG. 4 is a diagram showing positions where cleaning 504 is performed. First, the sample sucked by the sampling mechanism 107 from the sample cup 104 is dispensed into the reaction vessel stopped at the sample dispensing position 501. Next, it rotates 9 pitches as indicated by an arrow 505 until the reagent dispensing and stirring is performed at position 50 and stops (hereinafter, the rotation angle for one reaction vessel is referred to as one pitch). ). During this suspension period, the reagent aspirated by the reagent dispensing mechanism 108 is dispensed from the reagent bottle into the reaction container. At the same time as dispensing, stirring is performed by a stirring mechanism described in detail later. Further, the reaction disk rotates 24 pitches as indicated by an arrow 506 while traversing the photometric mechanism 503, and stops at a position 509 one pitch ahead of the dispensed position. The rotation and stop operation from the sample dispensing to this point is one cycle.
1サイクルが終了した時点で、 サンプル分注位置には次の反応容器が停止 しており、 以下同様な動作を繰り返す。 1サイクル中、 測光機構を横切る位. 置 5 0 7で反応容器内の被測定液の吸光度が計測され、 各サイクル毎の吸光 度変化 (反応過程) が測定されて行く。 このように、 本実施例では 1サイク ル毎に反応容器は 1ピッチづっ反時計周りにずれるように回転して行くが、 最初に試薬が分注された反応容器が洗浄機構 5 0 4の設置されている位置ま で達した時点で、 吸光度変化の計測は打ち切られ、 被測定液 (この時点から は廃液と呼ぶ) は吸引され、 反応容器の洗浄が開始される。 At the end of one cycle, the next reaction vessel has stopped at the sample dispensing position, and the same operation is repeated. During one cycle, the absorbance of the liquid to be measured in the reaction vessel is measured at a position crossing the photometric mechanism at position 507, and the change in absorbance (reaction process) in each cycle is measured. As described above, in this embodiment, the reaction container rotates counterclockwise by one pitch every cycle, but the reaction container into which the reagent is dispensed first is installed with the washing mechanism 504. At that point, the measurement of the absorbance change is stopped, the liquid to be measured (hereinafter called waste liquid) is aspirated, and washing of the reaction vessel is started.
次に、 本実施例における攪拌手段及びその機構について、 第 2図及び第 3 図を用いて説明する。 第 3図は、 試薬吐出と同時に攪拌を行う場合の、 被検 体液の状態の説明図である。 Next, the stirring means and its mechanism in this embodiment will be described with reference to FIG. 2 and FIG. FIG. 3 is an explanatory diagram of a state of a test subject fluid when stirring is performed simultaneously with ejection of a reagent.
装置全体を制御するメインコントローラ 1 1 2に接続された側方音源 2 0 5及び下方音源 2 0 6の駆動ドライバ 2 0 7は、 攪拌する液量すなわち分注 されているサンプルと分注される試薬の液量に関する情報 2 0 4を受け取る。 まず、 駆動ドライバ 2 0 7は、 液量に属する情報から反応容器内に満たされ ていく被測定液の液面高さの上昇 3 0 4を計算し、 その液面位置を含める最 適な音波照射領域を側方および下方音源について決定する。 そして、 側方の 照射領域に対応する音源のセグメントが、 液面の上昇 3 0 に追随するよう に矢印 3 0 3のように選択して駆動する。 このとき、 下方の音波強度は第 2 図の液面 2 0 9のように、 片側の液面が持ち上がる程度の強度分希となるよ うに駆動する。 即ち、 下方のアレー音源の一方側の音波強度が大きくなるよ うに駆動することで片側の液面を高くすることが可能となる。 一方、 側方の 音波強度は、 下方の音波強度以上の強度とし、 液面が対向する反応容器壁へ 向かって流動するように照射する。 これによつて、 反応容器内の被測定液に は矢印 2 1 0あるいは 3 0 6のような旋回流が発生する。 この流動によって サンプルと試薬は混合される。 The drive driver 207 of the side sound source 205 and the lower sound source 206 connected to the main controller 112 that controls the entire apparatus is dispensed with the amount of liquid to be stirred, that is, the sample being dispensed. Receive information 204 about reagent volume. First, the drive driver 2007 fills the reaction vessel with information belonging to the liquid volume. The rise of the liquid level of the liquid to be measured, 304, is calculated, and the optimal sound wave irradiation area including the liquid surface position is determined for the lateral and lower sound sources. Then, the segment of the sound source corresponding to the irradiation area on the side is selected and driven as shown by an arrow 303 so as to follow the rise 30 of the liquid level. At this time, the lower sound wave is driven so that the intensity of the lower sound wave is low enough to lift the liquid surface on one side as shown in the liquid surface 209 in FIG. That is, it is possible to increase the liquid level on one side by driving so that the sound wave intensity on one side of the lower array sound source is increased. On the other hand, the sound intensity on the side is set to be higher than the sound intensity on the lower side, and irradiation is performed so that the liquid surface flows toward the opposing reaction vessel wall. As a result, a swirling flow as indicated by an arrow 210 or 306 is generated in the liquid to be measured in the reaction vessel. This flow mixes the sample with the reagent.
以上のような攪拌操作が各サイクルにおいて、 試薬分注および攪拌位置に 停止した反応容器に対して逐一行なわれる。 In each cycle, the above-described stirring operation is sequentially performed on the reaction container stopped at the reagent dispensing and stirring position.
次に、 本実施例で用いた音源の構成について第 4図を用いて説明する。 音 源として、 圧電素子を用いる場合、 第 4図 (a ) に示すように一方面側の電 極 4 0 1を分割して、 反対面側の対向電極 4 ,0 5は反対側面全体に一枚電極 で構成する。 この時、 対向電極 4 0 5の一部は、 一方側の電極面側に折り曲 げて構成してある。 このように電極を折り曲げる事によって、 電源線との接 続を一方面側に集中して、 配線を容易にしたものである。 Next, the configuration of the sound source used in this embodiment will be described with reference to FIG. When a piezoelectric element is used as the sound source, the electrode 401 on one side is divided as shown in Fig. 4 (a), and the opposing electrodes 4, 05 on the opposite side are all over the opposite side. It is composed of single electrodes. At this time, a part of the counter electrode 405 is configured to be bent toward one electrode surface side. By bending the electrodes in this way, the connection with the power supply line is concentrated on one side, and wiring is facilitated.
ところで、 第 4図 (b ) に示すよう所望の照射領域 4 0 2に対応する電極 4 0 3に对して、 選択的に電圧 4 0 4を印加すれば、 機能的にアレイ状に配 置された音源と等価となる。 本実施例では、 このように電極を配置した一枚 の圧電素子を用いる事で、 攪拌機構の低コスト化を実現した。 このような構 成の音源は、 量産時に極めて有利で、 電極パターンをスクリーン印刷等で成 形すれば、 製作時間の短縮も可能である。 ところで、 本実施例における攪拌'混合の原理は、 従来の、 反応容器の外 部から音波を照射し、 反応容器内の被測定液内部に適当な音場強度分布を与 えて、 音響流動を誘起させる方法とは異なる。 すなわち、 本実施例では壁面 摩擦の影響を一切受けない、 気液界面付近での音響放射圧による流動を利用 するために、 気液界面近傍に音響が集中するように、 音源を操作している。 このため、 音響流動を利用した方法に比べより小さな音波強度で被測定液を 攪拌 ·混合する事が可能である。 By the way, as shown in FIG. 4 (b), when a voltage 404 is selectively applied to the electrode 403 corresponding to the desired irradiation area 402, it is functionally arranged in an array. It is equivalent to the sound source performed. In this embodiment, the use of a single piezoelectric element on which electrodes are arranged as described above has reduced the cost of the stirring mechanism. A sound source having such a configuration is extremely advantageous during mass production. If the electrode pattern is formed by screen printing or the like, the production time can be reduced. By the way, the principle of stirring and mixing in the present embodiment is based on the conventional method that a sound wave is irradiated from the outside of a reaction vessel to give an appropriate sound field intensity distribution inside a liquid to be measured in the reaction vessel to induce acoustic streaming. It is different from the method of making. That is, in this embodiment, the sound source is operated so that the sound is concentrated near the gas-liquid interface in order to utilize the flow due to the acoustic radiation pressure near the gas-liquid interface, which is not affected by the wall friction at all. . For this reason, it is possible to stir and mix the liquid to be measured with smaller sound intensity than the method using acoustic streaming.
また、 本実施例では、 試薬分注機構のノズル 3 0 1を、 第 3図に示すよう に配置して試薬分注 3 0 2と同時に上記超音波を発生させている。 このため、 矢印 3 5 0方向に液体の流れが発生する。 これにより、 旋回流 3 0 6は助長 されて、 超音波単独の旋回流の場合に比べて、 より効率のよい混合が行われ る。 これによつて、 装置の高速化に伴なうシーケンス上の割り当て時間の短 縮、 すなわち、 混合時間を短縮しても混合性能を低下させることなく対応す ることが可能となる。 In the present embodiment, the nozzles 301 of the reagent dispensing mechanism are arranged as shown in FIG. 3, and the ultrasonic waves are generated simultaneously with the reagent dispensing 302. Therefore, a liquid flow occurs in the direction of arrow 350. Thereby, the swirling flow 303 is promoted, and more efficient mixing is performed as compared with the case of the swirling flow of the ultrasonic wave alone. As a result, it becomes possible to reduce the allocation time in the sequence due to the increase in the speed of the apparatus, that is, to cope with the reduction of the mixing time without lowering the mixing performance.
従来の化学分析装置では、 上述したように、 試薬ピぺッタ及ぴ攪拌ヘラは いずれもロボットアームに備え付けられており、 反応容器上部の開口部より 分注、 攪拌操作を行うためロボットアームの干渉が生じ、 これらを同時に行 うことは不可能であった。 そこで、 従来の化学分析装置では、 必然的に第- 5 図(b )に示すように、 1サイクルにもう一つ停止期間を設けた。 すなわち、 試薬分注位置 5 0 2で停止させ、 その後、 矢印 5 0 8のように、 1 ピッチ回 転した位置に移動して停止させ、 そこで攪拌を行っていた。 しかし、 本実施 例では、 上述したように攪拌機構が反応容器の外部に設けた音波発生手段を 用いているため、 分注と攪拌の雨操作を同時に行うことが可能となる。 これ によって、 混合の効率が上がると共に、 装置における 1サイクルの時間を短 縮することも可能となる。 また、 分析処理速度を従来と同等すなわち 1サイ クルの時間はこれまでの化学分析装置と同程度に設定すれば、 それだけ攪拌 (及び試薬分注) の時間を長くとることができるので、 十二分な混合を行う ことも可能である。 In the conventional chemical analyzer, as described above, both the reagent pitter and the stirring spatula are provided on the robot arm. Interference occurred and it was impossible to do these at the same time. Therefore, in the conventional chemical analyzer, another stop period was inevitably provided in one cycle as shown in Fig. 5 (b). That is, it was stopped at the reagent dispensing position 502, and then moved to a position rotated by one pitch as shown by an arrow 508 and stopped there, and stirring was performed there. However, in the present embodiment, as described above, since the stirring mechanism uses the sound wave generating means provided outside the reaction vessel, it is possible to perform the dispensing and stirring rain operations at the same time. This increases the efficiency of mixing and shortens the time of one cycle in the device. In addition, the analysis processing speed is the same If the time of the cycle is set to be the same as that of the conventional chemical analyzer, the time of stirring (and dispensing of reagents) can be longer, so that sufficient mixing can be performed.
本来、 攪拌は複数の物質 (本実施例ではサンプルと試薬) の化学的な反応 を促進する補助的な裸作であり、 両者が反応容器に分注された時点で速やか に行われるべきである。 本実施では試藥分注と同時に攪拌混合を行うため、 攪拌のタイミングとしても従来の化学分析装置と比べ理想的な状態である。 第 6図は、 攪拌機構を備えた位置における、 恒温槽及び反応容器を収納し た反応ディスクの縦断面図である。 反応ディスク 1 0 1は、 回転シャフト 6 0 1を介してモーター 6 0 2に接続されている。 そして、 上述したシーケン スで反応ディスク 1 0 1を回転、 停止させる。 化学分析装置全体の設計にも よるが、 恒温槽の内側 (恒温槽と回転シャフトの間) の空間 603 は、 比較 的スペースをとる事が容易である。 本実施例では、 第 6図に示すよう恒温槽 の内壁部に音波発生手段を設け、 恒温層の温水が漏れないように外側に引き 出される配線分は樹脂モールドしてある。 この音波発生手段は、 壁面部分で はなく、 内側のスペースに設けられるように装置全体を設計することで、 装 置全体の省スペース化を図ることも可能である。 Essentially, agitation is an auxiliary nude that promotes the chemical reaction of multiple substances (in this example, the sample and the reagent) and should be performed as soon as both are dispensed into the reaction vessel. . In the present embodiment, the mixing and stirring are performed simultaneously with the dispensing of the reagent, so that the timing of the stirring is ideal compared to the conventional chemical analyzer. FIG. 6 is a longitudinal sectional view of a reaction disk containing a thermostat and a reaction vessel at a position provided with a stirring mechanism. The reaction disk 101 is connected to a motor 602 via a rotating shaft 601. Then, the reaction disk 101 is rotated and stopped in the above-described sequence. Depending on the chemical analysis apparatus overall design, the space 60 3 inside (between the thermostatic bath rotational shaft) of the thermostatic chamber is easier to take a relatively space. In this embodiment, as shown in FIG. 6, a sound wave generating means is provided on the inner wall of the constant temperature bath, and the wiring drawn out so as to prevent hot water in the constant temperature layer from leaking is resin-molded. By designing the entire apparatus so that the sound wave generating means is provided not in the wall but in the inner space, it is possible to reduce the space of the entire apparatus.
本発明の特徴は、 反応容器外部に音波発生手段を設け、 試薬の分注と同時 に攪拌を行うことである。 これによつて、 化学分析装置の処理速度の高速化 が達成できる。 なお、 第 2図に示す音波による攪拌機構を、 従来のヘラ式の 攪拌機構と置き換えるだけでも十分なメリットが得られる。 上述したように 本発明による攪摔機構は、 混合すベき被測定液に対して完全に非接触である ので、 ヘラ付着に伴なう上記諸問題は完全に解消される。 従って、 高速化を さほど要求されない化学分析装置では、 従来のヘラ攪拌機構の代替として本 攪拌機構を用いることで、 コンタミネーシヨンレスの化学分析装置を実現す ることが可能である。 また、 上述したように攪拌機構そのものが簡素である ため、 従来の化学分析装置と比べ高信頼でなおかつ化学装置全体の小型化も 可能である。 A feature of the present invention is that a sound wave generating means is provided outside the reaction vessel, and stirring is performed simultaneously with dispensing of the reagent. As a result, the processing speed of the chemical analyzer can be increased. It should be noted that sufficient advantages can be obtained simply by replacing the sound wave stirring mechanism shown in FIG. 2 with a conventional spatula type stirring mechanism. As described above, since the stirring mechanism according to the present invention is completely non-contact with the liquid to be measured to be mixed, the above-mentioned problems associated with the attachment of the spatula are completely eliminated. Therefore, in chemical analyzers that do not require much speed-up, a contamination-less chemical analyzer can be realized by using this stirring mechanism instead of the conventional spatula stirring mechanism. It is possible to In addition, since the stirring mechanism itself is simple as described above, it is more reliable than conventional chemical analyzers, and the size of the entire chemical device can be reduced.
これまで述べてきた実施例では高信頼性、 簡素性を重視して可動部の無い 攪拌機構の例である。 音源をアレイ化し、 使用する音源部を選択していく事 をその特徴としている。 他の実施例として、 音源部を可動する実施例につい て説明する。 第 7図に音源を可動して攪拌する構成を示す。 第 7図の実施例 では、 アレイ音源を用いる代わりに、 音源 7 0 3、 7 0 6に位置調整機構 7 0 2、 7 0 5を設けた例である。 第 2図の実施例と同様に、 メインコント ローラ 1 1 2は、 攪拌する液量と攪拌するタイミングに関する情報 2 0 4を 駆動ドライノ 7 0 1に送る。 駆動ドライバ 7 0 1は受け取った情報から、 液 面 2 0 9の高さに合わせて音波の照射位置を決定し、 位置調整機構 7 0 2、 7 0 5を制御して照射位置に音源部を移動する。 ついで; 攪拌タイミングの 情報に従って音波 7 0 を照射する。 その結果、 旋回流 7 0 8が発生し混合 が行なわれる。 なお本実施例では、 下方の音源の位置調整機構 7 0 5は上下 方向に移動するようにしているが、 左右方向に移動できないため、 音源部は 反応容器に対して予め一方側に片寄らせて設けてある。 側方の音源の位置調 整機構 7 0 2は、 上下方向と、 前後方向に移動可能に設けてある。 The embodiment described so far is an example of a stirring mechanism having no moving parts with emphasis on high reliability and simplicity. The feature is that sound sources are arrayed and the sound source section to be used is selected. As another embodiment, an embodiment in which the sound source unit is movable will be described. FIG. 7 shows a configuration in which the sound source is moved and stirred. In the embodiment shown in FIG. 7, instead of using the array sound source, the sound sources 703 and 706 are provided with position adjustment mechanisms 720 and 705, respectively. As in the embodiment shown in FIG. 2, the main controller 112 sends information 204 concerning the amount of liquid to be stirred and the timing of stirring to the drive dryer 701. Based on the received information, the drive driver 701 determines the irradiation position of the sound wave in accordance with the height of the liquid surface 209, and controls the position adjustment mechanism 702, 705 to move the sound source section to the irradiation position. Moving. Then, a sound wave 70 is applied according to the information on the stirring timing. As a result, a swirling flow 708 is generated and mixing is performed. In the present embodiment, the position adjustment mechanism 705 for the lower sound source is moved in the vertical direction, but cannot move in the left and right directions. It is provided. The side sound source position adjusting mechanism 720 is provided so as to be movable in the up-down direction and the front-back direction.
' これまでの実施例では、 反応容器の温度を一定に保っため、 反応容器は恒 温槽中に満たされた恒温水 2 1 1に浸されていた。 本発明における音波発生 手段の周波数は、 数 MH zの音波で、 水中であればよく伝播させることがで きるため、 反応容器外部に設けた音波発生手段でも、 反応容器内部に音波を 到達させる事が可能であった。 これに対して、 恒¾ を使わずに空気で温度 管理を行う空気恒温槽を用いた化学分析装置の場合には、 反応容器外部に音 波発生機構を設けると、 音波発生機構と反応容器の間に空気層が介在するた め音波の伝播が困難となる。 しかし、 空気恒温槽型の場合でも、 音波発生手' 段と反応容器の間を音響ィンピーダンスが水に近い材質の音波伝達機構 (音 響カップラ等) で結合することで音波を伝播させることができる。 その実施 例について次に述べる。 'In the examples so far, in order to keep the temperature of the reaction vessel constant, the reaction vessel was immersed in constant temperature water 211 filled in a constant temperature bath. The frequency of the sound wave generating means in the present invention is a sound wave of several MHz, which can be propagated well in water. Therefore, even if the sound wave generating means provided outside the reaction vessel makes the sound wave reach the inside of the reaction vessel. Was possible. On the other hand, in the case of a chemical analyzer using an air thermostat that controls the temperature with air instead of using a thermostat, if a sound wave generating mechanism is provided outside the reaction vessel, the sound wave generating mechanism and the reaction vessel There is an air layer between them This makes it difficult to propagate sound waves. However, even in the case of an air oven type, sound waves can be propagated by coupling the sound impedance between the sound wave generating means and the reaction vessel with a sound wave transmission mechanism (such as a sound coupler) whose material is similar to water. it can. The embodiment will be described below.
第 8図に空気恒温槽型の化学分析装置の攪拌部の断面図を示す。 本実施例 では、 音響カップラ 8 0 3、 8 1 0を備えた音源 8 0 2、 8 0 5に、 2軸 (音波の進行方向とそれに対して垂直方向) の位置調整機構 8 0 1、 8 0 4 が備え付けられている。 その他の構成は、 第 7図の実施例と同じである. 駆 動ドライバは、 反応容器に音響力ップラ 8 0 3、 8 1 0が接触するように移 動させる。 なお、 下方音源部は上下方向にのみ移動可能としているため、 予 め反応容器の中心よりずらして設けてある。 反応容器が移動中は、 音響カツ プラが反応容器に接触しないように待避させていることは言うまでもない。 このように、 音源部の位置を調節して、 音源と反応容器と'の音響的な伝ば経 路を確保する。 次いで、 攪拌タイミングの情報に従って音波を発生すれば、 空気型恒温槽の場合でもこれまでの実施例と同様な旋回流れ 7 0 6を癸生さ せ、 混合することが可能である。 FIG. 8 shows a cross-sectional view of the stirring section of the air-temperature-chamber type chemical analyzer. In this embodiment, a sound source 802, 805 provided with an acoustic coupler 803, 810 is provided with a position adjustment mechanism 801, 8 of two axes (the direction of sound wave propagation and the direction perpendicular thereto). 0 4 is provided. Other configurations are the same as those in the embodiment of FIG. 7. The drive driver moves the acoustic force pullers 803 and 810 to contact the reaction vessel. Since the lower sound source section can be moved only in the vertical direction, the lower sound source section is preliminarily offset from the center of the reaction vessel. It goes without saying that while the reaction vessel is moving, the acoustic coupler is retracted so as not to contact the reaction vessel. In this way, the position of the sound source is adjusted to secure an acoustic transmission path between the sound source and the reaction vessel. Next, if a sound wave is generated according to the information of the stirring timing, the swirling flow 706 similar to that in the previous embodiments can be mixed and mixed even in the case of the air-type constant temperature bath.
次に、 他の実施例として、 本攪拌機構を分注位置に加えて、 他の場所に補 助的な攪拌機構として追加した場合についで述べる。 第 9図に補助的な攪拌 機構を設けた場合の構成を示す。 第 9図(a)は第 6図(a)に示した実施例に 対し、 試薬分注との同時攪拌の位置以外に 2つの攪拌機構 9 0 1、 9 0 2を 設けた例である。 1サイクルの動作は、'第 6図(a)に示した実施例と同じで、 1サイクル後、 2サイクル後の停止期間中、 すなわち次の反応容器や、 次々 の反応容器が試薬分注及び攪拌を行っている時に、 補助攪拌機構で追加的な 攪拌を行っている。 このような補助的な加攪拌の機構は、 音源として用いて いる圧電素子を、 第 9図(b)のように製作することで容易に実現できる。 第 9図(b)は、 取り付ける恒温槽の曲率に合わせた一枚の圧電素子を、 反応容 器の位置 5 0 2、 9 0 1、 9 0 2にそれぞれ对応させて分割した電極を設け たものである。 第 9図(b)のような圧電素子は、 第 4図の圧電素子とほぼ同 じ工程で製作することができる。 本構成の音響発生装置とすることで、 攪拌 機構を容易に追加することが可能である。 また、 第 9図(b)では、 側方の音 源の例であるが、 同様に一枚の圧電素子にそれぞれの反応容器の位置に対応 した位置に霄極を加工することで、 下方音源も容易に製作することが可能で ある。 本構成のように補助攪拌機構を設ける事で、 高粘度サンプルや, 粘性 が高く混合しにくい試薬を用いた場合にも容易に十分な攪拌を行う事ができ る。 なお、 本実施例では 2段の攪拌機構を補助的に追加したが、 必に応じて それ以上追加することは容易である。 ' Next, as another embodiment, a case where this stirring mechanism is added to the dispensing position and added as an auxiliary stirring mechanism to another place will be described. Fig. 9 shows the configuration when an auxiliary stirring mechanism is provided. FIG. 9 (a) is an example in which two stirring mechanisms 901, 902 are provided in addition to the position of simultaneous stirring with reagent dispensing in the embodiment shown in FIG. 6 (a). The operation in one cycle is the same as that of the embodiment shown in Fig. 6 (a). After one cycle and during the stop period after two cycles, that is, the next reaction vessel and the next reaction vessel are dispensed with reagents. While stirring, additional stirring is performed by the auxiliary stirring mechanism. Such an auxiliary stirring mechanism can be easily realized by manufacturing a piezoelectric element used as a sound source as shown in FIG. 9 (b). No. Figure 9 (b) shows a single piezoelectric element that matches the curvature of the thermostat to be installed, and divided electrodes corresponding to the reaction vessel positions 502, 901, and 902, respectively. Things. The piezoelectric element as shown in FIG. 9 (b) can be manufactured by almost the same process as the piezoelectric element of FIG. With the sound generator of this configuration, it is possible to easily add a stirring mechanism. Fig. 9 (b) shows an example of a sound source on the side. Similarly, a single piezoelectric element is processed at the position corresponding to the position of each reaction vessel to produce a lower sound source. Can also be easily manufactured. By providing an auxiliary stirring mechanism as in this configuration, sufficient stirring can be easily performed even when a high-viscosity sample or a highly viscous reagent that is difficult to mix is used. In the present embodiment, a two-stage stirring mechanism is added as an auxiliary, but it is easy to add more as needed. '
以上説明したように、 本発明によれば、 キャリーオーバーレス '微小液量 の攪拌を可能とし、 より高速な分析処理能力を実現することができる。 また、 キャリーオーバーレス '微小液量の攪拌を可能とし、 より装置全体の小型化 図ることができる。 As described above, according to the present invention, it is possible to stir a carry-overless microfluidic liquid and realize a higher-speed analysis processing capability. In addition, the carryoverless method enables the stirring of a very small amount of liquid, thereby further reducing the size of the entire apparatus.
産業上の利用可能性 Industrial applicability
以上のように、 本発明は、 非接触で液体を攪拌混合する機構に関するもの で、 特に化学分析に装置に適用した場合について述べたが、 その他の非接触 で液体等を混合するものには適用可能である。 As described above, the present invention relates to a mechanism for mixing and mixing liquids in a non-contact manner, and particularly to a case where the present invention is applied to an apparatus for chemical analysis. It is possible.
Claims
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/JP2000/002320 WO2001077691A1 (en) | 2000-04-10 | 2000-04-10 | Chemical analyzer |
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| Application Number | Priority Date | Filing Date | Title |
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| PCT/JP2000/002320 WO2001077691A1 (en) | 2000-04-10 | 2000-04-10 | Chemical analyzer |
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| WO2001077691A1 true WO2001077691A1 (en) | 2001-10-18 |
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| WO (1) | WO2001077691A1 (en) |
Cited By (9)
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| WO2007015438A1 (en) * | 2005-08-03 | 2007-02-08 | Olympus Corporation | Mixing device and analysis device having the mixing device |
| JP2007040843A (en) * | 2005-08-03 | 2007-02-15 | Hitachi High-Technologies Corp | Automatic analyzer |
| WO2007023616A1 (en) * | 2005-08-23 | 2007-03-01 | Olympus Corporation | Analyzer, feeder, agitator and agitating method |
| JP2007181790A (en) * | 2006-01-10 | 2007-07-19 | National Maritime Research Institute | Melting equipment |
| WO2007099685A1 (en) * | 2006-02-28 | 2007-09-07 | Olympus Corporation | Stirrer and analyzer |
| WO2007099679A1 (en) * | 2006-02-28 | 2007-09-07 | Olympus Corporation | Stirrer and analyzer |
| JP2009121873A (en) * | 2007-11-13 | 2009-06-04 | Hitachi High-Technologies Corp | Automatic analyzer |
| JP2019124608A (en) * | 2018-01-17 | 2019-07-25 | 株式会社日立ハイテクノロジーズ | Chemical analyzer and sound wave stirrer used in chemical analyzer |
| US20230228783A1 (en) * | 2020-06-18 | 2023-07-20 | Hitachi High-Tech Corporation | Automatic Chemical Analysis Apparatus and Electrical Impedance Spectrometry Device |
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Cited By (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007015438A1 (en) * | 2005-08-03 | 2007-02-08 | Olympus Corporation | Mixing device and analysis device having the mixing device |
| JP2007040843A (en) * | 2005-08-03 | 2007-02-15 | Hitachi High-Technologies Corp | Automatic analyzer |
| WO2007023616A1 (en) * | 2005-08-23 | 2007-03-01 | Olympus Corporation | Analyzer, feeder, agitator and agitating method |
| JP2007181790A (en) * | 2006-01-10 | 2007-07-19 | National Maritime Research Institute | Melting equipment |
| JP2007232521A (en) * | 2006-02-28 | 2007-09-13 | Olympus Corp | Stirrer and analyzer |
| WO2007099679A1 (en) * | 2006-02-28 | 2007-09-07 | Olympus Corporation | Stirrer and analyzer |
| WO2007099685A1 (en) * | 2006-02-28 | 2007-09-07 | Olympus Corporation | Stirrer and analyzer |
| JP2007232522A (en) * | 2006-02-28 | 2007-09-13 | Olympus Corp | Stirrer and analyzer |
| US7808631B2 (en) | 2006-02-28 | 2010-10-05 | Beckman Coulter, Inc. | Stirrer and analyzer |
| JP2009121873A (en) * | 2007-11-13 | 2009-06-04 | Hitachi High-Technologies Corp | Automatic analyzer |
| JP2019124608A (en) * | 2018-01-17 | 2019-07-25 | 株式会社日立ハイテクノロジーズ | Chemical analyzer and sound wave stirrer used in chemical analyzer |
| US20230228783A1 (en) * | 2020-06-18 | 2023-07-20 | Hitachi High-Tech Corporation | Automatic Chemical Analysis Apparatus and Electrical Impedance Spectrometry Device |
| US12510553B2 (en) * | 2020-06-18 | 2025-12-30 | Hitachi High-Tech Corporation | Automatic chemical analysis apparatus and electrical impedance spectrometry device |
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