WO2006123771A1 - 分注量検出方法および吸液モニタ型分注装置 - Google Patents
分注量検出方法および吸液モニタ型分注装置 Download PDFInfo
- Publication number
- WO2006123771A1 WO2006123771A1 PCT/JP2006/310004 JP2006310004W WO2006123771A1 WO 2006123771 A1 WO2006123771 A1 WO 2006123771A1 JP 2006310004 W JP2006310004 W JP 2006310004W WO 2006123771 A1 WO2006123771 A1 WO 2006123771A1
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- WIPO (PCT)
- Prior art keywords
- suction
- liquid
- pipette tip
- pressure
- tip
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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
- G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
- G01N35/1009—Characterised by arrangements for controlling the aspiration or dispense of liquids
- G01N35/1016—Control of the volume dispensed or introduced
-
- 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
- G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
- G01N35/1009—Characterised by arrangements for controlling the aspiration or dispense of liquids
- G01N2035/1025—Fluid level sensing
Definitions
- the present invention relates to a dispensing amount detection method and a liquid amount monitoring type dispensing apparatus that detect a suction amount of a liquid by using a change in air pressure, and in particular, pipette tips for a liquid in which a biological material is suspended.
- the present invention relates to a method of monitoring liquid amount detection in a dispensing device that sucks in and dispenses into a test container by changing suction pressure, and a device to which the method is applied.
- Patent Document 1 a dispensing method in which a suction amount is detected and evaluated by sucking a liquid into a container force pipette tip with a dispensing device.
- Patent Document 1 Japanese Patent Laid-Open No. 62-64912
- Patent Document 2 Japanese Patent No. 306500
- the bubbles may be detected as the liquid level. If the liquid level is detected, it may be erroneously detected, which may cause a malfunction.
- the present invention has been made in view of the above-mentioned problems in the prior art, and the technical problem specifically set in order to solve this problem is the liquid liquid contained in the container. It is an object of the present invention to provide a dispensing amount detection method and a liquid absorption monitor type dispensing device that can detect the amount of liquid simply by measuring a pressure change that does not require detection of a surface.
- a problem-solving means that is specifically configured to cover all matters recognized as necessary for specifying a dispensing amount detection method and a liquid absorption monitor-type dispensing device that can effectively solve the problem. Is shown below.
- a first problem-solving means includes a pipette tip, a liquid suction / discharge mechanism for the pipette tip, a pressure sensor for detecting a pressure in the pipette tip, and the pipette
- the dispensing volume detection method that detects the suction state of the specified volume of the liquid to be sucked and discharged by the dispensing device having the tip lifting mechanism, up to the deepest part of the container that holds the liquid to be measured
- the shape of the pipette tip, the specified suction speed, and the suction I time! It is characterized in that to have a and extent.
- the rate of change (time differential value) based on the measured pressure change is calculated by comparing the measured pressure change with a predetermined threshold.
- the suction state may be detected.
- the “deepest part” is a position where the liquid contained in the container can be sucked, and is a position near or near the bottom of the container.
- the second problem solving means is that, in the suction detection step, the measured pressure change is compared with a predetermined threshold value, and the threshold force is also based on a pressure value that deviates. Thus, the suction state is detected.
- the third problem solving means according to the dispensing amount detection method is the same as that in the suction detection step. Based on the pressure value that deviates from the threshold force, it is detected whether there is insufficient suction or is empty.
- a fourth problem solving means related to the dispensing amount detection method is the same as that in the suction detection step.
- the presence or absence of the pipette tip is detected based on the presence or absence of the measured pressure change.
- the fifth problem solving means according to the dispensing amount detection method is the same as that in the suction detection step.
- the sixth problem solving means according to the dispensing amount detection method is characterized in that, in the insertion step, the tip of the pipette tip stops at a position where the bottom force of the container is spaced at a predetermined interval. It is.
- the seventh problem solving means related to the dispensing amount detection method is the same as that described above, wherein the pipette tip is connected to the narrow-diameter portion provided with the tip, and the suction-discharge mechanism in communication with the small-diameter portion. And the thinning portion is inserted into the liquid in the insertion step.
- examples of the shape of the pipette tip suitable for this dispensing amount detection method include, for example, the pipette tips of Design Registration No. 1068693 or No. 1068693-Class 1.
- an intermediate-diameter portion having an intermediate size between the small-diameter portion and the large-diameter portion may be provided at an intermediate position between them.
- a first problem-solving means includes a pipette tip, a lifting / lowering mechanism for the pipette tip, a liquid suction / discharge mechanism for the pipette tip, and the inside of the pipette tip.
- the lift mechanism is operated so that the tip of the pipette tip is inserted to the deepest part of the container that stores the liquid to be measured, and the pressure sensor that detects the pressure of the liquid to be measured, and the liquid is inserted into the pipette tip at a predetermined suction speed.
- the suction / discharge mechanism is operated so as to suck the pressure, and the measurement value of the pressure sensor is input, and the suction state is determined based on the measured pressure change, the shape of the pipette tip, the predetermined suction speed, and the suction time. And a control unit for detection.
- the control unit determines the measured pressure change in advance.
- the suction state is detected based on a pressure value that is out of the threshold force.
- the pipette tip has a narrow-diameter portion provided with the tip, and a large-diameter portion communicating with the narrow-diameter portion and connectable to the suction / discharge mechanism. It is characterized by.
- the specified liquid amount is obtained simply by measuring the pressure change without detecting the liquid level of the liquid contained in the container.
- the liquid suction state can be detected.
- the measured pressure change is compared with a preset threshold value, and based on the pressure value that is out of the threshold force, it is easy and high. It is possible to detect the suction state of the liquid of the liquid amount specified by reliability.
- the amount of the sucked liquid is insufficient due to the comparison with a preset threshold value. It can detect whether the liquid is empty or empty.
- the tip of the pipette tip is positioned at a certain distance from the bottom force of the container, so that the suction state becomes uniform and the liquid volume is measured. The reliability of the liquid is improved, and the dispensing amount can be detected with high accuracy.
- a pipette tip having a small-diameter portion and a large-diameter portion is used, and the liquid contacts only the small-diameter portion. Therefore, the influence of the insertion into the liquid can be minimized, and a minute amount of liquid can be accommodated in various shapes of containers.
- the control unit moves up and down. Operate the mechanism to insert the tip of the pipette tip to the deepest part of the container that contains the liquid to be measured, and operate the suction / discharge mechanism to suck the liquid into the pipette tip.
- the suction / discharge mechanism By inputting the pressure as the measured value of the pressure sensor and correcting the measured pressure and its change in consideration of the shape of the pipette tip, the predetermined suction speed and the suction time, a normal specified fluid volume is aspirated. It is possible to identify insufficient suction or empty state, and to accurately grasp the suction state of the specified liquid volume at the time of dispensing.
- the measured pressure change is compared with a predetermined threshold, and the suction is accurately performed based on the pressure value out of the threshold force.
- a time-series change of the pulling state can be obtained. As a result, it is possible to discriminate whether the normal designated liquid amount is sucked or insufficiently sucked from the obtained time-series change of the sucked state, and the sucked state at the time of dispensing can be accurately grasped.
- the pipette tip having a small diameter portion and a large diameter portion is used. Minimize, and can accommodate small volumes of liquids and containers of various shapes.
- the pipetter 10 in the embodiment is supported in the container 1 while being supported substantially vertically above the opening la of the container 1! Insert the tip (lower end) 3a into the liquid 2 to be spilled.
- a pressure sensor 7 connected from the side wall of the nozzle member 4 via a pipe or an air hose 6.
- the tip portion 3a of the pipette tip 3 is provided in a small diameter portion 3c having a thickness that can be inserted into the container 1, and the upper end portion 3b communicates with the small diameter portion 3c and the suction / discharge mechanism.
- the small diameter portion 3c and the large diameter portion 3d are funnel-shaped. Is connected via the transition part 3e. As the shape of the transition part 3e, there are other cases where there is a step or a tapered conical shape.
- the pressure measurement result by the pressure sensor 7 is transmitted to the control unit 8, and the control unit 8 draws the suction liquid amount and its time-series change based on the pressure measurement result and normal suction of the specified liquid amount, insufficient suction, or
- the suction state such as an empty state is identified and monitored, and the operation of the suction / discharge mechanism 5 is controlled according to the suction state.
- control unit 8 operates a lifting mechanism (not shown) (in the arrow direction A) to move the pipetter 10 in the vertical direction, and moves the tip 3a of the pipette tip 3 to the container.
- a lifting mechanism (not shown) (in the arrow direction A) to move the pipetter 10 in the vertical direction, and moves the tip 3a of the pipette tip 3 to the container.
- the tip 3a of the pipette tip 3 is inserted to a position close to the bottom of the container 1 so that the liquid can be sucked.
- Actuate structure 5 in the direction of arrow B to control the air to be taken in and out of pipette tip 3 and to suck or discharge liquid 2.
- this control unit 8 when the dispensing amount is detected, the tip 3a of the pipette tip 3 is lowered, and a position above the bottom of the container 1 by a certain dimension (for example, 1 mm) (hereinafter referred to as the deepest part). When it is positioned at, stop descending and fix the suction position.
- a certain dimension for example, 1 mm
- the suction / discharge mechanism 5 is operated to perform suction at a constant suction volume, so that the liquid in the container 1 is sucked, the normal specified liquid volume is suctioned, the suction force is insufficient or empty, and the pipette tip
- the suction is continued while monitoring the suction state, such as whether the tip 3a of 3 is clogged and the suction amount does not reach the predetermined amount, or whether the suction time has passed normally. If the specified suction time has passed without any abnormality, it is assumed that the specified amount of liquid has been sucked normally, and the suction / discharge mechanism 5 is stopped to stop the suction.
- the control unit 8 determines the result measured by the pressure sensor 7 as follows.
- the container When the tip 3a of the pipette tip 3 is located at the deepest part of the container 1, the container is empty if the pressure does not decrease below the set value.
- the pressure set value is set to -0.2 atm.
- the pressure set value is set to ⁇ 2 atm.
- the timeout time is a time for sucking a predetermined volume of liquid.
- the suction / discharge mechanism 5 and the lifting / lowering mechanism are returned to their original positions, and the container 1 containing the liquid to be dispensed is placed at the specified position of the dispensing device, and the dispensing device is ready for use. Complete the state (step 11).
- the control unit 8 initializes the data processing unit including the cpu, and transmits the data transmitted from the pressure sensor 7 to the digital data at a sampling rate of 80 times per lmsec (millisecond). To be able to analyze the pressure measurement results (step 12).
- the lifting mechanism is actuated downward, and the pipette tip 3 is lowered by a predetermined dimension, and the tip 3a of the pipette tip 3 is the deepest part of the container 1 containing the liquid (about lm m above the bottom).
- the suction / discharge mechanism 5 is operated to the suction side, and the liquid in the container 1 is sucked into the pipette tip 3 (step 13).
- the transmitted pressure information is AZD-converted by the control unit 8 and taken in as digital data at a predetermined sampling rate, data analysis is performed, the suction state is analyzed, and the state of each unit is monitored (step 14).
- the control unit 8 analyzes the data acquired at the specified sampling rate, and the suction is continued even after the set suction time determined based on the specified amount of liquid. 15) No empty suction (step 16), no clogging (step 17), liquid is sucked as specified Step 18) is monitored, and it is checked whether or not the set suction time has been reached (Step 19) . If the specified suction time determined based on the specified fluid volume has not been reached, the procedure returns to Step 15 and suction and its suction are performed. The state monitoring is continued, and if the specified suction time has been reached, the suction processing is terminated normally (step 20).
- the pipetter 10 After extracting the pipette tip 3 from the container 1, the pipetter 10 is moved to the position of the inspection container (not shown) that is arranged to receive the sucked liquid, and the lifting mechanism is moved downward. Then, the suction / discharge mechanism 5 is operated to the discharge side to discharge the liquid in the pipette tip 3 into the test container.
- the lifting mechanism is moved upward to move the pipette tip 3 to the upper side of the cuvette, and then the pipetter 10 is returned to the position where the container 1 is placed to perform dispensing work. Repeat.
- the control unit 8 takes in the atmospheric pressure as data from the pressure sensor 7 before suction (step 21), operates the suction / discharge mechanism 5 to the suction side, and measures the suction pressure (step 22)
- the nozzle member 4 and therefore the pipette tip 3 are lowered by a predetermined amount (step 23).
- Steps 25 and 27 the process of continuing the suction without passing through the following empty suction and liquid level detection processing steps. Proceed to step 26.
- step 25 If the liquid is not sucked, while the pipette tip 3 is lowered, the temporary pressure change when reaching the liquid level is monitored to detect whether or not the liquid has been sucked (step 25). ). At this time, if there is a set pressure change, the liquid level is detected. If the liquid level is detected, the process proceeds to the continuous suction process (step 26).
- Step 27 If there is no pressure change in the liquid level detection, the pressure change is continuously monitored, and the changes in both the amount of drop of the pipette tip 3 and the measured pressure are analyzed to determine whether or not empty suction is performed ( Step 27).
- stop suction immediately (step 28).
- control unit 8 samples the data from the pressure sensor 7 (step 31), and calculates the suction flow rate and suction amount from the pressure and elapsed time (step 32). ) Analyze the relationship between suction volume and pressure (step 33).
- step 35 If clogging is not found as a result of this analysis, the suction is continued, and the suction is completed when the specified amount of the specified amount of liquid is sucked (step 35). If clogging is recognized, the suction is stopped because the suction amount is insufficient (step 36). In this case, the sample related to container 1 where clogging has occurred is excluded after dispensing.
- FIG. 7 shows an example in which 500 ⁇ 1 of grease is sucked instead of the liquid.
- the pressure drops to about -2 atm per about 10msec, resulting in a clogged state. That is, the rate of change in pressure is about -0.2 atm / msec.
- this pressure value changes until the sucking time ends.
- the control unit 8 samples data from the pressure sensor 7 (step 41), and monitors the change in pressure over time (step 42). As a result of monitoring the pressure change, the pressure starts to drop suddenly, whether or not the pressure drop in the set range continues for the set time (step 43), then the pressure starts to rise sharply and set Whether the pressure increase in the specified range continues for the set time (Step 4 4), and whether or not the idle suction is started after this sudden pressure fluctuation (Step 45). If so, it is determined that the amount of liquid is insufficient, and suction is immediately stopped (step 46) and error processing is executed (step 47), and the processing step for monitoring the shortage of liquid is completed.
- Samples related to Container 1 with insufficient liquid volume are excluded after dispensing.
- insufficient liquid amount for example, two types of solutions having different viscosities (Lysis solution, DW solution) are used, and three specified liquid amounts are drawn (100 1, 200 ⁇ 1, (400 / zl) as a result of dispensing work when the liquid in the container is (1) no shortage, (2) the same amount as the suction amount, and (3) 50 1 shortage are summarized in Figure 8.
- the suction pressure of the highly viscous Lysis solution requires a stronger suction pressure, but the Lysis solution and the DW solution both have a suction curve without clogging, except when the liquid volume is insufficient. It is changing according to.
- Suction curve shows a different change from the case, and it can be clearly distinguished from the case of normal dispensing by the state of the change that stands out.
- the amount of liquid is about 50 1 short by evaluating by comparing with what point the standard suction curve deviates. Even in such a case, it becomes possible to detect a shortage of liquid.
- the pressure change waveform shown in Fig. 8 is clearly divided into three regions (1, II, III).
- the first region I corresponds to the small diameter portion 3c of the pipette tip 3
- the second region II corresponds to the transition portion
- the third region III corresponds to the large diameter portion. It corresponds to 3d.
- the change in pressure depends on the shape of the pipette tip.
- FIG. 9 is a perspective view showing the entire liquid absorption monitor type dispensing apparatus 50 according to the present embodiment.
- the liquid absorption monitor type dispensing device 50 has a base plate 51 on the lower side.
- An LM guide 52 is mounted on the base plate 51 along the X-axis direction (in a horizontal plane), and a stage 53 is connected to the LM guide 52. Is provided so as to be movable in the X-axis direction.
- the base plate 51 is provided with a main body portion 54 provided so as to be unable to move in a horizontal plane including the X-axis direction.
- the main body portion 54 includes a nozzle head 61 provided with six nozzle members 4 to which the pipette tip 3 is to be attached and the cylinder-type suction / discharge mechanism 5.
- the nozzle head 61 is movable in the vertical direction, and has six inner diameters slightly larger than the outer diameter of the pipette tip 3 and slightly larger than the outer diameter of the nozzle member 4 at positions corresponding to the nozzle members 4.
- a through hole is formed, and a prismatic remover 58 for removing the pipette chip 3 attached to the nozzle member 4 is provided.
- the stage 53 is movable in the X-axis direction so as to be under the main body portion 54.
- a tube hole 55a for placing or storing a container such as a sample tube at a position corresponding to the position of the six nozzle members 4 and the pipette tip 3 are mounted at a position corresponding to the position.
- a cartridge rack 56 is provided to be placed or accommodated at a position corresponding to the above position.
- the nozzle head 61 is inserted so that the nozzle member 4 is inserted from above into the pipette tip 3 accommodated in the tip hole 55b of the stage 53. Wear by lowering.
- nozzle head 61 Inside the nozzle head 61, there are six pressure sensor units (not shown in FIG. 9) each incorporating a pressure sensor 7 communicating with the nozzle member 4 via a thin tube, and each nozzle member It is provided for every four.
- a plunger 57 On the upper side of the nozzle head 61, a plunger 57 that slides in the cylinder of the suction / discharge mechanism 5 is provided.
- the plunger 57 is fixed by a P-axis motor 59 that is fixed to the nozzle head 61.
- the nozzle head 61, the plunger 57, and the P-axis motor 59 are driven in the vertical direction by the Z-axis motor 60 provided on the base plate 51. As a result, the tip of the pipette tip 3 attached to the nozzle member 4 can be lowered to the deepest part of the container.
- a magnet unit 62 and a magnet unit motor 63 are provided below the nozzle member 4 and are driven so that the magnet unit 62 approaches and separates from the axis of the nozzle member 4.
- the magnet unit 62 does not move up and down by the Z-axis motor 60 but is fixed in the vertical direction with respect to the base plate 51.
- main body portion 54 may be movable in a horizontal plane with respect to the stage 53 as long as the stage 53 and the main body portion 54 are relatively movable. Further, the number of nozzle members 4 and the like is not limited to six.
- the amount of sucked liquid can be obtained only by measuring the pressure change without detecting the liquid level of the liquid contained in the container.
- the liquid level can also be detected from the pressure measurement results.
- the force that the amount of sucked liquid is insufficient can be detected whether the liquid in the container is empty or empty.
- the tip of the pipette tip is positioned at a certain distance from the bottom of the container, the suction state becomes uniform, the reliability of the specified liquid volume measurement is improved, and the dispensed volume is accurately detected. be able to.
- the control unit operates the lifting mechanism to insert the tip of the pipette tip to the deepest part of the container that stores the liquid to be measured, and operates the suction / discharge mechanism to Liquid is sucked into the pipette tip, the pressure inside the pipette tip at the time of suction is also input as the pressure sensor force, and based on the measured pressure and its change and a predetermined threshold value, the pressure value deviating from the threshold value is By correcting in consideration of the shape of the chip, the predetermined suction speed and the suction time, the amount of suction liquid and its time-series change can be obtained with high accuracy.
- FIG. 1 is a partial perspective explanatory view showing a pipetter according to an embodiment of the present invention.
- FIG. 2 is a graph showing a pressure measurement result of a suction operation according to an embodiment of the present invention.
- FIG. 3 is a flowchart of a suction operation using a pipetter according to an embodiment of the present invention.
- FIG. 4 is a flowchart of liquid level detection and idle suction monitoring processing using the pipettor.
- FIG. 5 is a flowchart of clogging monitoring processing using the pipettor.
- FIG. 6 is a flowchart of a liquid shortage monitoring process using the pipettor.
- FIG. 7 is a graph showing the measurement result of the clogged state in the suction work according to the present invention.
- FIG. 8 is a graph showing the measurement result of the insufficient liquid amount in the suction work according to the present invention.
- FIG. 9 is an overall perspective view of a liquid absorption monitor type dispensing device according to an embodiment of the present invention.
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Abstract
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Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP06756360.1A EP1882951B1 (en) | 2005-05-19 | 2006-05-19 | Method of detecting dispensed quantity, and liquid suction monitoring dispensing apparatus |
US11/920,663 US8307722B2 (en) | 2005-05-19 | 2006-05-19 | Method of detecting dispensed quantity, and liquid suction monitoring dispensing apparatus |
JP2007516347A JP5122949B2 (ja) | 2005-05-19 | 2006-05-19 | 分注量検出方法および吸液モニタ型分注装置 |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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JP2005-147108 | 2005-05-19 | ||
JP2005147108 | 2005-05-19 |
Publications (1)
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WO2006123771A1 true WO2006123771A1 (ja) | 2006-11-23 |
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ID=37431340
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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PCT/JP2006/310004 WO2006123771A1 (ja) | 2005-05-19 | 2006-05-19 | 分注量検出方法および吸液モニタ型分注装置 |
Country Status (5)
Country | Link |
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US (1) | US8307722B2 (ja) |
EP (1) | EP1882951B1 (ja) |
JP (1) | JP5122949B2 (ja) |
TW (1) | TWI422801B (ja) |
WO (1) | WO2006123771A1 (ja) |
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JP2010256200A (ja) * | 2009-04-27 | 2010-11-11 | Aloka Co Ltd | 分注装置 |
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JP2013178171A (ja) * | 2012-02-28 | 2013-09-09 | Toshiba Corp | 自動分析装置 |
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JP2016090526A (ja) * | 2014-11-11 | 2016-05-23 | 株式会社東芝 | 自動分析装置 |
JP2019536030A (ja) * | 2016-11-15 | 2019-12-12 | テカン シュヴァイツ アクチエンゲゼルシャフト | 分注方法及び分注デバイス |
JP7221864B2 (ja) | 2016-11-15 | 2023-02-14 | テカン トレイディング アクチエンゲゼルシャフト | 分注方法及び分注デバイス |
CN108956632A (zh) * | 2018-05-31 | 2018-12-07 | 嘉兴懿铄精密模具有限公司 | 一种用于移液吸头的检测设备 |
WO2022029826A1 (ja) * | 2020-08-03 | 2022-02-10 | 株式会社日立ハイテク | 分注装置、及び方法 |
JP7516521B2 (ja) | 2020-08-03 | 2024-07-16 | 株式会社日立ハイテク | 分注装置、及び方法 |
Also Published As
Publication number | Publication date |
---|---|
EP1882951A1 (en) | 2008-01-30 |
JP5122949B2 (ja) | 2013-01-16 |
TWI422801B (zh) | 2014-01-11 |
US8307722B2 (en) | 2012-11-13 |
TW200702638A (en) | 2007-01-16 |
EP1882951B1 (en) | 2017-09-27 |
US20090211380A1 (en) | 2009-08-27 |
EP1882951A4 (en) | 2011-09-07 |
JPWO2006123771A1 (ja) | 2008-12-25 |
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