WO2021245989A1 - 自動分析装置 - Google Patents
自動分析装置 Download PDFInfo
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- WO2021245989A1 WO2021245989A1 PCT/JP2021/004769 JP2021004769W WO2021245989A1 WO 2021245989 A1 WO2021245989 A1 WO 2021245989A1 JP 2021004769 W JP2021004769 W JP 2021004769W WO 2021245989 A1 WO2021245989 A1 WO 2021245989A1
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- probe
- reagent
- sample
- liquid
- tip
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- 239000000523 sample Substances 0.000 claims abstract description 444
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 171
- 239000007788 liquid Substances 0.000 claims abstract description 165
- 238000007599 discharging Methods 0.000 claims abstract description 35
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- 230000007246 mechanism Effects 0.000 claims description 70
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- 230000000694 effects Effects 0.000 claims description 28
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- 238000001514 detection method Methods 0.000 claims 1
- 238000003756 stirring Methods 0.000 abstract description 41
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- 239000012295 chemical reaction liquid Substances 0.000 description 62
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- 239000008280 blood Substances 0.000 description 2
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- 230000002411 adverse Effects 0.000 description 1
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Images
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
- G01N35/1011—Control of the position or alignment of the transfer device
-
- 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
- G01N35/1002—Reagent dispensers
-
- 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
-
- 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
- G01N2035/1027—General features of the devices
- G01N2035/1048—General features of the devices using the transfer device for another function
- G01N2035/1058—General features of the devices using the transfer device for another function for mixing
Definitions
- the present invention relates to an automatic analyzer.
- an automatic analyzer that analyzes components such as blood, urine, and spinal fluid of a patient, (a) biochemistry that measures the amount of transmitted light or scattered light obtained by irradiating the reaction solution of a sample and a reagent with light.
- biochemistry that measures the amount of transmitted light or scattered light obtained by irradiating the reaction solution of a sample and a reagent with light.
- an automatic analyzer an immunoautomatic analyzer that reacts a reagent to which a labeled body is added with a sample, and measures the amount of emitted light of the labeled body.
- Patent Document 1 a technique for preventing liquid splattering when a liquid is discharged from a probe to a reaction vessel is disclosed (see Patent Document 1).
- the probe is discharged while being immersed in a liquid of several mm. It is not clear whether the liquid level above the probe tip and the liquid flow around the probe tip are poor and can be efficiently agitated by the ejection operation.
- An object of the present invention is to provide an automatic analyzer capable of efficiently stirring by a discharge operation.
- the probe rises while ejecting the sample or the reagent, so that the liquid in the container discharged from the probe is discharged.
- the distance between the liquid level in the container and the tip of the probe is gradually increased.
- FIG. 6 is a diagram schematically showing the movement of the dispensing probe 30 and its effect when the automatic analyzer 10 simultaneously dispenses a sample and a first reagent in the first embodiment.
- the relationship diagram between the height of the tip of the dispensing probe 30 from the bottom of the reaction vessel 14 and the height of the liquid level of the reaction liquid 36.
- FIG. 6 is a diagram schematically showing the movement of the dispensing probe 30 and its effect when the automatic analyzer 10 simultaneously dispenses a sample and a first reagent in the second embodiment.
- the relationship diagram between the height of the tip of the dispensing probe 30 from the bottom of the reaction vessel 14 and the height of the liquid level of the reaction liquid 36.
- FIG. 6 is a diagram schematically showing the movement of the dispensing probe 30 and its effect when the automatic analyzer 10 simultaneously dispenses a sample and a first reagent in the third embodiment.
- FIG. 4 is a diagram schematically showing the movement of the dispensing probe 30 and its effect when the automatic analyzer 10 simultaneously dispenses a sample and a first reagent in the fourth embodiment.
- FIG. 5 is a diagram schematically showing the movement of the dispensing probe 30 and its effect when the automatic analyzer 10 simultaneously dispenses a sample and a first reagent in the fifth embodiment.
- the relationship diagram between the height of the tip of the dispensing probe 30 from the bottom of the reaction vessel 14 and the height of the liquid level of the reaction liquid 36.
- FIG. 5 is a diagram schematically showing the movement of the dispensing probe 30 and its effect when the automatic analyzer 10 simultaneously dispenses a sample and a first reagent in the fifth embodiment.
- the relationship diagram between the height of the tip of the dispensing probe 30 from the bottom of the reaction vessel 14 and the height of the liquid level of the reaction liquid 36.
- FIG. 6 is a diagram schematically showing the movement of the dispensing probe 30 and its effect when the automatic analyzer 10 simultaneously dispenses a sample and a first reagent in the sixth embodiment.
- the relationship diagram between the height of the tip of the dispensing probe 30 from the bottom of the reaction vessel 14 and the height of the liquid level of the reaction liquid 36.
- FIG. 1 is a block diagram schematically showing an overall view of the automatic analyzer 10 according to the first embodiment.
- the automatic analyzer 10 mainly includes an analysis unit 1 that analyzes a mixed solution of a liquid sample and a reagent, a computer 3 (control unit) that controls the analysis unit 1, and an analysis control unit 8.
- the analysis control unit 8 controls the operation of each mechanism of the analysis unit 1. Details will be described later.
- the computer 3 is connected to the analysis control unit 8, the A / D converter 7, and the like via the interface 9.
- the computer 3 sends a command to the analysis control unit 8 and the like to control the operation of each mechanism.
- the A / D converted data (measurement value) obtained from the analysis unit 1 is taken into the computer 3.
- the computer 3 performs arithmetic processing using the captured data (measurement value). That is, the computer 3 can control each mechanism of the analysis unit 1 via the analysis control unit 8 and can execute data arithmetic processing.
- the interface 9 is connected to a printer 4 for printing, a memory 6 as a recording device, a keyboard 2 for inputting operation commands, and a display device 5 composed of a CRT display or a liquid crystal display.
- the memory 6 is composed of, for example, a hard disk memory or an external memory. Information such as analysis parameters, analysis item requests, calibration results, and analysis results is recorded in the memory 6.
- FIG. 2 is a plan view schematically showing the configuration of the analysis unit 1.
- the analysis unit 1 mainly includes a sample rack 25, a reagent disk 21, and a reaction disk (incubator) 15.
- the sample rack 25 holds the sample container 24.
- the reagent disk 21 holds the reagent container 22.
- the reaction disk 15 holds the reaction vessel 14 on its circumference.
- the analysis unit 1 further includes a dispensing mechanism 11, a dispensing mechanism cleaning unit 26, a reaction vessel cleaning unit 27, a light source 12, and a spectroscopic detector 13.
- the sample rack 25 is movable in the horizontal direction, and a plurality of sample containers 24 for holding biological samples such as blood (hereinafter referred to as samples) are placed.
- the reagent disk 21 can be rotated intermittently clockwise and counterclockwise, and a plurality of reagent containers 22 corresponding to the analysis items of the automatic analyzer 10 are placed.
- FIG. 2 the reagent disk 21 is partially broken and shown.
- the reagent disk 21 is circular in a plan view.
- two reagent containers 22 are arranged in the radial direction of the reagent disk 21 (two reference numerals 22 at both ends). That is, in the reagent disk 21, two circular rows of reagent containers 22 arranged so as to surround the center of the reagent disk 21 exist concentrically.
- the reagents in the two reagent containers 22 arranged in the radial direction may be different types of reagents from each other.
- the reaction disk 15 can be rotated intermittently clockwise and counterclockwise, and a plurality of reaction vessels 14 for reacting a sample and a reagent are placed on the circumference.
- the dispensing mechanism 11 sucked the sample from the sample container 24 placed on the sample rack 25, sucked the reagent from the reagent container 22 in the reagent disk 21, and sucked it into the reaction container 14 in the reaction disk 15. Discharge and dispense the liquid.
- the dispensing mechanism 11 does not only refer to the tip of the container that constitutes the flow path for sucking and discharging the liquid, but also the flow from the pump (for example, a syringe) for sucking and discharging the liquid to the tip. Shows the containers around the entire road.
- FIG. 2 shows a vertical rotation operation unit (moving unit) of the dispensing mechanism 11.
- the vertical rotation operation unit is an operation unit for changing the location where the liquid is sucked and discharged.
- the light source 12 is installed near the outer periphery of the reaction disk 15, and irradiates the reaction vessel 14 with light.
- the spectroscopic detector 13 is installed on the opposite side of the light source 12 with the reaction vessel 14 interposed therebetween, and measures the absorbance of light irradiated by the light source 12 on the sample, the reagent, or the mixed solution of the sample and the reagent in the reaction vessel. Measure optically.
- the light source 12 irradiates each of the plurality of reaction vessels 14 that move with the rotational movement of the reaction disk 15 with light at the timing when the reaction vessel 14 crosses a predetermined optical path.
- the spectroscopic detector 13 detects the light transmitted through the sample, the reagent, or the mixed solution of the sample and the reagent contained in each reaction vessel 14 for each wavelength of the inspection item.
- An analog signal such as the intensity of light detected by the spectroscopic detector 13 is input to the A / D converter 7 (see FIG. 1).
- the A / D converter 7 generates standard data or test data based on the input digital signal, and these generated data are taken into the computer 3.
- the reaction vessel cleaning unit 27 cleans the inside of each of the plurality of reaction vessels 14 for which the measurement by the spectroscopic detector 13 has been completed.
- the analysis unit 1 may have a stirring mechanism for stirring the liquid in the reaction vessel.
- the stirring mechanism include a method of immersing a spatula in a solution in a reaction vessel 14 and physically stirring the spatula by rotating the spatula, and a method of irradiating the solution with ultrasonic waves to generate a swirling flow. Be done.
- the analysis control unit 8 controls the operation of each of the plurality of units constituting the analysis unit 1.
- the analysis control unit 8 controls the rotational motion of each of the reagent disk 21 and the reaction disk 15 by driving a moving mechanism such as a disk.
- the analysis control unit 8 controls the horizontal movement of the sample rack 25 by driving a belt pulley mechanism or a ball screw mechanism.
- the analysis control unit 8 controls the vertical movement and the rotational movement of the dispensing mechanism 11 by driving the arm moving mechanism.
- the analysis control unit 8 controls the vertical movement of the reaction vessel cleaning unit 27 by driving the elevating mechanism.
- the analysis control unit 8 controls the suction / discharge operation of various pumps (described later with reference to FIG. 3) connected to the dispensing mechanism 11, and supplies cleaning water to the reaction vessel cleaning unit 27. Controls liquid feeding / stopping operation.
- FIG. 3 shows a schematic view of the dispensing mechanism 11.
- the dispensing mechanism 11 includes a dispensing probe 30, a dispensing arm 41, and a vertical rotation operating unit 42.
- the dispensing probe 30 is attached to one end of the dispensing arm 41, and the dispensing arm 41 is connected to the dispensing probe 30 and the vertical rotation operation unit 42.
- the vertical rotation operation unit 42 has a two-axis movement mechanism of vertical (vertical direction) and rotation.
- the dispensing mechanism 11 can be moved up and down and rotated by the vertical rotation operation unit 42. As a result, the dispensing mechanism 11 moves to the reagent suction position where the reagent container 22 (see FIG. 2) is installed to suck the reagent, and the sample container 24 (see FIG.
- the vertical rotation operation unit 42 is controlled by the analysis control unit 8 (see FIGS. 1 and 2).
- the dispensing flow path 47 is a flow path of the dispensing mechanism 11 that passes through the inside of the dispensing arm 41 and the vertical rotation operation unit 42.
- the dispensing probe 30 is connected to the metering pump 45 via a dispensing flow path 47 in the dispensing arm 41.
- the metering pump 45 has a plunger 43 and a drive unit 44, and is connected to the pump 46 through a valve 49.
- the metering pump 45 is controlled by the analysis control unit 8 (see FIGS. 1 and 2).
- the suction operation and the discharge operation by the dispensing mechanism 11 are executed by the plunger 43 fixed to the metering pump 45 moving up and down (reciprocating motion).
- a working fluid for example, pure water
- the dispensing mechanism 11 includes a liquid level detector 48 for detecting the liquid level of a sample, a reagent, and a mixed solution of the sample and the reagent.
- the liquid level detector 48 detects the liquid level by changing the capacitance according to the contact between the liquid level and the dispensing probe 30.
- FIG. 4 is a flowchart illustrating the measurement operation of the automatic analyzer 10. A series of analysis operations in the automatic analyzer 10 will be described with reference to FIG.
- Step S01 Preliminary operation
- the analysis unit 1 receives a command from the computer 3 to start the analysis operation via the interface 9
- the reaction vessel cleaning unit 27 starts cleaning the reaction vessel 14, and the pure water discharged from the reaction vessel cleaning unit 27 is used. And measure the water blank.
- This water blank measurement value serves as a reference for the absorbance subsequently measured in the reaction vessel 14.
- the sample container 24 moves to the sample dispensing position located on the circumference of the dispensing mechanism 11 in the rotation direction by the horizontal operation of the sample rack 25.
- the reagent disk 21 rotates so that the reagent container 22 of the corresponding analysis item is positioned at the reagent suction position located on the circumference of the dispensing mechanism 11 in the rotation direction.
- the dispensing mechanism 11 sucks air in the air and forms an air layer at the tip of the dispensing probe 30.
- the working fluid for example, pure water
- the reagent sucked from the reagent container 22 are contained in the dispensing probe 30. It is an air layer provided to prevent mixing.
- Step S02 After sucking the reagent, the dispensing mechanism 11 moves up and down to an aerial position, sucks air, and forms an air layer at the tip of the dispensing probe 30. This air layer is an air layer provided to prevent the sample sucked from the sample container 24 from being mixed with the reagent in the dispensing probe 30. Then, the dispensing mechanism 11 moves to the dispensing mechanism cleaning unit 26 by rotary motion and vertical motion, and cleans the tip of the dispensing probe 30 with cleaning water. After washing, the dispensing mechanism 11 moves to the sample suction position by rotational movement and vertical movement, and sucks the sample from the sample container 24 into the dispensing probe 30.
- Step S03 After the sample is sucked, the dispensing mechanism 11 moves to the dispensing mechanism cleaning unit 26 by rotary motion and vertical motion, and the tip of the dispensing probe 30 is washed with washing water. Next, the dispensing mechanism 11 moves to the dispensing position by rotary motion and vertical motion, and a predetermined amount of the sample and the reagent are simultaneously dispensed into the reaction vessel 14. Details of this sample and reagent dispensing will be described later.
- Step S04 After the sample and the reagent are dispensed, the dispensing mechanism 11 sucks a predetermined amount of the mixture in order to stir the mixture of the sample and the reagent in the reaction vessel 14, and then discharges the mixture into the reaction vessel 14 again. .. This stirs the mixture.
- This re-suction and re-discharge operation after discharging the sample and reagent is hereinafter referred to as pipette stirring.
- a stirring operation may be performed by a stirring mechanism other than pipette stirring.
- the dispensing mechanism 11 is a stirring mechanism having a function of immersing a spatula in a reaction solution and stirring by rotating the spatula, or irradiating ultrasonic waves and stirring by a swirling flow. If sufficient stirring can be performed only by the simultaneous ejection operation of the sample and the reagent by the dispensing mechanism 11, it is not necessary to perform these stirring operations in particular.
- the dispensing mechanism 11 moves to the dispensing mechanism cleaning unit by vertical movement and rotational movement, and cleans the tip of the dispensing probe 30 with washing water to prepare for the next dispensing operation.
- Step S05 After dispensing or stirring the sample and the reagent, the measurement by the spectroscopic detector 13 is started. Photometry is performed when the reaction vessel 14 crosses the luminous flux during the rotation of the reaction disk 15. The spectroscopic detector 13 performs the photometric measurement a plurality of times for the same reaction vessel 14 at intervals defined for each analysis item.
- Step S06 Depending on the analysis item, there is an item to add the second reagent.
- the reagent disk 21 is positioned so that the reagent container 22 of the corresponding analysis item is positioned at the reagent suction position located on the circumferential circumference of the dispensing mechanism 11 after a certain period of time has elapsed after discharging the sample and the first reagent. Rotates.
- the dispensing mechanism 11 moves to the reagent suction position by vertical movement and rotational movement.
- the dispensing mechanism 11 sucks air in the air and forms an air layer at the tip of the probe.
- the working fluid for example, pure water
- the dispensing probe 30 It is an air layer provided to prevent mixing inside.
- the dispensing mechanism 11 moves to the reagent dispensing position by rotational movement and vertical movement, the second reagent is sucked from the reagent container 22 into the dispensing probe 30.
- the dispensing mechanism 11 moves to the dispensing mechanism cleaning unit 26 by rotary motion and vertical motion, and cleans the tip of the dispensing probe 30 with washing water.
- the dispensing mechanism 11 moves to the dispensing position by rotary motion and vertical motion, and dispenses a predetermined amount of the second reagent into the reaction vessel 14.
- Step S07 Subsequently, the mixture in the reaction vessel 14 is stirred by a stirring mechanism such as pipette stirring or a spatula or ultrasonic waves. If the agitation can be sufficiently performed only by the operation of discharging the second reagent by the dispensing mechanism 11, these agitation operations may not be performed.
- a stirring mechanism such as pipette stirring or a spatula or ultrasonic waves. If the agitation can be sufficiently performed only by the operation of discharging the second reagent by the dispensing mechanism 11, these agitation operations may not be performed.
- Step S08 After dispensing or stirring the second reagent, the measurement by the spectroscopic detector 13 is continuously carried out.
- reaction vessel 14 After a lapse of a certain period of time, the reaction vessel 14 having been measured is washed by discharging the reaction solution in the reaction vessel 14 by the reaction vessel washing unit 27 to prepare for the next measurement. During those operations, including washing, another reaction vessel 14 performs analytical operations (dispensing, photometric operations, etc.) in parallel with another sample and reagent.
- the computer 3 calculates the concentration and the enzyme activity value from the obtained measured value (absorbance).
- the calculated concentration and enzyme activity value are stored in the memory 6 via the interface 9.
- the result is reported to the user via the display device 5. As a result, the analysis operation by the automatic analyzer 10 is completed.
- FIG. 5 is a diagram schematically showing the movement of the dispensing probe 30 and its effect when the automatic analyzer 10 simultaneously dispenses the sample and the first reagent in the first embodiment.
- FIG. 5 illustrates the operation of the dispensing probe 30 in step S03.
- the lowercase alphabet in FIG. 5 shows the flow of operation time at the time of ejection in the order of (a), (b), (c), (d), (e), and (f), and each schematic diagram shows each elapsed time. The situation at the time of discharge is schematically shown. Similarly, in the other figures described below, these lowercase alphabets represent the flow of time in the ejection operation.
- the analysis control unit 8 lowers the dispensing mechanism 11 to the vicinity of the bottom of the reaction vessel 14 (FIG. 5A).
- the lowering position of the dispensing probe 30 into the reaction vessel 14 is preferably about several millimeters from the bottom of the reaction vessel 14. The reason for this will be described later.
- the distance from the bottom of the reaction vessel to the tip of the dispensing probe 30 is set to about 1 to 2 mm.
- the sample 33, the reagent 32, and the system water 31 (pure water or the like) are held in the dispensing probe 30.
- the liquids in these dispensing probes 30 have a positional relationship of the sample 33, the reagent 32, and the system water 31 in the order of vertical upward from the tip side of the dispensing probe 30.
- the discharge liquid is discharged from the tip of the dispensing probe 30 in the order of the sample 33, the segmented air 37 (the layer between the sample 33 and the reagent 32), and the reagent 32. It will be discharged to 14.
- the analysis control unit 8 starts the discharge operation.
- the sample 33 is first discharged from the tip of the dispensing probe 30.
- the analysis control unit 8 controls the dispensing probe 30 at the same time as the discharge operation is started, or several milliseconds later (for example, before the tip of the dispensing probe 30 is immersed in the discharged sample 33 in the reaction vessel 14).
- the ascending operation is started (FIG. 5 (b)).
- the analysis control unit 8 controls to raise and discharge the dispensing probe 30 until the specified amount of sample and reagent is discharged.
- the analysis control unit 8 sets the ascending speed of the dispensing probe 30 so that the distance Da between the tip of the dispensing probe 30 and the liquid surface of the reaction solution 36 in the reaction vessel 14 increases with the passage of time. Control (FIGS. 5 (c) (d) (e)).
- the analysis control unit 8 includes a total discharge amount of the sample 33 and the reagent 32 (the height of the reaction liquid 36 discharged into the reaction vessel 14), a drive pulse and an ascending speed that give an increase amount of the dispensing probe 30.
- the data of the correspondence between the two is recorded. This data is set based on known data such as the size of the reaction vessel 14 and the time change (discharge rate) of the discharge amount. For example, in the first embodiment, the rate of change ⁇ of the distance Da between the tip of the dispensing probe 30 and the liquid level height of the reaction solution 36 (the horizontal axis is the elapsed time, and the vertical axis is the inclination when the distance Da is defined).
- the ascending speed and drive pulse of the dispensing probe 30 are given so that the speed becomes 8.0 m / s.
- the analysis control unit 8 controls the ascending speed of the dispensing probe 30 so as to have a constant or arbitrary rate of change ⁇ according to the total discharge amount of the dispensing probe 30.
- FIG. 6A shows a relationship diagram between the height of the tip of the dispensing probe 30 from the bottom of the reaction vessel 14 and the height of the liquid level of the reaction liquid 36.
- FIG. 6B shows the change in the elapsed time of the distance Da between the tip of the dispensing probe 30 and the liquid level of the reaction liquid 36.
- P1, P2, and P3 in FIG. 6AB indicate points of elapsed time.
- P * (* is an arithmetic number) displayed in the figure indicates points at each elapsed time, and the description thereof will be omitted hereafter.
- the ejection operation is started at the point P1
- the ascending operation of the dispensing probe 30 is started at the point P2
- the ejection operation / ascending operation is terminated at the point P3.
- the analysis control unit 8 starts the ejection operation of the dispensing probe 30. From the tip of the dispensing probe 30, the sample 33 is first discharged into the reaction vessel 14. At the time of P1, the dispensing probe 30 is stopped at a height of several millimeters above the bottom of the reaction vessel 14, and the ascending operation of the dispensing probe 30 has not started yet. Since the liquid level of the discharged liquid rises up to P2 where the ascending operation of the dispensing probe 30 starts, that is, between P1 and P2, the distance Da between the tip of the dispensing probe 30 and the liquid level Da. Becomes smaller with the passage of time.
- the analysis control unit 8 starts the ascending operation of the dispensing probe 30 at the elapsed time P2.
- the discharged liquid (sample 33 or reagent 32) is continuously discharged from the tip of the dispensing probe 30.
- the liquid discharged from the tip of the dispensing probe 30 at the time of P2 may be either the sample 33 or the reagent 32. That is, the analysis control unit 8 waits for the dispensing probe 30 until all the samples 33 are discharged (does not start the ascending operation), and then starts discharging the reagent 32 discharged from the tip of the dispensing probe 30. Therefore, the ascending operation of the dispensing probe 30 may be started. Further, the analysis control unit 8 may start the ascending operation of the dispensing probe 30 at the same time as the discharge of the sample 33 is started (at the elapsed time P1) or while the sample 33 is being discharged.
- the analysis control unit 8 causes the dispensing probe 30 to perform the ejection operation and the ascending operation until the specified amount is discharged (up to P3).
- the distance Da between the tip of the dispensing probe 30 and the liquid level of the reaction liquid 36 in the reaction vessel 14 increases with the passage of time until the specified amount is discharged (up to P3).
- the analysis control unit 8 ends the ejection operation and the ascending operation of the dispensing probe at the elapsed time P3 in which the specified amount of the sample 33 and the reagent 32 are discharged.
- the lowering position of the dispensing probe 30 into the reaction vessel 14 before the start of discharge is preferably near the bottom of the reaction vessel 14, that is, about several millimeters from the bottom of the reaction vessel 14.
- the segmented air 37 between the sample 33 and the reagent 32 bursts when discharged from the probe tip, and one or both of the sample 33 and the reagent 32 are scattered on the wall surface of the reaction vessel 14. Will be done. If the scattered liquid remains attached to the wall surface of the reaction vessel 14, the reaction of the reaction liquid does not proceed sufficiently, and there is a concern that the analysis result may be adversely affected.
- the technique of reducing the amount of sample used for measurement is also advancing. It is assumed that the sample used for the measurement is as small as about 40 ⁇ L at the most. Therefore, the position of the tip of the dispensing probe 30 at the start of discharge is set near the bottom of the reaction vessel 14 (set to 1 to 2 mm from the bottom in the first embodiment), and the discharge is started between the sample 33 and the reagent 32. The segmented air 37 is discharged near the bottom of the reaction vessel 14.
- the reagent continues to be discharged from a high position thereafter, so that the spattered liquid adhering to the reaction vessel 14 is a liquid. As the surface rises, it is buried in the reaction solution 36. In this way, by controlling the analysis control unit 8 to lower the dispensing probe 30 to the vicinity of the bottom of the reaction vessel 14 and start the discharge operation, the influence of scattering can be reduced and the analysis performance is improved. The effect is born.
- the elapsed time is the distance Da between the tip of the dispensing probe 30 and the liquid level of the reaction liquid 36.
- the agitation can be performed efficiently at the time of ejection, the time required for the subsequent additional agitation operation (pipette agitation, etc.) can be shortened, and the processing capacity is improved. Further, if the stirring can be sufficiently performed at the time of ejection, an additional mechanism for stirring (stirring by ultrasonic waves, etc.) becomes unnecessary, which leads to space saving of the device.
- the automatic analyzer 10 lowers the dispensing probe 30 to the vicinity of the bottom of the reaction vessel 14 and starts discharging, so that the liquid splashing position from the segmented air 38 between the sample 33 and the reagent 32 adheres. Can be suppressed near the bottom of the reaction vessel 14. Further, since the reagent 32 is discharged from a high position while the dispensing probe 30 is raised by starting the probe raising operation at the same time as the discharge start or several milliseconds later, the adhering liquid scattered in the reaction vessel 14 is the reaction liquid. As the liquid level of 36 rises, it is buried in the reaction liquid 36. As a result, the influence of the scattering on the measurement data can be reduced, and the analysis performance can be improved.
- the automatic analyzer 10 may have the following configuration of the automatic analyzer or a dispensing flow.
- the dispensing probe 30 sucks the sample 33 from the sample container 24 and discharges the sample 33 into the reaction container 14. Subsequently, after cleaning the tip of the dispensing probe 30 with the dispensing mechanism cleaning unit 26, the dispensing probe 30 sucks the reagent 32 from the reagent container 22. Then, after cleaning the tip of the dispensing probe 30 with the dispensing mechanism cleaning unit 26, the analysis control unit 8 places the dispensing probe 30 near the liquid level height of the sample 33 in the reaction vessel 14 (for example, above the liquid level). Lower to 1 mm).
- the analysis control unit 8 starts the ascending operation of the dispensing probe 30 at the same time as the ejection operation of the reagent 32 is started, or after a few milliseconds. Subsequently, the analysis control unit 8 controls the dispensing probe 30 to perform an ascending operation and a discharging operation until the specified amount of the reagent 32 is discharged. In addition, the analysis control unit 8 sets the ascending speed of the dispensing probe 30 so that the distance Da between the tip of the dispensing probe 30 and the liquid surface of the reaction solution 36 in the reaction vessel 14 increases with the passage of time. Control. As a result, the arrival position of the discharged liquid in the reaction liquid 36 in the height direction can be gradually changed. A large flow of liquid can be given to the entire reaction liquid, and the sample 33 and the reagent 32 can be efficiently stirred at the time of discharge.
- the automatic analyzer 10 may have the following configuration of the automatic analyzer or a dispensing flow.
- the automatic analyzer 10 includes two dispensing probes 30. That is, a sample probe for dispensing the sample 33 and a reagent probe for dispensing the reagent 32.
- the sample probe sucks the sample 33 from the sample container 24.
- the reagent probe sucks the reagent 32 from the reagent container 22.
- the analysis control unit 8 lowers the sample probe and reagent probe to the vicinity of the bottom of the reaction vessel 14, and removes the sample 33 from the sample probe to the reagent probe.
- the discharge of the reagent 32 is started from.
- the analysis control unit 8 starts the ascending operation of the dispensing probe 30 at the same time as the discharge is started or several milliseconds later. Subsequently, the analysis control unit 8 controls the dispensing probe 30 to perform an ascending operation and a discharging operation until the specified amount of the reagent 32 is discharged.
- the analysis control unit 8 sets the ascending speed of the dispensing probe 30 so that the distance Da between the tip of the dispensing probe 30 and the liquid surface of the reaction solution 36 in the reaction vessel 14 increases with the passage of time. Control. As a result, the arrival position of the discharged liquid in the reaction liquid 36 in the height direction can be gradually changed. A large flow of liquid can be given to the entire reaction liquid, and the sample 33 and the reagent 32 can be efficiently stirred at the time of discharge.
- the automatic analyzer 10 may have the following configuration of the automatic analyzer or a dispensing flow.
- step S06 the second reagent is discharged into the reaction vessel 14.
- the analysis control unit 8 lowers the dispensing probe 30 to the vicinity of the liquid level level (for example, 1 mm above the liquid level) of the reaction liquid (mixed liquid of the sample 33 and the reagent 32) in the reaction vessel 14. After that, the analysis control unit 8 starts the ascending operation of the dispensing probe 30 at the same time as the discharge operation of the second reagent is started, or after a few milliseconds.
- the analysis control unit 8 controls the dispensing probe 30 to perform an ascending operation and a discharging operation until the specified amount of the second reagent is discharged.
- the analysis control unit 8 sets the ascending speed of the dispensing probe 30 so that the distance Da between the tip of the dispensing probe 30 and the liquid surface of the reaction solution 36 in the reaction vessel 14 increases with the passage of time. Control.
- the arrival position of the discharged liquid in the reaction liquid 36 in the height direction can be gradually changed. A large flow of liquid can be given to the entire reaction liquid, and the reaction liquid (mixed liquid of sample 33 and reagent 32) and the second reagent can be efficiently stirred at the time of discharge.
- step S03 the distance Da between the tip of the dispensing probe 30 and the liquid level of the reaction liquid 36 in the reaction vessel 14 is time until the analysis control unit 8 finishes discharging the specified amount. It was explained that the ascending speed of the dispensing probe 30 is controlled so as to increase with the lapse of time. The procedure for raising the dispensing probe 30 is not limited to this.
- the analysis control unit 8 controls the distance Da so as to increase with the elapsed time for a predetermined time, and then the analysis control unit 8 controls the distance Da so as to decrease with the passage of time. Even in this case, the same effect as that of the first embodiment can be exhibited. Since the configuration of the automatic analyzer 10 is the same as that of the first embodiment, the differences regarding the dispensing operation will be mainly described below.
- FIG. 7 is a diagram schematically showing the movement of the dispensing probe 30 and its effect when the automatic analyzer 10 simultaneously dispenses the sample and the first reagent in the second embodiment.
- the time course of the tip position of the dispensing probe 30 in FIG. 7 will be described with reference to FIG. 8AB.
- FIG. 8A shows a relationship diagram between the height of the tip of the dispensing probe 30 from the bottom of the reaction vessel 14 and the height of the liquid level of the reaction liquid 36.
- FIG. 8B shows the change in the elapsed time of the distance Da between the tip of the dispensing probe 30 and the liquid level of the reaction liquid 36.
- the details of the second embodiment will be described with reference to FIG. 8AB.
- the same items as those in the first embodiment will be omitted.
- the analysis control unit 8 starts the ejection operation of the dispensing probe 30 (P4), and raises the probe of the dispensing probe 30 so that the distance Da increases with the elapsed time (P5 to P6). After a certain period of time has elapsed, the analysis control unit 8 stops the ascending operation of the dispensing probe 30 at the elapsed time P6 (the point before the end of discharging the specified amount). At the time of P6, the ejection operation is continuing. The analysis control unit 8 ends the ejection operation at the elapsed time P7 when the specified amount is ejected. That is, the analysis control unit 8 controls the distance Da to increase during the elapsed time P5 to P6, and controls the distance Da to decrease with the elapsed time P6 to P7.
- the automatic analyzer 10 moves the dispensing probe 30 so that the distance Da becomes large, and then fixes the vertical position of the dispensing probe 30 so that the distance Da becomes small.
- the dispensing probe 30 is moved to. Also in the second embodiment, the same effect as that of the first embodiment can be exhibited.
- step S03 the analysis control unit 8 controls so that the tip of the dispensing probe 30 is immersed in the liquid surface of the reaction liquid 36 when the discharge of the specified amount is completed (when the discharge of the reagent 32 is completed). May be good.
- the third embodiment a specific example thereof will be described. Even in this case, the same effect as that of the first embodiment can be exhibited. Since the configuration of the automatic analyzer 10 is the same as that of the first embodiment, the differences regarding the dispensing operation will be mainly described below.
- FIG. 9 is a diagram schematically showing the movement of the dispensing probe 30 and its effect when the automatic analyzer 10 simultaneously dispenses the sample and the first reagent in the third embodiment.
- the time course of the tip position of the dispensing probe 30 in FIG. 9 will be described with reference to FIG. 10AB.
- FIG. 10A shows a relationship diagram between the height of the tip of the dispensing probe 30 from the bottom of the reaction vessel 14 and the height of the liquid level of the reaction liquid 36.
- FIG. 10B shows the change in the elapsed time of the distance Da between the tip of the dispensing probe 30 and the liquid level of the reaction liquid 36.
- the details of the third embodiment will be described with reference to FIG. 10AB.
- the same items as those in the first embodiment will be omitted.
- the analysis control unit 8 starts the ejection operation of the dispensing probe 30 (P8), and controls the probe rising operation of the dispensing probe 30 so that the distance Da increases with the elapsed time (P9 to P10). After a certain period of time has elapsed, the analysis control unit 8 stops the ascending operation of the dispensing probe 30 at the elapsed time P10 (a time point before the specified amount has been discharged). At this time, the analysis control unit 8 stops the ascending operation of the dispensing probe 30 at a position lower than the liquid level height of the reaction liquid 36 after discharging the specified amount. After that, the discharge operation ends at the elapsed time P11.
- the tip of the dispensing probe 30 is in a state of being immersed in the reaction liquid 36.
- the amount of immersion at the tip of the dispensing probe 30 is preferably about several millimeters (for example, 4 mm) in order to reduce the contamination range of the tip of the dispensing probe.
- the liquid level may be detected by the liquid level detector 48 at the elapsed time P11. Due to the difference in wettability of the reaction solution 36 (due to the influence of the meniscus), the liquid level height of the reaction solution 36 is expected to be slightly different from the known data. Therefore, the liquid level may be detected by using the liquid level detector 48 after the discharge operation of the dispensing probe 30 is completed, and it may be confirmed whether the tip of the dispensing probe 30 is accurately immersed in the reaction liquid 36 after the discharge is completed.
- the automatic analyzer 10 controls the analysis control unit 8 to immerse the tip of the dispensing probe 30 in the reaction solution 36 when the reagent is discharged. For example, if the liquid drainage at the tip of the dispensing probe 30 is poor at the end of discharge and a liquid ball is formed at the tip of the dispensing probe 30, the liquid ball component is not discharged into the reaction vessel 14 and is specified. It may not be possible to dispense the amount accurately. If the tip of the dispensing probe 30 is immersed in the liquid surface at the end of discharge, the liquid ball can be immersed in the reaction liquid, and a specified amount can be accurately dispensed. As a result, it leads to improvement of analysis performance.
- the automatic analyzer 10 accurately determines whether or not the tip of the dispensing probe 30 is immersed in the liquid level of the reaction liquid 36 by detecting the liquid level by the liquid level detector 48 at the end of discharge. can do. If the liquid level detector 48 does not detect the liquid level, there is a concern that the dispensing performance may deteriorate due to the formation of liquid balls at the tip of the dispensing probe 30, so the analysis control unit 8 is displayed on the display device 5 via the interface 9. A data alarm that cannot detect the liquid level may be added. As a result, the user can know the cause of the data failure and can take appropriate measures such as requesting a re-inspection. Appropriate measurement data can be obtained by re-examination, which leads to improvement in the reliability of measurement results.
- step S03 the analysis control unit 8 controls to stop the tip of the dispensing probe 30 above the liquid level of the reaction liquid 36 when the discharge of the specified amount is completed (when the discharge of the reagent 32 is completed). May be good.
- the fourth embodiment a specific example thereof will be described. Even in this case, the same effect as that of the first embodiment can be exhibited. Since the configuration of the automatic analyzer 10 is the same as that of the first embodiment, the differences regarding the dispensing operation will be mainly described below.
- FIG. 11 is a diagram schematically showing the movement of the dispensing probe 30 and its effect when the automatic analyzer 10 simultaneously dispenses the sample and the first reagent in the fourth embodiment.
- the time course of the tip position of the dispensing probe 30 in FIG. 11 will be described with reference to FIG. 12AB.
- FIG. 12A shows a relationship diagram between the height of the tip of the dispensing probe 30 from the bottom of the reaction vessel 14 and the height of the liquid level of the reaction liquid 36.
- FIG. 12B shows the change in the elapsed time of the distance Da between the tip of the dispensing probe 30 and the liquid level of the reaction liquid 36.
- the details of the fourth embodiment will be described with reference to FIG. 12AB.
- the same items as those in the first embodiment will be omitted.
- the analysis control unit 8 starts the ejection operation of the dispensing probe 30 (P12), and controls the probe rising operation of the dispensing probe 30 so that the distance Da increases with the elapsed time (P13 to P14). After a certain period of time has elapsed, the analysis control unit 8 stops the ascending operation of the dispensing probe 30 at the elapsed time P14 (the time point before the specified amount has been discharged). At this time, the analysis control unit 8 stops the ascending operation of the dispensing probe 30 at a position higher than the liquid level height of the reaction liquid 36 after discharging the specified amount. After that, the discharge operation ends at the elapsed time P15. That is, at the elapsed time P15 when the specified amount of discharge is completed, the tip of the dispensing probe 30 is at a position higher than the liquid level of the reaction liquid 36.
- the automatic analyzer 10 controls the analysis control unit 8 so that the tip of the dispensing probe 30 is above the liquid level of the reaction liquid 36 at the end of discharge.
- the state in the dispensing probe 30 before the start of pipette stirring is liquid (system water or the like). ) Is filled.
- the tip of the dispensing probe 30 is stopped above the liquid level of the reaction liquid 36 at the end of discharge as in the fourth embodiment, the tip of the dispensing probe 30 is in the air. Therefore, air can be sucked without the need for additional ascending motion. As a result, the operating time from the start of ejection by the dispensing probe 30 to the end of stirring (pipette stirring) is reduced, and the effect of improving the processing capacity of the automatic analyzer 10 is produced.
- step S03 the analysis control unit 8 controls so that the tip of the dispensing probe 30 is immersed in the liquid surface of the discharged sample 33 or the reaction liquid 36 for a certain period of time after the discharge of the sample 33 starts or ends. May be good.
- the fifth embodiment a specific example thereof will be described. Even in this case, the same effect as that of the first embodiment can be exhibited. Since the configuration of the automatic analyzer 10 is the same as that of the first embodiment, the differences regarding the dispensing operation will be mainly described below.
- FIG. 13 is a diagram schematically showing the movement of the dispensing probe 30 and its effect when the automatic analyzer 10 simultaneously dispenses the sample and the first reagent in the fifth embodiment.
- the time course of the tip position of the dispensing probe 30 in FIG. 13 will be described with reference to FIG. 14AB.
- FIG. 14A shows a relationship diagram between the height of the tip of the dispensing probe 30 from the bottom of the reaction vessel 14 and the height of the liquid level of the reaction liquid 36.
- FIG. 14B shows the change in the elapsed time of the distance Da between the tip of the dispensing probe 30 and the liquid level of the reaction liquid 36.
- the details of the fifth embodiment will be described with reference to FIG. 14AB.
- the same items as those in the first embodiment will be omitted.
- the analysis control unit 8 starts the ejection operation of the dispensing probe 30 (P16).
- the analysis control unit 8 may control the sample 33 to be immersed in the discharged sample 33 or reaction solution 36 (mixed solution of the sample 33 and the reagent 32) for a certain period of time after the discharge of the sample 33 is completed. .. That is, the analysis control unit 8 is before the start of ejection so that the tip of the dispensing probe 30 is immersed in the ejected sample 33 and the reaction solution 36 (sample 33 and reagent 32) for a certain period of time after the completion of ejection of the sample 33.
- the amount of descent of the dispensing probe 30 into the reaction vessel 14 is controlled, and after immersion, the dispensing probe 30 is raised while discharging the reagent 32.
- the analysis control unit 8 is at the discharge start position for a certain period of time after the discharge of the sample 33 is completed until the tip of the dispensing probe 30 is immersed in the discharged sample 33 or the reaction solution 36 (sample 33 and reagent 32).
- the tip of the dispensing probe 30 may be made to stand by, and then the dispensing probe 30 may be controlled to rise while discharging the reagent 32.
- the immersion amount at the tip of the dispensing probe 30 is about several mm in order to reduce the contamination range at the tip of the nozzle.
- the analysis control unit 8 controls the dispensing probe 30 so that the immersion amount at the tip of the dispensing probe 30 is about 4 mm or less.
- the tip of the dispensing probe 30 is pointed at the sample 33 or the reaction solution 36 (sample 33 and the reagent) in the container for a certain period of time after the discharge of the sample 33 starts or ends.
- the segmented air 37 between the sample 33 and the reagent 32 subsequently discharged from the tip of the dispensing probe 30 It will be discharged in the sample 33 or in the reaction solution 36 of the sample 33 and the reagent 32.
- the tip of the dispensing probe 30 is in the liquid, it is possible to prevent the influence of the liquid splattering derived from the segmented air 37. That is, the analysis performance can be improved.
- step S03 the analysis control unit 8 lowers the probe tip to near the liquid level when the dispensing probe 30 discharges all of the sample 33 into the reaction vessel 14, and then starts discharging the sample 33 and the reagent 32. You may.
- the sixth embodiment a specific example thereof will be described. Even in this case, the same effect as that of the first embodiment can be exhibited. Since the configuration of the automatic analyzer 10 is the same as that of the first embodiment, the differences regarding the dispensing operation will be mainly described below.
- FIG. 15 is a diagram schematically showing the movement of the dispensing probe 30 and its effect when the automatic analyzer 10 simultaneously dispenses the sample and the first reagent in the sixth embodiment.
- the time course of the tip position of the dispensing probe 30 in FIG. 15 will be described with reference to FIG. 16AB.
- FIG. 16A shows a relationship diagram between the height of the tip of the dispensing probe 30 from the bottom of the reaction vessel 14 and the height of the liquid level of the reaction liquid 36.
- FIG. 16B shows the change in the elapsed time of the distance Da between the tip of the dispensing probe 30 and the liquid level of the reaction liquid 36.
- the details of the sixth embodiment will be described with reference to FIGS. 15 and 16AB.
- the same items as those in the first embodiment will be omitted.
- the analysis control unit 8 lowers the dispensing probe 30 into the reaction vessel 14 (FIG. 15 (a)). At this time, the analysis control unit 8 has the tip of the dispensing probe 30 up to the vicinity of the liquid level when all the specified amount of the sample 33 is discharged (for example, up to the same height as the liquid level, or within 1 mm above the liquid level). ) Lower.
- the analysis control unit 8 starts the ejection operation of the dispensing probe 30 (elapsed time P20). When the elapsed time P21, the height of the tip of the dispensing probe 30 is the same as the liquid level height of the discharged sample 33 or a position several millimeters above.
- the automatic analyzer 10 lowers the dispensing probe 30 to the vicinity of the liquid level when all the specified amount of the sample 33 is discharged into the reaction vessel 14, and then starts discharging the sample 33. ..
- the height of the tip of the dispensing probe 30 is the same as the height of the sample 33 or a position several mm above when all the samples are discharged, then from the tip of the dispensing probe 30.
- the segmented air 37 between the discharged sample 33 and the reagent 32 will be discharged in the air. By discharging the segmented air 37 in the air, it is possible to prevent bubbles derived from the segmented air 37 from being mixed into the liquid. If air bubbles are mixed in the reaction liquid and adhere to the optical path region of the light source 12 in the reaction vessel 14, the measurement data may be affected.
- the analysis performance is improved by preventing the air bubbles from being mixed.
- the analysis control unit 8 may change the ascending speed of the dispensing probe 30 according to the liquid property information of the discharged solution.
- the liquid property here means viscosity, polarity, contact angle and the like.
- the intramolecular force between the sample 33 and the reagent 32 also differs depending on the difference in the viscosity, polarity, contact angle, etc. of the discharged liquid.
- the height at which the discharged liquid reaches the inside of the reaction liquid 36, which is a mixed liquid of the sample 33 and the reagent 32 at the time of discharge, and the state of the liquid flow thereof also differ depending on the liquid property.
- the liquid property of this solution is associated with the change rate ⁇ of an appropriate distance Da having a large stirring effect at the time of ejection, and the data is recorded in the memory 6 in advance.
- the user may input the viscosity and contact angle information of the reagent of the analysis item to the analysis control unit 8 via the keyboard 2.
- Other configurations are the same as those in the first embodiment.
- the analysis control unit 8 reads out the rate of change ⁇ corresponding to the liquid property of the solution from the memory 6 before starting the discharge of the dispensing nozzle 31. Then, the analysis control unit 8 controls so as to give an appropriate ascending speed of the dispensing probe 30, which has a large stirring effect at the time of ejection.
- the viscosity information the pressure waveform is acquired at the time of suction of the sample 33 and the suction of the reagent 32, the computer 3 analyzes the viscosity of the sample 33 and the reagent 32 based on the pressure waveform, and the analysis result is input to the analysis control unit 8. You can also do it.
- the automatic analyzer 10 when the sample 33 and the reagent 32, which are different liquids, are simultaneously discharged by changing the ascending speed of the dispensing probe 30 according to the liquid property of the solution. It can be stirred efficiently.
- the experiment was carried out using the automatic analyzer 10 described in the first embodiment.
- the condition of the first embodiment was to control the ascending speed of the dispensing probe 30 so that the distance Da between the tip of the probe and the liquid surface of the reaction solution 36 increased with the elapsed time after the ascending of the dispensing probe 30 started.
- the conditions of the comparative example are that after the ascending of the dispensing probe 30 starts, the distance Da between the tip of the dispensing probe 30 and the liquid surface of the reaction solution 36 is constant regardless of the elapsed time, and the tip of the dispensing probe reacts.
- the ascending speed of the dispensing probe 30 was controlled so as to maintain the state of being immersed 2 mm from the liquid surface of the liquid 36. After the simultaneous ejection of the sample 33 and the reagent 32, no stirring such as pipette stirring or ultrasonic stirring was performed.
- aqueous solution to which a dye was added was used as the sample 33, and a colorless, transparent and viscous solution was used as the reagent 32.
- the sample 33 and the reagent 32 were simultaneously discharged, and the absorbance (the unique absorbance of the dye used as the sample) after a lapse of a predetermined time was measured. From the obtained absorbance and the absorbance in the state where the sample and the dye were completely miscible, the deviation rate (%) from the absorbance at the time of complete miscibility was calculated. The lower the deviation rate (%), the closer the state of stirring only for discharge is closer to the state of complete miscibility. In other words, it can be said that the lower the deviation rate (%), the more efficiently the stirring can be performed by the discharge operation.
- the absorbance fluctuation rate (%) for 5 minutes indicates the ratio of the range (maximum absorbance value-minimum absorbance value) of the absorbance data acquired multiple times in 5 minutes to the absorbance 5 minutes after ejection. If the stirring is not efficiently performed at the time of ejection, the absorbance fluctuates due to the diffusion phenomenon of the sample (dye liquid) even after the ejection is completed, so that the absorbance fluctuation rate (%) becomes large. That is, it can be said that the smaller the absorbance fluctuation rate (%) for 5 minutes, the more efficiently the stirring can be performed.
- FIG. 17 is a diagram showing the deviation rate (%) for each of the first embodiment and the comparative example. The measurement is performed multiple times under each condition, and the deviation rate (%) is plotted. From FIG. 17, in the first embodiment, the deviation rate (%) from the complete miscibility is lower, and the variation in the multiple measurements is also smaller.
- FIG. 18 is a diagram showing the absorbance volatility (%) for 5 minutes for each of the first embodiment and the comparative example. The measurement was carried out multiple times under each condition, and the absorbance volatility (%) was plotted. From FIG. 18, in the first embodiment, the absorbance volatility (%) is lower and the variation between measurements is smaller. Therefore, it can be seen that the first embodiment can be agitated more efficiently at the time of ejection. That is, if the ascending speed of the dispensing probe 30 is controlled so that the distance Da between the probe tip and the liquid level of the reaction solution 36 increases with the elapsed time after the ascending of the dispensing probe 30 starts, the sample and the reagent are simultaneously discharged. It can be stirred efficiently.
- the present invention is not limited to the above-described embodiment, and includes various modifications.
- the above-described embodiment has been described in detail in order to explain the present invention in an easy-to-understand manner, and is not necessarily limited to the one including all the described configurations.
- it is possible to replace a part of the configuration of one embodiment with the configuration of another embodiment and it is also possible to add the configuration of another embodiment to the configuration of one embodiment.
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Abstract
Description
図1は、実施形態1に係る自動分析装置10の全体図を概略的に示すブロック図である。自動分析装置10は主に、液体状の検体および試薬の混合液を分析する分析部1、分析部1を制御するコンピュータ3(制御部)、分析制御部8、を備えている。
分析部1が、インターフェース9を介してコンピュータ3より分析操作開始の指令を受けると、反応容器洗浄部27により反応容器14の洗浄が開始され、反応容器洗浄部27から吐出される純水を用いて、水ブランクを測定する。この水ブランク測定値は反応容器14で以後測定される吸光度の基準となる。反応ディスク15の1サイクルの動作(すなわち、一定の距離を移動させて一時停止する間欠動作の繰り返し)により、洗浄済み反応容器14が分注機構11の回転方向周上に位置する分注ポジションまで進むと、検体容器24はサンプルラック25の水平動作により、分注機構11の回転方向周上に位置する検体分注ポジションまで移動する。同時に、対応する分析項目の試薬容器22が分注機構11の回転方向周上に位置する試薬吸引位置に位置付けられるように、試薬ディスク21が回転する。
分注機構11は空中において空気を吸引し、分注プローブ30の先端に空気層を形成する。この空気層は、分注プローブ30の先端から分注流路47内に満たされている作動流体(例えば、純水)と、続いて試薬容器22から吸引する試薬が、分注プローブ30内で混ざることを防ぐために設ける空気層である。その後、分注機構11は回転移動および上下移動により試薬分注ポジションまで移動すると、試薬容器22から試薬を分注プローブ30内へ吸引する。
試薬吸引後、分注機構11は上下移動により空中位置まで移動し、空気を吸引して分注プローブ30の先端に空気層を形成する。この空気層は、次に続いて検体容器24から吸引する検体が分注プローブ30内で試薬と混ざることを防ぐために設ける空気層である。そして、分注機構11は回転運動および上下運動により分注機構洗浄部26まで移動し、分注プローブ30の先端を洗浄水にて洗浄する。洗浄後、分注機構11は回転運動および上下運動により検体吸引ポジションまで移動すると検体容器24から検体を分注プローブ30内へ吸引する。
検体吸引後、分注機構11は回転運動および上下運動により分注機構洗浄部26まで移動し、分注プローブ30の先端を洗浄水にて洗浄する。次いで、分注機構11は回転運動および上下運動により分注ポジションまで移動し、反応容器14に所定量の検体と試薬を同時に分注する。この検体および試薬分注の詳細は後述する。
検体と試薬が分注された後、反応容器14内の検体と試薬の混合液を攪拌するため、分注機構11は混合液を所定量吸引し、その後、再度反応容器14内に吐出をする。これにより混合液を攪拌する。この検体と試薬吐出後の再吸引および再吐出動作を以後、ピペット攪拌と記す。特に図示はしていないがピペット攪拌以外の攪拌機構による攪拌動作を実施してもよい。例えば、ヘラを反応液内に浸漬させてヘラの回転による攪拌、または超音波を照射して旋回流による攪拌などの機能を備える攪拌機構である。分注機構11による検体および試薬の同時吐出動作のみで十分に攪拌ができる場合は、特にこれらの攪拌動作を行う必要はない。分注機構11は上下運動および回転運動により分注機構洗浄部まで移動し、分注プローブ30の先端を洗浄水にて洗浄し、次の分注動作に備える。
検体と試薬の分注後または攪拌後に、分光検出器13による測定が開始される。測光は反応ディスク15の回転中に反応容器14が光束を横切ったときに実施される。分光検出器13により測光は分析項目毎に定められた時間間隔を空けて同一の反応容器14に対し複数回実行される。
分析項目によっては第2試薬を添加する項目がある。その場合、検体と第1試薬を吐出後の一定時間経過後に、対応する分析項目の試薬容器22が分注機構11の回転方向周上に位置する試薬吸引位置に位置付けられるように、試薬ディスク21が回転する。分注機構11は上下運動および回転運動により試薬吸引ポジションへ移動する。分注機構11は空中にて空気を吸引し、プローブ先端に空気層を形成する。この空気層は、分注プローブ30の先端から分注流路47内に満たされている作動流体(例えば、純水)と、続いて試薬容器22から吸引する第2試薬が、分注プローブ30内で混ざることを防ぐために設ける空気層である。その後、分注機構11は回転移動および上下移動により試薬分注ポジションまで移動すると、試薬容器22から第2試薬を分注プローブ30内へ吸引する。分注機構11は回転運動および上下運動により分注機構洗浄部26まで移動し、分注プローブ30の先端を洗浄水にて洗浄する。次いで、分注機構11は回転運動および上下運動により分注ポジションまで移動し、反応容器14に所定量の第2の試薬を分注する。
続いて、ピペット攪拌またはヘラまたは超音波などによる攪拌機構によって反応容器14内の混合液を攪拌する。分注機構11で第2試薬を吐出する動作のみで攪拌が十分に行える場合は、これらの攪拌動作は実施しなくてもよい。
第2試薬の分注後または攪拌後、引き続き分光検出器13による測定が継続して実施される。
一定時間経過後、測定を終えた反応容器14は、反応容器洗浄部27によって反応容器14内の反応液を排出されることで洗浄され、次の測定に備える。洗浄を含むそれらの動作の間に、別の反応容器14は、別の検体と試薬とを用いて平行して分析動作(分注、測光動作など)を実施する。コンピュータ3は、得られた測定値(吸光度)から濃度および酵素活性値を算出する。インターフェース9を介して、算出した濃度および酵素活性値をメモリ6に保存する。また、表示装置5を介してユーザにその結果を報告する。以上により、自動分析装置10による分析動作は終了する。
本実施形態1に係る自動分析装置10は、異なる液体である検体33と試薬32を同時吐出する際に、分注プローブ30の先端と反応液36の液面との間の距離Daを経過時間にともなって大きくすることにより、反応液36中の吐出液の高さ方面の到達位置を徐々に変化させることができる。これにより、反応液内全体に対して大きな液の流れを与えることができ、検体33と試薬32を効率よく吐出時に攪拌することができる。吐出時にて効率的に攪拌することができれば、その後の追加の攪拌動作(ピペット攪拌など)に要する時間を短縮することができ、処理能力が向上する。また、吐出時にて十分に攪拌することができれば、攪拌するための追加の機構(超音波による攪拌など)が必要なくなり、装置の省スペース化にもつながる。
実施形態1では、ステップS03において、分析制御部8は、規定量を吐出し終えるまで、分注プローブ30の先端と反応容器14内の反応液36の液面との間の距離Daが、時間経過と共に大きくなるよう分注プローブ30の上昇速度を制御することを説明した。分注プローブ30を上昇させる手順はこれに限定されない。
本実施形態2に係る自動分析装置10は、距離Daが大きくなるように分注プローブ30を移動させた後、分注プローブ30の垂直方向の位置を固定することにより、距離Daが小さくなるように分注プローブ30を移動させる。本実施形態2においても、実施形態1と同様の効果を発揮することができる。
ステップS03において、分析制御部8は規定量を吐出終了するとき(試薬32の吐出が終了するとき)に、分注プローブ30の先端を反応液36の液面内に浸漬するように制御してもよい。実施形態3では、その具体例を説明する。この場合であっても、実施形態1と同様の効果を発揮できる。自動分析装置10の構成は実施形態1と同様であるので、以下では主に分注動作に関する差異点を説明する。
本実施形態3に係る自動分析装置10は、分析制御部8が試薬を吐出終了するとき、分注プローブ30の先端を反応液36に浸漬させるよう制御する。例えば、吐出終了時の分注プローブ30の先端の液切れが悪く、分注プローブ30の先端に液玉が形成される条件であると、液玉分が反応容器14内に吐出されず、規定量を正確に分注することができないことがある。吐出終了時に分注プローブ30の先端が液面に浸漬していると、その液玉を反応液内に浸漬させることができ、正確に規定量を分注することができる。結果、分析性能の向上につながる。
ステップS03において、分析制御部8は規定量を吐出終了するとき(試薬32の吐出が終了するとき)に、分注プローブ30の先端を反応液36の液面より上に停止するよう制御してもよい。実施形態4では、その具体例を説明する。この場合であっても、実施形態1と同様の効果を発揮できる。自動分析装置10の構成は実施形態1と同様であるので、以下では主に分注動作に関する差異点を説明する。
本実施形態4に係る自動分析装置10は、分析制御部8が吐出終了時に分注プローブ30の先端を反応液36の液面高さより上になるよう制御する。例えば、図4ステップS04において、ピペット攪拌(吐出後に反応液36を再吸引・再吐出することによる攪拌)を実施する場合、ピペット攪拌開始前の分注プローブ30内の状態は液体(システム水など)で満たされている状態となる。ピペット攪拌により、分注プローブ30内にて再吸引する反応液36と分注プローブ30内の先端にある液体(システム水31など)の混合を避けるために、反応液36を再吸引する前に空気を吸引する必要がある。すなわち、反応液36とシステム水31の間に分節空気の層を形成する必要がある。もし、分注プローブ30の先端を反応液36内に浸漬させた状態で分注プローブ30の検体・試薬吐出動作を終了させた場合、この分節空気の層を形成するために、分注プローブ30の先端を反応液36の液中から引き抜く上昇動作が追加で必要となる。一方、本実施形態4のように、分注プローブ30の先端が吐出終了時の反応液36の液面高さより上で停止していれば、分注プローブ30の先端は空中にいる状態であるので、追加の上昇動作を必要とせずに空気を吸引できる。これにより、分注プローブ30による吐出開始から攪拌(ピペット攪拌)終了までの動作時間が少なくなり、自動分析装置10の処理能力を向上させる効果が生まれる。
ステップS03において、分析制御部8は検体33の吐出開始後または吐出終了後から一定時間、分注プローブ30の先端が、吐出された検体33または反応液36の液面に浸漬するよう制御してもよい。実施形態5では、その具体例を説明する。この場合であっても、実施形態1と同様の効果を発揮できる。自動分析装置10の構成は実施形態1と同様であるので、以下では主に分注動作に関する差異点を説明する。
本実施形態5に係る自動分析装置10は、検体33の吐出開始後または吐出終了後の一定時間の間、分注プローブ30の先端を、容器内の検体33または反応液36(検体33と試薬32)の液面に浸漬させる。これにより、例えば、全ての検体が吐出されたときにプローブ先端が液中に浸漬されていれば、続いて分注プローブ30の先端から吐出される検体33と試薬32の間の分節空気37は検体33の中で、または検体33と試薬32の反応液36中に吐出されることになる。このとき分注プローブ30の先端は液中にいるので、分節空気37由来の液飛び散りの影響を防止することができる。つまり、分析性能を向上することができる。
ステップS03において、分析制御部8は、分注プローブ30が反応容器14に検体33を全て吐出したときの液面高さ近辺までプローブ先端を下降させた上で、検体33や試薬32を吐出開始してもよい。実施形態6では、その具体例を説明する。この場合であっても、実施形態1と同様の効果を発揮できる。自動分析装置10の構成は実施形態1と同様であるので、以下では主に分注動作に関する差異点を説明する。
本実施形態6に係る自動分析装置10は、反応容器14に規定量の検体33を全て吐出したときの液面高さ近辺まで、分注プローブ30を下降させてから、検体33を吐出開始する。これにより、例えば、全ての検体が吐出されたときに分注プローブ30の先端高さが、検体33と同一の高さまたは数mm上の位置であれば、続いて分注プローブ30の先端から吐出される検体33と試薬32の間の分節空気37は空中で吐出されることになる。空中で分節空気37が吐出されることにより、分節空気37由来の気泡の液中への混入を防止することができる。気泡が反応液中に混入し、反応容器14中の光源12の光路領域に気泡が付着してしまうと、測定データに影響を及ぼすことがある。本実施形態6はこの気泡混入を防ぐことにより、分析性能の向上につながる。
ステップS03において、分析制御部8は、吐出する溶液の液性情報に応じて、分注プローブ30の上昇速度を変更してもよい。ここでいう液性とは、粘度、極性、接触角などである。吐出する液体の粘度、極性、接触角などの違いにより、検体33と試薬32の分子間力も異なってくる。このとき、吐出時の検体33と試薬32の混合液である反応液36内に対する、吐出液の液到達高さやその液流れの状況も液性によって異なってくる。本実施形態7においては、この溶液の液性と、吐出時の攪拌効果の大きい適切な距離Daの変化率αとを対応付けて、あらかじめメモリ6にデータとして記録させておく。これに代えて、測定開始前の分析項目依頼のときにユーザがキーボード2を介して該分析項目の試薬の粘度および接触角情報などを分析制御部8へインプットしてもよい。その他構成は実施形態1と同様である。
以下、本実施形態における、検体および試薬同時吐出時の攪拌効率を向上させる効果について、実験結果を用いて説明する。ただし、以下の実験結果は、本実施形態の効果について説明するために用いられており、本発明の技術的範囲が以下の実験結果によって限定されるものではない。
本発明は、前述した実施形態に限定されるものではなく、様々な変形例が含まれる。例えば、上記した実施形態は本発明を分かりやすく説明するために詳細に説明したものであり、必ずしも説明した全ての構成を備えるものに限定されるものではない。また、ある実施形態の構成の一部を他の実施形態の構成に置き換えることが可能であり、また、ある実施形態の構成に他の実施形態の構成を加えることも可能である。また、各実施形態の構成の一部について、他の構成の追加・削除・置換をすることが可能である。
2…キーボード
3…コンピュータ
4…プリンタ
5…表示装置
6…メモリ
7…A/D変換器
8…分析制御部
11…分注機構
12…光源
13…分光検出器
14…反応容器
15…反応ディスク
21…試薬ディスク
22…試薬容器
24…検体容器
25…サンプルラック
26…分注機構洗浄部
30…分注プローブ
31…システム水
32…試薬
33…検体
36…反応液
41…分注アーム
42…上下回転動作部
43…プランジャ
44…駆動部
45…定量ポンプ
46…ポンプ
47…分注流路
48…液面検出器
49…バルブ
Claims (13)
- 検体または試薬を容器に吸引または吐出するプローブと、
前記プローブを移動する移動機構、
前記移動機構を制御する制御部、
を備え、
前記制御部は、前記プローブが前記容器に対して前記検体を吐出し始めた後、前記プローブが前記検体または前記試薬を吐出しながら上昇するように前記移動機構を制御することにより、前記プローブから吐出された前記容器内の液体の液面高さが上昇するのにともなって、前記容器内の液面と前記プローブの先端との間の距離を次第に大きくする、
自動分析装置。 - 前記プローブは前記容器に対して前記検体を吐出する前、前記試薬を吸引し、該プローブの内部に前記試薬が存在している状態で、前記検体を吸引する、請求項1記載の自動分析装置。
- 前記プローブは、前記プローブの先端を前記容器の入口よりも下方に移動させた後、前記容器に対して前記検体を吐出し、
前記制御部は、前記プローブが前記容器に対して前記検体を吐出している間は、前記プローブを上下方向に移動させない、
請求項2記載の自動分析装置。 - 前記制御部は、前記プローブが前記検体または前記試薬を吐出しながら上昇し始めてから前記プローブが前記試薬を吐出し終えるまでの期間の少なくとも一部において、前記容器内の液面と前記プローブの先端との間の距離が次第に大きくなった後に次第に小さくなるように、前記移動機構を制御する、
請求項1記載の自動分析装置。 - 前記制御部は、前記プローブが前記検体または前記試薬を吐出しながら上昇し始めてから前記プローブが前記試薬を吐出し終えるまでの期間の少なくとも一部において、前記プローブの高さ方向の位置を固定することにより、前記容器内の液面と前記プローブの先端との間の距離を次第に小さくする、
請求項4記載の自動分析装置。 - 前記制御部は、前記プローブが前記試薬を吐出し終えるとき、前記容器内の液体に対して前記プローブの先端が浸漬しているように、前記移動機構を制御する、
請求項4記載の自動分析装置。 - 前記自動分析装置はさらに、前記容器内の液面高さを検知する液面検知器を備え、
前記制御部は、前記プローブが前記試薬を吐出し終えるとき、前記液面検知器による検出結果にしたがって、前記容器内の液体に対して前記プローブの先端が浸漬しているか否かを判定し、
前記制御部は、前記プローブが前記試薬を吐出し終えるとき、前記容器内の液体に対して前記プローブの先端が浸漬していない場合は、その旨のアラートを出力する、
請求項6記載の自動分析装置。 - 前記制御部は、前記プローブの先端が前記容器内の液面よりも上方の固定位置において静止するように、前記移動機構を制御し、
前記プローブは、前記固定位置で前記試薬を吐出し終える、
請求項4記載の自動分析装置。 - 前記制御部は、前記プローブが前記検体を吐出し始めてから前記プローブが上昇し始めるまでの期間の少なくとも一部において、前記プローブの先端が前記容器内の液体に対して浸漬するように、前記移動機構を制御する、
請求項2記載の自動分析装置。 - 前記プローブは、前記試薬と前記検体との間に分節空気を吸引し、
前記プローブは、前記プローブの先端が前記容器内の液体に浸漬している間に、前記検体を吐出し終えることにより、前記容器内の液体に対して前記分節空気を吐出する、
請求項9記載の自動分析装置。 - 前記制御部は、前記プローブが前記検体を吐出し始める前までに、前記プローブが前記容器に対して前記検体を全て吐出し終えたときにおける前記容器内の液面の上方1mm以内の高さまで、前記プローブの先端を下降させる、
請求項2記載の自動分析装置。 - 前記自動分析装置はさらに、前記検体の液特性または前記試薬の液特性を記述したデータを格納する記憶部を備え、
前記制御部は、前記データが記述している液特性にしたがって、前記プローブの上昇速度を制御する、
請求項1記載の自動分析装置。 - 前記液特性は、粘度または接触角のうち少なくともいずれかを含む、
請求項12記載の自動分析装置。
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EP4160218A1 (en) | 2023-04-05 |
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