WO2007132632A1 - Cleaning equipment and automatic analyzer - Google Patents
Cleaning equipment and automatic analyzer Download PDFInfo
- Publication number
- WO2007132632A1 WO2007132632A1 PCT/JP2007/058513 JP2007058513W WO2007132632A1 WO 2007132632 A1 WO2007132632 A1 WO 2007132632A1 JP 2007058513 W JP2007058513 W JP 2007058513W WO 2007132632 A1 WO2007132632 A1 WO 2007132632A1
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- WIPO (PCT)
- Prior art keywords
- air
- nozzle
- pressure
- liquid
- cleaning
- Prior art date
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Classifications
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L13/00—Cleaning or rinsing apparatus
- B01L13/02—Cleaning or rinsing apparatus for receptacle or instruments
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/14—Process control and prevention of errors
- B01L2200/143—Quality control, feedback systems
- B01L2200/146—Employing pressure sensors
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/02—Burettes; Pipettes
- B01L3/021—Pipettes, i.e. with only one conduit for withdrawing and redistributing liquids
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
- B01L3/5082—Test tubes per se
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N2035/00465—Separating and mixing arrangements
- G01N2035/00564—Handling or washing solid phase elements, e.g. beads
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/02—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
- G01N35/04—Details of the conveyor system
- G01N2035/0401—Sample carriers, cuvettes or reaction vessels
- G01N2035/0437—Cleaning cuvettes or reaction vessels
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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
- G01N2035/1025—Fluid level sensing
Definitions
- the present invention relates to a cleaning device that performs BZF cleaning of a reaction solution that has caused a heterogeneous reaction, and an automatic analyzer that includes the cleaning device and analyzes a sample such as blood or body fluid.
- Patent Document 1 Japanese Utility Model Publication No. 2-13978
- the present invention has been made in view of the above, and the reaction solution B / F It is an object to provide a cleaning device and an automatic analyzer that can accurately detect abnormality of the liquid level in the reaction container of the reaction solution and perform maintenance management easily. And
- the cleaning apparatus is configured to perform at least B / F cleaning of a reaction solution in which a heterogeneous reaction has occurred.
- This is a cleaning device equipped with a plurality of nozzle pairs consisting of a suction nozzle that sucks a part and a discharge nozzle force that discharges a predetermined B / F cleaning liquid, and is provided corresponding to each nozzle pair.
- a plurality of air nozzles that discharge air from above the leading ends of the suction nozzle and discharge nozzle, and a plurality of air that is connected to one of the plurality of air nozzles and supplies air to the connected air nozzles
- a supply means ; a plurality of pressure sensors for detecting air pressure in the vicinity of a base end portion of an air nozzle connected to each of the plurality of air supply means; and the plurality of pressure sensors.
- the cleaning device is based on the above invention, and the control means includes the air pressure in the vicinity of the base end portion of the plurality of air nozzles and a change in the pressure. Is characterized in that the discharge operation of the B / F cleaning liquid of the discharge nozzle corresponding to the air nozzle that takes a value that deviates from the predetermined range is stopped.
- An automatic analyzer is an automatic analyzer that analyzes a sample by causing a heterogeneous reaction in the sample to be analyzed, and includes the cleaning device according to any one of the above inventions. It is characterized by that.
- each of a plurality of nozzle pairs including a suction nozzle that sucks at least a part of a reaction solution that has caused a heterogeneous reaction and a discharge nozzle that discharges a predetermined B / F cleaning solution.
- a plurality of air nozzles for discharging air from above the respective tips of the suction nozzles and discharge nozzles forming a corresponding pair of nozzles, and the plurality of air nozzles are connected to the misalignment.
- Air supply means for detecting air pressure in the vicinity of the proximal end of the air nozzle connected to each of the plurality of air supply means, and air detected by the plurality of pressure sensors, respectively.
- a control means for individually controlling the discharge operation of the B / F cleaning liquid of each discharge nozzle in accordance with the change in the pressure, when performing BZF cleaning of the reaction liquid that has caused a heterogeneous reaction.
- it is possible to accurately detect abnormalities in the position of the reaction liquid contained in the reaction vessel, and maintenance management becomes easy.
- FIG. 1 is a diagram showing a configuration of a main part of an automatic analyzer according to an embodiment of the present invention.
- FIG. 2 is a diagram showing a configuration of a main part of a cleaning apparatus according to an embodiment of the present invention.
- FIG. 3 is an explanatory diagram showing an outline of an operation during B / F cleaning of the cleaning device according to one embodiment of the present invention.
- FIG. 4 is a diagram showing the air pressure detected in the case shown in FIG. 3 and the time variation of its pressure derivative.
- FIG. 5 is an explanatory diagram showing a situation in which an abnormality occurs in the operation during B / F cleaning of the cleaning device according to one embodiment of the present invention.
- FIG. 6 is a diagram showing the change in air pressure detected in the case shown in FIG. 5 and its pressure derivative over time.
- FIG. 7 is a diagram showing the relationship between the distance from the tip of the air nozzle to the pressure sensor and the air pressure in the pipe detected by the pressure sensor.
- FIG. 8 is a diagram showing the time change of the air pressure and the pressure derivative detected when the tip of the air nozzle is blocked by the liquid level in the reaction vessel at the start of the air discharge. It is.
- immunoassay is performed using a heterogeneous reaction.
- a first immune reaction antigen-antibody reaction
- a reaction vessel is applied as a solid phase. That is, it is assumed that a predetermined antibody is adsorbed in advance near the bottom of the inner wall of the reaction vessel.
- the reaction solution is subjected to B / F washing with a predetermined B / F washing solution and released without specifically binding to the antibody. And the antibody is separated and removed from the solid phase. Then, a second immune reaction is performed by adding an excess of the labeling enzyme. Even after this second immune reaction, the reaction solution is washed with BZF, and the released labeling substance, etc. is separated and removed from the solid phase by extra power IJ. Thereafter, a coloring substrate that exhibits the activity of the enzyme as a labeling substance is added to the reaction solution to cause a coloring reaction with the labeling substance in the reaction solution, and the amount of color development is optically measured. Finally, the concentration of the antigen to be analyzed in the sample is determined by performing a comparison operation between the data obtained by this measurement and the standard sample force data (calibration curve) with a known antigen concentration.
- an antigen that specifically binds to the antibody may be adsorbed on a solid phase in advance. It is also possible to analyze a sample by applying an immunoassay using a heterogeneous reaction other than the enzyme immunoassay described above.
- immunoassays include fluorescent immunoassay (FIA) using fluorescent substances as labeling substances, radioimmunoassay (RIA) using radioisotopes as labeling substances, and chemical enzymes using chemiluminescent substrates as labeling substances.
- FIA fluorescent immunoassay
- RIA radioimmunoassay
- chemiluminescent substrates as labeling substances
- examples include immunoassay (CLIA) and spin reagent immunoassay (SIA) using spin reagent as a labeling substance.
- FIG. 1 is a diagram schematically showing a configuration of a main part of an automatic analyzer according to an embodiment of the present invention.
- the automatic analyzer 1 shown in the figure dispenses a sample such as a sample and a reagent into a reaction vessel, and optically measures the reaction occurring in the reaction vessel, and the measurement mechanism 101 And control and analysis mechanism 201 that analyzes the measurement results in measurement mechanism 101, and these two mechanisms work together to automatically and continuously perform immunological analysis of the components of multiple samples. It is a device that performs automatically. In the following description, it is assumed that the automatic analyzer 1 performs an immunological measurement using a heterogeneous reaction.
- the measurement mechanism 101 includes a sample transfer unit 102 that stores and sequentially transfers a plurality of racks 22 on which sample containers 21 that store samples are mounted, and a carrier reagent container that stores a carrier reagent applied to an antigen-antibody reaction with the sample.
- a carrier reagent container holding unit 103 for holding the vessel 31 a liquid reagent container holding unit 104 for holding the liquid reagent vessel 41 for storing various liquid reagents, and a reaction vessel 51 for holding the reaction between the sample and the reagent.
- a container holding unit 105 is a sample transfer unit 102 that stores and sequentially transfers a plurality of racks 22 on which sample containers 21 that store samples are mounted, and a carrier reagent container that stores a carrier reagent applied to an antigen-antibody reaction with the sample.
- the carrier reagent container holding unit 103 is a wheel that holds the carrier reagent container 31, and a drive unit that is attached to the center of the bottom surface of the wheel and rotates the wheel with a vertical line passing through the center as a rotation axis.
- the liquid reagent container holding unit 104 and the reaction container holding unit 105 have a wheel and driving means for rotating the wheel.
- a constant temperature is maintained in each container holding portion.
- the liquid reagent container holding unit 104 is set to a temperature lower than room temperature in order to suppress the deterioration and denaturation of the reagent
- the reaction container holding unit 105 is set to a temperature similar to the human body temperature. .
- the measurement mechanism 101 includes a sample dispensing unit 106 that dispenses a sample accommodated in the sample container 21 on the sample transfer unit 102 into a reaction container 51 that is held by a reaction container holding unit 105, and a carrier test.
- the carrier reagent dispensing unit 107 for dispensing the carrier reagent contained in the carrier reagent container 31 on the drug container holding unit 103 into the reaction vessel 51 and the liquid reagent container 41 on the liquid reagent container holding unit 104
- the liquid reagent dispensing unit 108 for dispensing the liquid reagent into the reaction vessel 51 and the reaction vessel 51 for installing and removing the reaction vessel 51 from the reaction vessel holding unit 105
- a reaction vessel transfer unit 109 for transferring the reaction vessel.
- the sample container 21 is affixed with an information code recording medium in which identification information for identifying a sample contained in the container 21 is encoded and recorded in an information code such as a barcode or a two-dimensional code (see FIG. Not shown).
- each of the carrier reagent container 31 and the liquid reagent container 41 is shelled with an information code recording medium in which identification information for identifying the reagent contained therein is encoded and recorded in an information code (not shown).
- the measurement mechanism 101 includes an information code reading unit CR1 that reads an information code affixed to the specimen container 21, an information code reading part CR2 that reads an information code affixed to the carrier reagent container 31, and a liquid reagent container 41.
- An information code reading unit CR3 for reading the information code attached to the is provided.
- the sample dispensing unit 106, the carrier reagent dispensing unit 107, and the liquid reagent dispensing unit 108 are a thin tube probe that sucks and discharges a sample, and a vertical direction for moving the probe.
- Each arm is equipped with an arm that moves up and down and rotates horizontally, and an intake / exhaust mechanism using an intake / exhaust syringe.
- Each probe is cleaned by a separate cleaning unit (not shown) after a single dispensing operation.
- a separate cleaning unit not shown
- reaction vessel transfer unit 109 On the operation line of the reaction vessel transfer unit 109, a reaction vessel storage unit 119 for holding an unused reaction vessel 51 and a reaction vessel disposal unit 129 for discarding the used reaction vessel 51 are provided. .
- the reaction container transfer unit 109 may have any configuration as long as it can transfer the liquid without spilling even when the reaction container 51 contains the liquid.
- the automatic analyzer 1 includes a washing unit 110 that performs B / F washing of the carrier reagent, a stirring unit 111 that has a stirring bar that stirs the liquid contained in the reaction vessel 51, and the reaction fluid power in the reaction vessel 51. And a photometric unit 112 having a photomultiplier tube capable of detecting weak light emitted. When measuring the fluorescence generated from the reaction solution, a light source for irradiating excitation light may be provided as the photometric unit 112.
- FIG. 2 is an explanatory view schematically showing a schematic configuration of the cleaning unit 110 which is the cleaning apparatus according to this embodiment.
- the cleaning unit 110 shown in the figure includes a set of an air nozzle 2a that discharges air, a suction nozzle 2b that sucks liquid inside the reaction vessel 51, and a discharge nozzle 2c that discharges B / F cleaning liquid into the reaction vessel 51.
- a plurality of nozzle groups G are provided.
- the plurality of nodule groups G are provided above a part of the reaction vessels 51 held by the reaction vessel holding portion 105 and adjacent to each other along the circumference of the reaction vessel holding portion 105 in the same manner as the reaction vessel 51.
- the cleaning unit 110 detects the pressure of the air applied to the vicinity of the nose driving unit 3 that drives each nozzle group G and the base end of each air nozzle 2a, and the electric power corresponding to the detection result.
- a plurality of pressure sensors 4 that generate signals (analog signals) and a signal processing unit 5 that amplifies electric signals sent from the plurality of pressure sensors 4 and performs A / D conversion are provided.
- Each air nozzle 2a is connected to a different syringe 6 (air supply via a separate pipe 81). Means). The tip of each air nozzle 2a is located above the tips of the suction nozzle 2b and discharge nozzle 2c that make up the same nozzle group G, and the nozzle group G is lowered during the B / F cleaning to lower the reaction container. When inserted into 51, the reaction vessel 51 is positioned slightly below the upper end opening surface.
- the syringe 6 has a cylinder 6a and a piston 6b.
- air suction and discharge operations are performed, and this operation generates a single flow of air.
- This flow is transmitted to the air nozzle 2a communicated via the pipe 81.
- Each air supply means can also be realized by using a gas cylinder and a supply valve for adjusting the amount of air supplied from the gas cylinder.
- the suction nozzle 2b is connected to a buffer tank 8 via a pipe 82, and the buffer tank 8 is connected to a pump 9 realized by a vacuum pump.
- the liquid inside the reaction vessel 51 sucked by the pump 9 is discarded from the buffer tank 8 to the outside.
- the tip of the suction nozzle 2b extends below the tip of the other two nozzles.
- the tip of the suction nozzle 2b reacts.
- the liquid level in container 51 is first reached.
- the discharge nozzle 2c is connected to the syringe 10 via a pipe 83.
- the syringe 10 includes a cylinder 10a and a piston 10b, and a B / F cleaning liquid L is introduced into the pipe 83 and the cylinder 10a.
- Syringe 10 contains B / F cleaning liquid L via pipe 84.
- This pipe 84 has BZF cleaning liquid
- An injection valve 12 that controls the flow of L and a Bonn that sucks B / F cleaning liquid L from the liquid container 14
- Step 13 is intervening sequentially.
- B / F cleaning liquid L is introduced into piping 83 and cylinder 10a.
- the nozzle driving unit 3 drives three nozzles (air nozzle 2a, suction nozzle 2b, and discharge nozzle 2c) constituting each nozzle group G in a lump. For this reason, the relative positional relationship of the three nozzles in each nozzle group G does not change even when driven.
- the nozzle drive unit 3 can also drive each nozzle group G individually.
- the operation of the nozzle drive unit 3, the signal processing unit 5, the piston drive units 7 and 11, the pumps 9 and 13, and the injection valve 12 will be described later. It is controlled by the control unit 206 of the control analysis mechanism 201.
- FIG. 1 is merely a schematic illustration of the components of the measurement mechanism 101. That is, the mutual positional relationship between the components of the measurement mechanism 101 is a design matter that should be determined according to conditions such as the rotation mode of the wheel of the reaction container holding unit 105.
- the control analysis mechanism 201 includes an analysis operation unit 202 that performs an operation for analyzing the measurement result in the measurement mechanism 101, an input unit 203 that receives input of information necessary for analysis of the sample and an operation instruction signal of the automatic analyzer 1, and an analysis An output unit 204 that outputs information including the results, a storage unit 205 that stores information including the analysis results, and a control unit 206 that controls the automatic analyzer 1 are provided.
- the input unit 203 is realized by a keyboard, a mouse, a microphone, or the like.
- the output unit 204 is realized by a display (CRT, liquid crystal, plasma, organic EL, etc.), a printer, a speaker, and the like.
- the storage unit 205 includes a hard disk that magnetically stores various information, a memory that loads a program related to the process from the hard disk and electrically records it when the automatic analyzer 1 executes the process. Is provided.
- the storage unit 205 further includes an auxiliary storage device that can read information recorded on a recording medium such as a flexible disk, a CD-ROM, a DVD-ROM, an M0 disk, a PC card, and an xD picture card.
- the control unit 206 reads out the program stored in the storage unit 205 from the memory, thereby performing analysis calculation using the measurement result in the measurement mechanism 101, control of various operations of the automatic analyzer 1, and the like.
- control analysis mechanism 201 When the control analysis mechanism 201 having the above configuration receives the measurement result from the photometry unit 112, the analysis calculation unit 202 emits light of the reaction liquid in the reaction vessel 51 based on the measurement result sent from the photometry unit 112. The amount of the reaction solution is calculated, and in addition to the calculation result, the calibration parameters obtained from the standard sample and the analysis parameters included in the analysis information are used to quantitatively determine the components of the reaction solution.
- the analysis result obtained in this manner is output from the output unit 204 and is stored and stored in the storage unit 205.
- FIG. 3 is an explanatory diagram showing an outline of the operation of the cleaning unit 110 during B / F cleaning.
- the nozzle drive unit 3 moves the nozzle group G up and down with respect to the reaction vessel 51 under the control of the control unit 206, and after the immune reaction accommodated in the reaction vessel 51. Aspirate the liquid and discharge the B / F cleaning liquid a predetermined number of times.
- the Noznole group G is lowered toward the reaction vessel 51 that contains the liquid L1 that is the reaction solution after the immune reaction (state 1-1).
- the air nozzle 2a sucks air from the tip of the nozzle group G by the suction operation of the piston 6b by driving the piston drive unit 7 before or during the movement of the nozzle group G.
- the air nozzle 2a that has sucked in air stops after the descent of the nozzle group G to the reaction vessel 51 is completed and stops, and then the piston driving unit 7 drives the piston 6b to start discharging air.
- liquid level of liquid L2 which is a mixture of liquid L1 and B / F cleaning liquid L, is discharged when It must be below the bottom edge of Noznore 2c.
- nozzle group G is raised by the nozzle drive unit 3 (state 14), and the series of operations ends. Thereafter, a series of operations in states 11 to 14 are repeated a predetermined number of times.
- Fig. 4 is an explanatory view showing the time change of the pressure of the air inside the pipe 81 and the differential value (pressure differential) of the pressure in the vicinity of the base end portion of the air nozzle 2a.
- the pressure waveform W1 and pressure differential waveform W2 shown in the figure are the positive pressure of the air nozzle 2a.
- the tip force of the air nozzle 2a is the pressure of the air applied to the inside of the upper pipe 81 for a predetermined distance h (> 0). This is equivalent to that detected by the sensor 4 and output from the output unit 204 as a result of calculating the detected air pressure by the analysis calculation unit 202.
- the pressure differential waveform W2 asymptotically returns to the value before rising after rising sharply immediately after time t.
- control unit 206 determines that the operation of the cleaning unit 110 is normal.
- FIG. 5 is an explanatory diagram showing an example of a liquid level abnormality that occurs due to a malfunction in the suction operation of the suction nozzle 2b when the cleaning unit 110 performs B / F cleaning in the same procedure as described above.
- the nozzle group G is lowered in the state 2-1, the suction of the liquid L1 with the suction nozzle 2b [when the liquid L1 is not sufficiently sucked due to some trouble (State 2-2).
- State 2-2 some trouble
- the liquid volume of body L2 is higher than normal (the shaded area in the figure), and the liquid level of liquid L2 reaches the tip of Air Nozzle 2a in the process of discharging the same amount of BZF cleaning liquid L as normal Ma
- FIG. 6 is an explanatory diagram showing an outline of the time change of the air pressure and pressure differential detected by the pressure sensor 4 when an abnormality occurs in the suction operation of the suction nozzle 2b as described above (FIG. 6). And the downward direction is positive).
- the pressure waveform W3 is large at times t and t.
- the pressure differential waveform W4 also changes with the change of the pressure waveform W3. Two big rises. Of these, changes in each waveform at time ijt are normal and
- the change in each waveform at time t is that the liquid level of liquid L2 is at the tip of air nose 2a.
- control unit 206 sends out a control signal for stopping the driving of the piston drive unit 11, and the discharge nozzle Stop the discharge operation of B / F cleaning liquid L from 2c.
- FIG. 7 is a diagram showing the relationship between the distance from the tip of the air nozzle 2 a to the pressure sensor 4 and the air pressure in the pipe 81 detected by the pressure sensor 4.
- the air pressure when the tip of the air nozzle 2a is closed takes a constant value P regardless of the value of X (that is, regardless of the position of the pressure sensor 4).
- the amount of change ⁇ P detected by the pressure sensor 4 before and after the liquid L2 rises to the tip of the air nozzle 2a and closes the tip of the air nozzle 2a changes according to the position of the pressure sensor 4.
- Fig. 8 is an explanatory diagram showing an outline of the time change of the air pressure and its pressure derivative when an abnormality in the liquid level position is detected in a mode different from Fig. 6 (the downward direction is positive in the figure). To do).
- air is discharged from the air nozzle 2a at time t.
- the amount of change when the pressure at the time of starting is larger than the case shown in pressure waveform W1 or pressure waveform W3 is ⁇ ⁇ '.
- the pressure differential waveform W6 also changes with time t
- the present invention comprises a suction nozzle that sucks at least a part of a reaction liquid that has caused a heterogeneous reaction, and a discharge nozzle that discharges a predetermined B / F cleaning liquid.
- a suction nozzle that sucks at least a part of a reaction liquid that has caused a heterogeneous reaction
- a discharge nozzle that discharges a predetermined B / F cleaning liquid.
- a plurality of pressure sensors for detecting the pressure of air in the vicinity of the proximal end of the air nozzle connected to each of the plurality of syringes.
- the syringe for supplying air is provided for each air nozzle, compared with the case where the air supply to all the air nozzles is performed collectively with one syringe. Better detection sensitivity can be obtained.
- a particulate carrier such as glass or plastic having a diameter of 5 to 1 Omm may be used.
- the carrier analyzer that contains the carrier is stored in the automatic analyzer. What is necessary is just to further provide the carrier transfer part which transfers a support
- magnetic particles having a diameter of about 1 / im at most can be used as the solid phase.
- the magnetic particles are collected in one place in the reaction container by applying a magnetic field from the outside of the reaction container when performing the BZF cleaning.
- the present invention can also be applied to the case of detecting the level of a cleaning liquid or a reaction liquid of an automatic analyzer that performs biochemical analysis or genetic analysis using a heterogeneous reaction. it can.
- the present invention is useful for an automatic analyzer that automatically and continuously analyzes a component of a sample by reacting the sample with a reagent, and in particular, immunology of the component of the sample. This is suitable for performing statistical analysis.
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- Chemical Kinetics & Catalysis (AREA)
- Automatic Analysis And Handling Materials Therefor (AREA)
- Sampling And Sample Adjustment (AREA)
Abstract
Easy-to-maintain cleaning equipment in which abnormality in liquid level position of reaction liquid contained in a reaction container can be detected exactly when B/F cleaning of reaction liquid that has produced heterogeneous reaction is performed. An automatic analyzer is also provided. The cleaning equipment comprises a plurality of air nozzles provided in association with a plurality of pairs of nozzles each consisting of a nozzle for sucking at least part of the reaction liquid and an ejection nozzle for ejecting a predetermined B/F cleaning liquid and ejecting air from above the pointed ends of the pair of suction nozzle and the ejection nozzle, a plurality of air supply means connected with any of the plurality of air nozzles, respectively, and supplying air to the air nozzles, a plurality of pressure sensors connected with the plurality of air supply means, respectively, and detecting the pressure of air in the vicinity of the proximal end of the air nozzle, and a control means for controlling the ejection operation of B/F cleaning liquid of each ejection nozzle individually depending on the pressure of air detected by each of the plurality of pressure sensors and a variation in the pressure.
Description
明 細 書 Specification
洗浄装置および自動分析装置 Cleaning device and automatic analyzer
技術分野 Technical field
[0001] 本発明は、不均一系反応を生じた反応液の BZF洗浄を行う洗浄装置、および当 該洗浄装置を備えて血液や体液等の検体を分析する自動分析装置に関する。 背景技術 The present invention relates to a cleaning device that performs BZF cleaning of a reaction solution that has caused a heterogeneous reaction, and an automatic analyzer that includes the cleaning device and analyzes a sample such as blood or body fluid. Background art
[0002] 血液や体液等の検体を不均一系反応、例えば免疫学的分析により分析する際に は、固相に付着した抗原 (または抗体)と標識物質である抗体 (または抗原)との間で 抗原抗体反応を生じさせた後、所定の B/F洗浄液を加えることにより、その反応液 中で遊離している抗原や抗体を固相から分離洗浄する B/F洗浄処理が行われる。 [0002] When analyzing a sample such as blood or body fluid by heterogeneous reaction, for example, immunological analysis, between an antigen (or antibody) attached to a solid phase and an antibody (or antigen) as a labeling substance. After causing the antigen-antibody reaction in step B, a predetermined B / F washing solution is added to perform a B / F washing treatment for separating and washing the antigens and antibodies released in the reaction solution from the solid phase.
[0003] 従来、上述した B/F洗浄処理において、反応容器に収容される反応液がその反 応容器から溢れつつある状況を検知する技術として、 B/F洗浄液を吐出するノズル または反応容器内部の液体を攪拌する攪拌棒を導電性部材によって形成し、そのノ ズルの下端近傍位置に導電性部材から成る検出部を配設することにより、ノズノレまた は攪拌棒と検出部との間で生じる液面検知信号によって液面位置の異常を検知し、 この検知結果に基づいてノズルからの洗浄液の吐出を停止する技術が知られている (例えば、特許文献 1を参照)。 [0003] Conventionally, in the B / F cleaning process described above, as a technique for detecting a situation in which the reaction liquid stored in the reaction vessel is overflowing from the reaction container, a nozzle for discharging the B / F cleaning liquid or the inside of the reaction container A stir bar that stirs the liquid is formed of a conductive member, and a detection unit made of a conductive member is disposed in the vicinity of the lower end of the nozzle. A technique is known in which an abnormality in the liquid level position is detected by a liquid level detection signal, and discharge of the cleaning liquid from the nozzle is stopped based on the detection result (see, for example, Patent Document 1).
[0004] 特許文献 1 :実公平 2— 13978号公報 [0004] Patent Document 1: Japanese Utility Model Publication No. 2-13978
発明の開示 Disclosure of the invention
発明が解決しょうとする課題 Problems to be solved by the invention
[0005] し力、しながら、上述した従来技術では、導電性部材力 成るノズル、攪拌棒、または 検出部が B/F洗浄液などによって腐食されてしまうと、反応液の液面位置の異常を 適確に検知することができなくなってしまう恐れがあった。また、導電性部材の腐食を 防止するためには、それらを装置から取り外して定期的に洗浄等を行う必要があるが 、導電性部材は各種電装部品と接続されているために取り外すのが容易ではなぐ 保守管理に手間力 Sかかるという問題もあった。 However, in the above-described conventional technology, if the nozzle, the stirring rod, or the detection unit, which is a conductive member force, is corroded by the B / F cleaning liquid, the liquid level position of the reaction liquid is abnormal. There was a risk that it could not be detected accurately. In addition, in order to prevent corrosion of the conductive members, it is necessary to remove them from the apparatus and periodically clean them. However, since the conductive members are connected to various electrical components, they can be easily removed. However, there was also a problem that it took time and effort for maintenance management.
[0006] 本発明は、上記に鑑みてなされたものであり、不均一系反応を生じた反応液の B/
F洗浄を行う際、その反応液の反応容器内における液面位置の異常を適確に検知 することができ、保守管理も容易に行うことができる洗浄装置および自動分析装置を 提供することを目的とする。 [0006] The present invention has been made in view of the above, and the reaction solution B / F It is an object to provide a cleaning device and an automatic analyzer that can accurately detect abnormality of the liquid level in the reaction container of the reaction solution and perform maintenance management easily. And
課題を解決するための手段 Means for solving the problem
[0007] 上述した課題を解決し、 目的を達成するために、本発明に係る洗浄装置は、不均 一系反応を生じた反応液の B/F洗浄を行うために、前記反応液の少なくとも一部を 吸引する吸引ノズルおよび所定の B/F洗浄液を吐出する吐出ノズル力ゝら成るノズル 対を複数備えた洗浄装置であって、各ノズノレ対に対応して設けられ、該当するノズル 対をなす吸引ノズノレおよび吐出ノズノレの各先端部よりも上方からエアーを吐出する 複数のエアーノズノレと、前記複数のエアーノズルのいずれかに接続され、この接続さ れたエアーノズルにエアーを供給する複数のエアー供給手段と、前記複数のエアー 供給手段の各々に接続されたエアーノズルの基端部の近傍におけるエアーの圧力 をそれぞれ検知する複数の圧力センサと、前記複数の圧力センサがそれぞれ検知し たエアーの圧力および該圧力の変化に応じて各吐出ノズルの B/F洗浄液の吐出動 作を個別に制御する制御手段と、を備えたことを特徴とする。 [0007] In order to solve the above-described problems and achieve the object, the cleaning apparatus according to the present invention is configured to perform at least B / F cleaning of a reaction solution in which a heterogeneous reaction has occurred. This is a cleaning device equipped with a plurality of nozzle pairs consisting of a suction nozzle that sucks a part and a discharge nozzle force that discharges a predetermined B / F cleaning liquid, and is provided corresponding to each nozzle pair. A plurality of air nozzles that discharge air from above the leading ends of the suction nozzle and discharge nozzle, and a plurality of air that is connected to one of the plurality of air nozzles and supplies air to the connected air nozzles A supply means; a plurality of pressure sensors for detecting air pressure in the vicinity of a base end portion of an air nozzle connected to each of the plurality of air supply means; and the plurality of pressure sensors. There is characterized in that and a control means for individually controlling the discharge operation of the B / F cleaning liquid the discharge nozzles in response to changes in pressure and the pressure of the air has been detected, respectively.
[0008] また、本発明に係る洗浄装置は、上記発明におレ、て、前記制御手段は、前記複数 のエアーノズルのうちで自身の基端部の近傍におけるエアーの圧力および該圧力の 変化が所定の範囲を逸脱した値をとるエアーノズルに対応する吐出ノズノレの B/F洗 浄液の吐出動作を停止することを特徴とする。 [0008] Further, the cleaning device according to the present invention is based on the above invention, and the control means includes the air pressure in the vicinity of the base end portion of the plurality of air nozzles and a change in the pressure. Is characterized in that the discharge operation of the B / F cleaning liquid of the discharge nozzle corresponding to the air nozzle that takes a value that deviates from the predetermined range is stopped.
[0009] 本発明に係る自動分析装置は、分析対象の検体に不均一系反応を生じさせること によって当該検体の分析を行う自動分析装置であって、上記いずれかの発明に係る 洗浄装置を備えたことを特徴とする。 [0009] An automatic analyzer according to the present invention is an automatic analyzer that analyzes a sample by causing a heterogeneous reaction in the sample to be analyzed, and includes the cleaning device according to any one of the above inventions. It is characterized by that.
発明の効果 The invention's effect
[0010] 本発明によれば、不均一系反応を生じた反応液の少なくとも一部を吸引する吸引ノ ズノレおよび所定の B/F洗浄液を吐出する吐出ノズルから成る複数のノズル対の各 々に対応して設けられ、該当するノズノレ対をなす吸引ノズノレおよび吐出ノズルの各 先端部よりも上方からエアーを吐出する複数のエアーノズルと、前記複数のェアーノ ズルのレ、ずれかに接続され、この接続されたエアーノズノレにエアーを供給する複数
のエアー供給手段と、前記複数のエアー供給手段の各々に接続されたエアーノズノレ の基端部の近傍におけるエアーの圧力をそれぞれ検知する複数の圧力センサと、前 記複数の圧力センサがそれぞれ検知したエアーの圧力および該圧力の変化に応じ て各吐出ノズノレの B/F洗浄液の吐出動作を個別に制御する制御手段と、を備える ことにより、不均一系反応を生じた反応液の BZF洗浄を行う際、反応容器内部に収 容される反応液の液面位置の異常を適確に検知することが可能となり、保守管理も 容易となる。 [0010] According to the present invention, each of a plurality of nozzle pairs including a suction nozzle that sucks at least a part of a reaction solution that has caused a heterogeneous reaction and a discharge nozzle that discharges a predetermined B / F cleaning solution. Correspondingly provided, a plurality of air nozzles for discharging air from above the respective tips of the suction nozzles and discharge nozzles forming a corresponding pair of nozzles, and the plurality of air nozzles are connected to the misalignment. Multiple air supply to connected air nozzles Air supply means, a plurality of pressure sensors for detecting air pressure in the vicinity of the proximal end of the air nozzle connected to each of the plurality of air supply means, and air detected by the plurality of pressure sensors, respectively. And a control means for individually controlling the discharge operation of the B / F cleaning liquid of each discharge nozzle in accordance with the change in the pressure, when performing BZF cleaning of the reaction liquid that has caused a heterogeneous reaction. In addition, it is possible to accurately detect abnormalities in the position of the reaction liquid contained in the reaction vessel, and maintenance management becomes easy.
図面の簡単な説明 Brief Description of Drawings
[0011] [図 1]図 1は、本発明の一実施の形態に係る自動分析装置要部の構成を示す図であ る。 FIG. 1 is a diagram showing a configuration of a main part of an automatic analyzer according to an embodiment of the present invention.
[図 2]図 2は、本発明の一実施の形態に係る洗浄装置要部の構成を示す図である。 FIG. 2 is a diagram showing a configuration of a main part of a cleaning apparatus according to an embodiment of the present invention.
[図 3]図 3は、本発明の一実施の形態に係る洗浄装置の B/F洗浄時における動作 の概要を示す説明図である。 FIG. 3 is an explanatory diagram showing an outline of an operation during B / F cleaning of the cleaning device according to one embodiment of the present invention.
[図 4]図 4は、図 3に示す場合に検知されるエアーの圧力およびその圧力微分の時間 変化を示す図である。 [FIG. 4] FIG. 4 is a diagram showing the air pressure detected in the case shown in FIG. 3 and the time variation of its pressure derivative.
[図 5]図 5は、本発明の一実施の形態に係る洗浄装置の B/F洗浄時における動作 に異常が発生する状況を示す説明図である。 FIG. 5 is an explanatory diagram showing a situation in which an abnormality occurs in the operation during B / F cleaning of the cleaning device according to one embodiment of the present invention.
[図 6]図 6は、図 5に示す場合に検知されるエアーの圧力およびその圧力微分の時間 変化を示す図である。 [FIG. 6] FIG. 6 is a diagram showing the change in air pressure detected in the case shown in FIG. 5 and its pressure derivative over time.
[図 7]図 7は、エアーノズル先端から圧力センサまでの距離と圧力センサが検知する 配管内のエアーの圧力の関係を示す図である。 FIG. 7 is a diagram showing the relationship between the distance from the tip of the air nozzle to the pressure sensor and the air pressure in the pipe detected by the pressure sensor.
[図 8]図 8は、エアーの吐出を開始する時点でエアーノズルの先端が反応容器内の 液面によって閉塞されている場合に検知されるエアーの圧力およびその圧力微分の 時間変化を示す図である。 [FIG. 8] FIG. 8 is a diagram showing the time change of the air pressure and the pressure derivative detected when the tip of the air nozzle is blocked by the liquid level in the reaction vessel at the start of the air discharge. It is.
符号の説明 Explanation of symbols
[0012] 1 自動分析装置 [0012] 1 Automatic analyzer
2a エアーノズル 2a Air nozzle
2b 吸引ノズノレ
c 吐出ノズル 2b Nozzle suction c Discharge nozzle
ノズル駆動部 圧力センサ Nozzle drive unit Pressure sensor
信号処理部 Signal processor
、 10 シリンジ, 10 syringes
a、 10a シリンダb、 10b ビス卜ン 、 1 1 ピストン駆動部 バッファタンク 、 13 ポンプa, 10a Cylinder b, 10b Screw, 1 1 Piston drive part Buffer tank, 13 Pump
2 注入弁2 Injection valve
4 液体容器4 Liquid container
1 検体容器1 Sample container
2 ラック2 racks
1 担体試薬容器1 Carrier reagent container
1 液体試薬容器1 Liquid reagent container
1 反応容器1 Reaction vessel
1、 82、 83、 84 配管01 測定機構1, 82, 83, 84 Piping 01 Measuring mechanism
02 検体移送部02 Sample transfer section
03 担体試薬容器保持部04 液体試薬容器保持部05 反応容器保持部06 検体分注部03 Carrier reagent container holding part 04 Liquid reagent container holding part 05 Reaction container holding part 06 Sample dispensing part
7 担体試薬分注部 8 液体試薬分注部 9 反応容器移送部10 洗浄部
111 攪拌部 7 Carrier reagent dispensing part 8 Liquid reagent dispensing part 9 Reaction container transfer part 10 Washing part 111 Stirrer
112 測光部 112 Metering unit
119 反応容器格納部 119 Reaction container storage
129 反応容器廃棄部 129 Reaction vessel disposal section
201 制御分析機構 201 Control analysis mechanism
202 分析演算部 202 Analysis calculation unit
203 入力部 203 Input section
204 出力部 204 Output section
205 pL [思 p[5 205 pL [Thought p [5
206 制御部 206 Control unit
CR1、 CR2、 CR3 情報コード読取部 CR1, CR2, CR3 Information code reader
G ノズル群 G Nozzle group
L1、L2 液体 L1, L2 liquid
L B/F洗浄液 L B / F cleaning solution
BF BF
W1、W3、W5 圧力波形 W1, W3, W5 Pressure waveform
W2、W4、W6 圧力微分波形 W2, W4, W6 Pressure differential waveform
発明を実施するための最良の形態 BEST MODE FOR CARRYING OUT THE INVENTION
[0013] 以下、添付図面を参照して本発明を実施するための最良の形態(以後、「実施の形 態」と称する)を説明する。 Hereinafter, the best mode for carrying out the present invention (hereinafter referred to as “embodiment”) will be described with reference to the accompanying drawings.
[0014] <免疫分析処理の概要 > [0014] <Overview of immunoassay processing>
まず、本発明の一実施の形態に係る自動分析装置が行う免疫分析処理の概要を 説明する。この実施の形態では、不均一系反応を用レ、た免疫測定を行う。以下、そ の一例として酵素免疫測定法 (EIA)によって検体中の所定の抗原の濃度を測定す る場合を説明する。この免疫分析処理では、最初に検体中の所定の抗原に特異的 に結合する抗体によって感作された固相と検体とを混合させることによって 1回目の 免疫反応 (抗原抗体反応)を行わせる。以下の説明においては、固相として反応容 器を適用する。すなわち、反応容器の内壁底面付近には、予め所定の抗体が吸着し ているものとする。
[0015] 上述した 1回目の免疫反応の後、所定の B/F洗浄液によって反応液の B/F洗浄 を行い、抗体と特異的に結合せずに遊離してレ、る検体成分 (抗原を含む)や抗体を 固相から分離除去する。その後、標識物質である酵素を過剰に加えることによって 2 回目の免疫反応を行わせる。この 2回目の免疫反応後にも反応液の BZF洗浄を行 レ、、余乗 IJして遊離している標識物質等を固相から分離除去する。その後、標識物質 である酵素が活性を発現する発色基質を反応液に加えることによつて反応液中の標 識物質との間で発色反応を行わせ、発色した量を光学的に測定する。最後に、この 測定によって得られたデータと抗原の濃度が既知の標準検体力 得られたデータ( 検量線)との比較演算を行うことにより、分析対象の抗原の検体中の濃度を求める。 First, an outline of an immune analysis process performed by the automatic analyzer according to an embodiment of the present invention will be described. In this embodiment, immunoassay is performed using a heterogeneous reaction. As an example, a case where the concentration of a predetermined antigen in a specimen is measured by enzyme immunoassay (EIA) will be described below. In this immunoassay process, a first immune reaction (antigen-antibody reaction) is performed by mixing a solid phase sensitized with an antibody that specifically binds to a predetermined antigen in the sample and the sample. In the following explanation, a reaction vessel is applied as a solid phase. That is, it is assumed that a predetermined antibody is adsorbed in advance near the bottom of the inner wall of the reaction vessel. [0015] After the first immune reaction described above, the reaction solution is subjected to B / F washing with a predetermined B / F washing solution and released without specifically binding to the antibody. And the antibody is separated and removed from the solid phase. Then, a second immune reaction is performed by adding an excess of the labeling enzyme. Even after this second immune reaction, the reaction solution is washed with BZF, and the released labeling substance, etc. is separated and removed from the solid phase by extra power IJ. Thereafter, a coloring substrate that exhibits the activity of the enzyme as a labeling substance is added to the reaction solution to cause a coloring reaction with the labeling substance in the reaction solution, and the amount of color development is optically measured. Finally, the concentration of the antigen to be analyzed in the sample is determined by performing a comparison operation between the data obtained by this measurement and the standard sample force data (calibration curve) with a known antigen concentration.
[0016] なお、上記と同様にして検体中の所定の抗体の濃度を測定することも勿論可能で ある。この場合には、その抗体と特異的に結合する抗原を予め固相に吸着させてお けばよい。また、上述した酵素免疫測定法以外の不均一系反応を用いた免疫測定 法を適用することによって検体の分析を行うことも可能である。そのような免疫測定法 としては、蛍光物質を標識物質とする蛍光免疫測定法 (FIA)、放射性同位体を標識 物質とする放射性免疫測定法 (RIA)、化学発光基質を標識物質とする化学酵素免 疫測定法 (CLIA)、およびスピン試薬を標識物質とするスピン試薬免疫測定法 (SIA )などがある。 [0016] It is of course possible to measure the concentration of a predetermined antibody in a specimen in the same manner as described above. In this case, an antigen that specifically binds to the antibody may be adsorbed on a solid phase in advance. It is also possible to analyze a sample by applying an immunoassay using a heterogeneous reaction other than the enzyme immunoassay described above. Such immunoassays include fluorescent immunoassay (FIA) using fluorescent substances as labeling substances, radioimmunoassay (RIA) using radioisotopes as labeling substances, and chemical enzymes using chemiluminescent substrates as labeling substances. Examples include immunoassay (CLIA) and spin reagent immunoassay (SIA) using spin reagent as a labeling substance.
[0017] <自動分析装置の構成 > [0017] <Configuration of automatic analyzer>
図 1は、本発明の一実施の形態に係る自動分析装置要部の構成を模式的に示す 図である。同図に示す自動分析装置 1は、検体等の試料および試薬を反応容器にそ れぞれ分注し、その反応容器内で生じる反応を光学的に測定する測定機構 101と、 この測定機構 101の駆動制御を行うとともに測定機構 101における測定結果の分析 を行う制御分析機構 201とを有し、これら二つの機構が連携することによって複数の 検体の成分の免疫学的な分析を自動的かつ連続的に行う装置である。以後、自動 分析装置 1が不均一系反応を用いた免疫学的な測定を行うものとして説明する。 FIG. 1 is a diagram schematically showing a configuration of a main part of an automatic analyzer according to an embodiment of the present invention. The automatic analyzer 1 shown in the figure dispenses a sample such as a sample and a reagent into a reaction vessel, and optically measures the reaction occurring in the reaction vessel, and the measurement mechanism 101 And control and analysis mechanism 201 that analyzes the measurement results in measurement mechanism 101, and these two mechanisms work together to automatically and continuously perform immunological analysis of the components of multiple samples. It is a device that performs automatically. In the following description, it is assumed that the automatic analyzer 1 performs an immunological measurement using a heterogeneous reaction.
[0018] 最初に自動分析装置 1の測定機構 101について説明する。測定機構 101は、検体 を収容する検体容器 21が搭載された複数のラック 22を収納して順次移送する検体 移送部 102と、検体との抗原抗体反応に適用する担体試薬を収容する担体試薬容
器 31を保持する担体試薬容器保持部 103と、各種液体試薬を収容する液体試薬容 器 41を保持する液体試薬容器保持部 104と、検体と試薬とを反応させる反応容器 5 1を保持する反応容器保持部 105と、を備える。 First, the measurement mechanism 101 of the automatic analyzer 1 will be described. The measurement mechanism 101 includes a sample transfer unit 102 that stores and sequentially transfers a plurality of racks 22 on which sample containers 21 that store samples are mounted, and a carrier reagent container that stores a carrier reagent applied to an antigen-antibody reaction with the sample. A carrier reagent container holding unit 103 for holding the vessel 31, a liquid reagent container holding unit 104 for holding the liquid reagent vessel 41 for storing various liquid reagents, and a reaction vessel 51 for holding the reaction between the sample and the reagent. A container holding unit 105.
[0019] 担体試薬容器保持部 103は、担体試薬容器 31を保持するホイールと、このホイ一 ルの底面中心に取り付けられ、その中心を通る鉛直線を回転軸としてホイールを回 転させる駆動手段とを有する。液体試薬容器保持部 104および反応容器保持部 10 5も担体試薬容器保持部 103と同様、ホイールとホイールを回転させる駆動手段とを それぞれ有する。 [0019] The carrier reagent container holding unit 103 is a wheel that holds the carrier reagent container 31, and a drive unit that is attached to the center of the bottom surface of the wheel and rotates the wheel with a vertical line passing through the center as a rotation axis. Have Similarly to the carrier reagent container holding unit 103, the liquid reagent container holding unit 104 and the reaction container holding unit 105 have a wheel and driving means for rotating the wheel.
[0020] 各容器保持部内は一定の温度が保たれている。例えば、液体試薬容器保持部 10 4は、試薬の劣化や変性を抑制するために室温よりも低温に設定され、反応容器保 持部 105内は、人間の体温と同程度の温度に設定される。 [0020] A constant temperature is maintained in each container holding portion. For example, the liquid reagent container holding unit 104 is set to a temperature lower than room temperature in order to suppress the deterioration and denaturation of the reagent, and the reaction container holding unit 105 is set to a temperature similar to the human body temperature. .
[0021] また、測定機構 101は、検体移送部 102上の検体容器 21に収容されている検体を 反応容器保持部 105で保持する反応容器 51に分注する検体分注部 106と、担体試 薬容器保持部 103上の担体試薬容器 31に収容されている担体試薬を反応容器 51 に分注する担体試薬分注部 107と、液体試薬容器保持部 104上の液体試薬容器 4 1に収容されてレ、る液体試薬を反応容器 51に分注する液体試薬分注部 108と、反 応容器 51を反応容器保持部 105に設置したり反応容器保持部 105から取り除いたり するために反応容器 51を移送する反応容器移送部 109と、を備える。 In addition, the measurement mechanism 101 includes a sample dispensing unit 106 that dispenses a sample accommodated in the sample container 21 on the sample transfer unit 102 into a reaction container 51 that is held by a reaction container holding unit 105, and a carrier test. The carrier reagent dispensing unit 107 for dispensing the carrier reagent contained in the carrier reagent container 31 on the drug container holding unit 103 into the reaction vessel 51 and the liquid reagent container 41 on the liquid reagent container holding unit 104 The liquid reagent dispensing unit 108 for dispensing the liquid reagent into the reaction vessel 51 and the reaction vessel 51 for installing and removing the reaction vessel 51 from the reaction vessel holding unit 105 A reaction vessel transfer unit 109 for transferring the reaction vessel.
[0022] 検体容器 21には、その内部に収容する検体を識別する識別情報をバーコードまた は 2次元コード等の情報コードにコード化して記録した情報コード記録媒体が貼付さ れている(図示せず)。同様に、担体試薬容器 31および液体試薬容器 41にも、内部 に収容する試薬を識別する識別情報を情報コードにコード化して記録した情報コー ド記録媒体がそれぞれ貝占付されている(図示せず)。このため、測定機構 101は、検 体容器 21に貼付された情報コードを読み取る情報コード読取部 CR1、担体試薬容 器 31に貼付された情報コードを読み取る情報コード読取部 CR2、および液体試薬 容器 41に貼付された情報コードを読み取る情報コード読取部 CR3を備える。 [0022] The sample container 21 is affixed with an information code recording medium in which identification information for identifying a sample contained in the container 21 is encoded and recorded in an information code such as a barcode or a two-dimensional code (see FIG. Not shown). Similarly, each of the carrier reagent container 31 and the liquid reagent container 41 is shelled with an information code recording medium in which identification information for identifying the reagent contained therein is encoded and recorded in an information code (not shown). ) Therefore, the measurement mechanism 101 includes an information code reading unit CR1 that reads an information code affixed to the specimen container 21, an information code reading part CR2 that reads an information code affixed to the carrier reagent container 31, and a liquid reagent container 41. An information code reading unit CR3 for reading the information code attached to the is provided.
[0023] 検体分注部 106、担体試薬分注部 107、および液体試薬分注部 108は、検体の吸 引および吐出を行う細管状のプローブと、このプローブを移動するために鉛直方向
への昇降動作および水平方向への回転動作を行うアームと、吸排シリンジ等を用い た吸排機構とをそれぞれ備える。各プローブは、 1回の分注動作の後、個別に設けら れる洗浄部(図示せず)で洗浄される。なお、コンタミネーシヨンやキャリーオーバを防 止する意味では、プローブの先端に着脱自在なチップを装着し、 1回の分注動作ごと にチップを交換するデイスポーザブル方式を採用すればより好ましい。 [0023] The sample dispensing unit 106, the carrier reagent dispensing unit 107, and the liquid reagent dispensing unit 108 are a thin tube probe that sucks and discharges a sample, and a vertical direction for moving the probe. Each arm is equipped with an arm that moves up and down and rotates horizontally, and an intake / exhaust mechanism using an intake / exhaust syringe. Each probe is cleaned by a separate cleaning unit (not shown) after a single dispensing operation. In order to prevent contamination and carry-over, it is more preferable to use a disposable method in which a detachable tip is attached to the tip of the probe and the tip is replaced for each dispensing operation.
[0024] 反応容器移送部 109の動作線上には、未使用の反応容器 51を保持する反応容器 格納部 119と、使用後の反応容器 51を廃棄する反応容器廃棄部 129とが設けられ ている。反応容器移送部 109は、反応容器 51の内部に液体がある場合であってもそ の液体をこぼすことなく移送できるものであれば如何なる構成を有していてもよい。 [0024] On the operation line of the reaction vessel transfer unit 109, a reaction vessel storage unit 119 for holding an unused reaction vessel 51 and a reaction vessel disposal unit 129 for discarding the used reaction vessel 51 are provided. . The reaction container transfer unit 109 may have any configuration as long as it can transfer the liquid without spilling even when the reaction container 51 contains the liquid.
[0025] 引き続き自動分析装置 1の構成を説明する。 自動分析装置 1は、担体試薬の B/F 洗浄を行う洗浄部 110と、反応容器 51の内部に収容された液体を攪拌する攪拌棒 を有する攪拌部 111と、反応容器 51内の反応液力 発光する微弱な光を検出可能 な光電子増倍管を有する測光部 112と、を備える。なお、反応液から発生する蛍光を 測定する場合には、測光部 112として励起光を照射するための光源を設ければよい [0025] Next, the configuration of the automatic analyzer 1 will be described. The automatic analyzer 1 includes a washing unit 110 that performs B / F washing of the carrier reagent, a stirring unit 111 that has a stirring bar that stirs the liquid contained in the reaction vessel 51, and the reaction fluid power in the reaction vessel 51. And a photometric unit 112 having a photomultiplier tube capable of detecting weak light emitted. When measuring the fluorescence generated from the reaction solution, a light source for irradiating excitation light may be provided as the photometric unit 112.
[0026] 図 2は、この実施の形態に係る洗浄装置である洗浄部 110の概略構成を模式的に 示す説明図である。同図に示す洗浄部 110は、エアーを吐出するエアーノズル 2a、 反応容器 51内部の液体を吸引する吸引ノズル 2b、および反応容器 51の内部に B/ F洗浄液を吐出する吐出ノズル 2cを一組とするノズル群 Gを複数備える。この複数の ノズノレ群 Gは、反応容器保持部 105に保持される一部の反応容器 51の上方に、反 応容器 51と同様に反応容器保持部 105の円周に沿つて互いに隣接して設けられる FIG. 2 is an explanatory view schematically showing a schematic configuration of the cleaning unit 110 which is the cleaning apparatus according to this embodiment. The cleaning unit 110 shown in the figure includes a set of an air nozzle 2a that discharges air, a suction nozzle 2b that sucks liquid inside the reaction vessel 51, and a discharge nozzle 2c that discharges B / F cleaning liquid into the reaction vessel 51. A plurality of nozzle groups G are provided. The plurality of nodule groups G are provided above a part of the reaction vessels 51 held by the reaction vessel holding portion 105 and adjacent to each other along the circumference of the reaction vessel holding portion 105 in the same manner as the reaction vessel 51. Be
[0027] また、洗浄部 110は、各ノズル群 Gを駆動するノズノレ駆動部 3と、各エアーノズル 2a の基端部の近傍に加わるエアーの圧力をそれぞれ検知し、この検知結果に対応する 電気信号 (アナログ信号)を生成する複数の圧力センサ 4と、この複数の圧力センサ 4 からそれぞれ送られてくる電気信号を増幅して A/D変換を行う信号処理部 5とを備 る。 [0027] Further, the cleaning unit 110 detects the pressure of the air applied to the vicinity of the nose driving unit 3 that drives each nozzle group G and the base end of each air nozzle 2a, and the electric power corresponding to the detection result. A plurality of pressure sensors 4 that generate signals (analog signals) and a signal processing unit 5 that amplifies electric signals sent from the plurality of pressure sensors 4 and performs A / D conversion are provided.
[0028] 各エアーノズル 2aは、それぞれ別の配管 81を介して異なるシリンジ 6 (エアー供給
手段)に接続されている。各エアーノズル 2aの先端部は、同じノズノレ群 Gを構成する 吸引ノズノレ 2bおよび吐出ノズノレ 2cの各先端部よりも上方に位置しており、 B/F洗浄 時にノズル群 Gを下降して反応容器 51の内部に挿入したとき、反応容器 51の上端 開口面よりも若干下方に位置するようになっている。 [0028] Each air nozzle 2a is connected to a different syringe 6 (air supply via a separate pipe 81). Means). The tip of each air nozzle 2a is located above the tips of the suction nozzle 2b and discharge nozzle 2c that make up the same nozzle group G, and the nozzle group G is lowered during the B / F cleaning to lower the reaction container. When inserted into 51, the reaction vessel 51 is positioned slightly below the upper end opening surface.
[0029] シリンジ 6は、シリンダ 6aとピストン 6bとを有し、ピストン駆動部 7によってピストン 6b が移動することにより、エアーの吸引および吐出動作を行レ、、この動作によってエア 一の流れを生じさせ、この流れが配管 81を介して連通されるエアーノズル 2aに伝達 される。なお、各エアー供給手段は、ガスボンベと、このガスボンベからのエアー供給 量を調節する供給弁とを用いて実現することもできる。 [0029] The syringe 6 has a cylinder 6a and a piston 6b. When the piston 6b is moved by the piston drive unit 7, air suction and discharge operations are performed, and this operation generates a single flow of air. This flow is transmitted to the air nozzle 2a communicated via the pipe 81. Each air supply means can also be realized by using a gas cylinder and a supply valve for adjusting the amount of air supplied from the gas cylinder.
[0030] ところで、シリンジ 6の吐出圧力を、各エアーノズノレ 2aから吐出するエアーが反応容 器 51に収容される液体の液面を揺らさない程度の範囲で大きくしておけば、圧力セ ンサ 4の感度を良くするのと同時に、配管 81の振動による影響を軽減させることもで きる。この結果、エアーの圧力の安定した検知が可能となり、一段と好ましい。 [0030] By the way, if the discharge pressure of the syringe 6 is increased within a range where the air discharged from each air nozzle 2a does not shake the liquid level of the liquid stored in the reaction vessel 51, the pressure sensor 4 At the same time as improving the sensitivity, the influence of vibration of the pipe 81 can be reduced. As a result, the air pressure can be stably detected, which is more preferable.
[0031] 吸引ノズノレ 2bは、配管 82を介してバッファタンク 8に接続され、このバッファタンク 8 は、真空ポンプによって実現されるポンプ 9に接続されている。このポンプ 9によって 吸引された反応容器 51内部の液体は、バッファタンク 8から外部へ廃棄される。吸引 ノズノレ 2bの先端部は、他の二つのノズルの先端部よりも下方に延出しており、ノズノレ 群 Gを反応容器 51に対して下降させていったとき、その吸引ノズノレ 2bの先端が反応 容器 51内の液面に最初に到達する。 [0031] The suction nozzle 2b is connected to a buffer tank 8 via a pipe 82, and the buffer tank 8 is connected to a pump 9 realized by a vacuum pump. The liquid inside the reaction vessel 51 sucked by the pump 9 is discarded from the buffer tank 8 to the outside. The tip of the suction nozzle 2b extends below the tip of the other two nozzles. When the nozzle group G is lowered with respect to the reaction vessel 51, the tip of the suction nozzle 2b reacts. The liquid level in container 51 is first reached.
[0032] 吐出ノズノレ 2cは、配管 83を介してシリンジ 10に接続されている。このシリンジ 10は 、シリンダ 10aとピストン 10bとを有し、配管 83とシリンダ 10aの内部には B/F洗浄液 L が導入されている。また、シリンジ 10は、配管 84を介して B/F洗浄液 L を収容 [0032] The discharge nozzle 2c is connected to the syringe 10 via a pipe 83. The syringe 10 includes a cylinder 10a and a piston 10b, and a B / F cleaning liquid L is introduced into the pipe 83 and the cylinder 10a. Syringe 10 contains B / F cleaning liquid L via pipe 84.
BF BF BF BF
する液体容器 14に接続されている。この配管 84には、 BZF洗浄液 Connected to the liquid container 14. This pipe 84 has BZF cleaning liquid
L の流れを制御する注入弁 12と、液体容器 14から B/F洗浄液 L を吸引するボン An injection valve 12 that controls the flow of L and a Bonn that sucks B / F cleaning liquid L from the liquid container 14
BF BF BF BF
プ 13とが順次介在している。配管 83とシリンダ 10aの内部に B/F洗浄液 L を導入 Step 13 is intervening sequentially. B / F cleaning liquid L is introduced into piping 83 and cylinder 10a.
BF BF
する際には、注入弁 12を開きポンプ 13によって BZF洗浄液 L を吸引し、吐出ノズ When injecting, open the injection valve 12 and suck the BZF cleaning liquid L with the pump 13.
BF BF
ル 2c、シリンジ 10、配管 83および 84に B/F洗浄液 L を充填した後、注入弁 12を 2c, syringe 10, and pipes 83 and 84 are filled with B / F cleaning liquid L, then injection valve 12 is
BF BF
閉じてポンプ 13の動作を終了する。
[0033] ノズル駆動部 3は、各ノズノレ群 Gを構成する 3つのノズル(エアーノズノレ 2a、吸引ノ ズノレ 2b、および吐出ノズノレ 2c)を一括して駆動する。このため、各ノズル群 G内の 3つ のノズルの相対的な位置関係は、駆動しても変わることはなレ、。なお、このノズノレ駆 動部 3は、各ノズル群 Gを個別に駆動させることもできる。 Close and end the operation of the pump 13. [0033] The nozzle driving unit 3 drives three nozzles (air nozzle 2a, suction nozzle 2b, and discharge nozzle 2c) constituting each nozzle group G in a lump. For this reason, the relative positional relationship of the three nozzles in each nozzle group G does not change even when driven. The nozzle drive unit 3 can also drive each nozzle group G individually.
[0034] 以上説明した構成および作用を有する洗浄部 110において、ノズル駆動部 3、信 号処理部 5、ピストン駆動部 7および 11、ポンプ 9および 13、ならびに注入弁 12の動 作は、後述する制御分析機構 201の制御部 206によって制御される。 [0034] In the cleaning unit 110 having the configuration and operation described above, the operation of the nozzle drive unit 3, the signal processing unit 5, the piston drive units 7 and 11, the pumps 9 and 13, and the injection valve 12 will be described later. It is controlled by the control unit 206 of the control analysis mechanism 201.
[0035] 以上の構成を有する測定機構 101において、 1回の回転動作で反応容器保持部 1 05が回転する角度は予め定められており、その回転によって試料 Spや各種試薬の 分注等を同時多発的に行うことができるような構成となるように、全ての構成要素が配 置されている。この意味で、図 1はあくまでも測定機構 101の構成要素を模式的に示 すものに過ぎない。すなわち、測定機構 101の構成要素間の相互の位置関係は、反 応容器保持部 105のホイールの回転態様等の条件に応じて定められるべき設計的 事項である。 [0035] In the measurement mechanism 101 having the above-described configuration, the angle at which the reaction container holding unit 105 rotates by one rotation is determined in advance, and the sample Sp and various reagents are dispensed simultaneously by the rotation. All the components are arranged so that the configuration can be performed frequently. In this sense, FIG. 1 is merely a schematic illustration of the components of the measurement mechanism 101. That is, the mutual positional relationship between the components of the measurement mechanism 101 is a design matter that should be determined according to conditions such as the rotation mode of the wheel of the reaction container holding unit 105.
[0036] 続いて、自動分析装置 1の制御分析機構 201の構成を説明する。制御分析機構 2 01は、測定機構 101における測定結果を分析する演算を行う分析演算部 202、検 体の分析に必要な情報および自動分析装置 1の動作指示信号の入力を受ける入力 部 203、分析結果を含む情報を出力する出力部 204、分析結果を含む情報を記憶 する記憶部 205、および自動分析装置 1の制御を行う制御部 206を備える。 [0036] Next, the configuration of the control analysis mechanism 201 of the automatic analyzer 1 will be described. The control analysis mechanism 201 includes an analysis operation unit 202 that performs an operation for analyzing the measurement result in the measurement mechanism 101, an input unit 203 that receives input of information necessary for analysis of the sample and an operation instruction signal of the automatic analyzer 1, and an analysis An output unit 204 that outputs information including the results, a storage unit 205 that stores information including the analysis results, and a control unit 206 that controls the automatic analyzer 1 are provided.
[0037] 入力部 203は、キーボート、マウス、マイクロフォン等によって実現される。また、出 力部 204は、ディスプレイ(CRT、液晶、プラズマ、有機 EL等)、プリンタ、スピーカ等 によって実現される。 [0037] The input unit 203 is realized by a keyboard, a mouse, a microphone, or the like. The output unit 204 is realized by a display (CRT, liquid crystal, plasma, organic EL, etc.), a printer, a speaker, and the like.
[0038] 記憶部 205は、さまざまな情報を磁気的に記憶するハードディスクと、自動分析装 置 1が処理を実行する際にその処理に係るプログラムをハードディスクからロードして 電気的に記録するメモリとを備える。また、記憶部 205として、フレキシブルディスク、 CD-ROM, DVD-ROM, M〇ディスク、 PCカード、 xDピクチャーカード等の記 録媒体に記録された情報を読み取ることができる補助記憶装置をさらに備えてもよい
[0039] 制御部 206は、記憶部 205が記憶するプログラムをメモリから読み出すことにより、 測定機構 101における測定結果を用いた分析演算や、 自動分析装置 1の各種動作 の制御などを行う。 [0038] The storage unit 205 includes a hard disk that magnetically stores various information, a memory that loads a program related to the process from the hard disk and electrically records it when the automatic analyzer 1 executes the process. Is provided. The storage unit 205 further includes an auxiliary storage device that can read information recorded on a recording medium such as a flexible disk, a CD-ROM, a DVD-ROM, an M0 disk, a PC card, and an xD picture card. Good The control unit 206 reads out the program stored in the storage unit 205 from the memory, thereby performing analysis calculation using the measurement result in the measurement mechanism 101, control of various operations of the automatic analyzer 1, and the like.
[0040] 以上の構成を有する制御分析機構 201が測光部 112から測定結果を受信すると、 分析演算部 202が測光部 112から送られてきた測定結果に基づいて反応容器 51内 の反応液の発光量を算出し、この算出結果に加えて標準検体から得られる検量線や 分析情報に含まれる分析パラメータを用いることにより、反応液の成分等を定量的に 求める。このようにして得られた分析結果は、出力部 204から出力される一方、記憶 部 205に格納して記憶される。 [0040] When the control analysis mechanism 201 having the above configuration receives the measurement result from the photometry unit 112, the analysis calculation unit 202 emits light of the reaction liquid in the reaction vessel 51 based on the measurement result sent from the photometry unit 112. The amount of the reaction solution is calculated, and in addition to the calculation result, the calibration parameters obtained from the standard sample and the analysis parameters included in the analysis information are used to quantitatively determine the components of the reaction solution. The analysis result obtained in this manner is output from the output unit 204 and is stored and stored in the storage unit 205.
[0041] < BZF洗浄時における液面位置の異常検知処理 > [0041] <Liquid surface position abnormality detection processing during BZF cleaning>
次に、 BZF洗浄時における液面位置の異常検知処理について説明する。以下で は、一つのノズノレ群 Gの挙動に注目して説明を行うが、各ノズノレ群 Gにおいて同様の 異常検知処理が行われることはいうまでもない。 Next, the liquid level position abnormality detection process during BZF cleaning will be described. In the following, the explanation will be made by paying attention to the behavior of one nodule group G, but it goes without saying that the same abnormality detection processing is performed in each nodule group G.
[0042] 図 3は、洗浄部 110の B/F洗浄時における動作の概要を示す説明図である。同図 に示すように、ノズル駆動部 3は、制御部 206の制御のもと、ノズル群 Gを反応容器 5 1に対して上下動させ、反応容器 51の内部に収容されている免疫反応後の液体の 吸引、および B/F洗浄液の吐出を所定の回数だけ繰り返し行う。 FIG. 3 is an explanatory diagram showing an outline of the operation of the cleaning unit 110 during B / F cleaning. As shown in the figure, the nozzle drive unit 3 moves the nozzle group G up and down with respect to the reaction vessel 51 under the control of the control unit 206, and after the immune reaction accommodated in the reaction vessel 51. Aspirate the liquid and discharge the B / F cleaning liquid a predetermined number of times.
[0043] より具体的には、まず免疫反応後の反応液である液体 L1を収容する反応容器 51 に向けてノズノレ群 Gを下降させる(状態 1— 1)。エアーノズノレ 2aは、ノズル群 Gの移 動前または移動中にピストン駆動部 7の駆動によるピストン 6bの吸引動作によってそ の先端部からエアーを吸入しておく。エアーを吸入したエアーノズル 2aは、ノズル群 Gの反応容器 51への下降が終了して静止した後、ピストン駆動部 7がピストン 6bを駆 動することによってエアーの吐出を開始する。 [0043] More specifically, first, the Noznole group G is lowered toward the reaction vessel 51 that contains the liquid L1 that is the reaction solution after the immune reaction (state 1-1). The air nozzle 2a sucks air from the tip of the nozzle group G by the suction operation of the piston 6b by driving the piston drive unit 7 before or during the movement of the nozzle group G. The air nozzle 2a that has sucked in air stops after the descent of the nozzle group G to the reaction vessel 51 is completed and stops, and then the piston driving unit 7 drives the piston 6b to start discharging air.
[0044] 続いて、吸引ノズノレ 2bによって反応容器 51内の液体 L1を吸引する(状態 1— 2)。 [0044] Subsequently, the liquid L1 in the reaction vessel 51 is sucked by the suction nozzle 2b (state 1-2).
この吸引を所定の時間行った後、吐出ノズル 2cから所定量の BZF洗浄液 L を吐 After performing this suction for a predetermined time, a predetermined amount of BZF cleaning liquid L is discharged from the discharge nozzle 2c.
BF BF
出する(状態 1— 3)。図 3からも明らかなように、吐出ノズル 2cから吐出される BZF洗 浄液 L は、コンタミネーシヨンやキャリーオーバ等を防止するために、吐出が終了し (State 1-3). As is clear from FIG. 3, the BZF cleaning liquid L discharged from the discharge nozzle 2c is discharged to prevent contamination and carryover.
BF BF
た時点にぉレ、て、液体 L1と B/F洗浄液 L との混合液である液体 L2の液面が吐出
ノズノレ 2cの下端よりも下方でなければならない。最後に、ノズル駆動部 3によってノズ ル群 Gを上昇させ (状態 1 4)、一連の動作が終了する。この後、状態 1 1〜1 4 の一連の動作を所定回数だけ繰り返し行う。 The liquid level of liquid L2, which is a mixture of liquid L1 and B / F cleaning liquid L, is discharged when It must be below the bottom edge of Noznore 2c. Finally, the nozzle group G is raised by the nozzle drive unit 3 (state 14), and the series of operations ends. Thereafter, a series of operations in states 11 to 14 are repeated a predetermined number of times.
[0045] 図 4は、エアーノズル 2aの基端部近傍における配管 81内部のエアーの圧力および その圧力の微分値 (圧力微分)の時間変化を示す説明図である。同図に示す圧力波 形 W1および圧力微分波形 W2 (図で下向きを正とする)は、エアーノズノレ 2aの先端 力 所定の距離 h ( > 0)だけ上方の配管 81内部に加わるエアーの圧力を圧力セン サ 4によって検知し、この検知されたエアーの圧力を分析演算部 202で演算した結 果として出力部 204から出力されるものに相当する。 [0045] Fig. 4 is an explanatory view showing the time change of the pressure of the air inside the pipe 81 and the differential value (pressure differential) of the pressure in the vicinity of the base end portion of the air nozzle 2a. The pressure waveform W1 and pressure differential waveform W2 shown in the figure are the positive pressure of the air nozzle 2a. The tip force of the air nozzle 2a is the pressure of the air applied to the inside of the upper pipe 81 for a predetermined distance h (> 0). This is equivalent to that detected by the sensor 4 and output from the output unit 204 as a result of calculating the detected air pressure by the analysis calculation unit 202.
[0046] この図 4においては、時亥 に吐出ノズノレ 2cからの BZF洗浄液 L の吐出が開始さ [0046] In Fig. 4, the discharge of the BZF cleaning liquid L from the discharge nozzle 2c is started from time to time.
0 BF 0 BF
れた場合を示している。すなわち、圧力波形 W1は、吐出ノズル 2cが BZF洗浄液 L Shows the case. That is, the pressure waveform W1 indicates that the discharge nozzle 2c
BF BF
を吐出前および吐出時は、それぞれ異なる一定値を示す。したがって圧力微分波形 W2は、時刻 tの直後から急激に立ち上がった後、立ち上がる前の値に漸近的に戻 Before and during discharge, different constant values are shown. Therefore, the pressure differential waveform W2 asymptotically returns to the value before rising after rising sharply immediately after time t.
0 0
つて再び一定となる。圧力および圧力微分がそれぞれ圧力波形 W1および圧力微分 波形 W2に示すように変化した場合、制御部 206は、洗浄部 110の動作が正常であ ると判定する。 It becomes constant again. When the pressure and the pressure differential change as indicated by the pressure waveform W1 and the pressure differential waveform W2, respectively, the control unit 206 determines that the operation of the cleaning unit 110 is normal.
[0047] 図 5は、洗浄部 110が上記同様の手順で B/F洗浄を行う場合に、吸引ノズノレ 2bの 吸引動作の不具合に起因して生じる液面異常の例を示す説明図である。同図にお いては、状態 2—1においてノズル群 Gを下降させた後、吸引ノズル 2bで液体 L1を吸 弓 [した際、何らかの不具合が発生して液体 L1が十分に吸引されなかった場合を示し ている(状態 2— 2)。この結果、吐出ノズル 2cが B/F洗浄液 L を吐出する際に、液 FIG. 5 is an explanatory diagram showing an example of a liquid level abnormality that occurs due to a malfunction in the suction operation of the suction nozzle 2b when the cleaning unit 110 performs B / F cleaning in the same procedure as described above. In the same figure, after the nozzle group G is lowered in the state 2-1, the suction of the liquid L1 with the suction nozzle 2b [when the liquid L1 is not sufficiently sucked due to some trouble (State 2-2). As a result, when the discharge nozzle 2c discharges the B / F cleaning liquid L, the liquid
BF BF
体 L2の液量が正常時よりも多くなり(図中の斜線領域)、正常時と同じ量の BZF洗 浄液 L を吐出する過程で液体 L2の液面がエアーノズノレ 2aの先端部に到達するま The liquid volume of body L2 is higher than normal (the shaded area in the figure), and the liquid level of liquid L2 reaches the tip of Air Nozzle 2a in the process of discharging the same amount of BZF cleaning liquid L as normal Ma
BF BF
で上昇し、エアーノズル 2aの先端が液体 L2によって閉塞されてしまう(状態 2— 3)。 The tip of the air nozzle 2a is blocked by the liquid L2 (state 2-3).
[0048] 図 6は、上記の如く吸引ノズル 2bの吸引動作に異常が生じたとき、圧力センサ 4に よって検知されるエアーの圧力および圧力微分の時間変化の概要を示す説明図で ある(図で下向きを正とする)。同図に示す場合、圧力波形 W3は時刻 tおよび tで大 FIG. 6 is an explanatory diagram showing an outline of the time change of the air pressure and pressure differential detected by the pressure sensor 4 when an abnormality occurs in the suction operation of the suction nozzle 2b as described above (FIG. 6). And the downward direction is positive). In the figure, the pressure waveform W3 is large at times t and t.
0 1 きく変化しており、圧力微分波形 W4も圧力波形 W3の変化に伴って時刻 tおよび t
の 2回大きく立ち上がつている。このうち、時亥 ijtにおける各波形の変化は、正常時と 0 1 The pressure differential waveform W4 also changes with the change of the pressure waveform W3. Two big rises. Of these, changes in each waveform at time ijt are normal and
0 0
同様に吐出ノズル 2cから B/F洗浄液 L の吐出が開始されたことを示している。これ Similarly, the B / F cleaning liquid L starts to be discharged from the discharge nozzle 2c. this
BF BF
に対して、時刻 tにおける各波形の変化は、液体 L2の液面がエアーノズノレ 2aの先端 On the other hand, the change in each waveform at time t is that the liquid level of liquid L2 is at the tip of air nose 2a.
1 1
まで上昇してそのエアーノズノレ 2aの先端を閉塞したことを示している(図 5の状態 2_ 3を参照)。 It shows that the tip of the air nose 2a has been closed (see state 2_3 in Fig. 5).
[0049] このような圧力および圧力微分の挙動によって反応容器 51内の液面位置の異常 が検知された場合、制御部 206ではピストン駆動部 11の駆動を停止する制御信号を 送出し、吐出ノズル 2cからの B/F洗浄液 L の吐出動作を停止する。これにより、反 [0049] When an abnormality in the liquid level position in the reaction vessel 51 is detected by such behavior of pressure and pressure differential, the control unit 206 sends out a control signal for stopping the driving of the piston drive unit 11, and the discharge nozzle Stop the discharge operation of B / F cleaning liquid L from 2c. This
BF BF
応容器 51から液体 L2が溢れ出してしまうのを未然に防止することが可能となる。 It is possible to prevent the liquid L2 from overflowing from the reaction container 51.
[0050] 図 7は、エアーノズル 2aの先端から圧力センサ 4までの距離と圧力センサ 4が検知 する配管 81内のエアーの圧力の関係を示す図である。同図に示すように、エアーの 圧力 Pは、圧力センサ 4が設置される位置に依存しており、エアーノズノレ 2aの先端か らの距離 Xに比例している。したがって、比例定数を k ( >0)とすると、図 7において圧 力 Pとエアーノズル 2aの先端からの距離 Xとの関係を示す直線 Cは P = kxと表される FIG. 7 is a diagram showing the relationship between the distance from the tip of the air nozzle 2 a to the pressure sensor 4 and the air pressure in the pipe 81 detected by the pressure sensor 4. As shown in the figure, the air pressure P depends on the position where the pressure sensor 4 is installed, and is proportional to the distance X from the tip of the air nozzle 2a. Therefore, if the proportionality constant is k (> 0), the straight line C showing the relationship between the pressure P and the distance X from the tip of the air nozzle 2a in FIG. 7 is expressed as P = kx
[0051] これに対して、エアーノズノレ 2aの先端が閉塞されたときのエアーの圧力は、 Xの値 によらずに(すなわち、圧力センサ 4の位置に関わらずに)一定値 Pをとる。したがつ [0051] On the other hand, the air pressure when the tip of the air nozzle 2a is closed takes a constant value P regardless of the value of X (that is, regardless of the position of the pressure sensor 4). Gatsutsu
0 0
て、液体 L2がエアーノズノレ 2aの先端まで上昇してそのエアーノズル 2aの先端を閉 塞する前後で圧力センサ 4が検知する圧力の変化量 Δ Pは、圧力センサ 4の位置に 応じて変化する。図 7では、 x=hの位置に圧力センサ 4を配置した場合(図 2を参照 のこと)の Δ Ρの値 P -P ( = P—kh)を例示している。 Thus, the amount of change ΔP detected by the pressure sensor 4 before and after the liquid L2 rises to the tip of the air nozzle 2a and closes the tip of the air nozzle 2a changes according to the position of the pressure sensor 4. In FIG. 7, the value P −P (= P−kh) of Δ の when the pressure sensor 4 is arranged at the position of x = h (see FIG. 2) is illustrated.
0 1 0 0 1 0
[0052] 図 7からも明らかなように、圧力センサ 4がエアーノズノレ 2aの先端部に近く Xの値が 比較的小さい場合、シリンジ 6が動作しても小さなエアー圧力しか検知できない上、 Δ Ρの値は大きくなるため、測定に誤差を生じやすい。他方、圧力センサ 4がェアーノ ズノレ 2aの先端部から遠く Xの値が比較的大きい場合、検知する圧力は大きいが、 Δ Pの値が小さく精度が要求される。したがって、エアーの圧力および圧力微分に基づ いて反応容器 51の液面位置の異常を適確に検知するためには、圧力センサ 4の感 度を考慮した上で圧力センサ 4の設置位置を最適化することが好ましい。
[0053] 図 8は、図 6とは異なる態様で液面位置の異常を検知する場合のエアーの圧力およ びその圧力微分の時間変化の概要を示す説明図である(図で下向きを正とする)。こ の図 8に示す圧力波形 W5においては、時刻 tにエアーノズノレ 2aからエアーの吐出 [0052] As is clear from FIG. 7, when the pressure sensor 4 is close to the tip of the air nozzle 2a and the value of X is relatively small, only a small air pressure can be detected even if the syringe 6 is operated, and Δ Δ Since the value becomes large, an error is likely to occur in the measurement. On the other hand, when the pressure sensor 4 is far away from the tip of the airnozzle 2a and the value of X is relatively large, the detected pressure is large, but the value of ΔP is small and accuracy is required. Therefore, in order to accurately detect an abnormality in the liquid level position of the reaction vessel 51 based on the air pressure and pressure differential, the installation position of the pressure sensor 4 is optimal in consideration of the sensitivity of the pressure sensor 4. Is preferable. [0053] Fig. 8 is an explanatory diagram showing an outline of the time change of the air pressure and its pressure derivative when an abnormality in the liquid level position is detected in a mode different from Fig. 6 (the downward direction is positive in the figure). To do). In the pressure waveform W5 shown in Fig. 8, air is discharged from the air nozzle 2a at time t.
0 0
を開始した時点での圧力が圧力波形 W1や圧力波形 W3に示す場合よりも大きぐそ の変化量は Δ Ρ'である。圧力微分波形 W6も、圧力波形 W5の変化に伴って時刻 t The amount of change when the pressure at the time of starting is larger than the case shown in pressure waveform W1 or pressure waveform W3 is Δ Δ '. The pressure differential waveform W6 also changes with time t
0 で圧力微分波形 W2および W4よりも急激な立ち上がりを示す。これは、すでに液体 L 2がエアーノズノレ 2aの先端に達するまで上昇している場合に相当する。この場合に は、エアーの吐出を開始した直後、制御部 206の制御のもと、吐出ノズル 2cの吐出 動作が停止される。 0 indicates a more rapid rise than the pressure differential waveforms W2 and W4. This corresponds to the case where the liquid L 2 has already risen until it reaches the tip of the air nose 2a. In this case, immediately after the start of air discharge, the discharge operation of the discharge nozzle 2c is stopped under the control of the control unit 206.
[0054] 以上説明した本発明の一実施の形態によれば、不均一系反応を生じた反応液の 少なくとも一部を吸引する吸引ノズルおよび所定の B/F洗浄液を吐出する吐出ノズ ノレから成る複数のノズル対の各々に対応して設けられ、該当するノズル対をなす吸 引ノズノレおよび吐出ノズノレの各先端部よりも上方からエアーを吐出する複数のエア ーノズノレと、前記複数のエアーノズルのいずれかに接続され、この接続されたエアー ノズノレにエアーを供給する複数のシリンジと、この複数のシリンジの各々に接続され たエアーノズノレの基端部の近傍におけるエアーの圧力をそれぞれ検知する複数の 圧力センサと、この複数の圧力センサがそれぞれ検知したエアーの圧力および該圧 力の変化に応じて各吐出ノズノレの B/F洗浄液の吐出動作を個別に制御する制御 手段と、を備えることにより、不均一系反応を生じた反応液の B/F洗浄を行う際、反 応容器内部に収容される反応液の液面位置の異常を適確に検知することが可能と なり、保守管理も容易となる。 [0054] According to the embodiment of the present invention described above, it comprises a suction nozzle that sucks at least a part of a reaction liquid that has caused a heterogeneous reaction, and a discharge nozzle that discharges a predetermined B / F cleaning liquid. Any one of the plurality of air nozzles provided corresponding to each of the plurality of nozzle pairs and discharging air from above the suction nozzles and the nozzles of the discharge nozzles forming the corresponding nozzle pairs, and any of the plurality of air nozzles And a plurality of pressure sensors for detecting the pressure of air in the vicinity of the proximal end of the air nozzle connected to each of the plurality of syringes. And the discharge operation of the B / F cleaning liquid of each discharge nozzle according to the air pressure detected by each of the plurality of pressure sensors and the change in the pressure. Control means for controlling the reaction liquid, and when performing B / F cleaning of the reaction liquid that has caused a heterogeneous reaction, the liquid level position of the reaction liquid contained in the reaction vessel is accurately corrected. It becomes possible to detect and maintenance management becomes easy.
[0055] また、本実施の形態によれば、エアーノズノレごとにエアー供給用のシリンジが設け られているため、全てのエアーノズノレへのエアー供給を一つのシリンジで一括して行 う場合と比較して、より良好な検出感度を得ることができる。 [0055] Further, according to the present embodiment, since the syringe for supplying air is provided for each air nozzle, compared with the case where the air supply to all the air nozzles is performed collectively with one syringe. Better detection sensitivity can be obtained.
[0056] ここまで、本発明を実施するための最良の形態を詳述してきたが、本発明はその一 実施の形態によってのみ限定されるべきものではなレ、。例えば、固相として反応容器 を用いる代わりに、直径 5〜: 1 Ommのガラスまたはプラスチックなどの粒子状の担体( ビーズ)を使用してもよい。この場合には、 自動分析装置に、担体を収容する担体収
容部、および担体収容部から反応容器に担体を移送する担体移送部をさらに設け ればよい。 [0056] Although the best mode for carrying out the present invention has been described in detail so far, the present invention should not be limited only by the embodiment. For example, instead of using a reaction vessel as a solid phase, a particulate carrier (bead) such as glass or plastic having a diameter of 5 to 1 Omm may be used. In this case, the carrier analyzer that contains the carrier is stored in the automatic analyzer. What is necessary is just to further provide the carrier transfer part which transfers a support | carrier to a reaction container from a container part and a carrier accommodating part.
[0057] また、固相として、直径がたかだか 1 /i m程度(0.2〜0.8 /i m、より好ましくは 0.4〜 0.6 z m程度)の磁性粒子を用いることも可能である。この場合には、 BZF洗浄を行 う際に反応容器の外部から磁場を印加することにより、磁性粒子を反応容器内の一 箇所に集めておくようにする。 [0057] Further, as the solid phase, magnetic particles having a diameter of about 1 / im at most (0.2 to 0.8 / im, more preferably about 0.4 to 0.6 zm) can be used. In this case, the magnetic particles are collected in one place in the reaction container by applying a magnetic field from the outside of the reaction container when performing the BZF cleaning.
[0058] なお、本発明は、不均一系反応を用いる生化学的な分析や遺伝学的な分析を行う 自動分析装置の洗浄液や反応液等の液面を検知する場合にも適用することができ る。 [0058] It should be noted that the present invention can also be applied to the case of detecting the level of a cleaning liquid or a reaction liquid of an automatic analyzer that performs biochemical analysis or genetic analysis using a heterogeneous reaction. it can.
[0059] このように、本発明は、ここでは記載していないさまざまな実施の形態等を含みうる ものであり、特許請求の範囲により特定される技術的思想を逸脱しない範囲内にお いて種々の設計変更等を施すことが可能である。 [0059] As described above, the present invention can include various embodiments and the like not described herein, and various modifications can be made without departing from the technical idea specified by the claims. It is possible to make design changes.
産業上の利用可能性 Industrial applicability
[0060] 以上のように、本発明には、検体と試薬とを反応させることによって検体の成分を自 動的かつ連続的に分析する自動分析装置に有用であり、特に検体の成分の免疫学 的な分析を行う場合に適している。
As described above, the present invention is useful for an automatic analyzer that automatically and continuously analyzes a component of a sample by reacting the sample with a reagent, and in particular, immunology of the component of the sample. This is suitable for performing statistical analysis.
Claims
[1] 不均一系反応を生じた反応液の B/F洗浄を行うために、前記反応液の少なくとも 一部を吸引する吸引ノズルおよび所定の BZF洗浄液を吐出する吐出ノズルから成 るノズル対を複数備えた洗浄装置であって、 [1] In order to perform B / F cleaning of a reaction liquid that has caused a heterogeneous reaction, a nozzle pair consisting of a suction nozzle that sucks at least a part of the reaction liquid and a discharge nozzle that discharges a predetermined BZF cleaning liquid is provided. A plurality of cleaning devices,
各ノズル対に対応して設けられ、該当するノズル対をなす吸引ノズルおよび吐出ノ ズノレの各先端部よりも上方からエアーを吐出する複数のエアーノズノレと、 A plurality of air nozzles that are provided corresponding to each nozzle pair and discharge air from above the respective tip portions of the suction nozzle and discharge nozzle that form the corresponding nozzle pair;
前記複数のエアーノズノレのレ、ずれかに接続され、この接続されたエアーノズノレにェ ァーを供給する複数のエアー供給手段と、 A plurality of air supply means connected to the gaps of the plurality of air nozzles and supplying air to the connected air nozzles;
前記複数のエアー供給手段の各々に接続されたエアーノズルの基端部の近傍に おけるエアーの圧力をそれぞれ検知する複数の圧力センサと、 A plurality of pressure sensors for detecting the pressure of air in the vicinity of the base end of the air nozzle connected to each of the plurality of air supply means;
前記複数の圧力センサがそれぞれ検知したエアーの圧力および該圧力の変化に 応じて各吐出ノズノレの B/F洗浄液の吐出動作を個別に制御する制御手段と、 を備えたことを特徴とする洗浄装置。 And a control means for individually controlling the discharge operation of the B / F cleaning liquid of each discharge nozzle in accordance with the pressure of the air detected by each of the plurality of pressure sensors and the change in the pressure. .
[2] 前記制御手段は、 [2] The control means includes
前記複数のエアーノズノレのうちで自身の基端部の近傍におけるエアーの圧力およ び該圧力の変化が所定の範囲を逸脱した値をとるエアーノズノレに対応する吐出ノズ ルの B/F洗浄液の吐出動作を停止することを特徴とする請求項 1記載の洗浄装置 Among the plurality of air nozzles, the discharge pressure of the B / F cleaning liquid of the discharge nozzle corresponding to the air pressure where the air pressure near the base end of the air nozzle and the change in the pressure deviates from a predetermined range is taken. The cleaning apparatus according to claim 1, wherein the cleaning device is stopped.
[3] 分析対象の検体に不均一系反応を生じさせることによって当該検体の分析を行う 自動分析装置であって、 [3] An automatic analyzer for analyzing a sample by causing a heterogeneous reaction in the sample to be analyzed.
請求項 1または 2記載の洗浄装置を備えたことを特徴とする自動分析装置。
An automatic analyzer comprising the cleaning device according to claim 1.
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JP2016070864A (en) * | 2014-10-01 | 2016-05-09 | 東ソー株式会社 | Liquid discharge nozzle |
JP2018146373A (en) * | 2017-03-06 | 2018-09-20 | テラメックス株式会社 | Device and program for detecting pipette chip top end |
WO2019176295A1 (en) | 2018-03-15 | 2019-09-19 | 株式会社日立ハイテクノロジーズ | Automatic analyzing apparatus, and method for detecting flow path clogging of the automatic analyzing apparatus |
US20200278366A1 (en) * | 2018-03-16 | 2020-09-03 | Hitachi High-Technologies Corporation | Automatic Analysis Device |
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WO2009093578A1 (en) * | 2008-01-21 | 2009-07-30 | Olympus Corporation | Cleaning equipment and analyzer |
CN101965518A (en) * | 2008-01-21 | 2011-02-02 | 奥林巴斯株式会社 | Cleaning equipment and analyzer |
JP2016070864A (en) * | 2014-10-01 | 2016-05-09 | 東ソー株式会社 | Liquid discharge nozzle |
JP2018146373A (en) * | 2017-03-06 | 2018-09-20 | テラメックス株式会社 | Device and program for detecting pipette chip top end |
WO2019176295A1 (en) | 2018-03-15 | 2019-09-19 | 株式会社日立ハイテクノロジーズ | Automatic analyzing apparatus, and method for detecting flow path clogging of the automatic analyzing apparatus |
US11079402B2 (en) | 2018-03-15 | 2021-08-03 | Hitachi High-Tech Corporation | Automatic analyzing apparatus, and method for detecting flow path clogging of the automatic analyzing apparatus |
US20200278366A1 (en) * | 2018-03-16 | 2020-09-03 | Hitachi High-Technologies Corporation | Automatic Analysis Device |
US11971426B2 (en) * | 2018-03-16 | 2024-04-30 | Hitachi High-Tech Corporation | Automatic analysis device |
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