WO2006107016A1 - 生体サンプルの複合自動分析装置、自動分析方法、及び反応キュベット - Google Patents
生体サンプルの複合自動分析装置、自動分析方法、及び反応キュベット Download PDFInfo
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- WO2006107016A1 WO2006107016A1 PCT/JP2006/307040 JP2006307040W WO2006107016A1 WO 2006107016 A1 WO2006107016 A1 WO 2006107016A1 JP 2006307040 W JP2006307040 W JP 2006307040W WO 2006107016 A1 WO2006107016 A1 WO 2006107016A1
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/02—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
- G01N35/025—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations having a carousel or turntable for reaction cells or cuvettes
-
- 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
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/01—Arrangements or apparatus for facilitating the optical investigation
- G01N21/03—Cuvette constructions
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
- G01N21/251—Colorimeters; Construction thereof
- G01N21/253—Colorimeters; Construction thereof for batch operation, i.e. multisample apparatus
-
- 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
- B01L2200/02—Adapting objects or devices to another
- B01L2200/025—Align devices or objects to ensure defined positions relative to each other
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0848—Specific forms of parts of containers
- B01L2300/0851—Bottom walls
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/01—Arrangements or apparatus for facilitating the optical investigation
- G01N21/03—Cuvette constructions
- G01N2021/0325—Cells for testing reactions, e.g. containing reagents
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/01—Arrangements or apparatus for facilitating the optical investigation
- G01N21/03—Cuvette constructions
- G01N2021/0378—Shapes
- G01N2021/0382—Frustoconical, tapered cell
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
- G01N21/76—Chemiluminescence; Bioluminescence
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
- G01N21/77—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
- G01N21/82—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator producing a precipitate or turbidity
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/11—Automated chemical analysis
- Y10T436/113332—Automated chemical analysis with conveyance of sample along a test line in a container or rack
Definitions
- the present invention relates to a complex automatic analyzer for biological samples, an automatic analysis method, and a reaction cuvette.
- a serum immunoassay device for immunological items an antibody that specifically binds to each test target substance prepared as a reagent side or a labeled antibody or labeled antigen labeled with a fluorescent dye or the like is used. Then, after binding by the immunological reaction with the test substance in the sample, BZF separation is performed, and the hormone in the biological sample is detected with high sensitivity by heterogeneous measurement that detects the labeled antibody or labeled antigen. It is possible to measure the substances to be inspected.
- Patent Document 1 Japanese Patent Laid-Open No. 9281113
- Patent Document 2 Japanese Patent Laid-Open No. 2001-4636
- an object of the present invention is to be able to measure a plurality of types of analysis with different measurement accuracy, such as biochemical analysis and immunological analysis, with a single device, and also to reduce the force.
- the purpose of this is to provide a means that can reduce the size of the equipment and reduce the measurement time.
- the present inventor succeeded in developing a reaction cuvette suitable for such an automatic analyzer in the process of developing the apparatus.
- a sample supply unit comprising a plurality of biological samples
- a first measuring unit capable of force s and comprising a first optical system measuring means
- Sample transport means capable of transporting a biological sample from the sample supply unit to the reaction cuvette on the first measurement unit
- a second measurement unit that can hold a plurality of reaction cuvettes independent of each other and detachable independently of each other, and includes a second optical system measurement means;
- a cuvette transfer means capable of transferring the reaction cuvette on the first measurement unit to the second measurement unit
- reagent supply unit comprising reagents used for measurement in the first measurement unit and measurement in the second measurement unit
- Reagent transport means capable of transporting reaction reagents independently from each other from the reagent supply unit to the reaction cuvette on the first measurement unit and Z or the second measurement unit;
- the reaction cuvette on the second measurement unit after the biological sample is dispensed on the first measurement unit, is transferred from the first measurement unit to the second measurement unit and supported by the cuvette transfer means. And then
- Different measurement is performed between the first measurement unit and the second measurement unit.
- the measurement in the first measurement unit and the measurement in the second measurement unit are measurements having different measurement principles or detection forms.
- the second measurement unit performs measurement with higher accuracy than the measurement in the first measurement unit.
- the measurement in the first measurement unit is a biochemical measurement or latex agglutination measurement
- the measurement in the second measurement unit is an enzyme immunoassay
- the first measurement unit and the second measurement unit are of a rotatable disk type, and a mounting zone capable of transporting the reaction cuvette in the rotational movement direction is a disk peripheral portion.
- the force provided to the It is a rate type and is equipped with a loading zone that can transport the reaction cuvette in the reciprocating direction.
- a plurality of reaction cuvettes independent of each other can be detachably held independently of each other, provided with an optical system measurement means, It further includes one or more additional measurement units that perform measurements different from the measurements in the measurement unit and the measurements in the second measurement unit.
- the reaction cuvette on the additional measurement unit is transferred from the first measurement unit to the additional measurement unit by cuvette transfer means after the biological sample is dispensed on the first measurement unit.
- the additional measurement unit is a disc type that can rotate, and is provided with a mounting zone that can transport the reaction cuvette in the rotational movement direction at the periphery of the disc.
- the measurement in the first measurement unit is a colorimetric or turbidimetric measurement method
- the measurement in the second measurement unit is a chemiluminescence measurement method
- the measurement in the additional measurement unit is a blood coagulation time. It can be a measurement.
- the biological sample is directly supplied from the sample supply unit, and the measurement is performed without requiring the reagent supply from the reagent supply unit. It further includes one or more stand-alone measurement units capable of In this aspect, the independent measurement unit is, for example, a body fluid electrolyte measurement unit.
- At least one force abnormality sample detecting means of the measurement unit is provided.
- an optical detector including a light emitting diode and a diode array
- an optical detector including a lamp unit and a spectrometer
- Optical detector including photomultiplier as a light receiver
- the reagent supply unit has a plurality of concentric ring-shaped reagent storage lanes that can rotate independently and stop in the same direction or in the opposite direction.
- Each of the concentric ring-shaped reagent storage lanes stores a reagent to be supplied to the reaction cuvette carried on each of the first measurement unit and the second measurement unit.
- the reagent supply unit may further include a concentric ring-shaped reagent storage lane for storing a reagent to be supplied to a reaction cuvette carried by one or more of the additional measurement units.
- the reagent supply unit may further include a concentric ring-shaped reagent storage lane for storing a reagent to be supplied to a reaction cuvette carried on one or more of the independent measurement units.
- a reaction cuvette having an arcuate mounting protrusion provided by projecting the upper side force of the cuvette body is used as the reaction cuvette.
- the reaction cuvette has, for example, a recess having a curved wall surface on the bottom surface of the cuvette body, and the reaction cuvette further has an insertion port for a stirring rod tip at the center of the recess.
- the reaction cuvette may have a fixing protruding piece protruding downward from the lower surface of the mounting protrusion.
- the present invention also provides:
- a sample supply unit comprising a plurality of biological samples
- a first measurement unit that can hold a plurality of reaction cuvettes independent of each other so as to be detachable independently of each other, and includes a first optical system measurement means
- Sample transport means capable of transporting a biological sample from the sample supply unit to the reaction cuvette on the first measurement unit;
- a second measurement unit that can hold a plurality of reaction cuvettes independent of each other and detachable independently of each other, and includes a second optical system measurement means;
- a cuvette transfer means capable of transferring the reaction cuvette on the first measurement unit to the second measurement unit
- reagent supply unit comprising reagents used for measurement in the first measurement unit and measurement in the second measurement unit
- the reaction cuvette on the second measurement unit after the biological sample is dispensed on the first measurement unit, is transferred from the first measurement unit to the second measurement unit and supported by the cuvette transfer means. And then
- Different measurement is performed between the first measurement unit and the second measurement unit.
- the present invention also relates to a method for complex automatic analysis of biological samples.
- the present invention relates to a reaction cuvette, characterized in that a mounting projection provided so as to protrude from the upper side surface of the cuvette body has an arc shape.
- a recess having a curved wall surface is provided on the bottom surface of the cuvette body.
- an insertion port for the tip of the stirring rod is provided at the center of the recess.
- the mounting protrusion has a fixing protrusion protruding downward from the lower surface of the mounting protrusion.
- the automatic analyzer of the present invention has a plurality of measurement units, a plurality of types of analyzes with different measurement accuracy, such as biochemical analysis and immunological analysis, are measured by a single device. In addition, the measurement time can be shortened. Furthermore, since the components in the apparatus are shared, the apparatus can be made small and space saving can be realized.
- reaction cuvette of the present invention since the reaction cuvette of the present invention has an arcuate mounting protrusion, the stirring operation of each measurement unit on the reaction base can be carried out smoothly.
- FIG. 1 is a plan view schematically showing an arrangement state of units constituting a composite automatic analyzer of the present invention.
- FIG. 2 is a schematic explanatory view showing a measurement procedure in a first measurement unit.
- FIG. 3 is a schematic explanatory view showing a measurement procedure in a second measurement unit.
- FIG. 4 is a schematic explanatory view showing a measurement procedure in the third measurement unit and the fourth measurement unit.
- FIG. 5 is a perspective view of a reaction cuvette according to the present invention.
- FIG. 6 is a cross-sectional view of the reaction cuvette of FIG.
- FIG. 7 is a schematic cross-sectional view of a state in which the reaction cuvette of FIG. 5 is placed on a reaction base.
- FIG. 8 is a schematic cross-sectional view of a state where the reaction cuvette of FIG. 5 is placed on a reaction base and stirring is started.
- FIG. 9 is a perspective view of a reaction cuvette having a fixing protruding piece.
- FIG. 10 is a cross-sectional view of the reaction cuvette of FIG.
- FIG. 11 is a partial cross-sectional view of a reaction cuvette having a fixing protrusion piece according to another embodiment.
- 5 ⁇ ⁇ 'Third measuring unit 5a ⁇ ⁇ ' Transfer position; 5b-- • Additional reagent dispensing position; 5c ⁇ ⁇ ⁇ Optical measurement position
- FIG. 1 is a plan view schematically showing the arrangement state of each unit constituting the composite automatic analyzer 10 of the present invention.
- the complex automatic analyzer 10 of the present invention is 7 includes a sample supply unit 1, a first measurement unit 2, a second measurement unit 3, and a reagent supply unit 4, and can also include a third measurement unit 5 as an additional measurement unit.
- a fourth measurement unit 6 can be included as a measurement unit.
- the sample supply unit 1 includes a sample rack that detachably holds a sample cup filled with a plurality of biological samples (for example, a blood sample or a urine sample).
- the sample supply unit 1 transports a predetermined sample cup to the sample collection position 11 by moving in the direction of arrows A and Z or arrow B in FIG.
- a predetermined biological sample is dispensed into a reaction cuvette held on the first measurement unit 2 by a sample dispensing pipetter (not shown).
- the sample dispensing pipettor can be, for example, a suspended pipetter that hangs down on the ceiling part of the housing 7 and can move along a guide rail provided on the ceiling part.
- the sample supply unit 1 can be fixed and arranged at a predetermined position in the housing 7, and there is no need to provide a moving means for the sample supply unit 1.
- the first measurement unit 2 typically includes a rotary table type (disk type) reaction base 21, and a ring-shaped reaction cuvette is formed around the circumference of the reaction base 21 at the periphery.
- a mounting zone 22 is provided.
- the reaction base 21 can be rotated clockwise or counterclockwise (in the direction of arrow D), and can be rotated at a predetermined position (for example, a dispensing position of a sample or a reagent, a stirring position, a measurement position, a disposal position, etc.). Can be stopped.
- a plurality of reaction cuvettes 25 independent from each other can be detachably held in the reaction cuvette placement zone 22.
- a large number of reaction cuvettes 25 are arranged in a line in the circumferential direction with almost no gap between adjacent reaction cuvettes.
- the reaction cuvette 25 is shown as Interbow IV.
- the second measuring unit 3 also typically includes a rotary table type (disk type) reaction base 31, and a ring-shaped reaction cuvette around the circumference of the reaction base 31.
- a loading zone 32 is provided.
- the reaction base 31 is also rotated clockwise or counterclockwise (in the direction of arrow F). It can be stopped and stopped at a predetermined position (for example, reagent dispensing position, stirring position, measurement position, disposal position, etc.).
- the rotation and stop of the second measurement unit 3 can be synchronized with the rotation and stop of the first measurement unit 2 or can be performed independently of each other.
- a plurality of reaction cuvettes 25 independent of each other can be detachably held. Note that the reaction cuvette placement zone 32 is a force in which a large number of reaction cuvettes 25 are arranged in a row in the circumferential direction with almost no gap between adjacent reaction cuvettes. The reaction cuvette 25 is thinned out.
- the reagent supply unit 4 typically includes a rotary table type (disk type) reagent storage base 41, and the reagent storage base 41 includes a plurality of concentric ring-shaped reagent storage lanes 42a, 42b, 42c are provided.
- Each reagent storage lane 42a, 42b, 42c includes each measurement unit (for example, the first measurement unit 2, the second measurement unit 3, or further, an additional unit as an additional unit) of the composite automatic analyzer according to the present invention.
- 3 Reagent cup 43 for storing various reagents necessary for measurement in measurement unit 5) is stored.
- the reagent storage base 41 can be rotated clockwise or counterclockwise (in the direction of arrow K), and can be stopped at a predetermined position (for example, a reagent collecting position, a reagent cup attaching / detaching position, etc.).
- a predetermined position for example, a reagent collecting position, a reagent cup attaching / detaching position, etc.
- a large number of reagent cups 43 are arranged in a row in the circumferential direction with almost no gap between adjacent reagent caps.
- Figure 1 shows the reagent cups thinned out.
- the number of concentric reagent storage lanes is not limited to three, and two or more reagent storage lanes can be provided.
- the rotary table type reagent storage base 41 may have a structure that rotates as a single disk as a whole, or a plurality of concentric ring-shaped reagent storage lanes (for example, each reagent storage lane 42a, 42b, 42c) can also have a multiple ring structure that can rotate independently of each other. If multiple concentric reagent storage lanes have multiple ring structures that can rotate independently of each other, rotate the individual rings clockwise or counterclockwise independently of each other and stop independently of each other Thus, the reagent supply to various measurement units can be efficiently performed independently of each other.
- a biological sample of cup 11 is supplied by a sample dispensing pipettor (not shown) (see arrow C in FIGS. 1 and 2).
- the reaction cuvette 25 moves to the R1 reagent dispensing position 25b by the rotation of the reaction base 21, stops, and dispenses the R1 reagent from the reagent supply unit 4 (see arrow L in FIG. 2).
- This R1 reagent dispensing can be carried out, for example, by a suspended reagent dispensing pipetter (not shown) that hangs down on the ceiling portion of the housing 7 and is movable along a guide rail provided on the ceiling portion. .
- the suspended reagent dispensing pipetter moves to a position above the specified reagent cup 43a of the reagent supply unit 4, for example, reagent storage lane 42a, collects the R1 reagent, and then the first measurement unit.
- -It can be moved to the upper position of the reaction cuvette 25 held on the R1 reagent dispensing position 25b of the base 2 and dispensed into the reaction cuvette 25.
- the reaction cuvette 25 into which the biological sample and the R1 reagent have been dispensed in this way is moved to the stirring position 25c by the rotation of the reaction base 21, stops, and is subjected to a stirring operation. Subsequently, the reaction base 21 rotates to move to the R2 reagent dispensing position 25d and stops, and the R2 reagent is dispensed from the reagent supply unit 4 (see arrow M in FIG. 2). This R2 reagent dispensing can also be performed by the same suspended reagent dispensing pipettor (not shown).
- Suspended reagent dispensing pipetter moves to the upper position of the reagent supply unit 4, for example, a predetermined reagent cup 43b of the reagent storage lane 42b, collects the R2 reagent, and then continues to the first measurement unit 2.
- R2 reagent Can move to the upper position of the reaction cuvette 25 held on the dispensing position 25d and dispense into the reaction cuvette 25.
- the reaction cuvette 25 into which the biological sample, R1 reagent, and R2 reagent have been dispensed moves to the stirring position 25c by the rotation of the reaction base 21, stops, and receives the stirring operation again. It should be noted that another position can be prepared as the stirring position for the second stirring. Subsequently, the optical measurement position 25e is passed by the rotation of the reaction base 21, and the change based on the reaction in the reaction cuvette can be measured by transmitted light or scattered light during the passage. Measured by measuring means 26. When carrying out the optical measurement In addition, the reaction cuvette 25 can be stopped at the optical measurement position 25e. Subsequently, the reaction cuvette 25 is finally moved to the disposal position 25f, stops, is removed from the reaction base 21 by the pick-up means (not shown), and is discarded into the disposal chamber (not shown).
- sample dispensing and partial reagent dispensing are performed on the reaction base 21 of the first measurement unit 2. That is, first, the empty reaction cuvette 25 placed on the reaction cuvette placement zone 22 of the reaction base 21 of the first measurement unit 2 is stopped at the sample dispensing position 25a, A biological sample in a predetermined sample cup 11 of the sample supply unit 1 is supplied to the reaction cuvette 25 by a sample dispensing pipetter (not shown) (see arrow C in FIG. 3). Next, the reaction cuvette 25 is moved to the R1 reagent dispensing position 25b by the rotation of the reaction base 21 and stopped. From the reagent supply unit 4, for example, a suspended reagent dispensing pipetter (not shown) ) To dispense R1 reagent (see arrow L in Figure 3).
- the reaction cuvette 25 into which the biological sample and the R1 reagent have been dispensed moves to the stirring position 25c, stops, and receives a stirring operation, as described above. Next, it moves to the R2 reagent dispensing position 25d and stops, and the R2 reagent is dispensed from the reagent supply unit 4 (see arrow M in FIG. 3). Next, after receiving a stirring operation at the stirring position 25c as necessary, the reaction cuvette 25 moves to the cuvette transfer position 25t and stops.
- the reaction cuvette 25 is taken out from the reaction base 21 by pick-up means (not shown) at a cuvette transfer position 25t and transferred to the reaction base 31 of the second measurement unit 3 (see arrow E). Move to receiving position 35a. Next, the reaction cuvette 25 is moved to the R3 reagent dispensing position 35b and stopped as required by the rotation of the reaction base 31 (see arrow F), and the R3 reagent is dispensed from the reagent supply unit 4. (See arrow N in Figure 3). This R3 reagent dispensing can be performed, for example, by a suspended reagent dispensing pipettor (not shown).
- the suspended reagent dispensing pipetter moves to a position above the predetermined reagent cup 43c of the reagent supply unit 4, for example, the reagent storage lane 42c, collects the R3 reagent, and then continues to the second measurement unit 3.
- R3 reagent dispensing position Moves to the upper position of reaction cuvette 25 held on 35b And can be dispensed into the reaction cuvette 25. Note that this step is omitted if R3 reagent dispensing is not required. Further, in the first measurement unit 2, the R2 reagent can be dispensed at the R3 reagent dispensing position 35b without dispensing the R2 reagent.
- the reaction cuvette 25 to which the R3 reagent (or R2 reagent) has been dispensed in this manner is moved to the stirring position 35c by the rotation of the reaction base 31, stops, and is subjected to a stirring operation. Subsequently, the reaction cuvette 25 is subjected to the B / F separation operation at the B / F separation position 35d.
- BZF separation can be performed with a magnet. When using a magnet, it takes a relatively long time to collect the magnetic beads, so the stop time of the reaction base 31 is relatively long.
- the entire processing time is reduced due to the long stop time in the rotational movement. Can be prevented from becoming longer.
- the reaction cuvette 25 moves to the cleaning position 35e, stops, and receives the cleaning operation. Subsequently, it moves to the pickup position 35f, stops, and is transferred to the optical measuring means 33 by an appropriate pickup means (not shown).
- the optical measuring means 33 is a means that can measure, for example, chemiluminescence based on the reaction in the reaction cuvette. The optical measurement can also be performed on the reaction base 31. When the optical measurement is performed on the reaction base 31, the force measured when the reaction cuvette 25 passes through the optical measurement position (not shown), or the reaction cuvette 25 is placed at the optical measurement position. It is also possible to stop measurement at (not shown). After the measurement, it is removed from the optical measuring means 33 and discarded in a waste room (not shown).
- the composite automatic analyzer according to the present invention may include one or more additional measurement units in addition to the first measurement unit 2 and the second measurement unit 3.
- the additional measurement unit is configured to transfer a reaction cuvette in which a biological sample is dispensed on the first measurement unit 1 and a part of the reagent is further dispensed from the first measurement unit 1 to an appropriate cuvette transfer means. It can be a force that is received by (pre-feed type) or a type that is directly supplied with a biological sample from the sample supply unit 1 (direct feed type). Further, the additional measurement unit can be added from the reagent supply unit 4 to the additional reagent. It can be an additional reagent replenishing type that requires supply or an additional reagent unnecessary type that does not require the supply of additional reagent from the reagent supply unit 4.
- the composite automatic analyzer according to the present invention can be applied to the first measurement unit 2 and the second measurement unit 3, and can be applied to the additional measurement unit. It is also possible to provide one or more independent measuring units instead of a grid. In this independent measurement unit, the biological sample is directly supplied from the sample supply unit 1, and the measurement can be performed without requiring the reagent supply from the reagent supply unit 4.
- the independent measurement unit is, for example, a body fluid electrolyte measurement unit.
- a mode in which a pre-feed type and additional reagent replenishment type third measurement unit 5 as an additional measurement unit and a fourth measurement unit 6 as an independent type measurement unit will be described with reference to FIG. .
- the third measurement unit 5 of the pre-feed type and the additional reagent supplement type for example, blood coagulation time measurement can be performed separately from the measurement in the first measurement unit 2 and the second measurement unit 3.
- sample dispensing and partial reagent dispensing are performed on the reaction base 21 of the first measurement unit 2. That is, first, the empty reaction cuvette 25 placed in the reaction cuvette placement zone 22 of the reaction base 21 of the first measurement unit 2 is stopped at the sample dispensing position 25a and the same as described above.
- a biological sample is supplied from the sample supply unit 1 to the reaction cuvette 25 by a sample dispensing pipettor (not shown) (see arrow C in FIG. 4).
- a sample dispensing pipettor (not shown) (see arrow C in FIG. 4).
- the reaction cuvette 25 moves to the R1 reagent dispensing position 25b and stops, and the R1 reagent is removed from the reagent supply unit 4 by, for example, a suspended reagent dispensing pipettor (not shown). It is dispensed.
- the first measurement unit 2 only sample dispensing can be performed and reagent dispensing can be omitted.
- the reaction cuvette 25 moves to the cuvette transfer position 25s and stops.
- the reaction base 5 of the third measuring unit 5 is taken out from the reaction base 21 by pick-up means (not shown) and located at the transfer position 5a (shown by a broken line in FIG. 4). In 1 it is transferred to the receiving position 55a (see arrow G).
- This third measurement unit 5 is a circular rotary table type reaction, similar to the first measurement unit 2 and the second measurement unit 3 described above. It can also be a type including a base, but it can also be a type including a belt-like table type reaction base capable of linear reciprocating motion (in the direction of arrow H and vice versa).
- the third measurement unit 5 moves the additional reagent dispensing position 5b (indicated by the solid line in Fig. 4) by the linear sliding movement (in the direction of arrow H) of the reaction base 51.
- the reaction base 51 is provided with optical measuring means (not shown) at the position where the reaction cuvette 25 is placed.
- optical measuring means comprising a transmitting part and a receiving part for measuring transmitted light are provided on both sides of the position where the reaction cuvette 25 is placed. For example, transmitted light measurement at intervals of 0.1 second is performed. It can also be implemented. It should be noted that the optical measurement means 5c (see FIG. 4) is not installed on the reaction base 51, for example, by a linear slide movement (in the direction of arrow H) of the reaction base 51, as shown in FIG. The optical measurement position 5c is measured by an optical measurement means 57 that can measure, for example, a change based on the reaction in the reaction cuvette with scattered light. You can also. After the measurement, it moves to a disposal position (not shown), stops, is removed from the reaction base 51 by pick-up means (not shown), and is discarded into a disposal chamber (not shown).
- a biological sample is directly supplied from the sample supply unit 1 to the fourth measurement unit 6 which is a stand-alone measurement unit by a sample pipetting pipetter (not shown) (see arrow J in FIG. 4). ).
- the fourth measurement unit 6 can be, for example, a body fluid electrolyte measurement unit, in particular, an ion detection device including various ion selective electrodes. Examples of the ion selective electrode include a halogen ion selective electrode and an alkali metal ion selective electrode.
- the installation position, installation order (adjacent relationship), the measurement items of each measurement unit, and the types of optical system measurement means provided in each measurement unit Especially limited is not.
- sample dispensing from the sample supply unit to a plurality of mutually independent reaction cuvettes is performed collectively in the first measurement unit. It is preferable to place the unit and the first measurement unit in an adjacent proximity position.
- the movement of the sample transport means for dispensing becomes simple and short, so that the time for dispensing operation and the device mechanism can be simplified. That is, when compared with a conventional apparatus that individually performs sample dispensing for each measurement unit, the complex automatic analyzer according to the present invention performs sample dispensing in a batch in the first measurement unit. 2 Since the reaction cuvette is simply transferred to the measurement unit or additional measurement unit (such as the third measurement unit) by the cuvette transfer means, the overall processing time including the sample dispensing time is shortened, and the mechanism is It can be simplified.
- biochemical measurement or immunological measurement can be performed in the first measurement unit.
- the targets of biochemical measurements are those performed in normal biochemical clinical tests, such as various enzymes, carbohydrates, lipids, plasma (serum) proteins, non-protein nitrogen compounds, biological dyes, tumor markers And so on.
- the immunological measurement include immunological measurement using transmitted light and scattered light, such as immunoturbidimetric method and latex agglutination method.
- the measurement target include D-dimer, FDP, or HCV.
- the second measurement unit is a reaction system different from other measurement units, and can perform, for example, highly accurate measurement.
- a reaction with a specific affinity substance can be used.
- the reaction with a specific affinity substance includes, for example, an antigen-antibody reaction, a reaction with a complementary base of nucleic acid (DNA or RNA), or a reaction between a receptor and its ligand.
- the amount of the substance bound to the specific affinity substance is measured. In that case, by binding the specific affinity substance and the bound substance, it is itself! /, Which is bound to the bound substance by utilizing the fact that the property of the tracer changes.
- Uniform measurement method homogeneous method
- the homogenous method or the heterogeneous method can be carried out by the second measurement unit.
- a tracer it is possible to use a deviation from a method using a radioisotope or an enzyme immunoassay method (EIA) using an enzyme.
- the second measurement unit for example, FIA, EIA, or CLEIA can be performed.
- the measurement target include CEA, CA19-9, T3, T4, FT3, FT4, HBsAg, TAT, or TSH.
- blood coagulation time measurement or activity measurement using a synthetic substrate can be performed.
- the measurement of blood coagulation time include measurement of protobin time, active partial thromboplastin time, or fibrinogen.
- activity measurement using a synthetic substrate include measurement of plasminogen, plasmin inhibitor, or antithrombin.
- electrolyte measurement can be performed. Examples of the electrolyte measurement target include Na ions, K ions, and chlorine ions.
- the first measurement unit preferably performs measurement using transmitted light or scattered light, for example, a colorimetric measurement method or a turbidimetric measurement method.
- measurement using chemiluminescence or fluorescence, for example, CLEIA is preferably performed.
- a measurement using transmitted light or scattered light for example, a blood coagulation time measurement method.
- electromotive force for example, an ion selective electrode method.
- biochemical measurement or latex agglutination measurement is performed by a colorimetric or turbidimetric measurement method in the first measurement unit, and enzyme immunization is performed in the second measurement unit.
- a combination is preferred in which the biological measurement is performed by chemiluminescence and the blood clotting time is measured by the third measurement unit.
- the first optical system measurement means in the first measurement unit, the second optical system measurement means in the second measurement unit, and the third measurement as the additional measurement unit is preferably an optical detector different from each other.
- the first optical system measurement means, the second optical system measurement means, and the third optical system measurement means for example,
- an optical detector including a light emitting diode and a diode array
- an optical detector including a lamp unit and a spectrometer
- Optical detector including photomultiplier as a light receiver
- An optical detector including a light emitting diode and a diode array can be used, for example, for measurement of blood clotting time, and an optical detector including a lamp unit and a spectroscope, for example, for colorimetric measurement and turbidity measurement.
- An optical detector that includes a photomultiplier as a light receiver can be used for chemiluminescence measurement, for example.
- Abnormal samples are specimens with extremely high concentrations of test substances, and often cannot detect high concentrations. Abnormal samples also include non-specific samples (samples that aggregate magnetic latex). Such an abnormal sample can be detected, for example, by a change in absorbance.
- the present invention also relates to a reaction cuvette.
- FIG. 5 is a perspective view of a reaction cuvette 8 according to the present invention
- FIG. 6 is a sectional view thereof.
- FIG. 7 is a schematic cross-sectional view of a state in which, for example, the composite automatic analyzer shown in FIGS. 1 to 4 is placed on the reaction base 21 of the first measurement boot 2
- FIG. 3 is a schematic cross-sectional view showing a state in which the reaction cuvette is tilted by a stirring rod.
- the reaction cuvette 8 includes a pair of pickup protruding pieces 83, 83 at an upper end portion 82 of a substantially quadrangular columnar cuvette body 81, and a pair of mounting protruding pieces below it. 84, 84 are provided.
- Such a reaction cuvette 8 can be placed by inserting the lower part of the cuvette body 81 into a placement through-hole (or a placement depression or groove) provided in the reaction base of the measurement unit. .
- the pickup protruding piece 83 picks up the reaction cuvette placed on the reaction base 21 of the first measurement unit 2 and picks up the second measurement unit 3.
- the pickup protrusion 83 is attached to the measurement unit reaction base so that the pickup protrusion 83 can be held by the pickup means. It is necessary to provide it at a position that protrudes upward from the surface.
- the mounting protruding piece 84 is provided in the upper part of the cuvette body 81.
- the reaction base 21 or the first measurement unit 2 (or When the reaction cuvette is inserted and placed in the mounting through-hole (or mounting recess or groove) provided in the reaction base 31) of the second measurement unit 3, the reaction base 21 (or reaction base) It has a function as a locking piece to prevent it from falling in contact with the base surface of 31).
- the reaction cuvette 8 is provided with a hemispherical depression 86 on the bottom surface 85 of the cuvette body 81, and an insertion port 87 into which the tip of the stirring bar 91 can be inserted at the center of the depression 86.
- a hemispherical depression 86 on the bottom surface 85 of the cuvette body 81, and an insertion port 87 into which the tip of the stirring bar 91 can be inserted at the center of the depression 86.
- the reaction cuvette 8 according to the present invention having such a structure is inserted into the mounting through-hole of the reaction base 21, and is moved to the stirring operation position and stopped. Then, the tip of the stirring rod 91 of the stirring device (not shown) is inserted into the hemispherical recess 86. At this time, as shown in FIG. 7, the tip portion force of the stirring rod 91 is deflected in the circumferential direction from the middle point so as not to be inserted into the center portion of the bottom surface 85 of the reaction cuvette 8.
- the tip of the stirring rod 91 further pushes up the hemispherical depression 86 while pushing, it is finally inserted into the insertion port 87.
- the reaction cuvette 8 is also agitated when the tip of the stirring rod 91 collides with the wall surface of the hemispherical depression 86.
- the mounting protrusion 84 has a rectangular plate shape.
- the contact with the surface of the reaction base 21 becomes irregular and the reaction cuvette 8 is not smoothly stirred.
- the tip of the mounting protrusion 84 is arcuate, so that the contact with the surface of the reaction base 21 is not irregular, and the reaction cuvette 8 is smoothly stirred. Stir. Therefore, the reaction cuvette according to the present invention can be effectively used in an automatic analyzer that performs a stirring operation.
- the depression provided on the bottom surface of the reaction cuvette of the present invention has a curved wall surface.
- the shape of the curved wall surface is preferably such that the tip of the stirring rod that first contacts the peripheral wall surface of the recess is smoothly guided to the center of the recess in the course of the stirring operation. . Therefore, the curved wall surface can be, for example, a hemispherical force as shown in FIGS. 6 to 8, a hemispherical shape, a conical shape, or a truncated conical shape.
- the curved wall surface is hemispherical or hemispherical, it is preferable to provide an insertion port for the tip of the stirring rod at the center of the recess.
- the curved wall surface has a truncated cone shape
- the apex of the cone can function as an insertion port for the tip of the stirring rod.
- the reaction cuvette of the present invention can be stirred by the action from the outside as described above without the need to insert a stirring bar into the sample. It is advantageous when the measurement is included in the measurement item. This is because in the case of coagulation time measurement, if a stir bar is inserted into the sample and stirred, the coagulation system is affected and the measurement result may be inaccurate.
- the reaction cuvette of the present invention is advantageous in the case of measurements using transmitted light, for example, biochemical measurement items and turbidity measurement in LPIA.
- the reaction cuvette of the present invention preferably has a curved portion (semi-spherical bottom surface or semi-elliptical spherical bottom surface) at the inner bottom. If the inner bottom part does not have a curved part, the liquid may slide up on the inner wall surface of the cuvette due to capillary action, resulting in insufficient cleaning.
- highly sensitive chemical emission for example, Alkaline phosphatase-labeled antibodies, etc. may remain and cause errors.
- the reaction cuvette according to the present invention includes a pair of mounting protruding pieces as shown in Figs. On one or both lower surfaces of 84, 84, fixing protrusions 88, 88 can be provided.
- the fixing protruding piece 88 is a plate-like protrusion that protrudes downward from the bottom surface force of the mounting protruding piece 84, and is shown in FIG. 11 (partial cross-sectional view) at the outer front end opposite to the cuvette body side. A curved surface may be formed as shown.
- a recess or a groove is provided on the edge of the mounting through-hole on the surface of the reaction base on which the reaction cuvette is placed.
- the fixing protruding piece 88 can be inserted into the recess or groove, and the lower part of the cuvette body 81 can be inserted into the mounting through-hole.
- the fixing protruding piece 88 is provided on the lower surface of one or both of the loading cuvettes 84 and 84 for the reaction cuvette, and the depression for the fixing protruding piece 88 or the By providing the groove, the cuvette can be securely fixed and positioned.
- the device of the present invention has at least three or more different detection systems.
- the optical systems of the first measurement unit, the second measurement unit, and the third measurement unit are different from each other.
- the optical systems of the first measurement unit, the second measurement unit, and the third measurement unit are different from each other.
- Unit that uses transmitted light and scattered light detection device including lamp unit and spectrometer
- High-sensitivity detection unit in the case of chemiluminescence, the detector includes a photomultiplier detector
- Coagulation time detection unit detection device including LED and diode array
- the cuvette required for each detection system is stirred and picked up at a specific position (not shown) However, the cuvette is picked up by the arm of the device and attached to the cuvette hole at the specific position in the next process) and transported to each measurement unit, so that each detection proceeds independently and in parallel. By doing so, an efficient measurement becomes possible.
- each reagent ring can be driven individually by combining multiple rings on a concentric axis, for example, while having a single reagent table area. Can also do a lot.
- the multiple rings on the concentric axis naturally have different distances from the center, and the difference is used to dispense the reagent into the cuvette in a linear motion with respect to the position of each measurement unit. It is also possible to drive a syringe of this type, which leads to suppression of malfunctions due to downsizing or simple driving.
- all the cuvettes are configured such that a stirring operation is always performed in an intermediate step (for example, after mixing of a sample and a reagent) in any measurement unit.
- a stirring operation is always performed in an intermediate step (for example, after mixing of a sample and a reagent) in any measurement unit.
- the apparatus of the present invention for example, since there is a measurement unit for blood coagulation time, if the sample is stirred with a probe (stirring blade), a fibrin clot is wound, which is inconvenient. Is very effective. Since each cuvette is independent, the cuvette structure of the present invention is an important requirement for efficient stirring individually.
- the shape is also a quadrangular prism, the transmission distance of transmitted light can be strictly fixed, and variations in measurement results can be suppressed.
- the cuvettes in the measurement unit having a plurality of different detection system forces need to be independent from each other, and the cuvette is also used in order to enhance the stirring effect.
- the shape of the present invention is preferred.
- the device of the present invention obtains the measurement results from several different detection systems at once. It is excellent in that it can be used. In the prior art, measurement results are individually presented by individual measurement devices.
- the complex automatic analyzer according to the present invention can measure a plurality of types of analysis with different measurement accuracy, such as biochemical analysis and immunological analysis, by a single device.
- the reaction cuvette according to the present invention can be effectively used in an automatic analyzer that performs a stirring operation.
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Abstract
Description
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Priority Applications (6)
Application Number | Priority Date | Filing Date | Title |
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ES06730988T ES2859774T3 (es) | 2005-04-01 | 2006-04-03 | Aparato de análisis automático múltiple de muestras biológicas, procedimiento de autoanálisis y cubeta de reacción |
CA002603209A CA2603209A1 (en) | 2005-04-01 | 2006-04-03 | Biosample multiple autoanalyzer, method of autoanalysis and reaction cuvette |
JP2007511225A JP4712033B2 (ja) | 2005-04-01 | 2006-04-03 | 生体サンプルの複合自動分析装置、自動分析方法、及び反応キュベット |
US11/910,408 US9341640B2 (en) | 2005-04-01 | 2006-04-03 | Apparatus for multiple automatic analysis of biosamples, method for autoanalysis, and reaction cuvette |
EP06730988.0A EP1870713B1 (en) | 2005-04-01 | 2006-04-03 | Apparatus for multiple automatic analysis of biosamples, method for autoanalysis, and reaction cuvette |
CN2006800098075A CN101147071B (zh) | 2005-04-01 | 2006-04-03 | 生物样品的复合自动分析装置、自动分析方法以及反应杯 |
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JP2005105700 | 2005-04-01 | ||
JP2005-105700 | 2005-04-01 |
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WO2006107016A1 true WO2006107016A1 (ja) | 2006-10-12 |
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PCT/JP2006/307040 WO2006107016A1 (ja) | 2005-04-01 | 2006-04-03 | 生体サンプルの複合自動分析装置、自動分析方法、及び反応キュベット |
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US (1) | US9341640B2 (ja) |
EP (1) | EP1870713B1 (ja) |
JP (2) | JP4712033B2 (ja) |
KR (1) | KR101260400B1 (ja) |
CN (2) | CN101147071B (ja) |
CA (1) | CA2603209A1 (ja) |
ES (1) | ES2859774T3 (ja) |
HK (1) | HK1170304A1 (ja) |
WO (1) | WO2006107016A1 (ja) |
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Also Published As
Publication number | Publication date |
---|---|
JP5364064B2 (ja) | 2013-12-11 |
ES2859774T3 (es) | 2021-10-04 |
KR101260400B1 (ko) | 2013-05-09 |
EP1870713A1 (en) | 2007-12-26 |
US20080318323A1 (en) | 2008-12-25 |
CN101147071A (zh) | 2008-03-19 |
CA2603209A1 (en) | 2006-10-12 |
CN102565438A (zh) | 2012-07-11 |
CN101147071B (zh) | 2011-12-14 |
HK1170304A1 (en) | 2013-02-22 |
EP1870713B1 (en) | 2021-01-27 |
JP4712033B2 (ja) | 2011-06-29 |
JP2011017716A (ja) | 2011-01-27 |
US9341640B2 (en) | 2016-05-17 |
EP1870713A4 (en) | 2015-08-05 |
KR20080005363A (ko) | 2008-01-11 |
CN102565438B (zh) | 2014-05-07 |
JPWO2006107016A1 (ja) | 2008-09-25 |
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