JP2012255664A - Automatic analysis method - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an automatic analysis method with which analysis can be performed with Immuno-PCR method as a measurement principle, without providing any dedicated analysis apparatus.SOLUTION: In an immunity analysis unit AU1, an examinee and a first reagent are dispensed into a reaction vessel 11 and reacted in a thermostat bath, thereby forming a complex by coupling a primary antibody and a secondary antibody to a detection target. A solution for which a cleaning step has been finished is conveyed to a gene analysis unit AU2. In the gene analysis unit AU2, the solution for which the cleaning step has been finished is dispensed into the reaction vessel, a second reagent is dispensed and by repeating temperature conditions for thermal denaturation of target nucleic acid, anneal of primer nucleic acid with respect to the target nucleic acid and extension reaction of primer nucleic acid through a temperature cycle mechanism 27, the target nucleic acid is amplified. Thereafter, fluorescent depending on the quantity of amplified nucleic acid is detected by a fluorescence detection mechanism 29.

Description

  The present invention relates to an automatic analysis method for automatically analyzing a sample such as serum or urine, and more particularly to an automatic analysis method using an automatic analysis system including an immune analysis unit and a gene analysis unit.

  Immunological reaction based on immunological specific binding and Immuno-PCR (Polymerase Chain Reaction) method using gene amplification reaction as a method for measuring a trace amount of biological material in a specimen (for example, see Non-Patent Document 1) And analysis methods such as FACTT (Fluorescent amplification catalyzed by T7 polymerase technique) (for example, see Non-Patent Document 2) are known.

  Here, for example, in the Immuno-PCR method, a primary antibody and a secondary antibody are bound to a detection target by a primary antibody that can bind to the detection target and a secondary antibody that can bind to the detection target and is labeled with a nucleic acid. After forming the bound complex and removing the unreacted secondary antibody, the nucleic acid labeled to the secondary antibody is amplified by PCR, and the amplification product depending on the amount of template nucleic acid, that is, the concentration of the detection target, is quantified This is a method for analyzing a detection object. In this Immuno-PCR method, for example, the detection sensitivity is improved by 10 to 10,000 times compared to an ELISA (Enzyme-Linked ImmunoSorbent Assay) method (for example, see Non-Patent Document 3) in which a secondary antibody is labeled with an enzyme. , Fmol / L order or less can be detected.

  In the field of in-vitro diagnosis in clinical examinations, automatic analyzers are used for measuring biological substances such as tumor markers, infections, hormones, etc. EIA (enzyme immunoassay) based on the above-mentioned immunological specific binding, CLIA Immunoassay units based on the measurement principle (chemiluminescence immunoassay), ECLIA (electrochemiluminescence immunoassay) and the like are used.

  In addition, for infectious disease items for which detection sensitivity is insufficient in immunoassay methods, the automatic analyzer is a gene analysis unit based on a gene amplification reaction by PCR (Polymerase Chain Reaction) with a pathogen-derived gene as a measurement target Is used.

Science 258, 120-122 (1992) Nature medicen 12, 473-475 (2006) Immunochemistry 8, 871-874 (1971)

  Existing immunoanalyzers (automated analyzers equipped with immunoassay units) are measured using EIA (enzyme immunoassay), CLIA (chemiluminescence immunoassay), ECLIA (electrochemiluminescence immunoassay), etc. as measurement principles A reagent containing a specimen containing a target object, a primary antibody that can bind to the detection target, and a secondary antibody that can bind to the detection target and is labeled with a luminescent substance is dispensed into a reaction container, and the detection target is primary. A complex in which an antibody and a secondary antibody are bound to each other is formed, and a magnetic substance bound to the primary antibody is magnetically separated to remove unreacted secondary antibody and detect luminescence by the luminescent substance. Therefore, it is impossible to apply analysis items based on the immuno-PCR method, which includes a step of amplifying a nucleic acid labeled with a secondary antibody by PCR.

  On the other hand, gene analyzers (automated analyzers equipped with gene analysis units) are based on quantitative PCR that quantifies amplified genes using fluorescent dyes and quenching substances, and a purification solution containing a target nucleic acid and a nucleic acid amplification region A primer nucleic acid complementary to, and a reagent containing a nucleic acid extender and a substrate necessary for nucleic acid amplification are dispensed into a reaction container for thermal denaturation of the target nucleic acid, annealing of the primer nucleic acid to the target nucleic acid, and extension reaction of the primer nucleic acid. The target nucleic acid is amplified by repeating this temperature condition, and the fluorescence depending on the amount of the amplified nucleic acid is also detected. Therefore, it is not possible to apply an analysis item based on the immuno-PCR method, which includes a step of forming a complex in which a primary antibody and a secondary antibody are bound to a detection target and removing an unreacted secondary antibody. Is.

  That is, each of the conventional immune analyzers or gene analyzers alone cannot carry out analysis items based on the immuno-PCR method as a measurement principle. Therefore, in the operation of a clinical laboratory, a dedicated analyzer equipped with a mechanism for carrying out the steps of the Immuno-PCR method is required, which involves an economic burden.

  An object of the present invention is to provide an automatic analysis method capable of performing analysis based on the immuno-PCR method without providing a dedicated analyzer.

(1) In order to achieve the above object, the present invention provides an immunoassay unit, a gene analysis unit, and a sample transport for transporting a sample rack holding a sample container from the sample input unit to the immune analysis unit or the gene analysis unit. The immunoassay unit is installed in a reaction container installed in the constant temperature mechanism, a sample dispensing mechanism that dispenses the sample in the sample container conveyed by the sample rack, and the constant temperature mechanism. A magnetic substance from a reagent dispensing mechanism that dispenses a predetermined reagent from a reagent bottle held in an immunoreagent storage unit into the reaction container, and a reaction solution that has undergone a predetermined time reaction at a predetermined temperature in the constant temperature mechanism. A cleaning mechanism that magnetically separates and replaces the solution, a luminescence detection mechanism that detects luminescence of the luminescent label contained in the reaction solution after the cleaning process by the cleaning mechanism, and a cleaning mechanism that uses the cleaning mechanism A reaction container transfer mechanism for transferring the reaction container after completion of the process to the sample transport unit, wherein the gene analysis unit installs the reaction container held in the reaction container storage unit in the reaction container installation unit An installation mechanism, a sample dispensing mechanism for dispensing a sample in the sample container transported by the sample rack into a reaction container installed in the reaction container installation unit, and a reaction container installed in the reaction container installation unit In addition, a reagent dispensing mechanism that dispenses a predetermined reagent from a reagent bottle held in a genetic reagent storage unit, and a temperature cycle mechanism that repeats a cycle that holds a reaction container in which a specimen and a reagent are dispensed at a predetermined temperature for a predetermined time And an automatic analysis system having a fluorescence detection mechanism for detecting fluorescence of a fluorescent label contained in a reaction solution in which a predetermined temperature cycle is repeated by the temperature cycle mechanism, An automatic analysis method for dynamic analysis, in which a specimen including a measurement target and a primary antibody that can be bound to a detection target held in the immunoreagent storage unit of the immunological analysis unit can be bound to the detection target. A first nucleic acid containing a secondary antibody labeled with a luminescent substance, and a primer nucleic acid complementary to the target antibody amplification region of the secondary antibody held in the genetic reagent storage unit of the genetic analysis unit, Using a nucleic acid elongation enzyme necessary for nucleic acid amplification and a second reagent containing a substrate, in the immunoassay unit, the sample is dispensed by the sample dispensing mechanism into a reaction vessel installed in the constant temperature mechanism, The first reagent is dispensed by a reagent dispensing mechanism and reacted in the constant temperature bath to form a complex in which the primary antibody and the secondary antibody are bound to the detection target, and by the washing mechanism The magnetic substance bound to the primary antibody is magnetically separated to remove the unreacted secondary antibody, and the solution after the washing process is transferred to the specimen transport section by the reaction container transfer mechanism. Then, the sample transport unit transports the solution after the washing step to the gene analysis unit, and in the gene analysis unit, the sample dispensing mechanism moves the solution to the reaction container installed in the reaction container installation unit. The solution after the washing step is dispensed, and the second reagent held in the genetic reagent storage unit is dispensed into the reaction vessel installed in the reaction vessel installation unit by the reagent dispensing mechanism. The temperature cycle mechanism increases the target nucleic acid by repeating the temperature conditions for thermal denaturation of the target nucleic acid, annealing of the primer nucleic acid to the target nucleic acid, and extension reaction of the primer nucleic acid. And, by the fluorescence detection mechanism, by detecting the fluorescence depends on the amplified nucleic acid amount is obtained so as to analyze the analysis item as measurement principle the Immuno-PCR method.
By this method, an analysis based on the immuno-PCR method can be performed without providing a dedicated analyzer.

  (2) In the above (1), preferably, in the immunoassay unit, the same specimen is dispensed into the first and second reaction containers, respectively, and the reagent of the immunological analysis item is dispensed into the first reaction container. And after dispensing the first reagent into the second reaction vessel and washing the first and second reaction vessels with the thermostatic mechanism, the first reaction vessel When the analysis result is analyzed by a luminescence detection mechanism and the analysis result is lower than the measurement range of the immunological analysis item, the second reaction container is transported to the gene analysis unit by the sample transport mechanism, In the gene analysis unit, the second reagent is used to analyze analysis items based on the immuno-PCR method as a measurement principle.

  (3) In the above (1), preferably, in the immunoassay unit, a sample rack in which a sample is dispensed in the first reaction container and the sample stored in the sample container after the sample dispensing is installed Is transferred to the buffer unit, and the reagent of the immunological analysis item is dispensed into the first reaction container, and the first reaction container is washed with the thermostatic mechanism, and then the first reaction container is removed. When the analysis result is analyzed by the luminescence detection mechanism and the analysis result is lower than the measurement range of the immunological analysis item, the sample rack waiting in the buffer unit is moved to the start position of the sample transport unit by the retest transport unit. In the immunoassay unit, the specimen is dispensed into a second reaction container, the first reagent is dispensed into the second reaction container, and the second reaction container is filled with the second reaction container. After washing with a constant temperature mechanism, the specimen transport mechanism The conveyed to genetic analysis unit, in the genetic analysis unit, by using the second reagent, it is obtained so as to analyze the analysis item as measurement principle the Immuno-PCR method.

  According to the present invention, an analysis based on the immuno-PCR method can be performed without providing a dedicated analyzer.

It is a block diagram which shows the structure of the automatic analysis system using the automatic analysis method by one Embodiment of this invention.

Hereinafter, the configuration of an automatic analysis system using an automatic analysis method according to an embodiment of the present invention will be described with reference to FIG.
FIG. 1 is a block diagram showing a configuration of an automatic analysis system using an automatic analysis method according to an embodiment of the present invention.

  This analysis system includes an immune analysis unit AU1, a gene analysis unit AU2, a sample input unit 4, a sample transport unit 5, a retest transport unit 8, a standby buffer 6, a sample recovery unit 7, a control unit 1, Consists of

  The sample rack 2 is loaded into the sample loading unit 4. The sample rack 2 holds a plurality of sample containers 3. Each sample container 3 stores a sample to be analyzed.

  The sample rack 2 loaded into the sample loading unit 4 is transported by the sample transport unit 5 to the immune analysis unit AU1 and the gene analysis unit AU2. The sample stored in the sample container 3 held in the sample rack 2 is analyzed by the immune analysis unit AU1 and the gene analysis unit AU2. The sample rack 2 is transported to the standby buffer 6 and the sample recovery unit 7 by the sample transport unit 5. The standby buffer 6 waits until it is determined whether reexamination is necessary. If it is determined that reexamination is necessary, the sample rack 2 is returned to the start position (the left position in the figure) of the sample transport unit 5 by the retest transport unit 8, and again by the sample transport unit 5, the epidemiological analysis unit. It is transported to AU1 and gene analysis unit AU2. On the other hand, the sample that has been analyzed by the epidemiological analysis unit AU1 and the gene analysis unit AU2 is collected by the sample collection unit 7.

  The control unit 1 controls the operation of each unit such as the immune analysis unit AU1, the gene analysis unit AU2, the sample input unit 4, the sample transport unit 5, and the retest transport unit 8.

  The immunological analysis unit AU1 includes a specimen dispensing mechanism 10, a reaction container installation mechanism 12, a reagent dispensing mechanism 13, an immune reagent storage unit 14, a cleaning mechanism 16, a reaction container transfer mechanism 17, and a constant temperature mechanism 18. The light emission detection mechanism 19 is mainly configured.

  The reaction vessel installation mechanism 12 holds an arbitrary reaction vessel 11 from among the plurality of reaction vessels 11 held in the reaction vessel storage unit, moves to a predetermined position of the constant temperature mechanism 18 and installs it.

  The sample dispensing mechanism 10 aspirates a predetermined amount of sample from the sample container 3 held in the sample rack 2 supplied from the sample input unit 4 via the sample transport unit 5. Then, the sample dispensing mechanism 10 discharges and dispenses the aspirated sample into the reaction container 11 installed in the constant temperature mechanism 18.

  The immunoreagent storage unit 14 holds a plurality of reagent bottles 15. Each of the plurality of reagent bottles 15 stores a reagent used in the immunological analysis unit AU1. The reagent dispensing mechanism 13 sucks a predetermined reagent from the predetermined reagent bottle 15 and discharges it to the reaction container 11 into which the sample has been dispensed.

  The constant temperature mechanism 18 holds the reaction container 11 into which the specimen and the reagent are dispensed at a predetermined temperature for a predetermined time. The cleaning mechanism 16 magnetically separates the magnetic material from the reaction solution that has undergone the reaction for a predetermined time at the predetermined temperature in the thermostatic mechanism 18 and replaces the solution. The luminescence detection mechanism 19 detects the luminescence of the luminescent label contained in the reaction solution after the washing process by the washing mechanism 16 is completed.

  The reaction container transfer mechanism 17 transfers the reaction container that has completed the cleaning process by the cleaning mechanism 16 to the sample transport unit 5.

  The gene analysis unit AU2 includes a sample dispensing mechanism 20, a reaction container installation mechanism 22, a reagent dispensing mechanism 23, a gene reagent storage unit 24, a reaction container transport mechanism 27, a reaction container installation unit 28, and fluorescence detection. The mechanism 29 and the temperature cycle mechanism 30 are mainly configured.

  The reaction vessel installation mechanism 27 holds an arbitrary reaction vessel 21 from among the plurality of reaction vessels 21 held in the reaction vessel storage unit, moves to a predetermined position of the reaction vessel installation unit 28, and installs it.

  The sample dispensing mechanism 20 aspirates a predetermined amount of sample from the sample container 3 held in the sample rack 2 supplied from the sample input unit 4 via the sample transport unit 5. Then, the specimen dispensing mechanism 20 discharges and dispenses the sucked specimen into the reaction container 21 installed in the reaction container installation section 28.

  The gene reagent storage unit 24 holds a plurality of reagent bottles 25. Each of the reagent bottles 25 stores a reagent used in the gene analysis unit AU2. The reagent dispensing mechanism 23 sucks a predetermined reagent from a predetermined reagent bottle 25 and discharges it to the reaction container 21 into which the sample has been dispensed.

  The temperature cycle mechanism 30 repeats a cycle in which the reaction container 21 into which the specimen and the reagent or the reagent are dispensed is held at a predetermined temperature for a predetermined time. The fluorescence detection mechanism 29 detects the fluorescence of the fluorescent label contained in the reaction solution in which a predetermined temperature cycle is repeated by the temperature cycle mechanism 30.

  Next, a first analysis method for analysis items based on the immuno-PCR method as a measurement principle using the above analysis system will be described.

  Two types of reagents are used for analysis by the Immuno-PCR method. The first reagent is a reagent that includes a primary antibody that can be bound to a detection target and bound to a magnetic particle, and a secondary antibody that can bind to the detection target and is labeled with a nucleic acid. The reagent bottle 15 containing the first reagent is installed in the immune reagent storage unit 14 of the immune analysis unit AU1.

  The second reagent is a reagent containing a primer nucleic acid complementary to the target nucleic acid amplification region of the secondary antibody, a nucleic acid elongation enzyme necessary for nucleic acid amplification, and a substrate. The reagent bottle 25 containing the second reagent is installed in the gene reagent storage unit 24 of the gene analysis unit AU2.

  In the analysis method of the present embodiment, first, a first reagent including a specimen containing a measurement target, a primary antibody that can bind to the detection target, and a secondary antibody that can bind to the detection target and is labeled with a luminescent substance. The reaction product is dispensed into a reaction container to form a complex in which the primary antibody and the secondary antibody are bound to the detection target, and the unreacted secondary antibody is separated by magnetic separation of the magnetic material bound to the primary antibody. The removing step is performed in the immunoassay unit. Next, the solution after completion of this step is transferred to the gene analysis unit by the sample transport mechanism, and a primer nucleic acid complementary to the target nucleic acid amplification region of the secondary antibody, a nucleic acid extending enzyme necessary for nucleic acid amplification, and a substrate containing the substrate. 2 reagents are dispensed into a reaction vessel, and the target nucleic acid is amplified by repeating the temperature conditions for thermal denaturation of the target nucleic acid, annealing of the primer nucleic acid to the target nucleic acid, and extension reaction of the primer nucleic acid. The step of detecting the fluorescence depending on is performed in the gene analysis unit.

  Hereinafter, a specific first method of automatic analysis for implementing the above method using the configuration of each part of the automatic analysis system will be described.

  The operator requests an analysis item from the control unit 1, puts the sample rack 2 in which the sample container 3 containing the sample such as serum or urine to be measured is loaded into the sample loading unit 4 and starts the analysis To do.

  The sample stored in the sample container 3 is transported by the sample transport unit 5 from the sample input unit 4 to a position in the vicinity of the sample dispensing mechanism 10 of the immune analysis unit AU1. The sample dispensing mechanism 10 sucks a predetermined amount of sample from the sample stored in the sample container 3 and discharges it to the reaction container 11 installed at a predetermined position of the constant temperature mechanism 18 by the reaction container installation mechanism 12. Next, a predetermined amount of the first reagent out of the reagents installed in the immune reagent storage unit 14 by the reagent dispensing mechanism 13 is sucked and discharged into the reaction container 11. By holding the reaction vessel 11 in the thermostatic mechanism 18 for a predetermined time, an immune reaction proceeds, and a complex in which the primary antibody and the secondary antibody are bound to the detection target is formed. Note that magnetic particles are bound to the primary antibody, and labeled nucleic acid is bound to the secondary antibody.

  The reaction container transfer mechanism 17 moves the reaction container 11 that has completed the immune reaction to the cleaning mechanism 16. The cleaning mechanism 16 magnetically separates the magnetic particles and the liquid phase in the reaction solution and replaces the solution, thereby removing the secondary antibody that could not bind to the primary antibody containing the magnetic particles via the measurement object. Remove from phase. The reaction container 11 that has finished the cleaning process by the cleaning mechanism 16 is transported from the immunoassay unit AU1 to the sample transport unit 5 by the reaction container transport mechanism 17, and is set in an empty position of the sample rack 2.

  In the conventional immunological analysis item, the luminescence detection mechanism 19 detects the luminescence of the luminescent label labeled on the secondary antibody in the reaction vessel 11 that has completed the cleaning process by the cleaning mechanism 16.

  Next, the sample transport unit 5 transports the sample rack 2 in which the reaction container 11 is installed at the empty position of the sample rack 2 to the vicinity of the sample dispensing mechanism 20 of the gene analysis unit AU2. The sample dispensing mechanism 20 sucks a predetermined amount of the reaction solution from the reaction container 11 and discharges it to the reaction container 21 installed in the reaction container installation unit 28 by the reaction container installation mechanism 22.

  Next, the reagent dispensing mechanism 23 sucks a predetermined amount of the second reagent from the reagent bottle 25 installed in the gene reagent storage unit 24 and discharges the second reagent to the reaction container 21. Next, the reaction vessel 21 is installed in the temperature cycle mechanism 30 by the reaction vessel transport mechanism 27 and a predetermined temperature cycle is performed. In addition, the fluorescence detection mechanism 29 detects the amount of fluorescence that depends on the amount of amplified nucleic acid. Then, the number of temperature cycles and the result of the fluorescence measurement value are sent to the control unit 1, and the measurement object contained in the specimen is quantitatively or qualitatively analyzed.

  Next, another analysis method for analysis items based on the immuno-PCR method as a measurement principle will be described using the above analysis system. In the second analysis method, analysis items are analyzed based on the immuno-PCR method as a measurement principle based on the analysis results of conventional immune analysis items.

  As described above, in the immunological analysis item and the analysis item based on the Immuno-PCR method, the process of generating the complex of the measurement target, the primary antibody and the secondary antibody is common, and the labeling substance of the secondary antibody and the detection method Is a different analysis method. Therefore, when the label of the secondary antibody is a luminescent substance, it is analyzed with the same substance as the detection target in the normal immunoassay sensitivity, while when the label of the secondary antibody is a nucleic acid, it is highly sensitive by the Immuno-PCR method. Is possible.

  The control unit 1 of the analysis system first analyzes an immune analysis item when an analysis is performed to analyze an analysis item based on the immunological analysis item and the immuno-PCR method as the measurement principle for the same measurement object. When it is determined that more sensitive analysis is necessary based on the analysis result, analysis of an analysis item based on the immuno-PCR method is performed.

  In the analysis for carrying out the analysis item based on the immunological analysis item and the immuno-PCR method as a measurement principle, the second analysis method from the viewpoint of “rapidity” of the analysis result output, or “economic efficiency by reducing reagent consumption” It is possible to select the third analysis method from the viewpoint of "."

  First, the second analysis method when priority is given to the quickness of the analysis result output will be described below.

  The operator installs in the immune reagent storage unit 14 the reagent bottle 15 containing the reagent for the immunological analysis item and the first reagent necessary for the analysis item based on the immuno-PCR method. In addition, among the reagents necessary for the analysis item based on the immuno-PCR method, the reagent bottle 25 containing the above-mentioned second reagent is installed in the genetic reagent storage unit 24.

  When the analysis is started, in the immunological analysis unit AU1, the two reaction containers 11 are installed at predetermined positions of the constant temperature mechanism 18 by the reaction container transfer mechanism 17, and the sample container 3 is placed in each reaction container by the sample dispensing mechanism 10. The same specimen stored in the is dispensed. Next, the reagent for the immunological analysis item is dispensed into the first reaction container 11, and the reagent for the analysis item based on the immuno-PCR method (the above-mentioned first reagent) is dispensed into the second reaction container. Noted. Each reaction vessel 11 is held in the constant temperature mechanism 18 for a predetermined time, and then a cleaning process is performed in the cleaning mechanism 16.

  Thereafter, the reaction container 11 into which the reagent for the immunological analysis item is dispensed is analyzed by the luminescence detection mechanism 19, and the analysis result of the immunological analysis item is output to the control unit 1.

  If the analysis result of the immunological analysis item is within the measurement range of the immunological analysis item, the analysis of the analysis item based on the immuno-PCR method is canceled. That is, the reagent of the analysis item (the first reagent described above) based on the immuno-PCR method is already dispensed, and the reaction vessel 11 in which the cleaning process in the cleaning mechanism 16 has been performed is discarded.

  On the other hand, when the analysis result of the immunological analysis item is lower than the measurement range of the immunological analysis item, the analysis of the analysis item based on the immuno-PCR method is resumed. That is, the reaction vessel 11 that has already been dispensed with the analysis item reagent (the above-mentioned first reagent) based on the immuno-PCR method as the measurement principle and the washing step in the washing mechanism 16 is performed is the reaction vessel transport mechanism 17. Thus, the sample is transported from the immunological analysis unit AU1 to the sample transport unit 5 and installed in the empty position of the sample rack 2. The reaction container 11 is transported to the gene analysis unit AU2 by the sample transport mechanism 4.

  In the gene analysis unit AU2, the sample dispensing mechanism 20 sucks a predetermined amount of the reaction solution from the reaction container 11 and discharges it to the reaction container 21 installed in the reaction container installation unit 28 by the reaction container installation mechanism 22. Next, the reagent dispensing mechanism 23 sucks a predetermined amount of the above-mentioned second reagent from the reagent bottle 25 installed in the genetic reagent storage unit 24 and discharges it to the reaction container 21. Next, the reaction vessel 21 is installed in the temperature cycle mechanism 30 by the reaction vessel transport mechanism 27 and a predetermined temperature cycle is performed. In addition, the fluorescence detection mechanism 29 detects the amount of fluorescence that depends on the amount of amplified nucleic acid. Then, the number of temperature cycles and the result of the fluorescence measurement value are sent to the control unit 1, and the measurement object contained in the specimen is quantitatively or qualitatively analyzed.

  Therefore, in this second analysis method, when an analysis item based on the immuno-PCR method is required by judging the analysis result of the immunological analysis item, the analysis item based on the immuno-PCR method is determined. It is possible to report the analysis result quickly.

  Next, a third analysis method in the case where economics due to reagent consumption suppression is considered will be described below.

  The operator installs in the immune reagent storage unit 14 the reagent bottle 15 containing the reagent for the immunological analysis item and the first reagent necessary for the analysis item based on the immuno-PCR method. In addition, among the reagents necessary for the analysis item based on the immuno-PCR method, the reagent bottle 25 containing the above-mentioned second reagent is installed in the genetic reagent storage unit 24.

  When the analysis is started, first, only the immunological analysis items are analyzed in the immunological analysis unit AU1. The reaction container 11 is installed at a predetermined position of the constant temperature mechanism 18 by the reaction container transfer mechanism 17, and the sample stored in the sample container 3 is dispensed into the reaction container by the sample dispensing mechanism 10. Here, the sample rack 2 on which the sample housed in the sample container 3 that has been subjected to the sample dispensing is erected is transferred to the buffer unit 6 and waits until a judgment based on the analysis result of the immunological analysis item is presented.

  Next, the reagent of the immunological analysis item is dispensed into the reaction container 11. After the reaction container 11 is held in the constant temperature mechanism 18 for a predetermined time, a cleaning process is performed in the cleaning mechanism 16. Thereafter, the reaction container 11 into which the reagent of the immunological analysis item has been dispensed is analyzed by the luminescence detection mechanism 19, and the analysis result of the immunological analysis item is output to the control unit 1.

  Then, the analysis result of the immunological analysis item is output to the control unit 1, and if this analysis result is within the measurement range of the immunological analysis item, the analysis item analysis request based on the immuno-PCR method is canceled.

  On the other hand, when the analysis result of the immunological analysis item is lower than the measurement range of the immunological analysis item, the analysis of the analysis item based on the immuno-PCR method is started. That is, the sample rack 2 waiting in the buffer unit 6 is transported to the start position of the sample transport unit 4 by the retest transport unit 8. In the immunological analysis unit AU1, the reaction container 11 is placed at a predetermined position of the constant temperature mechanism 18 by the reaction container transfer mechanism 17, and the sample stored in the sample container 3 is dispensed into the reaction container by the sample dispensing mechanism 10. The Next, a reagent for analysis items (the above-mentioned first reagent) based on the immuno-PCR method is dispensed into the reaction vessel 11. After the reaction container 11 is held in the constant temperature mechanism 18 for a predetermined time, a cleaning process is performed in the cleaning mechanism 16.

  The reaction container 11 that has already been dispensed with the analysis item reagent (the first reagent described above) based on the immuno-PCR method and subjected to the washing process in the washing mechanism 16 is immunized by the reaction container transport mechanism 17. The sample is transported from the analysis unit AU1 to the sample transport unit 5 and installed in the empty position of the sample rack 2. The reaction container 11 is transported to the gene analysis unit AU2 by the sample transport mechanism 4.

  In the gene analysis unit AU2, the sample dispensing mechanism 20 sucks a predetermined amount of the reaction solution from the reaction container 11 and discharges it to the reaction container 21 installed in the reaction container installation unit 28 by the reaction container installation mechanism 22. Next, the reagent dispensing mechanism 23 sucks a predetermined amount of the above-mentioned second reagent from the reagent bottle 25 installed in the genetic reagent storage unit 24 and discharges it to the reaction container 21. Next, the reaction vessel 21 is installed in the temperature cycle mechanism 30 by the reaction vessel transport mechanism 27 and a predetermined temperature cycle is performed. In addition, the fluorescence detection mechanism 29 detects the amount of fluorescence that depends on the amount of amplified nucleic acid. Then, the number of temperature cycles and the result of the fluorescence measurement value are sent to the control unit 1, and the measurement object contained in the specimen is quantitatively or qualitatively analyzed.

  Therefore, in the third analysis method, when the analysis item request based on the immuno-PCR method is canceled by the determination of the analysis result of the immunological analysis item, the analysis item based on the immuno-PCR method is determined. It is possible to avoid reagent consumption.

DESCRIPTION OF SYMBOLS 1 ... Control part 2 ... Specimen rack 3 ... Specimen 4 ... Specimen input part 5 ... Specimen conveyance part 6 ... Standby buffer 7 ... Specimen collection part 8 ... Re-examination conveyance part AU1 ... Immune analysis unit 10,20 ... Specimen dispensing mechanism 11, 21 ... Reaction vessel
12, 22 ... Reaction container installation mechanism 13, 23 ... Reagent dispensing mechanism 14 ... Immune reagent storage unit 15 ... Immune reagent bottle 16 ... Washing mechanism 17, 27 ... Reaction container transport mechanism 18 ... Constant temperature mechanism 19 ... Luminescence detection mechanism AU2 ... Gene analysis unit 24 ... gene reagent storage unit 25 ... gene reagent bottle 28 ... reaction container installation unit 29 ... fluorescence detection mechanism 30 ... temperature cycle mechanism

Claims (3)

An immune analysis unit, a gene analysis unit, and a sample transport unit that transports a sample rack holding a sample container from the sample input unit to the immune analysis unit or the gene analysis unit,
The immunoassay unit comprises:
A sample dispensing mechanism for dispensing the sample in the sample container transported by the sample rack to the reaction container installed in the thermostat;
A reagent dispensing mechanism that dispenses a predetermined reagent from a reagent bottle held in an immune reagent storage unit into a reaction container installed in the thermostat;
A cleaning mechanism that magnetically separates the magnetic substance from the reaction solution that has undergone a predetermined time reaction at a predetermined temperature in the thermostatic mechanism;
A luminescence detection mechanism for detecting luminescence of the luminescent label contained in the reaction solution after the washing step by the washing mechanism;
A reaction container transfer mechanism that transfers the reaction container that has finished the cleaning process by the cleaning mechanism to the sample transport unit;
The gene analysis unit includes
A reaction vessel installation mechanism for installing the reaction vessel held in the reaction vessel storage unit in the reaction vessel installation unit;
A sample dispensing mechanism for dispensing the sample in the sample container transported by the sample rack to the reaction container installed in the reaction container installation unit;
A reagent dispensing mechanism that dispenses a predetermined reagent from a reagent bottle held in the genetic reagent storage unit into the reaction container installed in the reaction container installation unit;
A temperature cycle mechanism that repeats a cycle of holding a reaction container in which a sample and a reagent are dispensed at a predetermined temperature for a predetermined time;
Using an automatic analysis system having a fluorescence detection mechanism for detecting fluorescence of a fluorescent label contained in a reaction solution in which a predetermined temperature cycle is repeated by the temperature cycle mechanism,
An automatic analysis method for automatically analyzing the specimen,
A specimen containing a measurement target, a primary antibody that can be bound to the detection target, and a secondary antibody that can be bound to the detection target and labeled with a luminescent substance, held in the immunoreagent storage unit of the immunoassay unit A first reagent comprising,
Using a primer nucleic acid complementary to the target nucleic acid amplification region of the secondary antibody held in the gene reagent storage unit of the gene analysis unit, a nucleic acid extender necessary for nucleic acid amplification, and a second reagent containing a substrate ,
In the immunoassay unit,
In the reaction container installed in the thermostat, the sample is dispensed by the sample dispensing mechanism, the first reagent is dispensed by the reagent dispensing mechanism,
By reacting in the thermostat, a complex in which the primary antibody and the secondary antibody are bound to the detection target is formed,
Unreacted secondary antibody is removed by magnetic separation of the magnetic substance bound to the primary antibody by the washing mechanism,
The solution having been washed is transferred to the sample transport unit by the reaction container transfer mechanism,
The sample transport unit transports the solution after the washing step to the gene analysis unit,
In the gene analysis unit,
The sample dispensing mechanism dispenses the solution after the washing step into a reaction container installed in the reaction container installation unit,
The reagent dispensing mechanism dispenses the second reagent held in the genetic reagent storage unit into a reaction vessel installed in the reaction vessel installation unit,
By the temperature cycle mechanism, the target nucleic acid is amplified by repeating the temperature conditions for thermal denaturation of the target nucleic acid, annealing of the primer nucleic acid to the target nucleic acid, and extension reaction of the primer nucleic acid,
An automatic analysis method characterized in that an analysis item based on the immuno-PCR method is analyzed by detecting fluorescence depending on the amount of amplified nucleic acid by the fluorescence detection mechanism. The automatic analysis method according to claim 1,
In the immunoassay unit, the same sample is dispensed into the first and second reaction vessels,
In the first reaction container, dispense the reagent of the immunological analysis item,
Dispensing the first reagent into the second reaction vessel;
After washing the first and second reaction vessels with the thermostatic mechanism, the first reaction vessel is analyzed with the luminescence detection mechanism,
When the analysis result is lower than the measurement range of the immunological analysis item, the second reaction container is transported to the gene analysis unit by the sample transport mechanism,
An automatic analysis method characterized in that, in the gene analysis unit, an analysis item based on an immuno-PCR method is analyzed using the second reagent. The automatic analysis method according to claim 1,
In the immunoassay unit,
Dispense the sample into the first reaction vessel,
The sample rack in which the sample stored in the sample container after sample dispensing has been installed is transferred to the buffer unit,
In the first reaction container, dispense the reagent of the immunological analysis item,
After washing the first reaction container with the thermostatic mechanism, the first reaction container is analyzed with the luminescence detection mechanism,
When the analysis result is lower than the measurement range of the immunological analysis item, the sample rack waiting in the buffer unit is transported to the start position of the sample transport unit by the retest transport unit, and the immunoassay unit , Dispense the sample into the second reaction vessel,
Dispensing the first reagent into the second reaction vessel;
After the second reaction container is washed by the constant temperature mechanism, it is transported to the gene analysis unit by the sample transport mechanism,
An automatic analysis method characterized in that, in the gene analysis unit, an analysis item based on an immuno-PCR method is analyzed using the second reagent.

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