Abstract:
Herewith disclosed is a sample analyzer comprising: a measurement section configured to perform a measurement on a sample and generate a measurement value according to the concentration of an analyte in the sample; a memory storing a calibration curve; an analysis section; an output section; and an instruction receiver. When the instruction receiver receives an instruction to perform a diluting measurement on a calibration sample, the measurement section dilutes the calibration sample by a predetermined ratio and performs a measurement on the diluted calibration sample, and the analysis section determines the concentration of the analyte in the diluted calibration sample by applying a measurement value obtained from the diluted calibration sample to the calibration curve. Information generated based on the determined concentration and the known concentration is output.

Description:
RELATED APPLICATIONS 
       [0001]    This application is a divisional patent application of U.S. patent application Ser. No. 13/744,904, filed Jan. 18, 2013, which claims priority under 35 U.S.C. §119 to Japanese Patent Application No. 2012-009775 filed on Jan. 20, 2012, the entire content of which is hereby incorporated by reference. 
     
    
     FIELD OF THE INVENTION 
       [0002]    The present invention relates to a sample analyzer capable of diluting and measuring a sample. The present invention also relates to a sample analyzing method. 
       BACKGROUND OF THE INVENTION 
       [0003]    Sample analyzers such as immunoanalyzers determine the concentration of a component to be measured in a sample by applying a measurement value such as the light absorption to a calibration curve that has been prepared beforehand using a standard sample of known concentration. However, when the concentration of the component in the sample to be measured is too high and exceeds the concentration range covered by the calibration curve, it becomes difficult to accurately determine the concentration of the component to be measured even by applying the measurement value to the calibration curve. In this case, the sample is diluted to obtain a concentration that is within the concentration range covered by the calibration curve, so that the concentration of the component in the sample being measured can be determined by applying the measurement value of the diluted sample to the calibration curve. 
         [0004]    Japanese Laid-Open Patent Publication No. 2001-228155 discloses a method of determining antibody or antigen content in serum. According to this method, the concentration of the measurement target component contained in the sample is determined by diluting the sample of unknown concentration by a predetermined factor, applying the measured value of the diluted sample to the calibration curve and converting the measured value to the concentration of the measurement target component in the diluted sample, then multiplying the converted concentration by the dilution ratio in order to obtain the original concentration of the measurement target component contained in the undiluted sample. 
         [0005]    Various sources of error are inherent in the diluting measurement of the sample. For example, there is a very small error between the set dilution ratio and the actual dilution ratio when the apparatus dilutes the sample. Dilution may be repeated for a sample of extremely high concentration, and this error may increase according to the repeated dilutions. Furthermore, affinity between a reagent and a diluting solution may produce variance in linearity of dilution. That is, depending on the affinity of the reagent and the diluting solution, the reagent is not necessarily diluted at desired ratio. 
       SUMMARY OF THE INVENTION 
       [0006]    A first aspect of the present invention is a sample analyzer comprising: a measurement section configured to perform a measurement on a sample and generate a measurement value according to the concentration of an analyte in the sample; a memory storing a calibration curve that defines a relationship of a measurement value and a concentration of the analyte; an analysis section; an output section; and an instruction receiver for receiving an instruction to perform a measurement of a sample, wherein, when the instruction receiver receives an instruction to perform a diluting measurement on a calibration sample that contains a known concentration of the analyte, the measurement section dilutes the calibration sample by mixing a diluting fluid and the calibration sample by a predetermined ratio and performs a measurement on the diluted calibration sample; the analysis section determines the concentration of the analyte in the diluted calibration sample by applying a measurement value obtained from the diluted calibration sample to the calibration curve; and the output section outputs information generated based on the determined concentration and the known concentration. 
         [0007]    A second aspect of the present invention is a sample analyzer comprising: a measurement section configured to perform a measurement on a sample to quantify an analyte in the sample; and a computer; wherein the computer is programmed to perform (A) a calibration operation, and (B) a sample analysis operation, (A) the calibration operation comprising: (A-1) causing the measurement section to perform a measurement on a plurality of calibration samples, each containing an analyte of known concentration; (A-2) causing the measurement section to dilute a calibration sample containing an analyte of known concentration X at a predetermined ratio with a diluting fluid and to perform a measurement on the diluted calibration sample; (A-3) preparing a calibration curve based on the known concentrations of the calibration samples and the measurement results of (A-1); and (A-4) applying the measurement result of (A-2) to the prepared calibration curve to determine a converted concentration X0, (B) the sample analysis operation comprising: (B-1) causing the measurement section to dilute a sample to be measured at a predetermined ratio with a diluting fluid and to perform a measurement on the diluted sample; (B-2) applying the measurement result of (B-1) to the calibration curve prepared to determine a concentration Y0; and (B-3) using the concentration Y0 and the ratio of the known concentration X and the converted concentration X0 to determine the sample concentration Y. 
         [0008]    A third aspect of the present invention is a sample analyzing method comprising the steps of: diluting a calibration sample containing an analyte of known concentration X at a predetermined ratio by mixing with a diluting fluid, and measuring the diluted calibration sample; converting a measurement value of the diluted calibration sample in the computer to a converted concentration X0 by applying the measurement value to a previously prepared calibration curve; diluting a sample to be measured by the predetermined ratio by mixing with a diluting fluid, and measuring the diluted sample; converting a measurement value of the diluted sample to a converted concentration Y0 in the computer by applying the measurement value of the diluted sample to the calibration curve; and determining a concentration Y of the analyte contained in the sample to be measured in the computer by multiplying the concentration Y0 by the ratio of the known concentration X and the converted concentration X0. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0009]      FIG. 1  is a perspective view showing the general structure of an immunoanalyzer as an embodiment of the sample analyzer of the present invention; 
           [0010]      FIG. 2  is a plan view of the immunoanalyzer of  FIG. 1 ; 
           [0011]      FIG. 3  shows the structure of the control device; 
           [0012]      FIG. 4  is a flow chart of the sample measurement when the sample is not diluted; 
           [0013]      FIG. 5  is a flow chart of the sample measurement when the sample is diluted; 
           [0014]      FIG. 6  shows the flows of the calibration curve preparation and the correction coefficient calculation; 
           [0015]      FIG. 7  shows an example of a calibration curve; 
           [0016]      FIG. 8  shows the flow of the concentration conversion of a diluted sample; 
           [0017]      FIG. 9  shows a display example of a display input section; 
           [0018]      FIG. 10  shows an example of a calibration curve preparation request screen; and 
           [0019]      FIG. 11  shows an example of a calibration result screen. 
       
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
       [0020]    The embodiments of the sample analyzer of the present invention are described hereinafter with reference to the accompanying drawings.  FIG. 1  is a perspective view showing the general structure of the immunoanalyzer  1 .  FIG. 2  is a plan view of the immunoanalyzer  1  of  FIG. 1 . The general structure of the immunoanalyzer  1  is first described below. 
       [General Structure of Immunoanalyzer  1 ] 
       [0021]    The immunoanalyzer  1  examines various items such as hepatitis type-B, hepatitis type-C, tumor marker, and thyroid hormone contained in a serum sample (hereinafter referred to simply as “sample”) by utilizing an antigen/antibody reaction. The immunoanalyzer  1  has a measurement section  2 , sample transport section (sampler)  3 , and a control device  4 . The measurement section  2  is communicably connected to the sample transport section  3  and the control device  4  with communication enabled. The sample transport section  3  is configured to transport a rack holding a plurality of test tubes containing sample collected from a subject. The control device  4  has a display input section  410  that includes a touch panel. 
         [0022]    As shown in  FIG. 2 , the measurement section  3  has a sample dispensing arm  5 , R 1  reagent dispensing arm  6 , R 2  reagent dispensing arm  7 , R 3  reagent dispensing arm  8 , reactor  9 , cuvette supplier  10 , primary BF (bound free) separation section  11 , secondary BF separation section  12 , pipette tip supplier  13 , detection section  14 , R 4 /R 5  reagent supplier  15 , reagent installation section  16 , disposal section  17 , and controller  200 . The sample transport section  3  is configured to transport a rack holding a plurality of test tubes containing unprocessed sample. 
         [0023]    At first, the immunoanalyzer  1  mixes the sample to be measured with a buffer solution (R 1  reagent). The immunoanalyzer  1  adds a reagent (R 2  reagent) containing magnetic particles carrying capture antibody for binding to an antigen contained in the sample to the obtained mixture. The immunoanalyzer  1  attracts the magnetic particles in the mixture by a magnet (not shown in the drawing) of the primary BF (bound free) separation section  11  and removes the component that has not been bound to the capture antibody when magnetic particles are attracted. Then the immunoanalyzer  1  adds a labeling antibody (R 3  reagent) to the mixture. The labeling antibody is an antibody carrying an enzymatic marker. After the labeling antibody (R 3  reagent) has been added, the immunoanalyzer  1  attracts the magnetic particles in the mixture by a magnet (not shown in the drawing) of the secondary BF (bound free) separation section  12  and removes the R 3  reagent containing the unreacted labeling antibody from the mixture when the magnetic particles are attracted. The immunoanalyzer  1  then adds a dispersant (R 4  reagent) and a luminescent substrate (R 5  reagent), which luminesces by a reaction with the enzymatic marker carried by the labeling antibody to the mixture. The immunoanalyzer  1  then measures the amount of light produced by the reaction between the marker of the labeling antibody and the luminescent substrate. The antigen contained in the sample bound to the labeling antibody can be quantified through this process. 
         [0024]    The cuvette supplier  10  is configured to accommodate a plurality of cuvettes, and sequentially supplies the cuvettes one by one to the discharge position  1   b  where the sample dispensing arm  5  dispenses a quantity of sample. 
         [0025]    A pipette  6   a  for aspirating and dispensing R 1  reagent is attached to the R 1  reagent dispensing arm  6 . The R 1  reagent dispensing arm  6  aspirates the R 1  reagent in the reagent installation section  16  and dispenses (discharges) the aspirated R 1  reagent to a cuvette placed at the discharge position  1   b  via the pipette  6   a.    
         [0026]    The pipette tip supplier  13  moves a plurality of loaded pipette tips (not shown in the drawing) one by one to the tip installation position (not shown in the drawing). Thereafter, the pipette tip is mounted on the pipette end of the sample dispensing arm  5  at the tip installation position. 
         [0027]    The sample dispensing arm  5  aspirates the sample in the test tube moved to the sample aspirating position  1   a  by the sample transport section  3  using the installed pipette tip. This aspiration is accomplished through a hole  31   a  formed in a cover  31  that covers the transport path of the sample transport section  3 . The sample dispensing arm  5  dispenses (discharges) the aspirated sample into a cuvette at the discharge position  1   b . Prior to discharging the sample to the cuvette, the R 1  reagent was previously dispensed to the cuvette by the R 1  reagent dispensing arm  6 . Thereafter, the cuvette is moved to the reactor  9  by a catcher (not shown in the drawing) of the R 1  reagent dispensing arm  6 . 
         [0028]    A pipette  7   a  for aspirating and discharging R 2  reagent is attached to the R 2  reagent dispensing arm  7 . The R 2  reagent dispensing arm  7  aspirates the R 2  reagent in the reagent installation section  16  and dispenses (discharges) the aspirated R 2  reagent to a cuvette containing the R 1  reagent and the sample. 
         [0029]    The reactor  9  has an annular shape so as to circumscribe the reagent installation section  16 , which is circular, as shown in the drawing. The reactor  9  has a plurality of cuvette holders  9   a  arranged at equal spacing along the exterior. Cuvettes set in the cuvette holders  9   a  are heated to approximately 42 degrees centigrade. Hence, the heating promotes a reaction of the various reagents and the sample in the cuvette. The reactor  9  is configured to be rotatable in a clockwise direction (arrow A 1  direction), and moves the cuvette set in the cuvette holder  9   a  to each processing position where various processes (reagent dispensing and the like) are performed. 
         [0030]    The cuvette containing the sample, R 1  reagent and R 2  reagents is moved by a catcher (not shown in the drawing) from the reactor  9  to the primary BF separation section  11 . Primary BF separation is performed in the primary BF separation section  11 . The component in the sample that has not bonded to the capture antibody (R 2  reagent) is thus removed from the sample within the cuvette. Having completed primary BF separation, the cuvette is returned to the reactor  9  by the catcher (not shown). 
         [0031]    A pipette  8   a  for aspirating and discharging R 3  reagent is attached to the R 3  reagent dispensing arm  8 . The R 3  reagent dispensing arm  8  uses the pipette  8   a  to aspirate the R 3  reagent set at the reagent installation section  16 . The R 3  reagent dispensing arm  8  also uses the pipette  8   a  to dispense (discharge) the aspirated R 3  reagent into the cuvette which was moved from the primary BF separation section  11  to the reactor  9 . 
         [0032]    The cuvette containing the R 3  reagent and the sample is moved from the reactor  9  to the secondary BF separation section  12  by a catcher (not shown in the drawing). Secondary BF separation is performed in the secondary BF separation section  12 . The R 3  reagent including the unreacted labeled antibody is thereby removed. Having completed secondary BF separation, the cuvette is returned to the reactor  9  by the catcher (not shown). 
         [0033]    The R 4 /R 5  reagent supplier  15  sequentially dispenses R 4  and R 5  reagents to the cuvette. 
         [0034]    The reagent installation section  16  holds R 1  reagent, R 2  reagent, and R 3  reagent for each measurement item. The reagent installation section  16  is further provided with a sample diluting fluid (BSA buffer) used to dilute samples when performing diluting measurement of a sample. 
         [0035]    The detection section  14  obtains the amount of light produced during the reaction process between the luminescent substrate (R 5  reagent) and the labeling antibody (R 3  reagent) bonded to the antigen of the ample subjected to predetermined processing with a photomultiplier tube. The detection section  14  transmits the signals corresponding to the amount of light to the controller  200 . 
         [0036]    The disposal section  17  is a section for the disposal of cuvettes and waste fluid within the cuvettes after detection is completed, and the disposal section has an aspiration part (not shown) for aspirating waste fluid within the cuvette, and a disposal hole (not shown). After detection, the cuvette is moved from the detection section  14  to the disposal section  17  by a catcher (not shown), the waste fluid within the cuvette is aspirated by the aspiration part and the cuvette from which the waste fluid has been aspirated is discarded through the disposal hole in the disposal section  17 . 
         [0037]    The controller  200  of the measurement section  2  is configured by a CPU, and a memory section such as a ROM, RAM, hard disk, and controls each part of the measurement section  2  according to the signal received from the main body  400  of the control device  4 . The controller  200  receives the signals sent from the detection section  14 , converts the signals to numerical values, and analyzes the converted measurement values. The controller  200  transmits the analysis results to the main body  400  of the control device  4 . 
       Structure of the Control Device 
       [0038]      FIG. 3  shows the structure of the control device  4  in the immunoanalyzer  1 . The control device  4  is configured by a personal computer that includes a main body  400 , and display/input part  410 . The main body  400  has a CPU  401 , ROM  402 , RAM  403 , hard disk  404 , reading device  405 , I/O interface  406 , image output interface  407 , and communication interface  408 . 
         [0039]    The CPU  401  is capable of loading a computer program stored in the ROM  402  and executing the computer program in the RAM  403 . The RAM  403  is used when reading the computer program stored in the ROM  402  and recorded on the hard disk  404 . The RAM  403  is also used as the work area of the CPU  401  when the CPU  401  executes the computer programs. 
         [0040]    An operating system and application programs, as well as the data used when executing the operating system and application programs that are executed by the CPU  401 , are installed on the hard disk  404 . 
         [0041]    The reader  405  is a CD drive or DVD drive capable of reading computer programs and data recorded on a recording medium. 
         [0042]    The I/O interface  406  receives the signals output from the display/input section  410 . The image output interface  407  outputs image signals corresponding to the image data to the display/input section  410 . The display/input section  410  displays images based on the image signals received from the image output interface  407 , and outputs instructions received from the user through the screen of the display/input section  410  through the I/O interface  406 . 
         [0043]    Note that a keyboard image is displayed for receiving input text on the display/input section  410  when numerical values are input via the display/input section  410 . The user inputs the numerical value by pressing the numbers displayed on the image of the keyboard. 
         [0044]    The communication interface  408  transmits signals from the main body  400  to the controller  200  of the control section  2  on the main body  400  side, and receives signals sent from the controller  200  of the control section  2 . 
         [0000]    [Sample Measurement Flow (without Sample Dilution)] 
         [0045]    An embodiment of the method of measuring component in a sample collected from a subject using the previously mentioned immunoanalyzer  1  is described below. The description pertains to measuring a component in an undiluted sample based on the flow chart shown in  FIG. 4 . 
         [0046]    The controller  200  of the measurement section  2  first receives a measurement start signal from the main body  400  of the control device  4 , and in step S 401  the various drive mechanisms of the sample dispensing arm  5  and the like are placed on standby at the origin position, then the cuvette supplier  10  is actuated to deliver a new cuvette to the discharging position  1   b  of the sample dispensing arm  5 . 
         [0047]    In step S 402 , the controller  200  of the measurement section  2  rotates the R 1  reagent dispensing arm  6  until the tip of the pipette  6   a  of the R 1  reagent dispensing arm  6  is positioned above the R 1  reagent disposed on the reagent installation section  16 , and aspirates a predetermined amount of R 1  reagent using the pipette  6   a . Thereafter, the R 1  reagent dispensing arm  6  is rotated until the tip of the pipette  6   a  is positioned above the cuvette arranged at the discharging position  1   b , and the aspirated R 1  reagent is dispensed into the cuvette. 
         [0048]    In step S 403 , the controller  200  of the measurement section  2  aspirates a predetermined amount of sample in the test tube that has been moved to the sample aspirating position  1   a  by the sample transport section  3  using the pipette tip mounted on the pipette end of the sample dispensing arm  5  at the tip installation position. Thereafter, the sample dispensing arm  5  is rotated until the pipette tip mounted on the pipette end of the sample dispensing arm  5  is positioned above the cuvette disposed at the discharging position  1   b , and the aspirated sample is dispensed into the cuvette. 
         [0049]    In step S 404 , the controller  200  of the measurement section  2  actuates a catcher (not shown in the drawing) of the R 2  reagent dispensing arm  6  to move the cuvette disposed at the discharging position  1   b  to a predetermined cuvette holding section  9   a  of the reactor  9 . 
         [0050]    In step S 405 , the controller  200  of the measurement section  2  rotates the R 2  reagent dispensing arm  7  until the tip of the pipette  7   a  of the R 2  reagent dispensing arm  7  is positioned above the R 2  reagent disposed on the reagent installation section  16 , and aspirates a predetermined amount of R 2  reagent using the pipette  7   a . Thereafter, the R 2  reagent dispensing arm  7  is rotated until the tip of the pipette  7   a  is positioned above the cuvette arranged at the cuvette holding position  9   a , and the aspirated R 2  reagent is dispensed into the cuvette containing the R 1  reagent and sample. 
         [0051]    In step S 406 , the controller  200  of the measurement section  2  actuates a catcher (not shown in the drawing) to move the cuvette containing the sample and R 1  and R 2  reagents from the cuvette holding position  9   a  of the reactor  9  to the primary BF separation section  11 . 
         [0052]    In step S 407 , the controller  200  of the measurement section  2  performs primary BF separation to remove the component in the sample that is not bonded to the capture antibody from the sample in the cuvette. 
         [0053]    In step S 408 , the controller  200  of the measurement section  2  actuates a catcher (not shown in the drawing) to move the cuvette disposed at the primary BF separation section  11  after primary BF separation has been performed to the cuvette holding position  9   a  of the reactor  9 . 
         [0054]    In step S 409 , the controller  200  of the measurement section  2  rotates the R 3  reagent dispensing arm  8  until the tip of the pipette  8   a  of the R 3  reagent dispensing arm  8  is positioned above the R 3  reagent disposed on the reagent installation section  16 , and aspirates a predetermined amount of R 3  reagent using the pipette  8   a . Thereafter, the R 3  reagent dispensing arm  8  is rotated until the tip of the pipette  8   a  is moved to a position above the cuvette arranged at the cuvette holding position  9   a  of the reactor  9 , and the aspirated R 3  reagent is dispensed into the cuvette. 
         [0055]    In step S 410 , the controller  200  of the measurement section  2  actuates a catcher (not shown in the drawing) to move the cuvette containing the dispensed R 3  reagent from the cuvette holding position  9   a  of the reactor  9  to the secondary BF separation section  12 . 
         [0056]    In step S 411 , the controller  200  of the measurement section  2  performs secondary BF separation to remove the R 3  reagent containing the unreacted labeling antibody from the cuvette. 
         [0057]    In step S 412 , the controller  200  of the measurement section  2  actuates a catcher (not shown in the drawing) to move the cuvette disposed at the secondary BF separation section  12  after secondary BF separation has been performed to the cuvette holding position  9   a  of the reactor  9 . 
         [0058]    In step S 413 , the controller  200  of the measurement section  2  actuates a catcher (not shown in the drawing) to move the cuvette from the cuvette holding position  9   a  of the reactor  9  to the R 4 /R 5  reagent supplier  15 . Thereafter, the R 4 /R 5  reagent supplier  15  is actuated to dispense R 4  reagent into the cuvette. 
         [0059]    In step S 414 , the controller  200  of the measurement section  2  actuates a catcher (not shown in the drawing) to move the cuvette disposed at the R 4 /R 5  reagent supplier  15  to the cuvette holding position  9   a  of the reactor  9 . Thereafter, the R 4 /R 5  reagent supplier  15  is actuated to dispense R 5  reagent into the cuvette containing the R 4  reagent. 
         [0060]    In step S 415 , the controller  200  of the measurement section  2  actuates a catcher (not shown in the drawing) to move the cuvette containing the dispensed R 4  and R 5  reagents held at the cuvette holding position  9   a  of the reactor  9  to the detection section  14 . Thereafter, the amount of light produced in the reaction process between the marker of labeling antibody and the luminescent substrate is measured by a photomultiplier tube. The signal corresponding to the measured amount of light is transmitted to the controller  200 , converted to a numerical value and stored in memory. 
         [0061]    In step S 416 , the measured cuvette is moved from the detection section  14  to the disposal section  17  by a catcher (not shown in the drawing), and in the disposal section  17  the sample (waste liquid) remaining in the cuvette is aspirated by the aspirating unit, then the empty cuvette is discarded through the disposal hole of the disposal section  17 . 
       [Sample Measurement Flow (With Sample Dilution)] 
       [0062]    The following description pertains to measuring a component in a sample diluted 40 times based on the flow chart shown in  FIG. 5 . The immunoanalyzer of the present embodiment measures measurement items such as PIC (plasmin inhibitor complex) tumor marker, CEA (carcinoembryonic antigen), AFP (alpha fetoprotein), infection marker HBsAg (hepatitis type B antigen examination), HBsAb (hepatitis type B antibody examination) and the like. These measurement items, and especially for tumor marker, the concentration of the component to be measured is very high in the sample of a positive patient, and the measured values may exceed the range covered by the calibration curve (over range). In such cases, the analyte is diluted prior to measurement to ensure the measured value of the analyte is within the range covered by the calibration curve. The flow of the series of diluting and measuring the analyte is described below based on the flow shown in  FIG. 5 . 
         [0063]    Note that in the embodiment shown in  FIG. 5  steps S 501  through S 506  replace steps S 401  through S 405  of  FIG. 4 , and following step S 506  the same operations or processes are performed as in steps S 404  through S 416  of  FIG. 4 . Therefore, steps S 501  through S 506  specific to the embodiment of  FIG. 5  are described below and the steps S 404  through S 416  duplicated in  FIG. 4  are omitted for the sake of simplicity. 
         [0064]    The controller  200  of the measurement section  2  first receives a measurement start signal from the main body  400  of the control device  4 , and in step S 501  the various drive mechanisms of the sample dispensing arm  5  and the like are placed on standby at the origin position, then the cuvette supplier  10  is actuated to deliver a new cuvette (dilution cuvette) to the discharging position  1   b  of the sample dispensing arm  5 . 
         [0065]    In step S 502 , the controller  200  of the measurement section  2  rotates the R 1  reagent dispensing arm  6  until the tip of the pipette  6   a  of the R 1  reagent dispensing arm  6  is positioned above the sample diluting fluid disposed on the reagent installation section  16 , and aspirates a predetermined amount (for example, 195 μl) of diluting fluid using the pipette  6   a . Thereafter, the R 1  reagent dispensing arm  6  is rotated until the tip of the pipette  6   a  is positioned above the dilution cuvette arranged at the discharging position  1   b , and the aspirated diluting fluid is dispensed into the cuvette. 
         [0066]    In step S 503 , the controller  200  of the measurement section  2  aspirates the sample in the test tube that has been moved to the sample aspirating position  1   a  by the sample transport section  3  using the pipette tip mounted on the pipette end of the sample dispensing arm  5  at the tip installation position. Thereafter, the sample dispensing arm  5  is rotated until the pipette tip mounted on the pipette end of the sample dispensing arm  5  is positioned above the dilution cuvette disposed at the discharging position  1   b , and a predetermined amount (for example 5 μl) of the aspirated sample is dispensed into the dilution cuvette. Thus, the sample is diluted 5/(195+5)=40 times by the diluting fluid. 
         [0067]    In step S 504 , the controller  200  of the measurement section  2  actuates the cuvette supplier  10  and sets a new cuvette (measurement cuvette) at the discharging position  1   b  of the sample dispensing arm  5 . Note that the measurement cuvette and the dilution cuvette are same kind of cuvette and that both are supplied from the cuvette supplier  10 . Although the used dilution cuvette is transported along the same pathway as the measurement cuvette, BF separation, reagent dispensing, and optical measurement processes are fully skipped, and ultimately the dilution cuvette is discarded in the disposal section  17  without optical measurement. 
         [0068]    In step S 505 , the controller  200  of the measurement section  2  rotates the R 1  reagent dispensing arm  6  until the tip of the pipette  6   a  of the R 1  reagent dispensing arm  6  is positioned above the R 1  reagent disposed on the reagent installation section  16 , and aspirates a predetermined amount of R 1  reagent using the pipette  6   a . Thereafter, the R 1  reagent dispensing arm  6  is rotated until the tip of the pipette  6   a  is positioned above the measurement cuvette arranged at the discharging position  1   b , and the aspirated R 1  reagent is dispensed into the measurement cuvette. 
         [0069]    Then, in step S 506 , the controller  200  of the measurement section  2  aspirates the sample that has been diluted 40 fold within the dilution cuvette using the pipette tip mounted on the pipette end of the sample dispensing arm  5 . Thereafter, the sample dispensing arm  5  is rotated until the pipette tip mounted on the pipette end of the sample dispensing arm  5  is positioned above the measurement cuvette disposed at the discharging position  1   b , and a predetermined amount of the aspirated diluted sample is dispensed into the measurement cuvette. 
         [0070]    After step S 506 , steps S 404  through S 416  are performed and the amount of light is measured by the detection section  14 . The signal corresponding to the measured amount of light is transmitted to the controller  200 , converted to a numerical value and stored in memory. The measurement value (numerical value) corresponds to the concentration of the antigen (component) contained in the dilution sample. This value is applied to the calibration curve prepared in a manner described later, to obtain the converted concentration. 
       [Calibration Curve Preparation and Correction Coefficient Calculation] 
       [0071]    In the present embodiment, a calibration curve is prepared using a plurality of calibration samples containing known concentrations of measurement components prior to measuring the concentration of components in a measurement sample. A calibration curve is prepared for each measurement item. For example, a calibration curve is therefore prepared for the HBsAg measurement item using a plurality of calibration samples containing known concentrations of HBsAg, and a calibration curve is also prepared for the PIC measurement item using a plurality of calibration samples containing known concentrations of PIC. Correction coefficients are calculated to be used in the concentration calculation when a dilution sample is measured using the calibration curve. The calibration curve and the correction coefficient are stored in the ROM  202  of the controller  200 . 
         [0072]      FIG. 10  shows an example of a calibration curve preparation request screen shown on the display input section  410 . The calibration curve preparation request screen  100  includes an item selection column A 11 , calibrator selection column A 12 , number input column A 13 , diluting measurement number input column A 14 , OK button A 15 , and cancel button A 16 . The calibration curve preparation request screen  100  functions as an interface for receiving an instruction of a calibration curve preparation from the user to the immunoanalyzer  1 , and also functions as an interface for receiving an instruction of a calibration sample diluting measurement from a user to the immunoanalyzer  1  when a number is entered in the diluting measurement number input column A 14 . 
         [0073]      FIG. 6  shows examples of the flows of the calibration curve preparation and the correction coefficient calculation. The user inputs whether to prepare a calibration curve of a desired measurement item (whether to perform calibration for any measurement item) from the item selection column A 11  in the calibration curve preparation request screen  100  of  FIG. 10 . The item selection column A 11  is a pull-down menu, and displays a plurality of measurement items in a pull down format by clicking the cursor on the column. The user specifies one measurement item from the list. In the example shown in  FIG. 10 , PIC is selected as the measurement item. 
         [0074]    The user then selects the type of calibration sample to prepare the calibration curve from the calibrator selection column A 12 , and checks the check box corresponding to the desired calibration sample. In the example of  FIG. 10 , five calibration samples C 0  through C 4  including measurement component of known concentration are selected. Note that the concentration (hereinafter referred to as “indicated value”) of the measurement component included in calibration samples C 0  through C 4  is m 0  through m 4 , where m 0 &lt;m 1 &lt;m 2 &lt;m 3 &lt;m 4 . The number of calibration samples used when preparing a calibration curve is not limited to five, and may be four or less than four, or six or more than six. The indicated values of calibration samples C 0  through C 4  may be input beforehand by the user entering the value through the display input section  410  beforehand, or input beforehand by reading barcodes attached to the calibration samples C 0  through C 4  via a barcode reader that is not shown in the drawing, then storing the information in the controller  200  of the measurement section  2 . 
         [0075]    The user then inputs the number of measurements for calibration for each of the selected calibration samples C 0  through C 4  from the number input column A 13 . In the example of  FIG. 10 , a number is entered to measure each calibration sample one time. 
         [0076]    The user then choices the calibration sample to be used for diluting measurements among the calibration samples C 0  through C 4 , and determines the number of such measurements. The user enters this information from the diluting measurement number input column A 14 . In the example of  FIG. 10 , C 4  is selected as the calibration sample to be used for diluting measurement, and two is entered as the number of diluting measurements. 
         [0077]    When the above information is entered via the calibration curve preparation request screen  100  and the user selects the OK button A 15 , the input information is stored and calibration begins. When the cancel button A 16  is selected, the entered information is deleted. 
         [0078]    The user sets the calibration samples C 0  through C 4  in a sample rack and sets the sample rack in the sample transport section  3  before calibration. When the sample rack is set and the OK button A 15  is selected on the calibration curve preparation request screen  100 , the measurement section  2  start the measurement of the calibration sample according to the flow shown in  FIG. 6 . 
         [0079]    In step S 601 , the controller  200  of the measurement section  2  sequentially measures the calibration samples C 0  through C 4  according to the previously described steps S 401  through S 415  (refer to  FIG. 4 ), and obtains the measurement values (amount of light) F 0  through F 4 . In the example of  FIG. 10 , each calibration sample is measured once since the measurement number of each calibration sample is [1]. Note that each calibration sample also may be measured several times (for example, three times) to improve the accuracy of the obtained calibration. In such case the measurement value of each calibration sample is the average value of several measurement values obtained by a plurality of measurements. 
         [0080]    In step S 602 , the controller  200  of the measurement section  2  prepares a diluted calibration sample of user-specified calibration sample CX (X is selected from 0 through 4) which contains known concentration (referred as mX). The user-specified calibration sample CX is diluted 40 times. Measurements according to steps S 501  through S 506  and steps S 404  through S 415  (refer to  FIG. 5 ) are performed, and the measurement value FX′ is obtained and stored in memory. Since C 4  is selected as the calibration sample to be used for diluting measurement in the example of  FIG. 10 , a diluted calibration sample is prepared by diluting C 4  by 40 times and measurement is performed on it. 
         [0081]    Although steps S 601  and S 602  are listed as separate steps in the drawing, in the actual measurement flow, step S 602  is performed consecutively to the measurement of the calibration sample corresponding to step S 601 . For example, if the calibration sample C 3  is specified for diluting measurement, the diluting measurement of C 3  is performed following the undiluted measurement of C 3  in step S 601 , and thereafter the measurement of C 4  begins. 
         [0082]    In step S 603 , the controller  200  of the measurement section  2  reads the stored indicated values m 0  through m 4  and prepares the calibration curve such as shown in  FIG. 7  from the read indicated values m 0  through m 4  and the measurement values F 0  through F 4  obtained in step S 601 , then stores the prepared calibration curve together with the lot number of the calibration sample used to prepare the calibration curve in the ROM  202  of the controller  200 . To facilitate understanding, in the example shown in  FIG. 7 , the intersections of the known concentration m and the measured value F are plotted on a straight line, however in an actual case, the plurality of intersections may not be linear. Therefore, approximate algorithms like as the least squares method or the like is used to determine the regressive line and regressive curve as the calibration curve. 
         [0083]    In step S 604 , the controller  200  of the measurement section  2  applies the measurement value FX′ measured in step S 602  to the calibration curve prepared in step S 603  to obtain the converted concentration mX′. When the diluting measurements of a calibration sample have been performed twice or more, the converted concentration mX′ is calculated as the average value of the plurality of converted concentration values. 
         [0084]    In step S 605 , the controller  200  of the measurement section  2  reads the indicated value mX stored in correspondence with the diluting measurement calibration sample CX, calculates the correction coefficient R=mX/mX′ as the concentration ratio from the read indicated value mX and the converted concentration mX′ obtained in step S 604 , and stores the calculated correction coefficient R and the prepared calibration curve in the ROM  202  of the controller  200  in step S 606 . The calculation of the correction coefficient R is illustrated by way of example pertaining to the obtained measurement values shown in Table 1. 
         [0000]    
       
         
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 1 
               
               
                   
               
               
                   
                   
                   
                   
                   
                   
                 Measurement 
                 Converted 
               
               
                   
                   
                   
                   
                   
                   
                 value of diluting 
                 concentration 
               
               
                 Calibration sample 
                 C0 
                 C1 
                 C2 
                 C3 
                 C4 
                 measurement for C4 
                 of diluted C4 
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                 Indicated value 
                 0 
                 0.01 
                 0.1 
                 0.3 
                 1.2 
                   
                   
               
             
          
           
               
                 Measurement 
                 First 
                 523 
                 47,921 
                 496,882 
                 1,499,902 
                 5,537,675 
                 143,763 
                 0.0315 
               
               
                 value (count 
                 measurement 
               
               
                 value) 
                 Second 
                   
                   
                   
                   
                   
                 142,024 
                 0.0313 
               
               
                   
                 measurement 
               
             
          
           
               
                 Average 
                 523 
                 47,921 
                 496,882 
                 1,499,902 
                 5,537,675 
                 142,894 
                 0.0314 
               
               
                   
               
             
          
         
       
     
         [0085]    In this example, the indicated value of the calibration sample C 4  is 1.2, and since the average value of the converted concentration values of the diluted calibration sample C 4  is 0.0314, the dilution correction coefficient R is 38.21 according to the following equation. 
         [0000]      Dilution correction coefficient  R =1.2/0.0314=38.21. 
         [0086]    In step S 607 , the display input section  410  displays a calibration result screen  300  to show the correction coefficient R.  FIG. 11  shows a calibration result screen  300  that appears on the display input section  410 . The calibration result screen  300  has a correction coefficient display column B 11  where the correction coefficient R calculated in step S 605  is displayed. 
         [0087]    In the example of Table 1, the dilution correction coefficient R is 38.21 when the dilution ratio is set at 40 times, hence, in such case the error is 4.3% relative to expected value of 40. If the error from the dilution correction coefficient R displayed in the correction coefficient display column B 11  is calculated and the error is within the acceptable range, the user selects the validate button B 12  on the screen  300  to validate (approve) the calibration curve and the correction coefficient R. 
         [0088]    On the other hand, when the dilution ratio is 40 times and the correction coefficient R is, for example, 30, there is an error of 25% relative to the expected value  40 . In this case several causes should be considered, such as an error due to the quantifying accuracy of the pipette  5   a  of the sample dispensing arm  5  of the measurement section  2  or from the quantifying accuracy of the pipette  6   a  of the R 1  reagent dispensing arm  6 . Or there may be a problem in the diluting ability of the sample diluting fluid, hence, affinity of the sample diluting fluid and the reagent R 1  may not be so good that the dilution linearity is lost. These factors can be mitigated by the user readjusting the dispensing mechanisms to increase the quantifying accuracy, or replacing the sample diluting fluid. 
         [0089]    According to the above embodiment, the user can check whether the measurement section  2  is performing the desired dilution accurately by confirming whether the dilution correction coefficient R is within the desired range on the calibration result screen  300 . 
       [Diluted Sample Measurement and Concentration Conversion] 
       [0090]    Obtaining the concentration of a diluted sample using the calibration curve and correction coefficient determined according to the flow shown in  FIG. 6  is described below referring to the flow chart of  FIG. 8 . Note that in the description of  FIG. 8  the correction coefficient R is the correction coefficient determined at a dilution ratio of 40, and the dilution ratio of the sample is also  40 . 
         [0091]    First, in step S 701 , the controller  200  of the measurement section  2  dilutes a sample by 40 times to prepare a diluted sample according to steps S 501  through S 506  and performs a measurement on the diluted sample according to steps S 404  through S 415  to obtain the measurement value Ft. 
         [0092]    In step S 702 , the controller  200  of the measurement section  2  applies the measured value Ft obtained in step S 701  to the calibration curve prepared in step S 603  and stored in the ROM  202  of the controller  200  to acquire the converted concentration mt. 
         [0093]    In step S 703 , the controller  200  of the measurement section  2  calculates the concentration mt 0  by multiplying the converted concentration mt obtained in step S 702  by the correction coefficient R calculated and stored in the ROM  202  of the controller  200  in step S 605 . 
         [0094]    In step S 704 , the controller  200  of the measurement section  2  transmits the calculated concentration mt 0  to the control device  4 , and the main body  400  of the control device  4  shows the received result (concentration mt 0 ) on the display input section  410 .  FIG. 9  shows a partial example of the display on the display input section  410 . The result (concentration) of each measurement item is displayed in the measurement result column. When the sample has been diluted and measured, the dilution ratio is displayed in the dilution ratio column [1/40] shows that the sample was diluted by 40 times. And [1/1] shows that the sample was not diluted. When a diluting measurement has been performed, the dilution correction column shows whether a concentration calculation has been performed using the correction coefficient R or modified correction coefficient R′ (described later). Mark is displayed when concentration calculation has been performed using the correction coefficient R or the modified correction coefficient R′, and the column remains blank when concentration calculation has not been performed using the correction coefficient R or the modified correction coefficient R′. Whether the concentration calculation is performed using the correction coefficient R or the modified correction coefficient R′ can be specified by the user for each measurement item in a screen (not shown in the drawings) used to specify the start of a sample measurement. 
         [0095]    According to the above embodiment, the user can check whether the measurement section  2  is performing dilution with the desired dilution accuracy by the user confirming whether the dilution correction coefficient R is displayed on the calibration result screen  300  with the post dilution concentration and indicated value as comparative results, and that the dilution correction coefficient R is within the desired range. An accurate sample concentration can be determined by performing the diluting measurement of the sample and confirming the dilution accuracy. 
       Modifications 
       [0096]    Note that the present invention is not limited to the above described embodiment and may be variously modified insofar as such modification are within the scope of the claims. 
         [0097]    In the above embodiment, the dilution ratio (M 1 ) of a sample to be measured and the dilution ration (M 2 ) of the calibration sample used for determining the dilution correction coefficient R is same as 40 times. Even if the dilution ratios of M 1  and M 2  are different, the converted concentration mt 0  of the sample may be calculate as shown below. 
         [0098]    The concentration mt 0  can be calculated by multiplying the converted concentration mt by the modified correction coefficient R′ that derives from the correction coefficient R. The modified correction coefficient R′ may be a coefficient obtained by, multiplying the dilution correction coefficient R by M 1 /M 2 . For example, when the calibration sample dilution ratio (M 2 ) is 40 and the sample dilution ratio (M 1 ) is 80, M 1 /M 2  is 80/40=2. Then, the modified correction coefficient R′ is obtained by doubling the correction coefficient R. 
         [0099]    When the sample dilution ratio is M 2 ×M 2 , the modified correction coefficient R′ is obtained by squaring the correction coefficient R (R 2 ). For example, when the calibration sample dilution ratio is 40 and the sample dilution ratio is 1600, the square of the dilution correction coefficient R is used as the modified correction coefficient R′. 
         [0100]    In the above embodiment the dilution accuracy is evaluated by the user comparing the diluting measurement ratio and the displayed dilution correction coefficient R when the dilution correction coefficient R is shown in the calibration result screen  300 , however, the present invention is not limited to this method. For example, when the calibration sample C 4  indicated value is 1.2 and the average value of the concentration conversion value is calculated as 0.0314 for the diluted calibration sample C 4 , these values may be displayed in comparable manner. Furthermore, the controller  200  may be configured to determine whether the ratio of these values exceeds a predetermined value (for example, the set dilution ratio), and displays the determination result. 
         [0101]    Not only the dilution correction coefficient R, but also the dilution ratio can be displayed in calibration result screen  300 . In a further modification, the dilution correction coefficient R is calculated and the error between the dilution correction coefficient R and the dilution ratio is calculated and displayed on the calibration result screen  300 . In yet another modification, when the calculated error is outside a predetermined range, a warning is shown on the screen, and an audible sound is output to alert the user. 
         [0102]    Although the correction coefficient is calculated using one calibration sample selected by the user from among the plurality of calibration samples used to prepare the calibration curves in the above embodiment, the correction coefficient also may be determined for two or more calibration samples. For example, when the dilution measurements are performed on the calibration samples C 1  through C 3 , the correction coefficients R 1 , R 2 , and R 3  are determined as [32], [35], and [34] respectively. And the dilution ratio is 40. In this case, [33.7] is calculated as the average value of [32], [35], and [34]. This value is set as the correction coefficient R for diluting measurements where the dilution ratio is 40. In another case, for example, a sample is diluted and measured, and the converted concentration value is between the known concentration m 1  of the calibration sample C 1  and the known concentration m 2  of the calibration sample C 2  when the measurement value is applied to the calibration curve. In this case, the average value of the correction coefficient of the calibration sample C 1  [32] and the correction coefficient of the calibration sample C 2  [35] is 33.5 and this value is set as the correction value. Or the correction coefficient [32] is used when the converted concentration value is near m 1 , whereas the correction coefficient [35] is used when the converted concentration value is near m 2 . 
         [0103]    Although the correction coefficient is determined using one calibration sample selected among the calibration samples C 1  through C 4  used to prepare the calibration curve in the above embodiment, the present invention is not limited to this arrangement inasmuch as the correction coefficient also may be determined using a special calibration sample C 5  for determining a correction coefficient. 
         [0104]    Although the correction coefficient obtained from measuring the diluted calibration sample is stored in the memory section ROM  202  in the above embodiment, the correction coefficient not always have to be determined and stored in the memory. The concentrations of components contained in the sample can be calculated on the basis of a first concentration of a diluted sample and a known concentration of a calibration sample, and a second concentration of a diluted calibration sample. That is, when the dilution ratio of the sample is designated M 1  and the dilution ratio of the calibration sample is designated M 2 , the concentration of the component contained in the sample can be calculated as [the first concentration]×(known concentration of calibration sample/second concentration)×(M 1 /M 2 ). 
         [0105]    Although the above embodiment is described only in terms of using the predetermined correction coefficient R to determine the concentration of a sample, a mode for calculating the dilution ratio by multiplication using a conventional method where the dilution ratio is used on behalf of the correction coefficient, and a mode for calculating using a correction coefficient may be selectable. In this case, which mode was used to calculate the concentration is preferably displayed in an identifiable manner on the measurement result display screen as in  FIG. 9 . 
         [0106]    Although the above embodiment pertains to an immunoanalyzer that examines various items such as hepatitis type B, hepatitis type C, tumor marker, and thyroid hormone using a sample such a blood as an example of a sample analyzer, the present invention is not limited to this example inasmuch as the invention is applicable diluting measurement of samples in apparatuses for measuring the concentrations of components in the sample using a calibration curve.