Abstract:
Method for validating the accuracy of automated analyzers by performing an improved dye method procedure that uses at least first and second dye solutions in combination with gravimetric measurement of selected test solutions.

Description:
BACKGROUND 
       [0001]    Automated analyzers, including clinical biochemistry analyzers and other laboratory devices, have been conventionally used for many years. For example, automated clinical biochemistry analyzers are used to perform clinical testing on blood samples. These devices are required to produce results that are validated, and they must calibrated, i.e., re-validated, on a regular basis. 
         [0002]    Such analyzers have been calibrated using “standards” that are composed of the chemical substances present in test serums. However, the problems of accuracy of the calibration can arise, especially in terms of determining absolute values. 
         [0003]    A method for improving the accuracy of the calibration can be accomplished by determining the differences between large numbers of test results using standards performed independently through blind studies conducted by several groups. Although this technique can be used universally, it is still inadequate for use as a method for confirming accuracy, because it is burdensome and time consuming. 
         [0004]    In recent years, the certified accuracy of verification systems and devices has been determined by using analysis results obtained with a standard as true values based on a theoretical system for establishing the authenticity of world standards, and then determining accuracy by using trueness with respect thereto as a requirement for certification, and it is effective to realize validation techniques that coincide with these certification requirements. 
         [0005]    In contrast, a validation technique has been previously proposed that improves calibration accuracy by reducing the effect of evaporation by dispensing an amount of liquid targeted for automated analysis (for example, 1 μl to 1000 μl) as determined according to a standard validation method from a liquid targeted for testing, and validating based on a dye method. 
         [0006]    Validation techniques using dye methods consist of placing a prescribed amount of a reference solution containing a first dye component that absorbs light of a first wavelength in an absorbance detection container, measuring the optical absorbance of that wavelength component, placing a detection solution containing a second dye component that absorbs light of a second wavelength in the reference solution, and then measuring the optical absorbance of that wavelength component. 
         [0007]    Since a comparison of the optical absorbance of the reference solution and the optical absorbance of the detection solution measured in this manner yields a value corresponding to the amount of the detection liquid, the amount of the detection liquid can be validated based on the amount of the reference liquid (based on the specifications of international standard—ISO8655-part 7). 
         [0008]    Validation accuracy can be established for the elements used to determine accuracy of blood analysis results obtained by this dye method by firstly validating the light path length of the cell used for optical analyses, secondly validating the accuracy of dispensing of reaction reagents, thirdly validating the dispensing accuracy of biological specimens (blood), and fourthly validating high-temperature accuracy of the reaction layer. 
       SUMMARY 
       [0009]    The embodiments generally relate to methods for validating and/or calibrating with a high degree of accuracy automated analyzers having liquid dispensers. The present methods for validating the accuracy of automated analyzers are directed to performing an improved dye method validation procedure that uses at least a first dye solution and second dye solution in a target test liquid, measuring at the weight of the second dye solution, performing a first and second optical analysis on the target test liquid, and performing a computational analysis that determines any deviation between and among the first and second optical analyses and the weight measurement for the second dye solution. 
         [0010]    In one embodiment of the present method includes the steps of designating as a validation target an automated analyzer that sequentially carries out automated analyses by dispensing an automated analysis target liquid into a plurality of optical analysis cells by an analysis target liquid filling unit and sequentially filling a first dye solution dispensed from a first liquid holding unit into the plurality of optical analysis cells by using the analysis target liquid filling unit. Then, dispensing a second dye solution from a second liquid holding unit by using a diluent dispensing pipetter, and weighing, on the basis of a gravimetric method, a total weight of the diluent dispensing pipetter with the second dye solution using a diluent weighing unit, and pipetting the second dye solution into the optical analysis cells filled with the first dye solution. Measuring a target liquid in the optical analysis cells comprising the first and second dye solutions by an optical absorbance detection unit, based on a dye method, in order to determine the amount of liquid of the first dye solution as a target liquid volume measurement result, weighing, based on the gravimetric method, the diluent dispensing pipetter after pipetting the second dye solution by a pipetter weighing unit, and transferring the target liquid from the optical analysis cells to a reference value measurement unit by using a transfer pipetter and measuring, based on the dye method, to determine by an second optical absorbance detection unit the amount of the first dye solution as a reference liquid volume measurement result. Finally, validating the dispensing accuracy of the analysis target liquid dispensing unit of the automated analyzer by computing any deviation between and among the reference liquid volume measurement result and the target liquid volume measurement result and the measurement results of the pipetter weighing unit and the diluent weighing unit determined based on the gravimetric method. 
         [0011]    In another embodiment of the present method includes the steps of designating as a validation target an automated analyzer that sequentially carries out automated analyses by dispensing an automated analysis target liquid into a plurality of optical analysis cells by a first and second analysis target liquid filling units, and sequentially filling a first dye solution into the plurality of optical analysis cells by dispensing from a first liquid holding unit by using the first analysis target liquid filling unit. Then, dispensing a second dye solution from a second liquid holding unit by using a diluent dispensing pipette, and weighing the diluent dispensing pipetter with the second dye solution using a diluent weighing unit, and pipetting the second dye solution into the optical analysis cells filled with the first dye solution. In addition, placing a third dye solution into the optical analysis cells containing the first and second dye solutions, dispensed from a third liquid holding unit, using the second analysis target liquid filling unit. Measuring a target liquid in the optical analysis cells comprising the first, second and third dye solutions by an optical absorbance detection unit, based on a dye method, to determine an amount of the first dye solution as a target liquid volume measurement result, and weighing the diluent dispensing pipetter after pipetting the second dye solution by a pipetter weighing unit, and transferring the target liquid from the optical analysis cells to a reference value measurement unit by using a transfer pipetter and measuring, based on the dye method, to determine by an second optical absorbance detection unit the amount of the first dye solution as a reference liquid volume measurement result. Finally, validating the dispensing accuracy of the analysis target liquid dispensing unit of the automated analyzer by computing any deviation between and among the reference liquid volume measurement result and the target liquid volume measurement result and the measurement results of the pipetter weighing unit and the diluent weighing unit determined based on the gravimetric method. 
         [0012]    According to the present method, the accuracy of validation results for an automated analyzer can be improved by determining the amount of a validation target liquid based on measurement of the amount of a reference liquid with respect to the amount of the validation target liquid based on measurement of a target liquid by a dye method using first and second retroactive dye solutions, using a target value measurement result according to a gravimetric method. 
         [0013]    These and other objects, along with advantages and features of the present invention herein disclosed, will become apparent through reference to the following description and the accompanying drawings. Furthermore, it is understood that the features of the various embodiments described herein are not mutually exclusive and can exist in various combinations and permutations. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0014]      FIG. 1  is a schematic system diagram showing an embodiment of the present method. 
           [0015]      FIG. 2  is a typical absorbance curve results of the present method. 
           [0016]      FIG. 3  is a schematic system diagram showing the configuration of the second optical absorbance detection unit and a reference value measurement microplate. 
           [0017]      FIG. 4  is a typical graphical representation of the validation/calibration results of the present method. 
           [0018]      FIG. 5  is a schematic system diagram showing a second embodiment of the present method. 
       
    
    
     DESCRIPTION 
       [0019]    A clinical biochemistry automated analyzer RO, which is the validation target of the automated analyzer validation device  1 , holds sample blood serving as an analysis target in sample cups  19  on a sample rack  16 , dispenses a small prescribed amount of the sample blood from each of the sample cups  19  with a dispensing tube  18  that rotates in the direction indicated by arrow c in a sample filling unit  17  that composes a first analysis target filling unit, and fills the sample blood into optical analysis cells  2 . 
         [0020]    In addition, the clinical biochemistry automated analyzer RO holds a sample reagent, which develops a red color by reacting with a serum component to be analyzed at normal temperature, in a reagent bottle  14  on a reagent rack  11 , dispenses a small prescribed amount of the reagent with a dispensing tube  13  that rotates in the direction indicated by arrow b in a reagent filling unit  12  that composes a second analysis target filling unit, and fills the reagent into the optical analysis cells  2 . 
         [0021]    A plurality of the optical analysis cells  2  are sequentially arranged along a peripheral edge  3 A of a turntable  3  that rotates intermittently in the direction indicated by arrow a, and as a result thereof, when the dispensing tubes  18  and  13  of the sample filling unit  17  and the reagent filling unit  12  have rotated to a prescribed filling position, each of the optical analysis cells  2  is sequentially filled with the sample blood and the coloring reagent. 
         [0022]    Thus, the clinical biochemistry automated analyzer RO serving as the validation target of the automated analyzer validation device  1  is able to automatically analyze sample blood dispensed from the plurality of sample cups  19 A based on a chemical component contained in the serum thereof reacting in the optical analysis cells  2 . 
         [0023]    In  FIG. 1 , during a typical automated analysis operation, the automatic analyzer validation device  1  fills a dye solution having a first dye (red) serving as the sample liquid  19 A into the sample cups  19  serving as liquid retention portions that hold the sample blood when validating the clinical biochemistry automated analyzer RO serving as the validation target. 
         [0024]    As a result, the automated analyzer validation device  1  in the case of  FIG. 1  validates the amount dispensed by the sample dispensing unit  17 . 
         [0025]    In the automated analyzer validation device  1 , when the turntable  3  of the clinical biochemistry automated analyzer RO has been rotated intermittently in the direction indicated by arrow a, the optical analysis cells  2  are sequentially positioned at a reagent filling position P 1 , a sample filling position P 2 , a diluent filling position P 3  and a target measuring position P 4 . 
         [0026]    When an optical analysis cell  2  has been positioned at the sample filling position P 2 , the automated analyzer validation device  1  dispenses a prescribed amount of the sample liquid  19 A from the plurality of sample cups  19  with the dispensing tube  18  of the sample filling unit  17  provided on the sample rack  16  and fills the sample liquid  19 A into the optical analysis cell  2 . 
         [0027]    Incidentally, the amount dispensed by the sample filling unit  17  at this time is equal to the amount of sample blood dispensed when the clinical biochemistry automated analyzer RO performs automated analysis. 
         [0028]    The sample filling unit  17  aspirates the sample liquid  19 A from the plurality of sample cups  19  arranged in a row on the sample rack  16 , and as indicated by arrow c, rotates the dispensing tube  18  from the position of the sample cups  19  to the sample filling position P 2  and fills the aspirated sample liquid  19 A into the optical analysis cells  2  followed by returning the dispensing tube  18  to its original position of the sample cups  19 . 
         [0029]    In the case of this embodiment, a first dye solution is used for the sample liquid  19 A that demonstrates the optical characteristic of absorbing an optical component having a wavelength of 520 nm due to a first red dye. 
         [0030]    This first dye solution is a dye solution that contains a known error with respect to the red dye solution defined in the previously mentioned international standard ISO8655-7, and is referred to as a “retroactive first dye solution” since this characteristic can be made to be retroactive to the above-mentioned standard in consideration of this “known error”. 
         [0031]    The automated analyzer validation device  1  is made to fill a diluent  23 A from the diluent dispensing pipetter  21  when the optical analysis cells  2  have been positioned at the diluent filling position P 3 . 
         [0032]    Dispensing work performed by the diluent dispensing pipetter  21  is carried out manually by an analysis technician of the clinical biochemistry automated analyzer RO. 
         [0033]    During this dispensing work, a dispensing technician operates the diluent dispensing pipetter  21  and first aspirates a prescribed amount of a diluent  23 A from a diluent bottle  23  serving as a liquid holding portion arranged on a diluent rack  22 . 
         [0034]    In the case of this embodiment, a second dye solution is used for the diluent  23 A that demonstrates the optical characteristic of absorbing an optical component having a wavelength of 730 nm due to a second blue dye. 
         [0035]    This second dye solution is a dye solution that contains a known error with respect to the blue dye solution defined in the previously mentioned international standard ISO8655-7, and is referred to as a “retroactive second dye solution” since this characteristic can be made to be retroactive to the above-mentioned standard in consideration of this “known error”. 
         [0036]    When an optical analysis cell  2  has reached the target measuring position P 4  as a result of rotation of the turntable  3 , the automated analyzer validation device  1  detects the optical absorbance of a measurement target liquid  26  contained in the optical analysis cell  2  with an optical absorbance detection unit  25 , and transmits an optical absorbance detection signal S 1  to a target measurement result processing unit  27  having the configuration of a microcomputer. 
         [0037]    In this embodiment, the optical absorbance detection unit  25  comprises a detecting light L 1  emitted from a white light source  25 A being passed through the optical analysis cell  2 , the optical absorbance detection unit  25  extracts a light component of a prescribed measurement wavelength range with a filter  25 B and allows the light to enter a photoelectric converter  25 C. 
         [0038]    As a result, the detecting light L 1  enters the filter  25 B after the optical component of a wavelength corresponding to the optical absorbance characteristics of the dye present in a measurement target liquid  26  has been absorbed as a result of passing through the measurement target liquid  26 . 
         [0039]    In this embodiment, the measurement target liquid  26  contains a 520 nm wavelength component possessed by the red dye solution  19 A filled into the optical analysis cells  2  at the sample filling position P 2 , and a 730 nm wavelength component possessed by the blue dye solution  23 A filled at the diluent filling position P 3 . 
         [0040]    Thus, the wavelength components of the measurement target liquid  26  in the optical analysis cells  2  at the target measuring position P 4  are absorbed in accordance with the optical absorbance curve K 1  shown in  FIG. 2  for the 520 nm and 730 nm wavelength components. 
         [0041]    As a result, in the optical absorbance detection unit  25 , by calculating the following by the target measurement result processing unit  27  based on the ratio of the optical absorbance of the two wavelength components: 
         [0000]    
       
         
           
             
               
                 
                   
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         [0042]    V S =volume of red dye solution 
         [0043]    V B =volume of blue dye solution 
         [0044]    A S =optical absorbance of red dye solution (520 nm) 
         [0045]    A B =optical absorbance of blue dye solution (730 nm) 
         [0046]    K=correction value determined at time of shipment from factory 
         [0000]    the dispensed amount of the test liquid  19 A in the form of the red dye solution can be determined based on the dispensed amount of the diluent  23 A in the form of the blue dye solution. 
         [0047]    Here, formula (I) is specified as a liquid volume measurement method, based on the dye method according to international standard ISO8655-7, and indicates that the amount of the sample liquid  19 A dispensed by the dispensing tube  18 , namely the volume V S  of the sample liquid  19 A, can be determined as a value obtained by multiplying the ratio of the optical absorbance A S  of the sample liquid  19 A in the form of the red dye solution to the optical absorbance A B  of the diluent  23 A by the dispensed amount of the diluent in the form of the blue dye solution by the diluent dispensing pipetter  21 , namely the volume V B  of the diluent  23 A. 
         [0048]    In addition, since the ratio of the optical absorbance A S  of the sample liquid  19 A to the optical absorbance A B  of the diluent  23 A represents the degree of dilution of the sample liquid  19 A relative to the diluent  23 A, this indicates that the injection volume V S  of the sample liquid  19 A can be determined as the ratio of the injection volume of the sample liquid  19 A to the volume of the diluent  23 A contained in the optical analysis cells  2 . 
         [0049]    In this manner, the optical absorbance detection unit  25  and the target measurement result processing unit  27  compose a target liquid volume measurement unit for the measurement target liquid  26  in the optical analysis cells  2  at the target measuring position P 4 . 
         [0050]    As indicated by arrow d, the entire volume of the measurement target liquid  26  filled into the optical analysis cells  2  at the target measuring position P 4  is removed as a measurement target transfer liquid  26 A by a dispensing technician using the transfer pipetter  30 , and transferred to a reference value measurement microplate  32  on a reference value rack  31 . 
         [0051]    The entire volume of the measurement target liquid  26  is aspirated from the optical analysis cells  2  with the transfer pipetter  30  during manual work performed by a dispensing technician in the same manner as previously described with respect to the diluent dispensing pipetter  21 , and the measurement target liquid  26  is transferred to one of a plurality of retention grooves  33  provided in the reference value measurement microplate  32 . 
         [0052]    In addition to having the configuration previously described, the validation device  1  is provided with a balance  40 A that composes the diluent weighing unit  40  on the diluent rack  22 . 
         [0053]    The balance  40 A of the diluent weighing unit  40  weighs the total weight of the diluent dispensing pipetter  21  and the diluent  23 A contained therein as a result of a dispensing technician dispensing the diluent  23 A from the diluent bottle  23  using the diluent dispensing pipetter  21 , and placing on the balance  40 A that composes the diluent weighing unit  40 . 
         [0054]    In addition to recording the result W 1  of weighing in the diluent weighing unit  40 , the dispensing technician fills the diluent  23 A by transporting the diluent dispensing pipetter  21  retaining the dispensing liquid  23 A to the optical analysis cells  2  at the diluent filling position P 3 . 
         [0055]    Following this dispensing work, an operator executing diluent operation places the diluent dispensing pipetter  21  that has currently been used on a balance  46 A that composes the pipetter weighing unit  46  provided on a pipetter rack  45  for a weight result W 2 . It is within the scope of the present method to use weighing unit  46  to obtain this weight measurement for the empty pipette  21 . 
         [0056]    At this time, the pipetter weighing unit  46  determines the weight of the diluent dispensing pipetter  21  per se after having emptied the diluent  23 A into optical analysis cell  2 , and the dispensing technician records the result of that weighing. 
         [0057]    In this manner, the weight of the diluent  23 A filled into the optical analysis cells  2  by the dispensing technician at the diluent filling position P 3 , and thus the amount of the diluent  23 A dispensed by the diluent dispensing pipetter  21 , can be determined by a gravimetric method by comparing the weighing result obtained from the diluent weighing unit  40  and the weighing result obtained from the pipetter weighing unit  46 . 
         [0058]    As shown in  FIG. 3 , a second optical absorbance detection unit  41  is used to measure the amount of the measurement target transfer liquid  26 A placed in the retention grooves  33  of the reference value measurement microplate  32  using a dye method as a highly accurate reference value. 
         [0059]    The optical absorbance detection unit  41  has a white light source  41 A that emits a white light L 2 , and causes the white light L 2  to enter a photoelectric converter  41 C with respect to a filter  41 B after having passed through the measurement target transfer liquid  26 A. 
         [0060]    Here, as was previously described with respect to  FIG. 2 , the measurement target transfer liquid  26 A has optical absorbance characteristics such that a blue dye component of a wavelength of 730 nm of the diluent  23  and a red dye component of a wavelength of 520 nm of the sample liquid  19 A are absorbed as represented by the optical absorbance curve K 1 , and the filter  41 B extracts light of a wavelength range that includes these dye components followed by the light entering the photoelectric converter  41 C. 
         [0061]    The photoelectric converter  41 C is configured so as to arithmetically process the above-mentioned formula (1) at high accuracy, including known error (thus, making it retroactive), based on the specifications of the previously described international standard ISO8655-7, and as a result, an optical absorbance detection signal S 2  obtained from the photoelectric converter  41 C is transmitted to a reference measurement result processing unit  44  having the configuration of a microcomputer as a reference value representing the volume of the sample liquid  19 A contained in the measurement target transfer liquid  26 A at a high level of accuracy that is close to that of the measurement result obtained with a standard equivalent to the device of the aforementioned international standard. 
         [0062]    In this manner, the reference measurement result processing unit  44  retains the measurement result of the volume of the sample liquid  19 A contained in the measurement target transfer liquid  26 A with high accuracy as a reference value. 
         [0063]    The optical absorbance detection unit  41  determines measured values for reference values in this manner for the measurement target transfer liquid  26 A retained in all of the retention grooves  33  of the reference value measurement microplate  32 , and accumulates those measured values in the reference measurement result processing unit  44 . 
         [0064]    The reference value measurement result accumulated in the reference measurement result processing unit  44  of the reference value judgment unit  32  is transmitted to the dispensing accuracy judgment unit  47 A of the validation result processing unit  47  as a reference liquid volume signal S 21 . 
         [0065]    The dispensing accuracy judgment unit  47 A determines a difference between the target liquid volume signal S 11  obtained from the target measurement result processing unit  27  ( FIG. 1 ) and the reference liquid volume signal S 21  obtained from the reference value measurement result processing unit  44 , and validation result processing unit  47  confirms the amount dispensed by the diluent dispensing pipetter  21  using a gravimetric method based on the weighing results W 1  and W 2  of the diluent weighing unit  40  and the pipetter weighing unit  46 , respectively, as a validation result that expresses the measuring limit (uncertainty) of the clinical biochemistry automated analyzer RO serving as the validation target. 
         [0066]    It is within the scope of the present method to have the target measurement result processing unit  27 , the reference value measurement result processing unit  44  and the validation result processing unit  47  be a single microprocessor or computer or be distributed as shown. 
         [0067]    As shown in  FIG. 4 , in addition to plotting a coefficient of variation K 1  within the range of 0% to 3.0% on the horizontal axis, by further plotting a degree of accuracy K 2  within the range of −0.03 to +0.03 on the vertical axis, this validation result can be expressed according to whether or not the dispensing accuracy for the amount of the sample liquid  19 A dispensed from the sample cups  19  by the sample filling unit  17  lies within a dispensing accuracy curve DT. 
         [0068]    Here, the coefficient of variation K 1  represents the degree of variation of the validation result, while the degree of accuracy K 2  is equal to 0 when the validated dispensing amount is the true value, and the degree of variation from the true value K 2 =0 is represented as K 2 +0.01, +0.02 . . . or −0.01, −0.02 . . . . 
         [0069]    In this manner, when a validation result is within an area demarcated by the dispensing accuracy curve DT that passes through a target coefficient of variation K 1 =0 to K=10 and a target degree of accuracy K 2 =+K 20  to −K 20 , the dispensing accuracy of the automated analyzer serving as the validation target is validated to be within the allowed range. 
         [0070]    The method provides an automated analyzer RO is the validation target that sequentially carries out automated analyses by dispensing an automated analysis target liquid  19 A into a plurality of optical analysis cells  2  by way of sample filling unit  17 . A first dye solution  19 A is sequentially filled into the plurality of optical analysis cells  2  dispensing from a first liquid holding unit  19 , and together with dispensing a second dye solution  23 A from a second liquid holding unit  23  through the use of a diluent dispensing pipetter  21 . The total weight of the diluent dispensing pipetter  21  in the dispensing state, i.e., with the dye solution, is obtained, based on a gravimetric method, using a diluent weighing unit  40 . The second dye solution  23 A is dispensed into the optical analysis cells  2  which is already filled with the first dye solution  19 A. 
         [0071]    Thereafter, determining the amounts of liquid in the optical analysis cells  2  filled with the first and second dye solutions  19 A and  23 A by using an optical absorbance detection unit  25  (based on a dye method) to determine a target measured value, weighing the emptied diluent dispensing pipetter  21  (after having been filled with the second dye solution  23 A) using a pipetter weighing unit  46 , based on a gravimetric method. Transferring the contents of the optical analysis cells  2  filled with the first and second dye solutions  19 A and  23 A to a reference value measurement microplate  32  using a transfer pipetter  30  and measuring (based on a dye method) using a second optical absorbance detection unit  43  to obtain a reference measured value. Performing a computational analysis using all of the measured results obtained by the present method to validate the dispensing accuracy of the sample filling unit  17  of the automated analyzer RO by determining any deviation between and among the reference measured value and the target measured value determined based on a dye method and the deviation between measurement results of the pipetter weighing unit  46  and the diluent weighing unit  40  determined based on a gravimetric method. 
         [0072]    In  FIG. 5 , another embodiment of the present method, the same reference symbols are used to indicate those elements and features corresponding to  FIG. 1 . 
         [0073]    The automated analyzer validation device  1 X of  FIG. 5  differs from the automated analyzer validation device  1  of  FIG. 1  in that, in contrast to the automated analyzer validation device  1  of  FIG. 1  (directed to determining the dispensed amount of the sample liquid  19 A that is a red dye solution based on the dispensed amount of the diluent  23 A that is blue dye solution using a dye method), the validation device  1 X of  FIG. 5  determines the dispensed amount of a reagent solution  14 A that is a red dye solution based on the dispensed amount of the diluent  23 A and the sample liquid  19 B that are blue dye solutions. 
         [0074]    Namely, in the case of  FIG. 5 , the reagent solution  14 A dispensed from the reagent bottle  14  is filled into optical analysis cells  2  on the turntable  3  by a reagent filling unit  12  at a reagent filling position P 11 . 
         [0075]    In this case, a first dye solution demonstrating the optical characteristic of absorbing an optical component having a wavelength of 520 nm due to the first red dye solution is used for the reagent solution  14 A. 
         [0076]    Continuing, the diluent  23 A manually dispensed from the diluent bottle  23  by a dispensing technician is filled into the optical analysis cells  2  by the diluent dispensing pipetter  21  at a diluent filling position P 12 . 
         [0077]    In this case, a second dye solution demonstrating the optical characteristic of absorbing an optical component having a wavelength of 730 nm due to the second blue dye is used for the diluent  23 A. 
         [0078]    Here, prior to filling the diluent  23 A at the diluent filling position P 12 , the diluent dispensing pipetter  21  in the state of having dispensed the diluent  23 A is placed on the balance  40 A that composes the diluent weighing unit  40  and the total weight thereof is weighed. 
         [0079]    After having filled the diluent  23 A, the diluent dispensing pipetter  21  is placed on the balance  46 A that composes the pipetter weighing unit  46  and the weight of the pipetter  21  per se is weighed. 
         [0080]    Continuing, the sample liquid  19 B dispensed from the sample cups  19  by the sample filling unit  17  is filled into the optical analysis cells  2  at a sample filling position P 13 . 
         [0081]    In this case, a third dye solution demonstrating the optical characteristic of absorbing optical components having a wavelength of 730 nm due to the second blue dye in the same manner as the above-mentioned diluent  23 A is used for the sample liquid  19 B. 
         [0082]    Continuing, the optical absorbance of the measurement target liquid  26  in the optical analysis cells  2  is detected by the optical absorbance detection unit  25  at a measurement target position P 14 . 
         [0083]    Accompanying this, the entire volume of liquid filled into the optical analysis cells  2  is transferred to a reference value judgment pallet  32  of the reference value judgment unit  32  by the transfer pipetter  30  at the target measuring position P 14  as indicated by arrow d. 
         [0084]    In the configuration of  FIG. 5 , when an optical analysis cell  2  has been brought to the reagent filling position P 11  by the turntable  3 , the validation device  1 X dispenses a first dye solution in the form of the reagent solution  14 A from the reagent bottle  14  with the dispensing tube  13  of the reagent filling unit  12  and fills the optical analysis cell  2 . 
         [0085]    Continuing, after the second dye solution in the form of the diluent dispensed by the diluent dispensing pipetter  21  from the diluent bottle  23  by a dispensing technician has been filled into the optical analysis cells  2  filled with the reagent solution  23 A at the diluent filling position P 12 , the detection device  1 X fills the third dye solution in the form of the sample liquid dispensed from the sample cups  19  by the sample filling unit  17  into the optical analysis cells  2  at the sample filling position P 13 . 
         [0086]    In this manner, as a result of the red first dye solution of the first dye filled at the reagent filling position P 11 , the blue second dye solution of the second dye filled from the diluent dispensing pipetter  21  at the diluent filling position P 12 , and the blue third dye solution of the second dye filed by the sample filling unit  17  at the sample filling position P 13  being mixed in the optical analysis cells  2 , the optical absorbance detection unit  25  detects optical absorbance at the measurement target position P 14  by using this mixture as the measurement target liquid  26 . 
         [0087]    At this time, the optical absorbance detection unit  25  determines the volume of the red reagent solution  14 A serving as the first dye based on the ratio between the optical absorbance of the reagent solution  14 A serving as the red wavelength component of the first dye and the optical absorbance of the diluent solution  23 A and the sample liquid  19 B serving as blue wavelength components of the second dye in accordance with the above-mentioned formula (I) using a dye method based on the specifications of ISO8655-7, and accumulates that volume in the target measurement result processing unit  27 . 
         [0088]    Here, in conjunction with the liquid volume of the second dye (blue), although error occurs in the liquid volume of the first dye (red) in the above-mentioned formula (I) due to the sample liquid  19 B having been filled into the diluent  23 A, if the amount of the diluent  23 A (namely, the second dye solution) that composes the liquid volume of the second dye (blue) is known and the amount of the sample liquid  19 B (namely, the third dye solution) is known, then the amount of the reagent solution  14 A of the first dye (namely, the first dye solution) can be determined with high accuracy with little effect of evaporation in the dye method. 
         [0089]    When this is done, in the case of  FIG. 5  as well, in addition to weighing the total weight, including the diluent  23 A dispensed from the diluent bottle  23  by the diluent dispensing pipetter  21  in the diluent weighing unit  40 , a dispensing technician also weighs the weight of the diluent dispensing pipetter  21  after having filled the diluent  23 A at the diluent filling position P 12  in the pipetter weighing unit  46 . 
         [0090]    In this manner, the amount of the diluent  23 A dispensed by the diluent dispensing pipetter  21  can be confirmed by a gravimetric method according to the difference between the weighing result of the diluent weighing unit  40  and the weighing result of the pipetter weighing unit  46 . 
         [0091]    In addition, the dispensed amount of the measurement target transfer liquid  26 A transferred to the retaining grooves  33  of the reference value measurement microplate  32  by the transfer pipetter  30  is determined as a highly accurate reference value corresponding to a standard based on the dye method by the reference value judgment microplate  32  of  FIG. 3 . 
         [0092]    This reference value judgment result represents the dispensed amount of the red component contained in the measurement target transfer liquid  26 A transferred by the transfer pipetter  30 , namely the dispensed amount of the reagent solution  14 A of the first dye solution dispensed from the reagent bottle  14  by the reagent filling unit  12 , and this is accumulated in the reference value judgment result processing unit  44  of the reference value judgment microplate  32 . 
         [0093]    In this manner, the validation result processing unit  47  of the reference value judgment microplate  32  is able to determine a dispensing accuracy curve DT as previously described with respect to  FIG. 4  by comparing and judging the target liquid volume signal S 11  obtained from the target measurement result processing unit  27  and the reference liquid volume signal S 21  obtained from the reference value measurement result processing unit  44 . 
         [0094]    As a result, the validation device  1 X of  FIG. 5  is able to validate the dispensing accuracy of the reagent filling unit  12  of the clinical biochemistry automated analyzer RO serving as the validation target based on the resulting dispensing accuracy curve DT. 
         [0095]    In this manner, the liquid volume of the blue dye component can be measured according to a gravimetric method based on the weighing result of the diluent weighing unit  40  and the weighing result determined by the pipetter weighing unit  46 , and this can be confirmed based on a gravimetric method as the liquid volume V B  of the blue dye liquid in the arithmetic processing of the aforementioned formula (1) based on a dye method, thereby making it possible to even more reliably confirm certainty with respect to results of measuring the dispensed amount of the red component. 
         [0096]    Incidentally, if the amount of the reagent solution  14 A dispensed by the reagent filling unit  12  is determined according to a dye method using the configuration shown in  FIG. 5  after having determined the amount of the sample liquid  19 B dispensed by the sample filling unit  17  according to a dye method using the validation device  1  having the configuration shown in  FIG. 1 , validation of the dispensed amount of the sample filling unit  17  used to dispense blood and validation of the dispensed amount of the reagent filling unit  12  used to dispense a coloring reagent, which are both important elements of analysis results in the clinical biochemistry automated analyzer RO, can be carried out with high accuracy. 
         [0097]    The method of  FIG. 5  provides an automated analyzer RO is the validation target that sequentially carries out automated analyses by respectively dispensing an automated analysis target liquid  14 A into a plurality of optical analysis cells  2  by first and second analysis target liquid filling units  12  and  17 . A first dye solution  14 A is sequentially filled into the plurality of optical analysis cells  2  by dispensing from a first liquid holding unit  14  by using the first analysis target liquid filling unit  12 , and together with dispensing a second dye solution  23 A from a second liquid holding unit  23  using a diluent dispensing pipetter  21 , the total weight of the diluent dispensing pipetter  21  with the second dye solution  23 A is weighed by a diluent weighting unit  40 , based on a gravimetric method. A third dye solution  19 B, which the same dye as the second dye solution  23 A, is dispensed into the optical analysis cells  2  filled with the first and second dye solutions  14 A and  23 A from a sample cup  19  by using the sample filling unit  17 . 
         [0098]    Measuring the amounts of liquid in the optical analysis cells  2  filled with the first, second and third dye solutions, i.e.,  14 A,  23 A and  19 B, respectively, by an optical absorbance detection unit  25  (based on a dye method) in order to determine the amount of the first dye solution  14 A as a target value measurement result. Obtaining the weight of the diluent dispensing pipetter  21  after having been filled with the second dye solution  23 A by a pipetter weighing unit  46  based on a gravimetric method. 
         [0099]    Transferring the entire content from the optical analysis cells  2  filled with the first, second and third dye solutions, i.e.,  14 A,  23 A and  19 B, respectively, to a reference value measurement microplate  32  by using a transfer pipetter  30 . Based on a dye method, using a second optical absorbance detection unit to determine the amount of the first dye solution  14 A as a reference value measurement result. Performing a computational analysis to validate the dispensing accuracy of the analysis target liquid filling unit  12  of the automated analyzer RO, according to any deviation between and among the reference value measurement result and the target value measurement result, determined based on a dye method, and the deviation between the measurement results of the pipetter weighing unit  46  and the diluent weighing unit  40  determined based on a gravimetric method. 
         [0100]    Although the above-mentioned embodiments described the application of the present invention to a clinical biochemistry automated analyzer used for hematological testing, the present invention is not limited thereto, but rather can also be applied to a wide range of other clinical biochemistry automated analyzers. 
         [0101]    It is also within the scope of the present method to have the manual pipetting of the dye solutions and target liquids performed by a robotic handling device or automated dispensing units to have a fully automated process. In addition, the weighing of the pipette may be performed on a single weighing unit. 
         [0102]    The preferred embodiment of the invention is illustrative of the invention rather than limiting of the invention. It is to be understood that revisions and modifications may be made to methods and systems described herein while still providing a manufacturing automation system and an automated method for movement of material that fall within the scope of the included claims. All matters hitherto set forth herein or shown in the accompanying figures are to be interpreted in an illustrative and non limiting sense.