Patent Publication Number: US-2023139301-A1

Title: Automated analyzer

Description:
TECHNICAL FIELD 
     The present disclosure relates to an automatic analyzer. 
     BACKGROUND ART 
     The automatic analyzer is an instrument which, for example, analyzes a component or characteristic of an analyte by reacting the analyte with a reagent and analyzing the reaction. In some cases, a mixed liquid is created by mixing together a plurality of reagents. In this case, the mixed liquid is created by introducing the plural reagents into a mixed liquid chamber in which the reagents are mixed together. The resultant mixed liquid is fed to an analysis process or the like. 
     The following Patent Literature describes a reagent generator. With an aim to provide a simple configuration for easy creation of a reagent having a highly accurate concentration, the Patent Literature discloses a technique which includes: a conditioning tank for storing a reagent and a diluting liquid; a reagent feed unit for feeding a predetermined quantity of reagent to the conditioning tank; a diluting liquid feed unit for feeding, to the conditioning tank, a smaller quantity of diluting liquid than a quantity necessary for diluting the fed reagent to a desired concentration; a diluting liquid replenishment unit for replenishing the conditioning tank with an arbitrary quantity of diluting liquid; a detector for detecting a concentration of the reagent in the tank; and a control unit for controlling a replenishing operation of the diluting liquid replenishment unit, and which is characterized in that when a concentration of the detected reagent is higher than the desired concentration, the control unit calculates a replenishment quantity of the diluting liquid from a difference between the detected concentration and the desired concentration such as to attain the desired concentration, and that the control unit repeats the control operation of replenishing the conditioning tank with the diluting liquid by a quantity smaller than the calculated replenishment quantity (refer to the abstract). 
     CITATION LIST 
     Patent Literature 
     
         
         Patent Literature 1: Japanese Patent Application Laid-Open No. H9(1997)-033538 
       
    
     SUMMARY OF INVENTION 
     Technical Problem 
     According to the Patent Literature 1, the reagent is created in high concentration in a conditioning tank  7  (mixed liquid chamber), and a desired reagent is created by feeding pure water into the chamber. In a case where the mixed liquid is created in the mixed liquid chamber as just described, the mixed liquid remaining in the mixed liquid chamber may sometimes affect the subsequent creation of a new mixed liquid. 
     The present disclosure is made in view of the above-described problems and the object thereof is to provide an automatic analyzer which is adapted to relax the effect of the previously created mixed liquid when a mixed liquid is created anew. 
     Solution to Problem 
     The automatic analyzer according to the disclosure is configured to create a second mixed liquid after the creation of a first mixed liquid. In the creation a second mixed liquid, the automatic analyzer introduces a relaxation reagent into the mixed liquid chamber. The relaxation reagent is selected based on the characteristics of the first mixed liquid and relaxes the effect of the first reagent remaining in the mixed liquid chamber. 
     Advantageous Effects of Invention 
     In the creation of a mixed liquid, the automatic analyzer according to the present disclosure can relax the effect of the previously created mixed liquid. The other features, advantages and components of the present disclosure will become more apparent from the following detailed description thereof. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG.  1    is a schematic view showing a configuration example of an automatic analyzer  100  according to First Embodiment. 
         FIG.  2 A  is a schematic view explaining a procedure for creating a mixed liquid by a conventional automatic analyzer. 
         FIG.  2 B  is a schematic view explaining a procedure for creating a mixed liquid by an automatic analyzer  100  according to First Embodiment. 
         FIG.  3    shows an example explaining a liquid quantity of a relaxation reagent  133 . 
         FIG.  4    is a view explaining a procedure for creating a mixed liquid in Second Embodiment. 
         FIG.  5    shows an example explaining a liquid quantity of a relaxation reagent  133 . 
         FIG.  6    is an example of a user interface provided by a control unit  161 . 
     
    
    
     DESCRIPTION OF EMBODIMENTS 
     Example 1 
       FIG.  1    is a schematic view showing a configuration example of an automatic analyzer  100  according to First Embodiment. The automatic analyzer  100  is an instrument for analyzing a characteristic of an analyte by reacting the analyte with a reagent and analyzing the reaction. The automatic analyzer  100  includes: a mixed liquid chamber  110 ; a reagent introduction mechanism  120 ; a reagent container  130 ; a mixed liquid dispensing mechanism  140 ; reaction vessel  150 ; a control unit  161  and a memory unit  162 . 
     The mixed liquid chamber  110  is a vessel used for creating a mixed liquid by introducing a plurality of reagents therein (Sometimes, only one reagent is used). The reagent introduction mechanism  120  sucks up a reagent from the reagent container  130  and introduces the reagent into the mixed liquid chamber  110 . The reagent introduction mechanism  120  can be composed of, for example, a liquid dispensing nozzle or the like. The mixed liquid chambers  110  and the reagent containers  130  may be arranged by type. 
     The mixed liquid dispensing mechanism  140  dispenses the mixed liquid in the mixed liquid chamber  110  to the reaction vessel  150 . An analyte is introduced into the reaction vessel  150  by means of an unillustrated analyte introduction mechanism so that the mixed liquid reacts with the analyte on the reaction vessel. 
     The control unit  161  controls different parts (such as the reagent introduction mechanism  120  and the mixed liquid dispensing mechanism  140 ) of the automatic analyzer  100 . The memory unit  162  is a storage device for storing data used by the control unit  161 . The control unit  161  can be constructed by using hardware such as a circuit device implementing its functionality or otherwise, by using an arithmetic device such as CPU (central Processing Unit) executing software implementing its functionality. 
       FIG.  2 A  is a schematic view explaining a procedure for creating a mixed liquid by a conventional automatic analyzer. According to a conventional procedure for creating the mixed liquid, a first mixed liquid is created by introducing a first reagent  131  into the mixed liquid chamber  110  (the left-side chamber in  FIG.  2 A ), from which the first mixed liquid is sucked to be supplied to the subsequent process. Hereat, some of the first mixed liquid stays in the mixed liquid chamber  110  as a residual liquid  131 ′. In addition, the automatic analyzer creates a second mixed liquid by introducing a second reagent  132  into the mixed liquid chamber  110  where the residual liquid  131 ′ remains. The residual liquid  131 ′ contains components of the first reagent  131 . The residual components carry a potential to affect the second reagent (or the subsequent process using the second reagent  132 ), thus resulting in failure to accomplish accurate analysis. 
       FIG.  2 B  is a schematic view explaining a procedure taken by the automatic analyzer  100  according to First Embodiment for creating a mixed liquid. According to First Embodiment, the reagent introduction mechanism  120  sucks the first mixed liquid created using the first reagent  131  out from the mixed liquid chamber  110 . Subsequently, the reagent introduction mechanism  120  introduces a relaxation reagent  133  into the mixed liquid chamber  110  before introducing the second reagent  132  into the mixed liquid chamber  110 . The relaxation reagent  133  is a reagent capable of relaxing an effect of the residual liquid  131 ′ (or, the residual components of the first reagent  131 ) on the second reagent  132  (or the subsequent process using the second reagent  132 ). 
     Even though the residual liquid  131 ′ remains in the mixed liquid chamber  110 , the introduction of the relaxation reagent  133  is effective to relax the effect of the residual liquid and to ensure the accomplishment of an accurate subsequent process. Therefore, the problem caused by the residual liquid  131 ′ during the conventional process of creating the mixed liquid, as shown in  FIG.  2 A , can be dissolved. 
     The control unit  161  must have knowledge about the characteristics of the residual liquid  131 ′ before introducing the relaxation reagent  133  into the mixed liquid chamber  110 . That is, the control unit must previously gain knowledge about at least one of the component characteristics that can affect the second reagent  132  (or the subsequent process such as one that brings the second reagent  132  into reaction with the analyte). More specifically, a pH value and a molecular polarity of the residual liquid  131 ′ are equivalent to this characteristic. These characteristics of the residual liquid  131 ′ may previously be entered as the characteristics of the first reagent  131  and stored in the memory unit  162 . According to the data pieces, the control unit  161  can gain the knowledge about the characteristics of the residual liquid  131 ′ based on the data. 
     In a case where the pH value of the residual liquid  131 ′ is relaxed by the relaxation reagent  133 , what is required of the relaxation reagent  133  is to have a pH value of the opposite polarity to that of the residual liquid. Specifically, if the first reagent  131  is acidic, for example, a usable relaxation agent  133  may have basicity. If the first reagent  131  is basic, a usable relaxation reagent  133  may have acidity. 
     In a case where the molecular polarity of the residual liquid  131 ′ is relaxed by the relaxation reagent  133 , a usable relaxation agent  133  may have a molecular polarity capable of diluting the molecular polarity of the residual liquid  131 ′. If the first reagent  131  is an organic solvent, for example, pure water is usable as the relaxation agent  133 . Otherwise, any other suitable diluting liquid is also usable. Specifically, if the first reagent  131  has a high molecular polarity, a reagent having a lower molecular polarity than the above may be used as the relaxation agent  133 . If the first reagent  131  has a low molecular polarity, a reagent having a higher molecular polarity than the above may be used as the relaxation agent  133 . 
     When introducing the relaxation agent  133  into the mixed liquid chamber  110 , the control unit  161  needs to gain knowledge about a quantity of the residual liquid  131 ′. This is because the quantity of the relaxation reagent  133  also varies depending on the quantity of the residual liquid  131 ′. The quantity of the residual liquid  131 ′ can be typically defined as a dead volume of the mixed liquid chamber  110 . The term “dead volume” means a quantity of liquid inevitably remaining in the mixed liquid chamber  110  because of the incapability of the reagent introduction mechanism  120  from sucking up all the reagent in the mixed liquid chamber  110 . The dead volume can be calculated based on a configuration of the mixed liquid chamber  110  and a configuration of the reagent introduction mechanism  120  (specifically, a nozzle configuration). Data describing the dead volume may also be stored beforehand in the memory unit  162 . This allows the control unit  161  to figure out the dead volume according to the data, thus negating the need for calculating the dead volume each time. 
     In a case where only a part of the components of the residual liquid  131 ′ affects the subsequent process using the second reagent  132 , it is necessary to previously determine a ratio of the concerned component in the residual liquid  133 ′. This ratio can be determined based on the ratios of the reagents used for the creation of the first mixed liquid. For example, the ratios of the concerned reagents may be written in data describing the dead volume. 
       FIG.  3    shows an example explaining the quantity of the relaxation reagent  133 . In a process (a) of analyzing an analyte A (cycle  1 ), a mixed liquid containing pure water and an organic solvent in a ratio of 0:100 [μL] is supplied as a first mixed liquid. In a process (b) of analyzing an analyte B (cycle  2 ), a mixed liquid containing the pure water and the organic solvent in a ratio of 20:80 [μL] is supplied as a second mixed liquid. In these examples, the organic solvent in the cycle  1  is equivalent to the first reagent  131 , and the organic solvent in the cycle  2  is equivalent to the second reagent  132 . 
     It is assumed that 10 μL of organic solvent remains as the residual liquid  131 ′ in the mixed liquid chamber  110  after the end of the cycle  1 . In the cycle  2 , it is necessary to create a mixed liquid containing the pure water and the organic solvent in a ratio of 20:80=1:4. It is therefore necessary to maintain this ratio by relaxing the effect of the residual liquid  131 ′. In the cycle  2 , 2.5 μL of pure water is introduced as the relaxation reagent  133 . This gives a ratio of the pure water:the organic solvent (residual liquid  131 ′)=1:4. Hence, the ratio of the pure water:the organic solvent=1:4 can be maintained if a mixed liquid, as the second reagent  132 , containing the pure water and the organic solvent in a ratio of 20:80 [μL] is further supplied, the ratio of the pure water:the organic solvent=1:4 can be maintained. Thus, the effect of the residual liquid  131 ′ can be relaxed. 
     In a case where the pH value of the residual liquid  131 ′ is neutralized by the pH value of the relaxation reagent  133 , a liquid quantity of the relaxation reagent  133  is so set as to maintain the quantity of the acidic solvent or the quantity of the basic solvent in the second reagent  132 . For example, if the second reagent  132  contains neither the acidic solvent nor the basic solvent, the relaxation reagent  133  capable of perfectly neutralizing the pH value of the residual liquid  131 ′ may be introduced. For example, if the residual liquid  131 ′ has a pH value of 6.0 and has a volume of 10 μL, 10 μL of the relaxation reagent  133  having a pH value of 8.0 may be used. 
     By taking the above-described procedure, the control unit  161  relaxes the effect of the residual liquid  131 ′ during the use of the second reagent  132 . Subsequently, the control unit  161  analyzes the analyte by reacting the second reagent  132  with the analyte and obtains the results. The results of analysis can be obtained in the form of, for example, a spectral value of a component contained in the analyte. The control unit  161  determines that the effect of the residual liquid  131 ′ is adequately relaxed if a spectral area of the component in the analyte is within an allowable range (the quantity of the component assumed to be contained in the analyte). Otherwise, the control unit determines that the effect of the residual liquid  131 ′ is not adequately relaxed by the relaxation reagent  133  and outputs an alert message indicating the unsuccessful relaxation. It is also possible to use a spectral area of an internal standard substance in place of or in combination with the spectral area of the analyte component. Otherwise, the spectral area may also be replaced by a spectral peak value. The same applies to the following embodiments, as well. 
     Example 1: Summary 
     After discharging the first reagent  131  from the mixed liquid chamber  110 , the automatic analyzer  100  according to the first embodiment introduces the relaxation reagent  133  for relaxing the effect of the first reagent  131  into the mixed liquid chamber  110  before introducing the second reagent  133  into the mixed liquid chamber  110 . Thus, the effect of the residual liquid  131 ′ is relaxed so as to provide for a proper implementation of the subsequent process such as analysis using the second reagent  132 . 
     Example 2 
       FIG.  4    is a view explaining a procedure for creating a mixed liquid according to Second Embodiment of the disclosure. The first embodiment illustrates the example where after the discharge of the first reagent  131  from the mixed liquid chamber  110 , the relaxation reagent  133  is introduced into the mixed liquid chamber  110 , followed by introducing the second reagent  132  into the mixed liquid chamber  110 . According to the second embodiment, after the discharge of the first reagent  131  from the mixed liquid chamber  110 , a component equivalent to the relaxation reagent  133  is previously mixed in with the second reagent  132  and thereafter, the resultant second reagent  132  is introduced into the mixed liquid chamber  110 . This leads to the shortening of the process of introducing the relaxation reagent  133  into the mixed liquid chamber  110 . The other constitution is the same as that of the first Embodiment. 
     Example 3 
       FIG.  5    shows an example explaining a liquid quantity of a relaxation reagent  133 . The first reagent  131  and the second reagent  132  may sometimes have a plurality of characteristics affecting the analyte analysis process. According to  FIG.  5   , two characteristics including (a) molecular polarity of the organic solvent and (b) respective pH values of the acidic solvent and the basic solvent can each affect the analysis process. The quantities of components constituting the relaxation reagent  133  are determined for each of the characteristics affecting the process. The total sum of the component quantities is regarded as constituting a final relaxation reagent  133 . 
     According to the example shown in  FIG.  5   , the second reagent  132  in the cycle  2  is a mixed liquid where the pure water and the organic solvent are mixed in a ratio of 20:80 [μL]. Since 9 μL of pure water remains in the chamber as the residual liquid  131 ′, 36 μL of an organic solvent is used as the relaxation reagent  133 . This gives a mixed liquid containing the pure water and the organic solvent in a ratio of 9:36=1:4 and hence, the second reagent  132  can maintain the ratio of these reagents. 
     In some cases, the mixed liquid contains only one of either the acidic solvent or the basic solvent. In this case, the mixed liquid contains only one of either the acidic solvent or the basic solvent and may further contain a component other than these solvents as needed. It is assumed in the example shown in  FIG.  5    that both the acidic solvent and the basic solvent are contained in the second reagent  132  in the cycle  2  in a quantity of 0 μL (namely, the reagent is neutral). Since 1 μL of the acidic solvent remains as the residual liquid  131 ′, 1 μL of the basic solvent is used as the relaxation reagent  133 . Thus, the pH value of the acidic solvent and the pH value of the basic solvent virtually cancel each other out so that that the pH values of these solvents in the second reagent  132  can be maintained as assumed. Specifically, the control unit  161  previously selects a characteristic and a liquid quantity of the relaxation reagent  133  capable of neutralizing the second reagent residual liquid  131 ′ such that the respective pH values of the acidic solvent and basic solvent present in the second reagent  132  may not vary when the second reagent  132  is introduced into the mixed liquid chamber  110 . 
     Example 4 
       FIG.  6    is an example of a user interface provided by the control unit  161 . The user interface presents a quantity of reagent for each analysis cycle and also presents information indicating whether or not the effect of the first reagent  131  is fully relaxed by the relaxation reagent  133 . Criteria for determining whether the effect of the first reagent  131  is fully relaxed or not are just as described in the first embodiment. 
     The cycle  2  shown in  FIG.  6    is marked with an alert sign indicating that a part where the spectral area of the analyte component exceeds the allowable range is found. The control unit  161  can output to the memory unit  162 , for example, data describing contents shown in an upper part of  FIG.  6   . In addition, the control unit  161  can provide a user interface as shown in  FIG.  6    by outputting the contents of data to a device on a display. As illustrated by a hatched portion in a lower part of  FIG.  6   , what part of the component spectrum was out of the allowable range may be presented on the user interface. In the case of the example shown in the lower part of  FIG.  6   , it can be deduced that the component in the first reagent  131  that affects the component corresponding to the hatched portion could not be fully relaxed. 
     The user interface may be provided by a device other than the automatic analyzer  100 . For example, the control unit  161  may also be configured to store the data describing the contents shown in  FIG.  6    while another device may be configured to read the data and to present the user interface as shown in  FIG.  6   . 
     &lt;Modifications of Disclosure&gt; 
     The present disclosure is not limited to the above-described examples but can include a variety of modifications. The foregoing examples, for instance, are the detailed illustrations to clarify the disclosure. The disclosure is not necessarily limited to those including all the components described above. One component of one example can be replaced by another component of another example. Further, one component of one example can be added to the arrangement of another example. A part of the arrangement of each example permits addition of some component of another example, the omission thereof or replacement thereof 
     In the foregoing examples, the relaxation reagent  133  may be introduced between the first reagent  131  and the second reagent  132  in a certain cycle, as explained with reference to  FIG.  2 B , for example. In another cycle, as explained with reference to  FIG.  4   , the second reagent  132  and the relaxation reagent  133  may be collectively introduced. 
     According to the foregoing examples, the mixed liquid in the mixed liquid chamber  110  can be agitated by means of a mixer. For example, a functional capability of a mixer can be provided by vibrating the whole body of a plate carrying the mixed liquid chamber  110  thereon. 
     In the foregoing examples, the characteristic of the residual liquid  131 ′ and the characteristic of the relaxation reagent  133  need not be perfectly opposite. Even though the residual liquid  131 ′ has a pH value of 6.0 and the relaxation reagent has a pH value of 7.5, the pH value of the residual liquid  131 ′ can be neutralized by using the relaxation reagent  133  twice as much as the residual liquid  131 ′. Even though the residual liquid  131 ′ cannot be perfectly neutralized, all that is needed is to relax the pH value of the residual liquid to a degree that the subsequent step using the second reagent  132  is little affected. The same holds for the other characteristics such as the molecular polarity and the like of the residual liquid  131 ′. 
     In the foregoing examples, the quantities of the first reagent  131  and the second reagent  132  may be so defined as to establish an optimum component ratio in the analysis process for each analyte. In a case where a reagent having a pH value of 8.0 (basic) need be supplied in the analysis process of the analyte A, for example, the analysis process is performed as follows. A reagent having a stronger basicity is previously created as the first reagent  131 , and the pH value of the first reagent is neutralized in the subsequent step before performing the analysis process. 
     In the foregoing examples, examples of the reagent constituting the mixed liquid include: CAN (Acetonitrile); MeOH (methanol); suitable basic or acidic buffer liquids; and the like. 
     The foregoing examples illustrate the pH value and molecular polarity as examples of the characteristics of the residual liquid  131 ′ that affect the subsequent process. Regarding the other characteristics affecting the subsequent process, a reagent relaxing the effect of the residual liquid is also usable as the relaxation reagent. 
     REFERENCE SIGNS LIST 
     
         
           100  automatic analyzer 
           110  mixed liquid chamber 
           120  reagent introduction mechanism 
           130  reagent container 
           140  mixed liquid dispensing mechanism 
           150  reaction vessel 
           161  control unit 
           162  memory unit