Abstract:
A conventional automated analyzer has a mechanism for performing a stirring operation and a mechanism for performing a pipetting operation. The mechanisms are independent of each other. The time interval between the stirring operation and the pipetting operation is at least several seconds. A solid particle starts to settle out at the time of termination of the stirring operation. In the pipetting operation, an operation for suctioning a liquid is performed during a transient period of the process in which the solid particle settles out. The suction of the liquid containing a solid particle during the transition period of the process may cause a variation in the number of solid particles contained in the liquid pipetted. The problem is solved by means for simultaneously performing an operation for stirring a liquid reagent containing a solid particle and an operation for maintaining the reagent.

Description:
BACKGROUND OF THE INVENTION 
       [0001]    1. Field of the Invention 
         [0002]    The present invention relates to an automated analyzer for qualitatively and quantitatively analyzing a biological sample such as blood and urine, and more particularly to an automated analyzer having a stirring mechanism for stirring a reagent, a reaction solution, and the like. 
         [0003]    2. Description of the Related Art 
         [0004]    Since recent automated analyzers are capable of analyzing a lot of samples for a short time and providing analysis results with high reproducibility compared with conventional techniques, the automated analyzers have been widely used in inspection centers, large hospitals and the like. Analyses to be performed by an automated analyzer are mainly divided into a calorimetric analysis and an immune assay. The calorimetric analysis is to analyze the amount of a specific component contained in blood. The immune assay is to determine whether or not a specific antigen or a specific antibody is present in a sample. The immune assay is to be performed with sensitivity higher by two digits than that of the calorimetric analysis. The immune assay is to be performed using solid particles in general. In the immune assay, the concentration of a biological substance contained in a sample is measured by capturing a solid particle specifically coupled with a target biological substance by an antigen-antibody reaction occurring on a surface of the biological substance and measuring the amount of a labeled substance coupled with the solid particle coupled with the target substance. As the labeled substance, a radioactive substance had been used in the past. Recently, however, a luminous body for emitting light chemically or physically has been used to prevent a harmful substance from being generated. Since the specific gravity of the solid particle contained in a solution is high, the particle settles out onto the bottom of a vessel as time elapses. A liquid reagent containing the solid particle is stirred by means of a stirring mechanism periodically or immediately before pipetting. In this case, the stirring mechanism is separately located from a pipetting mechanism, and the stirring is performed at the time different from the pipetting. Such a technique for stirring a solid particle is described, for example, in JP-A-2002-311034. 
       SUMMARY OF THE INVENTION 
       [0005]    An automated analyzer described in JP-A-2002-311034 has a mechanism for performing a stirring operation and a mechanism for performing a pipetting operation. The mechanisms are independent of each other. The time interval between the stirring operation and the pipetting operation is at least several seconds. A solid particle starts to settle out at the time of termination of the stirring operation. In the pipetting operation, an operation for suctioning a liquid is performed during a transient period of the process in which the solid particle settles out. The timing of the pipetting is therefore limited. 
         [0006]    An object of the present invention is to provide an automated analyzer capable of pipetting a reagent under the condition that solid particles are constantly stirred regardless of the timing of the pipetting. 
         [0007]    To accomplish the object of the present invention, the automated analyzer according to the present invention has the following configuration. 
         [0008]    The automated analyzer includes a reagent vessel and a probe. The reagent vessel is adapted to accommodate a reagent containing a solid particle. The probe is adapted to pipette a predetermined amount of a liquid reagent present in the reagent vessel. The automated analyzer further includes a probe driver for moving the probe within the reagent before the reagent is suctioned by means of the probe. 
         [0009]    The solid particle is generally a spherical magnetic particle (beads). However, as long as particles that are not liquid are dispersed in a liquid, an effect of the present invention can be obtained. The probe is pipetting means capable of suctioning and delivering a target liquid by using means for generating pressure, such as a syringe or a bellows. There are some cases where a member, which directly contacts a liquid to be pipetted, is called a nozzle. The probe may include a nozzle as one of its constitutional elements and an arm for moving the nozzle to a target location. The movement of the probe within the reagent is performed in order to stir the solid particle contained in the reagent. The movement is not limited as long as a stirring effect can be obtained. For example, the probe may reciprocate or revolve. 
         [0010]    The automated analyzer does not require a special stirring mechanism only for contacting a liquid containing a solid particle and stirring the liquid. It is not necessary that a stirring mechanism be placed in another reagent and a liquid reagent containing a solid particle of cleaning water. Since the number of parts of the automated analyzer is reduced, the cost of a stirring mechanism and a space occupied by the analyzer can be reduced. The cost of the automated analyzer having a mechanism is therefore reduced. The automated analyzer is capable of performing a stirring operation and a pipetting operation simultaneously. This reduces the time for an analysis. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0011]      FIG. 1  is an explanatory diagram showing a first embodiment of the present invention. 
           [0012]      FIG. 2  is an explanatory diagram showing a second embodiment of the present invention. 
           [0013]      FIG. 3  is an explanatory diagram showing a third embodiment of the present invention. 
           [0014]      FIG. 4  is an explanatory diagram showing a fourth embodiment of the present invention. 
           [0015]      FIG. 5  is an explanatory diagram showing a fifth embodiment of the present invention. 
       
    
    
     DESCRIPTION OF THE PREFERRED EMBODIMENTS 
       [0016]    Embodiments of the present invention will be described with reference to the accompanying drawings. 
       First Embodiment 
       [0017]      FIG. 1  is a diagram showing an outline configuration of a pipetting mechanism according to a first embodiment of the present invention. 
         [0018]    In  FIG. 1 , the pipetting mechanism includes a probe  101 , tubes  102  to  104 , a syringe  105 , a first arm  106 , a second arm  107 , a column  113 , a first belt  114 , and a second belt  115 . 
         [0019]    The second arm  107  is connected with a first shaft  110  to which a rotation force about an axis  109  is transmitted through the first belt  114 . The second arm  107  rotates about the first shaft  110 . The first arm  106  is connected to a second shaft  108  whose central axis corresponds to the axis  109 . The first arm  106  rotates about the axis  109  in accordance with rotation of the second shaft  108 . The central axis of the column  113  is coaxial with the axis  109  of the second shaft  108 . The column  113  is connected with the second belt  115  rotating around a third shaft  111  and a fourth shaft  112 . The column  113  performs a translational motion. The first arm  106  performs a translational motion in accordance with the motion of the column  113 . 
         [0020]    Since the probe  101  is supported by the second arm  107 , the probe  101  is capable of three-dimensionally moving by means of a combination of movements of the second shaft  110 , the shaft  108 , and the column  113 . The tube  103  is provided in the probe  101 . The tube  103  is connected with the tubes  104  and  102 , and the syringe  105 . 
         [0021]    The probe  101  is capable of moving into a reagent vessel  118  in which a liquid reagent  116  containing solid particles  117  is present, and causing the liquid reagent  116  to be stirred by a three-dimensional movement of the probe  101 . The solid particles  117  are uniformly dispersed in the liquid reagent  116 . 
         [0022]    When the solid particles  117  are uniformly dispersed in the liquid reagent  116  and negative pressure is applied to the inside of the tube  103  by means of the syringe  105 , the liquid reagent  116  containing the solid particles  117  uniformly dispersed is held in the tube  103  due to the negative pressure. 
         [0023]    When the probe  101  moves into a vessel  119  and positive pressure is applied to the inside of the tube  103  by means of the syringe  105 , the liquid reagent  116  containing the solid particles  117  uniformly dispersed is pipetted into the vessel  119  due to the positive pressure. 
       Second Embodiment 
       [0024]      FIG. 2  is a diagram showing an outline configuration of a pipetting mechanism according to a second embodiment of the present invention. 
         [0025]    In  FIG. 2 , the pipetting mechanism includes a probe  201 , a stirring bar  218 , a first tube  202 , a second tube  203 , a syringe  204 , a first arm  205 , a column  211 , a first belt  212 , and a second belt  213 . 
         [0026]    The stirring bar  218  is connected with a first shaft  208  to which a rotation force about an axis  207  is transmitted through the first belt  212 . The stirring bar  218  rotates around the first shaft  208 . The first arm  205  is connected to a second shaft  206  whose central axis corresponds to the axis  207 . The first arm  205  rotates about the axis  207  in accordance with rotation of the second shaft  206 . The central axis of the column  211  is coaxial with the axis  207  of the second shaft  206 . The column  211  is connected with the second belt  213  rotating around a third shaft  209  and a fourth shaft  210 . The column  211  performs a translational motion. The first arm  205  performs a translational motion in accordance with the motion of the column  211 . 
         [0027]    Since the probe  201  is supported by the first arm  205 , the probe  201  is capable of two-dimensionally moving by means of a combination of movements of the shaft  206  and the column  211 . The second tube  203  is provided in the probe  201 . The second tube  203  is connected with the first tube  202  and the syringe  204 . 
         [0028]    The probe  201  is capable of moving into a reagent vessel  216  in which a liquid reagent  214  containing solid particles  215  is present, and causing the liquid reagent  214  to be stirred by a rotation movement of the stirring bar  218  or a two-dimensional movement of the probe  201 . The solid particles  215  are uniformly dispersed in the liquid reagent  214 . 
         [0029]    When the solid particles  215  are uniformly dispersed in the liquid reagent  214  and negative pressure is applied to the inside of the second tube  203  by means of the syringe  204 , the liquid reagent  214  containing the solid particles  215  uniformly dispersed is held in the second tube  203  due to the negative pressure. 
         [0030]    When the probe  201  moves into a vessel  219  and positive pressure is applied to the inside of the second tube  203  by means of the syringe  204 , the liquid reagent  214  containing the solid particles  215  uniformly dispersed is pipetted into the vessel  219  due to the positive pressure. 
       Third Embodiment 
       [0031]      FIG. 3  is a diagram showing an outline configuration of a pipetting mechanism according to a third embodiment of the present invention. 
         [0032]    In  FIG. 3 , the pipetting mechanism includes a probe  301 , a first tube  302 , a second tube  303 , a syringe  304 , an arm  305 , a column  310 , a belt  311 , a reagent vessel holder  316 , and a swing motion generator  317 . 
         [0033]    The arm  305  rotates about an axis  307  in accordance with rotation of a first shaft  306 . The central axis of the column  310  is coaxial with the axis  307 . The column  310  is connected with the belt  311  rotating around a second shaft  308  and a third shaft  309  and performs a translational motion. The arm  305  performs a translational motion in accordance with the motion of the column  310 . 
         [0034]    Since the probe  301  is supported by the arm  305 , the probe  301  is capable of two-dimensionally moving by means of a combination of movements of the shaft  306  and the column  310 . The second tube  303  is provided in the probe  301  and connected with the first tube  302  and the syringe  304 . 
         [0035]    The probe  301  moves into a reagent vessel  314  in which a liquid reagent  312  containing solid particles  313  is present. The probe  301  then contacts the liquid reagent  312 . The reagent vessel  314  is held and positioned by the reagent vessel holder  316 . Since the reagent vessel holder  316  moves by means of the swing motion generator  317 , the reagent vessel  314  swings. The liquid reagent  312  is then stirred. Therefore, the solid particles  313  are uniformly dispersed in the liquid reagent  312 . 
         [0036]    When the solid particles  313  are uniformly dispersed in the liquid reagent  312  and negative pressure is applied to the inside of the second tube  303  by means of the syringe  304 , the liquid reagent  312  containing the solid particles  313  uniformly dispersed is held in the second tube  303  due to the negative pressure. 
         [0037]    When the probe  301  moves into a vessel  315  and positive pressure is applied to the inside of the second tube  303  by means of the syringe  304 , the liquid reagent  312  containing the solid particles  313  uniformly dispersed is pipetted into the vessel  315  due to the positive pressure. 
         [0038]    In this method, after the probe is inserted into the reagent, only the reagent vessel then swings to stir the solid particles while the position of the probe is maintained for a fixed time. There is a demand to improve an efficiency of an analysis to be performed by an automated analyzer and to reduce the time for an analysis process such as pipetting and stirring. It is difficult that a pipetting nozzle moves for the stirring in order to improve accuracy of pipetting. It is, therefore, desirable that the nozzle be fixed during the pipetting. Even in this case, the reagent vessel can swing to stir the solid particles during the pipetting in the method shown in  FIG. 3 . Therefore, there is an advantage in the method shown in  FIG. 3 , compared with the method shown in  FIG. 1 . 
         [0039]    JP-A-S63-148166 discloses a technique in which a pipetting nozzle has a stirring wing. In the technique disclosed in JP-A-S63-148166, it is necessary that after pipetting, the stirring wing move in order to perform stirring. On the other hand, in the method shown in  FIG. 3 , the pipetting and the stirring can be performed simultaneously, resulting in a reduction in the time for the analysis. 
       Fourth Embodiment 
       [0040]      FIG. 4  is a diagram showing an outline configuration of a pipetting mechanism according to a fourth embodiment of the present invention. 
         [0041]    In  FIG. 4 , a probe  401  is a pipetting mechanism having a liquid contact section  407  and a non-liquid-contact section  406 . The liquid contact section  407  and the non-liquid-contact section  406  can be separated from each other. The liquid contact section  407  can be replaced with a new liquid contact section when there is an effect which has an adverse impact on an analysis result, such as abnormal pressure within the second tube  408  due to transformation of the liquid contact section  407 , contamination such as an attached substance which may impact on the analysis, and a change in the amount of a liquid pipetted. The replacement makes it possible to pipette, into a vessel  405 , a liquid reagent  402  containing solid particles  403  uniformly dispersed in a reagent vessel  404  with high reliability. 
       Fifth Embodiment 
       [0042]      FIG. 5  is a diagram showing an outline configuration of a pipetting mechanism according to a fifth embodiment of the present invention. 
         [0043]    In  FIG. 5 , the pipetting mechanism has a probe  501  having a portion which is to be contacted with a reagent solution  504  and is provided with a structural object  506 . When the relative position of the probe  501  with respect to the reagent solution  504  is changed due to the structural object  506 , mechanical resistance occurring between the probe  501  and a liquid reagent  502  is increased. The liquid reagent  502  can therefore be well stirred. This enhances the tendency that solid particles  503  are uniformly dispersed in the liquid reagent  502 . The time period for uniform dispersion of the solid particles  503  is reduced, while the time period when the solid particles  503  are in a uniformly dispersed state is increased. The accuracy of pipetting the liquid reagent  502  containing the solid particles  503  can be improved.