Abstract:
An automatic analyzer which assures uniformity in mixing effects regardless of sample quantity and test item and thus produces analysis results with high repeatability. The analyzer includes a device for adding a conditioning liquid into a reaction chamber so that the quantity of liquid in the reaction chamber becomes a predetermined quantity at latest just before mixing. The conditioning liquid may be a diluent or physiological saline as used for dilution of a sample or any other special liquid that adjusts the properties such as viscosity, surface tension, etc. of liquid to be mixed.

Description:
CLAIM OF PRIORITY 
       [0001]    The present application claims priority from Japanese application Ser. No. 2007-37309 filed on Feb. 19, 2007, the content of which is hereby incorporated by reference into this application. 
       BACKGROUND OF THE INVENTION 
       [0002]    1. Field of the Invention 
         [0003]    The present invention relates to an automatic analyzer and automatic analyzing method which carries out qualitative and quantitative analyses of biological or chemical samples such as blood and urine and more particularly to an automatic analyzer with a mixing device. 
         [0004]    2. Description of the Related Art 
         [0005]    It is known that conventional chemical or biochemical analyzers use a reaction liquid obtained by mixing a sample such as serum with a desired reagent as an object of analysis and measures its absorbance. This kind of analyzer is comprised of a mechanism for providing a sample and a reagent into a reaction chamber or cuvette, a mechanism for mixing a sample and a reagent in a reaction chamber, a mechanism for analyzing physical properties of a sample which is reacting or has finished reaction, and so on. 
         [0006]    A major technical problem in analyzers is reduction of the required quantities of sample and reagent for analysis. One reason for this is that as the number of test items increases, the quantity of sample available for one test item decreases. For example, in blood tests of infants, the quantity of blood sample available for analysis is very small. In addition, from the viewpoint of cost, there is demand for reduction of the quantity of reagent used in analysis. Because there is the growing tendency that advanced analysis techniques are introduced and expensive reagents are widely used. 
         [0007]    As the quantities of sample and reagent used for analysis were decreased, the size of reaction chambers was reduced. However, this has posed a new problem. For example, when the reaction liquid is mixed mechanically by a spatula or the like, the ratio of reaction liquid taken out or the ratio of rinse fluid taken in becomes larger, which affects the analysis result. One solution to this problem related to mixing is a non-contact mixing device using ultrasonic waves as described in JP-A No. 2003-35715. However, in this case, for the sample and reagent which are injected into a reaction chamber, their mixture ratio varies depending on the type of test, or test item. So the quantity of liquid to be measured in the chamber is different and complicated control work is needed for efficient mixing. 
         [0008]    The technique described in JP-A No. 2003-35715 uses a plurality of ultrasonic oscillators provided at different heights so that mixing efficiency does not deteriorate even when the liquid level of liquid to be mixed varies. In this case, complicated control work is needed to determine which oscillator should be activated according to the liquid level. Also it is desirable to adjust the intensity of oscillation depending on the properties of the liquid to be mixed (viscosity, etc). Not only in non-contact ultrasonic mixing but also in mechanical mixing with a spatula, a smaller quantity of liquid to be mixed makes it more difficult to ensure uniformity in mixing. 
         [0009]    An object of the present invention is to provide an automatic analyzer and analyzing method having a mixing device with a simple structure which is able to mix liquids uniformly regardless of the quantity of sample and liquid properties. 
       SUMMARY OF THE INVENTION 
       [0010]    In order to achieve the above object, the present invention provides an automatic analyzer as summarized below. 
         [0011]    The automatic analyzer includes a liquid adding device for adding a conditioning liquid into a reaction chamber, wherein the predetermined quantity of liquid is prepared in each reaction chamber before the mixing. 
         [0012]    The reaction chamber is a container in which a sample and a reagent are mixed to react with each other. The reaction liquid in the reaction chamber is analyzed qualitatively and quantitatively by an optical method (measurement of change in absorbance, etc). For the mixing device, various mixing methods are available. For example, a spatula is moved for mixing or the outside of the reaction chamber is irradiated with ultrasonic waves to agitate the liquid by acoustic radiation pressure. The conditioning liquid may be a diluent or physiological saline as used for dilution of a sample or any other special liquid that adjusts the properties of liquid to be mixed (viscosity, surface tension, etc). In automatic analyzers, the quantity of reagent is several times as much as the quantity of sample and the properties of liquid to be mixed largely depends on those of the reagent. Therefore, the properties of the conditioning liquid are optimized depending on those of the reagent and the properties of liquid to be mixed become almost identical regardless of test item. 
         [0013]    Therefore, according to the present invention, there is provided an automatic analyzer which assures uniformity in mixing effects regardless of sample quantity and test item and thus produces analysis results with high repeatability. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS  
         [0014]    The invention will be more particularly described with reference to the accompanying drawings, in which: 
           [0015]      FIG. 1  is a perspective schematic diagram of an automatic analyzer according to an embodiment of the present invention; 
           [0016]      FIG. 2  is a schematic diagram of a mixing mechanism provided in the automatic analyzer and its vicinity according to an embodiment of the present invention; 
           [0017]      FIG. 3  shows an example of a table according to an embodiment of the present invention; and 
           [0018]      FIG. 4  shows an explanatory table of a method of determining the quantity of conditioning liquid according to an embodiment of the present invention. 
           [0019]      FIG. 5  is a block diagram showing the composition of the control unit  13 . 
       
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT 
       [0020]    Next, a preferred embodiment of the present invention will be described referring to the accompanying drawings. 
         [0021]      FIG. 1  is a perspective schematic diagram showing the structure of an automatic analyzer according to an embodiment of the invention and  FIG. 2  is a schematic diagram showing a longitudinal sectional view of a mixing mechanism provided in the automatic analyzer and its vicinity. 
         [0022]    The automatic analyzer according to this embodiment is mainly composed of a sample disk  1 , a reagent disk  2 , a reaction disk  3 , a reaction bath  4 , a sampling mechanism  5 , a pipetting mechanism  6 , a mixing mechanism  7 , a photometric mechanism  8 , a rinsing mechanism  9 , and a controller  40 . The controller  40  further includes a display unit  10 , an input unit  11 , a memory  12 , and a control unit  13 . 
         [0023]    Referring to  FIG. 1 , in the sample disk  1 , plural sample containers  16  containing collected samples are arranged and fixed on the circumference of a circular disk  17  which is rotated in the circumferential direction in a way that it can be repositioned by a drive mechanism composed of a motor, a rotary shaft and so on (not shown). 
         [0024]    In the reagent disk  2 , plural reagent bottles  18   a , which contain reagents to be mixed with samples for reaction, and conditioning liquid bottles  18   b  are arranged and fixed on the circumference of a circular disk  19  which is surrounded by a temperature-controlled cold storage  20 . The circular disk  19  is rotated in the circumferential direction in a way that it can be repositioned by a ordinary drive mechanism composed of a motor, a rotary shaft and so on (not shown). 
         [0025]    The reaction disk  3 , equipped with plural reaction chamber holders  22  provided as a hole in the reaction disk  3  which hold reaction chambers  21  for samples and reagents, is circumferentially rotated and stopped repeatedly in a cycle by a drive mechanism  23  to transport the reaction chambers  21  intermittently. 
         [0026]    The reaction bath  4  is provided along the excursion of movement of the reaction chambers  21 . The reaction bath  4  serves as an incubation bath which uses, for example, a temperature-controlled liquid to control the reaction liquid in a reaction chamber  21  to a given temperature in order to accelerate chemical or biochemical reaction between the sample and reagent. The reaction chambers  21  move inside the reaction bath  4 . 
         [0027]    The sampling mechanism  5  includes a probe  24 , an arm  26  fitted to a support shaft  25  and a drive mechanism (not shown). The drive mechanism is provided for the movement of the probe  24  between the sample disk  1  and the reaction disk  3  with the support shaft  25  as the center of rotation. According to a predetermined sequence, The sampling mechanism  5  supplies a sample in a sample container  16  transported to a predetermined position by rotation of the sample disk  1 , to a reaction chamber  21 . 
         [0028]    Similarly, the pipetting mechanism  6  includes a probe  27 , an arm  29  fitted to a support shaft  28  and a drive mechanism(not shown). The drive mechanism enables the movement of the probe  27  between the reagent disk  2  and the reaction disk  3  with the support shaft  28  which operates as the center of rotation. According to a predetermined sequence, the pipetting mechanism  6  supplies a reagent in a reagent bottle  18   a  or a conditioning liquid in a conditioning liquid bottle  18   b  to a reaction chamber  21 . The reagent bottle  18   a  or conditioning liquid bottle  18   b  is transported to a predetermining position by rotation of the reagent disk  2 . The sample containers  16  and reagent bottles  18   a  contain different types of samples and reagents respectively and as much sample and reagent as needed are supplied to a reaction chamber  21 . Likewise, the conditioning liquid bottles  18   b  contain different types of conditioning liquids and as much conditioning liquid as needed is supplied to the reaction chamber  21 . 
         [0029]    Referring to  FIG. 1 , the mixing mechanism  7  is a non-contact mixing mechanism which irradiates the reaction chamber  21  transported to it (mixing position) with sonic waves sideways to mix the sample, reagent and conditioning liquid in the reaction chamber  21 . It includes a vibrating part  31  fixed in a position to permit the reaction chamber  21  in the mixing position to be irradiated with sonic waves sideways, a piezoelectric element driver  14  for driving a piezoelectric element  30  and a mixing mechanism controller  15 . The mixing mechanism controller  15 , which is connected with the control unit  13 , drives the piezoelectric element driver  14 . 
         [0030]    As shown in  FIG. 2 , in the mixing mechanism  7 , the piezoelectric element  30  as a sound source is provided to the vibrating part  31  with one side of it immersed in temperature-controlled water. The piezoelectric element  30  include a plurality of electrodes  32  which are driven at a given frequency by the piezoelectric element driver  14 . Irradiated direction of sonic wave is controlled by selecting on the electrode  32  which is to be driven. 
         [0031]    Referring to  FIG. 2 , a reaction chamber  21  including a sample and a reagent in it is fixed in the reaction disk  3  through a reaction chamber holder  22 . And as the reaction disk  3  rotates in the circumferential direction, the reaction chamber  21  moves as immersed in the reaction bath  4  with temperature-controlled water in it. 
         [0032]    Then as it arrives at the mixing position and stops, at least one of the piezoelectric elements  30 , which depend on the quantity and properties of the liquid for reaction, is oscillated at a prescribed frequency by the piezoelectric element driver  14 . Oscillating waves generated by the oscillated piezoelectric elements  30  are transmitted as sonic waves in the temperature-controlled water in the reaction bath  4  and reach the sample and reagent in the reaction chamber  21 . The transmitted oscillating waves cause swirls, which stimulate movement of the sample and mix the sample and the reagent. 
         [0033]    Looking back to  FIG. 1 , the photometric mechanism  8  measures properties of the sample in a photometric manner (measurement of absorbance of the reaction liquid in the reaction chamber  21 , etc). The rinsing mechanism  9  includes a plurality of nozzles  33  and a mechanism  34  for moving them up and down. It sucks the reaction liquid in the reaction chamber  21  and discharges the rinse fluid to rinse the chamber  21  transported to it (rinsing position). 
         [0034]    Again referring to the controller  40  of  FIG. 1 , the display unit  10  shows test items, test results and so on as various screen displays and the input unit  11  is used to enter test items and other information. The memory  12  stores predetermined sequences (programs) for controlling various mechanisms and other information (test items, etc). 
         [0035]    The automatic analyzer according to this embodiment further includes a syringe and a pump as components and all these components are controlled by the control unit  13 . 
         [0036]    The operation of the automatic analyzer will be described next. 
         [0037]    First, the reaction chamber  21  rinsed by the rinsing mechanism  9  is transported to the sample injection position by rotation of the reaction disk  3 . And then a sample container  16  with a sample in it is transported to the sampling position by rotation of the sample disk  1 . Similarly the reagent disk  2  transports a required reagent bottle  18   a  to the pipetting position. 
         [0038]    Then, the sampling mechanism  5  is activated to inject a sample from the sample container  16  transported to the sampling position into the reaction chamber  21  transported to the sample injection position using the probe  24 . The reaction chamber  21  with the injected sample in it is transported to the reagent injection position and a reagent is injected from the sample bottle  18   a  transported to the pipetting position on the reagent disk  2 , into the reaction chamber  21  transported to the reagent injection position, by the pipetting mechanism  6 . 
         [0039]    Then, the reaction chamber  21  is transported to the conditioning liquid injection position. Meanwhile, the reagent disk  2  transports a required conditioning liquid bottle  18   b  to the pipetting position and as the reaction chamber  21  arrives at the conditioning liquid injection position, a conditioning liquid is injected from the conditioning liquid bottle  18   b  into the reaction chamber  21  transported to the conditioning liquid injection position, by the pipetting mechanism  6 . 
         [0040]    The reaction chamber  21 , which now contains the injected sample, reagent and conditioning liquid, is transported to the mixing position where they are mixed by the mixing mechanism  7 . 
         [0041]    The absorbance of the reaction liquid thus mixed is measured by the photometric mechanism  8  while the reaction chamber  21  is passing between the light source and the photometer. This measurement cycle is made several times and after finishing all measurement cycles, the reaction chamber  21  is rinsed by the rinsing mechanism  9 . 
         [0042]    A series of steps as mentioned above are taken for each reaction chamber  21  so that the automatic analyzer makes analysis according to this embodiment. 
         [0043]    The characteristics of this embodiment will be explained below. 
         [0044]    This embodiment is characterized in that a conditioning liquid is injected in addition to the sample and reagent before the reaction chamber  21  arrives at the mixing position and thus the quantity and properties of liquid for reaction are controlled within prescribed ranges. 
         [0045]    For the above characteristics, the analyzer takes the following preparations under the control of the control unit  13 :
   (1) To determine the type of conditioning liquid   (2) To determine the injection quantity of conditioning liquid   
 
         [0048]    The first preparation is made, for example, by entry of the type of conditioning liquid suitable for each test item as a parameter through the input unit  11 . Alternatively, it is also possible that a look-up table of conditioning liquid types suitable for different test items as shown in  FIG. 3  is saved in the memory  12  in advance and for each test, the type of conditioning liquid is determined with reference to this look-up table. Another alternative approach is that barcode information is provided with each reagent. The barcode includes information on the type of conditioning liquid suitable for the reagent. And upon entry of the reagent, information on the type of conditioning liquid is also read from the barcode and saved in the memory  12  so that the type of conditioning liquid is determined automatically. 
         [0049]    For the second preparation, the injection quantity is determined, for example, by subtracting the sum of the quantities of sample and reagent from the target quantity of liquid as shown in  FIG. 4 . Then, the composition of the control unit  13  in the controller  40  is described in  FIG. 5 . According to the requested analyzing item, needed volume of sample, reagent and target volume of reaction liquid are extracted from the look-up table shown in  FIG. 4  and inputted in the control unit  13 . The look-up table is stored in the memory  12  in the controller  40 . 
         [0050]    In the control unit  13 , an output of the conditioning liquid volume calculating means  131  and the output of a reserved conditioning liquid detecting means  132  are compared in a comparing means  132  and the result is inputted in a output means  134 . Then the output means send a analyzing start command to the analyzer when the volume of the reserved conditioning liquid in the bottle  18   b  satisfy the needed volume. When the volume of the reserved conditioning liquid is less than the needed volume, The output means  134  send an analyzing inhibiting command to the analyzer. 
         [0051]    When the volume of reserved conditioning liquid is less than needed after the analyzing is started, a alarm adding means  135  add a alarm information to the analyzing result. 
         [0052]    These process is performed by the sequence program processed in the control unit  13 . And special hard logic circuit may also utilized instead. 
         [0053]    Properties of the liquid for reaction such as viscosity and wettability are controlled within ranges suitable for solution mixing by injection of a conditioning liquid. 
         [0054]    After the above two preparations are made, finally the conditioning liquid is injected in the reaction cuvette  21  to adjust the quantity and properties of liquid for reaction so that the required quantities of sample and reagent can be decreased without extremely reducing the size of the reaction chamber  21 . 
         [0055]    In other words, the required quantities of sample and reagent can be decreased without the possibility of encountering a new technical problem which might arise with reaction chamber size reduction. 
         [0056]    In addition, since the quantity and properties of the liquid for reaction are controlled within prescribed ranges, the mixing mechanism  7  can be simplified. 
         [0057]    In other words, the need for complicated control work involved in dealing with different liquid quantities and properties for different test items is eliminated and also the number of electrodes  32  can be decreased, which means that the mixing mechanism  7  can be simplified.