Abstract:
The present invention enables a lower cost, a smaller equipment size, and a simplified operation for analysis. The invention comprises the steps of tilting a container  29  containing a biological sample and ejecting the biological sample within the container  29  onto the central portion of a cartridge  33  mounted on a turntable  21;  rotating the turntable  21,  exerting a centrifugal force upon the biological sample on the cartridge  33,  and guiding the biological sample evenly into a plurality of reagent containing parts  41  arranged radially in the cartridge  33;  and analyzing the biological sample after it is guided into each of the reagent containing parts  41  and mixed with a reagent  42, 44  within each of the reagent containing parts  41.

Description:
FIELD OF THE INVENTION  
         [0001]    The present invention relates to a method and an apparatus for mixing a biological sample such as blood with a predetermined reagent and conducting a biochemical analysis, and to a cartridge for the biochemical analysis.  
         BACKGROUND OF THE INVENTION  
         [0002]    As a conventional biochemical analysis apparatus of this kind, a discrete type apparatus such as shown in FIG. 8 is well known.  
           [0003]    This discrete-type biochemical analysis apparatus  1  is generally comprised of a biological sample container retaining part  3  for holding biological sample containers  2 , a reaction container retaining part  5  for holding reaction container s  4 , a biological sample pipetter  6 , a diluent solution bottle  7  for containing a diluent solution, a reagent pipetter  8 , a reagent bottle  9  for containing a reagent, a photometer  10 , and a washing/drying device (not shown).  
           [0004]    In analyzing the biological sample in this arrangement, firstly, the diluent solution within the diluent solution bottle  7  is sucked by the biological sample pipetter  6  and mixed with the biological sample within the biological sample container  2  to dilute the biological sample and then this diluted biological sample is transferred into the reaction container  4 . Secondly, the reagent within the reagent bottle  9  is dispensed in to the reaction container  4  by the reagent pipetter  8  and mixed with the biological sample to measure and analyze the absorbance of the biological sample by the photometer  10 . Then, after completion of the analysis, the biological sample within the reaction container  4  is discarded and the reaction container  4  is washed and dried by the washing/drying device. Subsequently, the analysis is conducted in turn in the same manner for other biological samples.  
           [0005]    However, the conventional biochemical analysis method and the apparatus used therein as described above has required the pipetters  6 ,  8  for diluting the biological sample or adding the reagent into the biological sample, and the washing/drying device for washing and drying the reaction container  4  after completion of the analysis. Thus, there has been a problem in that the operation of biochemical analysis is troublesome and the biochemical analysis apparatus becomes complex and large.  
           [0006]    Further, since only the biological sample is made to be discarded after completion of the analysis, the biological sample needs to be chemically treated for discharging as a wastewater, which has caused a problem of increasing the cost of wastewater treatment.  
           [0007]    The present invention is made to solve these problems and provides a biochemical analysis method and an apparatus used therein as well as a cartridge for biochemical analysis, which enable a lower cost, a smaller equipment size, and a simplified operation for analysis.  
         SUMMARY OF THE INVENTION  
         [0008]    The present invention comprises the steps of tilting a container containing a biological sample and ejecting the biological sample within the container onto the central portion of a cartridge mounted on a turntable; rotating the turntable, exerting a centrifugal force upon the biological sample on the cartridge, and guiding the biological sample evenly into a plurality of reagent containing parts arranged radially in the cartridge; and analyzing the biological sample after it is guided into each of the reagent containing parts and mixed with a reagent therein.  
           [0009]    Preferably, the present invention further comprises the step of guiding the biological sample, which is ejected onto the cartridge having a plurality of pairs of first reagent containing part and second reagent containing part separated vertically by means of a pair of films, into each first reagent containing part to mix with a first reagent and, after analyzing the biological sample, pressing the cartridge from above, rupturing the pair of films by a cutter provided between the first reagent containing part and the second reagent containing part while coupling the first reagent containing part and the second reagent containing part, mixing the biological sample with a second reagent, and analyzing the biological sample.  
           [0010]    Also, the present invention further comprises the step of removing the analyzed cartridge from the turntable and mounting another cartridge to be analyzed next on the turntable.  
           [0011]    Further, the present invention comprises the step of moving a container retaining part, which holds a predetermined number of the containers, along the tangential direction of the turntable and stopping the container retaining part when the container containing the biological sample to be analyzed next comes to confront the turntable.  
           [0012]    Furthermore, the present invention comprises the step of injecting air into the tilted container and ejecting the biological sample within the container onto the cartridge.  
           [0013]    Further, the present invention comprises the step of moving the container retaining part, which holds the predetermined number of the containers, along the tangential direction of the turntable and discarding the container emptied by ejection of the biological sample into a container disposal unit.  
           [0014]    Also, the present invention comprises a turntable capable of mounting a cartridge thereon, the cartridge having a predetermined number of reagent containing parts arranged radially therein each containing a reagent; a biological sample ejecting mechanism part that tilts a container and ejects a biochemical sample within the container onto the central portion of the cartridge; a turntable control part that rotates the turntable, exerts a centrifugal force upon the biological sample on the cartridge, and guides the biological sample evenly into each of the reagent containing parts; and a measuring unit that mixes the biological sample with the reagent within each of the reagent containing parts and performs analysis on predetermined items.  
           [0015]    Preferably, the present invention further comprises a container retaining part provided movably along the tangential direction of the turntable and capable of retaining a predetermined number of containers each containing the biological sample.  
           [0016]    Also, the present invention further comprises a pressurizing part that presses the cartridge from above, wherein each of the reagent containing parts of the cartridge is separated vertically into a first reagent containing part and a second reagent containing part by means of a pair of films, the first reagent containing part and the second reagent containing part containing a first reagent and a second reagent respectively, a coupling part is provided between the first reagent containing part and the second reagent containing part, the coupling part having a cutter, and after the biological sample ejected onto the cartridge is guided into the first reagent containing part, mixed with the first reagent, and analyzed, the pair of films are ruptured by the cutter when the cartridge is pressed from above by the pressurizing part, while the first reagent containing part and the second reagent containing part are coupled by the coupling part and the biological sample is mixed with the second reagent and analyzed.  
           [0017]    Further, the present invention is constructed such that the cartridge has an annular protruded part formed between the central portion thereof and the reagent containing parts, the protruded part having a plurality of cutting parts formed therein to communicate the central portion with the reagent containing parts, and the biological sample ejected onto the central portion is guided through the cutting parts into the reagent containing parts.  
           [0018]    Furthermore, the present invention comprises a cartridge storing unit capable of storing a predetermined number of the cartridges and a cartridge disposal unit capable of containing analyzed ones of the cartridges, wherein the analyzed cartridge is removed from the turntable and discarded into the cartridge disposal unit, and another cartridge to be analyzed next is mounted onto the turntable from the cartridge storing unit.  
           [0019]    Also, the biological sample ejecting mechanism part comprises an air gun that injects air into the tilted container.  
           [0020]    Further, the present invention comprises a biological sample ejecting region provided in the central portion of the cartridge, and a plurality of reagent containing parts provided in the periphery of the biological sample ejecting region and communicating with the biological sample ejecting region; wherein the reagent containing part is separated vertically into a first reagent containing part and a second reagent containing part by means of a pair of films, the first reagent containing part and the second reagent containing part containing a first reagent and a second reagent respectively, a coupling part is provided between the first reagent containing part and the second reagent containing part, the coupling part having a cutter, and when pressed from above, the pair of films are ruptured by the cutter while the first reagent containing part and the second reagent containing part are coupled by the coupling part.  
           [0021]    Preferably, the present invention comprises an annular protruded part formed between the biological sample ejecting region and the reagent containing parts, the protruded part having a plurality of cutting parts formed therein to communicate the biological sample ejecting region with the reagent containing parts.  
           [0022]    Also, the protruded part is formed in two protruded parts, and the cutting parts for each of the protruded parts are arranged evenly such that the cutting parts of one protruded part are not aligned in a same radial direction with the cutting parts of the other protruded part.  
           [0023]    Then, the construction of the present invention described above enables to provide for a simplified analysis operation and a smaller analysis apparatus, as well as reduction of the disposal cost. 
       
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0024]    [0024]FIG. 1 is a plan view of a biochemical analysis apparatus according to an embodiment of the present invention;  
         [0025]    [0025]FIG. 2 is a front view of the biochemical analysis apparatus according to the embodiment of the present invention;  
         [0026]    [0026]FIG. 3 is a side view of the biochemical analysis apparatus according to the embodiment of the present invention;  
         [0027]    [0027]FIG. 4 is a schematic explanatory view illustrating the construction of a cartridge storing unit in the embodiment of the present invention;  
         [0028]    [0028]FIG. 5 is the plan view of a cartridge in the embodiment of the present invention;  
         [0029]    [0029]FIG. 6 is a cross-sectional view of a cartridge in the embodiment of the present invention;  
         [0030]    [0030]FIG. 7 is the cross-sectional view of FIG. 6 taken along the line B-B; and  
         [0031]    [0031]FIG. 8 is a schematic constructional view of a conventional example. 
     
    
     DESCRIPTION OF THE PREFERRED EMBODIMENT  
       [0032]    An embodiment of the present invention will now be described with reference to the drawings.  
         [0033]    FIGS.  1 - 7  illustrate a biochemical analysis apparatus  20  according to an embodiment of the present invention, which will be described below for an exemplary case where a serum is used as a biological sample.  
         [0034]    The biochemical analysis apparatus  20  comprises a turntable  21 , a container retaining part  22  provided to be lineally movable along the tangential direction of the turntable  21 , a barcode reading part  23  arranged in the opposite side of the turntable  21  across the container retaining part  22 , an air gun  24  arranged in the opposite side of the container retaining part  22  across the turntable  21 , a cartridge storing unit  25  provided in proximity to the side of the turntable  21 , a cartridge disposal unit  26  arranged in the opposite side of the cartridge storing unit  25  across the turntable  21 , a container disposal unit  27  arranged beside the cartridge disposal unit  26 , a measuring unit  28  arranged in proximity to the turntable  21 , and a pressurizing part (not shown) provided above the turntable  21 , wherein rotation of the turntable is controlled by a turntable control part (not shown).  
         [0035]    The container retaining part  22  forms a shape of laterally elongated box and is configured to be capable of retaining a predetermined number of containers  29  in an erected condition ( 10  containers in FIG. 1 and FIG. 2), wherein the outer surface of the container  29  has a barcode  30  attached thereto. Preferably, a cylindrical body for containing serum s separated by a biological sample separating apparatus according to a co-pending Japanese Patent Application No. 2002-74616 by the present inventor is used for the container  29 . In that case, since the serums within the cylindrical body are diluted beforehand by a diluent solution, there is no need for the biochemical analysis apparatus  20  to be provided with a mechanism for adding the diluent solution into the serums, thereby enabling a simpler and smaller apparatus to be provided. Also, since the cylindrical body can be placed directly in the container retaining part  22 , there is no need for the diluted serums within the cylindrical body to be transferred into another container, thereby enabling an improvement in working efficiency and reduction of the blood to be collected to a minute amount. Further, enabling the reduction of the blood to be collected to the minute amount also allows the blood collection to be conducted by a patient himself instead of an expert such as a doctor.  
         [0036]    As best shown in FIG. 4, the cartridge storing unit  25  forms a shape of longitudinally elongated cylindrical box and contains cold-reserving equipment  31  in a lower part thereof, wherein a predetermined number of cartridges  33  ( 10  cartridges in FIG. 4) are stacked above the cold-reserving equipment  31  via a cartridge lifting equipment  32 . The cartridge storing unit  25  also has an opening at the upper side surface thereof as a cartridge output port  34 .  
         [0037]    As best shown in FIGS.  5 - 7 , the cartridge  33  has a generally circular plane and is adapted to be stored in alignment within the cartridge storing unit  25  by a pair of recesses  35  formed on a circumferential side surface thereof. Also, the top surface of the cartridge  33  has a raised part  36  formed in the central portion thereof, and a first and a second annular protruded parts  37 ,  38  respectively are formed concentrically around the raised part  36 . The first and second protruded parts  37 ,  38  have a predetermined number of a first and a second cutting parts  39 ,  40  respectively formed radially therein (3 cutting parts in the first protruded part  37  and 6 in the second protruded part  38  in FIG. 6) by which the raised part  36  is communicated with the outer periphery of the second protruded part  38 , and the first cutting part  39  and the second cutting part  40  are evenly arranged such that they are not aligned in a same radial direction.  
         [0038]    Further, the cartridge  33  has a predetermined number of reagent containing parts  41  (12 containing pats in FIG. 6) disposed radially around the second protruded part  38 , and the reagent containing part  41  is divided vertically into a first reagent containing part  43  for containing a first reagent  42  and a second reagent containing part  45  for containing a second reagent  44 . Then, the bottom surface of the first reagent containing part  43  and the top surface of the second reagent containing part  45  are formed of a first and a second films  46 ,  47  respectively, and a coupling part  48  is provided between the first and the second films  46 ,  47 . The coupling part  48  comprises a cutter  49 , a pair of mating grooves  50  formed respectively on each side of the cutter  49 , and a pair of passage holes  54  perforated respectively between the cutter  49  and each of the mating grooves  50 , wherein the first reagent containing part  43  and the second reagent containing  44  are adapted to be coupled by side walls  51 ,  52  of the first and second reagent containing parts  43 ,  45  respectively being fitted into the pair of mating grooves  50 . In addition, a film  53  is attached on the top surface of the cartridge  33  excluding the raised part  36 .  
         [0039]    The operation of the biochemical analysis apparatus  20  will now be described.  
         [0040]    The container retaining part  22  holding 10 pieces of the container  29  that contains the diluted serums is moved laterally (rightward in FIG. 1 and FIG. 2) until the first container  29  (the rightmost container in FIG. 1 and FIG. 2) comes to confront the turntable  21  where the container retaining part  22  is stopped. After the barcode reading part  23  reads the barcode  30  of the container  29 , the container  29  is tilted toward the turntable  21  while the cartridge  33  is moved from the cartridge storing unit  25  to the turntable  21  and locked thereon. When the container  29  is tilted by 90 degrees or more, the air gun  24  injects air toward the inside of the container  29  so that the serums within the container  29  is ejected onto the raised part  36  of the cartridge  33  by the injection pressure.  
         [0041]    Once the serums are ejected onto the raised part  36 , the turntable  21  rotates at a high speed under the control of the turntable control part (not shown) and the centrifugal force acting on the serums moves them along the top surface of the turntable  21  toward the outer periphery thereof. Subsequently, the serums pass through the first cutting part  39 , between the first protruded part  37  and the second protruded part  38 , and through the second cutting part  40  in turn, until the serums are guided into each of the first reagent containing part  43  to mix with the first reagent  42 . At this moment, since the first and second cutting parts  39 ,  40  are arranged evenly such that they are not aligned in a same radial direction, the serums are evenly delivered to each of the first reagent containing parts  43 . Then, the turntable  21  is rotated by a predetermined angle (30 degrees in this case) at a time by the turntable control part and the measuring unit  28  performs the analysis on the predetermined items (12 items in this case). Once the analysis on the serums within the first reagent containing part  43  is completed, the cartridge  33  is pressed from above by the pressurizing part (not shown) so that the first and second films  46 ,  47  are ruptured by the cutter  49  while the side walls  51 ,  52  are fitted into the mating grooves  50  to couple the first reagent containing part  43  and the second reagent containing part  45 . This allows the serums to be received into the second reagent containing part  45  through the passage holes  54  and mixed with the second reagent  44 . Then, the turntable  21  is rotated again by 30 degrees at a time, and the measuring unit  28  performs the analysis on the 12 items for the serums within each of the second reagent containing parts  45 .  
         [0042]    Once all the analyses on the serums contained in each of the second reagent containing parts  45  are completed, the cartridge  33  is removed from the turntable  21  to be discarded and stored in the cartridge disposal unit  26 . Also, the container  29  that has been emptied by ejection of the serums is moved, after it is returned to the previous erected condition, by the container retaining part  22  to the position where it confronts the container disposal unit  27  and where it is discarded and stored in the container disposal unit  27 .  
         [0043]    Subsequently, the serums contained in other containers  29  are analyzed similarly and, once the analyses on the serums within all containers  29  (10 containers in this case) are completed, another set of containers  29  containing new serums are placed in the container retaining part  22  while a new set of cartridges  33  are placed in the cartridge storing unit  25 , and the analyses are conducted according to the same procedure as described above.  
         [0044]    It is noted that, although in the above embodiment the case of using the serum as the biological sample has been described, the present invention is also applicable to other biological samples than the serum, such as urine, feces, pleural effusion, ascites, saliva, and the like, and adaptable to not only an infectious disease but also a special examination by altering the type of the reagent within the reagent containing part  41  of the cartridge  33 .  
         [0045]    According to the present invention as described above, the mechanism for adding the reagent is not required since the reagent is contained beforehand in the cartridge, and also a washing/drying device for the container is not required since the container for containing the biological sample is disposable. Thus, the present invention enables a simplified analysis operation and a smaller analysis apparatus to be provided.  
         [0046]    Furthermore, since the cartridge is adapted to be discarded with the analyzed biological sample and reagent remaining within the cartridge, it becomes possible for the cartridge to be burnt out, which can provide for reduction of the disposal cost.