Abstract:
An analyzers that comprise a dispensing unit for dispensing a liquid and having a detachably installed dispensing tip, a transfer unit for transferring the dispensing unit, and a controller for controlling the transfer unit; wherein the controller monitors whether or not the dispensing tip is installed to the dispensing unit during a transfer period of the dispensing unit by the transfer unit and controls the transfer unit based on the monitoring result is disclosed. An analyzing methods are also described.

Description:
[0001]     This application claims priority under 35 U.S.C. § 119 to Japanese Patent Application No. 2004-008328 filed Jan. 15, 2004, the entire content of which is hereby incorporated by reference.  
       FIELD OF THE INVENTION  
       [0002]     The present invention relates to an analyzer, and specifically relates to an analyzer provided with a dispensing unit for dispensing liquid and having a detachably installed dispensing tip.  
       BACKGROUND  
       [0003]     Conventional devices are known which include a dispensing unit (syringe) provided with a detachably installed dispensing tip for suctioning and discharging a predetermined liquid (for example, Japanese Laid-Open Patent Publication No. 2001-59848). In the device disclosed in Japanese Laid-Open Patent Publication No. 2001-59848, whether or not the dispensing tip is installed or detached at the tip installation position and tip disposal position is detected by providing sensors for detecting the presence/absence of the tip.  
         [0004]     In the device disclosed in Japanese Laid-Open Patent Publication No. 2001-59848, however, when the tip is removed from the syringe, such as when the syringe is transported or when liquid is dispensed after the tip has once been installed to the syringe, it is not possible to detect that the tip has been removed. When dispensation is performed when the tip has been removed from the syringe (dispensing means), it is impossible to dispense a reliable quantity of liquid, with the result that the analysis result may be adversely affected.  
       SUMMARY  
       [0005]     The scope of the present invention is defined solely by the appended claims, and is not affected to any degree by the statements within this summary.  
         [0006]     An object of the present invention is to provide an analyzer and analyzing method capable of reliably monitoring the state of installation of the dispensing tip.  
         [0007]     A first aspect of the present invention is an analyzer including a dispensing unit for dispensing a liquid and having a detachably installed dispensing tip, a transfer unit for transferring the dispensing unit, and a controller for controlling the transfer unit; wherein the controller monitors whether or not the dispensing tip is installed to the dispensing unit during a transfer period of the dispensing unit by the transfer unit and controls the transfer unit based on the monitoring result.  
         [0008]     A second aspect of the present invention is an analyzer including a dispensing unit for dispensing a liquid and having a detachably installed dispensing tip, a transfer unit for transferring the dispensing unit, a capacitance sensor connected to the dispensing unit for outputting signals based on capacitance, and a controller for controlling the transfer unit; wherein the controller determines whether or not a dispensing tip is installed to the dispensing unit based on the output signal from the capacitance sensor.  
         [0009]     A third aspect of the present invention is an analyzing method including an installation step of installing a dispensing tip to a dispensing unit for dispensing a liquid, a transfer step for moving the dispensing unit to a predetermined position, a monitoring step for monitoring whether or not a dispensing tip is installed to the dispensing unit, and a removing step for removing the dispensing tip from the dispensing unit; wherein monitoring whether or not a dispensing tip is installed to the dispensing unit is executed during the execution of the transfer step. 
     
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0010]      FIG. 1  is a perspective view showing the overall structure of and embodiment of the analyzer (gene amplification detecting device) of the present invention;  
         [0011]      FIG. 2  is a perspective view showing the overall structure of the assay unit of the analyzer of the embodiment shown in  FIG. 1 ;  
         [0012]      FIG. 3  is a brief plane view of the assay unit of the analyzer of the embodiment shown in  FIG. 2 ;  
         [0013]      FIG. 4  briefly shows the structure of the syringe unit used in the embodiment of the analyzer shown in  FIG. 2 ;  
         [0014]      FIG. 5  is a cross-sectional view showing the structure of the pipette tip used in the embodiment of the analyzer shown in  FIG. 2 ;  
         [0015]      FIG. 6  is a perspective view storage state of the rack accommodating the pipette tips used in the embodiment of the analyzer shown in  FIG. 2 ;  
         [0016]      FIG. 7  is a circuit diagram showing the internal structure of the controller and the electrostatic capacitance sensor of the embodiment of the analyzer of  FIG. 2 ; and  
         [0017]      FIG. 8  is a graph explaining the method by which the controller judges whether or not a predetermined amount of reagent is present in the embodiment of the analyzer shown in  FIG. 7 . 
     
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS  
       [0018]     The preferred embodiment of the present invention is described hereinafter with reference to the drawings.  
         [0019]     The present embodiment is described in terms of a gene amplification detecting device as an example of the analyzer of the present invention. The gene amplification detecting device of the embodiment is an analyzer which supports cancer metastasis diagnosis in tissue excised in cancer surgery, by amplifying cancer-derived nucleic acids (mRNA) present within the excised tissue using the LAMP (loop-mediated isothermal amplification) method, and detecting the mRNA by measuring the turbidity of the liquid produced in conjunction with the amplification. Details of the LAMP method are disclosed in U.S. Pat. No. 6,410,278.  
         [0020]     The overall structure of the gene amplification detecting device and data processing part are described below with reference to  FIG. 1 . The gene amplification detecting device  100  includes an assay part  101 , and data processing part  102  connected to the assay part  101  through a communication line, as shown in  FIG. 1 . The data processing part  102  is a personal computer which includes a keyboard  102   a , mouse  102   b , and display  102   c.    
         [0021]     The assay unit  101  includes a dispensing mechanism  10 , sample container holder  20 , reagent container holder  30 , tip holder  40 , tip disposal part  50 , reaction detecting part  60  incorporating five reaction detecting block  60   a , and transfer unit  70  for moving the dispensing mechanism  10  in X- and Y-axis directions, as shown in  FIGS. 2 and 3 . A control circuit board  80  and power unit  90  for supplying electrical power to the entire apparatus including the control circuit board  80  are built into the assay unit  101 , as shown in  FIG. 2 . The control circuit board  80  controls the operation of the various parts of the assay unit  101 , and controls the input and output from/to external devices. Furthermore, an emergency stop switch  91  is provided at a predetermined location on the front of the assay unit  101 .  
         [0022]     The dispensing mechanism  10  includes an arm  11  which is moved in the X-axis direction and Y-axis direction (horizontal directions) by the transfer unit  70 , and two syringe units  12  capable of independently moving in the Z-axis direction (vertical direction) against the arm  11 . The syringe units  12  include a nozzle  12   a  on the tip of which is detachably mounted a pipette tip (dispensing tip)  41  described later, pump  12   b  for suctioning and discharging, motor  12   c  as a drive source for the pump  12   b , and a pressure sensor  12   e . In the pump  12   b , a suction function and a discharge function are obtained by converting the rotation of the motor  12   c  to a piston movement. Furthermore, the pressure sensor  12   e  detects the pressure during suction and discharge by the pump  12   b . The dispensing mechanism  10  is connected to an electrostatic capacitance sensor  12   d  through a lead wire  12   f . Whether or not suction and discharge are reliably performed can be detected by the electrostatic capacitance sensor  12   d  and the pressure sensor  12   e.    
         [0023]     In the present embodiment, the electrostatic capacitance sensor  12   d  includes an oscillation circuit  121 , resistor R 1 , buffer circuit  123 , detection circuit  124 , resistor R 2 , condenser C 2 , buffer circuit  126 , detection circuit  127 , differential amplification circuit  128 , and comparator  129 , as shown in  FIG. 7 . The oscillation circuit  121  oscillates a voltage having a frequency of several hundred kilohertz (in the present embodiment, approximately 800 kHz), and is connected to the resistors R 1  and R 2 . A lead wire  12   f  is connected between the resistor R 1  and buffer circuit  123 , and the nozzle  12   a  is connected to the lead wire  12   f  (refer to  FIG. 4 ). The electrostatic capacitance C 1  reflects the electrostatic capacitance of the dispensing mechanism  10  when a pipette tip  41  is not installed to the nozzle  12   a . Furthermore, it includes the electrostatic capacitance of the pipette tip  41  when the pipette tip  41  is installed to the nozzle  12   a . The electrostatic capacitance C 1  includes the electrostatic capacitance of the liquid and the pipette tip  41  when the pipette tip  41  installed to the nozzle  12   a  is immersed in the liquid. In this way, the electrostatic capacitance C 1  is a capacitance which changes depending on whether or not the pipette tip  41  is installed and in accordance with the amount of liquid into which the pipette tip  41  is immersed. The resistance value of the resistor R 1  and the electrostatic capacitance C 1 , which includes the pipette tip  41  before the pipette tip  41  is immersed in the liquid, are set in the vicinity of high-range cutoff of the oscillation frequency (approximately 800 kHz) of the oscillating circuit  121 . In this way the amplitude of the voltage value can be reduced as the electrostatic capacitance C 1  increases. The buffer circuit  123  is connected to the resistor R 1 , and connected to the buffer circuit  123  is a detection circuit  124  which has a function of converting the output voltage from the buffer circuit  123  to a DC signal.  
         [0024]     The resistor R 2  is connected to the condenser C 2  having a predetermined electrostatic capacitance, and the condenser C 2  is grounded. The resistor R 2  has a predetermined resistance value, and is set so as to have the same value as the resistance value of the resistor R 1 . The electrostatic capacitance of the condenser C 2  is set to the same value as the electrostatic capacitance C 1  when the pipette tip  41  is not installed to the nozzle  12   a . The electrostatic capacitance of the lead wire  12   f , and the wiring from the resistor R 2  to the condenser C 2  can be ignored since they are sufficiently small compared to the electrostatic capacitance C 1  and C 2 . The buffer circuit  126  is connected to the resistor R 2 , and connected to the buffer circuit  126  is the detection circuit  127  which has a function of converting the output voltage from the buffer circuit  126  to a DC signal. Furthermore, the outputs of the detection circuits  124  and  127  are respectively connected to the input terminals of the differential amplification circuit  128 . The differential amplification circuit  128  has a function of amplifying the difference in potentials of the output signal from the detection circuit  124  and the output signals from the detection circuit  127 . The differential amplification circuit  128  is constructed so as to change the gain (degree of amplification) in accordance with the magnitude of the electrostatic capacitance C 1 .  
         [0025]     The output of the differential amplification circuit  128  is connected to the inverted input terminal of the comparator  129 . A standard voltage, which is resistance-divided obtained by dividing a predetermined voltage (in the present embodiment, 5 V) by the resistors R 1  and R 2 , is input to the non-inverted input terminal of the comparator  129 . The comparator  129  outputs digital signals for the controller  82  to determine whether or not the pipette tip  41  is installed to the syringe unit  12 . Specifically, when a pipette tip  41  is installed to the nozzle  12   a , a signal higher than the standard voltage is input to the inverted input terminal of the comparator  129 , and a digital signal (for example, [0]) is output which represents a negative voltage. Furthermore, when a pipette tip  41  is not installed to the nozzle  12   a , a signal lower than the standard voltage is input to the inverted input terminal of the comparator  129 , and a digital signal (for example, [1]) is output which represents a positive voltage.  
         [0026]     In the present embodiment, the control circuit board  80  monitors whether or not a pipette tip  41  is installed to the syringe unit  12  of the dispensing mechanism  10  during the transfer period of the dispensing mechanism  10  by the transfer unit  70 , and controls the transfer unit  70  based on the monitoring result. The control circuit board  80  includes an A/D conversion circuit  81 , and the controller  82 , as shown in  FIG. 7 . The controller  82  is mainly a microcomputer, and includes a CPU, ROM, RAM and the like. The output signal of the differential amplification circuit  128  is input to the A/D conversion circuit  81 . The A/D conversion circuit  81  is provided to detect whether or not a predetermined amount or more of reagent is present. That is, it is possible for the controller  82  to control the threshold value (refer to  FIG. 8 ) for whether or not a predetermined amount or more of reagent is present by digitalization of the output signal of the differential amplification circuit  128  via the A/D conversion circuit  81 . The threshold value for determining whether or not a predetermined amount or more of reagent is present is set using the keyboard  102   a  and mouse  102   b  of the data processing unit  102  shown in  FIG. 1 . The output signals of the comparator  129  and A/D conversion circuit  81  are input to the controller  82 . The controller  82  controls the transfer unit  70 , and determines whether or not the pipette tip  41  is installed to the syringe unit  12 , determines whether or not a predetermined amount or more of reagent is present, and determines whether or not the tip of the pipette tip  41  is in contact with the liquid surface.  
         [0027]     As shown in  FIGS. 2 and 3 , a sample container table  21 , having five sample container holes  21   a  and holders  21   b , is removably inserted in a concavity (not shown) of the sample container holder  20 . Sample containers  22 , which accommodate soluble extract liquid (samples) prepared by processing (homogenizing, filtering, diluting) excised tissue beforehand, are placed in the five sample container holes  21   a  of the sample container holder  21 .  
         [0028]     A reagent container table  31 , having two primer reagent container holes  31   a  and one enzyme reagent container hole  31   b , and holder  31   c , is removably inserted in a concavity (not shown) of the reagent container holder  30 . The primer reagent container holes  31   a  of the reagent container holder  30  are provided at predetermined spacing along the Y-axis direction, and the enzyme reagent container holes  31   b  are provided only on the front left side. At the front left side of the primer reagent container holes  31   a  and enzyme reagent container holes  31   b  ( FIG. 3 ) are arranged a primer reagent container  32   a  accommodating a cytokeratin  19 (CK  19 ) primer reagent, and enzyme reagent container  32   b  accommodating CK 19  and a β-actin shared enzyme reagent. Furthermore, a primer reagent container  32   a  accommodating a β-actin primer reagent is arranged in the primer reagent container hole  31   a  on the front right side.  
         [0029]     Two racks  42  having 36 provided with holes  42  capable of accommodating 36 pipette tips  41  are removably inserted in two concavities (not shown) of a tip holder  40 . The tip holder  40  is provided with two release buttons  43 . When the release buttons  43  are pressed, the rack  42  can be removed. The pipette tip  41  is formed of a flexible resin material containing carbon, and has an internal filter  41   a . The internal filter  41   a  has a function of preventing erroneous flow of the fluid to the syringe unit  12 . The pipette tip  41  is irradiated by an electron beam when packed before shipment so as to not be adversely affected by nucleic acid amplification by resolving enzymes such as human saliva and the like which may adhere during the pipette tip  41  manufacturing process. Furthermore, the rack  42  in which the pipette tips  41  are loaded is stored with a bottom cover  44  and top cover  45  installed, as shown in  FIG. 6 , before being placed in the tip holder  40 .  
         [0030]     As shown in  FIG. 3 , the tip disposal unit  50  is provided with two tip disposal holes  50   a  for disposing of used pipette tips  41 . A narrow channel  50   b  having a width smaller than the tip disposal hole  50   a  is provided to link the tip disposal holes  50   a.    
         [0031]     Each reaction detection block  60   a  of the reaction detection unit  60  includes a reaction unit  61 , two turbidity detectors  62 , and cover close mechanism  63 , as shown in  FIG. 2 . Each reaction unit  61  is provided with two detection cell holes  61   a  for placement of a detection cell  65 , as shown in  FIG. 3 .  
         [0032]     As shown in  FIG. 3 , the turbidity detector  62  includes an LED light source  62   a , which is a blue color LED with a wavelength of 465 nm mounted on a base  64   a  arranged on one side surface of the reaction unit  61 , and a photodiode photoreceptor  62   b  mounted a base  64   b  arranged on the other side of the reaction unit  61 . A set of turbidity detectors  62  including one LED light source  62   a  and one photodiode photoreceptor  62  are arranged in pairs in the reaction detection block  60   a . Accordingly, the turbidity detection unit  62  including a total of 10 sets of LED light sources  62   a  and photodiode photoreceptors  62   b  are disposed in five reaction detection blocks  60   a . A LED light source  62   a  and its corresponding photodiode photoreceptor  62   b  are arranged such that light approximately 1 mm in diameter is emitted from the LED light source  62   a  and irradiates the bottom part of the detection cell  65  so that the light can be received by the photodiode photoreceptor  62   b . The LED light source  62   a  and the photodiode photoreceptor  62   b  have the functions of detecting the presence/absence of the detection cell by the intensity of the light received by the photodiode photoreceptor  62   b , and detecting (monitoring) in real time the turbidity of the liquid accommodated within the detection cell  65 .  
         [0033]     In the present embodiment, as shown in  FIGS. 2 and 3 , the transfer unit  70  includes a direct-drive guide  71  and ball screw  72  for moving the dispensing mechanism  10  in the Y-axis direction, stepping motor  73  for driving the ball screw  72 , direct-drive guide  74  and ball screw  75  for moving the dispensing mechanism  10  in the X-axis direction, and stepping motor  76  for driving the ball screw  75 . As shown in  FIG. 3 , a rail  71   a  of the Y-axis direct-drive guide  71  and a rail  72   a  of the X-axis direct-drive guide  72  are mounted on a frame  77 . As shown in  FIG. 3 , a support  72   b  for the other end of the ball screw  72  is mounted to the frame  77  through a stepping motor  73 . The linear moving part (not shown) of the ball screw  72  and the slide  71   b  of the Y-axis direct-drive guide  71  are mounted on the arm  11  of the dispensing mechanism  10 . A support  75   a  of one end of the ball screw  75  and a rail  74   a  of the X-axis direct-drive guide  74  are mounted on a support platform  78 . A support  75   b  for the other end of the ball screw  75  and a slide (not shown) of the X-direction direct-drive guide  74  are mounted on the frame  77 . A stepping motor  76  is mounted on the support  75   b  of the other end of the ball screw  75 . The movement of the dispensing mechanism  10  in the XY directions is accomplished by the rotation of the ball screws  72  and  75  via the stepping motors  73  and  76 .  
         [0034]     The operation of the gene amplification detection device  100  is described below with reference to  FIGS. 1 through 8 .  
         [0035]     First, as shown in  FIGS. 2 and 3 , a sample container  22  accommodating soluble extract liquid (sample) prepared by processing (homogenizing, filtering, diluting) excised tissue beforehand is placed in the sample container hole  21   a  of the sample container table  21 . Furthermore, a primer reagent container  32   a  accommodating CK 19  (cytokeratin) primer reagent, and enzyme reagent container  32   b  accommodating enzyme reagent of shared CK 19  and β-actin are respectively placed in the primer reagent container hole  31   a  and the enzyme reagent container hole  31   b  on the front left side. A primer reagent container  32   a  accommodating β-actin primer reagent is placed in the primer reagent container hole  31   a  on the front right side. Two racks  42  housing  36  disposable pipettes  41  are inserted in the concavities (not shown) of the tip holder  40 . In this case, since the initial position (origin position) of the arm  11  of the dispensing mechanism  10  is above the tip disposal unit  50  at a position a distance above the tip holder  40 , as shown in  FIGS. 2 and 3 , the two racks  42  can easily be inserted in the concavities (not shown) of the tip holder  40 . Furthermore, two cells  66   a  of the detection cell  65  are placed in two detection cell holes  61   a  of the reaction unit  61  of each reaction detection block  60   a.    
         [0036]     The operation of the assay unit  101  is started by the keyboard  102   a  or mouse  102   b  after setting the assay criteria and recording the samples has been accomplished using the keyboard  102   a  and mouse  102   b  of the data processing unit  102  shown in  FIG. 1 .  
         [0037]     When the operation of the assay unit  10  starts, the arm  11  of the dispensing mechanism  10  is moved from the start position to the tip placement position by the transfer unit  70 , and thereafter two syringe units  12  of the dispensing mechanism  10  are lowered in the tip holder  40 . In this way, since the tips of the nozzles  12   a  of the two syringe units  12  are pressed into the openings at the top of the two pipette tips  41 , a pipette tip  41  is automatically installed to the tips of the nozzles  12   a  of the two syringe units  12 , as shown in  FIG. 4 . Then, after the two syringe units  12  are lifted, the arm  11  of the dispensing mechanism  10  is moved in the X-axis direction above the two primer reagent containers  32   a , which accommodate CK 19  and β-actin, placed in the reagent container table  31  by the transfer unit  70 . Next, the tips of the two pipette tips  41  installed to the nozzles  12   a  of the two syringe units  12  are respectively inserted into the liquid surface of the CK 19  and β-actin primer reagents within the two primer reagent containers  32   a  by moving the two syringe units  12  downward. Then, the CK 19  and β-actin primer reagents within the two primer reagent containers  32   a  are suctioned by the pumps  12   b  of the syringe units  12 .  
         [0038]     When primer reagent is being suctioned, the tip of the pipette tip  41 , which is formed of electrically conductive resin, contacting the liquid surface is monitored by controller  82  based on the output of the electrostatic capacitance sensor  12   d  (refer to  FIG. 4 ), and the pressure during suctioning by the pump  12   b  is monitored by controller  82  based on the output of the pressure sensor  12   e  (refer to  FIG. 4 ). Whether or not suctioning is reliably performed can be monitored by the controller  82 .  
         [0039]     In this embodiment, during the period after the pipette tip  41  is installed to the syringe unit  12  until the syringe unit  12  is transferred to the tip disposal unit  50 , whether or not the pipette tip  41  has been removed from the syringe unit  12  is monitored a predetermined intervals (for example, intervals of 0.1 sec) by the controller  82 . The period of the transfer also includes not only the on-going transfer, but also the periods of stopping above the suction position and above the discharge position. In regard to details of the monitoring operation, since the electrostatic capacitance C 1  described using  FIG. 7  becomes identical to the electrostatic capacitance C 2  when the pipette tip  41  is not installed to the syringe unit  12 , the amplitude of the voltage input to the buffer circuit  123  becomes identical to the amplitude of the voltage input to the buffer circuit  126 . Therefore, since the output voltage of the differential amplification circuit  128  approaches 0 V, the output voltage of the differential amplification circuit  128 , which is input to the inverted input terminal of the comparator  129 , decreases to less than the standard voltage input to the non-inverted input terminal. As a result, the output signal of the comparator  129  becomes a signal (for example, [1]) representing a positive output voltage. On the other hand, because the electrostatic capacitance C 1  becomes greater than the electrostatic capacitance C 2  when a pipette tip  41  is installed to the syringe unit  12 , the amplitude of the voltage input to the buffer circuit  123  becomes smaller than the amplitude of the voltage input to the buffer circuit  126 . Therefore, since the output voltage of the differential amplification circuit  128  is greater than 0 V (approximately 0.6 V), the output voltage of the differential amplification circuit  128 , which is input to the non-inverted input terminal of the comparator  129 , becomes greater than the standard voltage input to the non-inverted input terminal. As a result, the output signal of the comparator  129  becomes a signal representing a negative output voltage (for example, [0]). Then, whether or not the pipette tip  41  is installed to the syringe unit  12  can be determined by the controller  82  determining whether the output signal of the comparator  129  is [0] or [1].  
         [0040]     When it is determined that the pipette tip  41  has been removed from the syringe unit  12  during the period when the syringe unit  12  is transferred from the tip holder  40  to the tip disposal unit  50 , an error message is displayed on the display  102   c  of the data processing unit  102  after the dispensing mechanism  10  has been transferred to the origin position by the transfer unit  70 . Thereafter, the user executes an error recovery process.  
         [0041]     In the present embodiment, whether or not a predetermined amount (for example, 20 μl) or more of primer reagent is present is monitored during the suctioning of the primer reagent. That is, since the electrostatic capacitance C 1  is large when a predetermined amount (for example, 20 μl) or more of primer reagent is present, there is a great decrease in the amplitude of the voltage. Therefore, the output value of the A/D conversion circuit  81  also increases because the output voltage of the differential amplification circuit  128  increases. As a result, the output value of the A/D conversion circuit  81  becomes greater than the threshold value shown in  FIG. 8 . In this case, the predetermined amount (for example, 20 μl) or more of primer reagent is determined to be present by the controller  82 . However, when the predetermined amount (for example, 20 μl) or more of primer reagent is not present, there is a slight decrease in the amplitude of the voltage because the electrostatic capacitance C 1  is small. Therefore, the output value of the A/D conversion circuit  81  also becomes small because the output voltage of the differential amplification circuit  128  is small. As a result, the output value of the A/D conversion circuit  81  is less than the threshold value shown in  FIG. 8 . In this case, it is determined that the predetermined amount (for example, 20 μl) or more of primer reagent is not present by the controller  82 . When it is determined that the predetermined amount (for example, 20 μl) or more of primer reagent is not present during suctioning, the dispensing mechanism  10  is moved to the origin position, and thereafter an error message is displayed on the display  102   c  of the data processing unit  102 . Subsequently, the user performs an error recovery process.  
         [0042]     After the primer reagent is suctioned and the two syringe units  12  are lifted, the arm  11  of the dispensing mechanism  10  is raised above the reaction detection block  60   a  positioned at the innermost side (inner front side of the apparatus) by the transfer unit  70 . This time the arm  11  of the dispensing mechanism  10  is moved so as to not pass above the other second through fifth reaction detection blocks counting from the inside. Then, at the innermost reaction detection block  60   a , two pipette tips  41  installed to the nozzles  12   a  of the two syringe units  12  are respectively inserted into the two cells  66   a  of the detection cell  65  by lowering the two syringe units  12 . Then, the two primer reagents CK 19  and β-actin are respectively discharged into the two cells  66   a  using the pumps  12   b  of the syringe units  12 . During the discharge (discharge time), the contact of the tip of the pipette tip  41  formed of conductive resin with the liquid surface is monitored by the controller  82  based on the output of the electrostatic capacitance sensor  12   d  (refer to  FIG. 4 ), and the discharge pressure of the pumps  12   b  is monitored by the controller  82  based on the output of the pressure detection sensor  12   e , similar to when suctioning. Whether or not the discharge is reliably accomplished can be monitored by the controller  82 . The suctioning and discharging of the subsequent enzyme reagent and sample can also be similarly monitored by the controller  82 .  
         [0043]     After the primer reagent is discharged and after the two syringe units  12  are lifted, the arm  11  of the dispensing mechanism  10  is moved in the X-axis direction above the tip disposal unit  50  by the transfer unit  70 . In the present embodiment, the time required for the dispensing mechanism  10  to be moved from above the tip holder  40  through a predetermined dispensing position to above the tip disposal unit  50  is approximately 30 seconds. Disposal of the pipette tip  41  is accomplished at the tip disposal unit  50 . Specifically, the pipette tips  41  are inserted into the two tip disposal holes  50   a  (refer to  FIG. 3 ) of the tip disposal unit  50  by lowering the two syringe units  12 . In this state, the pipette tips  41  are moved below the channel  50   b  by the transfer unit  70  moving the arm  11  of the dispensing mechanism  10  in the Y-axis direction. Then, the flange on the top surface of the pipette tip  41  comes into contact with the bottom surface of the bilateral sides of the channel  50   b  and receives a downward force from the bottom surface by the upward movement of the two syringe units  12 , such that the pipette tip  41  is automatically detached from the nozzle  12   a  of the two syringe units  12 . In this way the pipette tips  41  are disposed of in the tip disposal unit  50 . The pipette tips  41  which have been disposed of in the tip disposal unit  50  may be disposed directly, or washed and reused.  
         [0044]     The arm  11  of the dispensing mechanism  10  is again moved to the tip holder  40  by the transfer unit  70 . In the present embodiment, whether or not the pipette tip  41  is detached from the syringe unit  12  is monitored a predetermined intervals (for example, 0.1 seconds) during the period after the pipette tip  41  is disposed of in the tip disposal unit  50  until the dispensing mechanism is moved to the tip holder  40 . This monitoring operation is similar to the operation of monitoring whether or not the pipette tip  41  is not removed during the transfer to the tip disposal unit  50  after the pipette tip  41  has been installed to the syringe unit  12 . When the controller  82  determines that the pipette tip  41  is not detached (removed) from the syringe unit  12  during the period after the pipette tip  41  is disposed of in the tip disposal unit  50  until the dispensing mechanism is moved to the tip holder  40 , the dispensing mechanism  10  is moved to the origin position by the transfer unit  70 , and thereafter an error message is displayed on the display  102   c  of the data processing unit  102 . Subsequently, the user performs an error recovery process.  
         [0045]     The time required for the dispensing mechanism  10  to be moved from above the tip disposal unit  50  to above the tip holder  40  is approximately 5 seconds.  
         [0046]     After the syringe units  12  are moved to the tip holder  40 , two new pipettes  41  are automatically installed at the tip of the nozzles  12   a  of the two syringe units  12  by an operation similar to that previously described at the tip holder  40 . Then, the arm  11  of the dispensing mechanism  10  is moved in the X-axis direction by the transfer unit  70  above the enzyme reagent container  32   b  accommodating shared enzyme reagent of CK  19  and β-actin placed on the reagent container table  31 , and thereafter the enzyme reagent within the enzyme reagent container  32   b  is suctioned. Specifically, after one syringe unit  12  positioned above the enzyme reagent container  32   b  is lowered and enzyme reagent is suctioned, this syringe unit  12  is raised. Thereafter, the arm  11  of the dispensing mechanism  10  is moved in the Y-axis direction by the transfer unit  70  to position the other syringe unit  12  above the same enzyme reagent container  32   b . Then, after this other syringe unit  12  is lowered and has suctioned enzyme reagent from the same enzyme reagent container  32   b , this other syringe unit  12  is raised. Then, after the arm  11  of the dispensing mechanism  10  is moved above the innermost reaction detection block  60   a  by the transfer unit  70 , the shared enzyme reagent CK 19  and β-actin are discharged into two cells  66   a  of the detection cell  65 . In this case, the arm II of the dispensing mechanism  10  is moved so as to not pass above the other second through fifth reaction detection blocks counting from the inside. After the enzyme reagents have been discharged, the arm  11  of the dispensing mechanism  10  is moved above the tip disposal unit  50  by the transfer unit  70 , and disposal of the pipette tips  41  is accomplished.  
         [0047]     After the arm  11  of the dispensing mechanism  10  is moved again to the tip holder  40  by the transfer unit  70 , two new pipette tips  41  are automatically installed to the nozzles  12   a  of the two syringe units  12 . Then, the arm  11  of the dispensing mechanism  10  is moved in the X-axis direction above the sample container  22  accommodating a sample placed on the sample container table  21  by the transfer unit  70 , and subsequently the sample within the same sample container  22  is suctioned. Specifically, after one syringe unit  12  positioned above one sample container  22  is lowered and the sample is suctioned, this syringe unit  12  is raised. Thereafter, the arm  11  of the dispensing mechanism  10  is moved in the Y-axis direction by the transfer unit  70  to position the other syringe unit  12  above the same sample container  22 . Then, after this other syringe unit  12  is lowered and has suctioned the sample from the same sample container  22 , this other syringe unit  12  is raised. Then, after the arm  11  of the dispensing mechanism  10  is moved above the innermost reaction detection block  60   a  by the transfer unit  70 , the two syringe units  12  are lowered and the identical samples are discharged into two cells  66   a  of the detection cell  65 . In this case, the arm  11  of the dispensing mechanism  10  is moved so as to not pass above the other second through fifth reaction detection blocks counting from the inside.  
         [0048]     When sample is discharged into the two cells  66   a  of the detection cell  65 , the sample and enzyme reagent and primer reagent CK  19  and β-actin accommodated in the two cells  66   a  are mixed by multiple repetitions of the suction and discharge actions using the pump  12   b  of the two syringe units  12 . When dispensing the primer reagent, enzyme reagent, and sample, the fluid temperature within the detection cell  65  id maintained at approximately 20° C. Thereafter, the arm  11  of the dispensing mechanism  10  is lifted above the tip disposal unit  50  by the transfer unit  70 , and subsequently the disposal of the pipette tips  41  is accomplished.  
         [0049]     After the primer reagent, enzyme reagent, and sample are discharged into the cell  66   a , the cover closing operation of the cover  67   a  of the detection cell  65  is performed. After the cover closing operation is completed, the marker nucleic acid (mRNA) is amplified in a LAMP (nucleic acid amplification) reaction by raising the fluid temperature within the detection cell  65  from approximately 20° C. to approximately 65° C. Then, the turbidity induced by magnesium pyrophosphate generated in conjunction with the amplification is detected by a nephelometric method. Specifically, the fluid turbidity within the detection cell  65  during the amplification reaction is detected (monitored) in real time using the LED light source  62   a  and photodiode photoreceptor  62   b  shown in  FIG. 3 .  
         [0050]     In the present embodiment, the removal of the pipette tip  41  during transport after the pipette tip  41  has been installed can be detected because whether or not the pipette tip  41  is installed to the syringe unit  12  is monitored even during transfer after the pipette tip  41  is installed to the syringe unit  12  by monitoring whether or not the pipette tip  41  is installed to the syringe unit  12  at predetermined intervals in the period after the pipette tip  41  is installed to the syringe unit  12  until the syringe unit  12  is transferred to the tip disposal unit  50 , that is, during the period when the pipette tip  41  is moved from above the tip holder  40  to the sample container holder  20  and the reagent container holder  30 , during the period when moved from the reagent container holder  30  to the reaction detection unit  60 , and during the period when moved from the reaction detection unit  60  to the tip disposal unit  50 . In this way reliable analysis result can be obtained because inaccurate dispensation caused by removal of the pipette tip  41  after installation can be prevented. Furthermore, in the present embodiment, monitoring of whether or not the pipette tip  41  is installed to the syringe unit  12  can be reliably accomplished by monitoring at extremely short intervals of 0.1 second.  
         [0051]     In the present embodiment, whether or not the pipette tip  41  is removed can be detected when the pipette tip  41  is stopped at the suction position and discharge position and not only when the pipette tip  41  is removed during transfer after the pipette tip  41  is installed by monitoring the removal of the pipette tip  41  even when stopped at a predetermined suction position and discharge position during the transfer by the transfer unit  70  and not only during the period when the dispensing mechanism  10  is moved by the transfer unit  70 .  
         [0052]     In the present embodiment, monitoring whether or not the pipette tip  41  is installed to the syringe unit  12  is accomplished by monitoring electrostatic capacitance, and detection is accomplished not only when the pipette tip  41  is removed from the syringe unit  12 , but also when the pipette tip  41  contacts part of the assay unit  101  of the analyzer  100  while the syringe unit  12  is transferred, and when a user mistakenly touches the pipette tip  41 . Furthermore, the electrostatic capacitance of the pipette tip  41  is easily detected by forming the pipette tip  41  of an electrically conductive resin material.  
         [0053]     As described above, in the present embodiment, whether or not transfer occurs with the pipette tip  41  reliably detached is detectably during the period in which the dispensing mechanism  10  is moved from the tip disposal unit  50  to the tip holder  40  by monitoring whether the pipette tip  41  has been removed from the syringe unit  12  even during the period in which the dispensing mechanism  10  is moved from the tip disposal unit  50  to the tip holder  40 . In this way detachment of the pipette tip  41  can be reliably detected.  
         [0054]     In the present embodiment, in addition to detecting the presence/absence of the installed pipette tip  41 , it is possible to detect whether or not a predetermined amount or more of reagent is accommodated in the reagent container by monitoring whether or not a predetermined amount or more of reagent is accommodated in the reagent container by monitoring the electrostatic capacitance when the pipette tip  41  is inserted into the reagent container as described above.  
         [0055]     The previously described embodiment is to be understood to be an example in all aspects and not in any way limited. The scope of the present invention is described by the scope of the claims and not by the description of the embodiments described above, and all modification are to be understood to be included within the scope of the claims and the meanings and equivalences therein.  
         [0056]     For example, although the analyzer of the present invention has been described by way of example in an application to a gene amplification detection device for amplifying target nucleic acids by the LAMP method in the present embodiment, the present invention is not limited to this application and may be variously applied to gene amplification devices which amplify target nucleic acids by the polymerase chain reaction (PCR) method and ligase chain reaction (LCR) method. The analyzer of the present invention may further be applied to analyzers other than gene amplification devices.  
         [0057]     Although the embodiment is described in terms of monitoring the removal (detachment) of a dispensing tip by the electrostatic capacitance, the present invention is not limited to this arrangement, inasmuch as the removal (detachment) of the dispensing tip also may be monitored by the mass, pressure, amount of oscillation, electrical resistance, amount of reflected light, amount of transmitted light besides electrostatic capacitance.  
         [0058]     Although the embodiment is described in terms of monitoring the presence/absence of a pipette tip at predetermined intervals, the present invention is not limited to this arrangement inasmuch as the presence/absence of the pipette tip also may be monitored at a predetermined position during the transfer period of the syringe unit  12  rather than at predetermined intervals, for example, when the syringe unit  12  is above a dispensing position such as above the reagent container holder  30 , sample container holder  20 , or reaction detection unit  60 .  
         [0059]     Although the embodiment is described in terms of monitoring the presence/absence of a pipette tip every 0.1 seconds, the present invention is not limited to this arrangement inasmuch as accurate monitoring can be accomplished by monitoring at intervals shorter than one second.  
         [0060]     In the embodiment above, whether or not the reagent is present in a predetermined amount or more is monitored during suctioning, however, the present invention is not limited to this arrangement inasmuch as the residual amount of reagent may be monitored in addition to monitoring whether or not the reagent is present in a predetermined amount or more. The residual amount of reagent may be calculated by the controller  82  based on the output value of the A/D conversion circuit  81 .  
         [0061]     In the embodiment above, whether or not the reagent is present in a predetermined amount or more is monitored during suctioning of the primer reagent and enzyme reagent, however the present invention is not limited to this arrangement inasmuch as whether or not a sample is present in a predetermined amount or more also may be monitored during sample suctioning in addition to during the suctioning of the primer reagent and enzyme reagent.  
         [0062]     Although the embodiment has been described in terms of monitoring the presence/absence of a pipette tip during a first transfer period in which the dispensing mechanism  10  is moved from a predetermined position above the tip holder  40  through a predetermined dispensing position to a predetermined position above the tip disposal unit  50 , during a second transfer period in which the dispensing mechanism  10  is moved from a predetermined position above the tip disposal unit  50  to a predetermined position above the tip holder  40 , the period from the completion of the first transfer period to the start of the second transfer period (period of the tip disposal operation by the tip disposal unit  50 ), and the period from the end of the second transfer period to the start of the first transfer period (period of the tip installation operation by the tip holder  40 ), the present invention is not limited to this arrangement inasmuch as various arrangements are possible, such as monitoring only during the first transfer period, monitoring only during the second transfer period, monitoring during both the first transfer period and second transfer period, monitoring during the first transfer period and from the completion of the first transfer period to the start of the second transfer period and the like. Additional arrangements are also possible such as monitoring only during the period in which the pipette tip  41  is moved from above the tip holder  40  to the sample container holder  20  and reagent container holder  30 , monitoring only during the period in which the pipette tip  41  is moved from the sample container holder  20  to the reaction detection unit  60 , monitoring only during the period in which the pipette tip  41  is moved from the reagent container holder  30  to the reaction detection unit  60 , monitoring only during the period in which the pipette tip  41  is moved from the reaction detection unit  60  to the tip disposal unit  50  and the like. Furthermore, other suitable combinations of these monitoring periods are also possible.  
         [0063]     In the embodiment above, the controller  82  determines the presence/absence of an installed pipette tip  41  based on a comparison of the electrostatic capacitance C 1  and electrostatic capacitance C 2 , however, the present invention is not limited to this arrangement inasmuch as the presence/absence of the pipette tip  41  also may be determined by converting the magnitude of the electrostatic capacitance C 1  to a digital signal which is input to the controller  82 , which compares the input electrostatic capacitance C 1  with a standard value stored beforehand.  
         [0064]     Although the origin position of the dispensing mechanism  10  is above the tip disposal unit  50  in the above embodiment, the invention is not limited to this arrangement inasmuch as the origin position may be another position, such as above the tip holder  40  and the like.