Abstract:
A reaction apparatus for biorelated substances includes a reaction solution driver that drives a reaction solution that is provided for a reaction chip and contains a biorelated substance, a pressure transfer medium that is located between the reaction chip and the reaction solution driver and transfers a pressure variation from the reaction solution driver to the reaction solution, and a pressure detector that detects a pressure state of the pressure transfer medium.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS  
       [0001]     This is a Continuation Application of PCT Application No. PCT/JP 2004/012841, filed Sep. 3, 2004, which was not published under PCT Article 21(2) in Japanese.  
         [0002]     This application is based upon and claims the benefit of priority from prior Japanese Patent Application No. 2003-332128, filed Sep. 24, 2003, the entire contents of which are incorporated herein by reference. 
     
    
     BACKGROUND OF THE INVENTION  
       [0003]     1. Field of the Invention  
         [0004]     The present invention relates to a light measurement apparatus and method that are used for the tests of biorelated substances such as genes and read a microarray chip used for DNA analysis, epidemiological analysis, and the like and, more specifically, measure fluorescence or the like from the microarray chip.  
         [0005]     2. Description of the Related Art  
         [0006]     Recent technical developments in the gene engineering field are remarkable. For example, studies have been made to decipher human genome base sequences considered to amount to 100,000.  
         [0007]     On the other hand, a microarray technique is used for studies for searching for DNAs that have influences on various kinds of hereditary diseases in, for example, enzyme immunoassay methods and fluorescence antibody methods that are used for various kinds of diagnoses and use antigen-antibody reactions.  
         [0008]     The microarray technique is a technique that uses a microarray chip obtained by spotting cDNAs or oligo DNAs in the form of a matrix at a high density (intervals of several hundred μm or less) as probes on an Si wafer, slide glass, or membrane filter.  
         [0009]     In such a microarray technique, for example, a DNA that is labeled with a fluorescent dye and is extracted from a cell of an able-bodied person or a DNA that is labeled with a fluorescent dye and extracted from a cell of a test body having a heredity disease is dropped on each probe of the microarray chip by using a pipette. The DNA of each test body and a probe are hybridized, and excitation light for exciting each fluorescent dye is applied to each probe in this state, and fluorescence emitted from each probe is detected by a photodetector. Thereafter, a specific probe with which the DNA of each test body is hybridized is obtained from the result of fluorescence detection on the microarray chip. In addition, by comparing hybridized DNAs, a DNA that has expressed due to a disease or a defective DNA is specified.  
         [0010]     PCT (WO) 2003-509663 discloses an analysis-test apparatus having a substrate that orientates each through channel, a method therefor, and equipment using the apparatus. International Publication WO03/027673 brochure discloses a genetic testing apparatus and a target nucleic acid detection method.  
       BRIEF SUMMARY OF THE INVENTION  
       [0011]     The present invention is directed to, for example, a reaction apparatus for living organ related substances. A reaction apparatus of the present invention comprises reaction solution driving means for driving a reaction solution that is provided for a reaction chip and contains a biorelated substance, a pressure transfer medium that is located between the reaction chip and the reaction solution driving means and transfers a pressure variation from the reaction solution driving means to the reaction solution, and pressure detection means for detecting a pressure state of the pressure transfer medium.  
         [0012]     Advantages of the invention will be set forth in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention. Advantages of the invention may be realized and obtained by means of the instrumentalities and combinations particularly pointed out hereinafter. 
     
    
     BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING  
       [0013]     The accompanying drawings, which are incorporated in and constitute a part of the specification, illustrate presently preferred embodiments of the invention, and together with the general description given above and the detailed description of the preferred embodiments given below, serve to explain the principles of the invention.  
         [0014]      FIG. 1  shows a reaction vessel applied to a reaction apparatus according to an embodiment of the present invention;  
         [0015]      FIG. 2  shows a reaction chip housed in the reaction vessel shown in  FIG. 1 ;  
         [0016]      FIG. 3  schematically shows the arrangement of the reaction apparatus according to the embodiment of the present invention;  
         [0017]      FIG. 4  shows a sectional view of the incubator and reaction vessel shown in  FIG. 3 ;  
         [0018]      FIG. 5  shows the internal arrangement of the control unit shown in  FIG. 3 ;  
         [0019]      FIG. 6  shows variations in pressure inside a reaction solution driving tube when a pump is operated;  
         [0020]      FIG. 7A  shows variations in pressure in the reaction solution driving tube while reaction solution driving operation is not normally performed due to a crack in a solid-phase carrier of a reaction chip;  
         [0021]      FIG. 7B  shows variations in pressure in the reaction solution driving tube while reaction solution driving operation is normally performed; and  
         [0022]      FIG. 8  shows changes in pressure in the reaction solution driving tube while clogging or the like occurs in a conduit. 
     
    
     DETAILED DESCRIPTION OF THE INVENTION  
       [0023]     An embodiment of the present invention will be described below with reference to the views of the accompanying drawing.  
       First Embodiment  
       [0024]     This embodiment is directed to a reaction apparatus for living organ related substances such as genes.  FIG. 1  shows a reaction vessel applied to the reaction apparatus according to the embodiment of the present invention.  FIG. 2  shows a reaction chip housed in the reaction vessel shown in  FIG. 1 .  
         [0025]     As shown in  FIG. 1 , a reaction vessel  100  has an upper vessel half  101  and a lower vessel half  102 , which clamp and hold a reaction chip  103 . The upper vessel half  101  and the lower vessel half  102 , which are of polycarbonate, are fixed to each other by a proper technique using screws, an adhesive, or the like to hold the reaction chip  103 .  
         [0026]     The upper vessel half  101  has reaction solution storage portions  101   a , which store a reaction solution containing a biorelated substance to be tested. The reaction vessel  100  in this embodiment has four reaction solution storage portions  101   a . However, the number of reaction solution storage portions is not limited to four. For example, one reaction solution storage portion may be provided. The lower vessel half  102  has, on its side surface, connection portions  102   a  that transfer pressure for driving the reaction solution.  
         [0027]     The reaction chip  103  shown in  FIG. 2  is, for example, a DNA chip for DNA tests, but is not limited to this, and includes any kinds of chips for widely testing biorelated substances. The reaction chip  103  comprises a solid-phase carrier  105  and two support members  104  bonded to the upper and lower surfaces of the solid-phase carrier  105 . The two support members  104  have openings at positions corresponding to each other. Those portions of the solid-phase carrier  105  which are exposed from the openings of the support members  104  form reaction portions provided for reaction with a biorelated substance to be tested. The reaction portions are provided with spots, each of which has probes for capturing a specific biorelated substance. The solid-phase carrier  105  has many fine holes extending through up and down, and the probes are fixed in the respective holes.  
         [0028]     In this specification, “biorelated substances” include not only cells of animals, plants, microorganisms, and the like but also substances originating from viruses that cannot proliferate by themselves unless parasitizing such cells. Biorelated substances include substances in natural forms that are directly extracted/isolated from these cells, substances produced by using a gene optical technique, and chemically modified substances. More specifically, biorelated substances include hormones, enzymes, antibodies, antigens, abzymes, other proteins, nucleic acids, and the like.  
         [0029]     In addition, a “probe” means a substance that specifically binds with the above biorelated substance, and includes any one of substances in the following relationships: a ligand such as a hormone and its acceptor, an enzyme and its substrate, an antigen and its antibody, a nucleic acid having a specific sequence and a nucleic acid having a sequence complementary thereto, and the like.  
         [0030]     The solid-phase carrier  105 , positioned between the upper vessel half  101  and the lower vessel half  102 , allows the passage of the reaction solution stored in the reaction solution storage portion  101   a . That is, the reaction solution stored in the reaction solution storage portion  101   a  can pass through the solid-phase carrier  105  of the reaction chip  103  to flow back and forth between the upper vessel half  101  and the lower vessel half  102 .  
         [0031]      FIG. 3  schematically shows the arrangement of the reaction apparatus according to the embodiment of the present invention.  FIG. 4  shows a sectional view of the incubator and reaction vessel shown in  FIG. 3 .  
         [0032]     The reaction apparatus comprises an incubator  200 , which houses and holds the reaction vessel  100 , a pump  600  serving as a driving means for driving the reaction solution containing an biorelated substance in the reaction vessel  100 , a reaction solution driving tube  400 , which is a pressure transfer medium to transfer pressure variations from the pump  600  to the reaction solution, and a pressure sensor  500 , which is a pressure detection means for detecting the pressure state of the reaction solution driving tube  400 .  
         [0033]     The incubator  200  has a function of keeping the temperature of the reaction vessel  100  at a predetermined temperature in order to induce a reaction in the reaction vessel  100  or control a reaction in the reaction vessel  100 .  
         [0034]     The incubator  200  is divided into an upper incubator  201  and a lower incubator  202  that are foldably coupled to each other through a hinge  205  so as to be unfolded and folded through the hinge  205 .  FIG. 3  shows a state wherein the incubator  200  is unfolded.  FIG. 4  shows a state wherein the incubator  200  is folded.  
         [0035]     The lower incubator  202  has a recess that can house the reaction vessel  100 . When the operator sets the reaction vessel  100  in the recess of the lower incubator  202  and tilts a set lever (not shown) to the “mount” side, a pressure arm  203  acts to press the reaction vessel  100  against the incubator wall surface, thereby setting the reaction vessel  100 .  
         [0036]     The upper incubator  201  has a cover glass  204  functioning as an optical window. When the upper incubator  201  is folded to overlap the lower incubator  202 , the cover glass  204  is located immediately above the reaction solution storage portion  101   a  of the reaction vessel  100  and comes into tight contact therewith. With this structure, the reaction state of a spot exiting on the solid-phase carrier  105  of the reaction chip  103  can be measured from above the incubator  200  by an optical system (not shown) such as a microscope and a CCD camera  1000 .  
         [0037]     The CCD camera  1000  is built into an optical system (not shown) installed between the incubator  200  and a computer  800  and is electrically connected to the computer  800  through a dedicated cable  1000   a . The computer  800  comprises a camera interface PCI board (not shown), and issues an image sensing instruction to the CCD camera  1000  or captures a sensed image.  
         [0038]     The upper incubator  201  incorporates a heater  206  and a resistance temperature sensor  207 . The heater  206  and the resistance temperature sensor  207  are connected to a thermoregulator  300  through signal lines  300   a  and  300   b , respectively. Likewise, the lower incubator  202  incorporates a heater  208  and a resistance temperature sensor  209 . The heater  208  and the resistance temperature sensor  209  are connected to the thermoregulator  300  through the signal lines  300   c  and  300   d , respectively.  
         [0039]     The thermoregulator  300  controls the heaters  206  and  208  on the basis of the information obtained by the resistance temperature sensors  207  and  209  so as to keep the temperature of the reaction vessel  100  held in the incubator  200  at a designated temperature. The heater  206 , resistance temperature sensor  207 , heater  208 , resistance temperature sensor  209 , and thermoregulator  300  in the incubator  200  constitute a temperature control means for controlling the temperature of the reaction solution.  
         [0040]     The reaction solution driving tubes  400  are connected to the lower incubator  202 . A pressure transfer tunnel  202   a  is formed to extend from the connection end of each reaction solution driving tube  400  into the lower incubator  202 , and is connected to the connection portion  102   a  formed on a side surface of the lower vessel half  102  of the reaction vessel  100 . The reaction solution driving tubes  400  are filled with pure water.  
         [0041]     The pressure sensor  500  is connected inside each of the conduits of the reaction solution driving tubes  400 . The pressure sensor  500  is a pressure sensor of the gage pressure type that detects a pressure difference from the current pressure, and can measure pressures of −100 kPa to 100 kPa. More specifically, this sensor operates at a supply voltage of 5 V and outputs 2.48 V when it is placed under atmospheric pressure on its specifications, and the voltage of the sensor rises by 22.5 mV per kPa (up to 4.73 V at 100 kPa) under positive pressure, and drops by 22.5 mV per kPa (up to 0.23 V at −100 kPa) under negative pressure.  
         [0042]     The pressure sensors  500  are connected to a control unit  700  through connection cables and connectors  700   a  to  700   d . These connection cables are used to supply power to the pressure sensors  500  and interface output signals.  
         [0043]     The pump  600  is connected to one end of the reaction solution driving tube  400 . The pump  600  incorporates a 250-μL capacity injection syringe (not shown) and a syringe operation motor, and can suck a pressure transfer medium in the reaction solution driving tube  400  in increments of 1 μL within the range of 1 to 250 μL and transfer the pressure to the reaction vessel  100 .  
         [0044]     The pump  600 , which operates at a supply voltage of 24 V, incorporates a communication interface circuit (not shown) and a CPU for overall control. Communication connectors  600   a  and  600   b  and communication lines  600   c  and  600   d  are daisy-chained into one communication line to allow a maximum of 16 pumps  600  to be operated. In this embodiment, the pumps  600  are designed to communicate by RS-232C (9,600 bps).  
         [0045]     The thermoregulator  300  can perform temperature control on the two heaters  206  and  208 , and can communicate temperature setting information, current temperature information, and the like associated with the heaters through a communication line  300   e by RS-232C (9,600 bps). The computer  800  is connected to a keyboard  810  through a cable  810   a . Upon receiving various conditions (a temperature, the number of times of reaction solution driving operation, the number of times of image sensing operation with the CCD camera, and the like) for the hybridization of the reaction solution, which are input by the operator through the keyboard  810 , the computer  800 , for example, drives the respective constituent devices on the basis of instruction values and notifies the operator of the current state of hybridization.  
         [0046]     The computer  800  is connected to a monitor  900  through a cable  900   a . The monitor  900  displays a hybridization condition setting window by dedicated control software or a hybridization state. The computer  800  is connected to the control unit  700  through an RS-232C communication line  800   a.    
         [0047]      FIG. 5  shows the internal arrangement of the control unit  700  shown in  FIG. 3 . As shown in  FIG. 5 , an FPGA  705  is mounted in the central portion of the control unit  700 . The FPGA  705  is a semiconductor device whose internal circuit can be freely designed and rewritten, and can incorporate a soft-macro CPU core  706  as well as a ROM, RAM, and user logic.  
         [0048]     The FPGA  705  in this embodiment is an FPGA available from ALTERA, which is equipped with a Nios (registered trademark) processor, which is a soft-macro CPU. Building the CPU core  706  in the FPGA  705  makes it possible to be free from the influences of the discontinuation of production as in the case of existing CPUs and freely set/change the number of UARTs. This can also realize a multiprocessor mode having two or more CPUs arranged in an FPGA so as to meet future requirements for feature expansion and an increase in operation speed.  
         [0049]     In this embodiment, the CPU core  706  performs command transmission/reception in RS-232C communication with the computer  800 , RS-232C communication with the pumps  600 , and RS-232C communication with the thermoregulator  300 .  
         [0050]     A/D converters  701  are for converting voltages output from the pressure sensors  500  into 8-bit digital data. In this embodiment, voltages output from the pressure sensors  500  are respectively received by the connectors  700   a  to  700   d  and converted into digital data by the A/D converters  701 . The resultant 8-bit data are input to the FPGA  705  through signal lines  701   a  to  701   d . A signal  701   e  output from the FPGA  705  is an A/D clock having a frequency of 1 kHz. The FPGA  705  performs control to output the A/D clock  701   e  only when a voltage from the pressure sensor  500  is required and perform A/D conversion.  
         [0051]     RS-232C interface ICs  702 ,  703 , and  704  are for interfacing between CMOS voltages and RS-232C voltages. Since signals  705   a ,  705   b , and  705   c  on the FPGA  705  side are at the CMOS level and connectors  700   e ,  700   f , and  700   g  are at the RS-232C level, these interface ICs provide interface for the voltage difference between them.  
         [0052]     A specific example of the operation of the reaction apparatus according to this embodiment having the above arrangement will be described below.  
         [0053]     The operator turns on the main switch (not shown) to activate the respective devices of the reaction apparatus for biorelated substances and make them initialize by themselves. In addition, the operator unfolds the incubator  200  and places the reaction vessel  100  on the lower incubator  202 . The operator tilts the set level to the “mount” side. The pressure arm  203  then presses the reaction vessel  100  against a side surface of the lower incubator  202 , thereby completely setting the reaction vessel  100 . The operator folds the upper incubator  201  to cover the lower incubator  202 .  
         [0054]     Subsequently, the operator sets hybridization conditions by using the keyboard  810  of the computer  800  and the monitor  900 . When this operation is complete, the operator issues an instruction to start hybridization by using the keyboard  810 .  
         [0055]     Upon receiving the instruction to start hybridization, the computer  800  sends out operation parameters for the respective devices to the control unit through the communication line  800   a . In the control unit  700  that has received the operation parameters from the computer  800 , the CPU core  706  in the FPGA  705  operates to send out set temperatures of the incubator  200  (set temperatures of the upper incubator  201  and lower incubator  202 ) to the thermoregulator  300  through the communication line  705   c , RS-232C interface IC  704 , connector  700   g , and communication line  300   e.    
         [0056]     When the control unit  700  receives a parameter reception completion command and the current temperature data of the upper incubator  201  and lower incubator  202  from the thermoregulator  300 , the CPU core  706  operates to send out the size of the syringe incorporated in each pump, the operating minimum resolution, a driving current value for each syringe driving motor, and the like through the communication line  705   a , RS-232C interface IC  702 , connector  700   e , and communication line  600   c.    
         [0057]     In this embodiment, as shown in  FIG. 3 , the four pumps  600  are daisy-chained, and “a”, “b”, “c”, and “d” are automatically assigned as IDs for pump identification to the pumps in increasing order of distance from the communication line  600   c . When, therefore, the pump located nearest to the communication line  600   c  is to be operated, “a”+“command” are sent out. When the four pumps are to be simultaneously operated, “a”+“command”+“b”+“command”+“c”+“command”+“d”+“command” are continuously transmitted.  
         [0058]     Upon receiving parameter reception completion commands from all the pumps  600 , the control unit  700  continuously and repeatedly receives current temperature data of the upper incubator  201  and lower incubator  202  from the thermoregulator  300 . The control unit  700  continuously transmits the current temperature data of the upper incubator  201  and lower incubator  202  to the computer  800 .  
         [0059]     The computer  800  keeps receiving this data and is set in a standby state while displaying the message “Please wait until the set temperature is reached” or the like on the screen of the monitor  900  until the temperature set by the operator is reached.  
         [0060]     When the set temperature is reached, the computer  800  sends out, to the control unit  700 , commands to cause the four pumps  600  to perform 50-μL suction operation so as to perform hybridization in the reaction vessel  100 . Upon receiving the commands, the control unit  700  sends out commands to the pumps  600  to cause them to operate on the basis of instructions from the computer  800 . At the same time, the FPGA  705  in the control unit  700  sends out the A/D clocks  701   e  to the A/D converters  701  to cause them to A/D-convert voltages representing the pressures in the conduits that are output from the pressure sensors  500 . At the same time, the FPGA  705  receives digital data  701   a  to  701   d sent out from the A/D converters  701 .  
         [0061]      FIG. 6  shows variations in pressure in the reaction solution driving tube  400  when the pump is operated. Referring to  FIG. 6 , a state  6   a  is set before the start of the operation of the pump  600 . In this state, the internal pressure of the reaction solution driving tube  400  is equal to atmospheric pressure. The pressure sensor  500  outputs 2.48 V (reference voltage) under atmospheric pressure according to the specifications.  
         [0062]     Referring to  FIG. 6 , a state  6   b  is a state wherein the pump  600  is performing suction operation. As the suction operation proceeds, the pressure in the reaction solution driving tube  400  decreases. At this time, the FPGA  705  of the control unit  700  sends out the A/D clock  701   e  to the A/D converter  701 , converts a voltage output from the pressure sensor  500  into digital data in real time, and receives the data. Subsequently, the CPU core  706  calculates an actual pressure by subtracting the digital data currently obtained by A/D conversion from the reference voltage.  
         [0063]     At the current point of time, the subtraction result is a voltage value. The magnitude of the voltage value as the subtraction result may be regarded as a pressure, and changes in pressure may be monitored. Alternatively, since it is known that a voltage change of 22.5 mV occurs per kPa, as described above, the calculated voltage value may be divided by 22.5 mV to handle the actual pressure in kPa. In this embodiment, in order to increase the computation speed, the voltage value obtained by subtraction is used without performing any division.  
         [0064]     When the suction operation of the pump  600  is complete, a state  6   c  in  FIG. 6  is set. In the state  6   c , the pressure in the reaction solution driving tube  400  that has been a high negative pressure gradually returns to atmospheric pressure as the reaction solution moves. When the pressure approximately reaches atmospheric pressure at the final stage in the state  6   c , the movement of the reaction solution ends.  
         [0065]     Subsequently, when the pump  600  starts evacuation operation, a state  6   d  is set, and the pressure gradually increases. At this time, the CPU core  706  in the FPGA  705  calculates an actual pressure by subtracting the digital data currently obtained by A/D conversion from the reference voltage. Note, however, that subtraction is performed according to (digital data currently obtained by A/D conversion)−(reference voltage). This is because, since the pump  600  performs evacuation operation, a positive pressure is produced inside the reaction solution driving tube  400 . The CPU core  706  changes computation in accordance with the current operation state of the pump  600 .  
         [0066]     When the evacuation operation of the pump  600  is complete, a state  6   e  in  FIG. 6  is set, and the pressure gradually reaches atmospheric pressure. At this time, the reaction solution slowly returns to the reaction solution storage portion  101   a  of the upper vessel half  101  of the reaction vessel  100 . When normal reaction solution driving operation is performed, variations in pressure occur as shown in  FIG. 6 .  
         [0067]     If the solid-phase carrier  105  of the reaction chip  103  inside the reaction vessel  100  cracks and a large amount of reaction resolution leaks from the crack in the solid-phase carrier  105  of the reaction chip  103 , the pressure in the reaction solution driving tube  400  almost ceases to rise as shown in  FIG. 7A .  FIG. 7B  shows variations in pressure in the reaction solution driving tube  400  in a state wherein no crack is produced in the solid-phase carrier  105  of the reaction chip  103  and reaction solution driving is normally performed.  
         [0068]      FIG. 8  shows variations in pressure in the reaction solution driving tube  400  while clogging or the like occurs in the conduit. Referring to  FIG. 8 , a state  8   a  indicates a period during which the pump  600  performs suction operation. In a normal state wherein there is no problem in the solid-phase carrier  105  of the reaction chip  103  inside the reaction vessel  100 , when the pump  600  stops 50-pL suction operation, an output voltage from the pressure sensor  500  does not become equal to or lower than a voltage  8   b . If, however, clogging or the like occurs in the conduit, the pressure in the reaction solution driving tube  400  becomes much lower than the normal pressure, and the output voltage from the pressure sensor  500  drops to a voltage  8   c . That is, the pressure in the reaction solution driving tube  400  becomes much lower than the normal pressure.  
         [0069]     In addition, after the pump  600  stops 50-μL suction operation as well, the output voltage from the pressure sensor  500  does not change as indicated by a state  8   d . That is, the pressure is kept decreased and does not return to near atmospheric pressure.  
         [0070]     The pressure value of the reaction solution driving tube  400  that is set when suction operation is normally complete and the pump is stopped at the time of mounting of the reaction vessel  100  is stored as (reference voltage)−(output voltage from pressure sensor when pump is stopped) in a memory (not shown) in the FPGA  705  of the control unit  700 . In addition, the pressure value of the reaction solution driving tube  400  that is set when evacuation operation is normally complete and the pump is stopped at the time of mounting of the reaction vessel  100  is stored as (output voltage from pressure sensor when pump is stopped)−(reference voltage) in the memory.  
         [0071]     More specifically, the pressure value (voltage) set at the time of normal suction operation is 0.191 V to 0.233 V (in consideration of variations), and the output value (voltage) set at the time of normal evacuation operation is 0.285 V to 0.32 V (in consideration of variations). Therefore, at the time of suction operation, the FPGA  705  in the control unit  700  performs computation with the reference voltage on the basis of the digital data  701   a  to  701   d  sent out from the A/D converter  701  at the same time when the  600  starts operating, and keeps comparing the computation result with the voltage values stored in the memory.  
         [0072]     If the computation result falls within the range of 0.191 V to 0.233 V when the pump  600  finishes 50-μL suction operation, the control unit  700  judges that a normal state is set. The control unit  700  then returns a normal termination command to the computer  800 .  
         [0073]     If, however, the computation result falls within the range of 0 to 0.190 V even after the end of the 50-μL suction operation of the pump  600 , since it indicates that the pressure has not decreased below the specified value, the control unit  700  returns, to the computer  800 , an abnormal termination command indicating the occurrence of pressure leakage in the conduit, a crack in the solid-phase carrier  105  of the reaction chip  103 , or a failure to mount the reaction vessel  100  in the incubator  200 . Upon receiving this command, the computer  800  displays the message “A pressure abnormality has occurred. Please check the occurrence of a crack in the chip, a mount failure in the incubator, or pressure leakage in the piping system” or the like on the monitor  900  to call attention to the operator.  
         [0074]     In contrast, if the computation result is equal to or more than 0.234 V even when the pump  600  finishes 50-μL suction operation, since it indicates that the pressure has decreased below the specified value, the control unit  700  returns, to the computer  800 , an abnormal termination command indicating that clogging has occurred in the conduit. Upon receiving this command, the computer  800  displays the message “A pressure abnormality has occurred. Please check whether clogging has occurred in the piping system” or the like on the monitor  900  to call attention to the operator.  
         [0075]     When pump evacuation operation is to be performed, a similar algorithm is used. In evacuation operation, if the computation result falls within the range of 0.285 V to 0.32 V when the  600  finishes 50-μL evacuation operation, the control unit  700  judges that a normal state is set, and returns a normal termination command to the computer  800 .  
         [0076]     If the computation result falls within the range of 0 to 0.285 V even after the end of the 50-μL evacuation operation of the pump  600 , since it indicates that the pressure has not increased above the specified value, the control unit  700  returns, to the computer  800 , an abnormal termination command indicating the occurrence of pressure leakage in the conduit, a crack in the solid-phase carrier  105  of the reaction chip  103 , or a failure to mount the reaction vessel  100  in the incubator  200 . Upon receiving this command, the computer  800  displays the message “A pressure abnormality has occurred. Please check the occurrence of a crack in the chip, a mount failure in the incubator, or pressure leakage in the piping system” or the like on the monitor  900  to call attention to the operator.  
         [0077]     In contrast, if the computation result is equal to or more than 0.33 V even when the pump  600  finishes 50-μL suction operation, since it indicates that the pressure has increased above the specified value, the control unit  700  returns, to the computer  800 , an abnormal termination command indicating that clogging has occurred in the conduit. Upon receiving this command, the computer  800  displays the message “A pressure abnormality has occurred. Please check whether clogging has occurred in the piping system” or the like on the monitor  900  to call attention to the operator.  
         [0078]     When an abnormality has occurred, the operator can arbitrarily see a log of pressure values at the time of the operation of the pump as a graph on the monitor  900  by operating the keyboard  810 .  
         [0079]     As described above, the control unit  700  detects the occurrence of a pressure state abnormality by judging the pressure state detected by the pressure sensor  500  at a specific operation timing of the pump  600 . The occurrence of a pressure state abnormality is detected by comparing an output value (output voltage) from the pressure sensor  500  with a predetermined reference value (reference voltage). When the occurrence of a pressure state abnormality is detected, the control unit  700  displays a message indicating the occurrence of a pressure state abnormality on the monitor  900  through the computer  800 .  
         [0080]     If no pressure abnormality has occurred, the pump  600  repeats suction/evacuation operation by a designated number of times to make hybridization proceed, and finally images reaction results with the CCD camera  1000 , thereby completing the entire process. The computer  800  controls the CCD camera  1000  to perform image sensing with the CCD camera  1000  in synchronism with a state wherein the pump  600  finishes 50-μL suction operation and the reaction solution is completely gone from the reaction chip  103 .  
         [0081]     Upon detecting the occurrence of a pressure state abnormality, the control unit  700  restores the pressure state of the pump  600  to the initial state and performs termination processing. At the same time, the control unit  700  may return, to the computer  800 , a command to display a message for prompting the interruption of hybridization on the monitor  900 .  
         [0082]     In this case, the control unit  700  controls the pump  600  on the basis of the pressure state detected by the pressure sensor  500  such that while the pressure state is normal, the pump  600  is driven to continue hybridization, and when a pressure state abnormality is detected, the pump  600  is stopped.  
         [0083]     In addition, the pressure state detected by the pressure sensor  500  may be always displayed on the monitor  900 .  
         [0084]     This embodiment has been described on the assumption that the operation speed of the pump  600  is constant, and the reaction solution permeability of the reaction chip  103  to be used and the viscosity of the reaction solution to be used are constant. Assume that the reaction chips  103  to be used vary in reaction resolution permeability and reaction solutions to be used vary in viscosity. In this case, if the operation speed of the pump  600  is constant, the pressure in the reaction solution driving tube  400  greatly varies depending on the combination of the above values. If the reaction solution permeability of the reaction chip  103  is very high, and the viscosity of a reaction solution is low, no problem arises even when the operation speed of the pump  600  is high. Assume that the reaction solution permeability of the reaction chip  103  is very poor, and the viscosity of a reaction resolution is very high. In this case, if the reaction solution is driven while the operation speed of the pump  600  is kept high, a heavy distortion load acts on the reaction chip  103 . In the worst case, the reaction chip  103  may be damaged. If the operation speed of the pump  600  is always kept low to prevent the reaction chip  103  from being damaged even with the combination of the worst reaction solution permeability and the lowest viscosity of a reaction solution, it may take an unnecessarily long period of time for reaction solution driving. By only changing the control program without changing the arrangement of this embodiment, reaction solution driving can be performed such that the operation speed of the pump  600  is changed within a predetermined range so as to make the pressure in the reaction solution driving tube  400  fall within a predetermined range while monitoring the magnitude of the pressure and how it changes.  
         [0085]     In the reaction apparatus for biorelated substances, the operator activates each device and performs initialization by turning on the main switch (not shown). At this time, program checking operation for the piping system may be simultaneously performed. More specifically, after the reaction apparatus determines that a reaction vessel is not mounted, the control unit  700  issues an instruction to perform suction operation to the pump  600 . At the same time, computation with a reference voltage is performed on the basis of the digital data  701   a  to  701   d  sent out from the A/D converter  701 , and it is judged whether the computation result is equal to or less than a specified voltage value. If clogging has occurred in the piping system or the pressure transfer medium has deteriorated to have high viscosity, the computed voltage becomes higher than the specified voltage. Since no reaction vessel is mounted, this makes it possible for the reaction apparatus to judge that the piping system is abnormal.  
         [0086]     The above embodiment has exemplified the test of a gene reaction using a DNA chip. However, the present invention may be applied to the tests of other biorelated substances using another test chip comprising a substrate on that probes for testing a biorelated substance other than a gene are formed as solid-phase probes, e.g., the test of an immune reaction or the like. In addition, as substrates on that various kinds of probes are formed as solid-phase probes, substrates in various forms can be used. For example, two-dimensional substrates such as silicon and glass substrates, various kinds of beads, various kinds of porous substrates, and various kinds of gels can be used.  
         [0087]     Although the embodiments of the present invention have been described with reference to the views of the accompanying drawing, the present invention is not limited to these embodiments. The embodiments can be variously modified and changed within the spirit and scope of the invention.