Patent Publication Number: US-6989132-B2

Title: Liquid transfer apparatus and reaction vessel

Description:
BACKGROUND OF THE INVENTION 
     1. Field of the Invention 
     The present invention relates to a reaction vessel and a liquid transfer apparatus for handling a small amount of liquid. 
     The liquid transfer apparatus according to the present invention is to be used for, e.g., micropipet. More particularly, the liquid transfer apparatus is used for transferring a small amount of solution from a reaction vessel to another vessel. 
     The reaction vessel according to the present invention is to be used for pretreatment for any type of analysis; e.g., enzyme treatment, derivatization, or gene amplification. 
     2. Description of the Related Art 
     At the time of handling of a small amount of liquid sample (hereinafter called simply a “sample”), a 96-well or 384-well microtiter plate is used as a reaction vessel. Further, a capillary is used as a reaction vessel. A sample and a reagent are sealed and react with each other in the capillary. 
     A transfer pipet is used as a liquid transfer apparatus for handling a small amount of sample. The transfer pipet aspirates and discharges a sample in and from a tube-like nozzle by means of an aspirating and discharging mechanism, such as a syringe. 
     In relation to the scale of reaction conforming to the volume of the vessel, the cost of reagents becomes a heavy burden. For instance, in the fields of various screening and genotyping operations, a reduction in the scale of reaction (on the order of nanoliter) has been pursued. In addition, there exists demand for improved efficiency attained by means of simultaneously processing a lot of samples. 
     In the related-art liquid transfer apparatus using a syringe, however, for a reduction of the scales of reaction, there is limitation caused from the volume of the syringe. Further, there is another limitation that the liquid transfer apparatus becomes complicated in accordance with an increase in the number of channels assigned to the samples. Moreover, recycling of a few channels is troublesome, for reasons of an increase in a turnaround time because of a necessity of rinsing the nozzle and an increase in the time required to move nozzles. 
     In a case where reaction of a small amount of sample is effected in the reduced volume of a reaction vessel, the vessel must be sealed for preventing a change in the concentration of a reagent resulting from evaporation or cessation of reaction resulting from insufficient mixing. In a case where the vessel is sealed, in order to extract a sample after reaction, the hermetic state of the inside of the vessel must be broken. Hence, many precautions are to be taken, such as a precaution against a loss of the sample which would be induced by a change in the pressure of a minute space causing from opening and closing of the vessel. 
     SUMMARY OF THE INVENTION 
     An object according to the invention is to provide a liquid transfer apparatus and a reaction vessel which enable handling of a small amount of solution. 
     In order to attain the foregoing object, a liquid transfer apparatus according to the present invention comprises: 
     a capillary for aspirating liquid from one end thereof by means of capillarity; 
     a pressure mechanism for pressurizing an inside of the capillary from the other end of the capillary; and 
     a connection mechanism for bringing the other end of the capillary into an ambient pressure or a state in which the outer end of the capillary is connected to the pressure mechanism. 
     One end of the capillary is dipped into the solution while the other end of the capillary is opened to the ambient pressure by means of the connection mechanism. The solution is aspirated into the capillary by means of capillarity. The amount of solution to be aspirated is determined by an inner diameter and length of the capillary. Subsequently, the other end of the capillary is connected to the pressure mechanism by means of the connection mechanism. The inside of the capillary is pressurized by means of the pressure mechanism from the other end of the capillary, thereby discharging the solution to the outside. Therefore, a small amount of solution can be handled. Particularly, when the amount of liquid to be handle is fixed, such as in the case of application of the liquid transfer apparatus to predetermined pretreatment for an analysis system, there can embodied efficient transfer corresponding to a small amount of sample with a simple structure. Further, even in the case of a large number of samples, the samples can be transferred by means of increasing the number of capillaries. 
     The foregoing object also can be achieved by a reaction vessel, comprising: 
     a vessel substrate having at least one recess formed in one surface thereof; and 
     an elastic member for covering the surface of the vessel substrate in which the recess is formed. 
     After the solution has been stored in the recess of the vessel substrate, the elastic member is laid over the vessel substrate so that the elastic member covers the surface of the vessel substrate where the solution is stored in the recess. Thus, a hermetic reaction space to be used for reacting a small amount of solution can be formed. After reaction, the capillary is penetrated through the elastic member. By means of deformation of the elastic member, the inside of the reaction space is pressurized, thus extracting the solution into the capillary from the inside of the recess. 
     Further, in the above-mentioned reaction vessel, it is preferable that the vessel substrate has a discharge section formed on the bottom of the recess so that the discharge section becomes ruptured by pressure when the elastic member is urged toward the recess. 
     After the solution has been stored in the recess of the vessel substrate, the elastic member is laid over the vessel substrate so that the elastic member covers the surface of the vessel substrate where the solution is stored in the recess. Thus, a hermetic reaction space to be used for reacting a small amount of solution can be formed. After reaction, the elastic member is urged toward the inside of the recess, and thus the reaction space is pressurized, thereby rupturing the discharge section. Thus, the solution is recovered from the bottom of the recess. 
     Preferably, the connection mechanism has a hermetic space formation member and a switching mechanism. The hermetic space formation member forms a hermetic space between the other end of the capillary and the pressure mechanism. The switching mechanism brings the hermetic space into a sealed state or into an ambient pressure by means of switching action of a valve. 
     Preferably, the connection mechanism has a capillary support member and a pressure unit. The capillary support member is brought into hermetic contact with an outer periphery of the capillary. The pressure unit is removably connected to the capillary support member. The pressure unit forms a hermetic space between the other end of the capillary and the pressure mechanism when connected to the capillary support member. 
     Preferably, there action vessel further comprises a guide member having a through hole for guiding the capillary or an urging member which urges the elastic member toward the recess. The through hole is formed so as to correspond to the position of the recess. 
     Preferably, the reaction vessel further comprises a pair of heat conductive members for sandwiching the vessel substrate and the elastic member. 
     Preferably, a through hole for guiding the capillary or an urging member which urges the elastic member toward the recess is formed in the heat conductive member facing the elastic member and in the position corresponding to the position of the recess. 
    
    
     
       BRIEF DESCRIPTIONS OF THE DRAWINGS 
         FIGS. 1A through 1D  are illustrations showing operations of a liquid transfer apparatus according to a first embodiment of the present invention; 
         FIG. 2  is a schematic view showing a portion of the liquid transfer apparatus according to the first embodiment with a portion thereof being represented in cross section; 
         FIG. 3  is a schematic view showing a second embodiment of a liquid transfer apparatus with a portion thereof being represented in cross section; 
         FIGS. 4A through 4E  are illustrations showing operations of the liquid transfer apparatus according to the second embodiment of the present invention; 
         FIGS. 5A and 5B  are side cross-sectional views showing operation of a third embodiment of a liquid transfer apparatus; 
         FIG. 6A  is a side cross-sectional view showing a fourth embodiment of a liquid transfer apparatus of the present invention; 
         FIG. 6B  is a side elevation view showing the fourth embodiment of the liquid transfer apparatus of the present invention; 
         FIG. 7  is a cross-sectional view showing an embodiment of a reaction vessel; 
         FIG. 8  is a cross-sectional view showing an example process for extracting solution from a well according to the embodiment; 
         FIG. 9  is a cross-sectional view showing another example process for extracting solution from a well according to the embodiment; and 
         FIG. 10  is a cross-sectional view showing another embodiment of a reaction vessel. 
     
    
    
     DETAILED DESCRIPTIONS OF THE INVENTION 
       FIGS. 1A through 1D  are illustrations showing operations of a first embodiment of a liquid transfer vessel.  FIG. 2  is a schematic view showing a portion of the liquid transfer vessel according to the first embodiment with a portion thereof being represented in cross section.  FIGS. 1A through 1D  omit illustration of a three-way valve  7 , an air release channel  9 , a pressure channel  11 , and a pressure mechanism  13 . The configuration of the liquid transfer apparatus according to the first embodiment will now be described by reference to  FIGS. 1A through 2 . 
     The liquid transfer apparatus includes a plate-shaped support member  3  having a through hole formed therein. A capillary (capillary tube)  1  is fixedly into the through hole of the support member  3  while one end  1   a  is oriented downward and another end  1   b  is oriented upward. The space between the capillary  1  and the through hole of the support member  3  is hermetically sealed. 
     One end of a tube  5  is connected to a part of the surface of the support member  3  facing the end  1   b  of the capillary, so as to cover the end  1   b . The other end of the tube  5  is connected to the three-way valve  7 . The air release channel  9  and the pressure channel  11  connected to the pressure mechanism  13  are also connected to the three-way valve  7 . The three-way valve  7  switchably connects the tube  5  to the air release channel  9  or the pressure channel  11 . The pressure mechanism  13  supplies a pressurization gas to the pressure channel  11 , to thereby pressurize the inside of the capillary  1  by way of the three-way valve  7  and the tube  5 . For example, a compressor, a pressurized gas cylinder, or a syringing mechanism can be employed as the pressure mechanism  13 . 
     A hermetic space formation member constituting the liquid transfer apparatus according to the present invention is constituted of the support member  3  and the tube  5 . Further, a switching mechanism is constituted of the three-way valve  7 . A connection mechanism constituting the liquid transfer apparatus according to the present invention is constituted of the support member  3 , the tube  5 , the three-way valve  7 , the air release channel  9 , and the pressure channel  11 . 
     The operation of the liquid transfer apparatus will now be described by reference to  FIGS. 1A through 2 . 
     (1) As shown in  FIG. 1A , the capillary  1  is moved to a position above a vessel  17  having stored therein a solution to be transferred, such as a sample or a reagent. 
     (2) While the tube  5  is connected to the air release channel  9  via the three-way valve  7 , the vessel  17  is raised until the end  1   a  of the capillary  1  is dipped into the solution  15  as shown in  FIG. 1B . By means of capillarity, the solution  15  enters and fills the capillary  1 . The amount of solution  15  aspirated into the capillary  1  depends on the volume of the capillary  1 . For example, for the amount of solution of 0.5 mL, the capillary which has an inner diameter of 100 μm, an outer diameter 300 μm and a length of 64 mm is used. However, generally, the capillary which has an inner diameter of from 50 to 100 μm and an outer diameter of from 200 to 350 μm is used. Subsequently, the three-way valve  7  is switched so as to connect the tube  5  to the pressure channel  11 . 
     (3) After the end  1   a  of the capillary  1  has been separated from the solution  15  in the vessel  17  by means of lowering the vessel  17 , the capillary  1  is moved to another vessel  19  to which the solution is to be transferred, as shown in  FIG. 1C . 
     (4) Next, a pressurization gas is supplied to the pressure channel  11  by means of the pressure mechanism  13 , thus pressurizing the inside of the capillary  1  from the other end  1   b  of the capillary  1  by way of the three-way valve  7  and the tube  5 . Thus, the solution  15  held in the capillary  1  is discharged into the vessel  19 , as shown in  FIG. 1D . Hence, the amount of solution  15  determined by the volume of the capillary  1  is stored in the vessel  19 . 
     In the first embodiment, the liquid transfer apparatus has only one capillary. When solutions stored in a 96-well or 384-well titer plate are to be transferred, a plurality of capillaries are arranged so as to conform to the positions of wells on the plate. When the capillaries are pressurized with a pressure sufficiently greater than the tube resistance of the capillaries, a plurality of samples can be transferred concurrently. 
     The inside of the capillary  1  can be rinsed through repetition of dipping the end  1   a  into a rinsing liquid such that the inside of the capillary  1  is filled with the rinsing liquid, and then discharging the rinsing liquid to a drainage. 
     If the capillary  1  is made disposable, by hermetically holding an inexpensive capillary with an elastic member (elastomer), rinsing of the capillary  1  is obviated. 
       FIG. 3  is a schematic view showing a second embodiment of a liquid transfer apparatus with a portion thereof being represented in cross section. In the second embodiment, a capillary is disposable, and a diaphragm is employed as a liquid discharge mechanism. Those which are identical with the elements shown in  FIG. 1  are assigned the same reference numerals, and their explanations are omitted. 
     An elastomer  25  is sandwiched between a top plate  21  and a base plate  23 . The plates  21 , 23  respectively have a plurality of through holes to be used for receiving capillaries, and the through holes are formed in corresponding positions of the capillaries. The capillaries  1  are inserted into respective through holes of the top and base plates  21 ,  23  and penetrate through the elastomer  25  while the ends  1   a  of the capillaries are oriented downward and the other ends  1   b  are oriented upward. Thus, the capillaries  1  are hermetically secured by the elastomer  25 . Here, the top plate  21 , the base plate  23 , and the elastomer  25  constitute a capillary support member  27 . 
     The surface of the top plate  21  that faces away from the elastomer  25  is removably brought into hermetic contact with a pressure unit  33  via an O-ring  29 . The pressure unit  33  has a plurality of pressure chambers  31  for individually covering the ends  1   b  of the capillaries  1  and forming hermetic spaces. One wall surface of the individual pressure chamber  31  is formed from a diaphragm  35 . The pressure unit  33  has a common pressure chamber  37  at the space adjacent to the side of each diaphragm  35  that faces away from the pressure chamber  31 . The pressure unit  33  further has a tube  39  for connecting the common pressure chamber  37  to a pressure mechanism  41 . The common pressure chamber  37 , exclusive of the portion thereof connected to the tube  39 , is a hermetic space. The pressure mechanism  41  is for pressurizing a pressurization gas to the tube  39 , to thereby pressurize the inside of the common pressure chamber  37 . Among other devices, a compressor, a pressurized gas cylinder, or a syringing mechanism can be employed as the pressure mechanism  41 . 
     A connection mechanism constituting the liquid transfer apparatus according to the present invention is constituted of the capillary support member  27  having the top plate  21 , the base plate  23 , and the elastomer  25 , and the pressure unit  33  having the O-ring  29 , the pressure chambers  31 , the diaphragm  35 , the common pressure chamber  37 , and the tube  39 . 
       FIG. 4  shows operations of the liquid transfer apparatus shown in  FIG. 3 . 
     (1) The capillary support member  27  separated from the pressure unit  33  is moved to a position above a plurality of vessels  17  which are arranged so as to conform with the layout of the capillaries  1  and which store the solutions  15  to be transferred, as shown in  FIG. 4A . The capillaries  1  are located in positions above the corresponding vessels  17 . 
     (2) The ends  1   a  of the respective capillaries  1  are dipped into the solutions  15  by means of raising the vessels  17 , as shown in  FIG. 4B . Thus, the solutions  15  enter and fill the capillaries  1  by means of capillarity. The amount of solution  15  aspirated into each capillary  1  is determined by the volume of each capillary  1 . 
     (3) Next, the vessels  17  are lowered, thereby separating the ends  1   a  of the capillaries  1  from the solutions  15  of the vessels  17 . Subsequently, the capillary support member  27  is moved to a position above vessels  19  which are arranged so as to conform with the layout of the capillaries  1  and into which the solutions are to be transferred, as shown in  FIG. 4C . The capillaries  1  are located in positions above the corresponding vessels  19 . 
     (4) Then, the pressure unit  33  is attached to the capillary support mechanism  27  by means of the O-ring  29 . 
     (5) Via the tube  39 , a pressurization gas is supplied to the common pressure chamber  37  by means of the pressure mechanism  41 . As a result of the common pressure chamber  37  being pressurized, the diaphragm  35  is urged toward the pressure chambers  31 , thereby pressurizing the pressure chambers  31 . As a result of the pressure chambers  31  being pressurized, the capillaries  1  are pressurized from the other sides  1   b  to thereby discharging the solutions  15  held in the capillaries  1  into the vessels  19 . The solutions  15  whose amounts are determined by the volumes of the capillaries  1  are stored in the respective vessels  19 . 
     In the second embodiment, the pressure chamber  31  enclosing the end  1   b  of the capillary  1  is pressurized by the diaphragm  35 , thereby preventing occurrence of excessive inflow of a gas from the end  1   a  of the capillary  1  after discharge of the solution. Hence, there can be inhibited occurrence of bubbles in the solution  15  stored in the vessel  19  or evaporation of the solution  15 . 
     In the second embodiment, a plurality of capillaries  1  simultaneously discharge a solution by means of pressurizing the common pressure chamber  37 . If separate pressurization spaces are assigned to the respective pressure chambers  31  via a diaphragm  35 , discharge of a solution from an arbitrary capillary  1  can be selected. If there is provided a pressure unit corresponding solely to one capillary, discharge of a solution from an arbitrary capillary  1  can be selected. 
     In the second embodiment shown in  FIGS. 3 through 4E , the diaphragm  35  is urged toward the pressure chambers  31  by means of a pressurization gas. However, the present invention is not limited to such an embodiment. The diaphragm  35  may be fluctuated upward and downward by means of, for example, a solenoid or a piezoelectric element. 
       FIGS. 5A and 5B  are side cross-sectional views showing operation of a third embodiment of a liquid transfer apparatus. In the third embodiment, there is provided a solenoid as a pressure mechanism for urging the diaphragm  35  toward the pressure chambers  31 . Those which are identical with the elements shown in  FIG. 1  are assigned the same reference numerals, and their explanations are omitted. 
     The liquid transfer apparatus has the capillary support member  27  constituted of the top plate  21 , the base plate  23 , and the elastomer  25 . As same as in the case of the second embodiment shown in  FIG. 3 , a plurality of capillaries  1  are arranged in the capillary support member  27 . 
     The side of the top plate  21  that faces away from the elastomer  25  is removably brought into hermetic contact with a pressure unit  33   a  via the O-ring  29 . The pressure unit  33   a  has a plurality of the pressure chambers  31  for individually covering the ends  1   b  of the capillaries  1  and forming hermetic spaces. One wall surface of the individual pressure chamber  31  is formed from the diaphragm  35 . 
     The pressure unit  33   a  has a solenoid  34  serving as a pressure mechanism which is disposed in a position in the vicinity of the side of the diaphragm  35  that faces away from the pressure chamber  31 . The solenoid  34  is assigned to each of the pressure chambers  31 . The solenoid  34  has a core member  34   a , a coil  34   b , a spring  34   c , a power source  34   d , and a switch  34   e . The core member  34   a  has magnetic properties for urging the diaphragm  35  toward the pressure chamber  31 . The coil  34   b  and the spring  34   c  drive the core member  34   a  to slidably move. The power source  34   d  applies an electric current to the coil  34   b . The switch  34   e  controls energization of the coil  34   b . When the switch  34   e  is in an OFF state and no current flows into the coil  34   b , the core member  34   a  is urged toward the coil  34   b  by means of the spring  34   c . In contrast, when the switch  34   e  is in an ON state and an electric current flows to the coil  34   b , the core member  34   a  is urged toward the diaphragm  35  by means of the magnetic field caused by the coil  34   b.    
     A connection mechanism constituting the liquid transfer device according to the third invention is constituted of the capillary support member  27  having the top plate  21 , the base plate  23 , and the elastomer  25 , and the pressure unit  33   a  having the O-ring  29 , the pressure chamber  31 , and the diaphragm  35 . 
     The operation of the liquid transfer apparatus according to the third embodiment is described. 
     (A) As same as in the case of steps shown in  FIGS. 4A  through  4 C, the solution  15  is aspirated into the capillaries  1 , and the capillary support member  27  is moved to a position above the vessels  19 . Subsequently, the pressure unit  33   a  is attached to the capillary support mechanism  27  via the O-ring  29  as shown in  FIG. 5A . At this time, the switch  34   e  of the solenoid  34  remains deactivated, and the core member  34   a  remains urged toward the coil  34   b.    
     (B) The switch  34   e  is turned on, thereby applying an electric current to the coil  34   b  and causing the coil  34   b  to produce a magnetic field. Thereby, the core member  34   a  is moved toward the diaphragm  35 . The core member  34   a  urges the diaphragm  35  toward the pressure chamber  31 , thus pressurizing the pressure chamber  31  as shown in  FIG. 5B . The inside of the capillary  1  is pressurized from the end  1   b  by means of pressurizing the inside of the pressure chamber  31 , thereby discharging the solution  15  held in the capillary  1  into the vessel  19 . Thus, the solution  15  whose amount is determined by the volume of the capillary  1  is stored in the vessel  19 . 
     In the third embodiment, so long as a switch  34   a  assigned to a desired capillary  1  is turned on, the solution of an arbitrary capillary  1  can be selectively discharged by means of turning on the switch  34   a.    
       FIGS. 6A and 6B  show a fourth embodiment of a liquid transfer apparatus.  FIG. 6A  is a side cross-sectional view and  FIG. 6B  is a side elevation view. Those which are identical with the elements shown in  FIG. 1  are assigned the same reference numerals, and their explanations are omitted. 
     The capillary  1  is fixedly into the through hole of the support member  3  while one end  1   a  is oriented downward and another end  1   b  is oriented upward. The space between the capillary  1  and the through hole of the support member  3  is hermetically sealed. 
     A pressure chamber member  43  enclosing the end  1   b  is removably attached to the side of the support member  3  that faces the end  1   b  of the capillary  1 . A heater  47  is attached to an outer wall of the pressure chamber member  43 . A power supply  49  is electrically connected to the heater  47 . Circuitry constituted of the heater  47  and the power supply  49  is provided with a switch  50  for controlling application of power to the heater  47 . 
     In the fourth embodiment, after the solution has been aspirated into the capillary  1  by means of capillarity, the pressure chamber member  43  is attached to the support member  3  while the switch  50  remains off. Then, the switch  50  is then turned on, thereby energizing the heater  47 . By means of heat produced by the heater  47 , the internal pressure of the pressure chamber member  43  is increased, thereby pressurizing the inside of the capillary  1  from the end  1   b . Thus, the solution  15  held in the capillary  1  is discharged into the vessel  19 . 
     As mentioned above, the liquid transfer apparatus according to the present invention employs a capillary, and a solution is aspirated into the capillary by means of capillarity. The amount of solution to be aspirated is determined by means of the inner diameter and length of the capillary. Hence, a small amount of solution can be dealt with. Particularly, when the amount of liquid to be handled is fixed, such as application of the present invention to predetermined pretreatment of an analytical system, efficient transfer corresponding to a small amount of sample can be affected with simple structure. 
       FIG. 7  is a cross-sectional view showing an embodiment of a reaction vessel. 
     The reaction vessel has a vessel plate (vessel substrate)  51  consisting of, e.g., glass, silicon, or silicon rubber. A plurality of tapered recesses  53  for storing a solution  15  are formed in one surface of the vessel plate  51 . A cover plate  55  is made of elastomer, e.g., silicon rubber. The cover plate  55  is brought into hermetic contact with the surface of the vessel plate  51  in which the recesses  53  are formed. The top of each of the recesses  53  is sealed by the cover plate  55 , and thus the recesses  53  become hermetic reaction spaces. The hermetic spaces are formed easily by use of elastomer as a material of the cover plate  55 . 
     The vessel plate  51  and the cover plate  55  are sandwiched between a pair of metal plates (heat conductive members)  57 ,  59 . Through holes  57   a  for guiding the respective capillaries  1  are formed in the side of the metal plate  57  that faces the cover plate  55  and in the positions corresponding to the recesses  53 . Although not illustrated, a Peltier element is attached as a heating/cooling mechanism for effecting heat control is attached to each of the metal plates  57 ,  59 . 
     The metal plate  57  serves also as a guide member constituting the reaction vessel according to the present invention. 
     An example of operation required for preparing a sample through use of a reaction vessel will now be described. 
     (1) A fluid mixture consisting of, e.g., a sample and a reagent, is discharged into the recess  53  of the vessel plate  51 . The liquid transfer apparatus according to the present invention shown in  FIGS. 1 through 6B  can be used for the discharging operation. 
     (2) The cover plate  55  is provided on the surface of the vessel plate  51  having the recesses  53  formed therein. 
     (3) The vessel plate  51  and the cover plate  55  are sandwiched between the metal plates  57 ,  59 , thereby sealing the recess  53 . 
     (4) By means of the Peltier elements (not shown) attached to the metal plates  57 ,  59 , the plates are heated cyclically, thereby promoting reaction of the sample with the reagent in the recess  53 . 
       FIG. 8  is a cross-sectional view showing an example of process for extracting the solution from the recess in the reaction vessel shown in  FIG. 7 . 
     The capillary  1  is stuck into the cover plate  55  via the through hole  57   a  formed in the metal plate  57 . At this time, by means of an increase in the internal pressure of the recess  53  causing from deformation of the cover plate  55  made of elastomer and the capillarity of a capillary, the solution held in the recess  53  is aspirated into the capillary  1 . The sample thus-aspirated into the capillary  1  can be extracted to an arbitrary location by means of pressurizing the inside of the capillary  1 . 
     As a result of use of elastomer as material of the cover plate  55 , the capillary  1  penetrates through the cover plate  55  at the time of extraction of the solution held in the recess  53 , thereby enabling contact with the sample. Thus, there is no necessity for removing the coverplate  55  forming the hermetic space, thus preventing loss of the solution in the recess  53 . 
     The liquid transfer apparatus according to the present invention can be used for extracting a solution from the recess  53 . 
     So long as a plurality of capillaries  1  are provided, simultaneous processing of a plurality of samples can be affected. 
     Next, an example method of preparing the vessel plate  51  made from elastomer will be described. 
     (1) A mold having protuberances is formed on a silicon wafer by means of, e.g., chemical etching. 
     (2) In order to facilitate removal of the container plate in a post operation, the surface of the mold is processed with silane. The mold was subjected to silane treatment through use of 3% (v/v) dimethyloctadecylchlorosilane/0.025% H 2 O in toluene (a solution made by adding water in 0.025% volume ratio to toluene, and by adding dimethyloctadecylchlorosilane to the mixture in 3% volume ratio) for two hours. 
     (3) The mold is fixed in a molding box. 
     (4) The polymer material and hardener thereof are drawn into the molding box. For example, Sylgard 184 (produced by U.S. Dow Corning, and Sylgard is the tradename of Down Corning Co., Ltd.) and hardener thereof are mixed in proportions by weight of 10:1, and the mixture was hardened for four hours at 65°. 
     (5) The thus-hardened polymer material is removed from the mold, whereby a vessel plate having recesses into which the protuberances of the mold have been transferred is formed. 
     Further, PDMS (Poly(dimethylsiloxane)) plate is formed by the same manner as the vessel plate, and is used as the cover plate  55 . 
     Microprocessing of elastomer can be affected not by etching but by a replica method using a mold. Hence, a reaction vessel can be manufactured very inexpensively. As a result, the reaction vessel can be made disposable, thereby obviating a rinsing process or a risk of contamination. 
     In order to attain stable thermal conductivity at the time of heat control of the container plate  51  and the cover plate  55  or to cause the capillary  1  to penetrate through the cover plate  55  at the time of extraction of a sample, the thickness of polymer must be controlled in connection with the preparation method set forth. Use of spin coating for drawing polymer material into a mold is preferable. 
     As another preparation method of the vessel plate  51 , there may be provided a method of forming the recesses  53  in the surface of a silicon substrate or in the surface of a glass substrate, by use of an optical lithography technique and an etching technique. These methods facilitate an increase in the packing density of minute recesses. If the optical lithography technique or the etching technique is employed at the time of formation of the mold, an increase in the packing density of protuberances can be increased readily. Therefore, he packing density of minute recesses can be increased. 
       FIG. 9  is a cross-sectional view showing another example of process for extracting a solution from the recess of the reaction vessel shown in  FIG. 7 . At the time of extraction of a solution from the recess  53 , the internal pressure of the recess  53  is forcefully increased, thereby introducing the solution into the capillary  1  without failure. 
     A sleeve  60  has a tip end  60   a  matching in shape with the recess  53 . The capillary  1  is inserted and held in the sleeve  60 . After removal of the metal plate  57  from the cover plate  55 , the capillary  1  is penetrated through the cover plate  55 , and the cover plate  55  is urged toward the recess  53  by the sleeve  60 . Thus, the internal pressure of the recess  53  is increased, and the solution is introduced into the capillary  1 . Then, the capillary  1  is removed from the cover plate  55  while the position of the sleeve  60  is retained, the solution can be extracted from the recess  53 . 
     The sleeve  60  can be attached to the liquid transfer apparatus according to the present invention. 
       FIG. 10  is a cross-sectional view showing another embodiment of a reaction vessel. 
     The reaction vessel has a vessel plate  61  formed from, e.g., glass, silicon, or silicon rubber. A plurality of tapered recesses  63  for storing the solution  15  are formed in one surface of the vessel plate  61 . The bottom of each of the recesses  63  is thinly formed, to thereby form a discharge section  63   a.    
     A cover plate  65  is formed from elastomer e.g., silicon rubber. The cover plate  65  is brought into hermetic contact with the side of the vessel plate  61  in which the recesses  63  are formed. The top of each of the recesses  63  is sealed by the cover plate  65 , so that the recesses  63  become hermetic reaction spaces. 
     A guide plate (guide member)  67  is provided on the side of the cover plate  65  that faces away from the vessel plate  61 . A plurality of through holes  67   a  are formed in the guide plate  67  in the positions corresponding to the positions of the recesses  63 . The through holes  67   a  guid a pressurization shaft (urging member)  68  which urges the vessel plate  65  toward the recesses  63 . The tip end of the pressurization shaft  68  is formed roundly so as to conform with the geometry of the recess  63 . 
     A reservoir plate  69  is provided on the side of the vessel plate  61  that faces away from the recesses  63 . A plurality of recesses are formed as reservoirs  69   a  in the reservoir plate  69  in the positions corresponding to the positions of the discharge sections  63   a  of the recesses  61 . 
     The vessel plat  61  and the cover plate  65  are sandwiched between the guide plate  67  and the reservoir plate  69 . 
     At the time of extraction of a solution from the recess  63 , the pressurization shaft  68  is inserted into the through hole  67   a  of the guide plate  67 , thereby urging the cover plate  65  toward the inside of the recess  63  and compressing the internal space of the recess  63 . Eventually, the internal pressure of the recess  63  increases, and the discharge section  63   a  that is the thinnest portion in an internal wall of the recess  63  becomes ruptured. The solution is then discharged to the reservoir  69   a  from the recess  63 . 
     The present embodiment obviates a necessity for removing the cover plate  65  forming the hermetic space, thus preventing loss of the solution from the inside of the recess  63 . 
     If a heat conductive material is used for the guide plate  67 , the guide plate  67  can serve also as the heat conductive member constituting the reaction vessel according to the present invention. 
     At the time of formation of the vessel plate  61  shown in  FIG. 10  in the same manner as the vessel plate  51  made of elastomer, the thickness of the bottom of the recess  63 , that is, the thickness of the discharge section  63   a , is determined by the difference between the height of the protuberance of the mold and the thickness of the vessel plate  61 . The height of the protuberance of the mold is determined at the time of the formation of the mold, a suitable discharge section  63   a  can be obtained by controlling the thickness of the polymer material to be drawn into the mold by means of the spin-coating. 
     The embodiments of the liquid transfer apparatus and the reaction vessels according to the present invention have been described above. However, the present invention is not limited to the embodiments and is applied to various modifications within the scope of the invention claimed in the appending claims.