Abstract:
A liquid dispenser characterized by a dispensing head which is movable upward and downward as a whole and comprises a plurality of plungers supported by a plunger plate, drive means for moving the plunger plate upward and downward, a plurality of cylinders in which the plungers slidably fit, and a plurality of nozzles arranged at the lower ends of the cylinders and having configurations adapted to engage airtightly with holes for holding specific dispensing tips, the plurality of nozzles being supported by a single nozzle holder, which is built to be detachable from said dispensing head. According to the invention, only the nozzle holder that support nozzles has to be replaced with another holder conforming to dispensing tips of different dimensions. The arrangement facilitates the replacement and make the dispenser available at lower cost.

Description:
This application claims priority from Japanese Application No. 11-208875, filed Jul. 23, 1999, the entire contents of which are incorporated herein by reference. 
     BACKGROUND OF THE INVENTION 
     1. Field of the Invention 
     This invention relates to a liquid dispenser for liquid reagents, liquid samples and the like and, more specifically, to a holder-exchanger of such a dispenser for holding or replacing its dispensing tips. 
     2. Prior Art 
     In hospitals and various other institutions where blood test, immunological examination, chemical reaction, and other tests are carried out, it is customary that the blood, sample, reagent, or other object to be tested (hereinafter collectively called “liquid”) is simultaneously distributed in predetermined amounts among a number of wells, cuvettes, or other small containers (hereinafter simply called “wells”) using as many dispensing tips. 
     FIGS. 1 to  3  illustrate a liquid dispenser embodying the present invention. Except the mechanism for holding and replacing dispensing tips, the construction of the apparatus is known to the art. With this in view, a liquid dispenser of the prior art will now be explained with reference to the drawings. 
     FIG. 1 is a front view of the liquid dispenser, FIG. 2 is a side view, and FIG. 3 is a plan view of a stage assembly of the dispenser. The apparatus includes a horizontal base  1  and a housing frame of upright support  2 . The horizontal base  1  carries an X stage  3  movably in the X direction, and the X stage  3  supports thereon a Y stage  5  movably in the Y direction. The Y stage  5  in turn carries, by means of a frame plate  7 , a tip rack  9  having an array of holes (in 8 rows and 12 columns) arranged in order to hold a number of tips, at least one plate  11  having holes to support a number of wells in an equidistantly spaced arrangement of the same number, and a reagent or wash tank  13  holding a reagent or wash as the case may be. The X and Y stages  3 ,  5  can be driven independently of each other by an X-axis drive motor  15  or Y-axis drive motor  17  at a command from a control console. 
     The upright support  2  supports a Z-axis-movable dispensing head  19 , which carries plungers  21  and cylinders  23  in the same numbers and at the same intervals as the holes of the tip rack  9  and plate  11 . Tips  100  or  102  (usually either type, although two types are shown here) are fitted to nozzles that constitute the lower ends of the cylinders  23 . The dispensing head  19  is driven as a whole in the Z-axis direction by a Z-axis drive motor  27 , and the plungers  21  are driven by an S-axis motor  79 . 
     In operation, the X and Y stages  3 ,  5  are first driven to align the tip rack  9  to the nozzles of cylinders  23 , the dispensing head  19  is lowered in the Z-axis direction until the nozzle tips are fitted airtightly in the bores at the upper ends of dispensing tips  100  or  102  so that all the tips  100  or  102  are held by the nozzles, and then the dispensing head  19  is moved up. Next, the reagent tank  13  is aligned just below the nozzles holding the tips  100  or  102 , the dispensing head  19  is lowered, bringing the lower ends of the dispensing tips  100  or  102  into the reagent tank  13 , the plungers  21  are moved upward to draw by suction predetermined amounts of the reagent, and thus the dispensing head  19  is raised. Then the plate  11  is brought in place under the nozzles holding the dispensing tips  100  or  102 , the dispensing head  19  is lowered to position the tips  100  or  102  immediately above the wells containing the sample (blood or the like). Finally, the plungers  21  are forced downward to dispense the reagent into the sample wells. 
     The nozzles of the prior art constitute the lower ends of the cylinders, and the combinations of many cylinders and plungers arranged in an orderly manner are supported by a single supporting block. The amount to be dispensed depends on the size of the tips, and the outside diameter of the nozzles to fit in the holes at the ends of the tips must be changed in accordance with the dispensing amount. To meet this requirement, it has been common with conventional dispensers to provide a variety of support blocks that hold the plunger-cylinder combinations having nozzles designed for particular amounts to be dispensed and replace the whole unit of support block when required. 
     The necessity of providing a plurality of dispensing blocks, each of which having a number of plunger-cylinder combinations with nozzles carried by a support block, for different sizes of nozzles has made the dispensers expensive because their dispensing blocks call for high precision in manufacture. Moreover, the replacement of dispensing blocks is cumbersome and not easy. 
     SUMMARY OF THE INVENTION 
     The present invention solves the problems of the prior art by providing a dispenser in which nozzles are separated from cylinders and are supported by a common block as a nozzle block which alone can be replaced with another one when the necessity arises. 
     Thus the invention provides a liquid dispenser characterized by a dispensing head which is movable upward and downward as a whole and comprises a plurality of plungers supported by a plunger plate, drive means for moving the plunger plate upward and downward, a plurality of cylinders in which the plungers slidably fit, and a plurality of nozzles arranged at the lower ends of the cylinders and having configurations adapted to engage airtightly with holes for holding specific dispensing tips, the plurality of nozzles being supported by a single nozzle holder, which is built to be detachable from said dispensing head. 
     According to the invention, only the nozzle holder that support nozzles has to be replaced with another holder conforming to dispensing tips of different dimensions. The arrangement facilitates the replacement and make the dispenser available at lower cost. 
     The nozzles preferably have an annular extended head each and are loosely fitted in the support block, simply as inserted from above into the block. They are fitted in the holes at the upper ends of the dispensing tips by self-aligning and thereby achieve positive airtight engagement with the tips. 
     In a preferred form of the invention, an elastic seal plate such as of silicone rubber having openings aligned to the bores of the nozzles and cylinders is sandwiched between the upper surface of the nozzle holder and the plunger-cylinder block, whereby airtight fluid communication is easily established between the nozzles and cylinders. 
     In another preferred form of the invention, the means for attaching and detaching the nozzle holder in a predetermined point comprises vertical clamp plates having clamps adapted to be engaged with lower edges of the nozzle holder, elastic members that normally bias the clamp plates upward, and means for pressing the clamp plates downward against the urgings of the elastic members. The means for pressing the clamp plates downward may be a plunger plate and means for driving it. Once the clamp plates are forced downward, the nozzle holder descends too under its own weight to the point where it can be pulled off horizontally to replace with a nozzle holder carrying nozzles of a different size. 
     In a further preferred form of the invention, an eject plate is located under the nozzle holder to remove all dispensing tips simultaneously from the nozzles. The eject plate has a plurality of holes to allow the nozzles to extend through them with tip-fitting ends of the nozzles protruding beyond the bottom of the eject plate. The diameter of the holes of the eject plate is smaller than the outside diameter of the upper ends of the dispensing tips. The eject plate, when forced downward by the bottom surfaces of the clamps of clamp plates, can simultaneously release and remove all tips simultaneously from the nozzles. The plate is normally biased toward the nozzle plates by springs provided on the nozzle holder. As an alternative, the eject plate may be pressed downward by means other than the clamp plates. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS 
     FIG. 1 is a front view of a liquid dispenser embodying the present invention; 
     FIG. 2 is a right side view of the liquid dispenser of the invention; 
     FIG. 3 is a plan view of a stage assembly of the dispenser according to the invention; 
     FIG. 4 is a front view of a dispensing head of the dispenser according to the invention; 
     FIG. 5 is a right side view of the dispensing head of the dispenser, with the omission of a bracket; 
     FIG. 6 is a right side view of the dispensing head, with the bracket attached; 
     FIG. 7 is an enlarged front view of the essential parts of the dispending head; 
     FIG. 8 is a front view of the essential parts associated with the operation of an eject plate in accordance with the invention; and 
     FIG. 9 is a schematic front view of dispensing tips and a tip rack supporting them. 
    
    
     DESCRIPTION OF THE PREFERRED EMBODIMENT 
     Now the present invention will be more fully described below in connection with an embodiment thereof. 
     FIGS. 1 to  3  illustrate the general construction of a liquid dispenser embodying the invention, which is characterized by a dispensing head  19  having a mechanism for holding and replacing dispensing tips. 
     FIGS. 4 to  6  are enlarged views of the dispensing head  19 . Essential parts of the head  19  are shown in FIGS. 7 and 8. 
     FIG. 1 is a front view of the liquid dispenser, FIG. 2 is a side view, and FIG. 3 is a plan view of a stage assembly. The liquid dispenser includes a horizontal base  1  and a housing frame of upright support  2 . The horizontal base  1  carries an X stage  3  which is made movable in the X direction by X-axis linear guides  37 , and the X stage  3  supports thereon a Y stage  5  which is made movable in the Y direction by Y-axis linear guides  39  mounted on the X stage. The Y stage  5  carries thereon a frame plate  7  detachably secured in place with frame guide pins  8 . The frame plate  7  in turn carries a tip rack  9  (see FIG. 9) having an array of holes (e.g., in 8 rows and 12 columns as shown) arranged in order to hold a number of tips  100  or  102 , at least one plate  11  having holes to support a number of wells in an equidistantly spaced arrangement of the same number, and a reagent or wash tank  13  holding a reagent or wash as the case may be. There are also provided a feedwater inlet  41  for the wash, drain pipes  43 , a drain pipe joint  45 , a liquid level sensor  47 , a liquid level sensor connector  49 , etc. Those components have nothing to do with the subject of the present invention, and their detailed description is omitted. 
     The X stage  3  is driven in the X-axis direction, in response to a control signal received from a control console through a controller  35 , by an X-axis drive motor  15  with a pulley  31  and a timing belt  33 . Similarly, the Y stage  5  is driven independently of the X stage, in response to a control signal from the control console through the controller  35 , by a Y-axis drive motor  17  with a pulley. The position of the X stage  3  is detected by an X-axis sensor  51 . A Y-axis sensor (not shown) functions likewise. 
     The upright support  2  holds up a dispensing head  19  movably in the Z-axis direction. The dispensing head  19  has a frame  18  supported by a pair of linear bearings  53  vertically spaced apart and arranged in tandem. The linear bearings  53  are slidably guided in the Z-axis (vertical) direction by a pair of shaft-retaining plates  57  (only the upper one is shown) which too are vertically spaced apart and secured in tandem to the upright support  2 . A Z-axis motor  27 , mounted in the support frame  2 , drives the linear bearings  53  in the Z-axis direction via a coupling  61  and a ball screw  63  retained in position by a bearing  55 . 
     The construction of the dispensing head  19  will now be described with reference to FIGS. 4 to  6 . FIG. 4 is a front view, FIG. 5 is a right side view with the omission of a vertical bracket  65 , and FIG. 6 is a right side view with the bracket  65 . A cylinder block  67  is secured with clamps  69  to the frame  18  of the dispensing head  19 . On both front sides of the cylinder block  67 , vertical brackets  65  are supported by a horizontal bracket  77  fixed to the frame  18 . As shown in FIG. 4, the cylinder block  67  comprises two side blocks  71  and upper and lower blocks  73 ,  75  having am array of openings in a regular pattern to receive and support cylinders  23 . The upper block  73  supports the upper ends of the cylinders  23  and the lower block  75  supports the lower ends. 
     Moreover, in the frame  18  of the dispensing head  19  is mounted an S-axis motor  79 . The term S axis as used herein means the axis for motion in the vertical direction, as distinguished from the Z axis. The frame  18  also carries the horizontal bracket  77 , which in turn supports a vertical rotating shaft  83  through bearings  81 . The shaft is caused to rotate by the S-axis motor  79  through a pulley  85 , timing belt  84 , and pulley  87 . The rotating shaft  83  has a ball screw  89 , which bears up a horizontal plunger plate  91 . The ball screw  89  changes the rotation of the shaft to a movement in the S-axis (vertical) direction and moves the plunger plate  91  upward and downward. The plunger plate  91  is fixed to guide shafts  93 , which slide along guides secured to the frame  18  and through guide holes formed in the cylinder block to guide the plunger plate  91  vertically. To the plunger plate  91  are fixed the upper ends of a number of plungers  21  that fit in corresponding bores of cylinders  23 . The lower ends of the plungers  21  fit in the upper ends of the cylinders  23  and the both ends are airtightly joined with seals  95 . 
     In operation, the S-axis motor  79  is started and its power is transmitted through the pulley  85 , timing belt  84 , pulley  87 , and rotating shaft  83  to rotate the ball screw  89 , whereby the plunger plate  91  is driven downward or upward. The plungers  21  move into or out of the cylinders  23  a predetermined distance to draw a predetermined amount of air by suction or discharge it each. In this manner air can be introduced into or forced out of tips  100  or  102  by nozzles  101  so that a given liquid can be accurately dispensed in equal, predetermined amounts as will be explained in detail later. 
     The features of the invention will be described below in connection with FIGS. 7 and 8, in addition to FIGS. 4 to  6 . Under the cylinder block  67 , there is located a nozzle holder  97  which has a number of holes supporting an array of (small) nozzles  99  or (large) nozzles  101 , preferably fitting loosely, in an arrangement corresponding to the cylinders. Loosely received in the holes, the nozzles have allowances to move slightly for a proper airtight fit when their ends are engaged with the upper end openings of tips. In the absence of the allowances, some of the many tips could fail to fit properly and be left unengaged in the rack  9  (FIGS.  3  and  9 ). The nozzles  99  or  101  have an annular extended head each with which to be fitted in the holes of the nozzle holder  97 . The nozzle holder  97  is urged by clamps  104  at the lower ends of clamp plates  103  against the bottom of the cylinder block  67 , whereby the upper ends of the nozzles are forced in contact with the lower ends of the cylinders  23 . 
     Preferably, an elastic plate such as silicone plate  109  is sandwiched between the nozzle holder  97  and the bottom of the cylinder block  67  to establish airtight communication between the cylinders  23  and the nozzles  99  or  101 . 
     Each clamp plate  103  is supported by the vertical bracket  65  which in turn is held by the horizontal bracket  77 , in such manner that the clamp plate can slide vertically along the outer surface of the bracket. A pair of clamp plate guides  105  are fixed to the cylinder block  67  (FIG.  6 ), and the clamp plate  103  is formed with slots  111  in which the guides  105  fit. A plurality of tension springs  113  are secured at the upper ends to the bracket  65 , and the lower ends of the springs  113  are secured to the upper end of the clamp plate  103 . As a consequence, the clamp plate  103  is normally biased upward, forcing the nozzle holder  97  against the cylinder block  67  with the aid of the clamps  104  to provide desired airtight communication between the cylinders  23  and nozzles  99  or  101 . The strength of the springs  113  can be controlled by adjusting the positions of screws  115 . 
     In conjunction with FIGS. 4 to  6 , means for removing the nozzle holder  97  when required will now be explained. Release pins  117  are fixed to each clamp plate  103  and extend through slots formed in the bracket  65  to the inside. As it descends, the plunger plate  91  comes into contact with the release pins  117  and then forces them farther downward against the urgings of the springs  113 , and accordingly the clamp plate  103  comes down to release the nozzle holder  97 . Thus the nozzle holder  97  descends under its own weight until it rests on holding bends  108  of holder supports  107  secured to the cylinder block  75 . In this state the nozzle holder  97  can be horizontally pulled out together with the nozzles  99 . This state also allows the nozzle holder to be replaced with another holder of different dimensions. 
     Next, with reference to FIGS. 4,  7 , and  8 , means of removing the tips  100  or  102  as needed will be described. 
     The nozzle holder  97  has stoppers  119  fixed to the four corners of its underside, all in contact with an eject plate  123 . The eject plate  123  is elasticly pressed against the stoppers  119  by eject springs  125  held in place by spring pins  121 . The plate has throughholes in which the nozzles  99  or  101  extend their lower portions to expose the ends on which tips are to be fitted. For this purpose the lower ends of the throughholes are designed to be smaller in diameter than the upper ends of the tips  100  or  102 . Thus, when the eject plate  123  is pushed down, all the tips are dropped off. 
     Means of pushing down the eject plate  123  may be provided separately, but preferably the clamp plates  103 , as in the illustrated Figures, are utilized for that purpose too. The bottom surfaces of the clamps  104  at the lower ends of the clamp plate serve as surfaces to act on the eject plate  123 . From the state shown in FIGS. 4 and 6 the clamp plates  103  are forced downward by the descent of the plunger plate  91  to release the nozzle holder  97 . As the downward movement continues, the nozzle holder  97  comes to rest on the holding bends  108  of the holder supports  107 . A farther descent of the clamp plate causes the clamps  104  to fall past the holding bends  108  to the points shown in FIG.  8 . The eject plate  123  then drops away from the stoppers  119  against the urgings of the springs  125 , with the consequence that the tips drop off altogether. Subsequent ascent of the plunger plate permits the springs  125  to recover their elasticity to bring the eject plate  123  back to the original position, ready to receive new tips. 
     As has been described above, the present invention makes it possible to manufacture a liquid dispenser at lower cost than heretofore. Since its plunger-cylinder combinations are made separate from nozzles, and the nozzles are supported by a detachable nozzle holder, not only tips of different sizes can be replaced with ease but also the plunger-cylinder combinations can be used with all sizes of nozzles. 
     The adoption of an eject plate facilitates the removal of tips. 
     The use of an elastic seal plate such as of silicone permits airtight coupling of cylinders and nozzle despite the separate nozzle design.