Abstract:
A dispenser that is capable of simultaneously filling a large array of receivers (e.g., wells, etc.) with nano-liter volumes of liquid at high accuracy. The dispenser has a very simple construction, is quite compact, and has few if any moving parts.

Description:
STATEMENTS OF RELATED CASES 
     This case claims priority of U.S. Provisional Patent Application 60/386,147 filed Jun. 5, 2002. 
    
    
     FILED OF THE INVENTION 
     The present invention relates generally to liquid dispensers. More particularly, the present invention relates to liquid dispensers that are capable of simultaneously dispensing very small quantities of liquid to an array of receivers. 
     BACKGROUND OF THE INVENTION 
     Many research applications require that very small (i.e., nano-liter), precisely-metered quantities of liquid are dispensed, simultaneously, into an array of receivers (e.g., wells in a multi-well plate, etc.). This is very difficult to do for a number of reasons. 
     In particular, if a common liquid-holding manifold having an array of valves/nozzles is used for dispensing, it is difficult to ensure that liquid flows equally through all of the valves/nozzles. Any non-uniform accumulation of matter in the manifold, or partial occlusions of some valves/nozzles, will result in flow imbalances. Furthermore, it is difficult to precisely control all micro-valves in the array. 
     Consequently, a need exists for a dispenser that is capable of accurately and simultaneously dispensing very small quantities of liquid into a plurality of receivers. 
     SUMMARY OF THE INVENTION 
     A dispenser in accordance with the illustrative embodiment of the present invention is capable of simultaneously filling a large array of receivers (e.g., wells, etc.) with nano-liter volumes of liquid at high accuracy. The dispenser has a very simple construction, is quite compact, and has few if any moving parts. 
     In accordance with the illustrative embodiment, a liquid-retaining material (e.g., sponge, etc.) holds a predetermined amount of liquid. The liquid is released from the liquid-retaining material by the application of pressure. The liquid is forced, by the applied pressure, through an array of precisely-sized openings that are disposed in a plate that underlies the liquid-retaining material. Receivers that underlie the plate receive the droplets of liquid that pass through the openings. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  depicts a liquid dispenser in accordance with a first illustrative embodiment of the present invention. 
         FIG. 2  depicts a liquid dispenser in accordance with a second illustrative embodiment of the present invention. 
         FIG. 3  depicts a close-up of a dispensing nozzle for use in conjunction with the liquid dispensers of  FIGS. 1 and 2 . 
         FIG. 4  depicts a method in accordance with the illustrative embodiments of the present invention. 
     
    
    
     DETAILED DESCRIPTION 
     In accordance with the illustrative embodiment, a liquid-retaining material (e.g., a hydrophilic material, an open cell sponge, etc.) holds a predetermined amount of liquid. The liquid is released from the liquid-retaining material by the application of pressure from a pressure-applying device. The liquid is forced, by the applied pressure, through an array of precisely-sized openings that are disposed in a plate that underlies the liquid-retaining material. Receivers (e.g., wells of a multi-well plate, etc.) that underlie the plate receive the droplets of liquid that pass through the openings. 
       FIG. 1  depicts dispenser  100 A in accordance with a first illustrative embodiment of the present invention. Dispenser  100 A includes liquid-retaining material  102 , dispensing plate  104 , and roller  110 , interrelated as shown. 
     Liquid-retaining material  102  is filled with a predetermined amount of liquid. This can be done in a variety of ways, as is known to those skilled in the art. One way is to pour a predetermined amount of liquid onto liquid-retaining material  102 . Another way to do this is by saturating liquid-retaining material  102  with liquid and then removing a specific amount of liquid, such as by passing material  102  through appropriately-spaced rollers. 
     Liquid-retaining material  102  is positioned over dispensing plate  104 . The dispensing plate includes an array of spherical or conical indentations  106 . At the bottom of each such indentation is a precisely-sized opening  108  (e.g., 0.1 mm diameter, etc.). (See also,  FIG. 3. ) The openings are sized to generate a drop that contains less than one micro-liter of liquid. 
     Roller  110 , which serves as a pressure-applying device, contacts liquid-retaining material  102  and applies a consistent amount of downward-directed pressure to it. Liquid is forced out of liquid-retaining material  102  at the point of contact with roller  110 . The ejected liquid flows into indentations  106 . Droplet  112  containing a precise amount is formed by each opening  108 . Droplet  112  is received by wells  116  of multi-well plate  114 . In  FIG. 1 , plate  114  is an 8×12 multi-well plate, so that dispensing plate  104  is advantageously arranged with an 8×12 array of indentations  106 . Thus, as roller  110  engages material  102 , liquid is forced into 8 indentations  106  simultaneously. To dispense liquid into the next row of indentations  106 , liquid-retaining material  102  is moved past roller  110 , or the roller is moved over material  102 . In some other variations, dispensing plate  104  is arranged with a 16×24 array of indentations to accommodate a 384-well multi-well plate, and in yet other variations, dispensing plate  104  is arranged with a 32×48 array of indentations to accommodate a 1536-well plate. 
       FIG. 2  depicts dispenser  100 B in accordance with a second illustrative embodiment of the present invention. Dispenser  100 B includes liquid-retaining material  102 , dispensing plate  104 , housing  218 , and diaphragm  222 , inter-related as shown. 
     Housing  218  and dispensing plate  104  define pressure chamber  220 . Liquid-retaining material  102  overlies dispensing plate  104 , and diaphragm  222  overlies material  102 . A pulse of pressure (e.g., via a hose connection that is not depicted, etc.) is supplied or otherwise generated within pressure chamber  220  above diaphragm  222 . As a result, diaphragm  222  is forced downward thereby squeezing liquid-retaining material  102 . This squeezing forces at least some liquid out of liquid-retaining material  102  and through openings  108  in dispensing plate  104 . In this embodiment, the pressure chamber, diaphragm and the device that delivers or generates the pulse of pressure compose the pressure-applying device. 
     Droplets  112  are dispensed, simultaneously, into wells  116  of underlying multi-well plate  114 . A very low CV (coefficient of variation) is expected because the internal fluidic pressure will be evenly and instantaneously distributed across the entire internal volume and surface of material  102 . 
     For dispenser  100 B, liquid-retaining material  102  can be loaded with a predetermined amount of liquid by, for example, advancing material  102  through a cassette or cartridge that contains liquid, in the manner in which film is advanced through a camera. The cartridge would be located before pressure chamber  220 . Alternatively, a roll of material  102  can be disposed in liquid. A portion of material  102  is advanced into chamber  220 , liquid is dispensed, and the emptied material is drawn out of chamber  220 . Additional material  102  laden with liquid is sequentially advanced into chamber  220  for dispensing. Liquid-retaining material  102  can be cycled back to receive more liquid and then again advanced in chamber  220 . 
     Until pressure is applied, such as by roller  110  in the first embodiment, or by a pulse of pressure in the second embodiment, liquid-retaining material  102  retains liquid. Consequently, dispensers  100 A and  100 B do not require valves. 
       FIG. 4  depicts method  400  for dispensing liquid in accordance with the illustrative embodiments of the present invention. In accordance with operation  402 , liquid is added to liquid-retaining material  102 . Those skilled in the art will be able to provide material  102  with a predetermined amount of liquid, such as by using the techniques described above or other techniques that might occur to them in view of the present teachings. 
     In operation  404 , pressure is applied to liquid-retaining material  102 . The applied pressure forces at least some liquid out of the liquid-retaining material. Pressure can be applied in any of a variety of ways such as, without limitation, the roller technique or the pressure-pulse technique that have already been described. 
     The liquid that is forced out of liquid-retaining material  102  is directed, as per operation  406 , through sized openings to create droplets containing a desired volume of liquid. This is done, in the illustrative embodiments, by positioning liquid-retaining material  102  on top of dispensing plate  104 . The indentations  106  in dispensing plate  104  collect the liquid, which then passes through a hole at the bottom of each indentation. 
     It is to be understood that the above-described embodiments are merely illustrative of the present invention and that many variations of the above-described embodiments can be devised by those skilled in the art without departing from the scope of the invention. It is therefore intended that such variations be included within the scope of the following claims and their equivalents.