Liquid dispenser

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.

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.

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. 1depicts dispenser100A in accordance with a first illustrative embodiment of the present invention. Dispenser100A includes liquid-retaining material102, dispensing plate104, and roller110, interrelated as shown.

Liquid-retaining material102is 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 material102. Another way to do this is by saturating liquid-retaining material102with liquid and then removing a specific amount of liquid, such as by passing material102through appropriately-spaced rollers.

Liquid-retaining material102is positioned over dispensing plate104. The dispensing plate includes an array of spherical or conical indentations106. At the bottom of each such indentation is a precisely-sized opening108(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.

Roller110, which serves as a pressure-applying device, contacts liquid-retaining material102and applies a consistent amount of downward-directed pressure to it. Liquid is forced out of liquid-retaining material102at the point of contact with roller110. The ejected liquid flows into indentations106. Droplet112containing a precise amount is formed by each opening108. Droplet112is received by wells116of multi-well plate114. InFIG. 1, plate114is an 8×12 multi-well plate, so that dispensing plate104is advantageously arranged with an 8×12 array of indentations106. Thus, as roller110engages material102, liquid is forced into 8 indentations106simultaneously. To dispense liquid into the next row of indentations106, liquid-retaining material102is moved past roller110, or the roller is moved over material102. In some other variations, dispensing plate104is arranged with a 16×24 array of indentations to accommodate a 384-well multi-well plate, and in yet other variations, dispensing plate104is arranged with a 32×48 array of indentations to accommodate a 1536-well plate.

FIG. 2depicts dispenser100B in accordance with a second illustrative embodiment of the present invention. Dispenser100B includes liquid-retaining material102, dispensing plate104, housing218, and diaphragm222, inter-related as shown.

Housing218and dispensing plate104define pressure chamber220. Liquid-retaining material102overlies dispensing plate104, and diaphragm222overlies material102. A pulse of pressure (e.g., via a hose connection that is not depicted, etc.) is supplied or otherwise generated within pressure chamber220above diaphragm222. As a result, diaphragm222is forced downward thereby squeezing liquid-retaining material102. This squeezing forces at least some liquid out of liquid-retaining material102and through openings108in dispensing plate104. In this embodiment, the pressure chamber, diaphragm and the device that delivers or generates the pulse of pressure compose the pressure-applying device.

Droplets112are dispensed, simultaneously, into wells116of underlying multi-well plate114. 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 material102.

For dispenser100B, liquid-retaining material102can be loaded with a predetermined amount of liquid by, for example, advancing material102through 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 chamber220. Alternatively, a roll of material102can be disposed in liquid. A portion of material102is advanced into chamber220, liquid is dispensed, and the emptied material is drawn out of chamber220. Additional material102laden with liquid is sequentially advanced into chamber220for dispensing. Liquid-retaining material102can be cycled back to receive more liquid and then again advanced in chamber220.

Until pressure is applied, such as by roller110in the first embodiment, or by a pulse of pressure in the second embodiment, liquid-retaining material102retains liquid. Consequently, dispensers100A and100B do not require valves.

FIG. 4depicts method400for dispensing liquid in accordance with the illustrative embodiments of the present invention. In accordance with operation402, liquid is added to liquid-retaining material102. Those skilled in the art will be able to provide material102with 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 operation404, pressure is applied to liquid-retaining material102. 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 material102is directed, as per operation406, through sized openings to create droplets containing a desired volume of liquid. This is done, in the illustrative embodiments, by positioning liquid-retaining material102on top of dispensing plate104. The indentations106in dispensing plate104collect 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.