AU2003249687A8

AU2003249687A8 - Liquid transfer device

Info

Publication number: AU2003249687A8
Application number: AU2003249687A
Authority: AU
Inventors: Jonathan Pearson; David Frank Moore; Alistair Taylor; Stuart Elmes
Original assignee: Matrix Technologies LLC
Current assignee: Matrix Technologies LLC
Priority date: 2002-06-04
Filing date: 2003-06-04
Publication date: 2009-07-30
Also published as: WO2003101369A3; WO2003101369A2; AU2003249687A1

Description

WO 03/101369 PCT/US03/17443 LIQUID TRANSFER DEVICE FIELD OF THE INVENTION The present invention relates to a device for transferring, controlled amounts of liquid, and more particularly to a device by which controlled amounts of liquid can be simultaneously transferred to a plurality of target locations upon demand. BACKGROUND Arrays of tens of thousands of different biological solutions printed in known positions onto a substrate are useful for researchers in Molecular Biology. The more compact that these arrays cai be made, the more sensitive are the analyses that can be performed. It is generally desired to place these fluids with good positional accuracy and consistency of amount deposited. The transfer of either all or a part of the biological solution from one storage vessel to another is another useful procedure for the scientist. This may, for example, take the form of transferring a few drops of a solution from a vessel with topological discontinuities to another vessel with topological discontinuities or for example from a vessel with topological discontinuities to a surface with regions of hydrophobicity or hydrophilicity which define where the dispensed drop or drops are contained. One known technique for transferring liquid is illustrated in Figure 1 and is described in patent WO 97/15394. It takes the concept of the microtitre plate and drills a hole into the bottom of the sample well. To cause the droplets contained within the well to be ejected, the air pressure on the surface of the liquid in the well is raised by sealing the whole top of the microtitre plate with an o-ring and cover and then applying an impulse to the cover. By pressing down onto the lid of the sample well WO 03/101369 PCT/US03/17443 the air above the sample contained within is compressed, this compressive wave then presses onto the liquid causing a momentum transfer which will, with sufficient-over pressure, cause the liquid to be ejected from the nozzle hole in the bottom of the well. In this type of device, the use of air as the medium of momentum transfer causes a broadening of the imparted momentum pulse width, which can have the effect of increasing the volume of liquid dispensed at the nozzle. Furthermore, as the amount of liquid in the well is decreased, the ratio of air to liquid in the well increases and alters the momentum transfer characteristics of the system, whereby the dispensed volume will change over time. In addition, if one of the wells does not contain any liquid, sufficient air pressure may not be developed above the surface of the fluid in the other wells as a result of the air escaping out of the empty wells nozzle. Another known technique is illustrated in Figure 2 and is described in WO 00/24511. In this technique, each of the wells is individually sealed with an air tight membrane. A series of pneumatic passages allows each of the wells to potentially be ejected individually although in practise they are generally fired simultaneously. With this construction, the remainder of the wells still function even if one well is empty of fluid. Another known technique is illustrated in Figure 3, which is a schematic representation of the device described in patent DE11913076. In this device the samples are stored around the edge of the dispensing head in holes, which may be 3 4mm in diameter, and fed to respective nozzles at the centre via micromachined channels. The routing of all the microchannels is configured to achieve uniform ejection characteristics for each of the nozzles. Pneumatic pressure is applied to the volume of air sitting above all of the nozzles simultaneously using a piston which drives into a flexible cover or membrane that sits above all of the nozzles. 2 WO 03/101369 PCT/US03/17443 To improve the sharpness of the momentum pulse, a clever scheme of fast acting pneumatic valves has been employed which evacuates the air above the nozzles a timed instant after the over pressure has been applied. This allows more control over the dispensing and in theory smaller drops to be dispensed. SUMMARY It is an aim of the present invention to provide an improved liquid transfer technique with which a sharp momentum pulse can be achieved. According to a first aspect of the present invention, there is provided a liquid transfer system for dispensing controlled amounts of liquid upon demand, including a reservoir structure defining a plurality of reservoirs each having at least one outlet nozzle commonly provided at a lower side of the reservoir structure, a plurality of momentum transfer components each supported for vertical movement in a respective one of the plurality of reservoirs from a rest position in which a lower surface of the momentum transfer component is located within the respective reservoir facing the nozzle, and an actuator provided externally of the reservoir structure for accelerating the momentum transfer components downwards relative to the reservoir structure, so as, in use, to dispense a controlled amount of liquid through the reservoir nozzles. According to another aspect of the present invention, there is provided a liquid transfer device for dispensing controlled amounts of liquid upon demand, the liquid transfer device including a reservoir structure defining a plurality of reservoirs each having at least one outlet nozzle commonly provided at a lower side of the reservoir structure, and wherein each reservoir is also provided with a momentum transfer component supported on the reservoir structure for vertical movement from a rest position in which a lower surface of the momentum transfer component is located within the respective reservoir facing the nozzle and an upper portion projects out of 3 WO 03/101369 PCT/US03/17443 the reservoir at an upper side of the reservoir structure opposite said lower side at which said nozzles are located; the upper portion facilitating the use of an external actuator to accelerate the respective momentum transfer component downwards relative to the reservoir to dispense a controlled amount of liquid. According to another aspect of the present invention, there is provided a use of the liquid transfer system or liquid transfer device according to the present invention for the transfer of biological materials. According to another aspect of the present invention, there is provided a use of the liquid transfer system or liquid transfer device according to the present invention for simultaneously filling a selected number or all of an array of storage vessels with liquid, or for producing a microarray on a substrate surface. According to another aspect of the present invention, there is provided a method of improving dispensing performance in a liquid transfer device that operates by relatively accelerating a momentum transfer component supported in a reservoir from a rest position towards an outlet nozzle of the reservoir, the method including reducing the distance of the momentum transfer component from the outlet nozzle in the rest position. BRIEF DESCRIPTION OF THE DRAWINGS Embodiments of the present invention are described hereunder, by way of non limiting example only, with reference to the accompanying drawings, in which: Figures 1 to 3 illustrate known liquid transfer devices; Figures 4 and 5 illustrate components of a liquid transfer device according to an embodiment of the present invention; Figure 6 illustrates the assembly of a liquid transfer device according to an embodiment of the present invention; 4 WO 03/101369 PCT/US03/17443 Figure 7 illustrates a liquid transfer device according to another embodiment of the present invention; Figure 8 illustrates a liquid transfer device according to another embodiment of the present invention; Figure 9 illustrates an example of a construction for the momentum transfer component of the type of device shown in Figure 8; Figure 10 illustrates a liquid transfer device employing the liquid transfer device of Figure 9; Figures 11 to 16 illustrate examples of momentum transfer devices for use in the type of device shown in Figures 7 and 8; Figures 17 and 18 illustrate further embodiments of the present invention; Figures 19 and 20 illustrate further embodiments of the present invention; Figures 21 and 22 illustrate examples of uses of the liquid transfer device of the present invention; and Figures 23 and 24 illustrate further embodiments of the liquid transfer device of the present invention including features for limiting the downward movement of the momentum transfer component; and Figure 25 illustrates a further embodiment of a liquid transfer device according to the present invention; Figure 26 illustrates an embodiment of a liquid transfer system according to the present invention; Figure 27 explains the dimensions of an embodiment of a liquid transfer device according to the present invention; Figure 28 illustrates the use of roughened momentum transfer components in an embodiment of a liquid transfer device according to the present invention; Figure 29 is a graph illustrating how using a momentum transfer component with a roughened surface can improve the uniformity of volume deposition; Figure 30 illustrates a further embodiment of a liquid transfer device according to the present invention; and 5 WO 03/101369 PCT/US03/17443 Figure 31 illustrates an example of a snap-back mechanism for use in relation to the present Invention. DETAILED DESCRIPTION An example of a liquid transfer device according to the present invention is shown in Figures 4 and 5.. A planar reservoir structure 6 defines an ordered 2D-array of elongate cylindrical reservoirs 2 spaced at regular pitch and each having a nozzle 4 at its lower end and a relatively large opening 8 at its upper end. The reservoirs are orientated parallel to each other and are of substantially identical shape. The diameter of the outlet nozzle 4 is selected according to the desired size of the ejected droplets. . As a second component of the device, there is provided a lid component 10 comprising a flexible membrane 12 with momentum transfer components 14 embedded into it. Each momentum transfer component includes a portion 16 above the membrane and a portion 18 below the membrane, which when the lid is fitted to the reservoir structure as shown in Figure 6, has a lower surface which lies over the nozzle 4 but slightly spaced from it, as shown by the broken line in Figure 6. When the lid component 10 is assembled onto the reservoir structure 6, a sufficient impulse applied to the upper portion of any of these momentum transfer components will cause liquid to be ejected from the respective nozzle of the respective reservoir, and the elasticity of the membrane automatically restores the momentum transfer component to its rest position. It can be seen that the present invention is a passive structure, which is acted upon by an external actuation. The construction is shown in Figures 4 and 5 is for a 5x5 format, but the device of the present invention could be produced in other formats, such as 8 x 12 format at 9mm pitch to match those of microtitre plates. The reservoirs 20 and momentum 6 WO 03/101369 PCT/US03/17443 transfer components 22 are shown as circular cross-section but could, for example, also be square, triangular or other polygonal. Although not shown in Figures 4 to 6, air holes are provided in the portions of the elastic membrane around the momentum transfer components to allow pressure equalisation between inside and outside the reservoirs after firing, and facilitates liquid from the bulk of the reservoir filling the space between the bottom of the momentum transfer component and the nozzle upon restoration of the momentum transfer component to the rest position in preparation for the next firing. The planar reservoir structure could, for example, be a microtitre plate of the kind described in W097/15394. A combined storage and dispensing device according to the present invention can be produced relatively simply by building momentum transfer block structures onto a lid which is used as standard for capping microtitre plates. The elastic membrane is designed taking into account the level of force that is to be used to displace the momentum transfer block. For example, it may be desired that a droplet be ejected by the force imparted by a 1g mass impacting into the top part of the device at 1m/s. The elastic membrane is preferably made not too flexible, in order to avoid an undesirable level of smearing out of the response of the input impulse. The maximum speed at which successive drops can be ejected is decided by the design of the momentum transfer column and associated supporting elastic membrane. The momentum transfer column can be designed to ensure that the "on" force is applied as a sharp impulse to the fluid. The "off' force is controlled by the speed at which the system returns to its initial state. The stiffer the whole structure, the higher its effective spring constant and the faster it will restore itself. This in turn gives rise to an overall sharper impulse into the fluid, and it has been found that a stiffer structure gives rise to overall smaller droplets being ejected. 7 WO 03/101369 PCT/US03/17443 The momentum transfer column is also designed taking into account the level of force that is to be used to displace it. In general, the smaller the area of the lower face of the momentum transfer component compared to the nozzle diameter the less efficient the transfer of the momentum impulse into the fluid that is required to eject a droplet. The dimensions are selected such that a droplet can be ejected by the application of an impulse that is less than the maximum breaking stress of the device material. The diameter of the momentum transfer component bottom should generally be greater than 0.1mm. The distance of the bottom of momentum transfer component from the nozzle orifice is also selected according to the degree of pressure desired to eject a droplet. Generally, the greater the distance between the bottom of the momentum transfer component and the nozzle the higher the applied impulse required to eject a droplet. Generally, the distance between the bottom of the momentum transfer component and the nozzle plate should be in the range of 1pm - 2000ptm. Relatively small spacings may be achieved using relatively precise micromachining techniques to manufacture the device. In a variation, the momentum transfer component is designed such that the diameter of the portion below the elastic membrane increases along its length towards its bottom. Such a design can help to prevent the stiffness of the device becoming excessively great whilst making it easier for a given momentum impulse to build up sufficient pressure to cause ejection of a droplet. With reference to Figure 27, systems having the following geometries have, for example, been developed: Example 1: For a device compliant with 96 well microtitre plate consumables 8 WO 03/101369 PCT/US03/17443 Supporting membrane thickness (a) of 300 microns. Reservoir diameter (b) of 5.2mm. A gap distance (c) between the bottom of the piston and the nozzle of 500 microns. A piston diameter (d) of 2.5mm. A reservoir depth (e) of 10mm, although lower profile devices have been equally used where the depth is only 5mm. Example 2: Also for a device compliant with 96 well microtitre plate consumables Supporting membrane thickness of 300 microns. Reservoir diameter of 5.2mm. A gap distance between the bottom of the piston and the nozzle of 500 microns. A piston diameter of 2.5mm. A reservoir depth of 5mm. Example 3: For a device complaint with 384 well microtitre plate consumables: Supporting membrane thickness of 300 microns. Reservoir diameter of 2.5mm. A gap distance between the bottom of the piston and the nozzle of 500 microns. A piston diameter of 1mm. A reservoir depth of 10mm. Example 4: Also For a device complaint with 384 well microtitre plate consumables: Supporting membrane thickness of 300 microns. Reservoir diameter of 2.5mm. A gap distance between the bottom of the piston and the nozzle of 500 microns. A piston diameter of 1mm. A reservoir depth of 5mm. 9 WO 03/101369 PCT/US03/17443 It has been found that the uniformity of volume deposition with variations in the amount of liquid in the reservoir can be improved by using momentum transfer components with roughened surfaces as schematically shown in Figure 28. A rapid prototyping process of the kind described later was used to manufacture momentum transfer components with surface roughnesses of (a) 300 microns, (b) 600 microns and (c) 900 microns. It was found that a surface roughness of 300 microns best reduced the effect of the fluid fill height on the deposition volume. The improved performance is shown by the graph of Figure 29 in comparison with a momentum transfer component having a smooth surface. The test fluid used for the comparison was 1.5M Betaine monohydrate. It has also been found that the uniformity of volume deposition with varying fluid fill height can be improved by appropriately constricting a lower portion of the diameter as shown in Figure 30. A system having the following geometries has, for example, been developed: Example 5: For a device complaint with 384 well microtitre plate consumables: Supporting membrane thickness (a) of 300 microns Upper Reservoir diameter (f of 2.5mm. Lower reservoir diameter of (b) 1.5mm. Height of lower reservoir portion (h) is 3mm. Height of upper reservoir portion (g) is 3mm. A gap distance between the bottom of the piston and the nozzle (c) of 500 microns. A piston diameter (d) of 1mm. A reservoir depth (e) of 6mm. 10 WO 03/101369 PCT/US03/17443 The following constructions can, for example, be used to facilitate refilling of the reservoirs with liquid. One way of doing this is to construct the device such that the lid component including the elastic membrane and momentum transfer components is removable from the reservoir structure base (e.g. microtitre plate). Another option as illustrated in Figures 7 and 8 is to provide each momentum transfer component with a through hole extending from the upper end to a side wall to allow the reservoir to be filled via such through hole. In the embodiment illustrated in Figures 7 and 8, this is achieved by providing the momentum transfer component as a tube-shaped structure closed at its lower end (to provide a momentum transfer surface above the nozzle) but open at its upper end and having one or more holes (slots) formed in the side wall of the tube. This "hollow" construction has the advantage of more fully exploiting the available space for liquid storage, which increases in importance the smaller the pitch between reservoirs. In this construction, additional air holes provided in the elastic membrane, as shown in Figure 8, facilitate the filling of the reservoir with liquid, by allowing air to escape Figures 9 to 16 illustrate examples of alternative designs for the momentum transfer component and associated elastic membrane. Figure 9 illustrates an example of a construction for the momentum transfer component shown in Figure 8. The device is tube-shaped, closed at its lower end and open at its upper end and including two slots 30 arranged opposite to each other in the side wall. The portion of the elastic membrane covering the reservoir opening is also shown, and includes two air holes 32. Figure 10 shows how these momentum transfer components are fitted into the respective reservoirs. The elastic membrane is not shown. 11 WO 03/101369 PCT/US03/17443 Figure 11 illustrates an example of a momentum transfer component that is similar to that of Figure 9 but is of square section. The air holes in the membrane are not shown. Figure 12 illustrates an example of a momentum transfer component similar to that of Figure 9 except that it includes four fluid exit slots in the tube side wall rather than two. Again, the air holes in the membrane are not shown. Figure 13 illustrates another example of a momentum transfer component. The device includes a solid cylindrical body with upper and lower portions 16, 18 about a porous elastic membrane 12. The porosity of the plate allows liquid in, air out and decreases the stiffness of the elastic membrane. Figures 14 and 15 show perspective and side views of another example of a momentum transfer component similar to that of Figure 9 except that the upper portion 16 above the elastic membrane 12 is of greater diameter than the lower portion 18 (both portions are of smaller diameter than that of the reservoir). The air holes in the membrane are not shown. Figure 16 illustrates another embodiment of the present invention, in which the momentum transfer component (which may be of solid or hollow construction) is supported on a membrane which has a weak link 40 manufactured into it which extends 360 degrees and which acts like a hinge allowing more flexibility in an otherwise relatively stiff structure. Air holes in the membrane 12 are not shown. 12 WO 03/101369 PCT/US03/17443 In all the embodiments described above, the momentum transfer component is supported by an elastic membrane at the top of the planar reservoir structure 2. However, it may also be supported -elastically for vertical movement at one or more locations below the top of the planar reservoir structure. One example of such a construction is shown in Figure 17(a) and Figure 17(b), which shows a horizontal cross-section. The momentum transfer component includes a solid column 50 that is elastically supported in the reservoir by two sets of three spokes 52 which are secured to the side walls of the reservoir. The additional bottom set of spokes increases the stability of the structure. Figures 18(a) and 18(b) illustrate a variation of the design shown in Figure 17 but with 2 sets of 2 spokes. This type of construction may be produced by forming the hub 50 and spokes 52 as an integral part of the reservoir structure. Another alternative design for optimising injection of the fluid into the space between the bottom of the momentum transfer component and the nozzle is shown in Figure 19(a), Figures 19 (b) and 19(c) (which are horizontal cross sections at different levels) and Figure 20. For the purpose of explanation, these figures show a cylindrical unit cell, a plurality of which are integrally combined together in the final device. Each reservoir of the planar reservoir structure 58 includes a main reservoir 60 in which the momentum transfer component 62 is located above the nozzle (not shown) and a separate fluid channel 64 that is only connected to the main reservoir 60 at a lower portion thereof. The momentum transfer component 62 is elastically supported within the main reservoir 60 by an elastic membrane 66 secured to the top side of the planar reservoir structure, and which has air holes through to the main reservoir and a hole for accessing the fluid channel 64. This design allows fluid to be injected at the base of the momentum transfer component mininising the risk that air becomes trapped between the bottom of the momentum transfer column and the nozzle (not shown) at the bottom of the main reservoir. 13 WO 03/101369 PCT/US03/17443 Prototypes of the above-described devices have been made using conventional rapid prototyping techniques such as selective laser sintering (SLS) and stereolithography. Both these techniques have yielded working devices at low cost. It is envisaged that the device could be mass-produced using injection moulding. For those structures that are not suited to one-part injection moulding, a two part (or multi-part) manufacturing process can be used. For example, a first part could define the array of reservoirs including the nozzles, and a second part the lid including the momentum transfer components. These two parts can then either be bonded together or interlocked using snap fit components, which have been designed into the two parts structures. The nozzle holes could depending on their required size and hence manufacturing resolution, be made in a one-part moulding process as an integral part of the reservoir structure, or formed in a subsequent process using a technique such as, for example, lithography, laser machining or ultrasonic drilling. These devices are useful for transferring small quantities of different samples from one microtitre format structure to another (plate-to-plate transfer), as illustrated in Figure 21. In one example, the device would be contained on a robot that would retrieve the device from a refrigerated storage area either on or off the machine in some modular structure. After removing any casing that could be used for either physical or environmental protection during storage the destination plate would be brought underneath the dispensing plate. To actuate all the momentum transfer components simultaneously a tool could be used, which is a series of (for the 96 well device) 96 lightweight pins positioned in a free-floating 2D grid. It is used to impact the momentum transfer components to eject fluid from the nozzles. To do this the pin tool is rapidly brought down into contact with the tops of the momentum transfer components. Any variations in the heights of the momentum transfer components are accounted for by the free-floating nature of the pins in the pin tool. The force it generates as it strikes the dispensing head is sufficient to eject fluid from 14 WO 03/101369 PCT/US03/17443 the dispensing head into all the respective wells on the empty miicrotitre plate. Ejection volumes depend on the velocity and mass of the individual pins, the size of the nozzle and the geometry of the momentum transfer component and associated device. The devices could, for example, be designed for the storage of liquid over a relatively long period of time. Alternatively, the device is used to dispense the required reagents and then the liquid removed from the reservoirs using centrifugation or pipetting. The device could then be either cleaned and re-used, or disposed of, in which case it is preferably of a design that can be manufactured at low cost. The devices also have use in the preparation of microarrays of biological material, such as DNA, on, for example, a microscope slide as illustrated in Figure 22. A sub section of the reservoirs could be actuated using a pin tool array as discussed above with the number and distribution of pins matching the configuration of the desired array. The device could also be used in the preparation of subsets of existing libraries of samples. In this technique individual reservoirs can be actuated using an individual pin or a user definable array pattern of pins to selectively eject reagent into/onto the required substrate. The above-described devices can give sharp and consistent momentum pulses (which allows droplets of consistently relatively small size to be dispensed) for the dispensing of a relatively large number of droplets of liquid from a single reservoir because the momentum of the momentum transfer component is applied directly to the liquid (rather than via a cushion of air) even when the reservoir becomes almost emptied of its liquid content. Furthermore, since the momentum transfer component includes a portion that extends out of the upper end of the reservoir (opposite to that at which 15 WO 03/101369 PCT/US03/17443 the nozzle is formed), the actuation mechanism can be external to the liquid transfer device and yet maintain the in-line aspect of the design. This also makes the device readily combinable with different types of actuation mechanism depending on the level of performance required, and it also avoids the problem of insulating against contact with corrosive or conductive fluids, which is generally necessary with designs in which the actuation mechanism is provided between the nozzle and a reservoir. In some embodiments, the gap between the wall of the reservoir and the momentum transfer component is substantially the same along the entire length of the portion of the momentum transfer component that resides in the reservoir, and/or the reservoir and momentum transfer components are both cylindrical and arranged concentrically. The ejected volume depends on several factors, one of which is the stiffness of the supporting membrane. Tolerances during the manufacturing process may result in variations in the stiffness of the membrane from batch to batch and/or between individual momentum transfer components from a common batch. In a preferred embodiment, the device is designed so that momentum transfer component is sufficiently close to the nozzle plate in the rest position so that upon the required actuation level the two parts touch thereby limiting the downward movement of the device and compensating for any variations in the stiffness of the supporting membrane. This is can be achieved in one variation by, as shown in Figures 23 and 24, providing on either the momentum transfer component or the reservoir wall defining the outlet nozzle at least one projecting stand-off that provides this limiting action whilst maintaining a separation between a part of the lower face of the momentum transfer component and the outlet nozzle throughout the actuation. In Figure 23, a plurality of standoffs 70 are manufactured on the lower reservoir wall 72 so as to project upwards into the reservoir towards the momentum transfer component. In Figure 24, a plurality of standoffs 74 are provided on the lower 16 WO 03/101369 PCT/US03/17443 portion of the momentum transfer component so as to project from the momentum transfer component towards a portion of the lower reservoir wall defining the outlet nozzle. In the above-described embodiments, the momentum transfer components can be accelerated downwards relative to the reservoir towards the outlet nozzles by either holding the reservoir structure stationary and displacing the momentum transfer component downwards or by holding the momentum transfer component stationary and displacing the nozzle plate upwards. According to an alternative embodiment of the present invention, each momentum transfer component is provided as a discrete component that can be inserted into and withdrawn from the respective reservoir separately from the other momentum transfer components. One example of a design for such a type of momentum transfer component is shown in Figure 25. The momentum transfer components are provided as individual caps 80 that can be inserted, by for example using a robot, into the individual reservoirs after they have been filled with liquid. Each cylindtical momentum transfer component is provided with an elastic supporting member 82 that rests on top of the reservoir structure when the momentum transfer component is inserted into the respective reservoir with its lower surface facing the outlet nozzle in the rest position. The elastic supporting member thus assists the setting of the respective momentum transfer component in the rest position ready for actuation and also serves to automatically return the momentum transfer component back to the rest position after each actuation. Where the actuator is provided separately from the momentum transfer component, a preferred actuator includes plungers for impacting against the tops of the momentum transfer components, stepper motors for repeatedly driving the plungers down into impact with the momentum transfer component, and a snap-back 17 WO 03/101369 PCT/US03/17443 mechanism to avoid any plunger delivering multiple impulses to the respective momentum transfer component upon a single actuation. An example of a snap-back mechanism is illustrated schematically in Figure 31. With reference to Figure 31, in A, the plunger 100 is driven down with an associated lever spring system 106 by the stepper motor (not shown) at a constant speed towards the top of the momentum transfer component 102, giving the desired impact force. During the impact the plunger is pushed upwards relative to the lever spring system 106, and the end of the lever 103 is pushed over the lip 104 on the plunger (by virtue of the circular surface at the end of the lever 103) and towards the sloping ramp, 105 (as seen in B). The lever-spring system, 106, couples with the ramp and rapidly pulls the plunger away from the surface (as seen in C). In this way, any vibrations of the plunger after this point will not affect drop ejection in anyway. The actuator is set up such that the stepper motor reaches its cruise velocity before impact of the plunger with the momentum transfer component, and then decelerates sometime after the impact whereby the impact will always be consistent. It was also found that once a critical velocity was reached drops would start ejecting, but increasing the speed further appeared to have little effect on the drop size. According to another alternative embodiment, the momentum transfer components are not supported by the reservoir structure, but it is the actuator that supports the momentum transfer components in the rest position as well as providing the force for the acceleration the momentum transfer components when a droplet is to be dispensed from the respective reservoir. The actuator also functions to return the momentum transfer component back to the rest position after each actuation. In one example, the momentum transfer components are removably supported by the actuator, thereby facilitating replacement of the momentum transfer components. In one example, the 'momentum transfer components are designed to be disposable or readily cleanable after each use to prevent contamination when a reservoir is emptied 18 WO 03/101369 PCT/US03/17443 and filled with a new different liquid or when the same momentum transfer component is used for dispensing a different liquid from a different reservoir. In one preferred variation as shown in Figure 26, each momentum transfer component 86 is made of two parts, a first part 88 that is not intended to come into contact with the fluid in the reservoirs and which is permanently supported by the actuator 84, and a second lower part 90 that is readily detachable from the first part and made, of a low cost material, such as for example injection moulded plastic part. The lower part, which is immersed in the liquid, can be disposed of after it has been used to dispense fluid out of the liquid reservoir through the methods outlined previously. A feature of all the above-described devices and systems is that the momentum transfer component is designed with respect to the reservoir such that the space between the lower surface of the momentum transfer component and the outlet nozzle is in fluid communication with a part of the reservoir above the lower surface of the momentum transfer component. After each actuation, the space between the lower surface of the momentum transfer component and the outlet nozzle is automatically filled with fluid from the bulk of the reservoir as the momentum transfer component returns to the rest position in preparation for the next actuation. This replenishing action is facilitated by the top of reservoir being open for pressure equalisation with the outside, in some cases by the use of air holes or perforations in the elastic membrane supporting the momentum transfer component on the reservoir structure. In each of the systems described above, a controlled amount of fluid is dispensed by displacing the momentum transfer component down towards the outlet nozzle at a rate sufficient to propagate acoustic waves and cause a directional pressure front in the fluid that is sufficiently high to cause a droplet to be ejected from the outlet nozzle. The above-described devices and systems are adapted to deliver a volume of liquid less than 1 millilitre per reservoir and per actuation. The devices can be adapted to 19 WO 03/101369 PCT/US03/17443 deliver amounts of liquid less than 1 nanolitre (i.e. in the picolitre range). For microarraying, the devices would typically be adapted to deliver 100 to 2000 picolitres per actuation per reservoir. The applicant draws attention to the fact that the present invention may include any feature or combination of features disclosed herein either implicitly or explicitly or any generalisation thereof, without limitation to the scope of any definitions set out above. In view of the foregoing description it will be evident to a person skilled in the art that various modifications may be made within the scope of the invention. 20

Claims

1. A liquid transfer system for dispensing controlled amounts of liquid upon demand, including a reservoir structure defining a plurality of reservoirs each having at least one outlet nozzle commonly provided at a lower side of the reservoir structure, a plurality of momentum transfer components each supported for vertical movement in a respective one of the plurality of reservoirs from a rest position in which a lower surface of the momentum transfer component is located within the respective reservoir facing the nozzle, and an actuator provided externally of the reservoir structure for accelerating the momentum transfer components downwards relative to the reservoir structure, so as, in use, to dispense a controlled amount of liquid through the reservoir nozzles.

2. A liquid transfer system according to claim 1, wherein each momentum transfer component is elastically supported for vertical movement in the respective reservoir such that, in use, the momentum transfer component is automatically restored to the rest position after an actuation.

3. A liquid transfer system according to claim 1 or claim 2, wherein each momentum transfer component includes a lower part including said lower surface detachable from an upper part.

4. A liquid transfer system according to any of claims 1 to 3, wherein the momentum transfer components are supported so as to be readily withdrawable from out of the reservoirs.

5. A liquid transfer device for dispensing controlled amounts of liquid upon demand, the liquid transfer device including a reservoir structure defining a plurality of reservoirs each having at least one outlet nozzle commonly provided at a lower 21 WO 03/101369 PCT/US03/17443 side of the reservoir structure, and wherein each reservoir is also provided with a momentum transfer component supported on the reservoir structure for vertical movement from a rest position in which a lower surface of the momentum transfer component is located within the respective reservoir facing the nozzle and an upper portion projects out of the reservoir at an upper side of the reservoir structure opposite said lower side at which said nozzles are located; the upper portion facilitating the use of an external actuator to accelerate the respective momentum transfer component downwards relative to the reservoir to dispense a controlled amount of liquid.

6. A liquid transfer device according to claim 5, wherein each momentum transfer component is elastically supported for vertical movement in the respective reservoir such that, in use, the momentum transfer component is automatically restored to the rest position after an actuation.

7. A liquid transfer device according to claim 5 or claim 6, wherein the momentum transfer components are removably supported by the reservoir structure to facilitate filling the reservoirs with liquid.

8. A liquid transfer device according to claim 5, wherein the momentum transfer component is hollow and includes at least one hole in a side wall thereof to allow liquid to freely move between the inside of the momentum transfer component and a portion of the reservoir outside the momentum transfer component.

9. A liquid transfer device according to claim 8 wherein the momentum transfer component also has an opening at the upper portion through which the reservoir can be replenished with liquid. 22 WO 03/101369 PCT/US03/17443

10. A liquid transfer device according to claim 5, wherein each reservoir is associated with a respective fluid channel extending from the upper side of the reservoir structure to the bottom of the respective reservoir to facilitate the introduction of liquid into the portion of the reservoir between the momentum transfer component and the nozzle.

11. A use of a liquid transfer system according to claim 1 or a liquid transfer device according to claim 5 for the transfer of biological materials.

12. A use according to claim 11, wherein the biological materials are selected from the group consisting of polyoligonucleotides, peptides and antibodies.

13. A use of a liquid transfer system according to claim 1 or a liquid transfer device according to claim 5 for simultaneously filling a selected number or all of an array of storage vessels with liquid.

14. A use of a liquid transfer system according to claim 1 or a liquid transfer device according to claim 5 for producing a microarray on a substrate surface.

15. A method of transferring a controlled amount of liquid to a target, the method including the steps of: providing a device according to claim 5; filling the reservoir with liquid; and applying an impulse to at least one of the momentum transfer devices via the respective upper portion to impel the momentum transfer device down towards the nozzle.

16. A method according to claim 15, wherein the impulse is applied by impacting the upper portion of the momentum transfer component with a moving-mass. 23 WO 03/101369 PCT/US03/17443

17. A liquid transfer system including the liquid transfer device according to claim 5- and an external actuator for accelerating the respective momentum transfer component downwards relative to the reservoir to dispense a controlled amount of liquid

18. A liquid transfer system according to claim 17 further including a robotic system for automating the handling and use of the liquid transfer device and external actuator.

19. A method of improving dispensing performance in a liquid transfer device that operates by relatively accelerating a momentum transfer component supported in a reservoir from a rest position towards an outlet nozzle of the reservoir, the method including reducing the distance of the momentum transfer component from the outlet nozzle in the rest position.

20. A liquid transfer system according to claim 1 or claim 5, wherein the external surface of a portion of the momentum transfer component for insertion into liquid in the reservoir is roughened so as to optimize the uniformity of deposition volume with variations in the amount of liquid in the reservoir.

21. A liquid transfer system according to claim 20, wherein said external surface of a portion of the momentum transfer component for insertion into liquid in the reservoir is roughened so as to have an average surface feature size of about 300 icrons.

22. A liquid transfer system according to claim 1 or claim 5, wherein for a given reservoir capacity the internal shape of the reservoir is selected in relation to the external shape of the momentum transfer component so as to optimize the 24 WO 03/101369 PCT/US03/17443 uniformity of deposition volume with variations in the amount of liquid in the reservoir.

23. A liquid transfer system according to claim 21, wherein a lower portion of the reservoir in which a lower portion of the momentum transfer component is located is constricted compared to an upper portion of the reservoir.

24. A liquid transfer system according to claim 1, wherein the actuator includes plungers for impacting against the top of the momentum transfer components, motors for driving the plungers down for impact with the momentum transfer components, and a mechanism to avoid multiple impulses being delivered by a plunger to the respective momentum transfer component at the time of an actuation.

25. A liquid transfer system according to claim 5, further including an external actuator, said actuator including plungers for impacting against the top of the momentum transfer components, motors for repeatedly driving the plungers down for impact with the momentum transfer components, and a mechanism to avoid multiple impulses being delivered by a plunger to the respective momentum transfer component at the time of an actuation. 25