Liquid transfer devices are used in the transfer of relatively small amounts of samples to a substrate to form a micro or macro array, which arrays are used in the screening of chemicals, particularly biological materials. In some cases, it is desired to deposit a number of different chemicals at different locations.

One type of liquid transfer device designed for such a purpose is described in copending international application no. PCT/GB01/02239, whose entire content is incorporated herein by reference. The device includes a reservoir structure defining a plurality of reservoir channels, a nozzle structure secured to the reservoir structure and defining a plurality of dispensing nozzles, each nozzle associated with a respective reservoir channel for the dispensing of liquid from the reservoir channel, and an actuator structure sandwiched between the reservoir structure and the nozzle structure for controlling the passage of liquid from the reservoir channels to the outlet nozzles.

It is an aim of the present invention to provide an actuator structure for use in a liquid transfer device, particularly of the type described in PCT/GB01/02239.

According to one aspect of the present invention, there is provided an actuator structure comprising an array of piezoelectric cantilevers defined by an array of slots in a continuous piezoelectric structure, each piezoelectric cantilever supported for deflection upon stimulation of a piezoelectric effect.

Such actuator structure has use, for example, in a liquid transfer device comprising an array of outlet nozzles for holding liquid for transfer, an actuator structure for actuating the release of liquid from the outlet nozzles, and a reservoir structure for replenishing the outlet nozzles after a release of liquid, wherein the deflection of a cantilever stimulates, in use, the release of a controlled amount of liquid from a respective outlet nozzle.

According to another aspect of the present invention, there is provided a liquid storage and transfer device for the storage and transfer of liquids at irregular intervals, the device including a reservoir structure defining a plurality of independent reservoir channels, a nozzle structure secured to the reservoir structure and defining a plurality of outlet nozzles, and an actuator structure sandwiched between the reservoir structure and the nozzle structure for actuating the release of liquid from the outlet nozzles, the outlet nozzles being replenished after each release with liquid from the reservoir channels via a plurality of through holes defined by the actuator structure; wherein the actuator structure comprises an array of piezoelectric cantilevers each associated with a respective outlet nozzle and supported for deflection upon stimulation of a piezoelectric effect, such deflection stimulating the release of a controlled amount of liquid from the respective outlet nozzle.

According to another aspect of the present invention, there is provided a method of preparing an actuator structure for use in a liquid transfer device for actuating the release of liquid from an outlet nozzle, the method including the steps of preparing a continuous piezoelectric structure and forming a slot in the piezoelectric structure to define a piezoelectric cantilever, the piezoelectric cantilever supported for deflection upon stimulation of a piezoelectric effect.

According to another aspect of the present invention, there is provided a liquid storage and transfer device, the device including a reservoir structure defining a

plurality of independent reservoir channels, a nozzle structure secured to the reservoir structure and defining a plurality of outlet nozzles, and an actuator structure sandwiched between the reservoir structure and the nozzle structure for actuating the release of liquid from the outlet nozzles, the outlet nozzles being replenished after each release with liquid from the reservoir channels via a plurality of through holes defined by the actuator structure ; wherein the actuator structure includes a first electrode layer, a piezoelectric layer comprising a continuous layer of piezoelectric material formed on a first surface of the first electrode layer, and an array of independently addressable sub-electrodes formed on a surface of the piezoelectric layer opposite to the first electrode layer, each sub-electrode associated with a respective one or combination of the outlet nozzles, such that, in use, a portion of the piezoelectric material between the first electrode layer and a selected sub- electrode is activated to release liquid from one or more outlet nozzles associated with the selected sub-electrode by the application of a voltage across the first electrode layer and the selected sub-electrode, and wherein the device is adapted such that the application of a voltage across the first electrode and a selected sub-electrode to stimulate the release of liquid from the one or more outlet nozzles associated with the selected sub-electrode does not stimulate the release of liquid from outlet nozzles associated with adjacent sub-electrodes.

In one embodiment, the adaptation of the device such that the application of a voltage across the first electrode and a selected sub-electrode exclusively stimulates the release of liquid from the one or more outlet nozzles associated with the selected sub-electrode lies in spacing the sub-electrodes sufficiently apart to achieve this effect.

In one embodiment, one or more grounding electrodes are provided on a surface of the piezoelectric layer between the sub-electrodes, such that the piezoelectric effect produced upon application of a voltage across the first electrode and a selected sub-

electrode exclusively stimulates the release of liquid from the one or more outlet nozzles associated with the selected sub-electrode.

In another embodiment, trenches are defined in the piezoelectric layer between the sub-electrodes, the trenches extending from the surface of the piezoelectric layer on which the second electrode layer is formed towards the first electrode layer such that the piezoelectric effect produced upon application of a voltage across the first electrode and a selected sub-electrode exclusively stimulates the release of liquid from the one or more outlet nozzles associated with the selected sub-electrode.

According to another aspect of the present invention, there is provided a liquid storage and transfer device, the device including a reservoir structure defining a plurality of independent reservoir channels, a nozzle structure secured to the reservoir structure and defining a plurality of outlet nozzles, each outlet nozzle associated with a respective one of the plurality of reservoir channels, and an actuator structure sandwiched between the reservoir structure and the nozzle structure for actuating the release of liquid from the outlet nozzles, the outlet nozzles replenished after each release with liquid from the reservoir channels via a plurality of through holes defined by the actuator structure; wherein the actuator structure includes a first electrode layer, a piezoelectric layer formed on a first surface of the first electrode layer and comprising an array of blocks of piezoelectric material located in a matrix for isolating the blocks from each other, each block of piezoelectric material associated with one or a combination of the outlet nozzles, and a second electrode layer formed on a surface of the piezoelectric layer opposite to the first electrode layer, such that, in use, the blocks of piezoelectric material are activated to stimulate the release of liquid from the outlet nozzles by applying a voltage across the first and second electrode layers.

In one embodiment, the second electrode layer comprises an array of independently addressable sub-electrodes, each sub-electrode associated with one or more blocks of piezoelectric material, such that, in use, those one or more blocks of piezoelectric material may be activated independently of other blocks of piezoelectric material.

In those aspects of the present invention where the reservoir structure defines a plurality of independent reservoir channels, the channels may be simultaneously filled with different types of liquids, thus allowing the device to be used for the storage and transfer of a plurality of liquids. In one embodiment, each outlet nozzle is associated with a respective one of the plurality of reservoir channels. In one embodiment, each reservoir channel is sealed at its end opposite to the actuator structure to prevent liquid escaping from the reservoir channels as vapour.

In the devices described above, the reservoir channels are independent in the sense that they do not communicate with each other thus allowing, where required, each reservoir to be filled with different liquids without cross-contamination between the liquids.

According to another aspect of the present invention, there is provided a use of the type of liquid storage and transfer devices described above for the storage of, and dispensing of droplets at irregular intervals of, a liquid containing a biomaterial.

According to another aspect of the present invention, there is provided a use of the type of liquid transfer devices described above for preparing a microarray for performing screening of chemicals, particularly biological binding molecules such as peptides, proteins antibodies and oligonucleotides such as DNA, in a high throughput format.

According to another aspect of the present invention, there is provided a method of storing a plurality of liquids and dispensing them at irregular intervals using a device of the type described above, including the steps of filling the reservoir channels with the plurality of liquids via inlets of the reservoir channels and then sealing the inlets of the reservoir channels to substantially prevent the evaporation of the liquids from the reservoir channels.

Embodiments of the present invention are described in detail hereunder, by way of example only with reference to the accompany drawings, in which: Figure 1 shows a schematic view of a liquid transfer device according to a first embodiment of the present invention; Figure 2 shows a schematic view of a liquid transfer device according to a second embodiment of the present invention; Figure 3 shows a schematic view of a liquid transfer device according to a third embodiment of the present invention; Figures 4 to 8 illustrate an example of a method for producing the device shown in Figure 1 ; Figure 9 shows a plan view of an actuator structure for use in the device of Figure 2; Figure 10 shows another example of the patterned electrode for the device of Figure 2 ; Figures 11 and 12 are schematic cross-sectional views of a section of the actuator structures used in the devices of Figures 1 and 2, respectively for explaining the operation of the actuator structures; Figure 13 shows a plan view of a section of an actuator structure according to another embodiment of the present invention; Figure 14 (b) shows a plan view of a section of an individual actuator of an actuator structure according to another embodiment of the present invention, and Figure 14 (b) shows a cross-section taken through line A-A of Figure 14 (a); and

Figures 15 to 17 show schematic cross-sectional views of three different types of cantilever structures for use in the actuator structure shown in Figure 13.

A liquid transfer device according to a first embodiment of the present invention is shown in Figure 1. It includes an actuator structure 4 sandwiched between a reservoir structure 2 and a nozzle structure 6. The reservoir structure defines a plurality of parallel reservoir channels 8 for the storage of liquid 10. A plastic layer 12 covers the inlet of each reservoir channel to prevent the evaporation of liquid from the channels.

This covering layer is nonetheless designed such that it allows the equalisation of pressure between the inside of each channel and the exterior of the device. This may be achieved for example by the use of a semipermeable membrane or a layer having small pressure-equalisation holes above each reservoir channel.

The nozzle structure 6 defines a plurality of outlet nozzles 14 for dispensing liquid from the device.

The actuator structure includes a piezoelectric layer 18 sandwiched between a continuous first electrode layer 16 and a patterned second electrode layer defining a plurality of sub-electrodes 20. The piezoelectric layer 18 comprises a 2D array of blocks of piezoelectric material 22 located in a matrix of a non-conducting elastic polymer 24, each piezoelectric block 22 positioned between the first electrode layer and a respective sub-electrode such that upon application of an appropriate voltage between the first electrode and the sub-electrode, the piezoelectric block is activated.

A protective layer 27 is provided over the array of sub-electrodes.

Although not shown in Figure 1, the piezoelectric blocks are each preferably centered over the central axis of the respective outlet nozzle.

The piezoelectric blocks are tightly fitted in the matrix, such that liquid cannot pass from the reservoir channels to the outlet nozzles other than via the through holes 26, described below. The matrix is made of a material that allows such a tight-fit to be maintained as the piezoelectric blocks are repeatedly activated and deactivated. The matrix, may be made of polymeric materials/adhesives such as epoxy or silicone which is both waterproof and flexible. In a preferred embodiment, a material that cures without shrinkage is selected. For example, a material that cures through cross- linking polymerisation may be used.

The actuator structure 4 also defines a plurality of through holes 26 extending from the respective reservoir channel to the respective nozzle through the protective layer, the piezoelectric layer and the first electrode layer. The through holes allow liquid to pass from the reservoir channels to the outlet nozzles to replenish the outlet nozzles with liquid after the actuated release of liquid from the outlet nozzles. In use, liquid is dispensed from a selected outlet nozzle reservoir channel by the application of an appropriate voltage between the first electrode layer and the associated sub-electrode to activate the respective piezoelectric block. A shock wave is imparted into the liquid held in the outlet nozzle causing a controlled amount of the liquid to be released from the outlet nozzle. After release, the outlet nozzle is refilled by liquid from the respective reservoir channel via the respective through hole under the influence of surface tension.

A liquid transfer device according to a second embodiment of the present invention is shown in Figure 2. The device is similar to that shown in Figure 1 except that the piezoelectric layer comprises a continuous layer of piezoelectric material 30 sandwiched between a continuous first electrode layer 16 and a patterned second electrode layer defining a 2D array of activating sub-electrodes 32 contacting the portions of the piezoelectric layer adjacent the reservoir channels and grounding electrodes 34 between the activating electrodes 32.

The actuator structure 4 also defines a plurality of through holes 26 extending from each reservoir channel to the respective nozzle through the protective layer, the piezoelectric layer and the first electrode layer. In use, liquid is dispensed from a selected outlet nozzle by the application of an appropriate voltage between the first electrode layer and the associated sub-electrode to activate the respective piezoelectric block, which then imparts a shock wave into the liquid held in the outlet nozzle causing a predetermined amount of the liquid to be released from the outlet nozzle.

The grounding electrodes serve to localize the piezoelectric effect thus preventing the application of a voltage between the selected activating sub-electrode and the first ground layer from inadvertently activating those portions of the piezoelectric layer associated with adjacent activating sub-electrodes, by the effect shown in Figure 12.

The grounding electrodes act as grounding shields, without which the piezoelectric effect would not be as localised, allowing the outlet nozzles to be spaced at a relatively small pitch without the problem of cross-talk. The provision of such grounding electrodes also increases the efficiency of the device.

An insulating layer 36 is provided over the array of activating electrodes and grounding electrodes to prevent the electrode from coming into contact with a conducting media, which would otherwise short out the electric field required for the piezoelectric effect. Although the insulating layer is shown in Figures 1,2 and 3 as being relatively thick compared to the diameter of the through holes, the insulating layer can in fact be relatively thin. Such a thin insulating layer could be deposited by a fluid deposition technique after the through holes have been formed without causing the through holes to become unduly blocked.

A liquid transfer device according to a third embodiment of the present invention is shown in Figure 3. The device is identical to that shown in Figure 2 except that the grounding electrodes are replaced by a series of trenches 40 etched into the

continuous layer of piezoelectric material 30 to prevent the application of a voltage between the selected activating sub-electrode and the first ground layer from inadvertently activating those portions of the piezoelectric layer associated with adjacent activating sub-electrodes, by the effect shown in Figure 11. This structure also has the benefit of decoupling the material being flexed from the surrounding bulk material.

A protective layer 26 is provided over the array of activating sub-electrodes and grounding electrodes to prevent the electrode from coming into contact with a conducting media, which would otherwise short out the electric field required for the piezoelectric effect.

Although not shown in Figures 2 and 3, the active portions of the piezoelectric layer i. e. those portions between the sub-electrodes and the bottom ground electrode are each preferably centered over the central axis of the respective outlet nozzle.

A method for producing the device shown in Figure 1 is described below with reference to Figures 4 to 8. A piece of piezoelectric material 52 is bonded to a stainless steel sheet 54 using a conductive epoxy (not shown). The piezoelectric material already has electrodes (such as nickel electrodes) on its surface. The piezoelectric material may have already been poled or may be in an unpoled state with a view to carrying out a poling at a later stage of the production process.

Next, the piece of piezoelectric material 52 is then cut horizontally and vertically using, for example, a diamond saw to define an array of piezoelectric blocks 56 bonded to the stainless steel sheet 54. Other processes such as, for example, laser ablation may be used to cut the piece of piezoelectric material 52.

Next a rim of non-conducting media 58 is bonded on the outside edge of the stainless steel sheet. The top of the rim 58 is level with the top of the piezoelectric blocks 56. This provides a mould for the next step of the process.

A non-conducting elastic polymer 60 is used to fill the spaces between the rim 58 and the piezoelectric blocks 56 to form an elastic matrix on setting. The elastic polymer is selected to have a low shrinkage upon setting so that it stays in intimate contact with the piezoelectric blocks 56 and prevents any unduly large gaps being generated between the blocks and the matrix. Alternatively, the elastic matrix could be formed by placing, for example, stainless steel sheet on top of the piezoelectric blocks and then filling the space between the two stainless steel sheets with the elastic polymer.

A pre-fabricated electrode pattern comprising an array of electrodes 62 supported on a non-conducting media, such as Kapton tape, is bonded on top of the resulting structure, each of the electrodes 62 positioned over a respective block of piezoelectric material. Electrical contact is made between the bottom electrode, defined by the stainless steel plate to which the piezoelectric blocks are bonded, and the electrode 62 via address lines that extend from each piezoelectric block to the edge of the structure. A protective layer (not shown) is then formed over the top of the resulting structure, and through holes 66 are formed through the Kapton tape, elastic matrix polymer and stainless steel sheet, each through hole located next to a respective electrode 62 to allow, the passage of liquid between the reservoir channel and outlet nozzle associated with the electrode. The holes can be formed, for example, by laser drilling. The laser drilling could also be used to generate reference holes for lining up the actuator structure and the reservoir and nozzle structures between which it is sandwiched in the final device.

A method for producing the device shown in Figure 2 is described hereunder with reference to Figure 9. A piece of poled piezoelectric material 70 with nickel electrodes

formed on opposite surfaces thereof is subject to laser etching to burn away selected portions of the electrode coating on one surface to leave a patterned electrode comprising a plurality of independently addressable activating electrodes 72 and a single ground electrode that extends between the activating electrodes 74. The laser etching may also be used to make alignment marks or holes in the piece of piezoelectric material. The laser etching may be done in two steps: a coarse raster removal followed by finer trimming.

Some preferred variations include forming the electrodes by evaporation or by chemical etching of a continuous layer of electrode material, and using an unpoled block of PZT and carrying out the poling at the end of the production process.

The upper surface of the resulting structure is then covered with a thin (for example, 0.1 to 1 microns) coating of insulating material, and then through holes are formed through the insulating material, piezoelectric material and the bottom nickel electrode, each through hole located to connect a respective reservoir channel and outlet nozzle in the liquid deposition device. The through holes may be drilled using a second laser or the same laser used to define the electrode pattern. Alternatively, the insulating coating may be formed by a vapour deposition technique after the through holes are formed, the relative thinness of the insulating coating ensuring that the pre- formed through holes are not unduly blocked.

In the actuator structure shown in Figure 9, each independently addressable electrode is associated with a pair of outlet nozzles, such that pairs of outlet nozzles can be activated independently of other outlet nozzles. This is only one example.

Alternatively, each independently addressable electrode could be associated with a single output nozzle or with more than two outlet nozzles, such as four outlet nozzles using, for example, an electrode pattern as shown in Figure 10.

An actuator structure for use in another embodiment of a liquid transfer device according to the present invention is shown in plan view in Figure 13. It includes an array of cantilevers 102 defined by slots 100 formed, by for example laser drilling, into a substantially planar structure including at least one layer of piezoelectric material (such as PZT). Each cantilever is designed to deflect upon stimulation of the piezoelectric material. Single cantilevers (as shown in Figure 13) or combinations of cantilevers may be independently actuated via an array of electrodes which are in electrical contact with the cantilevers 102 and which are addressable via electrical connectors 104 provided at one or more edges of the actuator structure.

In one embodiment, as shown in Figure 15, the piezoelectric cantilever is a unimorph cantilever comprising a layer of piezoelectric material 122 is laminated to a layer of an elastic substrate 118 via an electrically conducting adhesive 120 or a solder layer or otherwise joined together for electrical connection. In the embodiment shown in Figure 15, the elastic substrate is made of an electrically conducting material such as brass, stainless steel, or tin foil, and also serves as an electrode. The arrow indicates the direction of poling of the piezoelectric material. The piezoelectric cantilever is designed to deflect towards an outlet nozzle upon application by a power source 125 of an appropriate voltage Q V between the elastic substrate and the upper electrode 124 formed in electrical contact with the upper surface of the layer of piezoelectric material 122.

In another embodiment, as shown in Figure 16, the piezoelectric cantilever is a bimorph cantilever comprising two layers of piezoelectric material 128,132 laminated together via an electrically conducting adhesive 130. As shown by the arrows in Figure 16, the two layers of piezoelectric material are poled in opposite directions such that the cantilever is deflected towards an outlet nozzle upon application of an appropriate voltage between lower and upper electrodes 134,126 respectively formed in electrical contact with the lower and upper layers of piezoelectric material 122. The

arrow indicates the direction of poling of the piezoelectric material. The piezoelectric cantilever is designed to deflect upon application of an appropriate voltage 0 V between the lower and upper electrodes In another embodiment, as shown in Figure 17, the piezoelectric cantilever is another type of bimorph cantilever comprising two layers of piezoelectric material 138,142 laminated on opposite surfaces of an intermediate electrode 140. As shown by the arrows in Figure 17, the two layers of piezoelectric material are poled in identical direction such that the cantilever is deflected towards an outlet nozzle upon application of an appropriate common electric potential to the intermediate electrode 140 with respect to both the upper and lower ground electrodes 136,144.

In each of Figures 15 to 17, the area marked with hashing is a schematic indication of the structure about which the cantilever is supported for deflection.

Arrays of the actuators shown in Figures 15 to 17 are formed by preparing a continuous piezoelectric structure including continuous layers of the component materials including the piezoelectric materials, electrode materials and elastic substrate (in the case of Figure 15), and then forming an array of the slots 100 in the continuous structure to define an array of cantilevers. As shown in the embodiment shown in Figure 14 (a), which shows a plan view of an individual actuator without the protective coating applied, the electrodes and the addressing circuitry is formed by then further selectively removing portions of the overlying electrode layer to define an array of electrodes 106 and the lines 107 for independently addressing the electrodes. In the embodiment shown in Figures 14 (a) and 14 (b), there is selectively removed the minimum amount of electrode material necessary to define the electrodes and the addressing circuitry. More of the layer of electrode material can be removed where desirable.

As shown in the cross-sectional view in Figure 14 (b), in one embodiment of the liquid transfer device according to the present invention, the actuator structure (which is of the type shown in Figure 15, but could also be of the type shown in Figure 16 or Figure 17), is positioned between an outlet nozzle structure 112 defining an array of outlet nozzles 110 and a channel reservoir structure 114, each cantilever actuator being associated with a respective outlet nozzle 110 of the outlet nozzle structure. The device is adapted such that deflection of the cantilever stimulates the release of a controlled amount of liquid from the outlet nozzle. In this embodiment, the slot 100 defines the through hole through which the outlet nozzle is replenished via a surface tension effect with liquid from the respective channel reservoir 116 after each release of liquid. The upper electrode 106 is used in combination with the electrically conductive elastic substrate to apply a voltage across the piezoelectric layer to stimulate deflection of the cantilever. A protective layer 108 is provided over the upper electrode which protects it from the liquid stored in the overlying channel reservoir 116.

In each of the embodiments shown in Figures 13 to 17, the outlet nozzle structure and channel reservoir structure may be modified as in each of the previously described embodiments. For example, a plastic layer 12 may be provided to cover the inlet of each reservoir channel to prevent the evaporation of liquid from the channels whilst allowing the equalisation of pressure between the inside of each channel and the exterior of the device.

In each of the embodiments described above, any type of piezoelectric material may be used. One example is PZT. In each of the above-described embodiments, the protective/insulating layer may, for example, be made of silicon nitride, polyimide, TaC-tetrahedrally amorphous carbon (DLC), or parylene.

It is noted that the configuration of the above-described devices in which the actuators are sandwiched between an array of independent reservoir channels and an array of respective outlet nozzles is in contrast to the design conventionally employed in ink-jet printing devices, in which outlet nozzles actuated from above are fed from the side with a common liquid from a common reservoir.