Acoustofluidic device, system and method of operation

Abstract

An acoustic manipulation device is disclosed for acoustic treatment of a fluid volume. The acoustic manipulation device comprises a transducer and a superstrate. The transducer comprises a transducer piezoelectric material and transducer electrodes configured to apply an electric field to the transducer piezoelectric material, the transducer having a transducer acoustic wave transmission surface and the transducer being operable to generate and propagate acoustic waves to the transducer acoustic wave transmission surface. The superstrate has a superstrate acoustic wave transmission surface detachably coupled to the transducer acoustic wave transmission surface. The superstrate further has or is coupled to a fluid volume acoustic wave transmission surface, the fluid volume acoustic wave transmission surface being configured to receive a fluid volume for interaction with acoustic waves generated by the transducer and transmitted to the fluid volume via the superstrate. The superstrate comprises a superstrate piezoelectric material.

Description

[0001] ACOUSTOFLUIDIC DEVICE, SYSTEM AND METHOD OF OPERATION

[0002] Field of the Invention

[0003] The present invention relates to an acoustofluidic device, acoustofluidic system and a method of operation of an acoustofluidic system. The invention relates particularly, although not exclusively, to the treatment of fluid volumes using acoustic energy such as for nebulisation. Other treatments of fluid volumes are contemplated, such as manipulation, streaming and particle concentration.

[0004] Background

[0005] Acoustic manipulation systems are known for the manipulation (such as nebulisation) of fluids on a piezoelectric transducer or on a surface of a superstrate coupled to a piezoelectric transducer.

[0006] For example, the use of a coupling layer is proposed in W02007128045A1 .

[0007] The use of a superstrate on top of the transducer to isolate nebulisation from the transducer is proposed in WO2021062494 A1 .

[0008] According to CA3095450A1 , it has been proposed to be advantageous to decouple the liquid supply system from the surface acoustic wave (SAW), due to heat, attenuation, and the spatial location of liquid.

[0009] Furthermore, US10404232B2 proposes the use of a lithium niobate single crystal for the transducer and a disposable substrate. The resultant arrangement uses a Lamb wave mode, with a limited frequency range due to its simple electrode configuration.

[0010] AU2015345130A1 proposes nebulisation of liquids from cavity arrangements, coupled to the SAW transducer by a liquid coupling layer.

[0011] WO20121 14076A1 proposes the manipulation of the SAWs themselves using phononic structures, which in turn permits engineering of the SAW distribution with respect to the liquid sample.

[0012] The present inventors have realised that further useful developments of acoustofluidic devices and systems are possible, which may allow more commercially useful applications of acoustofluidic technology. The present invention has been devised in light of the above considerations.

[0013] Summary of the Invention

[0014] Accordingly, in a first aspect, the present invention provides an acoustic manipulation device for acoustic treatment of a fluid volume, the acoustic manipulation device comprising: a transducer comprising a transducer piezoelectric material and transducer electrodes configured to apply an electric field to the transducer piezoelectric material, the transducer having a transducer acoustic wave transmission surface and the transducer being operable to generate and propagate acoustic waves to the transducer acoustic wave transmission surface; a superstrate having a superstrate acoustic wave transmission surface detachably coupled to the transducer acoustic wave transmission surface, the superstrate further having or being coupled to a fluid volume acoustic wave transmission surface, the fluid volume acoustic wave transmission surface being configured to receive a fluid volume for interaction with acoustic waves generated by the transducer and transmitted to the fluid volume via the superstrate, wherein the superstrate comprises a superstrate piezoelectric material.

[0015] The present inventors have found that the use of a piezoelectric material for the superstrate provides significant technical advantages in terms of the coupling between the transducer and the superstrate and therefore the efficiency and reproducibility of coupling acoustic energy from the transducer and into the fluid volume.

[0016] By “fluid volume”, it is intended that this covers liquids, mixtures and solids and liquids (e.g. suspensions of solid particles in liquid), flowable solid materials (e.g. flowable solid powder) and fluidizable materials (fluidizable solid powder).

[0017] In a second aspect, the present invention provides an acoustic manipulation system for acoustic treatment of a fluid volume, the system including an acoustic manipulation device according to the first aspect and a fluid delivery mechanism for delivering fluid to the fluid volume acoustic wave transmission surface.

[0018] In a third aspect, the present invention provides a method for the treatment of a fluid volume, the method including: providing a transducer comprising a transducer piezoelectric material and transducer electrodes configured to apply an electric field to the transducer piezoelectric material, the transducer having a transducer acoustic wave transmission surface and the transducer being operable to generate and propagate acoustic waves to the transducer acoustic wave transmission surface; providing a superstrate having a superstrate acoustic wave transmission surface and detachably coupling the superstrate acoustic wave transmission surface to the transducer acoustic wave transmission surface, the superstrate further having or being coupled to a fluid volume acoustic wave transmission surface, dispensing a fluid volume at the fluid volume acoustic wave transmission surface; and treating the fluid volume by operating the transducer to generate acoustic waves and transmit the acoustic waves to the fluid volume via the superstrate, wherein the superstrate comprises a superstrate piezoelectric material.

[0019] Optional features of the present invention will now be set out, which may be combined singly or in any combination with any aspect of the invention, unless the context demands otherwise. The transducer may comprise a plate of single crystal transducer piezoelectric material. The single crystal has a first transducer crystallographic direction. Similarly, the superstrate may comprise a plate of single crystal superstrate piezoelectric material having a first superstrate crystallographic direction. When the superstrate is coupled to the transducer, there may be a predetermined orientation relationship between the first transducer crystallographic direction and the first superstrate crystallographic direction.

[0020] The material of the transducer piezoelectric material and the material of the superstrate piezoelectric material may have substantially the same crystal structure. Optionally, the composition and / or unit cell parameters of the materials may be different. The first transducer crystallographic direction and the first superstrate crystallographic direction may be the same crystallographic direction.

[0021] In some embodiments, the first transducer crystallographic direction is parallel, plus or minus 25 degrees, to the first superstrate crystallographic direction. In some embodiments, the first transducer crystallographic direction is parallel, plus or minus 20 degrees (or plus or minus 15 degrees, or plus or minus 10 degrees, or plus or minus 9 degrees, or plus or minus 8 degrees, or plus or minus 7 degrees, or plus or minus 6 degrees, or plus or minus 5 degrees, or plus or minus 4 degrees, or plus or minus 3 degrees, or plus or minus 2 degrees, or plus or minus 1 degree) to the first superstrate crystallographic direction. The orientation of the first transducer crystallographic direction relative to the first superstrate crystallographic direction is of particular importance to influence the coupling efficiency between the transducer and the superstrate when using a SAW transducer. The orientation may also be used to selectively excite different modes in the superstrate, for example SAWs, thickness-mode vibrations, Lamb waves, shear waves, or mixed-mode waves. Additionally, the superstrate material, cut, dimensions, metallisation, and driving frequency may also be used to excite different modes. The corresponding transducer parameters may also be used to the same effect. Without wishing to be bound by theory, this may be due to the coupling into different combinations of modes to produce different surface displacement patterns. Different modes may have advantages for different applications, for example, nebulisation or sensing. For example, a SAW can leak energy into a fluid, but a shear horizontal wave cannot. This could be used in a liquid sensing context, as certain modes will be damped a liquid is present.

[0022] In some embodiments, the superstrate may comprise a polycrystalline superstrate piezoelectric material. Although such a material with a random grain orientation may be acceptable in some circumstances, in some embodiments, the superstrate piezoelectric material may have a preferred crystalline orientation amongst the grains. For example, the grains may have a biaxial preferred crystalline orientation.

[0023] In some embodiments, the superstrate may have a layered structure. For example, the superstrate may have a main body and a layer formed on the main body. The layer may provide the superstrate piezoelectric material, formed on the main body. In this case, the main body need not be formed from a piezoelectric material. The layer of superstrate piezoelectric material may be a single crystalline layer (e.g. an epitaxial layer formed on the main body, which may itself be single crystal). The material of the transducer piezoelectric material and the material of the superstrate piezoelectric material may have substantially the same composition. The material of the transducer piezoelectric material and the material of the superstrate piezoelectric material may be selected independently from lithium niobate and lithium tantalate, for example. Alternatively, quartz, lead zirconate titanate, barium titanate, zinc oxide, potassium niobate, gallium orthophosphate, lead metaniobate, or aluminium nitride could be used for example.

[0024] In some embodiments, the superstrate acoustic wave transmission surface and the transducer acoustic wave transmission surface are shaped to provide uniform contact pressure across their overlapping area.

[0025] One or both of the superstrate acoustic wave transmission surface and the transducer acoustic wave transmission surface may have a surface roughness Ra of not more than 10OOnm. For example, one or both of the superstrate acoustic wave transmission surface and the transducer acoustic wave transmission surface may have a surface roughness Ra of not more than 900nm, not more than 800nm, not more than 700nm, not more than 600nm, not more than 500nm, not more than 400nm, not more than 300nm, not more than 200nm, not more than 100nm, not more than 90nm, not more than 80nm, not more than 70nm, not more than 60nm, not more than 50nm, not more than 40nm, not more than 30nm, not more than 20nm, or not more than 10nm. It is considered that a lower surface roughness improves the acoustic coupling between the transducer and the superstrate.

[0026] One or both of the transducer piezoelectric material and the superstrate piezoelectric material may have an electro-mechanical coupling coefficient of at least 1 %, more preferably at least 2%, at least 3% or at least 4%. For example, an electro-mechanical coupling coefficient of about 5% is typical for exciting SAWs on 128-YX cut lithium niobate and about 23% for the thickness mode in 36-YX cut lithium niobate. The electro-mechanical coupling coefficient of the transducer piezoelectric material and the superstrate piezoelectric material may be similar, so that for example the ratio of the transducer piezoelectric material electro-mechanical coupling coefficient to the superstrate piezoelectric material electro-mechanical coupling coefficient may be in the range 0.5-2, more preferably in the range of 0.8-1 .3, still more preferably in the range 0.9-1 .1 . Table 1 in V. T. Rathod (A Review of Acoustic Impedance Matching Techniques for Piezoelectric Sensors and Transducers, Sensors 2020, 20(14), 4051 - https: / / doi.org / 10.3390 / s20144051) provides typical coupling coefficients for bulk waves in different piezoelectric materials. Joshi and Jin (Electromechanical coupling coefficients of ultrasonic Lamb waves, J. Acoust. Soc. Am. 94, 261-267 (1993) - https: / / doi.Org / 10.1121 / 1.407084) provides information on coupling coefficients for Lamb waves, for example in lithium niobate.

[0027] In some embodiments, the superstrate acoustic wave transmission surface is in solid-to-solid contact with the transducer acoustic wave transmission surface. For example, the transducer acoustic wave transmission surface may comprise exposed transducer piezoelectric material. The superstrate acoustic wave transmission surface may comprise exposed superstrate piezoelectric material. In some embodiments, one or both of the transducer acoustic wave transmission surface and the superstrate acoustic wave transmission surface comprises a coating layer formed of non-piezoelectric material. For example, this may be a passivation layer or an electrically conducting layer. Such a coating layer (or other intervening layer between the transducer and the superstrate) may for example have a Young’s modulus of at least 5 GPa, or at least 10 GPa. The intention here is to exclude liquid coupling layers, gel coupling layers or elastic adhesive coupling layers, for example.

[0028] In some embodiments, the interface between the transducer and the superstrate is free of a coupling layer.

[0029] The method according to the third aspect may further include detaching the superstrate from the transducer and then coupling a further superstrate to the transducer for treatment of a further fluid volume. Alternatively, the original superstrate may be detached and reattached, for example after an intervening operation such as cleaning to allow re-use.

[0030] In some embodiments, the fluid volume is treated to nebulise the fluid volume.

[0031] In some embodiments, the fluid volume is treated to carry out particle acoustophoresis on particles suspended in the fluid volume.

[0032] In some embodiments, the orientation of the superstrate relative to the transducer is checked and adjusted as necessary based on a measurement of acoustic coupling between the transducer and the superstrate.

[0033] The invention includes the combination of the aspects and preferred features described except where such a combination is clearly impermissible or expressly avoided.

[0034] Embodiments and experiments illustrating the principles of the invention will now be discussed with reference to the accompanying figures in which:

[0035] Fig. 1 shows a schematic view of a system for the preparation and analysis of nebulised droplets according to a reference arrangement.

[0036] Fig. 2 shows a modification of the arrangement of Fig. 1 , being according to an embodiment of the invention.

[0037] Fig. 3 shows a modification of the arrangement of Fig. 2, being according to another embodiment of the invention. Fig. 4 shows a schematic view of another system according to a reference arrangement for the acoustic treatment of a fluid volume.

[0038] Fig. 5 shows a schematic view of another system according to another reference arrangement for the acoustic treatment of a fluid volume.

[0039] Fig. 6 shows a schematic view of a system for the acoustic treatment of a fluid volume, according to an embodiment of the invention.

[0040] Fig. 7 shows typical time series data obtained during transient thermal measurement experiments. Note that increasing the temperature of the liquid in these experiments (and other experiments reported here) is intended to provide information on transfer of energy (in the form of thermal losses) due to acoustic streaming in a highly viscous liquid (in this case glycerol), in order to provide information on the coupling of acoustic energy from the transducer into the superstrate. In practical applications such as polymerase chain reactions, rapid temperature cycling in microfluidic volumes can be useful for speeding up the nucleic acid amplification process, with utility in e.g. point of care diagnostics; while in some other applications this is not required.

[0041] Figs. 8 and 9 show plots of the average fluid temperature as a function of time, extracted from time series data. Fig. 8 shows the results when using a coupling layer and Fig. 9 shows the results when not using a coupling layer.

[0042] Fig. 10 shows average fluid temperature during transient measurements, comparing different rotations of a lithium niobate superstrate relative to the transducer, without a coupling layer present.

[0043] Fig. 11 shows a schematic view of another system according to a reference arrangement for the acoustic treatment of a fluid volume incorporating microparticles.

[0044] Fig. 12 shows a schematic view of a system for the acoustic treatment of a fluid volume incorporating microparticles, according to an embodiment of the invention.

[0045] Fig. 13 shows a 10 microlitre droplet with suspended particles prior to centrifugation.

[0046] Fig. 14 shows the 10 microlitre droplet of Fig. 16 with suspended particles after centrifugation.

[0047] Fig. 15 shows the normalized pixel intensity as a function of time for 5 pm polystyrene particles suspended in a 10 pL DI water droplet placed on different superstrate configurations.

[0048] Fig. 16 shows streaming velocity measured through particle tracking. Particles were suspended in 10 pL Deionised water droplet placed on the superstrate surface. Fig. 17(A)-(F) show alternative configurations for a coupling-layer free superstrate approach. (A) One face of the superstrate is completely in contact with the transducer. (B) One face of the superstrate is surface partially in contact with the transducer. (C) Superstrates stacked on top of each other. One face of one superstrate is in contact with the transducer. (D) A superstrate modified with a coating or layer on one or more faces. (E) A superstrate bonded via one or more faces to another substrate. (F) A superstrate having a microstructured upper surface, forming channels.

[0049] Figs. 18 and 19 show two basic configurations of the coupling layer-free superstrate concepts.

[0050] Fig. 20 shows a schematic view of another system for the acoustic treatment of a fluid volume, according to an embodiment of the invention.

[0051] Fig. 21 shows a schematic view of another system for the acoustic treatment of a fluid volume, according to an embodiment of the invention.

[0052] Fig. 22 shows a schematic view of another system for the acoustic treatment of a fluid volume, according to an embodiment of the invention.

[0053] Fig. 23 shows a schematic view of another system for the acoustic treatment of a fluid volume, according to an embodiment of the invention.

[0054] Fig. 24 shows aerosol size characterisation using laser diffraction system for nebulisation performed at different frequencies applied to a SAW transducer in an arrangement similar to Fig. 4. Aerosol size is in the range optimal for respiratory drug delivery (nasal, throat, lung). Note that modulating the signal, such as increasing the frequency, is shown here to change the particle size distribution of the aerosol (here the particle size is reduced with increasing signal frequency).

[0055] Fig. 25(A) shows a coupling layer-free superstrate configuration where the superstrate is modified with a microfluidic channel. Fig. 25(B) shows a view from the top into the microchannel which is randomly filled with microparticles, before operation of the transducer. Fig. 25(C) shows a view corresponding to Fig. 24(B), but after microparticle alignment into the centre of the microchannel due to acoustophoresis.

[0056] Fig. 26 shows a micrograph of an arrangement of a superstrate oriented at an arbitrary angle with respect to a transducer.

[0057] Fig. 27-35 show results of transient thermal measurements at different angles between the superstrate and the transducer, from about 0 degrees to about 90 degrees.

[0058] Figs. 36 plots the fluid equilibrium temperature as a function of superstrate orientation, extracted from the results shown in Figs. 27-36. Fig. 37 shows a further micrograph, of a LiNbOs superstrate on a transducer having a main IDT (top of transducer in image) as the transmitter and a liquid sensing IDT (bottom of transducer in image) as the receiver, and the measurement of the angle between the superstrate and the transducer.

[0059] Fig. 38 plots S21 against the superstrate rotation angle, measured as shown in Fig. 37, for different superstrates.

[0060] Fig. 39 shows a micrograph of a superstrate that has had its outer profile shaped by laser milling and an array of channels also formed by laser milling.

[0061] Fig. 40 shows a micrograph of part of Fig. 39 at a higher magnification.

[0062] Fig. 41 shows the height profile of the channel indicated in Fig. 40.

[0063] Fig. 42 shows a micrograph of another superstrate that has had its outer profile shaped by laser milling and an array of channels also formed by laser milling.

[0064] Fig. 43 shows a micrograph of another superstrate that has had its outer profile shaped by laser milling and an array of channels also formed by laser milling.

[0065] Fig. 44 shows a micrograph of another superstrate that has had its outer profile shaped by laser milling.

[0066] Fig. 45 shows a micrograph of two other superstrates that have had their outer profile shaped by laser milling and an array of channels also formed by laser milling.

[0067] Fig. 46 shows micrographs of part of Fig. 45 at a higher magnification and the height profile of the channel indicated in Fig. 45.

[0068] Fig. 47 shows the cumulative particle size distribution for an aerosol generated from a superstrate having the form shown in the inset of Fig. 47.

[0069] Fig. 48 shows the particle size distribution for the cumulative particle size distribution of Fig. 47.

[0070] Fig. 49 shows aerosol size characterisation by laser diffraction system for nebulisation performed using the arrangement in Fig. 20. Aerosol size is in the range that is particularly useful for respiratory drug delivery (nasal, throat, lung).

[0071] Fig. 50 shows a SAW transducer and superstrate configuration according to an embodiment of the invention. Fig. 51 shows (top) Laser Doppler Vibrometer (LDV) measurement areas on the SAW device and superstrate configuration shown in Fig. 50, and (bottom) LDV measurement results showing surface displacement magnitude at the indicated measurement areas on the superstrate and transducer.

[0072] Fig. 52 shows a selection of different transducer designs that can be coupled to a superstrate for use in various embodiments of the present invention.

[0073] Fig. 53 shows an embodiment in which a non-SAW transducer is coupled to a superstrate via an electrode free region to allow direct contact between the exposed piezoelectric surface on the transducer and the superstrate.

[0074] Fig. 54 shows a modification of the embodiment of Fig. 53 in which the superstrate overhangs the transducer at one end.

[0075] Fig. 55 shows Laser Doppler Vibrometer (LDV) measurement points on the non-SAW transducer and superstrate configuration shown in Fig. 54 and LDV measurement results showing surface displacement magnitude of small areas on the superstrate and transducer.

[0076] Fig. 56 shows an embodiment having a non-SAW transducer and superstrate configuration wherein the superstrate covers an electrode and electrode-free area on the transducer surface.

[0077] Fig. 57 shows an embodiment having a non-SAW transducer and superstrate configuration wherein the superstrate overhangs from one end of the transducer and covers a surface area on the transducer with and without electrode coverage.

[0078] Fig. 58 shows an embodiment of the present invention wherein the transducer is smaller than the superstrate.

[0079] Fig. 59 shows an embodiment of the present invention wherein more than one small transducer couples locally into a single superstrate for selective surface actuation.

[0080] Fig. 60 shows drawings of a transducer and superstrate and a corresponding assembled transducer and superstrate configuration enabling nebulisation from the surface of the superstrate when liquid is dispensed via the dispensing tip.

[0081] Fig. 61 shows the aerosol size distribution when using the arrangement shown in Fig. 60 when nebulising from a superstrate surface at different frequencies using a single transducer with fundamental frequency of 3 MHz and harmonics at 6 MHz and 10 MHz.

[0082] Fig. 62a shows a plan view of a pillar array that has been laser etched into a lithium niobate substrate. Fig. 62b shows a close up plan view of some of the pillars of Fig. 62a showing length scales.

[0083] Fig. 62c shows a perspective view of some of the pillars of Fig. 62a.

[0084] Fig. 63 shows pillar height measurement for the pillars of the substrate of Fig. 62a.

[0085] Detailed Description of the Invention

[0086] Aspects and embodiments of the present invention will now be discussed with reference to the accompanying figures. Further aspects and embodiments will be apparent to those skilled in the art. All documents mentioned in this text are incorporated herein by reference.

[0087] Various piezoelectric materials, such as lithium niobate and lithium tantalate, are utilized in the field of acoustofluidics to generate ultrasound waves to actuate, transport and manipulate microfluidic volumes and suspended micro- and nanometre objects [1 , 2], Various wave types, including surface waves [Ref. 1] and bulk waves [Ref. 3] can be generated using transducers comprising such piezoelectric materials. Acoustic energy transfer into the liquid through compression, attenuation and non-linear interactions gives rise to acoustofluidic phenomena such as acoustic streaming, acoustophoresis, micro-cavitation, jetting and atomization, which find applications for example in the biomedical industry [Ref. 4], For example, in open microfluidic systems, the manipulation of micro and nanolitre droplets, along with suspended micro- and nanometre sized objects, has been used for diagnostic and analytical applications [Refs. 5, 6, 7]. Furthermore, precise and selective control over micro- and nanometre objects in closed microfluidic channels using streaming, radiation and / or Bjerknes forces has enabled functions such as particle sorting, filtering, separation, modification (e.g. lysis, coating) and concentration in analytical applications [Ref. 8], Furthermore, atomization and aerosol generation [Ref. 9] have been applied for drug delivery to the lungs [Ref. 10],

[0088] However, acoustofluidic platforms based on lithium niobate face challenges such as high transducer costs, material wear / contamination from interactions with liquids [Ref. 11] or corrosive substances, and the need for precise alignment [Ref. 12] when performing acoustofluidic applications directly on the transducer.

[0089] To address these challenges, researchers have introduced the concept of superstrates placed on top of the piezoelectric material [Refs. 13, 14, 15, 16], The acoustic energy is coupled into the superstrate and the fluidic manipulations are performed on its surface. To ensure sufficient energy transmission between the piezoelectric materials and the superstrate, coupling layers are employed, ranging from viscous fluids (e.g. water, glycerol) to elastic solids such as adhesives [Ref. 17], However, while the superstrate concept isolates the piezoelectric transducer from acoustofluidic functions, the present inventors have realised that it presents challenges concerning the coupling layer’s composition, thickness, durability and application method to the surface of the piezoelectric material or superstrate. Variation in coupling layer thickness or composition impacts the acoustic energy transmission [Refs. 17, 18], increases heat generation and impedes efficient acoustofluidic manipulation. In cases where the superstrate serves as a disposable or consumable item within a platform, the need for a robust and reliable coupling layer solution is an important consideration for functional systems.

[0090] Furthermore, where the coupling layer is a liquid, operation of the system can lead to losses from the liquid coupling layer, by evaporation and / or nebulisation, further affecting the thickness and uniformity of the coupling layer over time.

[0091] Part of the insight on which the present invention is based is that there are two particular types of challenge encountered in acoustofluidic applications: those pertaining to fluid manipulation directly on the piezoelectric transducer and the utilization of the superstrate concept. In various embodiments of the present invention, it is found to be possible to remove the necessity for a coupling layer. In some embodiments, superstrates are employed that are composed of materials akin to those of the transducer. In this case, it is found to be particularly advantageous to align crystalline orientations of the transducer and superstrate. For example, when the transducer comprises lithium niobate, the superstrate material may either match or closely resemble lithium niobate (e.g., lithium tantalate), facilitating coupling-layer-free transmission of acoustic energy via electro-mechanical interaction between the transducer and the superstrate. Consequently, this enables non-permanent, coupling-layer-free superstrate / transducer systems for acoustofluidic applications.

[0092] From one perspective, the superstrate can itself be considered to be a solid coupling medium facilitating acoustic transmission from a transducer to another substrate, thereby isolating acoustofluidic functions from the transducer surface.

[0093] Before considering the structure and operation of embodiments of the invention in more detail, it is of interest to consider some reference arrangements previously devised that are particularly concerned with the nebulisation of fluids, with reference to Figs. 1-3. In those reference arrangements, the coupling of acoustic energy from a piezoelectric transducer into a superstrate was studied. This is of particular interest for the nebulisation of liquids using surface acoustic waves (SAWs), although the use of different acoustic energy is also contemplated in orderto achieve the advantages of the invention, and different fluid treatment than nebulisation is contemplated, for example, thickness mode transducers and Lamb mode transducers. The reference arrangements build on some of the inventors’ previous work PCT / EP2024 / 061412 (unpublished at the time of writing)) in which the ability to control the aerodynamic particle size distribution (APSD) through use of different microstructures and input powers was demonstrated.

[0094] Figure 1 shows a previous system for the preparation of nebulised droplets.

[0095] In the system of Figure 1 , there is a nebuliser device 10 comprising an acoustic wave transducer 12 having a transducer piezoelectric material substrate 14 and an electrode arrangement 16, typically in the form of an interdigitated electrode arrangement. The electrode arrangement 16 is located on the top surface of the transducer piezoelectric material substrate 14, which in this reference arrangement is a planar plate. There is also a region of the top surface of the substrate 14 where the electrode arrangement is not located. This region includes a fluid volume acoustic wave transmission surface 18 onto which a liquid is to be dispensed, as described later.

[0096] The system includes a dispenser 20 which comprises a reservoir 22 and a dispensing conduit 24, which in this example is a needle. The dispenser may also include a pump (not shown) in order to cause flow of and meter the liquid from the dispenser 20.

[0097] In operation, a suitable electrical drive signal is applied to the electrode arrangement 16. In combination with the transducer piezoelectric material substrate 14, this forms the transducer 12 that generates surface acoustic waves (SAWs) that propagate along the fluid volume acoustic wave transmission surface 18. The SAWs interact with the liquid located on the fluid volume acoustic wave transmission surface 18 to produce nebulised droplets of the liquid. The nebulised plume 28 is indicated schematically in Figure 1 .

[0098] In the arrangement shown in Figure 1 , the end of the dispensing needle 24 is spatially separated from the fluid volume acoustic wave transmission surface 18, and not in contact with the transducer 12, such that the dispenser 22 is isolated from the SAWs propagating to and along the acoustic wave interaction surface 18. This configuration is particularly useful when the liquid is a suspension formulation since acoustic clustering of non-soluble particles in the formulation in the dispenser is avoided.

[0099] In some arrangements, the drops 26 fall under gravity from the end of the dispensing needle 24 onto the fluid volume acoustic wave transmission surface 18 at a predetermined flow rate. In other embodiments, the needle 24 may be in fluid contact with the fluid volume acoustic wave transmission surface 18 during dispensing the liquid, i.e. there may be formed a liquid bridge between the needle 24 and the fluid volume acoustic wave transmission surface 18 during dispensing the liquid.

[0100] The effect of the SAWs propagating along the fluid volume acoustic wave transmission surface 18 results in some acoustic streaming of the liquid along the surface, as shown schematically in Figure 1 by the sessile drop 27 being located slightly offset from the position at which drops 26 impact the fluid volume acoustic wave transmission surface 18. It will be understood that different modes of delivery of the liquid to the fluid volume acoustic wave transmission surface 18 are possible, for example by metering the isolated volumes of suspension formulation by spraying, slug flow or other equivalent approach.

[0101] In experimental testing of various arrangements where the particle size characteristics of the nebulised plume 28 are of interest, the nebulised plume 28 is drawn into a particle size analyser 30. This may for example be an Andersen Cascade Impactor (ACI) with inlet 32, eight stages 34 of the cascade and flow pump 36 to generate the air flow indicated in Figure 1 as drawing the nebulised plume 28 towards and into the inlet 32. The ACI may be interchangeable with a Next Generation Impactor (NGI) and it is expected that both types of analyser obtain comparable results. In a modified reference arrangement, similar to Figure 1 , the dispensing needle may be configured in contact with the transducer acoustic wave transmission surface during dispensing the liquid. As such, the needle dispenses the liquid directly onto the upper surface of the transducer piezoelectric material substrate. Alternatively, the needle can be configured to be out of direct contact with the transducer acoustic wave transmission surface during dispensing the liquid, but close enough that when dispensing liquid there remains a liquid bridge between the upper surface of the transducer piezoelectric material substrate and the needle.

[0102] Fig. 2 shows a modification of the arrangement of Fig. 1 , being according to an embodiment of the invention, with the ACI omitted.

[0103] In the system of Figure 2, there is a nebuliser device 110 comprising an acoustic wave transducer 112 having a transducer piezoelectric material substrate 114 and an electrode arrangement 116, typically in the form of an interdigitated electrode arrangement. The electrode arrangement 116 is located on the top surface of the transducer piezoelectric material substrate 114, which in this embodiment is a planar plate. Typically, the transducer piezoelectric material substrate 114 is a single crystal material. There is also a region of the top surface of the substrate 114 where the electrode arrangement is not located. This region includes a transducer acoustic wave transmission surface 118 on which a superstrate 160 is placed. A liquid is dispensed onto the upper surface of the superstrate 160, in a similar manner to the dispensing of liquid in relation to Figure 1 . A dispenser 120 comprises a reservoir 122 and a dispensing conduit 124, which in this example is a needle. The dispenser may also include a pump (not shown) in order to cause flow of and meter the liquid from the dispenser 120.

[0104] In operation, a suitable electrical drive signal is applied to the electrode arrangement 116. In combination with the transducer piezoelectric material substrate 114, this forms the transducer 112 that generates surface acoustic waves (SAWs) that propagate along the transducer acoustic wave transmission surface 118.

[0105] Superstrate 160 has a superstrate acoustic wave transmission surface 162 (in this embodiment, the lower surface of the superstrate 160) detachably coupled to the transducer acoustic wave transmission surface 118. The superstrate 160 has a fluid volume acoustic wave transmission surface 164 (in this embodiment, the upper surface of the superstrate). The fluid volume acoustic wave transmission surface 164 is configured to receive a fluid volume 127 for interaction with acoustic waves generated by the transducer and transmitted to the fluid volume 127 via the superstrate 160.

[0106] The SAWs interact with the liquid located on the fluid volume acoustic wave transmission surface 164 to produce nebulised droplets of the liquid. The nebulised plume 128 is indicated schematically in Figure 2. Other features of the arrangement and operation of Figure 2 are similar to Figure 1 as already described.

[0107] Fig. 3 shows another embodiment of the invention. The arrangement is similar to Figure 2 and so will not be repeated in detail. Superstrate 160 is located on top of transducer 112. Dispensing needle 124 is configured in contact with the superstrate upper surface during dispensing the liquid. As such, the needle dispenses the liquid directly onto the upper surface of the superstrate. Alternatively, the needle can configured to be out of direct contact with the upper surface of the superstrate during dispensing the liquid, but close enough that when dispensing liquid there remains a liquid bridge between the upper surface of the superstrate and the needle.

[0108] As mentioned above, the present invention is not necessarily limited to the manipulation or treatment of fluid volumes by nebulisation. Accordingly, some additional disclosure is set out below with reference to Figures 4-6 in which the fluid volume is subjected to acoustic energy, here taking SAW as one suitable example of acoustic energy.

[0109] Figure 4 shows a schematic view of another system according to a reference arrangement for the acoustic treatment of a fluid volume. In the system of Figure 4, there is an acoustofluidic device 210 comprising a surface acoustic wave transducer 212 having a transducer piezoelectric material substrate 214 and an electrode arrangement 216, typically in the form of an interdigitated electrode arrangement. The electrode arrangement 216 is located on the top surface of the transducer piezoelectric material substrate 214, which in this reference arrangement is a planar plate. There is also a region of the top surface of the substrate 214 where the electrode arrangement is not located. This region includes a transducer acoustic wave transmission surface 218. Superstrate 260 is coupled to the transducer piezoelectric material substrate 214 via a liquid coupling layer 261. Fluid volume 227 is located on the upper surface of the superstrate 260. Acoustic waves (in this case surface acoustic waves represented generally at 217) are transmitted along the transducer acoustic wave transmission surface 218 and couple into the superstrate via the liquid coupling layer 261 . Although such an arrangement is convenient in a research setting, in practice the liquid coupling layer is not stable over periods of time and is difficult to replicate from one use of the system to the next.

[0110] Figure 5 shows another arrangement, similar to Figure 4, except that the superstrate has leg portions 260a, 260b which make contact with the transducer surface, and serve to define a gap in which the liquid coupling layer can be located.

[0111] Figure 6 shows a schematic view of a system for the acoustic treatment of a fluid volume according to an embodiment of the invention. In the system of Figure 6, there is an acoustofluidic device 210 comprising an acoustic wave transducer 212 having a transducer piezoelectric material substrate 214 and an electrode arrangement 216, typically in the form of an interdigitated electrode arrangement. The electrode arrangement 216 is located on the top surface of the transducer piezoelectric material substrate 214, which in this embodiment is a planar plate. There is also a region of the top surface of the substrate 214 where the electrode arrangement is not located. This region includes a transducer acoustic wave transmission surface 218.

[0112] Superstrate 260 is directly coupled to the transducer piezoelectric material substrate 214. The superstrate has a superstrate acoustic wave transmission surface 262 detachably coupled to the transducer acoustic wave transmission surface 218. Fluid volume 227 is located on the upper surface of the superstrate 260, this upper surface corresponding to the fluid volume acoustic wave transmission surface 264. In operation, the fluid volume 227 interacts with acoustic waves generated by the transducer and transmitted to the fluid volume 227 via the superstrate.

[0113] In the embodiment of Figure 6, the superstrate comprises a plate of superstrate piezoelectric material. As described in more detail below in relation to experimental testing, it is found that this can provide efficient and reproducible coupling of acoustic waves into the superstrate and to the fluid volume.

[0114] Also in the embodiment of Figure 6, the superstrate acoustic wave transmission surface 262 is in solid-to- solid contact with the transducer acoustic wave transmission surface 218. It is found unexpectedly that this can give efficient and reproducible coupling of acoustic waves into the superstrate and to the fluid volume.

[0115] As explained in more detail below, transmission of acoustic energy into the superstrate and the resulting acoustofluidic manipulation can be achieved by using identical or similar piezoelectric materials for the superstrate and transducer. Furthermore, the transmission of acoustic energy into the superstrate and the resulting acoustofluidic manipulation can be achieved by placing the superstrate on the vibrating surface of the transducer (independent of type of wave, e.g. bulk vs surface wave and transducer side) without the need for a coupling layer.

[0116] In some embodiments, the superstrate may be urged against the transducer, for example by clamping. Alternatively, the superstrate can be simply placed on the transducer (without additional force other than the weight of the superstrate and the fluid volume) to achieve suitable transmission of acoustic energy and acoustofluidic manipulation.

[0117] In some embodiments, suitable transmission of acoustic energy into the superstrate and the resulting acoustofluidic manipulation is achieved with polished superstrates (surface roughness (e.g. Ra) < 10 nm) or with unpolished superstrates (surface roughness (e.g. Ra) > 10 nm). Corresponding suitable surface finishes apply also to the transducer.

[0118] In some embodiments, the acoustic waves may be travelling or standing surface acoustic waves.

[0119] Various vibrational modes such as thickness, Lamb and SAW modes can be used in different transducer designs by suitable patterning of the electrodes. This can include, for example, interdigitated electrodes in various configurations (standard SAW, SPUDT, slanted, chirped, focusing).

[0120] In some embodiments, there may be two or more superstrates. For example, there may be a stack of superstrates. Spatial and localised coupling layer free transmission of acoustic energy and acoustofluidic manipulation can for example be achieved using thin or small geometric superstrates (0.1 - 1 mm) attached to other substrates that contain a surface or microfluidic features for acoustofluidic manipulations. As described below, the transducer can be smaller than the superstrate. In this case, for example, multiple transducers can be coupled to the same superstrate.

[0121] Using embodiments of the present invention, transmission of acoustic energy and acoustofluidic manipulation can be achieved independent of superstrate geometry (thickness, shape). As will be understood, the superstrate geometry may affect the surface displacement at a particular frequency due to resonance effects.

[0122] In some embodiments, the superstrate or the transducer may be further modified. For example, there may be a coating (e.g. for passivation, such as silicon dioxide, and / or for protection). There may be provided features for additional functionality such as conducting, semi-conducting and photoconducting elements for application such as sensing, micro- and nanoparticle manipulations including biological systems (viruses, bacteria, fungi, mammalian cells, single cell organisms).

[0123] Further modifications of the superstrate or the transducer include further structural alterations or additions such as introduction of micro- and / or nano-cavities (channels, holes, etc), and the addition of phononic and photonic structures. These can be formed through etching, machining, drilling or bonding, for example.

[0124] Transmission of acoustic energy and acoustofluidic manipulation can be achieved at any suitable applied ultrasound frequency.

[0125] The superstrate may be made in a way to be a disposable, recyclable and cleanable (and re-usable) part of the acoustofluidic system.

[0126] In some embodiments, the acoustic energy transmission into the superstrate allows nebulisation of liquids from the superstrate which can be used, for example, for respiratory drug delivery. For example, the acoustic energy transmission into the superstrate allows aerosolization of liquids with the aerosol size being in the range suitable and / or optimal for respiratory drug delivery.

[0127] In some embodiments, the acoustic energy transmission into the superstrate allows for liquid manipulation for open microfluidic concepts (e.g. sessile droplet). Additionally or alternatively, the acoustic energy transmission into the superstrate may allow for liquid manipulation for closed microfluidic concepts (e.g. micro- and / or nanochannels).

[0128] In the work reported below, quantification has been carried out of coupling layer free acoustic energy transmission through measurements of heat generation in microlitre droplets on the superstrate surface. Comparisons are made with other superstrate materials (glass, silicon) with and without a coupling layer. Note that increasing the temperature of the liquid in these experiments (and other experiments reported here) is intended to provide information on transfer of energy (in the form of thermal losses) due to acoustic streaming in a highly viscous liquid (in this case glycerol), in order to provide information on the coupling of acoustic energy from the transducer into the superstrate. Therefore, the temperature measurements reported here are merely intended to provide a useful indication of the coupling efficiency of acoustic energy from the transducer to the liquid sample, via the superstrate. It should be noted that, in some practical applications such as polymerase chain reactions, rapid temperature increases and temperature cycling is highly desirable for e.g. ultra-fast PCRs at the point of care.

[0129] Also quantified is coupling layer free acoustic energy transmission by measurement of acoustic streaming velocities inside microlitre droplets with suspended microparticles. Comparisons are made with other superstrate materials (glass, silicon) with and without a coupling layer.

[0130] Also quantified is coupling layer free acoustic energy transmission through measurement of centrifugation time to concentrate microparticles inside of microliter droplets (microcentrifugation). Comparisons are made with varying superstrate materials (glass, silicon) with and without coupling layer.

[0131] In the examples considered below, nebulisation was performed at a surface of the superstrate, the surface being one or more of a top, bottom, edge or recess of the superstrate.

[0132] Initial aerosol size characterisation was carried out for nebulised liquids from the superstrate.

[0133] Microlitre droplet actuation was carried out on the superstrate (open microfluidics). Particle manipulation was carried out on the superstrate in microlitre droplets (open microfluidics).

[0134] Particle manipulation was also carried out on the superstrate in microchannels (closed microfluidics).

[0135] Acoustofluidic manipulations were carried out using superstrates of different cuts, geometries, shapes and with different surface alterations (e.g. metal, SiCh coatings).

[0136] Also demonstrated was coupling layer free acoustic manipulation at different ultrasound frequencies, and / or using different SAW transducer designs, and / or using travelling and standing surface acoustic waves. Furthermore, also demonstrated was coupling-layer free acoustic manipulation on superstrates that form vertical stacks on the transducer.

[0137] A useful measure of the efficiency of acoustic coupling from a transducer into a liquid drop on a superstrate can be obtained by measuring the change in temperature of the liquid drop during operation of the transducer. Acoustic actuation of a fluid results in heat generation due to thermal and viscous losses. In the present work, acoustic energy transmission into a liquid via different superstrates was therefore quantified using transient thermal measurements under continuous acoustic actuation. Greater transmission leads to greater heat generation and therefore higher temperature of the liquid drop. Rectangular superstrates were used (with dimensions 10x5x1 mm), consisting of glass, single crystal silicon and single crystal 128° Y- cut lithium niobate. These superstrates were placed on a single crystal 128° Y- cut lithium niobate SAW transducer, driven at 13.56 MHz with 1 W of power. Superstrates were tested both with and without a 2 pl deionised (DI) water coupling layer between the transducer and the superstrate. A 10 pl sessile drop of glycerol was placed on each superstrate and the liquid temperature was measured over 100 seconds with an IR camera (FLIR E60bx) operating at 30 fps, with each measurement beginning as the RF power to the transducer was turned on.

[0138] The measurements reported below compared the performance of an arrangement corresponding to Figure 7 (with a liquid coupling layer) and Figure 9 (without a liquid coupling layer).

[0139] Figure 7 shows typical time series data obtained during the transient thermal measurement experiments. This series is for a lithium niobate superstrate without a coupling layer. It is clear from this that the heat generation primarily occurs within the fluid drop due to the acoustic actuation, hence the fluid temperature can be used as a measure of the acoustic energy transmitted to the fluid.

[0140] From the time series data for each run, the average fluid temperature as a function of time was extracted and is plotted in Figures 8 and 9. With the inclusion of a coupling layer, substantial heating of the fluid is observed with all superstrates, indicating good initial transmission of acoustic energy. With the coupling layer removed, the heating with the glass and silicon superstrates is significantly reduced, whereas the lithium niobate is largely unchanged. This demonstrates the potential of a lithium niobate superstrate for coupling-layer free actuation. In Figures 8 and 9, shaded regions indicate standard deviation over three trials.

[0141] The acoustic energy transmission through a lithium niobate superstrate is affected in part by the relative crystal orientations of the transducer substrate and the superstrate. Without wishing to be bound by theory, this is considered to be due to the crystal structure of the lithium niobate giving rise to anisotropy in the acoustic wave speeds and changes to the coupling coefficients for different wave modes. This was verified experimentally by performing thermal measurements for different planar rotations of the lithium niobate superstrate relative to the transducer, the results of which are shown in Figure 10, which shows average fluid temperature during transient measurements, comparing different rotations of a lithium niobate superstrate relative to the transducer, without a coupling layer present. Transmission is maximised when the crystal axes of the substrate and superstrate are aligned or substantially aligned, and minimised when they are perpendicular. For the perpendicular case, the different wave speeds either side of the interface result in an acoustic impedance mismatch, leading to reflection of acoustic energy from the interface. With respect to the 90 degree and 45 degree results, the 90 degree results are higher than the 45 degree results probably due to the 90 degree experiment having a higher starting temperature. We note that the difference between the 45 and 90 degree results does not change significantly over time, indicating the heating is more or less at the same rate. We now turn to a consideration of streaming velocity and microparticle centrifugation time as a further proxy for acoustic energy transmission.

[0142] Individual superstrates with rectangular shape (1 mm thickness, 10 mm long, 5 mm wide) made from glass, silicon and 128° Y- cut lithium niobate were used to investigate coupling of acoustic energy under various configurations (Figures 11 and 12). The arrangements of Figures 11 and 12 correspond to Figures 4 and 6, respectively, except for the fluid sample, explained below.

[0143] Coupling was studied with and without coupling layer (2 pL of DI water). Acoustic energy transmission was quantified by measuring streaming velocities and particle centrifugation time within a 10 pL droplet (DI water) positioned at the centre of the superstrate surface (Figures 11 and 12).

[0144] The transmission of acoustic energy into the droplet induces acoustic streaming, wherein suspended 5 pm polystyrene particles (0.1 wt%) experience drag forces. The velocity of these particles (i.e., streaming velocity) is directly proportional to the drag force, which in turn is proportionate to the amount of acoustic energy coupled into the droplet. Particle velocities were measured using a particle tracking software (Diatrack version 3.04).

[0145] Moreover, acoustic streaming in combination with acoustic radiation forces create an acoustofluidic centrifuge system that drives suspended particles into the centre of the droplet. The centrifugation time is inversely proportional to the transmitted acoustic energy. Enhanced coupling correlates with increased acoustic streaming and radiation forces, resulting in reduced centrifugation times. The particle centrifugation process was recorded with a camera. Particle accumulation increases pixel intensities locally in the centre of the droplet over time while reducing the overall intensity across the droplet. The pixel intensity of the images were obtained using Matlab and each experiment was repeated three times. Figure 16 shows the 10 pL droplet with suspended particles prior to centrifugation. Figure 14 shows the 10 microlitre droplet with suspended particles after centrifugation.

[0146] A continuous acoustic signal was produced by a SAW transducer generating a surface acoustic wave (SAW) at 13.56 MHz. The measured forward power into the transducer was 0.5 W.

[0147] Figure 15 shows the normalized pixel intensity as a function of time for 5 pm polystyrene particles suspended in a 10 pL DI water droplet placed on different superstrate configurations. Note, silicon and glass superstrate configurations without a coupling layer are not shown due to the lack of acoustic energy transmission and streaming.

[0148] Table 1 summarizes the results of the particle centrifugation study for various superstrate configurations.

[0149] Acoustic energy transmission including centrifugation in coupling layer-free configurations was only achieved for LN superstrates. Moreover, this configuration also demonstrated the shortest centrifugation time when compared to silicon, glass as well as LN superstrates utilizing a coupling layer.

[0150] Table 1 - Particle centrifugation time for various superstrate configurations.

[0151] Superstrates Particle centrifugation time (s)

[0152] LN w / o coupling layer 1 .33 ± 0.38

[0153] Silicon w / o coupling layer not achieved

[0154] Glass w / o coupling layer not achieved

[0155] Silicon with coupling layer 2.33 ± 1 .04

[0156] Glass with coupling layer 6.83 ± 1 .01

[0157] LN with coupling layer 11.92 ± 3.36

[0158] Figure 16 provides a summary of the quantification of acoustic streaming via particle velocity measurements. Please note that for glass and silicon superstrate configurations without coupling layer the lack of acoustic energy transmission led to undetectable particle movement. The results show that the induced acoustic streaming in a coupling layer-free LN superstrate configuration is comparable to configurations of glass and silicon superstrates requiring a coupling layer. The results correlate well with the centrifugation times measured in Figure 15.

[0159] We now turn to consider some alternative transducer and superstrate configurations

[0160] Figure 17 shows alternative configurations of the coupling layer-free superstrate approach which may be utilized for specific applications. For instance, Figure 17(D) depicts a configuration where the superstrate is modified with a coating or a layer. Such a layer can be made of one or more metals to create metal electrodes for sensing applications (e.g. impedance spectroscopy) or for introduction of other functions based on electrokinetic effects such as dielectrophoresis, electrophoresis, electrolysis, and / or electroosmosis. Moreover, Figure 17(E) depicts a configuration where the superstrate is bonded to another substrate (e.g. glass, silicon, plastic). The size and position of the superstrate allows localised coupling into the substrate to facilitate localised acoustofluidic manipulations on the substrate surface. The substrate may be structured to create microfluidic channels for acoustofluidic manipulations, as shown for example in Figure 17 (F). Suitable channel can be formed via laser milling, as described later.

[0161] We now turn to consider some suitable applications of the coupling layer-free superstrate approach.

[0162] Figures 18 and 19 show two basic configurations of the coupling layer-free superstrate concepts. One configuration (Figure 18) is termed open microfluidics which can be used for applications such as droplet manipulation (see particle centrifugation above) or aerosol generation / nebulisation for drug delivery to the respiratory system. The other configuration (Figure 19) uses a closed microfluidic approach. Here the acoustic energy is transmitted into the fluid inside e.g. microfluidic channels or cavities to perform particle manipulations such as concentrating, filtering, mixing through acoustophoresis and acoustic streaming.

[0163] Figure 20 shows a modification of the arrangement of Figure 3. The same or corresponding features are given the same reference numbers. Here, nebuliser device 110 comprises an acoustic wave transducer 112 having a transducer piezoelectric material substrate 114 and an electrode arrangement 116, typically in the form of an interdigitated electrode arrangement. The electrode arrangement 116 is located on the top surface of the transducer piezoelectric material substrate 114, which in this embodiment is a planar plate. Typically, the transducer piezoelectric material substrate 114 is a single crystal material. There is also a region of the top surface of the substrate 114 where the electrode arrangement is not located. This region includes a transducer acoustic wave transmission surface 118 on which a superstrate 160 is placed. Unlike Figure 3, the superstrate 160 overhangs from an end of the transducer piezoelectric material substrate 114. A dispenser 120 comprises a reservoir 122 and a dispensing conduit 124, which in this example is a needle. The dispenser may also include a pump (not shown) in order to cause flow of and meter the liquid from the dispenser 120. Again unlike Figure 3, the liquid is dispensed close to the forward edge of the superstrate, to be nebulised from the forward face 163 of the superstrate.

[0164] Figure 21 shows a different modification of the arrangement of Figure 3. The same or corresponding features are given the same reference numbers. Here, nebuliser device 110 comprises an acoustic wave transducer 112 having a transducer piezoelectric material substrate 114 and an electrode arrangement 116, typically in the form of an interdigitated electrode arrangement. The electrode arrangement 116 is located on the top surface of the transducer piezoelectric material substrate 114, which in this embodiment is a planar plate. Typically, the transducer piezoelectric material substrate 114 is a single crystal material. There is also a region of the top surface of the substrate 114 where the electrode arrangement is not located. This region includes a transducer acoustic wave transmission surface 118 on which a superstrate 160 is placed. Unlike Figure 3, the superstrate 160 has a microchannel or an array of microchannels formed in its upper surface. A dispenser 120 comprises a reservoir 122 and a dispensing conduit 124, which in this example is a needle. The dispenser may also include a pump (not shown) in order to cause flow of and meter the liquid from the dispenser 120. The liquid is dispensed into the microchannels and is nebulised from the microchannels.

[0165] Figure 22 shows a modification of the arrangement of Figure 20. The same or corresponding features are given the same reference numbers. Here, nebuliser device 110 comprises a first acoustic wave transducer 112a having a first transducer piezoelectric material substrate 114a and an electrode arrangement, typically in the form of an interdigitated electrode arrangement. The electrode arrangement is located on the top surface of the first transducer piezoelectric material substrate 114a, which in this embodiment is a planar plate. Typically, the first transducer piezoelectric material substrate 114a is a single crystal material. There is also a region of the top surface of the first substrate 114a where the electrode arrangement is not located. This region includes a first transducer acoustic wave transmission surface 118a.

[0166] Unlike Fig. 20, nebuliser device 110 further comprises a second acoustic wave transducer 112b having a second transducer piezoelectric material substrate 114b and an electrode arrangement, typically in the form of an interdigitated electrode arrangement, although other electrode arrangements are possible. A thickness mode transducer could also be used for one or both of transducers 112a, 112b. The electrode arrangement is located on the bottom surface of the second transducer piezoelectric material substrate 114b, which in this embodiment is a planar plate. Typically, the second transducer piezoelectric material substrate 114b is a single crystal material. There is also a region of the bottom surface of the second substrate 114b where the electrode arrangement is not located. This region includes a second transducer acoustic wave transmission surface 118b.

[0167] Superstrate 160 is placed in a sandwich configuration between the first 118a and second 118b acoustic wave transmission surfaces and protrudes from between them. As in Fig. 20, a dispenser 120 comprises a reservoir 122 and a dispensing conduit 124, which in this example is a needle. The dispenser may also include a pump (not shown) in order to cause flow of and meter the liquid from the dispenser 120. The liquid is dispensed close to the forward edge of the superstrate 160, to be nebulised from the forward face 163 of the superstrate. With this configuration, it is considered that it is possible to achieve a higher aerosol output.

[0168] Figure 23 shows a similar arrangement to Figure 22 except that there is a first dispenser 120a and a second dispenser 120b. First dispenser 120a comprises a first reservoir 122a and a first dispensing conduit 124a. The liquid is dispensed close to the forward edge of the top surface 164a of the superstrate 160, to be nebulised from close to the forward edge of the superstrate 160. Second dispenser 120b comprises a second reservoir 122b and a second dispensing conduit 124b. The liquid is dispensed close to the forward edge of the bottom surface 164b of the superstrate 160, to be nebulised from close to the forward edge of the superstrate 160. In this configuration, a higher aerosol output can be achieved when nebulising from both surfaces of the superstrate using two dispensing points.

[0169] The following sections showcase example applications of the coupling layer-free superstrate concept.

[0170] Nebulisation of fluids can be achieved using a configuration such as shown in Fig A coupling layer- free superstrate configuration is used where the superstrate is placed on a SAW transducer and a travelling SAW is coupled into the superstrate to nebulise fluid dispensed via a needle onto the surface of the superstrate. The aerosol size distribution generated under different SAW frequency was measured using a laser diffraction system. Figure 24 shows the distribution density of the aerosol for 13.56 MHz and 27.33 MHz. The obtained aerosol size distributions are optimal for respiratory therapy (throat, nasal, lung). is in closed microfluidic channels can be achieved for example using a closed microfluidic channel configuration as shown Figure 25(A). The superstrate is modified to contain a microfluidic channel. Figure 25(B) shows an image of the microfluidic channel filled with fluid and suspended microparticles. Acoustic energy transmission into the superstrate into microchannel gives rise to acoustophoresis effects under certain resonance conditions. In this case, a standing wave is created with a single pressure node in the centre. Microparticles experience an acoustic radiation force directed toward the pressure node causing an alignment / localisation / concentrating effect in the microchannel centre, as shown in Figure 25(C). Additional work has been carried out to consider in more detail the effect of the crystallographic orientation relationship between the transducer and the superstrate.

[0171] Transient thermal measurements were carried out in a similar manner to those reported above, but by including further variations of the angle of the superstrate relative to the transducer. For the transducer, black LiNbOs was used with a 5.5 mm IDT with a thermal pad. The transducer was subject to continuous driving at 13.53 MHz, 140 mVpp (~ 1 W). The superstrate was a 5x10 mm rectangle of LiNbOs (thickness 1 mm, single-side polished 128-YX). The polished side was oriented downwardly to couple to the transducer directly, without a coupling layer. A 10 pL droplet of 100% glycerol was placed on the upper surface of the superstrate.

[0172] Recording was carried out for 120 s at 30 fps, turning RF power on after 5 s. The relative orientation between the transducer and the superstrate was measured via photograph, comparing straight edges of the transducer and the superstrate. All measurements were performed three times, reseating superstrate and measuring angle each time.

[0173] Figure 26 shows a micrograph of the arrangement, with the superstrate oriented at an arbitrary angle with respect to the transducer. The electrodes are connected to the IDT which occupies around the top half of the transducer.

[0174] Figures 27-35 show the results of the transient thermal measurements at different angles, from about 0 degrees to about 90 degrees. Averaged transient measurements are shown for each angle. The plot titles are measured rotation angles (deg). The shaded regions indicate standard deviation. The red dashed lines indicate average saturation temperature.

[0175] Extracting the fluid equilibrium temperature as a function of superstrate orientation from the results shown in Figures 27-35 yields the plot shown in Figure 36. Heating of the fluid is maximised when the superstrate is aligned with the transducer. This is as expected. There is a greater standard deviation in the results close to 0 degrees. This indicates high sensitivity to the orientation around 0 degrees.

[0176] Figure 37 shows a further micrograph, of a LiNbOs superstrate on a transducer having a main IDT (top of transducer in image) as the transmitter and a liquid sensing IDT (bottom of transducer in image) as the receiver. A 2-port measurement was carried out, testing at 13.656 MHz. Transmission was quantified using: 21=(y receive) / (ffsencl)

[0177] In addition to the use of a LiNbOs superstrate, silicon and glass superstrates, all with roughly similar dimensions, were tested.

[0178] The results are shown in Figure 38, which plots S21 against the superstrate rotation angle, measured as shown in Fig. 37. LiNbOs shows distinct dip when crystal axes are aligned, indicating strong transmission to the superstrate. Checking for the reduction in S21 is potentially also useful for sensing whether superstrate is correctly placed, so that the superstrate orientation can be adjusted as necessary in order to provide the required repeatable coupling between the transducer and the superstrate.

[0179] Fig. 39 shows a micrograph of a superstrate that has had its outer profile shaped by laser milling and an array of channels also formed by laser milling. Fig. 40 shows a micrograph of part of Fig. 39 at a higher magnification. Fig. 41 shows the height profile of the channel indicated in Fig. 40.

[0180] Fig. 42 shows a micrograph of another superstrate that has had its outer profile shaped by laser milling and an array of channels also formed by laser milling.

[0181] Fig. 43 shows a micrograph of another superstrate that has had its outer profile shaped by laser milling and an array of channels also formed by laser milling.

[0182] Fig. 44 shows a micrograph of another superstrate that has had its outer profile shaped by laser milling.

[0183] Fig. 45 shows a micrograph of two other superstrates that have had their outer profile shaped by laser milling and an array of channels also formed by laser milling. Fig. 46 shows micrographs of part of Fig. 45 at a higher magnification and the height profile of the channel indicated in Fig. 45.

[0184] Fig. 47 shows the cumulative particle size distribution for an aerosol generated from a superstrate having the form shown in the inset of Fig. 47. The dispensing tip is placed into the microchannel to allow nebulisation from inside the microchannel.

[0185] Fig. 48 shows the particle size distribution for the cumulative particle size distribution of Fig. 47.

[0186] Fig. 49 shows aerosol size distribution obtained by laser diffraction system for nebulisation performed using the arrangement in Fig. 20.

[0187] The same or corresponding features are given the same reference numbers as in previous embodiments described above.

[0188] When an acoustic wave is excited on a lithium niobate substrate (transducer), it generates both mechanical surface deformation and a dynamic alternating electric field due to the material's strong piezoelectric properties. If a second lithium niobate substrate (superstrate) is brought into direct contact with the first, this electromechanical activity can couple into the second substrate through two main mechanisms. First, mechanical coupling occurs as the surface vibrations from the acoustic wave on the first substrate are physically transferred across the contact interface, inducing corresponding strain or even wave propagation in the second substrate. This requires intimate contact with minimal air gaps and is influenced by the acoustic impedance match and surface quality. Second, electrostatic coupling arises from the fringing electric fields generated by the acoustic wave; these fields can penetrate into the adjacent substrate and, because lithium niobate is also piezoelectric, induce mechanical deformation there as well. This field-driven interaction is akin to capacitive coupling and can excite waves or localized strain in the second substrate without direct mechanical transmission. Together, these mechanisms enable energy transfer from the excited transducer substrate to the adjacent superstrate, and are influenced by factors such as superstrate alignment, material orientation, frequency matching, and thickness.

[0189] A SAW device and superstrate configuration is shown in Fig. 50. Here, nebuliser device 110 comprises a surface acoustic wave transducer 112 having a transducer piezoelectric material substrate 114 and an electrode arrangement 116, in the form of an interdigitated electrode arrangement. The electrode arrangement 116 is located on the bottom surface of the transducer piezoelectric material substrate 114, which in this embodiment is a planar plate. There is also a region of the bottom surface of the substrate 114 where the electrode arrangement is not located. This region includes a transducer acoustic wave transmission surface 118 on which a superstrate 160 is placed. The superstrate 160 overhangs from an end of the transducer piezoelectric material substrate 114. A dispenser 120 comprises a reservoir 122 and a dispensing conduit 124, which in this example is a needle. The dispenser may also include a pump (not shown) in order to cause flow of and meter the liquid from the dispenser 120.

[0190] The orientation of the SAW device 112, particularly the interdigitated electrodes (IDTs) 116 is of importance. The superstrate 160, placed in contact with the transducer 112, receives the SAW, which, without wishing to be bound by theory, continues to propagate along the superstrate surface as a surface wave.

[0191] Laser Doppler Vibrometer (LDV) measurements of small surface areas of the arrangement in Fig. 50 are shown in Figure 51 . This shows the surface displacements and wave propagation patterns on both the SAW transducer and both sides of the superstrate. The preservation of the SAW wavelength across these regions indicates that the wave continues propagating as a SAW on the superstrate.

[0192] However, the uniformity of surface displacement differs between LDV 1 (on the SAW transducer) and LDV 2 and 3 (on different sides of the superstrate), likely due to scattering effects or misalignment between the superstrate and transducer. While the absolute displacement magnitudes vary across the measurements, they should not be interpreted as relative intensity differences between the top and bottom surfaces of the superstrate.

[0193] Without wishing to be bound by theory, the surface in direct contact with the transducer appears to experience larger displacements, potentially making it more suitable for applications such as nebulisation, where high surface energy or momentum transfer is advantageous.

[0194] Fig. 52 provides an overview of various transducer designs applicable to the coupling layer-free superstrate concept. On the far left, it illustrates a typical surface acoustic wave (SAW) device with an interdigitated electrode arrangement, the electrode arrangement formed on only one surface of the piezoelectric substrate. SAW electrode designs and configurations vary widely, typically limited to one side of the device. These include single-phase unidirectional arrangements, slanted IDTs, chirped IDTs (for frequency tuning), focusing IDTs, standing wave IDTs, and spiral electrode configurations to compensate for axis-dependent changes in wave speeds. The dimensions and shapes of these electrodes determine the resonance frequencies and harmonics of the SAW device. In contrast, other transducer types, as shown in Figure 52, feature electrodes on both sides of the piezoelectric material, enabling the creation of wave modes such as thickness-mode vibrations, Lamb waves, shear waves, or mixed-mode waves through the bulk of the material. These vibrations can couple to the superstrate if there is an exposed piezoelectric surface on at least one side of the transducer that interfaces with the exposed surface of the superstrate. Figure 52 shows a variety of transducer designs with varying levels of electrode coverage, where resonance frequencies and harmonics are primarily defined by the thickness of the piezoelectric substrate. For example, a 1 mm thick substrate may yield a resonance frequency of around 3.3 MHz, while a 0.5 mm thick substrate may produce a frequency of around 6.6 MHz. Additionally, different crystal cuts can produce predominantly thickness-mode vibrations or other modes such as Lamb-type, shear-type, or mixed-mode vibrations.

[0195] A non-SAW transducer configuration is shown in Figure 53. The superstrate 160 is in contact with an exposed piezoelectric surface on the transducer 112 to allow acoustic energy coupling.

[0196] Figure 54 shows a similar configuration to Fig. 53 but with superstrate 160 overhanging from the transducer surface. Such an arrangement allows for the localisation of the nebulisation region spaced from the transducer. It also allows for both sides of the superstrate 160 to be used.

[0197] In Fig. 53 and Fig. 54, the dispenser 120 is as described in previous embodiments.

[0198] Fig. 55 illustrates the measurement areas from a laser Doppler vibrometer applied to a non-SAW transducer and superstrate configuration similar to that shown in Fig. 54 and as shown at the top of Fig. 55, along with the resulting surface displacement and wave patterns. Without wishing to be bound by theory, it is believed that in this configuration, Lamb-type waves are excited on the transducer and subsequently coupled into the superstrate, where they propagate as Lamb-type waves. However, in other configurations, shear thickness, thickness-mode vibrations and mixed-mode vibrations are likely also contributing to the coupling into the superstrate.

[0199] In contrast to previously shown configurations, Figs. 56 and 57 show an arrangement where the superstrate 160 is not only in contact with the exposed piezoelectric surface area but also the electrode 116a area of the transducer 112. Electrode thicknesses of 1 pm are typically used and while likely influencing coupling efficiency due to an air gap, the electric field strength is sufficient to induce coupling and liquid manipulation including nebulisation. Note, the reference numbers used correspond to features of previous embodiments and so are not described in detail here. In general, when metal coatings are applied to the interface of the coupling region, whether on the superstrate, transducer, or both, it significantly influences the coupling of acoustic energy between the two materials.

[0200] When the transducer or superstrate or both are fully coated with metal (electrode), the electric field generated by the piezoelectric material in the transducer cannot penetrate into the superstrate as effectively. The metal layers act as electrical conductors that shield the underlying piezoelectric surfaces from interacting with each other. This shielding prevents the electric field from coupling into the superstrate, thereby hindering the transfer of energy.

[0201] When only part of the coupling region is covered by metal, leaving some of the piezoelectric surface exposed, as in Figs. 56 and 57, the electric field from the transducer can interact with the exposed piezoelectric region of the superstrate. This allows for efficient coupling of acoustic energy through both mechanical and electrostatic coupling mechanisms, as there is still direct contact between the transducer and superstrate's piezoelectric surfaces.

[0202] When the superstrate has a metal coating on the side that is not in direct contact with the transducer, the electric field generated by the transducer can still interact with the exposed piezoelectric surface on the side that is in contact with the transducer. The metal coating on the non-contact side does not shield the coupling process and vibration because it does not interfere with the electric field interaction between the transducer and the exposed piezoelectric region of the superstrate. The electrical shorting by the metal coating on one or more sides of the transducer or superstrate does, however, have an impact on the phase velocities of the piezoelectric waves within the materials, which can alter the coupling efficiency due to an impedance mismatch.

[0203] Partial metal coverage can be strategically used to create localized or precise coupling regions by exposing specific areas of the piezoelectric surface, allowing for controlled and focused energy transfer. By selectively coating certain regions of the coupling interface with metal while leaving other regions exposed, it’s possible to define the exact location where the acoustic energy should be coupled from the transducer to the superstrate. This approach can be particularly useful for applications where it is wanted to direct the acoustic waves or electric field in a specific area, enabling targeted effects like localized strain, wave propagation, or energy transfer. Patterning of the metal coating can also be used to influence the wavelengths of the waves excited in the superstrate and may allow for mode conversion between the transducer and superstrate.

[0204] For example, if a particular area of the superstrate needs to be excited with a specific frequency or mode of vibration, partial metal coating allows for the precise control of where and how much energy is transferred. This can also minimize interference in areas that do not require coupling, improving efficiency and selectivity in the system. By varying the pattern, size, and location of the metal coating, it is possible to fine-tune the coupling behaviour to suit specific requirements. In addition to localized coupling achieved through selective metal coverage, the transducer itself can be made significantly smaller than the superstrate, as shown in Fig. 58 where the superstrate 160 overhangs the transducer at both ends. Note, this arrangement is applicable to SAW transducers as well as non- SAW transducers. As in Figs. 56 and 57 the superstrate 160 is not only in contact with the exposed piezoelectric surface area but also the electrode 116a area of the transducer 112. This smaller transducer size also allows for the integration of multiple transducers with a single superstrate, as shown in Fig. 59. Transducers 112a, 112b, 112c are each coupled to superstrate 160. The superstrate 160 is not only in contact with the exposed piezoelectric surface area but also the electrode 116 area of each transducer 112a, 112b, 112c. Such an arrangement enables precise, localized coupling across different regions of the superstrate's surface. This approach facilitates individual actuation of liquid volumes on the superstrate, providing the flexibility to control multiple actuation points simultaneously or independently. Such a configuration can be particularly advantageous for applications requiring fine control over localized areas, such as microfluidic systems, precision patterning, or targeted surface manipulation. Note, the reference numbers used correspond to features of previous embodiments and so are not described in detail here.

[0205] Fig. 60 shows an example of an assembled transducer 112 and superstrate 160 configuration including nebulisation, shown by the nebulised plume 128.

[0206] Fig. 61 shows the aerosol size distribution when nebulising using a configuration as shown in Figure 60.

[0207] It has been demonstrated that structures on the scale of the acoustic wavelength can function as effective waveguides and frequency-selective filters. This is typically achieved by introducing periodic arrays of micro- or nanoscale features into the superstrate, commonly referred to as phononic structures. These engineered features can filter specific acoustic wave modes and frequencies, as well as guide acoustic waves to precise locations on the superstrate enabling highly localized fluid manipulation for advanced microfluidic applications.

[0208] When implemented in materials such as lithium niobate and materials deposited on lithium niobate (e.g. semi-conductors), which possesses strong piezoelectric and electro-optic properties, these structures can also interact with light. If designed with dimensions compatible with optical wavelengths, the same periodic patterns can function as photonic structures, allowing for light confinement, guiding, or filtering. This dual functionality enables the integration of acousto-optic or opto-mechanical capabilities on a single platform.

[0209] Figs. 62a-c and 63 illustrate an example of a structured superstrate 360 incorporating a well-defined array of pillars. This configuration demonstrates the feasibility of fabricating phononic-photonic structures directly into single-crystal piezoelectric lithium niobate superstrates. Fig. 62a shows the overall arrangement and dimensions of the array. Fig. 62b shows the dimensions of individual pillars in two dimensions. Fig. 62c shows the arrangement of the array in a third dimension. Fig. 63 shows the dimensions of the pillars in the third dimension. This superstrate concept, in combination with e.g. surface acoustic waves on e.g. lithium niobate, opens up new industrial opportunities in acousto-optic and quantum photonic technologies. By dynamically modulating the local electric field and strain environment at the nanoscale, the platform can enable precise spatial and temporal control of excitons in adjacent semiconducting or 2D material layers.

[0210] Excitons are bound pairs of electrons and holes formed when a semiconductor absorbs light, acting as mobile carriers of energy without net charge. They are central to many light-matter interaction processes and offer key advantages in low-power optoelectronics, quantum light sources, and photonic computing due to their ability to mediate efficient, tuneable optical transitions.

[0211] Exciton control has significant implications for next-generation optoelectronic devices, including tuneable light emitters, exciton-based modulators, and on-chip single-photon sources for quantum communication. Additionally, the ability to acoustically transport and manipulate excitons across large surface areas supports the development of integrated photonic circuits, quantum memory architectures, and programmable light-matter interfaces, making the technology highly relevant for both telecom and advanced computing industries.

[0212] The superstrate and transducer in any of the embodiments can be transparent, for example, by double sided polishing. Such a device enables the combination of acoustic manipulation with a wide range of optical detection methods (e.g. fluorescence, absorbance, Raman).

[0213] ***

[0214] The features disclosed in the foregoing description, or in the following claims, or in the accompanying drawings, expressed in their specific forms or in terms of a means for performing the disclosed function, or a method or process for obtaining the disclosed results, as appropriate, may, separately, or in any combination of such features, be utilised for realising the invention in diverse forms thereof.

[0215] While the invention has been described in conjunction with the exemplary embodiments described above, many equivalent modifications and variations will be apparent to those skilled in the art when given this disclosure. Accordingly, the exemplary embodiments of the invention set forth above are considered to be illustrative and not limiting. Various changes to the described embodiments may be made without departing from the spirit and scope of the invention.

[0216] For the avoidance of any doubt, any theoretical explanations provided herein are provided for the purposes of improving the understanding of a reader. The inventors do not wish to be bound by any of these theoretical explanations. Any section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described.

[0217] Throughout this specification, including the claims which follow, unless the context requires otherwise, the word “comprise” and “include”, and variations such as “comprises”, “comprising”, and “including” will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integers or steps.

[0218] It must be noted that, as used in the specification and the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise. Ranges may be expressed herein as from “about” one particular value, and / or to “about” another particular value. When such a range is expressed, another embodiment includes from the one particular value and / or to the other particular value. Similarly, when values are expressed as approximations, by the use of the antecedent “about,” it will be understood that the particular value forms another embodiment. The term “about” in relation to a numerical value is optional and means for example + / - 10%.

[0219] References

[0220] A number of publications are cited above in order to more fully describe and disclose the invention and the state of the art to which the invention pertains. Full citations for these references are provided below. The entirety of each of these references is incorporated herein.

[0221] 1 . LY Yeo, JR Friend. Surface Acoustic Wave Microfluidics. Annu Rev Fluid Meeh 46, 379-406 (2014).

[0222] 2. Ding X, Li P, Lin SC, Stratton ZS, Nama N, Guo F, Slotcavage D, Mao X, Shi J, Costanzo F, Huang TJ. Surface acoustic wave microfluidics. Lab Chip. 2013 Sep 21 ;13(18):3626-49. doi: 10.1039 / c3lc50361e. PMID: 23900527; PMCID: PMC3992948.

[0223] 3. S. Collignon, O. Manor, J. Friend, Adv. Funct. Mater. 2018, 28, 1704359. https: / / doi.Org / 10.1002 / adfm.201704359

[0224] 4. Rufo, J., Cai, F., Friend, J. et al. Acoustofluidics for biomedical applications. Nat Rev Methods Primers

[0225] 2, 30 (2022). https: / / doi.org / 10.1038 / s43586-022-00109-7

[0226] 5. Wixforth, Achim. (2003). Acoustically driven planar microfluidics. Superlattices and Microstructures. 33. 389-396. 10.1016 / j.spmi.2004.02.015.

[0227] 6. Destgeer, Ghulam & Cho, Hyunjun & Ha, Byung Hang & Jung, Jin & Park, Jinsoo. (2016). Acoustofluidic particle manipulation inside a sessile droplet: Four distinct regimes of particle concentration. Lab on a chip. 16. 10.1039 / c5lc01104c. 7. Wixforth , Achim & Strobl, Christoph & Gauer, Ch & Toegl, A & Scriba, Jurgen & Guttenberg, Zeno. (2004). Acoustic manipulation of small droplets. Analytical and bioanalytical chemistry. 379. 982-91 .

[0228] 10.1007 / S00216-004-2693-z.

[0229] 8. Rasouli, Mohammadreza & Martinez Villegas, Karina & Tabrizian, Maryam. (2023). Acoustofluidics - changing paradigm in tissue engineering, therapeutics development, and biosensing. Lab on a Chip. 23. 10.1039 / D2LC00439A.

[0230] 9. A Qi, LY Yeo, JR Friend. Interfacial Destabilization and Atomization Driven by Surface Acoustic Waves. Phys Fluids 20, 074103 (2008).

[0231] 10. LY Yeo, JR Friend, MP McIntosh, ENT Meeusen, DA Morton. Invited Paper: Ultrasonic Nebulization Platforms for Pulmonary Drug Delivery. Expert Opin Drug Deliv 7, 663-679 (2010).

[0232] 11. Roudini, Mehrzad & Rossello, Juan & Manor, Ofer & Ohl, Claus-Dieter & Winkler, Andreas. (2023). Acoustic resonance effects and cavitation in SAW aerosol generation. Ultrasonics Sonochemistry. 98.

[0233] 106530. 10.1016 / j.ultsonch.2023.106530.

[0234] 12. Witte, C & Reboud, Julien & Wilson, Rab & Cooper, Jonathan & Neale, Steven. (2014). Microfluidic resonant cavities enable acoustophoresis on a disposable superstrate. Lab on a chip. 14.

[0235] 10.1039 / c4lc00749b.

[0236] 13. Ryan P. Hodgson, Ming Tan, Leslie Yeo, James Friend; Transmitting high power rf acoustic radiation via fluid couplants into superstrates for microfluidics. Appl. Phys. Lett. 12 January 2009; 94 (2): 024102. https: / / doi.Org / 10.1063 / 1.3049128

[0237] 14. Kiing S. Wong, Lillian Lee, Yew M. Hung, Leslie Y. Yeo, and Ming K. Tan

[0238] Analytical Chemistry 2019 91 (19), 12358-12368 DOI: 10.1021 / acs.analchem.9b02850

[0239] 15. Kolesnik K, Rajagopal V, Collins DJ. Optimizing coupling layer and superstrate thickness in attachable acoustofluidic devices. Ultrasonics. 2024 Feb;137:107202. doi: 10.1016 / j. ultras.2023.107202. Epub 2023 Nov 13. PMID: 37979521.

[0240] 16. Reboud, Julien & Bourquin, Yannyk & Wilson, Rab & Pall, Gurman & Jiwaji, Meesbah & Pitt, Andrew & Graham, Anne & Waters, Andy & Cooper, Jonathan. (2012). Shaping acoustic fields as a toolset for microfluidic manipulations in diagnostic technologies. Proceedings of the National Academy of Sciences ofthe United States of America. 109. 15162-7. 10.1073 / pnas.1206055109.

[0241] 17. William Naundrup Bode, Henrik Bruus; Numerical study of the coupling layer between transducer and chip in acoustofluidic devices. J. Acoust. Soc. Am. 1 May 2021 ; 149 (5): 3096-3105. https: / / doi.org / 10.1121 / 10.0004871 18. Langelier, Sean & Yeo, Leslie & Friend, James. (2012). UV epoxy bonding for enhanced SAW transmission and microscale acoustofluidic integration. Lab on a chip. 12. 2970-6. 10.1039 / c2lc40085e.

Claims

Claims:1 . An acoustic manipulation device for acoustic treatment of a fluid volume, the acoustic manipulation device comprising: a transducer comprising a transducer piezoelectric material and transducer electrodes configured to apply an electric field to the transducer piezoelectric material, the transducer having a transducer acoustic wave transmission surface and the transducer being operable to generate and propagate acoustic waves to the transducer acoustic wave transmission surface; a superstrate having a superstrate acoustic wave transmission surface detachably coupled to the transducer acoustic wave transmission surface, the superstrate further having or being coupled to a fluid volume acoustic wave transmission surface, the fluid volume acoustic wave transmission surface being configured to receive a fluid volume for interaction with acoustic waves generated by the transducer and transmitted to the fluid volume via the superstrate, wherein the superstrate comprises a superstrate piezoelectric material.

2. An acoustic manipulation device according to claim 1 wherein the transducer comprises a plate of single crystal transducer piezoelectric material having a first transducer crystallographic direction3. An acoustic manipulation device according to claim 1 or claim 2 wherein the superstrate comprises a plate of single crystal transducer piezoelectric material having a first superstrate crystallographic direction.

4. An acoustic manipulation device according to claim 3 as dependent on claim 2 wherein, when the superstrate is coupled to the transducer, there is a predetermined orientation relationship between the first transducer crystallographic direction the first superstrate crystallographic direction.

5. An acoustic manipulation device according to claim 4 wherein the material of the transducer piezoelectric material and the material of the superstrate piezoelectric material have substantially the same crystal structure and wherein the first transducer crystallographic direction and the first superstrate crystallographic direction are the same crystallographic direction.

6. An acoustic manipulation device according to claim 4 or claim 5 wherein the first transducer crystallographic direction is parallel, plus or minus 10 degrees, to the first superstrate crystallographic direction.

7. An acoustic manipulation device according to any one of claims 1 to 6 wherein the material of the transducer piezoelectric material and the material of the superstrate piezoelectric material have substantially the same composition.

8. An acoustic manipulation device according to any one of claims 1 to 7 wherein the material of the transducer piezoelectric material and the material of the superstrate piezoelectric material are selected independently from lithium niobate and lithium tantalate.

9. An acoustic manipulation device according to any one of claims 1 to 8 wherein the superstrate acoustic wave transmission surface and the transducer acoustic wave transmission surface are shaped to provide uniform contact pressure across their overlapping area.

10. An acoustic manipulation device according to any one of claims 1 to 9 wherein one or both of the superstrate acoustic wave transmission surface and the transducer acoustic wave transmission surface have a surface roughness Ra of not more than 1000nm.

11. An acoustic manipulation device according to any one of claims 1 to 10 wherein the transducer piezoelectric material and the superstrate piezoelectric material each have an electro-mechanical coupling coefficient of at least 1%.

12. An acoustic manipulation device according to any one of claims 1 to 11 wherein the superstrate acoustic wave transmission surface is in solid-to-solid contact with the transducer acoustic wave transmission surface.

13. An acoustic manipulation device according to any one of claims 1 to 12 wherein the transducer acoustic wave transmission surface comprises exposed transducer piezoelectric material and the superstrate acoustic wave transmission surface comprises exposed superstrate piezoelectric material.

14. An acoustic manipulation device according to any one of claims 1 to 11 wherein one or both of the transducer acoustic wave transmission surface and the superstrate acoustic wave transmission surface comprises a coating layer formed of non-piezoelectric material.

15. An acoustic manipulation device according to claim 14 wherein the coating layer has a Young’s modulus of at least 5 GPa.

16. An acoustic manipulation device according to any one of claims 1 to 15 wherein the interface between the transducer and the superstrate is free of a coupling layer.

17. An acoustic manipulation device according to any of claims 1 to 16, wherein the superstrate comprises a layered structure, the layered structure comprising a main body and a layer of the superstrate piezoelectric material.

18. An acoustic manipulation device according to any one of claims 1 to 17, wherein the superstrate acoustic wave transmission surface is detachably coupled to at least one of the transducer electrodes.

19. An acoustic wave manipulation device according to claim 18, wherein two edges of the superstrate acoustic wave transmission surface are not in contact with the transducer.

20. An acoustic wave manipulation device according to claim 19, further comprising a second transducer comprising a second transducer acoustic wave transmission surface and second transducer electrodes, wherein the superstrate acoustic wave transmission surface is further detachably coupled to the second transducer acoustic wave transmission surface, the fluid volume acoustic wave transmission surface being configured to receive a second fluid volume for interaction with acoustic waves generated by the second transducer.

21. An acoustic manipulation device according to any one of claims 1 to 20, wherein the superstrate piezoelectric material comprises a plurality of phononic-photonic structures.

22. An acoustic manipulation system for acoustic treatment of a fluid volume, the system including an acoustofluidic device according to any one of claims 1 to 21 and a fluid delivery mechanism for delivering fluid to the fluid volume acoustic wave transmission surface.

23. A method for the treatment of a fluid volume, the method including: providing a transducer comprising a transducer piezoelectric material and transducer electrodes configured to apply an electric field to the transducer piezoelectric material, the transducer having a transducer acoustic wave transmission surface and the transducer being operable to generate and propagate acoustic waves to the transducer acoustic wave transmission surface; providing a superstrate having a superstrate acoustic wave transmission surface and detachably coupling the superstrate acoustic wave transmission surface to the transducer acoustic wave transmission surface, the superstrate further having or being coupled to a fluid volume acoustic wave transmission surface, dispensing a fluid volume at the fluid volume acoustic wave transmission surface; and treating the fluid volume by operating the transducer to generate acoustic waves and transmit the acoustic waves to the fluid volume via the superstrate, wherein the superstrate comprises a superstrate piezoelectric material.

24. A method according to claim 23 further including detaching the superstrate from the transducer and then coupling a further superstrate to the transducer for treatment of a further fluid volume.

25. A method according to claim 23 or claim 24, further including detaching the transducer from the superstrate and then coupling a further transducer to the superstrate for a different treatment of the fluid volume.

26. A method according to claim 23 or claim 24 wherein the fluid volume is treated to nebulise the fluid volume.

27. A method according to claim 23 or claim 24 wherein the fluid volume is treated to carry out particle acoustophoresis on particles suspended in the fluid volume.

28. A method according to claim 23 or claim 24, wherein the fluid volume is treated to produce any one or more of acoustic streaming, acoustic cavitation, and thermoacoustic effects.

29. A method according to claim 23 or claim 24 wherein the orientation of the superstrate relative to the transducer is checked and adjusted as necessary based on a measurement of acoustic coupling between the transducer and the superstrate.

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