Transducer atomiser device

Abstract

Disclosed is an atomiser device comprising a piezoelectric substrate having a first surface and an interdigital transducer (IDT) on the first surface. The IDT includes electrodes having an array of interleaved fingers at least partially surrounding a focal region and is configured to generate a surface acoustic wave (SAW) directed toward the focal region to atomise liquid in contact with the first surface.

Description

"Transducer atomiser device"

[0000] The present application claims priority to Australian Provisional Patent Application number 2025900102, filed 14 January 2025, the entire contents of which are incorporated herein by reference.Technical Field

[0001] The present disclosure relates generally to devices for atomising liquids and more specifically to devices using acoustic vibration for liquid atomisation.Background

[0002] Atomisation of liquids may be achieved by various ultrasonic modes, including surface acoustic wave (SAW) generation and thickness-mode vibration.

[0003] SAW atomisers operate using a piezoelectric substrate, patterned with an interdigital transducer to generate the SAW. A SAW is a sound wave that propagates along the surface of the piezoelectric substrate. The SAW interacts with liquid in contact with the substrate, producing capillary waves on the surface of the liquid and inducing acoustic radiation forces and acoustic streaming. This interaction ultimately causes dispersion of the liquid into a fine mist of droplets.

[0004] Thickness-mode atomisers utilise bulk acoustic vibrations in the thickness direction of a piezoelectric element. When driven at its resonant frequency, the element oscillates through its thickness, transmitting energy to the liquid and forming standing waves that eject droplets. Thickness-mode atomisers typically operate at lower frequencies than SAW atomisers and may produce larger droplets.

[0005] Atomisers are widely used in nebulisers for medical applications. For example, an atomiser may convert liquids into aerosols, enabling inhalation-based delivery of therapeutic agents. These devices may facilitate administration of a range ofmedicaments, by producing fine droplets that can be efficiently absorbed through the respiratory tract.

[0006] Any discussion of documents, acts, materials, devices, articles or the like which has been included in the present specification is not to be taken as an admission that any or all of these matters form part of the prior art base or were common general knowledge in the field relevant to the present disclosure as it existed before the priority date of each of the appended claims.Summary

[0007] The present disclosure relates to an atomiser device including an interdigital transducer.

[0008] According to one aspect of the present disclosure, there is provided an atomiser device, the device comprising:a piezoelectric substrate having a first surface, andan interdigital transducer (IDT) on the first surface, the IDT comprising electrodes having an array of interleaved fingers at least partially surrounding a focal region,wherein the IDT is configured to generate a surface acoustic wave (SAW) in the first surface, the SAW directed toward the focal region, to atomise a liquid in contact with the first surface.

[0009] In some examples, the atomiser device may include a thickness-mode transducer. The thickness mode transducer may include at least one electrode pair. The thickness-mode electrode pair may comprise a first electrode (a “top electrode”) on the first surface and a second electrode (a “bottom electrode”) on a second surface of the piezoelectric substrate, opposite the first surface. The thickness-mode electrode pair may be configured to drive an acoustic vibration substantially through the thickness of the substrate. In some examples, the device may be selectively operable in a SAW mode, a thickness-mode, or simultaneously in both modes.

[0010] In some examples, the atomiser device may form part of a nebuliser unit. For example, the atomiser device as described herein may form part of a medical nebuliser unit. The nebuliser unit may be configured to provide atomised liquid to a patient for inhalation. In some examples, the liquid may be water. In other examples, the liquid may comprise a medicament. In some examples, the medicament may comprise a vaccine, such as a DNA or mRNA vaccine. In some examples, the medicament may comprise one or more of antibodies (e.g. monoclonal antibodies), oligonucleotides, immunoglobulins, stem cells, exosomes and small molecule drugs.

[0011] One or more of the interleaved fingers may form a broken loop substantially surrounding the focal region. The interleaved fingers may be curved. In some examples, one or more of the interleaved fingers may have a substantially circular shape. For example, one or more of the interleaved fingers may have a substantially circular shape with a gap to form the broken loop. The interleaved fingers may be arranged substantially concentrically. The focal region may be positioned at a centre of the concentric interleaved fingers.

[0012] In some examples, the spacing between adjacent interleaved fingers may be substantially constant. In other examples, the spacing between adjacent interleaved fingers may vary.

[0013] In some examples, the spacing between adjacent interleaved fingers may be configured to provide a desired resonant frequency. In some examples, the spacing between adjacent interleaved fingers may be configured to provide a resonant frequency of greater than about 1 MHz. For example, the resonant frequency may be between about 1 MHz and about 1 GHz, between about 1 MHz and about 500 MHz, between about 1 MHz and about 100 MHz, between about 10 MHz and about100 MHz, or between about 10 MHz and about 50 MHz, such as about 10 MHz, about 20 MHz, about 30 MHz, about 40 MHz, about 50 MHz, about 60 MHz, about 70 MHz, about 80 MHz, about 90 MHz, about 100 MHz, about 200 MHz, about 300 MHz, about 400 MHz, about 500 MHz. In some examples, spacing between adjacent interleaved fingers may be configured to provide a resonant frequency of less than or equal toabout 1 MHz. For example, the resonant frequency may be between about 100 kHz and about 1 MHz, between about 200 kHz and about 1 MHz, between about 300 kHz and about 1 MHz, between about 500 kHz and about 1 MHz, or between about 700 kHz and about 1 MHz, such as about 100 kHz, about 200 kHz, about 300 kHz, about 400 kHz, about 500 kHz, about 600 kHz, about 700 kHz, about 800 kHz, about 900 kHz or about 1 MHz.

[0014] The IDT may be configured to generate a travelling surface acoustic wave and / or a standing acoustic wave in the first surface.

[0015] The atomiser device may comprise a fluid supply member for supplying a fluid to the first surface of the substrate. The fluid supply member may be configured to supply the fluid at a substantially constant rate.

[0016] The fluid supply member may comprise a liquid reservoir. The liquid reservoir may be configured to retain a predetermined volume of liquid to be atomised.

[0017] The fluid supply member may comprise a piston movable within the liquid reservoir to expel liquid from the liquid reservoir. The fluid supply member may comprise an actuating mechanism configured to move the piston. The piston may comprise a threaded region engageable with a correspondingly threaded drive member, such that rotation of the drive member may cause axial translation of the piston. The actuation mechanism may include an actuator. The actuator may be actuable to rotate the drive member. In some examples, the actuator may be manually actuable by the user. In some examples, the actuator may include a resilient spring.

[0018] In some examples, the actuating mechanism may include an electric stepper motor configured to move the piston.

[0019] The piezoelectric substrate may comprise a hole extending through a thickness of the piezoelectric substrate. The hole may be positioned at least partially within the focal region. In some examples, the hole 150 may have a substantially circular shape. Adiameter (or maximum width dimension) of the hole may be between about 0.1 mm and about 3 mm. For example, a diameter (or maximum width dimension) of the hole may be about 0.1 mm, about 0.2 mm about 0.3 mm, about 0.4 mm, about 0.5 mm, about 0.6 mm, about 0.7 mm, about 0.8 mm, about 0.9 mm, about 1.0 mm, about 1.5 mm, about 2.0 mm, or about 3.0 mm. The hole may be configured to provide a fluid conduit through the thickness of the substrate. The hole may allow the fluid to be atomised to be provided to the first surface of the piezoelectric substrate and / or to a side of the piezoelectric substrate opposite the first surface.

[0020] A region of the device (e.g. the substrate) may be coated with a non-conductive material. The non-conductive material may substantially cover the interleaved IDT fingers. A region of the substrate may be substantially free from the non-conductive material. For example, one or more portions of the IDT electrodes configured for electrical connectivity with an external circuit may be free from the non-conductive material. The non-conductive material coating may have a thickness of at least about 100 nm. The non-conductive material coating may have a thickness of less than about 2 pm.

[0021] The IDT electrodes may be formed from two or more metal layers, including at least an adhesive layer and a conductive layer.

[0022] The atomiser device may be configured to receive one or more drive signals. The one or more drive signals may be independent or coordinated drive signals.

[0023] The atomiser device may comprise a controller in communication with the 0IDT and / or the thickness-mode transducer. The controller may be configured to provide one or more drive signals to the IDT electrodes and / or the thickness-mode electrodes. In some examples, the device may comprise a controller in communication with the IDT electrodes and / or the thickness-mode electrodes and configured to provide one or more drive signals to either the IDT electrodes or the thickness-mode electrode pair, or both the IDT electrodes and the thickness-mode electrodes. In some examples, the controller is configured to provide a plurality of drive signals. In some examples,the plurality of drive signals may be independent. In some examples, the plurality of drive signals may be coordinated.

[0024] In some examples, the atomiser device may comprise a plurality of piezoelectric substrates, each substrate having a first surface and a corresponding plurality of interdigital transducer (IDT) on the respective first surfaces of the plurality of piezoelectric substrates. Each IDT may comprise electrodes having an array of interleaved fingers at least partially surrounding a respective focal region. Each IDT may be configured to generate a surface acoustic wave (SAW) in the respective first surface, the SAW directed toward the focal region, to atomise a liquid in contact with the respective first surface.

[0025] In some examples, the drive signal may be amplitude modulated. In some examples, the drive signal may be modulated at a frequency between about 0.5 kHz and about 40 kHz. In some examples, the drive signal may be amplitude modulation at a frequency configured to be effective for sterilising liquid in contact with the first surface. In some examples, the controller may apply amplitude modulation to one or more drive signals provided to either or both of the IDT and the thickness-mode electrode pair.

[0026] According to another aspect of the present disclosure, there is provided an atomiser device, the device comprising:a piezoelectric substrate having a first surface, andan interdigital transducer (IDT) on the first surface,wherein the IDT is configured to generate a surface acoustic wave (SAW) in the first surface to atomise a liquid in contact with the first surface,a controller in communication with the IDT and configured to provide a drive signal to the IDT.

[0027] The drive signal may be amplitude modulated. In some examples, the drive signal may be amplitude modulated at a frequency between about 0.5 kHz and about 100 kHz, such as between about 0.5 kHz and about 50 kHz, such as between about0.5 kHz and about 40 kHz. In some examples, the amplitude modulation is effective to promote sterilisation of a liquid in contact with the first surface.

[0028] According to another aspect of the present disclosure, there is provided a method of atomising a liquid, comprising providing the liquid in contact with a surface of an atomiser according to examples disclosed herein; and operating the atomiser to atomise the liquid. In some examples, the liquid may contain one or more medicaments.

[0029] According to another aspect of the present disclosure, there is provided a method of pulmonary delivery of a medicament to a user, comprising: atomising a liquid containing the medicament using an atomiser according to examples disclosed herein; and providing the atomised liquid containing the medicament to the user for inhalation. In some examples, the atomised liquid may be provided to the user via a nebuliser device (for example including a nebuliser mask).

[0030] Throughout this specification the word "comprise", or variations such as "comprises" or "comprising", will be understood to imply the inclusion of a stated element, integer or step, or group of elements, integers or steps, but not the exclusion of any other element, integer or step, or group of elements, integers or steps.Brief Description of Drawings

[0031] Embodiments will now be described by way of example only with reference to the accompanying drawings in which:

[0032] Figure 1 shows a top view of an atomiser device including an IDT according to one example of the present disclosure;

[0033] Figure 2 shows an enlarged view of the array of interleaved electrode fingers of the IDT of Figure 1;

[0034] Figure 3 shows a photograph of a portion of an IDT according to another example of the present disclosure, patterned on a piezoelectric substrate;

[0035] Figure 4 shows a photograph of a portion of an atomiser device according to another example of the present disclosure, including a hole extending through the piezoelectric substrate;

[0036] Figure 5 is an illustration of a surface acoustic wave (SAW) generated in the surface of a piezoelectric substrate by the IDT of Figure 1, showing displacement along a reference line based on measurement data obtained using a laser doppler vibrometer;

[0037] Figure 6 is an illustration of a surface acoustic wave (SAW) generated in the surface of a piezoelectric substrate by the IDT of Figure 1, showing displacement within a reference area based on measurement data obtained using a laser doppler vibrometer;

[0038] Figure 7 is an exploded view of a fluid supply member according to one example of the present disclosure;

[0039] Figure 8 is a partial cut-away top view of the fluid supply member according to Figure 7;

[0040] Figure 9 is a partial cut-away perspective view of a fluid supply member according to another example of the present disclosure;

[0041] FigurelO shows a top view of an atomiser device according to another example of the present disclosure, including an IDT and a thickness-mode transducer;

[0042] Figure 11 is a cross-sectional side view of the atomiser device of Figure 10, showing the first and second electrodes of the thickness-mode transducer relative to the IDT;

[0043] Figure 12 is a block diagram of an atomiser according to an embodiment of the present disclosure including a controller providing a drive signal to the IDT and / or thickness-mode transducer;

[0044] Figure 13 shows Dynamic Light Scattering (DLS) size distributions by intensity for LNP Original (Panel A), LNP 200 (Panel B), and LNP 400 (Panel C);

[0045] Figure 14 shows Luciferase reporter expression in HEK293T (Panel A) and A549 (Panel B) cells following incubation with untreated LNP-mRNA and SAW-treated LNP-mRNA for 16 hours;

[0046] Figure 15 is a graph showing a reduction in influenza A virus infectivity increasing acoustic energy; and

[0047] Figure 16 shows functional evaluation of mRNA-LNP delivery in lungrelevant models.Detailed Description

[0048] An atomiser device according to examples of the present disclosure is represented in the figures as item 10.

[0049] Figure 1 shows one example of an atomiser device 10 according to the present disclosure. The atomiser device 10 comprises a piezoelectric substrate 100 having a first surface 110. The piezoelectric substrate 100 comprises a second surface 115 on a side of the substrate opposite the first surface 110 (e.g. as shown in Figure 11). In the illustrated example, the substrate 100 is shown as rectangular. However, other shapes for the substrate (e.g. circular, ellipsoid, polygonal, irregular etc.) are also contemplated.

[0050] An interdigital transducer (IDT) 200 is arranged on the first surface 110. In the illustrated examples, the IDT 200 comprises electrodes 210 having an array of interleaved electrode fingers 220.

[0051] The IDT 200 is configured to generate a surface acoustic wave (SAW) in the first surface 110 of the piezoelectric substrate 100, to atomise a liquid in contact with the first surface 110. The SAW may comprise a travelling surface acoustic wave and / or a standing acoustic wave in the first surface 110.

[0052] In the context of the IDT, the first surface 110 of the piezoelectric substrate 100 may be considered an “active surface”. As used herein, the term “active surface” refers to the region of the substrate that includes, or is associated with, components configured to generate surface acoustic waves, such as the interdigital transducer (IDT) 200. The term is not intended to exclude other regions of the substrate from being acoustically active. In examples where additional transducers (e.g., thickness-mode transducers) are present, the entire substrate may participate in acoustic energy transmission.

[0053] Similarly in the context of the IDT, the second surface may be considered an “inactive surface”. As used herein, “inactive surface” refers to the opposite side of the substrate relative to the active surface, which may lack an IDT or similar surface-patterned components. The term does not imply that this side is acoustically inactive in all examples or exclude this side from transmitting acoustic energy in embodiments where the substrate operates in thickness mode or other bulk vibration modes. For example, in configurations employing a thickness-mode transducer, acoustic energy may propagate through or from both sides of the substrate.

[0054] The piezoelectric substrate 100 may be formed from a piezoelectric material. In some examples, the piezoelectric material may comprise at least one of lithium niobate, black lithium niobate, lead zirconate titanate, zinc oxide on sapphire, or other suitable piezoelectric material. In some examples the piezoelectric substrate is 128 degree Y-cut lithium niobate. The piezoelectric substrate may have a single side polish. The piezoelectric substrate may have a double side polish. In some examples, the material of the piezoelectric substrate 100 may be selected for biocompatibility.

[0055] The array of interleaved fingers 200 may at least partially surround a focal region 120 in the piezoelectric substrate 100. In some examples the array of interleaved fingers 200 may substantially, or may completely surround the focal region 120. The IDT 200 may be configured to direct the SAW toward the focal region. For example, the interleaved fingers 220 may be configured to generate a SAW focused toward the focal region 120, such that the SAW converges toward the focal region 120. It will be understood that the SAW travels in both directions from the IDT i.e. inwardly toward the focal region and also outwardly from the array of interleaved fingers 200. The array of interleaved fingers 200 may be configured such that waves travelling away from the focal region are dispersed, while waves travelling toward the focal region are concentrated.

[0056] As shown in Figure 1, in this example, the interleaved array as a whole completely surrounds the focal region 120. Each of the fingers 220 may form a loop substantially surrounding the focal region 120. In this example, each of the fingers 220 forms a loop around the focal region 120 broken by a single gap in the loop. The fingers 220 may be shaped substantially as an incomplete circle, or a “C” shape.

[0057] In each IDT electrode 210, the IDT electrode fingers 220 may be electrically connected to an IDT electrode contact pad 230. The IDT electrode contact pads 230 may be configured (e.g. by size or shape) to facilitate pin connection to an external circuit. The IDT electrode contact pads may have a dimension in at least one direction of at least 3 mm. In some examples, IDT electrode contact pads 230 may be square in shape having dimensions about 3 mm by about 3 mm. In other examples, the IDT electrode contact pads 230 may have other shapes (e.g. circle, rectangle, irregular etc) and / or other dimensions (e.g. 4 mm, 5 mm, 6 mm) as appropriate for facilitating electrical connection to an external circuit.

[0058] The IDT may comprise two IDT electrode contact pads 230, corresponding to a pair of IDT electrodes 210, as shown in Figure 1. In some examples, the IDT may comprise more than two IDT electrodes 210. In some examples, the IDT may comprise more than two IDT electrode pads 230.

[0059] The IDT electrode contact pads 230 may be positioned on opposing sides of the array of interleaved electrode fingers 220. For example, the IDT electrode contact pads 230 may be positioned on diametrically opposite sides of the array of interleaved electrode fingers 220, as shown in Figure 1. Opposing positioning may facilitate easier connection to external circuit pins. However, other positioning of the IDT electrode contact pads 230 relative to the array of interleaved electrode fingers 220 is also contemplated. For example, the IDT electrode contact pads 230 may be positioned on the same side of the array of interleaved IDT electrode fingers 220.

[0060] The array of interleaved IDT electrode fingers 220 is shown in greater detail in Figure 2. The IDT electrodes 210 may comprise respective stem portions 240 connecting between the contact pads 230 and the array of interleaved IDT electrode fingers 220. The stem portions 240 may be substantially straight. The IDT may be symmetrical about an axis defined by the stem portions 240. Each of the fingers 220 may extend from the stem portion 240. In some examples, the fingers 220 may extend laterally on either side of the stem portion 240 in a bifurcated pattern. For example, the fingers 220 may extend symmetrically on either side of the stem portion 240, as shown in Figure 2. The fingers 220 may extend (at least initially) orthogonally to the axis defined by the stem portion 240.

[0061] The fingers 220 may extend from the stem portion 240 to form the open loop, partially surrounding the focal region 120. In this example, the gap in the loop may be positioned directly opposite the stem portion 240, in line with the axis of symmetry. However, other positions for the gap are also contemplated. For example, the gap may be positioned off-centre, such as in closer proximity to the stem portion on one side, or directly adjacent to the stem portion on one side.

[0062] One or more of the interleaved fingers 220 may have a curved shape. Curved interleaved fingers 220 may mitigate the abrupt loss of waves in Y- direction experienced with linear IDT arrays. In some examples, one or more of the interleaved fingers 220 may have a linear, or non-curved shape.

[0063] One or more of the interleaved fingers 220 may have a substantially circular shape. In the example shown in Figure 2, each of the fingers 220 has a circular shape. In this example, each of the fingers 220 forms a broken circular loop around the focal region. The interleaved fingers 220 may be arranged substantially concentrically. The focal region 120 may be positioned at a centre of the concentric interleaved fingers.

[0064] In some examples, the spacing between adjacent fingers 220 may be substantially constant. In other examples, the spacing between adjacent fingers 220 may vary.

[0065] The fingers 220 may have terminal ends 221 adjacent to the gap in the loop, as shown for example in Figure 3. Each finger 220 may have a pair of terminal ends 221. The terminal ends 221 may be positioned opposite each other. The terminal ends 221 of the fingers 220 connected to a first electrode may be positioned either side of the stem 240 connected to the other electrode. In some examples, the terminal ends of the fingers 220 may be substantially blunt. For example, the fingers 220 may terminate in substantially straight, flat edges. The flat edges may be substantially perpendicular to the tangent of the curve (e.g. the circle shape) at that point. In other examples, the terminal ends of the fingers 220 may be tapered or rounded. A distance between the terminal ends 221 and the stem 240 may be substantially equal to the spacing between adjacent fingers 220.

[0066] In some examples, the atomiser device 10 may comprise a thickness mode transducer. One example of an atomiser device 10 including a thickness mode transducer 400 is shown in Figures 10 and 11.

[0067] The thickness-mode transducer 400 may comprise a thickness-mode electrode pair 410, 420. As used herein, the term “thickness-mode electrode pair” refers to any arrangement of two or more electrically conductive surfaces or structures configured to establish an electric field across at least a portion of the piezoelectric substrate 100 to allow inducing thickness-mode vibration. The term is not limited to discrete, separate electrodes, but encompasses configurations where one electrode is integrated with ahousing, substrate, or common ground, as well as patterned or segmented electrodes that collectively function to apply an electric potential difference across the piezoelectric substrate 100.

[0068] The thickness-mode electrode pair 410, 420 may comprise opposing first and second electrodes 410, 420 located on opposite major faces of the substrate. The thickness-mode electrode pair 410, 420 may be configured to drive acoustic vibration substantially through the thickness of the piezoelectric substrate 100.

[0069] In some examples, the thickness-mode electrode pair 410, 420 may comprise a first electrode (“top electrode”) 410 on the first surface 110 and a second electrode (“bottom electrode”) 420 on the second surface 115 of the substrate opposite the first surface. The first and second thickness-mode electrodes may define a parallel-plate arrangement configured to facilitate driving bulk acoustic vibration substantially through the thickness of the substrate. The first thickness-mode electrode may be located proximal to the focal region or spaced from the focal region. In the illustrated example, the first thickness-mode electrode is located spaced laterally from the IDT 200 (specifically adjacent to one of the IDT electrode contact pads 230). In this example the first thickness-mode electrode is substantially rectangular. However, other shapes or configurations for the first thickness-mode electrode are also contemplated. The second thickness-mode electrode may be coextensive with, or larger than the first thickness-mode electrode.

[0070] The thickness-mode electrodes may be formed from one or more metal layers (for example, including adhesive and / or conductive layers as described above with reference to the IDT). A non-conductive coating may be provided over selected regions of the thickness-mode electrode pair to inhibit short-circuiting in the presence of liquid, with contact pads left substantially uncoated for electrical connectivity. The device may include electrical isolation features (e.g. guard rings or isolation trenches) to mitigate coupling between the IDT 200 and the thickness-mode transducer.The frequency at which an interdigital transducer (IDT) device vibrates is typically described as its resonant frequency (or operating frequency or fundamental frequency). This frequency depends on the specific configuration of the IDT and the substrate and may be approximated by the relationship:vfsAW=where:• / SAW is the SAW resonant (or operating) frequency,• v is the speed of sound in the substrate material, and• is the wavelength of the SAW.

[0071] The wavelength of the SAW, , may be expressed as: = 4d where d is the electrode width (assuming that all electrode fingers have the same width and that the distance between adjacent electrodes fingers is equal to the electrode finger width).

[0072] In practice, due to variations in material properties and fabrication resolution, actual resonant frequency of the IDT may differ from theoretical (or design) resonant frequency. Further, the IDT may vibrate at other frequencies than the resonant frequency. For example, the IDT may vibrate at harmonics (integral multiples of the resonant frequency). In one example, the spacing between adjacent fingers 220 of the IDT 200 is approximately 50 micrometres to produce a resonant frequency of about 20 MHz. In one example, the spacing between adjacent fingers of the IDT is approximately 30 micrometres to produce a resonant frequency of about 30 MHz (e.g. about 33-34 MHz). In one example, the spacing between adjacent fingers of the IDT is approximately 25 micrometres to produce a resonant frequency of about 40 MHz. Other spacings between the fingers 220 are also contemplated to provide a desired resonant frequency.

[0073] In some examples, the IDT 200 may be configured to provide a resonant frequency fSAWof greater than about 1 MHz. For example, the resonant frequency fSAWmay be between about 1 MHz and about 1 GHz, between about 1 MHz and about 500 MHz, between about 1 MHz and about 100 MHz, between about 10 MHz andabout 100 MHz, or between about 10 MHz and about 50 MHz, such as about 10 MHz, about 20 MHz, about 30 MHz, about 40 MHz, about 50 MHz, about 60 MHz, about 70 MHz, about 80 MHz, about 90 MHz, about 100 MHz, about 200 MHz, about 300 MHz, about 400 MHz, about 500 MHz.

[0074] In some examples, the IDT 200 may be configured to provide a resonant frequency fSAWof less than or equal to about 1 MHz. For example, the resonant frequency fSAWmay be between about 100 kHz and about 1 MHz, between about 200 kHz and about 1 MHz, between about 300 kHz and about 1 MHz, between about 500 kHz and about 1 MHz, or between about 700 kHz and about 1 MHz, such as about 100 kHz, about 200 kHz, about 300 kHz, about 400 kHz, about 500 kHz, about 600 kHz, about 700 kHz, about 800 kHz, about 900 kHz or about 1 MHz.

[0075] For embodiments including a thickness-mode transducer, the approximate fundamental frequency may be expressed as:where:• fthickness is the fundamental thickness-mode resonant frequency, • v is the acoustic velocity in the substrate, and• t is the substrate thickness.

[0076] The thickness-mode transducer may also operate at one or more harmonics of this fundamental frequency to align with or complement the IDT SAW frequency. Thickness-mode transducers naturally support odd and even harmonics, e.g. :fn — n x / Q, where / Q — fthickness

[0077] The device may be operated at the fundamental frequency, fthickness,or atpreselected harmonics of the thickness-mode frequency. In some examples, higher-order harmonics may be selected to match or complement the SAW frequency generated by the IDT, or to bracket a selected SAW operating frequency to enhance acoustic coupling.

[0078] In some examples, the atomiser device 10 may be configured to promote atomisation while minimising disruption to delicate biomolecules. For example, the atomiser 10 may be configured for generating an aerosol from a liquid containing mRNA, DNA, and / or other delicate molecules for pulmonary delivery to a subject. The atomiser 10 may be configured to substantially preserve one or more characteristics of the molecules relative to pre-atomisation values. In some examples, the atomiser 10 may be configured to atomise liquid containing lipid nanoparticles encapsulating messenger RNA (LNP-mRNA). The atomiser may be configured to provide a post-atomisation nanoparticle size, encapsulation efficiency, and / or mRNA integrity within specified tolerance bands of pre-atomisation values.

[0079] In some examples, SAW tuning via circular IDT geometry selection may be used to target a preselected frequency configured to promote atomisation while minimising disruption to mRNA or other delicate biomolecules, with thethickness-mode operated at a resonant or harmonic frequency to reinforce atomisation and improve efficiency.

[0080] In some examples, a resonant frequency (e.g. one or both of fSAWor ftmcknes ) may be selected for suitability for atomising liquids containing delicate compounds, or active biological components. The frequency may be selected to facilitate atomisation of the liquid without inducing damage to such components within the liquid. In some such examples, the IDT 200 and / or the thickness-mode transducer 400 may be configured or operated to provide a resonant frequency of above 1MHz.

[0081] In some examples, the resonant frequency fSAWand / or thickness may be selected for suitability for sterilising the liquid during atomisation of the liquid.

[0082] As used herein, the term “sterilisation” refers to an at least partial inactivation and / or neutralising of infectious agents such as viruses, bacteria, fungi or other pathogens or undesirable biologically active contaminants within the liquid being atomised. Sterilisation may include reducing or inhibiting biological activity of such infectious agents during atomisation. The extent of sterilisation may be determined, forexample, by a percentage reduction in biological activity relative to a baseline measurement. Without being bound to theory, sterilisation may be achieved by inducing mechanisms such as hydrodynamic shear, cavitation or molecular disruption.

[0083] Sterilisation may be promoted by applying a resonant frequency and / or amplitude modulation at one or more selected frequencies or frequency ranges. For example, a resonant frequency may be selected in order to kill viruses, bacteria, fungi or other biological components during nebulisation. In some such examples, the IDT 200 and / or the thickness-mode transducer 400 may be configured or operated to provide a resonant frequency of below 1MHz. In some examples, the atomiser device 10 may comprise a fluid supply member 300. The fluid supply member may be configured for supplying a fluid to the piezoelectric substrate 100. For example, the fluid supply member may be configured to supply fluid to the first surface 110 of the piezoelectric substrate 100 and / or the to second surface 115 of the piezoelectric substrate 100.

[0084] One example of a fluid supply member 300 is shown in Figure 7. The fluid supply member 300 in this example includes a linear motion dosing mechanism. The fluid supply member 300 may be configured to supply the fluid at a substantially constant rate.

[0085] The fluid supply member 300 includes a liquid reservoir 303. The liquid reservoir 303 may be configured to retain a predetermined volume of the liquid to be atomised. In one example, the liquid reservoir 303 has a capacity of 3 mL. However, other capacity volumes are also contemplated. The internal volume of the liquid reservoir 303 may be configured by modulating one or more dimensions of the liquid reservoir 303, such as a height of the liquid reservoir.

[0086] In some examples, the liquid reservoir 303 may be configured to hold the liquid to be atomised and / or one or more other liquids. For example, the liquid reservoir 303 may be configured to hold a priming liquid and / or a cleaning liquid. Theliquid reservoir 303 may include one or more separate cartridges for holding the one or more liquids.

[0087] The fluid supply member 300 may include a piston 307. The piston may be configured be received within the reservoir 303 and to translate relative to the reservoir 303. For example, the piston may be configured to translate in an axial direction relative to the reservoir 303.

[0088] The piston 307 may be configured for fluid-tight sealing engagement with the reservoir 303. In some examples, the fluid supply member 300 may include a sealing element configured to seal between the piston 307 and the reservoir 303. The sealing element may include an o-ring. The piston 307 may include a recess 308 configured to receive the sealing member. In some examples the piston 307 may be configured to engage the reservoir 303 to provide a seal via an interference fit.

[0089] The fluid supply member 300 may further include an outlet member 309. In some examples, the outlet member 309 may be integral with the reservoir 303. In some examples the outlet member 309 may be a separate component configured to engage the reservoir. This may enable different outlet members 309 (e.g. providing different properties such as different flow rates) to be fitted to the reservoir 303.

[0090] The outlet member 309 may be configured to engage the reservoir 303 to partially close the reservoir 303. The outlet member 309 may be configured for sealing engagement with the reservoir 303. The outlet member 309 may be configured to engage the reservoir 303 by an interference fit with the reservoir 303. In some examples, the reservoir 303 includes a sealing member. In some examples, the reservoir 303 sealing member comprises an o-ring. The reservoir 303 may include a recess 304 configured to receive the o-ring. In some examples, the outlet member 309 may be configured for threaded engagement with the fluid reservoir 303. In such cases, the sealing member 304 may not be required. In some examples, the fluid reservoir 303 and the outlet member 309 may be integrally formed as a single part.

[0091] When the piston 307 is translated within the reservoir 303, liquid stored in the reservoir 303 is ejected out of the outlet member 309. For example, the fluid may be ejected through an outlet aperture extending through the outlet member 309. When the piston 307 is stationary, internal pressures in the reservoir 303 may prevent the liquid from discharging out of the outlet 309 due to the sealing engagement between the piston 307 and the reservoir 303.

[0092] In some examples, the outlet member 309 may include an outlet pipe directed axially away from the reservoir 303. The outlet pipe may be provided in fluid connection with the outlet aperture. The outlet pipe may include a substantially straight portion, such as the cylindrical portion shown in Figure 9. The outlet pipe may include a conical portion. In some examples, the outlet member 309 may include a siphon pipe. In some examples, the outlet member 309 may include flexible tubing.

[0093] In some examples, the fluid supply member 300 may include a nib 322 configured for inserted into the outlet of the outlet member 309. The nib 322 may be formed from a capillary material. The nib 322 may be elongate. The nib 322 may have a thickness of about 3 mm. The nib 322 may include a tapered distal end portion. The nib 322 may be configured to receive the liquid when the piston 307 mechanism is actuated to discharge the liquid. The nib 322 may be configured to provide a controlled delivery of small volumes of liquid. In some examples the liquid may be delivered to a piezoelectric substrate, such as piezoelectric substrate 100, via the nib 322, for example via the tapered distal end portion.

[0094] The nib 322 may be configured to contact the first surface 110 of the piezoelectric substrate 100. The nib 233 may contact the substrate at a location including electrodes of the IDT 200 and / or the thickness-mode transducer or at a region free from electrodes. The nib 322 may be configured to contact the first surface 110 of the piezoelectric substrate lOOat an angle of at least 45 degrees to a plane defined by the first surface of the piezoelectric substrate 100. In some examples, the distal end portion of the nib 322 is flexible. The distal end portion of the nib 322 may includehair-like projections. In other examples, the nib 322 may contact the second surface 115 of the piezoelectric substrate 100.

[0095] In some embodiments the reservoir 303 is configured to be re-fillable. The reservoir 303 may be configured to be re-fillable through the outlet member 309, for example through the outlet aperture. In some embodiments the reservoir is re-filled via another refilling apertures of the reservoir 303.

[0096] In some examples the piston 307 may be configured to translate substantially along an entire length of the reservoir 303. The piston 307 may be configured to discharge all of the liquid retained within the reservoir 303. In some examples the piston 307 may be configured such that a predefined remnant volume of liquid is retained in the reservoir 303.

[0097] The piston 309 may include a threaded portion 319. The threaded portion 319 may be configured to facilitate axial translation of the piston 307 by engagement with a corresponding threaded portion. The threaded portion 319 may be provided proximal of the sealing member (e.g. as located in recess 308).

[0098] The fluid supply member 300 may comprise an actuation mechanism. The actuation mechanism may include a drive member 305. The threaded portion 319 of the piston 307 may be configured for engagement with a corresponding threaded portion on the drive member 305. Rotation of the drive member 305 may be configured to cause axial translation of the piston in the distal direction relative to the reservoir 303.

[0099] In some examples, the threaded portion 319 is a shaft having an external thread. The drive member 305 may have a corresponding internal thread 320. The drive member 305 may comprise an internal thread 320 provided in a bore extending through the drive member 305. In some examples, the threaded portion 319 of the piston 307 is configured to be received within the bore of the drive member 305, such that the threaded portion 319 passes at least partially through bore of the drive member 305. The piston 307 may be configured (e.g. by a length of the threaded portion 319) suchthat a proximal end of the threaded portion 319 of the piston 307 is flush with a proximal surface 315 of the drive member 305 when the piston 307 is in a starting position, for example as shown in Figure 8. In some examples the threaded portion 319 may be configured to seat within the bore of the drive member 305, such that the bore of the drive member 305 and the proximal surface 315 of the piston 307 together define a cavity when the piston 307 is in the starting position.

[0100] In some examples, the drive member 305 and piston 307 may be configured such that rotation of the drive member 305 in a first direction effects translation of the piston 307 in the distal direction to discharge liquid from the reservoir 303. The first direction may be a clockwise direction or an anti-clockwise direction. Rotation of the drive member 305 in a second direction, opposite to the first direction, may effect translation of the piston 307 in the proximal direction to retract the piston relative to the reservoir 303. In some examples, retraction of the piston 307 may enable filling of the reservoir 303 by suction.

[0101] The actuation mechanism of the fluid supply member 300 may include an actuator 302. The actuator 302 may be configured to actuate the drive member 305 to cause rotation of the drive member 305. In some examples, the actuator 302 may be configured to actuate the drive member 305 in a clockwise direction and / or in an anticlockwise direction.

[0102] In some examples, the actuation mechanism may be manually driven by a user. In some examples, the actuation mechanism may be mechanically and / or electrically driven. For example, the fluid supply member 300 may be configured to activate the actuator 302 in response to an electrical signal from a controller. For example, the fluid supply member 300 may be configured to activate the actuation mechanism in response to input from a user. Input from the user may be provided via a user interface and / or from a connected computing device, (for example, a mobile phone with an associated app). In some examples, the controller and / or the computing device may be configured to control the dose size and / or dose frequency. The controller and / or the computing device may be configured to monitor and / or record parameters includingone or more of delivered dose volume, remaining reservoir volume, time of use or other parameters.

[0103] In some examples, the fluid supply member 300 may be configured to drive the actuation mechanism in response to a signal indicative of the user’s breathing. For example, the atomiser device 10 may include one or more sensors (e.g. air flow and / or pressure sensors) configured to sense data indicative of breathing of the user. In some examples, the atomiser device 10 may be included in a nebuliser device, e.g. including a mask. The nebuliser device may comprises one or more sensors configured to sense data indicative of breathing of the user. This may enable dose delivery at a suitable rate based on the breathing cadence of the user, without exposing the transducer to excessive liquid.

[0104] The engagement of the actuator 302 and the drive member 305 is shown in detail in Figure 8. The actuator 302 may include an arm 312 configured to be engaged by a user. The arm 312 may be flexible and configured to resiliently deform under force. In some examples, the force may be manually applied by a user. In some examples, the arm 312 may be mechanically and / or electrically driven, for example in connection with an electric motor. In other examples, the fluid delivery member 300 may not include the arm 213 but may include a motor (e.g. an electric motor such as a stepper motor) configured to drive the drive member 305. In other examples, the fluid delivery member 300 may include a motor, linear actuator or similar configured to directly drive the piston 307.

[0105] In the illustrated example, the arm 312 comprises a resilient spring. In the illustrated example, the drive member 305 includes teeth 313 on its outer surface. When the user applies force to the arm 312, a detent 321 of the actuator 302 engages with one of the teeth of the drive member 305 to rotate the drive member 305. Once the force on the arm 312 is released, the arm 312 returns to its resting position.

[0106] The deformation of the arm 312 may be limited by a stop member. In the illustrated example, the stop member is provided by casing walls 311 of the reservoir303. Rotation of the drive member 305 by the arm 312 is arrested when the arm 312 reaches its maximum travel within the casing walls 311.

[0107] The actuator 302 may also include a stopping detent 314, configured to engage with at least one tooth 313 of the drive member 305 to inhibit backwards motion of the drive member 305. This may inhibit spontaneous or pressure driven reversal of the motion of the drive member 305.

[0108] During actuation of the drive member 305 by the control arm 12 the actuator 302 is prone to twisting forces. The actuator 302 may include at least one stabilising member 316. The stabilising member 316 may be configured to engage with the casing walls 311 to secure the actuator 302 within the casing walls 311. Further, the casing walls may include an engagement feature 317 configured to engage the actuator 302 to secure the actuator within the casing walls. The stabilising member 316 and / or engagement feature 317 may be configured to inhibit twisting of the actuator 302 within the casing walls 311 and to inhibit release of the drive member 305 from its position. In some examples the fluid supply member 300 may include other mechanisms for securing actuator 302 within the casing 311, such as one or more fasteners.

[0109] The spring action of the actuator 302 allows the actuation mechanism to be rapidly re-actuated by repeat presses of the arm 312 by the user. When the piston 307 reaches its maximum displacement within the reservoir 303, further movement of the drive member 305 will be inhibited by the fully displaced piston 307 and further actuation of the arm 312 will no longer be possible. The mechanism may be configured to allow a finite, predefined, and / or adjustable number of actuations of the actuator 302, corresponding to a number of possible drive member 305 rotations and corresponding piston 307 translation motions.

[0110] A pitch of the threaded portions 319, 320 may be configured to provide a desired linear translation of the piston when the drive member 305 is rotated. The ratio of gearing on the drive member 305 and the pitch of the threaded portions 319, 320may be selected in combination to allow the axial translation of the piston 307 per actuation of the actuator 302 to be configured with great precision. By configuring the translation distance of the piston 307 in combination with the size of the head of the piston 307, a precise liquid volume displacement can be achieved. The actuation mechanism may facilitate repeated constant liquid volume delivery.

[0111] In some examples, the actuation mechanism of the fluid supply member 300 may be configured to provide a predefined liquid volume displacement per actuation of the arm 312. In some examples, the fluid supply member 300 may be configured to displace a volume of a single droplet per actuation of the arm 312, for example, the fluid supply member 300 may be configured to displace a volume of a between about 2 pL and about 5 pL. In other examples, the fluid supply member 300 may be configured to displace a greater volume per actuation of the arm 312. For example, the fluid supply member 300 may be configured to displace a volume of between about 2 pL and about 1500 pL per actuation of the arm, such as between about 2 pL and about 50 pL, such as about 2 pL, about 3 pL, about 4 pL, about 5 pL, about 10 pL, about 20 pL, about 30 pL, about 40 pL, about 50 pL, about 60 pL, about 70 pL, about 80 pL, about 90 pL, about 100 pL, about 150 pL, about 200 pL, about 300 pL, about 400 pL, about 500 pL, about 1000 pL, or about 1500 pL per actuation.

[0112] During translation of the piston 307 driven by the drive member 305 and actuator 302, the drive member 305 must withstand force equal to that of the friction forces overcome as the piston 307 to translates axially against the walls of the reservoir 303. In some examples a retaining member 306 may be configured to engage with the drive member 305 to enable the drive member 305 to resist these forces. In the illustrated example, the retaining member 306 is in the form of a locking clip. The retaining member may be configured to engage a groove 318 in the drive member 305 to retain the drive member 305 in position relative to the reservoir 303.

[0113] In some examples, the fluid supply member 300 may include a cap 301. The cap may be configured to retain the drive member 305 relative to the fluid reservoir 303.

[0114] In some examples, the fluid supply member 300 may include an adapter 310. The adapter 310 may be configured for threaded engagement with the outlet member 309. The adapter 310 may be configured to facilitate for installation of destination apparatus that is intended to receive the liquid from the outlet member 309. In some examples, the external adapter 310 does not need to be present for the fluid supply member 300 to operate.

[0115] In some examples, the fluid supply member 300 may include a wick configured to supply the fluid to the focal region 120.

[0116] In some examples, the fluid supply member 300 includes a fluid cartridge for retaining a predetermined volume of the fluid to be atomised.

[0117] In some examples, the piezoelectric substrate 100 may comprise a hole 150 extending through a thickness of the piezoelectric substrate 100. An example of a device 10 including a hole 150 is shown in Figure 4. The hole 150 may be positioned at least partially within the focal region 120. In some examples, the hole 150 may be positioned fully within the focal region 120. As shown in Figure 4, in some examples, the hole 150 may extend through a region of the substrate 100 comprising the interleaved array of fingers 220 of the IDT 200. In some examples, the hole 150 may have a substantially circular shape. A diameter (or maximum width dimension) of the hole may be between about 0.1 mm and about 3 mm. For example, a diameter (or maximum width dimension) of the hole may be about 0.1 mm, about 0.2 mm about 0.3 mm, about 0.4 mm, about 0.5 mm, about 0.6 mm, about 0.7 mm, about 0.8 mm, about 0.9 mm, about 1.0 mm, about 1.5 mm, about 2.0 mm, or about 3.0 mm. In some examples, the hole may be sized relative to a size of the IDT 200. The hole may extend from a side of the piezoelectric substrate 100 opposite the “active” first surface 110 (for example, an “inactive” second surface 115 of the substrate 100) to the active first surface 110. In some examples, the piezoelectric substrate 100 may comprise a plurality of holes extending through the substrate. The hole 150 may allow the fluid to be atomised to be provided to the first surface 110 of the piezoelectric substrate 100 and / or to a side of the piezoelectric substrate 100 opposite the first surface 110.

[0118] In some examples, the hole 150 may be substantially circular. However, other shapes for the hole are also contemplated. For example, the hole may have an elliptical, irregular curved or polygonal shape. A diameter, or maximum width, of the hole may be about 0.5 mm. In some examples, the diameter of the hole may be configured relative to a dimension of the wick of the fluid supply member 300.

[0119] The diameter of the hole may be configured to minimise a distance between an edge of the hole to a nearest electrode finger 220 of the IDT 200. In some examples, a maximum distance from the edge of the hole to a nearest electrode finger 220 is about 0.1 mm. In some examples, the hole 150 may overlap with one or more of the fingers 220 of the IDT 200. In some examples, the hole may extend as far as the second-last IDT finger 220 on the outer edge.

[0120] The hole may function as a fluid conduit between the second surface 115 and the first surface 110. In some examples, the fluid supply member 300 may be configured to supply fluid (for example via a wick) to the second surface 115 of the piezoelectric substrate 100. In some examples, the fluid supply member 300 may be configured to supply fluid to both the second surface 115 and the first surface 110 of the piezoelectric substrate 100 simultaneously. The fluids supplied to the second surface 115 and the first surface 110 may be the same fluid or may be different fluids. The hole may be configured to facilitate mixing of the fluids prior to or during atomization.

[0121] In some examples, one or more regions of the piezoelectric substrate 100 may comprise a surface treatment. For example, a region of the piezoelectric substrate 100 may be coated with a non-conductive material. The coated region may include a region on which the array of interleaved fingers 220 are positioned, such that the array of interleaved fingers 220 are coated with non-conductive material. The non-conductive coating may help to prevent short circuiting between fingers 220 of opposing polarity when liquid is provided to the first surface. The electrode contact pads 230 may be substantially uncoated to facilitate electrical connection with an external circuit. The non-conductive material may be selected to have a low modulus of elasticity, forexample greater than about 3 GPa, about 5 GPa, about 10 GPa or higher. The non-conductive material may include silicon dioxide or silicon nitride, for example, or other suitable non-conductive and non-elastic material.

[0122] A thickness of the non-conductive material coating may be selected in order to provide adequate electrical insulation to the array of interleaved fingers 220. Generally, a thicker coating will provide better insulative qualities. The thickness may be additionally or alternatively selected in order to maximise efficiency of the device 10 and minimise surface roughness, or improve adhesion between the coating and the IDT and / or substrate, or any intermediate layers. Generally, a thinner coating will provide improved efficiency, adhesion and surface qualities. The non-conductive material coating may have a thickness of at least about 100 nm. The non-conductive material coating may have a thickness of less than about 2 pm. For example, the non-conductive coating may have a thickness of about 100 nm, about 150 nm, about 200 nm, about 300 nm, about 500 nm, about 1 m, about 1.5 pm or about 2 pm.

[0123] The electrodes 210 of the IDT 200 may be formed from a metal. The IDT electrodes 200 may include at least a conductive metal. In some examples, the IDT electrodes 210 comprise two or more metal layers. The two or more metal layers may include at least an adhesive layer and a conductive layer. The adhesive layer may be a base layer. The conductive layer may be a top layer. In some examples, the adhesive layer comprises one or more of titanium or chromium. In some examples, the conductive layer comprises one or more of aluminium, copper, gold or silver. The top layer may be selected for biocompatibility and / or low reactivity. In some examples, the IDT electrodes 210 may comprise three or more layers. In some examples, the IDT electrodes 210 comprise a base layer, a top layer and one or more intermediate layers. In some examples, the conductive layer may be an intermediate layer. For example, the IDT may comprise an adhesive layer, a conductive layer and a top layer configured to provide enhanced biocompatibility and / or aesthetics. The top layer may comprise one or more of gold, silver and titanium. The adhesive layer may be configured to enhance adhesion between the piezoelectric substrate 100 and one or more other layers of theIDT electrodes 210. In one example, the IDT electrodes comprise a base layer of titanium, an intermediate layer of aluminium and a top layer of gold.

[0124] The atomiser device 10 may comprise, or may be configured to operate in connection with, a controller. The controller may be in communication with the IDT 200 and / or the thickness mode transducer 400. The controller may be configured to provide a drive signal (or input signal) to the IDT 200 and / or the thickness mode transducer 400. In some examples, the drive signal may be a radiofrequency (RF) signal. Figure 12 shows one example of a controller 500 integrated with the atomiser device 10 and connected to the IDT 200 and the thickness-mode transducer 400.However, the controller 500 may be separate from the atomiser device 10.

[0125] In some examples, a drive signal may include amplitude modulation (AM). For example, the drive signal may be configured to produce a modulated SAW. For example, the drive signal may include amplitude modulation configured to produce an amplitude modulated SAW. The amplitude modulation (AM) may be applied using a carrier signal, distinct from the operating (resonant) frequency / SAW,and having a lower frequency than / SAW- F°rexample, the lower-frequency carrier signal may be in the kHz range, while the SAW operating (resonant) frequency remains in the MHz range (for example, greater than about 1 MHz, such as between about 1 MHz and about 1 GHz) according to the ranges as set out above in relation to the resonant frequency / SAW) while the AM carrier may be in the kHz range, (e.g., lower kHz range, for example as set out below). The AM carrier signal may be superimposed on, or coordinated with, the SAW frequency. Amplitude modulation may be configured to achieve desired outcomes such as efficiency optimisation and / or promoting sterilisation.

[0126] In some examples, the controller may be configured to provide a drive signal including amplitude modulation at a frequency of between about 0.5 kHz and about 100 kHz. In some examples, the controller may be configured to provide a drive signal including amplitude modulation at a frequency of between about 0.5 kHz and about 40 kHz. In some examples, the controller may be configured to provide a drive signalincluding amplitude modulation at a frequency of between about 10 kHz and about 50 kHz. In some examples, the controller may be configured to provide a drive signal including amplitude modulation at a frequency of between about 100 kHz and about 1 MHz. In some examples the controller may be configured to provide a drive signal including amplitude modulation at a frequency of between about such as about 0.5 kHz, about 1 kHz, about 2 kHz, about 3 kHz, about 5 kHz, about 10 kHz, about 20 kHz, about 30 kHz, about 40 kHz, about 50 kHz, about 60 kHz, about 70 kHz, about 80 kHz, about 90 kHz, or about 100 kHz. The controller may be configured to modulate the drive signal based on one or more of a sine wave, square wave, triangle wave or sawtooth wave.

[0127] Amplitude modulation of the drive signal the IDT may provide benefits for optimising aerosol delivery, including one or more of enhanced signal control, improved power efficiency or reduced electrical noise, which may allow for miniaturisation and improved scalability of the device.

[0128] In some examples, the atomiser device 10 operates in a dual-mode configuration. Combined operation may concentrate energy at the liquid interface on the first surface 110, while introducing higher turbulence associated withthickness-mode vibration. In such examples, the interdigital transducer (IDT) 200 on the first surface 110 may generate a surface acoustic wave (SAW). The thickness-mode transducer 400 comprises electrodes 410, 420 on opposing major faces 110, 115 of the piezoelectric substrate 100 and may drives bulk acoustic energy through the thickness between surfaces 110 and 115. The circular geometry of the IDT electrodes 210 focuses acoustic energy toward the focal region 120 on the first surface 110. The thickness-mode excitation may be produced by driving the electrode pair 410, 420 at or near a thickness resonance set by the substrate thickness between surfaces 110 and 115. Thickness mode vibration may increase local turbulence in fluid proximal to the focal region 120 and may enhance energy transfer into the liquid during atomisation.

[0129] In some examples, the IDT 200 may incorporate single phase unidirectional transducer (SPUDT) features within the electrodes 210 and finger geometry 220.SPUDT implementation may include, for example, patterned electrode segments configured to introduce phase shifts between adjacent fingers 220, such that constructive interference occurs for waves propagating inward toward the focal region 120 and destructive interference occurs for waves propagating outward. In some examples, dummy fingers and / or reflector sections may be positioned adjacent to active fingers 220 to cancel outward-propagating waves. The geometry of the fingers 220 may include offset gaps or asymmetrical lengths to reinforce unidirectional propagation. Integration of SPUDT features with the circular IDT 200 may enhance energy focusing toward the focal region 120 and / or increase acoustic energy density at the liquid interface on the first surface 110. Waves propagating outward from the array of fingers 220 may be dispersed, and waves propagating inward may be concentrated.

[0130] Frequency control may be provided by the spacing of adjacent fingers 220 of the electrodes 210 and / or by the thickness-mode resonance of the substrate 100. The spacing of the fingers 220 sets the SAW wavelength and the corresponding SAW operating frequency on the first surface 110. In some examples, the SAW frequency is set to match the thickness-mode fundamental or a harmonic. Frequency alignment may enable constructive superposition between SAW fields and thickness-mode fields. Constructive superposition may improve coupling of acoustic energy at the focal region 120 and may increase atomisation efficiency. Coupling between the SAW field and the thickness-mode field may reduce the required drive power at the IDT 200 and / or at the electrodes 410, 420, and / or may decrease thermal load on components of the atomiser 10. Mitigation of stray acoustic modes may promote cleaner plume formation and / or improved stability of the atomised output on the first surface 110.

[0131] One or more parameters (e.g. geometric parameters) of the thickness-mode transducer 400 and the circular IDT 200 may be selected to adjust coupling and / or output characteristics. For example, the thickness of the electrodes 410, 420 may control how acoustic energy is distributed through the substrate 100 and may allow tuning of vibration intensity and turbulence for improved drug delivery efficiency. Adjusting the electrode geometry 410, 420 may support access to sub-harmonics or resonance behaviours and may assist in optimising droplet size distribution. Thespacing of the interleaved fingers 220 in the IDT 200 may provide precise SAW frequency tuning to synchronise with thickness-mode behaviour. This preserves tunability of the circular device geometry and enables constructive superposition between SAW and thickness-mode waves when aligned. Fine control of energy focusing and plume stability may be achieved by selecting finger spacing and aperture relative to the focal region 120. In some examples, manufacturing methods may support integration of circular finger patterns with thickness-mode structures and allow tighter tolerances for frequency alignment and mode synchronisation. In further examples, the substrate 100 may support additional acoustic energy forms, including surface acoustic waves, Bluestein-Gulayev waves, Lamb waves, Love waves, flexural waves, thickness-mode vibrations, mixed-mode waves, longitudinal waves and shear waves.

[0132] In some examples, amplitude modulation may promote sterilisation of the liquid to be nebulised, which may be desirable in certain applications. For example, low-frequency amplitude modulation (such as in the range of about 0.5 kHz to about 100 kHz, such as up to about 50 kHz, such as up to about 40 kHz, such as about 40 kHz) may affect the integrity of biological molecules and / or cells by mechanisms such as DNA uncoiling, protein denaturisation, sonoporation of cells or molecular scission via induced hydrodynamic shear and / or cavitation. The amplitude modulation may be configured to be effective to promote sterilisation of liquid in contact with the first and / or second surface 110, 115 of the piezoelectric substrate 100. For example, the frequency of the amplitude modulation may be selected to be effective to promote sterilisation of the liquid.

[0133] Sterilisation and / or minimisation of any biologically active components of the liquid may be desirable in applications where the liquid is to be inhaled, such as in a medical nebulizer. In some cases, however, it may be desirable to preserve a biological activity of one or more components of the liquid, such as in the case of use of the device for pulmonary delivery of mRNA vaccines, or other applications where the fluid contains sensitive biologically active components. In such examples, the frequency ofthe amplitude modulation may be selected to avoid or inhibit damage to molecules and / or cells within the liquid.

[0134] In some examples, an atomiser device 10 may comprise a plurality of piezoelectric substrates 100 arranged in a stacked configuration. Each piezoelectric substrate 100 may include an IDT 200 and / or a thickness-mode transducer 400 as described above. Stacking may provide redundancy as a fail-safe mechanism to ensure uninterrupted atomisation. For example, two, three or more IDTs may be provided as a typical configuration. Each substrate 100 may have substantially identical characteristics or may be different from each other. The transducers 200, 400 may be operable independently or in coordination. In some examples, the controller may selectively power one or more of the transducers as needed to maintain performance or compensate for failure of an individual transducer. In some examples, stacking may be employed to increase atomisation efficiency, such as for atomising highly viscous fluids or formulations requiring higher energy input. The stacked substrates 100 may be configured to operate simultaneously and / or sequentially, with coordinated and / or independent drive signals. This arrangement may allow improved throughput, enhanced reliability, and adaptability for different fluid properties.Example 1

[0135] Examples of an atomiser device 10 according to the present disclosure were fabricated for testing using photolithography and sputter deposition techniques. Figure 3 shows a photograph of a portion of the piezoelectric substrate with the electrodes formed on the first surface. In this figure, the underlying piezoelectric substrate appears dark, while the reflective surface of the electrodes appears white.

[0136] In the present example, the IDT 200 was formed on the substrate using photolithography and sputter deposition techniques. The IDT comprised a base layer of Ti at 20-40 nm thickness, an intermediate layer of aluminium at 200 nm thickness and a top layer of gold at 20 nm thickness. SiO2 deposition was performed over the array of interleaved fingers 220 to form a non-conducting layer.

[0137] The devices were tested for their ability to generate converging SAW in the substrate. A Laser Doppler Vibrometer (LDV) system was used to measure the surface velocity and displacement of the SAW. As shown in Figure 5, data from the LDV may be visualised using computer software to reveal the propagation of traveling waves along the surface of the piezoelectric substrate, providing real-time data on the wave's velocity, amplitude, and direction. This allows for precise characterisation of the surface acoustic wave, enabling optimisation of the IDT design for more efficient atomisation or particle manipulation. As shown in Figure 6, the LDV can also reveal the collective waves around the focal region 120 of the device 10, providing real-time data on the wave shape, velocity and / or amplitude. The LDV data indicated that the device 10 generates a SAW in the first surface 110 of the piezoelectric substrate 100, converging toward the focal region 120.Example 2

[0138] Atomisation of medicaments containing messenger RNA-lipid nanoparticles (mRNA-LNP) using conventional mesh nebulisers may compromise the integrity of the mRNA-LNP formulation. Experiments as set out below were performed to determine the effects of acoustic atomisation mRNA-LNP. The mRNA-LNP used for characterisation comprised an Onpattro-like LNP formulation (LNP 420). Onpattro is a siRNA LNP product indicated for hereditary transthyretin-mediated amyloidosis.

[0139] With reference to Figure 13, a single LNP formulation was characterised in an untreated state (LNP Original) and after surface acoustic wave exposure at two drive levels, 200 mVpp (LNP 200) and 400 mVpp (LNP 400), using Dynamic Light Scattering (DLS). Figure 13 shows Dynamic Light Scattering (DLS) size distributions by intensity for LNP Original (Panel A), LNP 200 (Panel B), and LNP 400 (Panel C). LNP Original shows a narrow nanoscale population with minimal aggregation. LNP 200 and LNP 400 exhibit additional micron-scale aggregate populations (~l-5 pm) indicative of energy-dependent destabilisation and aggregation following acoustic exposure.

[0140] LNP Original exhibited the smallest and most uniform particle population, with a Z-average diameter of approximately 84 nm and a poly dispersity index (PDI) of about 0.22. LNP 200 and LNP 400 displayed increased Z-average diameters (about 170 nm and 130 nm, respectively) and elevated PDIs (>0.35), indicating greater heterogeneity after acoustic energy input. Intensity- and volume-weighted distributions revealed the emergence of micron-scale aggregate populations (~l-5 pm) in LNP 200 and LNP 400, while LNP Original showed minimal aggregation. These data indicate that increasing acoustic drive promotes nanoparticle destabilisation and aggregation, demonstrating the sensitivity of mRNA-LNP physicochemical integrity to applied acoustic power.

[0141] In vitro cellular assays were performed to assess the ability of lipid nanoparticles (LNPs) to deliver functional mRNA following surface acoustic wave (SAW) nebulisation. Reporter expression was evaluated in HEK293T and A549 epithelial cells using luciferase activity as a readout. HEK293T cells are human embryonic kidney-derived cells engineered for high transfection efficiency, while A549 cells are human lung alveolar type II epithelial cells commonly used to model respiratory biology and drug delivery.

[0142] Figure 14 shoes Luciferase reporter expression in HEK293T (Panel A) and A549 (Panel B) cells following incubation with untreated LNP-mRNA and SAW-treated LNP-mRNA for 16 hours. Luminescence was measured as relative luciferase activity. Error bars represent standard error of the mean (SEM). Statistical analysis was performed using an unpaired Student’s t-test (n = 3). NS indicates P > 0.05; *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001.

[0143] Luciferase assays demonstrated robust reporter expression in both cell types after treatment with untreated LNP-mRNA and SAW-treated LNP-mRNA formulations (Figure 14, Panels A-B). No significant difference in luminescence was observed between SAW-treated and untreated groups under standard operating conditions, indicating that SAW nebulisation does not impair mRNA delivery ortranslation in epithelial cells. Control samples exhibited near-background luminescence, confirming assay specificity.

[0144] Flow cytometric analysis further validated these findings at the single-cell level. Representative histograms revealed a substantial increase in GFP-positive cell populations following treatment with both SAW-treated and untreated LNP-mRNA in HEK293T and A549 cells, compared with controls. The comparable GFP-positive fractions observed between SAW-treated and untreated conditions indicate preserved cellular uptake and intracellular mRNA expression following acoustic nebulisation.Example 3

[0145] Influenza A virus (strain X31) was nebulised using SAW-based acoustic processing at increasing drive levels (250-400 mVpp) and assessed for viral infectivity using a luciferase-based assay and NP FITC flow cytometry. As shown in Figure 15, Luciferase measurements showed a substantial reduction in viral activity following nebulisation (atomisation) compared with pre-nebulised controls. Nebulised samples exhibited a significant reduction in signal with increasing acoustic power. Blank controls remained at background levels. Statistical significance is indicated (*p < 0.05). Flow cytometry using an NP FITC-conjugated antibody targeting influenza A / X31 nucleoprotein further validated the reduction in viral infectivity as shown in Table 1 below. Reduction percentage in this study was variable between 11%-35% for the frequencies explored. These findings demonstrate a power-dependent loss of viral infectivity during acoustic nebulisation, supporting the potential for integrated sterilisation during atomisation.Table 1: Flow cytometry detection of influenza A nucleoprotein (NP) following acoustic nebulisation under different conditions.NP refers to influenza A nucleoprotein detected by flow cytometry. The numeric value represents mean fluorescence intensity (MFI) for NP staining, indicating relative viral infectivity.Example 4

[0146] With reference to Figure 16, Functional performance of lipid nanoparticle (LNP)-formulated mRNA was assessed in lung-relevant biological systems. Luciferase reporter mRNA was encapsulated in LNPs and delivered to lung-derived cell populations. Reporter activity was measured as luminescence intensity following treatment. Increased luciferase activity relative to untreated controls confirmed successful mRNA delivery and translation within lung cells. To evaluate uptake in non-immune lung cell populations, LNPs carrying GFP mRNA were administered, and geometric mean fluorescence intensity (gMFI) was quantified. GFP expression was detected across non-immune cell populations, indicating that transfection was not restricted to immune cells and supporting broad cellular uptake within lung tissue. Temporal stability of mRNA expression was assessed by measuring luciferase activity at 3, 8, 16, 24, and 32 hours post-treatment. Reporter expression increased progressively over the time course, demonstrating sustained mRNA translation ratherthan transient expression. Collectively, these results confirm that LNP -mediated mRNA delivery remains functional in lung-relevant systems.

[0147] It will be appreciated by persons skilled in the art that numerous variations and / or modifications may be made to the above-described embodiments, without departing from the broad general scope of the present disclosure. The present embodiments are, therefore, to be considered in all respects as illustrative and not restrictive.

Claims

CLAIMS:

1. An atomiser device, the device comprising:a piezoelectric substrate having a first surface, andan interdigital transducer (IDT) on the first surface, the IDT comprising electrodes having an array of interleaved fingers at least partially surrounding a focal region,wherein the IDT is configured to generate a surface acoustic wave (SAW) in the first surface, the SAW directed toward the focal region, to atomise a liquid in contact with the first surface.

2. The atomiser device of claim 1, wherein one or more of the interleaved fingers forms a broken loop substantially surrounding the focal region.

3. The atomiser device of claim 2, wherein one or more of the interleaved fingers has a substantially circular shape.

4. The atomiser device of claim 3, wherein the interleaved fingers are arranged substantially concentrically.

5. The atomiser device of claim 4, wherein the focal region is positioned at a centre of the concentric interleaved fingers.

6. The atomiser device of any one of the preceding claims, wherein a spacing between adjacent interleaved fingers is substantially constant.

7. The atomiser device of any one claim 6 wherein the spacing between adjacent interleaved fingers is configured to provide a resonant frequency of greater than about 1 MHz.

8. The atomiser device of claim 7, wherein the spacing between adjacent interleaved fingers is configured to provide a resonant frequency of between about 1 MHz and about 500 MHz.

9. The atomiser device of any one of the preceding claims, wherein the IDT is configured to generate a travelling surface acoustic wave and / or a standing acoustic wave in the first surface.

10. The atomiser device of any one of the preceding claims, comprising a fluid supply member for supplying a fluid to the first surface of the substrate.1 l.The atomiser device of claim 10, wherein the fluid supply member is configured to supply the fluid at a substantially constant rate.

12. The atomiser device of claim 10 or claim 11, wherein the fluid supply member comprises:a liquid reservoir;a piston movable within the liquid reservoir to expel liquid from the liquid reservoir; andan actuating mechanism configured to move the piston.

13. The atomiser device of claim 12, wherein the piston comprises a threaded region engagable with a correspondingly threaded drive member, wherein rotation of the drive member causes axial translation of the piston.

14. The atomiser device of any one of the preceding claims, wherein the piezoelectric substrate comprises a hole extending through a thickness of the piezoelectric substrate in the focal region.

15. The atomiser device of claim 14, wherein the hole is substantially circular.

16. The atomiser device of claim 15, wherein a diameter of the hole is about 0.5 mm.

17. The atomiser device of any one of claims 14 to 16, wherein the hole is configured to provide a fluid conduit through the thickness of the substrate such that the fluid to be atomised may be provided to the first surface of thepiezoelectric substrate and / or to a second surface of the piezoelectric substrate opposite the first surface.

18. The atomiser device of any one of the preceding claims, wherein a region of the substrate including the interleaved fingers is coated with a non-conductive material.

19. The atomiser device of claim 18, wherein the non-conductive material coating has a thickness of at least 100 nm.

20. The atomiser device of any one of the preceding claims, wherein the IDT electrodes are formed from two or more metal layers, including at least an adhesive layer and a conductive layer.

21. The atomiser device of any one of the preceding claims comprising a controller in communication with the IDT and configured to provide a drive signal to the IDT.

22. The atomiser device of claim 21, wherein the drive signal is amplitude modulated.

23. The atomiser device of claim 22, wherein the drive signal is amplitude modulated at a frequency between about 0.5 kHz and about 40 kHz.

24. An atomiser device, the device comprising:a piezoelectric substrate having a first surface, andan interdigital transducer (IDT) on the first surface,wherein the IDT is configured to generate a surface acoustic wave (SAW) in the first surface to atomise a liquid in contact with the first surface,a controller in communication with the IDT and configured to provide a drive signal to the IDT, wherein the drive signal is amplitude modulated at a frequency between about 0.5 kHz and about 40 kHz.

25. The atomiser device of claim 23 or claim 24, wherein the amplitude modulation is effective to promote sterilisation of a liquid in contact with the first surface.

26. The atomiser device of any one of the preceding claims, comprising:a plurality of piezoelectric substrates, each substrate having a first surface, and a corresponding plurality of interdigital transducer (IDT) on the first surfaces of the plurality of piezoelectric substrates, each IDT comprising electrodes having an array of interleaved fingers at least partially surrounding a focal region,wherein each IDT is configured to generate a surface acoustic wave (SAW) in the respective first surface, the SAW directed toward the focal region, to atomise a liquid in contact with the respective first surface.

27. The atomiser device of any one of the preceding claims, further comprising a thickness-mode transducer comprising a first electrode on the first surface of the piezoelectric substrate and a second electrode on a second surface of the piezoelectric substrate opposite the first surface.

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