Acoustic microfluidic device with increased utilization rate of acoustic wave energy

Abstract

An apparatus, comprising: an electroacoustic transducer on a substrate; a power source for supplying electromagnetic wave energy to the electroacoustic transducer; and a source of a substance capable of moving to the substrate, wherein the electroacoustic transducer and the substrate are configured to generate acoustic wave energy that is used to move the substance from the source to the substrate and manipulate the substance on the substrate.

Description

Technical Field

[0001] The present invention relates to an acoustic microfluidic device having an increased utilization rate of acoustic wave energy. Background Art

[0002] Acoustic microfluidic devices such as surface acoustic wave (SAW) nebulizing or atomizing devices have been proposed for pulmonary drug delivery and various other microfluidic applications. The SAW microfluidic device includes interdigital transducers (IDTs) on a piezoelectric substrate. RF power is applied to the IDTs to generate SAWs, and the SAWs pass through the liquid on the substrate to generate aerosol droplets. The substrate is carefully selected as rotated Y-cut lithium niobate to suppress the propagation of bulk waves within the substrate, such that only pure SAWs are used for atomization.

[0003] Current SAW microfluidic devices have a limited nebulizing or atomizing rate between 1 μl / min and 100 μl / min. Such a low atomizing rate is not sufficient for effective patient dosing in pulmonary drug delivery. Merely increasing the RF power level and / or the liquid supply rate to achieve an increased atomizing rate sufficient for effective patient dosing is not practical.

[0004] Increasing the RF power level results in an increased thermal load on the substrate and / or components of the device, and leads to the need for a large and bulky power supply. In addition, increasing the RF power level also increases the likelihood of collateral damage to the delivered drug due to the denaturation of complex molecules or cells. Finally, increasing the liquid supply rate causes the device to flood and completely stop atomizing.

[0005] In this context, there is a need for an acoustic microfluidic device having an increased utilization rate of input RF power and output acoustic wave energy to provide enhanced microfluidic manipulation performance. Summary of the Invention

[0006] According to the present invention, there is provided a device comprising:

[0007] an electroacoustic transducer on a substrate;

[0008] a power supply for supplying electromagnetic wave energy to the electroacoustic transducer; and

[0009] a source of a substance capable of moving to the substrate;

[0010] wherein the electroacoustic transducer and the substrate are configured to generate acoustic wave energy that is used to move the substance from the source to the substrate and manipulate the substance on the substrate.

[0011] The acoustic wave energy may include SAWs propagating along a first surface of the substrate, a second opposite surface of the substrate, or a combination thereof.

[0012] The substrate can have a thickness comparable to the wavelength of the acoustic wave energy.

[0013] The acoustic wave energy can include a combination of SAW and surface reflector waves (SRBW). As used herein, "SRBW" refers to a bulk acoustic wave (BAW) that propagates along a first surface and a second surface by internal reflection through a substrate between the first surface and the second surface. The combination of SAW and SRBW can be used to move a substance from a source to the substrate and manipulate the substance on the substrate.

[0014] The acoustic wave energy can include a combination of SAW and standing acoustic waves in an electroacoustic transducer, wherein the SAW is used to move a substance from a source along the substrate to the electroacoustic transducer as a thin liquid film, and wherein the standing acoustic waves in the electroacoustic transducer are used to atomize or nebulize the thin liquid film.

[0015] The source of the substance can be disposed on, in, or adjacent to a surface of the substrate, a side edge of the substrate, an end edge of the substrate, or a combination thereof.

[0016] The electroacoustic transducer can include one or more interdigital transducers disposed on a first surface of the substrate, a second surface of the substrate, or a combination thereof.

[0017] The substrate can include a single crystal piezoelectric substrate, such as rotationally Y-cut lithium niobate or lithium tantalate.

[0018] The power supply, the substrate, and the source can be integrated in a universal serial bus (USB) holder.

[0019] The power supply can include a battery.

[0020] The substance can be a movable substance including a liquid, a solid, a gas, or a combination or mixture thereof. The substance can include a functional agent or therapeutic agent selected from the group consisting of drugs, soluble substances, polymers, proteins, peptides, DNA, RNA, cells, stem cells, odors, fragrances, nicotine, cosmetics, pesticides, insecticides, and combinations thereof.

[0021] The substance can be atomized or nebulized at a rate equal to or greater than 1 ml / min.

[0022] The present invention also provides a method, comprising:

[0023] Moving a substance from its source to a substrate using hybrid acoustic wave energy; and

[0024] Manipulating the substance on at least one surface of the substrate using hybrid acoustic wave energy;

[0025] Wherein the hybrid acoustic wave energy includes surface acoustic waves propagating along at least one surface of the substrate and bulk acoustic waves internally reflected between at least one surface of the substrate and at least one other surface of the substrate.

[0026] The present invention also provides an inhaler or nebulizer for pulmonary drug delivery comprising the above device.

[0027] The present invention also provides an eye wear for ocular drug delivery comprising the above device.

[0028] The present invention also provides an electronic cigarette comprising the above device.

[0029] The present invention also provides an odor generator comprising the above device.

[0030] The present invention also provides a method comprising using the above device to perform microfluidic operations on a substance, wherein the microfluidic operations include atomization, nebulization, movement, delivery, mixing, ejection, flow, centrifugation, capture, separation, sorting, coating, encapsulation, manipulation, desalination, purification, stripping, delamination and combinations thereof.

[0031] The present invention also provides a method comprising using the above device to atomize or nebulize a soluble substance to produce particles, powders or crystals having a diameter of 1 nm to 1 mm.

[0032] The present invention also provides a method comprising using the above device to coat or encapsulate drug molecules for therapeutic purposes within particles or powders having a diameter of 1 nm to 1 mm.

[0033] The present invention also provides a method comprising using the above device to purify or desalinate a liquid by separating salts, crystals or impurities from the liquid.

[0034] The present invention also provides a method comprising using the above device to peel a material from a three-dimensional (3D) bulk form into a two-dimensional (2D) exfoliated form.

[0035] The material may include graphene, boron nitride (BN), transition metal dichalcogenides (TMDs), transition metal oxides (TMOs), black phosphorus, silicene, germanene and combinations thereof.

[0036] The 3D bulk form of the material may include the material in a liquid or an embedded material.

[0037] The 2D exfoliated form of the material may include sheets, quantum dots (QDs), flakes, layers, films or combinations or assemblies or structures thereof.

[0038] The 2D exfoliated form of the material may have a lateral dimension between 1 nm and 2000 nm. BRIEF DESCRIPTION OF THE DRAWINGS

[0039] Embodiments of the present invention will now be described, by way of example only, with reference to the accompanying drawings, in which:

[0040] Figure 1 is a schematic diagram of an acoustic microfluidic device according to an embodiment of the present invention;

[0041] Figure 2 is a schematic diagram of an alternative embodiment of the device;

[0042] Figure 3 is a perspective view of another alternative embodiment of the device;

[0043] Figures 4 to 6 is Figure 3 a photograph of the device;

[0044] Figures 7(a) to 7(c) is a laser Doppler vibrometry (LDV) image and a schematic diagram of a device configured to generate pure SAW;

[0045] Figures 8(a) and 8(b) are LDV images and schematic diagrams of devices configured to generate pure SRBW and pure SAW, respectively;

[0046] Figures 9(a) to 9(c) is an LDV image, a graph of droplet size and volume, and a schematic diagram of a device configured to generate pure SRBW;

[0047] Figures 10(a) to 10(c) is an LDV image, a graph of droplet size and volume, and a schematic diagram of the device when configured to generate pure SAW;

[0048] Figures 11(a) to 11(c) is an LDV image, a graph of droplet size and volume, and a schematic diagram of the device when configured to generate a combination of SAW and SRBW;

[0049] Figure 12 and Figure 13 are the LDV distributions of a combination of SAW and SRBW and pure SAW, respectively;

[0050] Figure 14 is a schematic diagram of an eye-wear for ocular drug delivery including the device;

[0051] Figure 15 is Figure 2 a photograph of the device;

[0052] Figure 16 is a schematic diagram of a device configured to exfoliate 3D bulk material into 2D exfoliated material;

[0053] Figure 17 is a transmission electron microscope (TEM) image of 2D QDs formed by the device; and

[0054] Figure 18It is an atomic force microscope (AFM) image of a thin film of 2D QDs. Detailed implementation

[0055] Figure 1 and Figure 2 Fig. shows an acoustic microfluidic device 10 according to an embodiment of the present invention. The device 10 generally may include an electroacoustic transducer 12 on a substrate 14 and a power source (not shown) for supplying electromagnetic wave energy such as RF power to the electroacoustic transducer 12. The device 10 may also include a source 16 of a substance capable of moving to the substrate 14. The substance may include a material or material in a form capable of being moved from the source 16 to the substrate 14 by acoustic energy. The substance may include a liquid, a solid, a gas, or a combination or mixture thereof. For example, the substance may include a material or material such as a liquid, a solution, a dispersion, etc.

[0056] The electroacoustic transducer 12 may include a large number of IDT electrodes disposed on a first surface 18 of the substrate 14, a second opposite surface 20 of the substrate 14, or a combination thereof. Other equivalent or alternative electroacoustic transducers may also be used. The substrate 14 may be a single crystal piezoelectric substrate, such as a rotated Y-cut lithium niobate (LN) or lithium tantalate. For example, the substrate 14 may include a 128° rotated Y-axis, X-axis propagating lithium niobate crystal cut (128YX LN). Other equivalent or alternative piezoelectric substrates may also be used.

[0057] Although not shown, one end of the substrate 14 may be mechanically fixed and supported between two or more contact probes providing RF power. In addition, one supported end of the substrate 14 may be mounted via one or more springs and / or fixing means on the first surface 18 opposite the IDT finger electrodes 12 to create a minimum contact area with the substrate 14 to minimize the damping of the vibration energy applied to the substrate 14 through the electroacoustic transducer 12. Thus, the substrate 14 may protrude from the mechanical fixing means at one elastically supported end of the substrate 14 in a manner similar to a tuning fork, such that the substrate 14 can achieve maximum acoustic vibration at the relatively free end of the substrate 14.

[0058] The source 16 of the substance may be disposed above, within, or in contact or non-contact relation adjacent to the first surface 18 and / or the second surface 20 of the substrate 14 via a side edge 22 of the substrate 14, an end edge 24 of the substrate 14, or a combination thereof. Referring to Figure 1 , in one embodiment, the source 16 may include a container 26 of a liquid substance and a wick 28 arranged to contact the side edge 22 and / or the end edge 24 of the substrate 14. Referring to Figure 2 , in another embodiment, the source 16 may include only the container 26 arranged to directly contact the end edge 24 of the substrate 14. Other equivalent or alternative substance source arrangements may also be used.

[0059] The electroacoustic transducer 12 and the substrate 14 can be configured to generate acoustic wave energy that is used not only to move (e.g., suck out, draw out, and / or dilute) a liquid substance from a source 16 onto the substrate 14 as a thin liquid film, but also to atomize or fog the thin liquid film. For example, in one embodiment of the device 10, the acoustic wave energy can be in the form of SAWs that propagate along the first surface 18 of the substrate 14, the second surface 20 of the substrate 14, or both the first surface 18 and the second surface 20 of the substrate 14. That is, the SAWs can propagate along the first surface 18, around the end edge 24, and along the second surface 20 of the substrate 14. Although not intended to be limited by any particular theory, it is believed that the SAWs can propagate in both forward and reverse directions with respect to the electroacoustic transducer 12 on each of the first surface 18 and the second surface 20 of the substrate 14. It is believed that the SAWs traveling in opposite directions on the first surface 18 and / or the second surface 20 can at least partially be responsible for sucking out, drawing out, and diluting the liquid substance from the container 26 and / or the wick 28.

[0060] The use of the acoustic wave energy traveling along the second surface 20 is contrary to conventional SAW microfluidic devices that use only the first surface 18. This manifestation and utilization of the available acoustic wave energy can be achieved by configuring the substrate 14 such that the substrate 14 has a thickness comparable (e.g., approximately equal) to the wavelength of the SAWs. In other words, the device 10 can be configured to satisfy the relationship λ SAW / h ∼ 1, where h represents the thickness of the substrate 14, and λ SAW represents the SAW wavelength corresponding to the resonant frequency of the device 10. The SAW wavelength can be determined at least in part based on the configuration of the electroacoustic transducer 12, such as the pitch of the IDT electrodes. A mass loading of a large number of IDT fingers (e.g., equal to or greater than about 40 to 60 fingers) and a low-frequency IDT design between about 10 MHz and 20 MHz can be selected to give an optimal combination of SAWs and SRBW. Other equivalent or alternative configurations of the electroacoustic transducer 12 and the substrate 14 can also be used.

[0061] In addition, in another embodiment of the device 10, by configuring the thickness of the substrate 14 to be comparable to the wavelength of the acoustic wave energy, the acoustic wave energy can be manifested as a surface-reflected bulk wave (SRBW) that propagates along the first surface 18 and the second surface 20 by internal reflection through the substrate 14 between the first surface 18 and the second surface 20. Again, while not intended to be limited by any particular theory, it is believed that the SRBW can also propagate in both forward and reverse directions with respect to the electroacoustic transducer 12 on each of the first surface 18 and the second surface 20 of the substrate 14. It is believed that the SRBW traveling in opposite directions on the first surface 18 and / or the second surface 20 can at least partially be responsible for sucking, pumping, and rarefying the liquid substance from the container 26 and / or the core 28. Then, a combination of SAW and SRBW can be used not only to suck the liquid substance from the liquid supply 16 onto the substrate 14 as a thin liquid film, but also to atomize the thin liquid film. For example, in Figure 1 the illustrated embodiment, a combination of SAW and SRBW traveling along both the first surface 18 and the second surface 20 of the substrate 14 can be used not only to suck the liquid substance from the source 16 onto the first surface 18 of the substrate 14 as a thin liquid film, but also to atomize or fog the thin liquid film on the first surface 18 of the substrate 14.

[0062] In yet another embodiment of the device 10, the electroacoustic transducer 12 and the substrate 14 can be configured to generate acoustic wave energy that can be manifested as a standing wave in or on the electroacoustic transducer 12. SAW can be used to suck the liquid substance from the source 16 along the substrate 14 and suck it onto the electroacoustic transducer 12 as a thin liquid film. Then, the standing wave can be used to directly atomize the thin liquid film on the electroacoustic transducer 12. For example, in Figure 2 the illustrated embodiment, SAW traveling along the first surface 18 of the substrate 14 can be used to suck the liquid substance from the source 16 along the first surface 18 and suck it onto the electroacoustic transducer 12 as a thin liquid film. Then, the standing wave in or on the electroacoustic transducer 12 can be used to directly atomize or fog the thin liquid film. Since the acoustic wave energy on the IDT 12 is the strongest, the efficiency here is the highest in terms of microfluidic manipulation. In other words, by sucking, flowing, and rarefying the liquid film from the container 26 to the IDT 12 and directly atomizing it on the IDT 12, a very high and effective atomization rate can be achieved, such as equal to or greater than 1 ml / min. Figure 15 A strong aerosol jet or liquid stream directly generated on the IDT 12 in this embodiment of the device 10 is shown.

[0063] Referring to Figure 3 and Figure 4, in one embodiment of the device 10, the power source, substrate 14, and source 16 may be integrated on the USB holder 30. For example, the resilient support and coupler for one support end of the substrate 14 described above may be integrated in the body of the USB holder 30. Additionally, the power source for the electroacoustic transducer 12 may be integrated in or provided via the USB holder 30. For example, the power source may include a battery integrated in the USB holder 30.

[0064] Furthermore, the source 16 of the liquid substance may be integrated on the USB holder 30. For example, the source 16 may also include a source body 31 disposed below the USB holder 30 to fluidly connect the container 26 to the wick 28. The container 26 may be disposed at the rear of the USB holder 30, and the wick 28 may be disposed on the source body 31 adjacent to the free end edge 24 of the substrate 14. The wick 28 may fluidly contact the lower side edge 22 of the substrate 14 between the first surface 18 and the second surface 20.

[0065] As described above, the electroacoustic transducer 12 and the substrate 14 may be configured together such that the device 10 generates a combination of SAW and SRBW, and the combination of SAW and SRBW may be used together to move or aspirate the liquid substance from the source 16 onto each of the first surface 18 and the second surface 20 of the substrate 14 as a thin liquid film, and atomize or fog the thin liquid film on each of the first surface 18 and the second surface 20 to generate two opposite outwardly directed jets, streams, or mists of liquid aerosol droplets. Figure 5 and Figure 6 A pair of aerosol jets generated by this embodiment of the device 10 is shown.

[0066] The embodiments of the device 10 described above can be used to atomize or nebulize a liquid substance at an atomization rate greater than 100 μl / min, such as equal to or greater than 1 ml / min. The liquid substance can include functional or therapeutic agents selected from the group consisting of drugs, soluble substances, polymers, proteins, peptides, DNA, RNA, cells, stem cells, odors, fragrances, nicotine, cosmetics, pesticides, insecticides, and combinations thereof. Other equivalent or alternative functional or therapeutic agents such as biological substances, pharmaceutical substances, aromatic substances, cosmetic substances, antibacterial substances, antifungal substances, mildew-proof substances, disinfectants, herbicides, fungicides, insecticides, fertilizers, etc. can be mixed, dissolved, dispersed, or suspended in the liquid. The device 10 can also be used to atomize or nebulize a soluble substance to produce particles, powders, or crystals having a diameter of 1 nm to 1 mm. In addition, the device 10 can be used to coat or encapsulate drug molecules for therapeutic purposes within particles or powders having a diameter of 1 nm to 1 mm. The device 10 can also be used for other equivalent or alternative bio-microfluidics, microfluidics, microparticles, nanoparticles, nanomedicine, microcrystallization, microencapsulation, and micronization applications. For example, the device 10 can be configured to perform acoustic microfluidic operations on a substance, the acoustic microfluidic operations including: atomization, nebulization, moving, transporting, mixing, jetting, flowing, centrifuging, capturing, separating, sorting, coating, encapsulating, manipulating, desalting, purifying, stripping, layering, and combinations thereof. Other alternative or equivalent microfluidic operations can also be performed using the device 10.

[0067] The device 10 can be implemented with battery power in a compact size at a low cost with a low form factor such that the device is suitable for incorporation into a variety of other devices, systems, and apparatuses. For example, the device 10 can be incorporated into an inhaler or nebulizer for pulmonary drug delivery or configured as an inhaler or nebulizer. The device 10 can also be incorporated into an electronic cigarette to atomize a liquid containing nicotine and / or flavor. The device 10 can also be configured as an odor generator and incorporated into a game controller. Alternatively, the device 10 can be incorporated into an eye-wear 36 for ocular drug delivery, such as goggles or glasses, as Figure 14 shown. The power source 38 for the device 10 can be provided in the arm of the eye-wear 36. The eye-wear 36 can be used for the delivery of aerosols, particles, and powders including drugs, as well as polymer particles encapsulating drugs, for treating ocular conditions. Other equivalent or alternative applications of the device 10 can also be used.

[0068] The device 10 described above can also be used to purify or desalinate a liquid by separating salts, crystals, particles, impurities, or combinations thereof from the liquid. For example, atomization of a salt solution by the device 10 can result in the generation of aerosol droplets comprising the same solution, and evaporation of the aerosol droplets results in the formation of precipitated salt crystals. Due to their mass, the salt crystal precipitates can be separated inertially from the water vapor, which upon condensation leads to the recovery of purified water. Then, expanding (or increasing the number of) the device 10 into a platform comprising many devices 10 in parallel can result in an energy-efficient method for large-scale desalination. Alternatively, a miniaturized platform of a single or several devices 10 can be used as a battery-operated portable water purification system, which is potentially useful in third-world settings.

[0069] In other embodiments, the device 10 can be used to exfoliate materials from a 3D bulk form into a 2D exfoliated form. The materials can include, for example, graphene, BN, TMD, TMO, black phosphorus, silicene, germanene, and combinations thereof. Other equivalent or alternative materials can also be used. The 3D bulk aggregated form of the materials can include materials in a liquid or intercalating materials. The 2D exfoliated form of the materials can include sheets, QDs, flakes, layers, films, or combinations or pluralities or structures thereof. The 2D exfoliated form of the materials can have a lateral dimension, for example, between 1 nm and 2000 nm.

[0070] In these embodiments, the HYDRA device 10 can be used to provide a unique high-throughput rapid exfoliation method to produce large sheets and QDs of, for example but not limited to, TMO, TMD, and many other 2D materials in water using high-frequency acoustic waves generated by the HYDRA device 10 or using intercalating materials in the presence of a pre-exfoliation step. As Figure 16 shown, atomization of the bulk solution using the HYDRA device 10 can result in the shearing of sandwich bonds within the 3D bulk material to produce single or multiple layers of flakes. In the illustrated embodiment, the 3D bulk material solution 33 can be fed via a conduit 26 along the midline of the substrate 14 of the HYDRA device 10 by means of a paper core 28. The high-frequency acoustic waves generated during atomization can result in the shearing of the 3D bulk material 33 in flight to form the 2D exfoliated material 32. Figure 17 is a TEM image showing HYDRA atomization droplets having several layers of MoS2 QDs. Figure 18It is an AFM image of a film covering 2μm x 2μm of MoS2 QDs. In this application, the HYDRA device 10 can provide the ability to produce large-area coverage by continuously atomizing 2D materials on a substrate that produces tunable film patterns and thicknesses suitable for, but not limited to, applications such as field effect transistors (FETs), memory devices, photodetectors, solar cells, electrocatalysts for hydrogen evolution reaction (HER), and lithium-ion batteries.

[0071] In the past few years, the research on 2D materials has become one of the most booming fields in nanoscience. Although this field was initially dominated by the research on graphene, it has since been expanded to include a wide range of 2D materials, including: BN; TMDs such as MoS2 and WSe2; TMOs such as MoO3 and RuO2; and many other materials including black phosphorus, silicene, and germanene. These materials are very diverse and have been used in a wide range of applications from energy to electronics to catalysis.

[0072] To prepare large quantities of 2D nanosheets from their 3D bulk materials, previously proposed nanosheet production methods include mechanical exfoliation or liquid-phase exfoliation (LPE) (or the "scotch tape method"). Since high-quality single monolayers are produced by mechanical exfoliation, this method is commonly used for essential sheet production and basic research. However, due to the low yield and drawbacks of this method in controlling sheet size and number of layers, it is not suitable for large-scale practical applications.

[0073] In the LPE method, layered crystals, usually in powder form, are exfoliated by sonication or shear mixing in a solution of a suitable solvent or surfactant. After centrifuging to remove any unexfoliated powder, this method gives a dispersion containing a large number of high-quality nanosheets. Chemical exfoliation can greatly increase the yield compared to mechanical exfoliation. However, sonication during this process will introduce defects in the 2D lattice structure and reduce the sheet size to a few thousand nanometers, thus limiting the application of 2D nanosheets in the fields of large-scale integrated circuits and electronic devices.

[0074] Recently, the controllable preparation of 2D TMDs with large-area uniformity has presented significant challenges. The chemical vapor deposition (CVD) method has attracted extensive attention due to its ability to synthesize 2D TMDs at the wafer scale, showing great potential for practical applications such as large-scale integrated electronic devices. This method can not only fabricate continuous monolayer films of a certain thickness but also, importantly, directly grow layered heterostructures that largely avoid interface contamination introduced during the layer-by-layer transfer process. However, this method has low production yields, is time-consuming, and requires specialized knowledge. Against the backdrop described above, the embodiments of the device 10 of the present invention provide a useful alternative to conventional CVD, LPE, and mechanical exfoliation methods.

[0075] The present invention will now be described in more detail by way of example only with respect to the following examples. These examples are intended to illustrate the invention and should not be construed as limiting the generality of the disclosure described throughout this specification.

[0076] Example 1: Pure SAW

[0077] Referring to Figures 7(a) to 7(c) , an acoustic wave microfluidic device 10 can be fabricated by patterning a 40-pair finger 10 nm Cr / 250 nm Al IDT 12 with a mm aperture on a 128YX LN substrate 14 (Roditi Ltd, London, UK) using standard lithography techniques. Note that the device 10 is inverted with respect to Figure 1 such that the lower side of the substrate 14 constitutes the surface along which the IDT 12 generates SAWs. The device 10 is generally similar to the device 10 described above and depicted in the previous images, except that the orientation of the IDT 12 is shown on the lower surface. The relevant design parameter can be the ratio between λ determined by the width and gap of the IDT fingers 12 SAW and the thickness h of the substrate 14. A variety of progressive cases can be demonstrated in these examples by keeping h constant throughout and changing the resonant frequency f of the device 10 to thereby change λ SAW . SAWs can be generated by applying a sinusoidal electrical input with a resonant frequency of 10 MHz to the IDT 12 having a signal generator (SML01, Rhode & Schwarz, North Ryde, New South Wales, Australia) and an amplifier (ZHL-5W-1 Mini-Circuits, Mini-Circuits, Brooklyn, New York 11235-0003, USA). Deionized (DI) water at room temperature can be used as the test fluid.

[0078] Thus, a conventional pure SAW device is when λ SAW<<1h case, i.e., when the frequency is relatively large, as shown in the schematic diagram of Fig. 7(c) and the lower row of Fig. 8(b). In this configuration, the SAW energy confined within the penetration depth adjacent to the lower surface along which the SAW is generated rapidly decays with the length scale exp(–βz) through the thickness of the substrate 14, where β is the attenuation coefficient of the SAW in the solid along the vertical z direction such that the SAW is completely attenuated before reaching the top side of the substrate 14. In other words, due to the leakage of the SAW energy through the substrate 14, there is no vibration present on this surface (i.e., the side on which the IDT 12 is patterned). Instead, although the SAW energy decays with exp(–αx) along the propagation direction x of the substrate surface, the SAW on the lower surface propagates to the edge and if not reflected by a set of IDT 12 continues to propagate around to the top side, where α is the longitudinal attenuation coefficient of the SAW in the unbounded fluid, i.e., in air or in a fluid if one is present on the device 10. This can be seen from the LDV scan images (LDV; UHF-120; Polytec PI, Waldbronn, Germany) of Fig. 7(a) and Fig. 7(b) which confirm the presence of SAW on both sides of the substrate 14. Another evidence of the SAW can be seen from the lower row of the LDV scan in Fig. 8(a) in the opposite direction, considering that due to Eckart flow, drops with a height much larger than λ SAW are translated in the direction of SAW propagation, and when the SAW is applied to the top and bottom surfaces, the millimeter-sized static drop 38 is transported under the SAW.

[0079] Example 2: Pure SRBW

[0080] Referring to the schematic diagram in the top row of Fig. 8(b), if the thickness of the substrate 14 becomes comparable to the SAW wavelength at medium frequencies (i.e., λ SAW / h ∼ 1), it can be seen that the energy associated with the SAW propagating along the lower side of the substrate is transmitted through the thickness of the substrate and thus is not completely attenuated at the top side of the substrate 14. When such a body wave exists through the thickness of the substrate 14, due to the phase mismatch with the SAW and multiple internal reflections within the substrate 14, such a body wave appears as a surface body wave traveling along the top side, and this body wave can be called SRBW. The unique characteristics of such waves may have been previously overlooked, or only referred to as general body acoustic waves or jointly combined with a wide range of other prosthetic body wave modes through the thickness of the substrate 14 only as general body acoustic waves - perhaps as a result of the long-standing view since the 1950s: such waves are undesirable and should be suppressed.

[0081] The existence of pure SRBW can be confirmed from the LDV scans and the reverse drop translation behavior shown in the upward trace of Fig. 8(b). When SRBW is suppressed by placing an absorbing gel 40 (Geltec Ltd, Yokohama, Japan) on the top side of the substrate 14, pure SAW exists. It can be seen that the pure SAW not only translates the sessile drop 38 along the propagation direction along the lower side of the substrate 14, but also pushes the drop around the edge to the top side. In contrast, when the SAW is absorbed by the gel 40 at the lower side edge to prevent it from looping back to the top side, the SRBW drives the drop to translate along the propagation direction of the SRBW, which is opposite to the direction in which the SAW would translate the drop to make it travel around the edge and onto the top side of the substrate 14.

[0082] Example 3: Hybrid SAW / SRBW

[0083] Fig. 11(c) shows a device 10 configured to utilize a combination of SAW and SRBW on two faces of the substrate 14 to obtain effective microfluidic manipulation, i.e., by requiring λ SAW ~1. Compared with Figures 9(a) to 9(c) the microfluidic manipulation or atomization driven by pure SRBW or pure SAW shown in Figs. 10(a) to 10(c) respectively, Figs. 11(a) and 11(b) show a significant enhancement in microfluidic manipulation or atomization performance (e.g., an increase in the order of magnitude of the atomization rate) when the two phenomena are combined, which can be referred to hereinafter as HYbriD Resonant Acoustics (HYDRA). On the other hand, as determined by laser diffraction (Spraytec, Malvern Instruments, Malvern, UK), the size distribution of the generated aerosol indicates that the mean aerodynamic diameter lies in the range of 1 μm to 3 μm for optimal dose delivery to the pulmonary alveolar region. Aerosols outside this range mainly deposit in the upper respiratory tract as they cannot follow the inhaled airflow trajectories in the highly branched network of the respiratory system, whereas aerosols below this range tend to be exhaled.

[0084] Figure 12 is an example LDV distribution of the mixed SAW / SRBW generated in this example, while Figure 13 is an example LDV distribution of the pure SAW generated in Example 1.

[0085] Embodiments of the present invention provide small, compact, low-cost, and battery-powered acoustic microfluidic devices with increased acoustic wave energy utilization for a wide range of microfluidic applications and operations, including those requiring an increased microfluidic atomization or nebulization rate of equal to or greater than 1 ml / min. In addition to atomization and nebulization of fluids and droplets, the microfluidic operations performed by the embodiment devices can include all other alternative or equivalent types of acoustic microfluidic operations on lithium niobate (and other piezoelectric substrates), including but not limited to fluid delivery, mixing, ejection, sorting, centrifugation, particle capture, particle sorting, coating, encapsulation, manipulation, and combinations thereof. Different embodiments of the present invention are configured differently to use different combinations of different modes of acoustic wave energy SAW, SRBW, and standing acoustic waves to optimize the net acoustic wave energy available for atomizing liquids. This results in an acoustic microfluidic device that can provide a very high and efficient microfluidic manipulation rate of fluids, droplets, liquids, or reactions compared to previously proposed devices.

[0086] For the purposes of this specification, the word "comprising" means "including but not limited to", and the word "comprises" has a corresponding meaning.

[0087] The above embodiments are described by way of example only and modifications are possible within the scope of the appended claims.

Claims

1. An apparatus for manipulating matter using acoustic wave energy, the apparatus comprising: an electroacoustic transducer on a substrate; a power source for supplying electromagnetic wave energy to the electroacoustic transducer; and a source of matter capable of moving to the substrate; wherein the electroacoustic transducer and the substrate are configured to generate acoustic wave energy that is used to move the matter from the source to the substrate and to manipulate the matter on the substrate; wherein the acoustic wave energy includes a surface wave component and a body wave component; and wherein the apparatus is configured such that the substrate has a thickness approximately equal to the wavelength of the surface wave component.

2. The device according to claim 1, wherein The surface wave component includes surface acoustic waves propagating along a first surface of the substrate, an opposite second surface of the substrate, or a combination thereof.

3. The device according to claim 1, wherein, The body wave component includes body acoustic waves propagating between the first surface and the second surface.

4. The device according to claim 3, wherein The propagation between the first surface and the second surface is effected by internal reflection through the substrate between the first surface and the second surface.

5. The device according to claim 1, wherein The acoustic wave energy further includes a standing wave component propagating in the electroacoustic transducer.

6. The device according to claim 1, wherein The source of the matter is disposed on, in, or adjacent to a surface of the substrate, a side edge of the substrate, an end edge of the substrate, or a combination thereof.

7. The device according to claim 1, wherein The power source, the substrate, and the source are integrated in a universal serial bus holder.

8. The device according to claim 1, wherein The apparatus is configured to atomize or nebulize the matter at a rate equal to or greater than 1 ml / min.

9. The device according to claim 1, wherein, The apparatus is configured to atomize or nebulize the matter to produce particles, powders, or crystals having a diameter of 1 nm to 1 mm.

10. The device according to claim 1, wherein The matter includes a single crystal piezoelectric substrate.

11. The device according to claim 1, wherein The matter includes a functional or therapeutic agent selected from the group consisting of drugs, soluble substances, polymers, proteins, peptides, DNA, RNA, cells, stem cells, odors, fragrances, nicotine, cosmetics, pesticides, insecticides, and combinations thereof.

12. The device according to claim 1, wherein The manipulation of the matter includes atomization, nebulization, movement, delivery, mixing, ejection, flow, centrifugation, capture, separation, sorting, coating, encapsulation, manipulation, desalination, purification, stripping, layering, or combinations thereof.

13. An inhaler or nebulizer for pulmonary drug delivery, comprising the apparatus according to claim 1.

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