FIELD OF INVENTION

[0001] The present invention relates to the field of droplet ejectors.

[0002] In one form, the invention relates to on-demand production of droplets at controlled frequency.

[0003] In one particular aspect the present invention is suitable for use in inkjet printing.

[0004] In another particular aspect the present invention is suitable for use in drug delivery, particularly delivery of drugs to the respiratory tract.

[0005] In another particular aspect the present invention is suitable for use in spectroscopic devices.

[0006] It will be convenient to hereinafter describe the invention in relation to inkjet printing however, it should be appreciated that the present invention is not limited to that use only and is suitable for a wide range of other applications.

BACKGROUND ART

[0007] It is to be appreciated that any discussion of documents, devices, acts or knowledge in this specification is included to explain the context of the present invention. Further, the discussion throughout this specification comes about due to the realisation of the inventor and/or the identification of certain related art problems by the inventor. Moreover, any discussion of material such as documents, devices, acts or knowledge in this specification is included to explain the context of the invention in terms of the inventor's knowledge and experience and, accordingly, any such discussion should not be taken as an admission that any of the material forms part of the prior art base or the common general knowledge in the relevant art in Australia, or elsewhere, on or before the priority date of the disclosure and claims herein. [0008] The ability to eject tiny volumes of fluid on-demand has numerous applications in inkjet printing, drug delivery systems (such as nebulizers used in asthma treatment) and spectroscopy including x-ray spectroscopy of biological samples (such as protein crystals) which have a need for rapid ejection of samples from a culture environment to air or vacuum. Furthermore, spectroscopic imaging requires these droplets to be precisely located in space.

[0009] Inkjet printing devices are generally termed 'acoustic liquid droplet ejectors'. The methods by which they operate can be classified based on their microfluidic actuation techniques which include bulk piezo activation ¹⁰ , Lamb Wave ¹¹ or surface acoustic wave (SAW) based activation ¹² , or are dependent on nozzle design. These actuation techniques of the prior art are discussed in the following paragraphs.

Nozzle Free Droplet Ejection

[0010] Nozzle free droplet ejection is described in a number of prior art documents including Roessler et al J. Synchrotron Radiation 20, 805-808 (2013); Bogan et al Nano Letters (2008). doi:10.1021/nl072728k; Aerni et al Analytical chemistry (2006). doi:10.1021/ac051534r; US 6,155,671 (Fukumoto et al); US 4,697,195 (Quate et al); US 5,063,396 (Shiokawa et al); US 8,991 ,722 (Friend et al)

[001 1] For inkjet printing applications the technology has focused on the use of an acoustic beam to eject droplets from a free surface without the use of nozzles ¹¹ . This has been disclosed in the literature in the context of a variety of methods for protein crystal imaging. In particular, conventional inkjet technologies have been used in combination with carrier substrates to perform a two-step process of sample preparation, which is followed by imaging ^3,5 .

[0012] As previously identified, the two major drawbacks of this approach are lower throughput and a minimum sample size being dictated by the carrier membrane thickness ⁴ . The atomisation and ejection of droplets from a liquid surface using Rayleigh mode waves has been has also been demonstrated ¹² ' ¹⁴ , however this relies on the voltage applied to the transducers alone to control the droplet formation. [0013] To address this issue others have sought to stabilize the interface through the use of wide nozzles ^{9, 13} . The nozzles can be large compared to the size of the acoustic beam ¹³ thus working similarly to a free surface ejection method. Alternatively a wide beam which excites higher vibration the interface ⁹ can be utilized to produce continuous steams of droplets.

Aerodynamic Nozzle

[0014] Aerodynamic nozzles of the prior art are described, for example in Bogan et al Nano Letters (2008). doi:10.1021/nl072728k; DePonte et al Gas dynamic virtual nozzle for generation of microscopic droplet streams. (2008); Weierstall et al (2008). http://link.springer.com/article/10.1007/s00348-007-0426-8; Chapman et al Nature (201 1 ). doi:10.1038/nature09750

[0015] Currently the favoured method of droplet production for use in x-ray spectroscopy is continuous production through aerodynamic capillary nozzles. The droplets are typically produced through electrospray then focused ⁴ or produced solely ⁶ using an aerodynamic nozzle. The continuous jet of fluid so formed, breaks up into droplets based on a Plateau-Rayleigh instability, which can be unpredictable and lead to a wide polydispersity. To address this, bulk acoustic methods have been explored to regulate droplet production ^7,8 .

Focused Acoustic Beam

[0016] Focused acoustic beam technology has been described in the prior art in for example, Collins et al Lab Chip 13,3225-3231 (2013); Dentry et al Lab on a Chip (2014). doi:10.1039/c3lc50933h; US 6,296,346 (Seo); and US 8,991 ,722 (Friend et al)

[0017] The use of a focused SAW device to atomise larger droplets of liquid has been demonstrated ^{14, 1} in the horizontal plane. The use of the vertical component of the radiating acoustic force has also been explored for microfluidic pumping applications ² , however, it has not previously been harnessed for droplet production. SUMMARY OF INVENTION

[0018] An object of the present invention is to provide improved on-demand production of droplets.

[0019] Another object of the present invention is to provide improved control of size and number during droplets production.

[0020] A further object of the present invention is to alleviate at least one disadvantage associated with the related art.

[0021] It is an object of the embodiments described herein to overcome or alleviate at least one of the above noted drawbacks of related art systems or to at least provide a useful alternative to related art systems.

[0022] In a first aspect of embodiments described herein there is provided a droplet ejector comprising (i) a thin-film membrane having a discontinuity, such as a hole or aperture, in association with (ii) a controllable signal source for providing a signal for transmission through a signal channel to the discontinuity.

[0023] Typically the discontinuity is located between an upper surface and a lower surface of the thin-film membrane.

[0024] The signal channel is typically filled with liquid and the ejector device of the present invention is capable of rapid, on-demand ejection of a controlled number of micrometer diameter droplets of the liquid. The droplet ejection frequency can easily be tuned by modifying one or more of the membrane geometry, the power applied to the signal source or the pulse time. For example, localised pressure can controllably deform the membrane interface causing a number of droplets to be ejected on-demand.

[0025] An ejector according to the present invention can produce 10,000 droplets/sec at a 1V pulse. Pulse length can be controlled to microsecond accuracy through a switch effectively tuning the droplet generation frequency. [0026] Typically the controllable signal source is a piezoelectric substrate associated with electrodes, such as interdigitated electrodes patterned on the piezoelectric substrate.

[0027] In another aspect of embodiments described herein there is provided a method of ejecting droplets of a liquid, the method comprising the steps of:

(i) using a controllable signal source to provide a signal, and

(ii) transmitting the signal through said liquid present in a signal channel to a discontinuity located in a thin-film membrane.

[0028] In a preferred embodiment, a focused travelling SAW is transmitted from electrodes associated with the controllable signal source. On passing through the liquid filled channel an acoustic beam is created. Typically, when the acoustic beam reaches a liquid-gas interface at the discontinuity in the form of a through hole it imparts a pressure force that controllably deforms the interface to produce a desired number of droplets on- demand.

[0029] In a preferred embodiment the thin-film membrane is a polymer such as polydimethylsiloxane (PDMS). The use of a thin membrane is important as it allows for a second channel to be formed above the first (such as in a SiN layer), so that the ejection device and method of the present invention can be used, for example, in droplet production in closed microfluidic systems.

[0030] In another preferred embodiment, the present invention comprises the use of a number of acoustic beams in combination to enable steering of ejected droplets in addition to accurate droplet size control. Typically the droplets are of about 65 to 80 mm diameter. Typically the droplets are of picolitre volume.

[0031] Other aspects and preferred forms are disclosed in the specification and/or defined in the appended claims, forming a part of the description of the invention. [0032] In essence, embodiments of the present invention stem from the realization that the size and/or number of droplets produced from a liquid reservoir can be controlled at a liquid-gas interface by supplying localized, well-defined forcing with precisely defined features. Furthermore, it has been realised that the use of a liquid filled channel may act as a type of wave guide to the liquid-gas interface.

[0033] Advantages provided by the present invention comprise the following:

• superior control of the interface through precisely defined features to generate the required size and number of droplets;

• on-demand production of droplets at a controlled frequency;

• improved efficiency by reducing the energy loss though acoustic coupling between successive layers of solids and liquids;

• individual droplets can be produced from a nozzle on demand, as opposed to streams of droplets;

• multiple focused beams of acoustic energy can be used to enable well defined steering of ejected droplets without the need for devices such as reflecting boards;

• the combination of an off-device pressure source and local forcing can control the liquid interface; and

• the use of localized well defined forcing, with precisely defined features.

[0034] The on-demand method of production also allows for more controllable droplet production. The ability to produce individual droplets from a nozzle on-demand as opposed to streams of droplets extends the application of this technology beyond printing to particle/cell encapsulation and imaging. The use of multiple focused beams of acoustic energy could lead to well defined steering of ejected droplets without the need for reflecting boards ¹² . [0035] Applications of the device and method of the present invention could include:

• process in spectroscopy, including X-ray compatible devices,

• ultrafast crystallography, and

• microplates, with the wells replaced by picolitre volume droplets,

• inkjet printing, and

• drug delivery, such as through nebulisers.

[0036] Further scope of applicability of embodiments of the present invention will become apparent from the detailed description given hereinafter. However, it should be understood that the detailed description and specific examples, while indicating preferred embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the disclosure herein will become apparent to those skilled in the art from this detailed description.

BRIEF DESCRIPTION OF THE DRAWINGS

[0037] Further disclosure, objects, advantages and aspects of preferred and other embodiments of the present application may be better understood by those skilled in the relevant art by reference to the following description of embodiments taken in conjunction with the accompanying drawings, which are given by way of illustration only, and thus are not limitative of the disclosure herein, and in which:

FIG. 1 illustrates a schematic side (FIG. 1 a) and top view (FIG. 1 b) of one embodiment of the device of the present invention operating in horizontal mode. A further schematic side view (FIG. 1 c) of an embodiment of the device shows the droplets (12) generated by the device. FIG. 2 illustrates an experimental demonstration (side view) of on-demand droplets ejected into air. Frequency and size of droplets can be controlled by tuning actuation power/ pulse length and membrane geometry

FIG. 3 illustrates side (FIG. 3a) and top views (FIG. 3b) of one embodiment of the device of the present invention operating in horizontal mode.

FIG. 4 (derived from reference 3) illustrates an example of current protein crystal imaging technique bulk piezo used to eject droplets onto conveyor belt (25) and including a sample holder (27), coupling column (29), transducer (31 ) and goniometer attachment plate (33).

FIG. 5 (derived from reference 6) illustrates examples of current protien crystal imaging techniques areodynamic nozzle (37) for direct injection into vaccum chamber.

DETAILED DESCRIPTION

[0038] The invention presented here is capable of rapid, on-demand ejection of a controlled number of micrometer diameter aqueous droplets into a gas, such as air or a vacuum. In one embodiment the device consists of a thin-film membrane (1 ) containing a precisely microfabricated hole placed on top of a piezoelectric substrate (3) adjacent a PDM (11 ) and forming a channel (13), as shown in FIG. 1 .

[0039] In a particularly preferred embodiment interdigitated electrodes (5) patterned on the substrate are used to excite a focused travelling SAW (7), which subsequently leads to the development of an acoustic beam radiating upwards at the Rayleigh angle (FIG. 1 ). When this beam reaches the liquid/air interface (9) it imparts a pressure force to controllably deform the interface to produce a required number of droplets (12) on- demand.

[0040] FIG. 2 shows a stream of droplets (15) produced with a prototype device based on the embodiment illustrated in FIG. 1 . The ejection frequency can easily be tuned, by modifying the membrane geometry, applied power and pulse time. [0041] The operation of this embodiment of the device is depicted in FIG. 1 in vertical mode, but a horizontal mode operation is also possible, as depicted in FIG. 3.

[0042] The use of a thin membrane is important as it allows for a second channel to be formed above the first and this ejection technique could be used for droplet production in closed microfluidic systems. A further enhancement could be the use of a number of acoustic beams in combination as this would enable steering of ejected droplets as well as accurate size control.

[0043] Compared with the nozzle free droplet ejection devices of the prior art, the present invention provides a superior control of the interface through precisely defined features to generate required size and number of droplets. The present invention also offers on-demand production of droplets (not possible with aerodynamic nozzles of the prior art) at a controlled frequency. This is a crucial requirement ⁸ for some types of spectroscopy, such as protein crystallization studies, which requires handling of difficult to obtain, expensive, biological samples.

[0044] Furthermore, compared with the prior art use of Lamb waves ¹⁰ , the present invention provides improved efficiency by reducing the energy loss through acoustic coupling between successive layers of solids and liquids.

[0045] In a particularly preferred application the present invention can be used in medical devices such as nebulisers to effectively provide on-demand particle diameter control. Typically, using nebulisers of the prior art, larger particles (> 5 micron) tend to deposit in the mouth while fine particles (< 5 micron) have the greatest potential for lung deposition. The use of a nebuliser according to the present invention can facilitate new asthma therapies that specifically target the small airways of the lungs.

[0046] In accordance with the present invention, nozzles having a diameter of 5 to 100 micrometer have been nanofabricated. The dimensions of the nozzle thus control the particle size.

[0047] Nozzles of this type can be integrated into devices, and computational studies used to determine the precise nozzle location for optimum results. It is particularly desirable for the nozzle/microfluidic system to be precisely aligned with the electrodes. Furthermore, pulse parameters can be characterised to control droplet size and frequency for a given nozzle geometry.

[0048] While a single line of droplets of well controlled size can be generated using the present invention, it is also possible to provide a grid of nozzles to increase throughput.

[0049] While this invention has been described in connection with specific embodiments thereof, it will be understood that it is capable of further modification(s). This application is intended to cover any variations uses or adaptations of the invention following in general, the principles of the invention and including such departures from the present disclosure as come within known or customary practice within the art to which the invention pertains and as may be applied to the essential features hereinbefore set forth.

[0050] As the present invention may be embodied in several forms without departing from the spirit of the essential characteristics of the invention, it should be understood that the above described embodiments are not to limit the present invention unless otherwise specified, but rather should be construed broadly within the spirit and scope of the invention as defined in the appended claims. The described embodiments are to be considered in all respects as illustrative only and not restrictive.

[0051] Various modifications and equivalent arrangements are intended to be included within the spirit and scope of the invention and appended claims. Therefore, the specific embodiments are to be understood to be illustrative of the many ways in which the principles of the present invention may be practiced. In the following claims, means-plus-function clauses are intended to cover structures as performing the defined function and not only structural equivalents, but also equivalent structures.

[0052] "Comprises/comprising" and "includes/including" when used in this specification is taken to specify the presence of stated features, integers, steps or components but does not preclude the presence or addition of one or more other features, integers, steps, components or groups thereof. Thus, unless the context clearly requires otherwise, throughout the description and the claims, the words 'comprise', 'comprising', 'includes', 'including' and the like are to be construed in an inclusive sense as opposed to an exclusive or exhaustive sense; that is to say, in the sense of "including, but not limited to".

References:

1. Collins, D., Alan, T., Helmerson, K. & Neild, A. Surface acoustic waves for on- demand production of picoliter droplets and particle encapsulation. Lab Chip 13, 3225-3231 (2013).

2. Dentry, M., Friend, J. & Yeo, L. Continuous flow actuation between external reservoirs in small-scale devices driven by surface acoustic waves. Lab on a Chip (2014). doi:10.1039/c3lc50933h

3. Roessler, C. G.et al. Acoustic methods for high-throughput protein crystal mounting at next-generation macromolecular crystallographic beamlines. Journal of Synchrotron Radiation 20, 805-808 (2013).

4. Bogan, MJ, Benner, WH, Boutet, S & Rohner, U. Single particle X-ray diffractive imaging. Nano Letters (2008). doi:10.1021/nl072728k.

5. Aerni, HR, Cornett, DS & Caprioli, RM. Automated acoustic matrix deposition for MALDI sample preparation. Analytical chemistry (2006). doi:10.1021/ac051534r.

6. DePonte, Weierstall & Schmidt. Gas dynamic virtual nozzle for generation of microscopic droplet streams. (2008).

7. Weierstall, U, Doak, RB, Spence, J. & Starodub, D. Droplet streams for serial crystallography of proteins. Experiments in (2008). at http://link.springer.com/article/10.1007/s00348-007-0426-8

Chapman, H. et al. Femtosecond X-ray protein nanocrystallography.

(201 1 ). doi:10.1038/nature09750.

9. Fukumoto, H., Aizawa, J., Matsuo, H., Narumiya, H. & Nakagawa, K. Liquid ejector which uses a high-order ultrasonic wave to eject ink droplets and printing apparatus using same. US Patent 6,155,671 Seo, OG, Nam, S, Choi, BL & Song, YJ. Apparatus for jetting ink utilizing lamb wave and method for manufacturing the same. US Patent 6,296,346 Quate, CF & Khuri-Yakub, BT. Nozzleless liquid droplet ejectors. US Patent 4,697,195 Shiokawa, S, Matsui, Y & Ueda, T. Droplets jetting device. US Patent 5,063,396 Khuri-Yakub, BT, Elrod, SA & Quate, CF. Perforated membranes for liquid contronlin acoustic ink printing. US Patent 5,028,937

Friend, J, Yeo, L, Morton, MM, Qi, A, Ho, J & Rajapaksa, A. Microfluidic apparatus for the atomisation of a liquid. US Patent application 8,991 ,722 B2