Surface Acoustic Wave Nebulisation

The large surface accelerations, millions of g’s, as the surface acoustic wave (SAW) passes along the surface gives rise to rapid interfacial destabilisation, which leads towards the nebulisation of a drop or a film. It is therefore possible to generate monodispersed 1-3 μm order aerosol drops. Current projects are exploiting this for pulmonary drug delivery, nanomedicine as well as an efficient chip-based interface for mass spectrometry. In addition, we have also shown that the SAW nebulisation constitutes a simple but yet rapid one-step method for the synthesis of 100 nm polymeric or protein nanoparticles, or even the encapsulation of proteins, peptides, DNA and other therapeutic molecules or stem cells within a shell (or multilayers of polyelectrolyte shell coatings) comprised of a biodegradable polymeric excipient as a vehicle for controlled release drug delivery. One significant advantage of the device over other nebulisation methods is its ability to efficiently deliver large and complex molecules and cells with little denaturation. This is because the high frequencies employed do not permit cavitation in the sample and the field reverses at much shorter time scales than the hydrodynamic relaxation time associated with molecular shearing. 
Simultaneous drop translation and atomisation of a polymer solution can also be used to generate long-range homogeneous spatial ordering of polymer patterns without requiring physical or chemical templating, as shown. The polymer spot size and spacing is highly controllable through a single parameter alone, namely the SAW frequency or wavelength.
Representative Publications
  1. A Qi, LY Yeo, JR Friend. Interfacial Destabilization and Atomization Driven by Surface Acoustic Waves. Phys Fluids 20, 074103 (2008).
  2. JR Friend, LY Yeo, DR Arifin, A Mechler. Evaporative Self-Assembly Assisted Synthesis of Polymer Nanoparticles by Surface Acoustic Wave Atomization. Nanotechnology 19, 145301 (2008).
  3. M Alvarez, JR Friend, LY Yeo. Rapid Generation of Protein Aerosols and Nanoparticles via SAW Atomisation. Nanotechnology 19, 455103 (2008).
  4. M Alvarez, JR Friend, LY Yeo. Surface Vibration Induced Spatial Ordering of Periodic Polymer Patterns on a Substrate. Langmuir 24, 10629 (2008).
  5. M Alvarez, LY Yeo, JR Friend. Rapid Production of Protein Loaded Biodegradable Microparticles Using Surface Acoustic Waves. Biomicrofluidics 3, 014102 (2009).
  6. A Qi, JR Friend, LY Yeo, DA Morton, MP McIntosh, L Spiccia. Miniature Inhalation Therapy Platform Using Surface Acoustic Wave Microfluidic Atomization. Lab Chip 9, 2184–2193 (2009).
  7. A Qi, L Yeo, J Friend, J Ho. The Extraction Of Liquid, Protein Molecules and Yeast Cells From Paper Through Surface Acoustic Wave Atomization. Lab Chip 10, 470–476 (2010).
  8. LY Yeo, JR Friend, MP McIntosh, ENT Meeusen, DA Morton. Invited Paper: Ultrasonic Nebulization Platforms for Pulmonary Drug Delivery. Expert Opin Drug Deliv 7, 663–679 (2010).
  9. MK Tan, JR Friend, OK Matar, LY Yeo. Capillary Wave Motion Excited by High Frequency Surface Acoustic Waves. Phys Fluids 22, 112112 (2010).
  10. J Ho, MK Tan, D Go, L Yeo, J Friend, H-C Chang. Paper-Based Microfluidic Surface Acoustic Wave Sample Delivery and Ionization Source for Rapid and Sensitive Ambient Mass Spectrometry. Anal Chem 83, 3260–3266 (2011).
  11. A Qi, P Chan, J Ho, A Rajapaksa, J Friend, L Yeo. Template-Free Synthesis and Encapsulation Technique for Layer-by-Layer Polymer Nanocarrier Fabrication. ACS Nano 5, 9583–9591 (2011).
  12. DJ Collins, O Manor, A Winkler, H Schmidt, JR Friend, LY Yeo. Atomization Off Thin Water Films Generated by High Frequency Substrate Wave Vibrations. Phys Rev E 86, 056312 (2012).
  13. T Vuong, A Qi, M Muradoglu, BH-P Cheong, OW Liew, CX Ang, J Fu, L Yeo, J Friend, TW Ng. Precise Drop Dispensation on Superhydrophobic Surfaces Using Acoustic Nebulization. Soft Matter 9, 3631–3639 (2013).
  14. L Bllaci, S Kjellström, L Eliasson, JR Friend, LY Yeo, S Nilsson. Fast Surface Acoustic Wave-Matrix-Assisted Laser Desorption Ionization Mass Spectrometry of Cell Response from Islets of Langerhans. Anal Chem 85, 2623–2629 (2013).
  15. J Blamey, LY Yeo, JR Friend. Microscale Capillary Wave Turbulence Excited by High Frequency Vibration. Langmuir 29, 3835–3845 (2013). 
  16. A Rajapaksa, A Qi, LY Yeo, R Coppel, JR Friend. Enabling Practical Surface Acoustic Wave Nebulizer Drug Delivery via Amplitude Modulation. Lab Chip 14, 1858–1865 (2014).
  17. AE Rajapaksa, JJ Ho, A Qi, R Bischof, T-H Nguyen, M Tate, D Piedrafita, MP McIntosh, LY Yeo, E Meeusen, RL Coppel, JR Friend. Effective Pulmonary Delivery of an Aerosolized Plasmid DNA Vaccine via Surface Acoustic Wave Nebulization. Respir Res 15, 60 (2014).
  18. KM Ang, LY Yeo, JR Friend, YM Hung, MK Tan. Nozzleless Spray Cooling Using Surface Acoustic Waves. J Aerosol Sci 79, 48–60 (2015).
  19. C Cortez-Jugo, A Qi, A Rajapaksa, JR Friend, LY Yeo. Pulmonary Monoclonal Antibody Delivery via a Portable Microfluidic Nebulization Platform. Biomicrofluidics 9, 052603 (2015).
  20. KM Ang, L Yeo, J Friend, YM Hung, MK Tan. Acoustically Enhanced Heat Transport. Rev Sci Instrum 87, 014902 (2016).
  21. Y Wang, AR Rezk, JS Khara, LY Yeo, PLR Ee. Stability and Efficacy of Synthetic Cationic Antimicrobial Peptides Nebulized Using High Frequency Acoustic Waves. Biomicrofluidics 10, 034115 (2016).
  22. KM Ang, LY Yeo, YM Hung, MK Tan. Graphene-Mediated Microfluidic Transport and Nebulization via High Frequency Rayleigh Wave Substrate Excitation. Lab Chip 16, 3503–3514 (2016).
  23. L Alhasan, A Qi, AR Rezk, LY Yeo, PPY Chan. Assessment of the Potential of a High Frequency Acoustomicrofluidic Nebulisation Platform for Inhaled Stem Cell Therapy. Integr Biol 8, 12–20 (2016) [Article featured as Integrative Biology Hot Article; coverart selected for journal front cover].
  24. M Yousefi, O Pourmehran, M Gorji-Bandpy, K Inthavong, L Yeo, J Tu. CFD Simulation of Aerosol Delivery to a Human Lung via Surface Acoustic Wave Nebulization. Biomech Model Mechanobiol 16, 2035–2050 (2017).
  25. KS Wong, WTH Lim, CW Ooi, LY Yeo, MK Tan. In-Situ Generation of Plasma-Activated Aerosols via Surface Acoustic Wave Nebulization for Portable Spray-Based Surface Bacterial Inactivation. Lab Chip 20, 1856–1868 (2020).
  26. PCL Kwok, A McDonnell, P Tang, C Knight, E McKay, SP Butler, A Sivarajah, R Quinn, L Fincher, E Browne, LY Yeo, H-K Chan. In Vivo Deposition Study of a New Generation Nebuliser Utilising Hybrid Resonant Acoustic (HYDRA) Technology. Int J Pharm 580, 119196 (2020).
  27. AE Rajapaksa, LAH Do, D Suryawijaya Ong, M Sourial, D Veysey, R Beare, W Hughes, W Yang, RJ Bischof, A Mcdonnell, P Eu, L Yeo, PV Licciardi, EK Mulholland. Pulmonary Deposition of Radionucleotide-Labeled Palivizumab: Proof-of-Concept Study. Front Pharmacol 11, 1291 (2020).
  28. S Marqus, L Lee, T Istivan, RYK Chang, C Dekiwadia, H-K Chan, LY Yeo. High Frequency Acoustic Nebulization for Pulmonary Delivery of Antibiotic Alternatives Against Staphylococcus aureus. Eur J Pharm Biopharm 151, 181–188 (2020).
  29. NSL Chew, KS Wong, WS Chang, CW Ooi, LY Yeo, MK Tan. Nanoscale Plasma-Activated Aerosol Generation for In Situ Surface Pathogen Disinfection. Microsyst Nanoeng 8, 41 (2022).
  30. C Cortez-Jugo, S Masoumi, PPY Chan, J Friend, L Yeo. Nebulization of siRNA for Inhalation Therapy Based on a Microfluidic Surface Acoustic Wave Platform. Ultrason Sonochem 88, 106088 (2022).
  31. CC Woo, SN Nia, D Gouwanda, LY Yeo, MK Tan. Efficient Modulated Acoustic Nebulisation for Aerosol Delivery and Detection of Plasma-Activated Water for Surface Disinfection and Decontamination. Surf Interfaces 41, 103162 (2023).
Press Releases
  1. Drug Delivery’s a Blast, Chemical Technology, 15 May 2009.    
  2. Earthquake on a Wafer Could Boost Asthma Relief, New Scientist, 28 May 2009.
  3. Delivering Medicines, ABC Catalyst (Special Edition: Little Wonders – Medical Nanotechnology), Television Broadcast date: 25 August 2011 (Australian Broadcasting Corporation).
  4. What a Sound Idea, The Economist, 2 June 2012.

HYbriD Resonant Acoustics (HYDRA)

More recently, we have discovered a new class of sound waves—for the first time in over 60 years—what we term as surface reflected bulk waves (SRBW). We show, quite counterintuitively, that it is possible to obtain an order-of-magnitude improvement in microfluidic manipulation efficiency, and, in particular, nebulisation, through a unique hybrid combination of surface and bulk waves without increasing complexity or cost. The 5 ml/min nebulisation rate output of these HYDRA devices therefore promises to circumvent a major technological limitation faced by SAW microfluidic nebulisation devices (see above) that constitutes the dominant hurdle in their practical deployment for pulmonary drug delivery: a highly inadequate nebulisation rate (typically 0.1 ml/min) which prevents sufficient drug from being delivered in a practical inhalation period through a portable miniature consumer drug delivery platform.

Representative Publications
  1. AR Rezk, JK Tan, LY Yeo. HYbriD Resonant Acoustics (HYDRA). Adv Mater 28, 1970–1975 (2016) [Article coverart selected for journal back cover p 2088].
  2. EP Nguyen, L Lee, AR Rezk, YM Sabri, SK Bhargava, LY Yeo. Hybrid Surface and Bulk Resonant Acoustics for Concurrent Actuation and Sensing on a Single Microfluidic Device. Anal Chem 90, 5335–5342 (2018).
  3. H Ahmed, L Lee, C Darmanin, LY Yeo. A Novel Acoustomicrofluidic Nebulization Technique Yielding New Crystallization Morphologies. Adv Mater 30, 1602040 (2018) [Article coverart selected as journal frontispiece 30, 1870018].
  4. ​PCL Kwok, A McDonnell, P Tang, C Knight, E McKay, SP Butler, A Sivarajah, R Quinn, L Fincher, E Browne, LY Yeo, H-K Chan. In Vivo Deposition Study of a New Generation Nebuliser Utilising Hybrid Resonant Acoustic (HYDRA) Technology. Int J Pharm 580, 119196 (2020).
  5. S Marqus, L Lee, T Istivan, RYK Chang, C Dekiwadia, H-K Chan, LY Yeo. High Frequency Acoustic Nebulization for Pulmonary Delivery of Antibiotic Alternatives Against Staphylococcus aureus. Eur J Pharm Biopharm 151, 181–188 (2020).
  6. AE Rajapaksa, LAH Do, D Suryawijaya Ong, M Sourial, D Veysey, R Beare, W Hughes, W Yang, RJ Bischof, A Mcdonnell, P Eu, L Yeo, PV Licciardi, EK Mulholland. Pulmonary Deposition of Radionucleotide-Labeled Palivizumab: Proof-of-Concept Study. Front Pharmacol 11, 1291 (2020).

​Press Releases
  1. Hybrid Sound Wave a ‘Game-Changer’ for Vaccines and Nebulisers, The Australian, 7 January 2016.