Miniature inhalation therapy platform using surface acoustic wave microfluidic atomization

Abstract

Pulmonary drug administration requires direct delivery of drug formulations into the lower pulmonary tract and alveoli of the lung in the form of inhaled particles or droplets, providing a distinct advantage over other methods for the treatment of respiratory diseases: the drug can be delivered directly to the site of inflammation, thus reducing the need for systemic exposure and the possibility of adverse effects. However, it is difficult to produce droplets of a drug solution within a narrow monodisperse size range (1-10 microm) needed for deposition in the lower pulmonary tract and alveoli. Here, we demonstrate the use of surface acoustic wave microfluidic atomization as an efficient means to generate appropriate aerosols containing a model drug, the short-acting beta2 agonist salbutamol, for the treatment of asthma. The mean aerosol diameter produced, 2.84+/-0.14 microm, lies well within the optimum size range, confirmed by a twin-stage impinger lung model, demonstrating that approximately 70 to 80% of the drug supplied to the atomizer is deposited within the lung. Our preliminary study explores how to control the aerosol diameter and lung delivery efficiency through the surface tension, viscosity, and input power, and also indicates which factors are irrelevant-like the fluid density. Even over a modest power range of 1-1.5 W, SAW atomization provides a viable and efficient generic nebulization platform for the delivery of drugs via the pulmonary route for the treatment of various diseases. The control offered over the aerosol size, low power requirements, high delivery efficiency, and the miniaturization of the system together suggest the proposed platform represents an attractive alternative to current nebulizers compatible with microfluidic technologies.

UV epoxy bonding for enhanced SAW transmission and microscale acoustofluidic integration

“…[1][2][3] Despite only being recently demonstrated, the pairing of SAW and standard microfluidic structures has already proven useful for structure-independent mixing enhancement, 4,5 generation of macromolecule seeded aerosols and nanoparticles for pulmonary drug delivery, 6,7 particle separation and concentration, [8][9][10][11][12] surface micro-patterning, 13 ELISA automation and binding enhancement, 14,15 and development of rotational micromotors for MEMS. 16 Still, the most tantalizing prospects in acoustofluidics lie in fluidic actuation.…”

Surface Acoustic Waves: A New Paradigm for Driving Ultrafast Biomicrofluidics

“…If the power is not focused to a point underneath the drop or if the input power to the IDTs is increased further, the entire drop is completely destabilized and atomizes to produce a monodisperse distribution of aerosol droplets with a mean diameter of around 1-10 µm [18]. These monodispersed micron order droplets are particularly useful as drug-carrying vehicles for pulmonary drug delivery in which 2-5 µm order aerosol drops are typically required for optimum dose efficiency in order to deliver the maximum amount of drug to the lower respiratory airways for direct local administration to target organs [19].The power required, typically 1 W or less, is at least a factor of ten smaller than that of ultrasonic atomizers which use Langevin transducers and single lead zirconium titanate element thickness-mode piston atomizers operating between 10 kHz and 1 MHz. At these lower frequencies, drug molecules, DNA or proteins are susceptible to denaturing as cavitation becomes prevalent.…”

Influence of Viscosity in Fluid Atomization with Surface Acoustic Waves

“…The principle of fluid atomization using surface acoustic waves on piezoelectric chips was demonstrated by Kurosawa et al in 1995 [1] [2]. Since then, this phenomenon has been investigated regarding the underlying physical phenomena [3]- [6] or possible applications, including inhalation therapy [7] [8], olfactory displays [9], micro-and nanoparticle synthesis [10]- [12], thin film deposition [13]- [15] and mass spectroscopy of non-volatile fluids [16]- [18].…”