Rapid Enhancement of Cellular Spheroid Assembly by Acoustically Driven Microcentrifugation.

Intense acoustically driven microcentrifugation flows are employed to enhance the assembly of cellular spheroids in the microwell of a tissue culture well plate. This ability to interface microfluidics with commonly used tissue culture plasticware is a significant advantage as it can potentially be parallelized for high throughput operation and allows existing analytical equipment designed to fit current laboratory formats to be retained. The microcentrifugation flow, induced in the microwell coated with a low adhesive hydrogel, is shown to rapidly enhance the concentration of cells into tight aggregates within a minute-considerably faster than the conventional hanging drop and liquid overlay methods, which typically require days-while maintaining their viability.

Assessment of the potential of a high frequency acoustomicrofluidic nebulisation platform for inhaled stem cell therapy.

Despite the promise of stem cell therapy for lung therapeutics and repair, there are few viable means for directly delivering stem cells to locally target the respiratory airways via inhalation. This is not surprising given the significant challenges in aerosolising stem cells, particularly given their susceptibility to damage under the large stresses involved in the nebulisation process. Here, we present promising results using a microfluidic acoustic nebulisation platform that is not only low cost and portable, but also its high MHz order frequencies are effective for preserving the structural and functional integrity of mesenchymal stem cells (MSCs) during the nebulisation process.

Pulmonary monoclonal antibody delivery via a portable microfluidic nebulization platform.

Nebulizers have considerable advantages over conventional inhalers for pulmonary drug administration, particularly because they do not require coordinated breath actuation to generate and deliver the aerosols. Nevertheless, besides being less amenable to miniaturization and hence portability, some nebulizers are prone to denature macromolecular drugs due to the large forces generated during aerosolization. Here, we demonstrate a novel portable acoustomicrofluidic device capable of nebulizing epidermal growth factor receptor (EGFR) monoclonal antibodies into a fine aerosol mist with a mass median aerodynamic diameter of approximately 1.

Effective pulmonary delivery of an aerosolized plasmid DNA vaccine via surface acoustic wave nebulization.

Background: Pulmonary-delivered gene therapy promises to mitigate vaccine safety issues and reduce the need for needles and skilled personnel to use them. While plasmid DNA (pDNA) offers a rapid route to vaccine production without side effects or reliance on cold chain storage, its delivery to the lung has proved challenging. Conventional methods, including jet and ultrasonic nebulizers, fail to deliver large biomolecules like pDNA intact due to the shear and cavitational stresses present during nebulization.

Enabling practical surface acoustic wave nebulizer drug delivery via amplitude modulation.

A practical, commercially viable microfluidic device relies upon the miniaturization and integration of all its components--including pumps, circuitry, and power supply--onto a chip-based platform. Surface acoustic waves (SAW) have become popular in microfluidic manipulation, in solving the problems of microfluidic manipulation, but practical applications employing SAW still require more power than available via a battery. Introducing amplitude modulation at 0.

Hydroxypropyl cellulose methacrylate as a photo-patternable and biodegradable hybrid paper substrate for cell culture and other bioapplications.

In addition to the choice of appropriate material properties of the tissue construct to be used, such as its biocompatibility, biodegradability, cytocompatibility, and mechanical rigidity, the ability to incorporate microarchitectural patterns in the construct to mimic that found in the cellular microenvironment is an important consideration in tissue engineering and regenerative medicine. Both these issues are addressed by demonstrating a method for preparing biodegradable and photo-patternable constructs, where modified cellulose is cross-linked to form an insoluble structure in an aqueous environment. Specifically, hydroxypropyl cellulose (HPC) is rendered photocrosslinkable by grafting with methylacrylic anhydride, whose linkages also render the cross-linked construct hydrolytically degradable.

Uniform mixing in paper-based microfluidic systems using surface acoustic waves.

Paper-based microfluidics has recently received considerable interest due to their ease and low cost, making them extremely attractive as point-of-care diagnostic devices. The incorporation of basic fluid actuation and manipulation schemes on paper substrates, however, afford the possibility to extend the functionality of this simple technology to a much wider range of typical lab-on-a-chip operations, given its considerable advantages in terms of cost, size and integrability over conventional microfluidic substrates. We present a convective actuation mechanism in a simple paper-based microfluidic device using surface acoustic waves to drive mixing.

Template-free synthesis and encapsulation technique for layer-by-layer polymer nanocarrier fabrication.

The encapsulation of therapeutic molecules within multiple layers of biocompatible and biodegradable polymeric excipients allows exquisite design of their release profile, to the extent the drug can be selectively delivered to a specific target location in vivo. Here, we develop a novel technique for the assembly of multilayer polyelectrolyte nanocarriers based on surface acoustic wave atomization as a rapid and efficient alternative to conventional layer-by-layer assembly, which requires the use of a sacrificial colloidal template over which consecutive polyelectrolyte layers are deposited. Polymer nanocarriers are synthesized by atomizing a polymer solution and suspending them within a complementary polymer solution of opposite charge subsequent to their solidification in-flight as the solvent evaporates; reatomizing this suspension produces nanocarriers with a layer of the second polymer deposited over the initial polymer core.

The extraction of liquid, protein molecules and yeast cells from paper through surface acoustic wave atomization.

Paper has been proposed as an inexpensive and versatile carrier for microfluidics devices with abilities well beyond simple capillary action for pregnancy tests and the like. Unlike standard microfluidics devices, extracting a fluid from the paper is a challenge and a drawback to its broader use. Here, we extract fluid from narrow paper strips using surface acoustic wave (SAW) irradiation that subsequently atomizes the extracted fluid into a monodisperse aerosol for use in mass spectroscopy, medical diagnostics, and drug delivery applications.

Miniature inhalation therapy platform using surface acoustic wave microfluidic atomization.

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.