Shih K. Lin

Miniaturized multiple Fourier-horn ultrasonic droplet generators for biomedical applications

Here we report micro-electro-mechanical system (MEMS)-based miniaturized silicon ultrasonic droplet generators of a new and simple nozzle architecture with multiple Fourier horns in resonance but without a central channel. The centimetre-sized nozzles operate at one to two MHz and a single vibration mode which readily facilitates temporal instability of Faraday waves to produce monodisperse droplets. Droplets with diameter range 2.2-4.6 μm are produced at high throughput of 420 μl min(-1) and very low electrical drive power of 80 mW. We also report the first theoretical prediction of the droplet diameter. The resulting MHz ultrasonic devices possess important advantages and demonstrate superior performance over earlier devices with a central channel and thus have high potential for biomedical applications such as efficient and effective delivery of inhaled medications and encapsulated therapy to the lung.

Faraday instability-based micro droplet ejection for inhalation drug delivery

We report here the technology and the underlying science of a new device for inhalation (pulmonary) drug delivery which is capable of fulfilling needs unmet by current commercial devices. The core of the new device is a centimeter-size clog-free silicon-based ultrasonic nozzle with multiple Fourier horns in resonance at megahertz (MHz) frequency. The dramatic resonance effect among the multiple horns and high growth rate of the MHz Faraday waves excited on a medicinal liquid layer together facilitate ejection of monodisperse droplets of desirable size range (2-5 µm) at low electrical drive power (<1.0 W). The small nozzle requiring low drive power has enabled realization of a pocket-size (8.6 × 5.6 × 1.5 cm3) ultrasonic nebulizer. A variety of common pulmonary drugs have been nebulized using the pocket-size unit with desirable aerosol sizes and output rate. These results clearly provide proof-of-principle for the new device and confirm its potential for commercialization.

In situ preparation of an ultra-thin nanomask on a silicon wafer

Porous nanomasks have been prepared in situ on an insulating silicon wafer by anodization of an aluminum film grown on it. Ultra-thin nanomasks, around 50 nm thick, were fabricated by utilizing a stop signal, a vivid color appearing at the air-electrolyte interface, and the process involved showed excellent repeatability. Finally, 2D nanoscale p-n junction arrays were fabricated on a silicon on insulator (SOI) wafer using the ultra-thin nanomasks prepared. The experimental results are in good agreement with the simulated results on the characteristics of the anodization process involved.

Pocket-sized ultrasonic nebulizer for inhalation drug delivery

Silicon-based MHz ultrasonic multiple Fourier horns in resonance are capable of producing high-throughput micrometer-sized droplets at low drive power. The centimeter-sized nozzles together with low power requirement enabled most recent realization of the first pocket-sized ultrasonic nebulizer (8.6 × 5.6 × 1.5 cm3) that contains nozzle, IC electronic driver, cell-phone battery, micro pump, drug reservoir, and liquid feed. A variety of common drugs for asthma, chronic obstructive pulmonary disease (COPD), diabetics, cyanide poisoning, pulmonary fibrosis, etc. such as albuterol, Humulin U-100, cobinamide, interferon-γ, and budesonide suspension have been nebulized with desirable aerosol size and throughput.

MEMS-based silicon ultrasonic twin-nozzle nebulizer for inhalation drug delivery

A versatile silicon-based ultrasonic nebulizer that utilizes a twin-nozzle of multiple Fourier horns at 1-2 MHz drive frequencies has been realized to perform simultaneous aerosolization of cobinamide and magnesium thiosulfate drug solutions. The drive frequency of the individual nozzle for a desirable aerosol diameter was individually designed. Using the 2.0 MHz 4-Fourier horn twin-nozzle aerosols of the two drug solutions with mass median diameter (MMD) of 3.0±0.1μm and geometrical standard deviation (GSD) of 1.18±0.02 and total flow rate up to 400μL/min were produced.

Faraday Waves-Based Integrated Ultrasonic Micro-Droplet Generator and Applications

An in-depth review on a new ultrasonic micro-droplet generator which utilizes megahertz (MHz) Faraday waves excited by silicon-based multiple Fourier horn ultrasonic nozzles (MFHUNs) and its potential applications is presented. The new droplet generator has demonstrated capability for producing micro droplets of controllable size and size distribution and desirable throughput at very low electrical drive power. For comparison, the serious deficiencies of current commercial droplet generators (nebulizers) and the other ultrasonic droplet generators explored in recent years are first discussed. The architecture, working principle, simulation, and design of the multiple Fourier horns (MFH) in resonance aimed at the amplified longitudinal vibration amplitude on the end face of nozzle tip, and the fabrication and characterization of the nozzles are then described in detail. Subsequently, a linear theory on the temporal instability of Faraday waves on a liquid layer resting on the planar end face of the MFHUN and the detailed experimental verifications are presented. The linear theory serves to elucidate the dynamics of droplet ejection from the free liquid surface and predict the vibration amplitude onset threshold for droplet ejection and the droplet diameters. A battery-run pocket-size clogging-free integrated micro droplet generator realized using the MFHUN is then described. The subsequent report on the successful nebulization of a variety of commercial pulmonary medicines against common diseases and on the experimental antidote solutions to cyanide poisoning using the new droplet generator serves to support its imminent application to inhalation drug delivery.

Micrometer-sized droplet ejection from a millimeter-sized spherical water drop using a megahertz multiple-fourier horn ultrasonic nozzle

A new phenomenon on droplet ejection, namely, one large spherical water drop ejecting simultaneously a very large number of monodisperse micro droplets was observed and studied in detail. An ultrasonic nozzle with multiple-Fourier horns in resonance enables controlled excitation of megahertz Faraday waves on the spherical water surface which leads to the ejection of 3.5-4.4μm monodisperse droplets at a high rate (>107 droplets per second). This is in stark contrast to the RayleighPlateau instability, which ejects one droplet at a time.

MEMS-based multiple fourier-horn silicon ultrasonic atomizer for inhalation drug delivery

Silicon-based centimeter-sized 1.0 - 2.0 MHz ultrasonic nozzles that employ multiple-Fourier horns and external liquid feeding have been realized to produce micrometer-sized (2.2 to 4.6μm) monodisperse droplets at high throughput (600μl/min) and low electrical drive power (<;1 W). A preliminary battery-operated atomizer module has been constructed for inhalation drug delivery.