2004 OPEN FORUM Abstracts
MEMS-Based ultrasonic Atomizer for measles vaccine delivery
M. Meacham, H. Noh PhD, F. L. Degertekin PhD, and A. G. Fedorov
PhD – G. W. Woodruff School of Mechanical Engineering, The
Georgia Institute of Technology, Atlanta, GAP.
Rota PhD and M. Papania MD MPH – Centers for Disease Control
and Prevention, Atlanta, GA
A comprehensive review of measles vaccination delivery methods indicates that aerosol inhalation exhibits the greatest potential of nonpercutaneous routes (Cutts et al., Biologicals, 25:323-338, 1997). In fact, this method has been shown to generate serological responses that exceed those achieved by injection. Typical nebulizers used for inhalation are not well suited to widespread vaccination programs in undeveloped regions due to lack of portability, and other common aerosol delivery devices, e.g., pressurized Metered Dose Inhalers (pMDI), are unable to produce the monodisperse droplets necessary for effective aerosol inhalation. In this study we demonstrate the unique capabilities of a micromachined (MEMS) ultrasonic atomizer as a new, promising technology for aerosol delivery of the measles vaccine that overcomes the shortcomings of current devices. The micromachined atomizer (Fig. 1a) we recently developed (Meacham et al., Rev. Sci. Inst., 75(5): 1347-1352, 2004) utilizes cavity resonances in the 1 – 5 MHz range along with the acoustic wave focusing properties of a liquid horn to generate a jet of droplets. When the piezoelectric transducer is driven at the resonant frequency of the fluid chamber, a standing acoustic wave develops with the peak pressure gradient occurring near the tip of the nozzle. We use micro-fabrication technology to produce the atomizer: anisotropic KOH-wet etching is used to establish the pyramidal horns along the crystallographic planes of a single-crystal silicon wafer, and the nozzle orifice is opened using inductively coupled plasma (ICP) etching. For effective aerosolized vaccine delivery, the target droplet generation rate is 0.15 cm3 during a 30 s run with half of the ejected volume in the 1– 5 µm range. The ultrasonic atomizer we developed is capable of meeting this requirement by operating at a frequency of ~1MHz using 100, 5 µm nozzles arranged in a 10x10 array. We used a Phase Doppler Particle Analyzer (PDPA) to find that ejection from 4 µm orifices results in almost monodisperse 5 µm droplets. Virus viability following ejection from an array of 8µm orifices was analyzed by comparing the potency of ejected virus to two control samples. As shown in Fig. 1b, the control samples CVC1 and CVC2 exhibit a potency of 103.4 plaque forming units (pfu) per dose. The potency of the ejected virus was approximately 103 pfu as long as the ejection temperature did not exceed 50°C. These results unambiguously indicate that the MEMS ultrasonic atomizer we developed is capable of delivering aerosolized measles vaccine, while meeting the most stringent requirements on delivery efficacy (droplet size, distribution, and volume) as well as virus viability.