2004 OPEN FORUM Abstracts
MEMS-Based ultrasonic Atomizer for measles vaccine delivery
J.
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.
