Transdermal Extraction of Interstitial Fluid by Low‐Frequency Ultrasound Quantified with 3H2O as a Tracer Molecule

The transdermal extraction of interstitial fluid by low‐frequency ultrasound offers a potential minimally invasive method of obtaining a fluid sample for at‐home blood glucose monitoring. Here we show that the application of low‐frequency ultrasound (20 kHz) enhances the transdermal transport of interstitial fluid across hairless rat skin. Using 3 H 2 O as a tracer injected intravenously, a measurable amount of water (>1 μL) was extracted without producing any histologic evidence of injury, even after repeated exposures. Piezoelectric transducers were imbedded in the extraction chamber and used to correlate ultrasound spectral properties to the amount of fluid extracted. Results indicate that the highest amount of water extracted occurs when the acoustic coupling media on the surface of the skin is cavitating, resulting in mild ablation of the stratum corneum and a reduction in its resistance to water mass transfer. © 2000 Wiley‐Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 89: 1170–1179, 2000