- Transdermal extraction of clinically relevant analytes offers a potentially noninvasive method of diagnostics. However, development of such a method is limited by the low permeability of skin. In this paper, we present a potential method for noninvasive diagnostics based on ultrasonic skin permeabilization and subsequent extraction of interstitial fluid (ISF) across the skin using vacuum. ISF extracted by this method was collected and analyzed for glucose and other analytes. Glucose concentration in the extracted fluid correlates well with blood glucose concentration over a range of 50–250 mg/dl. A mathematical model describing vacuum-induced transport of ISF through ultrasonically permeabilized skin is presented as well. The model accounts for convective, as well as diffusive, transport processes across blood capillaries, epidermis, and the stratum corneum. The overall predictions of the model compare favorably with the experimental observations.