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One of the proposed ways to induce transdermal convection of body fluids out of the body for non-invasive metabolite monitoring refers to the use of focused ultrasound transducer arrays. Propagation of 5 MHz focused ultrasound beam through thin porous polymer membranes (pore size 15-50 nm), resulted in significant rapid fluid flow through the membrane towards the focal region. The flow rate through the intact human skin, however, is rather insignificant for diagnostic applications. The important question becomes how to increase skin permeability and permit higher convection rates. Pretreatment of the skin with low frequency, 20 kHz, ultrasound for short time (few minutes) prior to exposure to a high frequency focused ultrasound beam tremendously increases the amount of fluid convected across the skin. Low frequency ultrasound causes cavitation in the stratum corneum resulting in a breakup of lipid bilayers that temporarily opens transdermal pathways for fluid and metabolite transfer. In vitro experiments have shown that the significant amount of glucose could be extracted through the human skin via fluid convection caused by a high frequency focused ultrasound beam, after short (5 min) pretreatment of stratum corneum by 20 kHz ultrasound. The results promise an excellent method to induce sufficient transdermal flow of body fluids for noninvasive diagnostic purposes. |
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