A method of enhancing the permeability of the skin (120, 274) to an analytic for diagnostic purposes or to a drug for therapeutic purposes is described utilizing micro-pore and optionally sonic energy and a chemical enhancer. If selected, the sonic energy may be modulated by means of frequency modulation, amplitude modulation, phase modulation, and/or combinations thereof. Micro-pore is accomplished by (a) ablating the stratum corneum (274) by localized rapid heating of water such that water is vaporized, thus eroding cells； (b) puncturing the stratum corneum (274) which a micro-lancet calibrated to form a micro-pore of up to about 1000 m in diameter (c) ablating the stratum corneum (274) by focusing a tightly focused beam of sonic energy onto the stratum corneum (274)； (d) hydraulically puncturing the stratum corneum (274) with a high-pressure jet of fluid to form a micro-pore of up to about 1000 m in diameter； or (e) puncturing the stratum corneum (274) with short pulses of electricity to form a micro-pore of up to about 1000 m in diameter.
