a Photograph of SKH-1 hairless mouse being treated with parallel plate electrode under isoflurane inhalation anesthesia. (Inset) Close-up of one of the plates of parallel plate electrode showing it recessed by 0.5 mm to allow a space for a conductive agar gel to be placed on it [7]. b Typical response of a melanoma to three applications of 100 pulses (300 ns, 40 kV/cm, 0.5 Hz) 30 min apart on day 0 followed by a single application on day 4 using a 5 mm diameter parallel plate electrode on mouse #102. Collection of seven matched sets of images of the same tumor all taken on the day indicated in the lower left corner of the transillumination image [7]. c Blood flow in melanoma before and after nsPEF application. (A) 3-D reconstruction of volume of melanoma; (B) power Doppler reconstruction of blood flow before field application. (C) 3-D reconstruction of volume of the same melanoma shown in (A) generated about 15 min after 100 pulses (300 ns, 40 kV/cm, 0.5 Hz). (D) Power Doppler reconstruction of blood flow in the same tumor shown in (B) generated about 15 min after 100 pulses (300 ns, 40 kV/cm, 0.5 Hz) [7]. d Location of electropores with respect to electric field. (A) One electropore at pole of each hemisphere when induced electric field strength, E, is equal to the minimum transmembrane electric field strength needed to cause dielectric breakdown, ET. (B) Additional electropores induced at greater distance from poles when E > ET. (C) Net negative charged entity inside spherical membrane is inhibited from diffusing through electropores if movement is against transmembrane electric field. (D) Net positive charged entity inside spherical membrane can diffuse out since movement is in same direction as electric field in vicinity of pore [49]. e Photographs of formalin-fixed, paraffin-embedded cross-sections of porcine buccal mucosae. Hematoxylin and eosin staining: (A) Control, untreated. (B) Control, passive permeation after an 8 h treatment period. Slightly enlargement of 2–3 cell layers (arrows) [50]