## 3 Results and Discussion
### Argon and Helium Plasma Jet Irradiation Increases the Transdermal Permeability of Porcine Skin  
The plasma-induced transdermal absorption rate was determined on pig skin, which is known to be most similar to human skin [30]. To optimize the most effective absorption rate condition, we first investigated the transdermal permeability according to the exposure duration of the atmospheric-pressure helium or argon plasma. As shown in Figure 4, the helium or argon plasma was irradiated for 0, 10, 30, and 60 s in the quartered regions of the porcine skin at a distance of 4 mm from the skin surface. Subsequently, a dye reagent (aniline blue cream) was equivalently applied to the quartered porcine skin. After 10 h, the transdermal permeability was analyzed by colorimetric changes depending on the absorbed amount of aniline blue dye. As shown in Figure 4B, argon plasma remarkably facilitated the transdermal absorption of aniline blue on porcine skin in an exposure time-dependent manner. This consequently resulted in approximately 2.5-fold higher permeation after argon plasma irradiation for 60 s. In addition, the time-dependent irradiation of helium plasma also showed an increased absorption ratio of aniline blue dye and finally saturated from the exposure time of 30 s (Figure 4C). When the plasma irradiation distance movedto 8 mm, there was no significant influence on the absorption rate after irradiation of the argon and helium plasma (Figure 5). Taken together, argon and helium plasma exhibited the most transdermal permeability of aniline blue dye on porcine skin when irradiated for approximately 30 s at a plasma irradiation distance of 4 mm. In addition, argon plasma-treated porcine skin showed higher transdermal permeability than helium plasma. To further investigate the change in temperature by plasma irradiation, we measured the skin temperature after plasma exposure for 10, 30, 60 s at distance of 4 mm. As shown in Figure 6, the skin temperature after exposure of argon plasma for 0, 10, 30, and 60 s was 21.4, 22, 4, 25.9 and 28.7, respectively, and helium plasma was 21.4, 22, 4, 25.9 and 28.7, respectively. The argon and helium plasma treatment for 60 s increased the surface temperature up to approximately 7 \({}^{\circ}\)C and 4 \({}^{\circ}\)C, respectively. Figure 2: IV curve and electrical waveform of argon and helium plasma jets. The gas flow rates of argon and helium were fixed at 2 slm. (**A**) DC input voltage and DC Discharged current for argon and helium plasma. The breakdown voltage were 6 V for argon and 4 V for helium, The DC input voltage for transdermal permeability experiment were fixed 18 V and 12 V in argon and helium gas, respectively. (**B**) Waveforms of the inverted AC applied voltage and discharge current for the argon and helium plasma at DC input voltage 18 V and 12 V, respectively. The applied RMS voltages were 2.54 kV for argon and 1.73 kV for helium, and their RMS discharge currents were 11.01 mA and 6.21 mA, respectively. Figure 4: Transdermal absorption of aniline blue dye on porcine skin by argon and helium plasma irradiation at a distance of 4 mm (**A**) The quartered area of the rectangular area in porcine skin was treated with argon or helium plasma for 0, 10, 30, or 60 s at a distance of 4 mm between the plasma jet and the surface of the skin and thereafter stained with aniline blue dye. The transdermal permeability of aniline blue dye on porcine skin was quantified and normalized to that of the nontreated control. (**B,C**) Data are presented as means \(\pm\) S.D. **_p_ < 0.01, ***_p_ < 0.001 compared to the nontreated control (one-way ANOVA, [PERSON]’s post hoc test) with argon (**B**) or helium (**C**). n = 3 independent samples per group. Figure 3: Optical emission spectroscopy of argon and helium plasma jets with a wavelength range from 200–900 nm.