Electrochemical Evaluation and Control of Skin Function Via Transepidermal Potential
Authors: Abe Yuina , Konno Hajime , Takizawa Ryohei , Yamauchi Takeshi , Yamasaki Kenshi , Nishizawa Matsuhiko 
Published: December 2020

The epidermis at the forefront of the skin, wraps around the entire body and acts as a barrier to prevent the loss of internal moisture and the invasion of foreign substance. Its involvement in the transduction of external stimuli has been reported, and there has been growing interest in its intelligent aspects in recent years. A potential difference, called the transepidermal potential (TEP), is generated across the epidermis, and its magnitude is about tens of mVs where its surface is negative [1]. Active ion transportation by the epidermal keratinocytes is seemed to generate TEP, and its value changes according to the state of epidermal wounds and barrier. Unfortunately, the lack of an appropriate method for TEP measurement has hindered the progress of the research for decades. As TEP is generated across the epidermis, measuring electrodes have to be connected to the outside of the epidermis (surface of the skin) and the inside of the epidermis (tissue under the epidermis). Typically, a wound is created as an electrical path to the subepidermal tissue, despite its invasiveness. As an alternative, sublingual mucosa was utilized as a potential reference, suffering from the interference of other tissues. In this study, we developed a minimally invasive measurement method and applied it to the evaluation and control of skin function.
To measure relatively small resting potential, a pair of reversible Ag/AgCl electrodes were connected to the inside and outside of the epidermis via a salt bridge. A commercially available painless medical micro-needle (Nanopass 34G, Terumo) was employed to support the salt bridge for subepidermal connection. The external diameter of the needle was 0.18 mm (34 G), which minimized the damage accompanied by the insertion. The salt bridge was made biocompatible from Ringer's solution and agarose, and held in the hydrophilized needle, which could quickly soak up tissue fluid and stabilize the ionic conduction. Then the needle salt bridge for subepidermal tissue and a tubular salt bridge for the surface of the epidermis were bundled into a measuring probe (Figure 1A) [2].
For ex vivo measurement, porcine skin samples were used to observe the disruption and recovery of epidermal barrier induced by visible light stimulation. In vivo measurements were performed on human participants. All procedures performed in studies involving human participants were in accordance with the standards of the Ethics Committee of Graduate School of Engineering, Tohoku University (16A-5) and with the 1964 Helsinki declaration and its later amendments.
In vivo measurements in human participants successfully observed a decrease in TEP according to the experimental barrier disruption, accompanied by an increase in the amount of water evaporation across the skin (Figure 1B) [3]. The penetration depth of the needle was about 1 mm, allowing access into the epidermis with minimal invasion. Compared to the water evaporation, which requires the controlled atmosphere for measurement, TEP was reflected by the electrical properties of the inside of the epidermis, and expected to be suitable for on-demand measurement. TEP of porcine skin sample also showed decrease along with the barrier disruption, and application of electrical potential that have been reported to therapeutic effect on skin barrier [4] caused greater recovery (Figure 1C). These results indicate that the developed device would be a practical tool for less-invasive TEP potential, and suggest further application of it in the electrical diagnosis and cure.

References

[1] A. T. Barker, L. F. Jaffe, and J. W. Vanable Jr., “The glabrous epidermis of cavies contains a powerful battery.”, Am. J. Physiol., 242, R358–R366, (1982)
[2] Y. Abe et al., “Minimally-invasive transepidermal potentiometry with microneedle salt bridge”, Biomed. Microdevices, 18, 55, (2016)
[3] Y. Abe et al., “Red light-promoted skin barrier recovery: Spatiotemporal evaluation by transepidermal potential”, PLoS One, 14, e0219198, (2019)
[4] M. Denda, and N. Kumazawa, “Negative electric potential induces alteration of ion gradient and lamellar body secretion in the epidermis, and accelerates skin barrier recovery after barrier disruption”, J. Invest. Dermatol., 118, 65–72, (2002)

Figure 1