Due to advances in telemedicine, mobile medical care, wearable health monitoring, and electronic skin, great efforts have been directed to non-invasive monitoring and treatment of disease. These processes generally involve disease detection from interstitial fluid (ISF) instead of blood, and transdermal drug delivery. However, the quantitative extraction of ISF and the level of drug absorption are greatly affected by the individual’s skin permeability, which is closely related to the properties of the stratum corneum (SC). Therefore, measurement of SC impedance has been proposed as an appropriate way for assessing individual skin differences. In order to figure out the current status and research direction of human SC impedance detection, investigations regarding skin impedance measurement have been reviewed in this paper. Future directions are concluded after a review of impedance models, electrodes, measurement methods and systems, and their applications in treatment. It is believed that a well-matched skin impedance model and measurement method will be established for clinical and point-of care applications in the near future.

Skin penetration is related to efficiencies of drug delivery or ISF extraction. Normally, the macro-electrode is employed in skin permeability promotion and evaluation, which has the disadvantages of easily causing skin damage when using electroporation or reverse iontophoresis by alone; furthermore, it has large measurement error, low sensitivity, and difficulty in integration. To resolve these issues, this paper presents a flexible interdigital microelectrode for evaluating skin penetration by sensing impedance and a method of synergistical combination of electroporation and reverse iontophoresis to promote skin penetration. First, a flexible interdigital microelectrode was designed with a minimal configuration circuit of electroporation and reverse iontophoresis for future wearable application. Due to the variation of the skin impedance correlated with many factors, relative changes of it were recorded at the end of supply, different voltage, or constant current, times, and duration. It is found that the better results can be obtained by using electroporation for 5 min then reverse iontophoresis for 12 min. By synergistically using electroporation and reverse iontophoresis, the penetration of skin is promoted. The results tested in vivo suggest that the developed microelectrode can be applied to evaluate and promote the skin penetration and the designed method promises to leave the skin without damage. The electrode and the method may be beneficial for designing noninvasive glucose sensors.