Reverse Iontophoresis: Noninvasive Glucose Monitoring in Vivo in Humans

Abstract

Purpose. To demonstrate that “reverse iontophoresis” can be used to noninvasively obtain information about systemic glucose levels in vivo in humans.

Methods. The passage of current across the skin in vivo drives ions into the tissue, from the electrode chambers positioned on the skin surface, and simultaneously pulls ions from the body in the opposite direction. Because of the net negative charge on the skin, under normal conditions, the membrane is permselective to cations, and a potential gradient also results, therefore, in electroosmotic convection of solvent in the direction of counterion flow (i.e., from anode to cathode). Thus, it is also possible to enhance the transport of polar, yet uncharged, species using iontophoresis. In an earlier study, the in vitro extraction of glucose, by “reverse iontophoresis” was established, and extension of the approach to an in vivo model was indicated. The idea has therefore been further explored in vivo in humans.

Results. Using small, simple, prototypical electrode chambers, attached to the ventral forearm surface, direct current iontophoresis at 0.25 mA/cm² for periods of up to 1 hour, and a sensitive analytical procedure to measure the quantities of glucose extracted, it has been shown that iontophoretic sampling of glucose is feasible. However, the shorter periods (15 minutes or less) of extraction considered yield results which are “contaminated” (it is believed) by glucose that is a product of lipid metabolism within the skin. While this material is expected to complicate the initial calibration of the approach, the problem is effectively resolved within one hour, by which time the glucose arriving in the electrode chambers on the skin surface is expected to directly reflect the subcutaneous tissue concentration.

Conclusions. Based upon these initial observations, further investigation can now be directed towards optimization of electroosmotic flow and sampling time, improved reproducibility and the development of a practical assay methodology.