Non-Invasive Blood Glucose Monitoring

An Explanation of Iontophoresis

Iontophoresis is the application of a small electric current to enhance the transport of both charged and polar, neutral components across the skin. When an electric field is established across a membrane, ions on either side will migrate in the direction dictated by their charge. This occurs through electromigration and electoosmosis.⁶

Reverse Iontophoresis

Instead of using a small charge to move particles into the skin, reverse iontophoresis can be used to pull up desired charged particles. Knowing the properties of interstitial fluid will allow it to be more or less selectively drawn up.

Figure 1. Reverse Iontophoresis: a schematic diagram illustrating the experimental setup. Constant current is delivered to the anode and cathode by electromigration(2), electroosmosis(3), and (to negligable extent typically) passive diffusion(1). Anionic compounds are attracted into the anode chamber by electromigration(2), while convective solvent flow(3) opposes this phenomenon (again passive diffusion is negligable).1

Electromigration

Conventionally, in iontophoresis, a constant current is applied, such that the flow of electrons is translated into an ion flux across the skin. A power supply establishes the electric field that causes electrons to migrate in the 'electrical' portion of the circuit and ions to flow in the 'ionic' part (Figure 1). It follows that the number of electrons flowing through the 'electrical' portion of the circuit is exactly balanced by the amount of ionic charge flowing through the skin.

The sum of the individual ionic charges flowing across the skin must equal the number of electrons 'delivered' by the power supply; in other words, there is competition among all the ions present to carry the charge. Furthermore, with respect to electromigration, only the ionized fraction of the analyte is extractable and this will depend on the relevant pKa. Similarly, for analytes that are bound to proteins, it is clear that only the free fraction can significantly contribute to charge transport across the skin.

In summary, it can be concluded that an ion can function as a major charge carrier if it is small, fully charged, at high concentration, and not significantly protein-bound. In reverse iontophoresis, the major charge carriers are Na+ and Cl-. Na+ is the major charge carrier in iontophoresis in the outward direction towards the cathode (much as Cl- performs the same function towards the anode).⁶

Electroosmosis

At physiologic pH, the skin is negatively charged and cation permselective. When an electric field is imposed across this type of membrane, there is convective or electroosmotic solvent flow induced in the anode to the cathode direction. An important limitation occurs when the skin accumulates the analyte of interest such that the initial extraction sample contains mostly information about this local 'reservoir' (this is the case for glucose). A 'warm-up' period is necessary, therefore, before readings reflective of systemic levels are obtained.⁶

Application to Prototype

Our prototype will not incorporate reverse iontophoresis. Though reverse iontophoresis is part of our design, we do not have the time, means, or budget to apply this feature to our prototype for IPRO day. The reason why we want reverse iontophoresis in our design, however, is because it will greatly decrease the amount of time needed to withdraw the interstitial fluid through the skin. By combining the vaccuum, sonophoresis, and reverse iontophoresis we would be able to draw up enough interstitial fluid quickly and efficiently without inconviencing the patient.