209 THE DIABETES CONTROL AND COMPLICATIONS TRIAL of 1992 demonstrated that the rigorous control of blood glucose levels through a combination of frequent glucose measurements and insulin injections can reduce the occurrence of long-term complications in type 1 diabetes. However, patient compliance with this intensive treatment is low, one of the primary reasons being that current methods of blood glucose self-testing are expensive, painful, cumbersome, aesthetically unpleasant, and inconvenient. In addition, patients have the fear of increased frequency of hypoglycemic episodes, which increase with intensive therapy. As a result, intensive research and commercial activity has focused on the development of simple painless techniques of monitoring glucose with increased frequency. Techniques under investigation can be categorized as noninvasive, minimally invasive, and invasive (i.e., implantable sensors). Noninvasive and so-call minimally invasive monitoring methods have been areas of intense research for nearly the past decade. The techniques fall into two general categories: transdermal spectroscopy and interstitial fluid sampling. The latter is the subject of the article by Tierney and colleagues from Cygnus, Inc. The primary technique for interstitial fluid sampling researched thus far has been reverse iontophoresis as personified by the Cygnus GlucoWatch, an integrated iontophoresis extraction system and glucose sensor that recently received a panel recommendation for Food and Drug Administration (FDA) approval. In brief, when an electric field is applied between two electrodes placed on the skin, anions in the skin will move to the anode and cations move toward the cathode. This results in an electro-osmotic flow of interstitial fluid toward these electrodes. Because the majority of ions transported are Na 1 , the primary glucose flux is to the cathode. The interstitial fluid is collected in and diluted by the electrolyte that electrically couples the electrodes to the skin. Glucose can then be measured using a glucose sensor in contact with the electrolyte. A significant advantage of this method over transdermal spectroscopy is that a physiologically relevant fluid sample is collected. Interstitial fluid has been shown in a number of studies to have a glucose concentration identical to or closely correlated to that in plasma, though there are significant variation from study to study as a result of differing collection methods. The volume of interstitial fluid collected using reverse iontophoresis is small, primarily because the fluid is transported through hair follicles and sweat ducts. The extracted interstitial fluid sample is diluted in the hydrogel electrolyte used to couple the electrode to the skin. As a result, glucose concentrations in the receiver are low which makes electrochemical glucose sensing a challenge. Subject to these constraints, Cygnus has developed a glucose oxidase based electrochemical sensor to measure glucose in the extracted fluid. The main