Search

An ultra-miniaturized electrochemical biosensor for continuous glucose monitoring (CGM) is presented. The aim of this work is to demonstrate the possibility of an overall reduction in sensor size to allow minimally invasive glucose monitoring in the interstitial fluid in the dermal region, in contrast to larger state-of-the-art systems, which are necessarily placed in the subcutaneous layer. Moreover, the reduction in size might be a key factor to improve the stability and reliability of transdermal sensors, due to the reduction of the detrimental foreign body reaction and of consequent potential failures. These advantages are combined with lower invasiveness and discomfort for patients. The realized device consists of a microfabricated three-electrode enzymatic sensor with a total surface area of the sensing portion of less than 0.04mm 2 , making it the smallest fully integrated planar amperometric glucose sensor area reported to date. The working electrode and counter electrode consist of platinum and are functionalized by drop casting of three polymeric membranes. The on-chip iridium oxide (IrOx) pseudo-reference electrode provides the required stability for measurements under physiological conditions. The device is able to dynamically and linearly measure glucose concentrations in-vitro over the relevant physiological range, while showing sufficient selectivity to known interfering species present in the interstitial fluid, with resolution and sensitivity (1.51nA/mM) comparable to that of state-of-art commercial CGM systems. This work can therefore enable less invasive and improved CGM in patients affected by diabetes., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The incidence of insulinopenic diabetes mellitus is constantly increasing, and in addition, approximately a third of all hyperinsulinemic diabetic patients develop insulinopenia. Optimal glycemic control is essential to minimize the risk for diabetes-induced complications, but the majority of diabetic patients fail to achieve proper long-term glucose levels even in clinical trials, and even more so in clinical practice. Compliance with a treatment regimen is likely to be higher if the procedure is simple, painless, and discreet. Thus, insulin has been suggested for nasal, gastrointestinal, and inhalation therapy, but so far with considerable downsides in effect, side effects, or patient acceptance. The stratum corneum is the main barrier preventing convenient drug administration without the drawbacks of subcutaneous injections. Recently, devices with miniaturized needles have been developed that combine the simplicity and discretion of patch-based treatments, but with the potential of peptide and protein administration. As this review describes, initial comparisons with subcutaneous administration now suggest microneedle patches for active insulin delivery are efficient in maintaining glycemic control. Hollow microneedle technology could also prove to be efficient in systemic as well as local delivery of other macromolecular drugs, such as vaccines., (© 2014 Diabetes Technology Society.)

This paper presents the first microneedle-based transdermal patch with integrated active dispensing functionality. The electrically controlled system consists of a low-cost dosing and actuation unit capable of controlled release of liquid in the microliter range at low flow-rates and minimally invasive, side-opened, microneedles. The system was successfully tested in vivo by insulin administration to diabetic rats. Active infusion of insulin at 2 mul/h was compared to passive, diffusion-driven, delivery. Continuous active infusion caused significantly higher insulin concentrations in blood plasma. After a 3-h delivery period, the insulin concentration was five times larger compared to passive delivery. Consistent with insulin concentrations, actively administered insulin resulted in a significant decrease of blood glucose levels. Additionally, insertion and liquid injection was verified on human skin. This study shows the feasibility of a patch-like system with on-board liquid storage and dispensing capability. The proposed device represents a first step towards painless and convenient administration of macromolecular drugs such as insulin or vaccines.