NUMBAT - Biofunctional nanoporous hydrogel on microneedle-based enzymatic biosensors for minimally invasive monitoring of glucose

NUMBAT aims at the research on innovative concepts for the fabrication of minimally invasive systems for glucose monitoring in the dermal interstitial fluid and their implementation in a production line. To this end, short microneedles with small tip radii are fabricated on flexible foils by a novel 3D-microstereolithography printer prototype, which will be set-up within the frame of the project. The biofunctionalisation of the penetrating tips is realised by inkjet printing a biocompatible hydrogel, which embeds a glucose-specific enzyme in its nanoporous network, in order to realise third-generation electrochemical glucose sensors.

A good management of blood glucose levels is a requirement of every diabetes therapy. Regular measurements of blood glucose levels help to avoid too high and too low levels and resulting secondary diseases. The common method, to draw blood from the fingertips several times a day with a lancing device, is a burden to the patients, and improper handling can easily lead to wrong results. Continuous glucose monitoring systems have recently entered the market. Due to their high measurement frequency, circadian fluctuations of the glucose level are far better registered, and faulty operation by the patient is avoided. The application of the sensor heads, however, is not painless, as the sensors consist of several millimetres long needles, which are introduced into the subcutaneous tissue. This procedure has to be repeated every 1-2 weeks and bears a certain risk of infection and the occurrence of allergic skin reactions.

The project NUMBAT aims at the research on innovative concepts for the fabrication of minimally invasive systems for glucose monitoring and their implementation in a production line. The concept is based on microneedles with small tip radii and heights around 500 µm, which measure the glucose level in the dermal interstitial fluid. The microneedles are placed on a flexible foil and can be applied to the skin like a patch on a daily basis. The use of microneedles improves tissue compatibility as compared to conventional systems. A further improvement is achieved by coating the penetrating tips with a biocompatible hydrogel. The hydrogel also plays an essential role in the measurement of the glucose level. By embedding a glucose-specific enzyme in the nanoporous network of the hydrogel, the working electrode of the electrochemical sensor is biofunctionalised. In this way, novel third-generation electrochemical glucose sensors are realised. In contrast to their conventional counterparts, these sensors require no additional substrate for the enzymatic reaction and no potentially toxic mediators. At present, there is no cost-effective fabrication method for the mass production of polymeric microneedles on a flexible substrate. An essential goal of NUMBAT is therefore also the setup of a 3D-microstereolithography printer and a printing process for the fabrication of the microneedles.

The glucose sensing properties of the fabricated sensors will be characterised in use-oriented environments. This will allow the optimisation of individual process steps and forms the basis for a product with high market potential.

Project Nr . 858701, funded in the frame of the FFG „Produktion der Zukunft“ Program – 19. Call