The main objective of this proposal is the fabrication of 3D-printed wearable electrochemical sensors (ring type) suitable for glucose determination in human sweat. Diabetes is one of the most serious disease and it is considered as a major mortality factor. The frequent measurement of glucose in blood is necessary in order the appropriate treatment and nutrition to be establish. The research effort has led to the development and commercialization of portable glucose meters, which integrate electrodes with immobilized enzyme (glucose oxidase) that catalyzes glucose oxidation. However, their use requires the sampling of patient’s blood which is painful while the frequent sampling is avoided.

Alternative glucose monitoring technology provides real-time monitoring. These systems are based on subcutaneous implantation of enzyme sensors that measure the glucose level in the intracellular fluid of the skin. Today, there are such commercially available systems, but their wide acceptance is restricted due to the need for frequent calibration and the possibility of patient’s infection.

These disadvantages can be addressed by non-invasive methods. The last decade, the development of wearable sensors has gained widespread research interest. These sensors are in the form of a bracelet or adhesive tape and they are integrated in electronic devices with wireless data transmission. The measurement of glucose by wearable sensors is carried out in the intercellular fluid of the skin and in sweat. In sweat the glucose level is about 1/100 of this in blood. However, the glucose wearable sensors have not yet been exploited commercially.

3D-printing is based on a CAD design of the desired 3D virtual object followed by formation of the actual object by the operation of one printer, which heats the thermoplastic-based materials to a semi-molten state before extrusion and solidification. Recently, 3D-printing have been applied in the field of electronics, and its introduction to fabrication of electrochemical sensors offers many advantages, as it: uses low-cost desktop-sized equipment, provides flexibility in the design, involves extremely low capital, operational and materials costs, offers high flexibility in the choice of materials, leads to batch-to batch precision and uniformity, does not produce waste, ensures full design transferability between 3D platforms. Up to now, 3D printed sensors modified with Metal Organic Frameworks (MOFs) have not been reported in the literature.

MOFs are porous crystalline multidimensional polymeric complexes and consist of metal ions or clusters and of organic polytopic bridging ligands. The modular nature of MOFs allows the fine-tuning of their properties either by selecting the appropriate building groups or by modifying some structural features after their synthesis (post-synthetic modifications). Of particular interest are MOFs that are water stable and suitable for applications in humid environments and water solutions. There are 22 papers in the literature reporting modified electrodes by MOFs for glucose detection. In these papers, MOFs cover the surface of the electrode sorbing the glucose from the solution thereby facilitating its electrochemical oxidation to glycolactate. Recently, our groups have developed new MOFs based on oxalamide ligands. The presence of amides in the backbone of the polytopic ligands imposes on MOFs structural rigidity, high thermal stability (> 400 ° C) and water stability-insolubility. Also, these MOFs have been used by our group as active ingredients for the fabrication of electrodes to detect heavy metal ions in water samples.

This proposal focuses on the development of novel MOFs based on amide bridging ligands that will be stable in water to selectively saturate glucose from aqueous solutions and artificial sweat. The novel MOFs will be integrated in 3D-printed sensors. These sensors will be embodied into wearable devices for real-time monitoring of glucose levels.

The following four publications in scientific journals resulted from this project:

1. Koukouviti, E., Plessas, A. K., Pagkali, V., Economou, A., Papaefstathiou, G. S., & Kokkinos, C. “3D-printed electrochemical glucose device with integrated Fe(II)-MOF nanozyme.” Microchimica Acta, 2023, 190(7), 1-9. https://doi.org/10.1007/s00604-023-05860-6
2. Oikonomopoulos, P., Pagkali, V., Kritikou, E., Panara, A., Kostakis, M. G., Thomaidis, N.S., Tziotzi, T. G., Economou, A., Kokkinos, C. & Papaefstathiou, G. S. “Oxalamide Based Fe(II)-MOFs as Potential Electrode Modifiers for Glucose Detection” Chemistry, 2023, 5(1), 19-30. https://doi.org/10.3390/chemistry5010002
3. Koukouviti, E., Plessas, A. K., Economou, A., Thomaidis, N., Papaefstathiou, G. S. & Kokkinos, C. “3D Printed Voltammetric Sensor Modified with an Fe(III)-Cluster for the Enzyme-Free Determination of Glucose in Sweat” Biosensors, 2022, 12(12), 1156. https://doi.org/10.3390/bios12121156
4. Vasiliou, F., Plessas, A. K., Economou, A., Thomaidis, N., Papaefstathiou, G. S. & Kokkinos, C. “Graphite paste sensor modified with a Cu(II)-complex for the enzyme-free simultaneous voltammetric determination of glucose and uric acid in sweat.” J. Electroanal. Chem. 2022, 917, 116393. https://doi.org/10.1016/j.jelechem.2022.116393