Influence of enzyme immobilization and skin-sensor interface on non-invasive glucose determination from interstitial fluid obtained by magnetohydrodynamic extraction

We integrated a magnetohydrodynamic fluid extractor with an amperometric glucose biosensor to develop a wearable device for non-invasive glucose monitoring. Reproducible fluid extraction through the skin and efficient transport of the extracted fluid to the biosensor surface are prerequisites for non-invasive glucose monitoring. We optimized the enzyme immobilization and the interface layer between the sensing device and the skin. The monitoring device was evaluated by extracting fluid through porcine skin followed by glucose detection at the biosensor. The biosensor featured a screen-printed layer of Prussian Blue that was coated with a layer containing glucose oxidase. Both physical entrapment of glucose oxidase in chitosan and tethering of glucose oxidase to electrospun nanofibers were evaluated. Binding of glucose oxidase to nanofibers under mild conditions provided a stable biosensor with analytical performance suitable for accurate detection of micromolar concentrations of glucose. Hydrogels of varying thickness (95-2000 mu m) as well as a thin (30 mu m) nanofibrous polycaprolactone mat were studied as an interface layer between the biosensor and the skin. The effect of mass transfer phenomena at the biosensor-skin interface on the analytical performance of the biosensor was evaluated. The sensing device detected glucose extracted through porcine skin with an apparent (overall) sensitivity of-0.8 mA/(M.cm(2)), compared to a sensitivity of-17 mA/(M.cm(2)) for measurement in solution. The amperometric response of the biosensor correlated with the glucose concentration in the fluid that had been extracted through porcine skin with the magnetohydrodynamic technique.Peer reviewe

Sampling of fluid through skin with magnetohydrodynamics for noninvasive glucose monitoring

Out of 463 million people currently with diabetes, 232 million remain undiagnosed. Diabetes is a threat to human health, which could be mitigated via continuous self-monitoring of glucose. In addition to blood, interstitial fluid is considered to be a representative sample for glucose monitoring, which makes it highly attractive for wearable on-body sensing. However, new technologies are needed for efficient and noninvasive sampling of interstitial fluid through the skin. In this report, we introduce the use of Lorentz force and magnetohydrodynamics to noninvasively extract dermal interstitial fluid. Using porcine skin as an ex-vivo model, we demonstrate that the extraction rate of magnetohydrodynamics is superior to that of reverse iontophoresis. This work seeks to provide a safe, effective, and noninvasive sampling method to unlock the potential of wearable sensors in needle-free continuous glucose monitoring devices that can benefit people living with diabetes.Peer reviewe

Pilot study in human healthy volunteers on the use of magnetohydrodynamics in needle-free continuous glucose monitoring

The benefits of continuous glucose monitoring (CGM) in diabetes management are extensively documented. Yet, the broader adoption of CGM systems is limited by their cost and invasiveness. Current CGM devices, requiring implantation or the use of hypodermic needles, fail to offer a convenient solution. We have demonstrated that magnetohydrodynamics (MHD) is effective at extracting dermal interstitial fluid (ISF) containing glucose, without the use of needles. Here we present the first study of ISF sampling with MHD for glucose monitoring in humans. We conducted 10 glucose tolerance tests on 5 healthy volunteers and obtained a significant correlation between the concentration of glucose in ISF samples extracted with MHD and capillary blood glucose samples. Upon calibration and time lag removal, the data indicate a Mean Absolute Relative Difference (MARD) of 12.9% and Precision Absolute Relative Difference of 13.1%. In view of these results, we discuss the potential value and limitations of MHD in needle-free glucose monitoring.Peer reviewe

Electrochemically prepared composites of graphene oxide and conducting polymers: Cytocompatibility of cardiomyocytes and neural progenitors

The cytocompatibility of cardiomyocytes derived from embryonic stem cells and neural progenitors, which were seeded on the surface of composite films made of graphene oxide (GO) and polypyrrole (PPy-GO) or poly(3,4-ethylenedioxythiophene) (PEDOT-GO) are reported. The GO incorporated in the composite matrix contributes to the patterning of the composite surface, while the electrically conducting PPy and PEDOT serve as ion-to-electron transducers facilitating electrical stimulation/sensing. The films were fabricated by a simple one-step electropolymerization procedure on electrically conducting indium tin oxide (ITO) and graphene paper (GP) substrates. Factors affecting the cell behaviour, i.e. the surface topography, wettability, and electrical surface conductivity, were studied. The PPy-GO and PEDOT-GO prepared on ITO exhibited high surface conductivity, especially in the case of the ITO/PPy-GO composite. We found that for cardiomyocytes, the PPy-GO and PEDOT-GO composites counteracted the negative effect of the GP substrate that inhibited their growth. Both the PPy-GO and PEDOT-GO composites prepared on ITO and GP significantly decreased the cytocompatibility of neural progenitors. The presented results enhance the knowledge about the biological properties of electroactive materials, which are critical for tissue engineering, especially in context stimuli-responsive scaffolds. © 2019 Elsevier B.V.Czech Science FoundationGrant Agency of the Czech Republic [19168615]; Ministry of Education, Youth and Sports of the Czech Republic - Program NPU I [L01504]; Jane and Aatos Erkko Foundation (Finland