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

酶固定化和皮肤传感器界面对磁流体萃取间质液无创葡萄糖测定的影响

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作者:Emily Kemp, Tommi Palomäki, Ida A Ruuth, Zhanna A Boeva, Teemu A Nurminen, Risto T Vänskä, Laura K Zschaechner, Alejandro García Pérez, Tuuli A Hakala, Melissa Wardale, Edward Haeggström, Johan Bobacka

Abstract

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 μm) as well as a thin (30 μm) 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·cm2), compared to a sensitivity of -17 mA/(M·cm2) 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.

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