Sampling of fluid through skin with magnetohydrodynamics for noninvasive glucose monitoring

Abstract

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.

Figure 1

(a) 3D model construction of MHD with the extraction cell cut out to reveal the main parts of the cell: GelMA hydrogel at the bottom, porcine skin on top of the hydrogel, electrode wells filled with buffer (PBS, 10 mM, pH 7.4) and Ag/AgCl electrodes (ø = 1 mm, length = 2.5 cm). (b) The extraction chamber is positioned between two neodymium magnets (size: 70 mm × 70 mm × 30 mm). (c) Schematic picture of glucose extraction using MHD. An electric current is established between the two electrode chambers filled with buffer solution. The electric current induces electro-osmotic flow from the anode through the skin towards the cathode. A current density profile (J) in the presence of a magnetic field (B) generates a Lorentz force (F) that drives the interstitial fluid towards the skin surface.

Figure 2

(a) Measured amount of glucose collected in the cathodic electrode well after 10 min extraction with passive diffusion, reverse iontophoresis, and MHD using 125 mT, 200 mT and 300 mT magnetic fields. Each extraction was done at room temperature (22 ± 1 °C) using GelMA hydrogel with 5 mM glucose, and an extraction current of 300 µA. P-values were calculated using an unpaired t-test. (b) The amount of actively extracted glucose was calculated by subtracting the contribution of passive glucose diffusion. (c) Measured voltage curves during extraction. Voltage between the extraction electrodes was measured during each extraction. (d–f)Amount of extracted glucose in relation to the number of hair follicles and thickness of the skin samples. (d) Pictures from a porcine skin sample after extraction at the electrode well area, where the individual hair follicles are marked with arrows. (e) Number of hair follicles and total amount of glucose measured (extraction + diffusion) for both iontophoresis and MHD with 300 mT magnetic field. (f) Thickness of porcine skin and total amount of glucose measured (extraction + diffusion) for both iontophoresis and MHD with 300 mT magnetic field. (g) Total extracted glucose with different glucose concentrations in the GelMA hydrogel (p = 0.0002 from an F-test) (B = 300 mT, I = 300 µA). In figs (a–c) the bars show the average from at least 6 individual experiments and the error bars represent standard deviation of the mean.

Figure 3

(a) The effect of extraction time on total amount of extracted glucose for diffusion, reverse iontophoresis (300 µA) and MHD (300 µA and 300 mT). The bars represent the average from at least 4 individual experiments and the error bars represent standard deviation of the mean. The values of individual experiments are indicated with the circles on top of the bar graphs. Dotted line on the bar graphs serves as a guide for the eye and represent the contribution of diffusion. The p-values were calculated using an unpaired t-test. (b) Amounts of actively extracted glucose after the effect of passive glucose diffusion is subtracted. This data indicates that MHD extraction is more effective that reverse iontophoresis also in shorter extraction times. Furthermore, most of the active extraction occurring at the early time points of the extraction.

Figure 4

(a) Photographs of porcine skin samples used in this study either with reverse iontophoresis or MHD. No damage apart from minor imprints from the electrode wells were visible. (b) Skin water loss was measured at room temperature using a Tewameter before and after extraction (delta = after extraction-before extraction). The Tewameter readings measured after reverse iontophoresis (n = 22) and extraction with MHD (n = 23) were not statistically different from the values measured for samples where no active extraction was applied (n = 17). Individual data points are represented with circles and the boxes behind the data points represent the standard error. The thin, horizontal lines mark the mean values, and the error bars depict standard deviation of the dataset. The p-values were calculated using an unpaired t-test.