Novel glucose-responsive of the transparent nanofiber hydrogel patches as a wearable biosensor via electrospinning

Abstract

Micro- and nanofiber (NF) hydrogels fabricated by electrospinning to typically exhibit outstanding high porosity and specific surface area under hydrated conditions. However, the high crystallinity of NFs limits the achievement of transparency via electrospinning. Transparent poly(vinyl alcohol)/β-cyclodextrin polymer NF hydrogels contacted with reverse iontophoresis electrodes were prepared for the development of a non-invasive continuous monitoring biosensor platform of interstitial fluid glucose levels reaching ~ 1 mM. We designed the PVA/BTCA/β-CD/GOx/AuNPs NF hydrogels, which exhibit flexibility, biocompatibility, excellent absorptivity (DI water: 21.9 ± 1.9, PBS: 41.91 ± 3.4), good mechanical properties (dried: 12.1 MPa, wetted: 5.33 MPa), and high enzyme activity of 76.3%. Owing to the unique features of PVA/β-CD/GOx containing AuNPs NF hydrogels, such as high permeability to bio-substrates and rapid electron transfer, our biosensors demonstrate excellent sensing performance with a wide linear range, high sensitivity(47.2 μA mM^-1), low sensing limit (0.01 mM), and rapid response time (< 15 s). The results indicate that the PVA/BTCA/β-CD/GOx/AuNPs NF hydrogel patch sensor can measure the glucose concentration in human serum and holds massive potential for future clinical applications.

Figure 1

(a) Schematic illustration of the patch-type glucose sensor using PVA/BTCA/β-CD/GOx/AuNPs NF hydrogels on electrodes and the glucose-sensing mechanism for the noninvasive real-time monitoring of glucose in sweat. (b) Schematic illustration of the preparation of the PVA/BTCA/β-CD/GOx/AuNPs complex dope solution for electrospinning. (c) Process of transparent PVA/BTCA/β-CD/GOx/AuNPs nanofibrous hydrogels (containing optical and SEM images).

Figure 2

(a) FT-IR spectra and (b) XRD of PVA, β-CD, BTCA, PVA/BTCA, PVA/BTCA/β-CD, PVA/BTCA/GOx, PVA/BTCA/β-CD/GOx, and PVA/BTCA/β-CD/GOx/AuNPs NFs. The stretching and bending modes of different functional groups are indicated by γ and δ, respectively.

Figure 3

SEM micrographs of (a) PVA/BTCA, (b) PVA/BTCA/β-CD, (c) PVA/BTCA/GOx, (d) PVA/BTCA/β-CD/GOx, (e) PVA/BTCA/β-CD/GOx/AuNPs hydrogel NFs, (f) average diameters of each sample, and (g) elemental mapping of carbon (yellow), oxygen (green), and gold (red) elemental dispersions in the PVA/BTCA/β-CD/GOx/AuNPs NFs.

Figure 4

XPS spectrum of hydrogel NFs for the confirmation of the formation of inclusion compounds of secondary binding energy spectrum of carbon of (a) PVA/BTCA, (b) PVA/BTCA/β-CD, (c) PVA/BTCA/GOx, (d) PVA/BTCA/β-CD/GOx, and (e) PVA/BTCA/β-CD/GOx/AuNPs.

Figure 5

Tensile stress–strain curves for PVA/BTCA, PVA/BTCA/β-CD, PVA/BTCA/GOx, PVA/BTCA/β-CD/GOx, and PVA/BTCA/β-CD/GOx/AuNPs hydrogel NF (a) in a dry state, (b) in a hydrated state, (c) absorption ratio for distilled water, and (d) absorption ratio for PBS solution.

Figure 6

Analysis of enzymatic activity of (a) PVA/BTCA/β-CD/GOx/AuNPs, (b) PVA/BTCA/β-CD/GOx, and (c) PVA/BTCA/GOx hydrogel NFs after heat treatment using a glucose oxidase activity kit and UV–Vis spectroscopy. The colorimetric (535 – 570 nm) product of GOx produced by the GOx activity kit via d-glucose oxidation and reaction with the probe to produce hydrogen peroxide (H₂O₂), (d) absorbance at a wavelength of 570 nm, which is the maximum absorbance of each sample.

Figure 7

(a) CVs of PVA/BTCA, PVA/BTCA/β-CD, PVA/BTCA/GOx, PVA/BTCA/β-CD/GOx, and PVA/BTCA/β-CD/GOx/AuNPs hydrogel NFs hydrated by PBS (pH 7.4); Scan rate: 0.1 Vs⁻¹; (b) three-electrode measurement of patch-type PVA/BTCA/β-CD/GOx/AuNPs hydrogel NFs hydrated (c) CVs of PVA/BTCA/β-CD/GOx/AuNPs at varied absorbed d-glucose concentrations (0.1–0.5 mM) at pH 7.4 and 25 °C; Scan rate: 0.1 V s⁻¹ and amperometric responses to successive addition of d-glucose (0.1–0.5 mM) at − 0.2 V (vs. Ag/AgCl) on the PVA/BTCA/GOx (d), PVA/BTCA/β-CD/GOx/AuNPs (e), PVA/BTCA/β-CD/GOx (f). The inset (e) shows the calibration plot of the steady-state current as a function of d-glucose concentration.