Wearable glucose sensors have attracted significant attention for enabling non-invasive blood glucose measurement without discomfort and risk of infection. However, it is a challenge to simultaneously realize wearable adaptability, biodegradability, and excellent sensing performance. Herein, a cellulose paper-based non-invasive biosensor relying on reverse iontophoresis was designed to detect glucose in interstitial fluid (ISF), and two different enzyme immobilization strategies have been compared. The results showed inkjet-printed cellulose paper-based biosensor (IPB) performances better than the drop-coated cellulose paper-based biosensor (DPB). IPB has twice response current more than DPB in detection range (0–10 mM). In sensitivity, IPB is 1.170 μA/mM three times higher than the DPB (0.376 μA/mM). Besides, IPB's electron-transfer resistance (Rct) is 7.27 kΩ smaller than DPB (Rct = 10.51 kΩ) about 30 %. More importantly, IPB exhibited a good reproducibility (RSD, 4.82 %), which was much less than DPB (RSD, 18.35 %). Furthermore, the IPB realizes noninvasive continuous glucose monitoring over 6 h in volunteer experiments with great analytical performance comparable to commercial devices (Pearson correlation 0.732). Cellulose paper-based glucose sensors with inkjet printing provide non-invasive access to statistically significant diagnostic information, simple and cost-effective, which promotes the application of flexible, wearable, degradable bioelectrodes in continuous glucose monitoring at home, providing a concept for full integration in a compact and portable way in the future.
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