A soft, edible electrode made from alginate and polydopamine detects glucose under intestinal conditions, opening a path toward swallowable sensors for diabetes monitoring.
(Nanowerk Spotlight) Glucose monitors worn on the skin have transformed diabetes management, but they measure sugar levels only after glucose has entered the bloodstream. The small intestine, where dietary glucose actually crosses into the body, lies beyond the reach of current monitoring devices.
For people with type 2 diabetes, this matters because postprandial glucose absorption, the surge in blood sugar following a meal, originates precisely there. A sensor capable of measuring glucose directly in the intestine could enable real-time, site-specific monitoring and potentially interface with drug-release systems targeting intestinal glucose uptake.
Ingestible sensors could fill this gap: a device swallowed like a pill, transmitting biochemical measurements as it travels through the digestive tract, then exiting naturally without retrieval. Building such devices, however, has meant confronting a fundamental materials problem.
Conventional electronics depend on rigid metals and non-degradable plastics. These materials risk complications if a device becomes lodged. The gut environment poses additional challenges: acidic conditions in the stomach, alkaline fluid in the intestine, constant mechanical motion, and enzymes designed to break down foreign matter.
Researchers working on soft, flexible electronics have developed conductive hydrogels that combine gel-like softness with the ability to carry electrical signals. These water-rich materials have proven useful for neural interfaces and wearable sensors. Adapting them for ingestion required an additional constraint: every component must be safe to eat and capable of breaking down harmlessly.
The device conducts both ions and electrons without any metal scaffold and functions as a glucose sensor under conditions that simulate the human small intestine. The authors describe this as the first demonstration of quantitative glucose sensing in simulated intestinal fluid using a fully edible electrode.
A) Representative photograph of a free-standing Ca2+-crosslinked alginate–pDA hydrogel electrode (3.5% w/v). B) Cyclic voltammograms (CVs) recorded in 10 mm HEPES buffer (pH 7.2, 100 mm KCl) containing 10 mm [Fe(CN)6]3−/4− for electrodes prepared with 3.5% (w/v) alginate, at scan rates ranging from 5 to 300 mV s−1. C) CVs of the same electrodes in blank supporting electrolyte (HEPES 10 mm, pH 7.2, 100 mm KCl) in the absence of redox probe, used to extract capacitive currents and estimate double-layer capacitance. D) Electroactive area (AEA, red) and double-layer capacitance (Cdl, blue) determined for electrodes containing 3.0% and 3.5% (w/v) alginate (common reference formulation considered as baseline for comparisons: 3.5% w/v alginate, 5% w/v glycerol, 1 mL pDA per batch). E–J) Electrochemical impedance spectroscopy (EIS) analysis. Equivalent circuit models employed for fitting are reported in panels (E,H). F,G) Nyquist and Bode plots, respectively, for 3.0% w/v alginate electrodes, fitted with the circuit shown in (E). H,J) Nyquist and Bode plots, respectively, for 3.5% w/v alginate electrodes, fitted with the circuit shown in (I). Experimental data are shown as black squares, and red lines correspond to fits. (Image: Reproduced from DOI:10.1002/advs.202516912, CC BY) (click on image to enlarge)
Sodium alginate forms the electrode’s structural foundation. This polysaccharide, derived from brown seaweed, already appears in many food products as a thickener. When exposed to calcium ions, alginate chains link together into a stable three-dimensional network. The researchers used 3.5% alginate by weight, with 5% glycerol added to improve flexibility.
Alginate alone does not conduct electricity well. To address this limitation, the team incorporated polydopamine, a synthetic material inspired by the adhesive proteins that allow mussels to grip wet rocks. Polydopamine contains molecular structures called catechols, ring-shaped chemical groups that can accept and donate electrons. These catechols also bind strongly to calcium ions, weaving the polydopamine into the alginate network and creating pathways for electrical charge to flow.
Silver nanoparticles provided the catalytic activity needed for sensing. The researchers synthesized these particles using quercetin, a plant-derived compound, as the reducing agent. The resulting nanoparticles averaged 34 nm in diameter and included triangular and faceted shapes known to enhance catalytic activity toward hydrogen peroxide reduction.
Food-grade glucose oxidase served as the biological recognition element. When glucose encounters this enzyme, a chemical reaction produces hydrogen peroxide. The silver nanoparticles then convert this peroxide into an electrical signal, which can be measured at the electrode surface.
Electrochemical tests characterized the optimized electrode’s performance. The material exhibited an electroactive surface area of 1.99 ± 0.07 cm² and a double-layer capacitance of 10.1 ± 0.3 μF. Impedance measurements yielded a charge-transfer resistance of 7.7 ± 0.6 kΩ, a relatively low value indicating efficient electron movement through the polydopamine domains.
Four-point conductivity measurements confirmed that the complete formulation achieved bulk conductivity of 5.3 ± 0.7 mS cm⁻¹, far exceeding the 0.35 ± 0.05 mS cm⁻¹ measured for polydopamine alone. This improvement demonstrates that the calcium-crosslinked matrix successfully establishes mixed ionic and electronic conduction pathways without requiring a metal current collector.
The team tested glucose sensing in USP simulated intestinal fluid, a standard laboratory preparation that mimics the pH and salt content of the small intestine. Operating at −0.25 V, the biosensor responded linearly to glucose concentrations between 50 μM and 1 mM, with a detection limit of 10.4 μM. Sensitivity reached 34.4 μA mM⁻¹ cm⁻² when normalized by electrode area.
The enzyme’s affinity for glucose, measured by its Michaelis constant, was 0.35 ± 0.08 mM, indicating that glucose oxidase retained its normal activity within the hydrogel.
Selectivity tests examined whether other compounds in intestinal fluid might interfere with glucose measurements. Fructose, galactose, uric acid, dopamine, lactate, and several other substances produced signals less than 0.8% of the glucose response. Ascorbic acid showed higher interference at 4.3%, but this level remained acceptable for practical sensing.
The biosensor maintained at least 95% of its initial activity after 20 hours of continuous operation and retained 90% response after 30 days of storage at 4 °C.
Polydopamine played a critical role in enzyme retention. Comparative tests showed that plain calcium-alginate hydrogels released 95% of their enzyme payload within six hours. The polydopamine-containing version lost only about 12%. The catechol groups form chemical bonds with amine groups on the enzyme surface, anchoring the protein in place and preventing it from washing out.
Mechanical testing revealed that incorporating glucose oxidase substantially stiffened the material, with tensile strength reaching approximately 14 MPa and Young’s modulus measuring about 65 MPa. Wide-angle X-ray scattering confirmed that calcium crosslinking introduced semicrystalline domains while the overall structure remained intact. Biocompatibility tests using Caco-2 cells, a laboratory model of intestinal lining, showed no significant toxicity after 24 hours of exposure.
The study represents a proof of concept rather than a finished medical device. Testing occurred in simulated fluids, not living animals or humans. Practical ingestible sensors would require solutions for wireless data transmission, onboard power, protective packaging, and predictable transit times through the gut.
The researchers suggest that such sensors could eventually be integrated into capsules that monitor glucose during digestion and communicate with external devices. They also propose pairing sensors with drug-release systems capable of dispensing SGLT1 inhibitors or other glucose-modulating agents in response to detected spikes, enabling treatment tailored to individual responses.
What this work establishes is that the fundamental electrochemistry of biosensing can function in an entirely edible format. A soft, biodegradable hydrogel built from seaweed-derived polymers and mussel-inspired chemistry detected physiologically relevant glucose levels under intestinal conditions. For the field of ingestible bioelectronics, that demonstration removes one significant barrier on the path toward devices that could monitor metabolism from within.
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