By combining zwitterionic chemistry with nanomaterials, researchers have created a self-cleaning biosensor coating that keeps drug monitors accurate inside the body’s toughest environments.
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The research team has developed a nanostructured antifouling coating that dramatically improves the performance and stability of the electrochemical aptamer-based (E-AB) biosensors used to monitor vancomycin, an antibiotic.
Published in Nano Today, the study presents a hybrid surface built from poly-sulfobetaine methacrylate (SBMA) and polydopamine (PDA), and applied to an electrode composed of gold nanoparticles and Ti3C2 MXene, an advanced 2D material known for its conductivity and high surface area.
Biofouling Remains a Barrier in Sensor Tech
Biofouling is the accumulation of proteins, cells, and other biological material on sensor surfaces and is one of the biggest issues preventing the successful use of biosensors in real-world clinical and wearable applications.
Hydrophilic coatings, polymer brushes, and other such antifouling approaches can limit long-term stability and, in some instances, can interfere with electrochemical signal transduction.
Zwitterionic polymers, including SBMA, could be a solution. Their balanced positive and negative charges create a superhydrophilic hydration layer that resists unwanted adsorption. When combined with PDA, which acts as a bioadhesive and platform for polymer grafting, the result is a stable, high-performance surface that resists biofouling while preserving sensor sensitivity.
A Hybrid Nanostructured Coating
To construct the zwitterionic coating, researchers first electrodeposited gold nanoparticles onto the sensor surface, then layered them with Ti3C2 MXene to form a highly conductive, rough substrate. This nanostructuring increased the effective surface area and provided more sites for stable coating attachment.
Next, a PDA layer was formed through mild oxidative polymerization, enabling strong adhesion to the gold/MXene surface. Once this step was carried out, SBMA was grafted onto the PDA matrix, producing a dense, uniform zwitterionic coating that repels fouling agents while maintaining electrochemical accessibility.
The sensor was functionalized with a vancomycin-specific aptamer and tested using cyclic voltammetry and square wave voltammetry. It was then exposed to complex biological matrices, including milk, blood, serum, and artificial interstitial fluid (ISF), to assess performance.
The results were notable: in BSA- and serum-spiked samples, the coated sensors exhibited less than 8.5 % signal drift over 24 hours of continuous electrochemical interrogation, compared to over 27 % for uncoated controls.
When tested in tissue-mimicking phantom gels and ex vivo porcine skin, the sensors maintained more than 90 % of their initial signal, demonstrating performance in physiologically relevant conditions.
Outperforming PEG and Withstanding Wear
As a control, the researchers tested the new coating against polyethylene glycol (PEG), a widely used antifouling material. While both coatings showed similar sensitivity, the SBMA@PDA coating displayed greater resistance to hydrolytic degradation and signal loss over time.
Mechanical tests underlined the coating’s resistance. When integrated into a wearable microneedle patch designed for ISF sampling, the coated sensors withstood repeated insertions into tissue without significant loss of function. The high surface-to-volume ratio of the nanostructure also supported rapid, sensitive vancomycin detection at clinically relevant concentrations.
To evaluate selectivity, the team exposed the sensors to high concentrations (10×) of potential interferents, including cortisol, dopamine, and flucloxacillin. The coated sensors showed minimal cross-reactivity, and readings taken were consistent. The sensors’ accuracy was further verified by comparing results in artificial serum to those from a commercial ELISA test, with strong agreement observed.
Conclusion
By combining gold nanoparticles with MXene and layering them with a stable SBMA@PDA copolymer, the researchers have created a durable platform that supports accurate, continuous detection of vancomycin and potentially other drugs.
Compared to PEG-based surfaces, their novel coating demonstrates superior long-term antifouling performance. Although the technology has not yet been tested in vivo, its success in simulated biological environments, including blood and skin, is an important step toward future clinical translation.
Embedding such coatings into wearable devices like microneedle patches could enable real-time, personalized drug monitoring, helping clinicians adjust dosages based on immediate physiological feedback.
Journal Reference
Duan H., et al. (2025). Antifouling zwitterionic coating enhances electrochemical aptamer-based sensors for therapeutic drug monitoring. Nano Today, 66, 102892. DOI: 10.1016/j.nantod.2025.102892, https://www.sciencedirect.com/science/article/pii/S1748013225002646