New biomimetic design offers extended in vivo monitoring of blood chemistry, overcoming long-standing challenges like biofouling.
Study: A biochemical sensor with continuous extended stability in vivo. Image Credit: Suan Taang/Shutterstock.com
In a recent study published in Nature Biomedical Engineering, researchers unveiled a biomimetic sensor design modeled on the mucosal lining of the human gut. This sensor, which mimics the layered architecture of the intestinal tract, offers a durable and stable platform for continuous biochemical monitoring, even in complex environments like whole blood.
Background
Long-term in vivo sensing in blood has been notoriously difficult due to persistent issues such as biofouling, where proteins, cells, and other biomolecules stick to sensor surfaces, leading to false readings and eventual failure. Many current sensor technologies rely on biological recognition elements like enzymes, antibodies, or aptamers, which are prone to degradation and non-specific interactions.
While solutions like antifouling coatings and microfluidic filtration have helped mitigate some of these issues, their effects tend to be short-lived. Nanostructured biosensors with porous electrodes have shown some improvement in resisting shear forces and minimizing non-specific adsorption, but maintaining sensor performance for more than a few hours or days remains a challenge.
The intestinal mucosa, with its microvilli and protective glycocalyx layer, offers a compelling biological template. This natural structure not only shields receptors from fouling and microbial interference but also supports the sensitive detection of biochemical signals.
The Current Study
Taking cues from this biological system, the team developed a synthetic sensor called the Stable Electrochemical Nanostructured Sensor for Blood In Situ Tracking (SENSBIT). The device features a 3D nanoporous gold (npAu) surface—resembling intestinal microvilli—with pore diameters around 17 nanometers. This allows space for aptamer-based molecular switches while excluding larger interfering molecules.
These aptamers are chemically tailored to bind specific targets, such as the antibiotic kanamycin, and are coupled with redox tags for electrochemical readouts using square-wave voltammetry. To further protect the sensor, a hyperbranched polyethylene glycol (PEG) coating, mimicking the intestinal glycocalyx, is applied to reduce non-specific protein adhesion and immune detection.
The sensor is assembled in a stepwise process: first creating the nanoporous gold scaffold, then functionalizing it with aptamers, and finally applying the PEG layer. In vitro testing involved exposing the sensor to undiluted human serum to evaluate signal stability, sensitivity, and long-term functionality. For in vivo testing, the sensors were implanted in the blood vessels of freely moving rats for more than a week, with continuous tracking of both performance and analyte levels.
Results and Discussion
In vitro, the sensor retained over 70 % of its baseline signal after a full month in complex biological fluids. It produced reliable calibration curves, and the layered design effectively protected the aptamers from fouling and breakdown, which is key for maintaining both sensitivity and specificity.
In vivo results were equally promising. After a week of implantation, sensors maintained over 60 % of their original signal strength. They successfully tracked real-time fluctuations in kanamycin concentrations, delivering continuous pharmacokinetic data even under the dynamic conditions of flowing blood, where traditional sensors typically fail quickly.
The researchers attribute this extended performance to the integrated, biomimetic structure. The nanoporous gold mimics microvilli to enhance surface area and reduce fouling, the PEG layer offers an antifouling shield, and the aptamer switches provide precise target recognition. Together, these elements form a stable and resilient sensing interface.
Conclusion
This work presents a robust, biomimetic electrochemical sensor capable of extended in vivo monitoring of blood-borne biomarkers. Inspired by the natural architecture of the gut lining, SENSBIT combines structural innovation with molecular precision to achieve both sensitivity and long-term stability. The successful tracking of antibiotic levels over days in freely moving animals highlights the sensor’s clinical potential.
Looking ahead, this technology could support real-time monitoring in applications ranging from personalized medicine to chronic disease management, offering a durable platform for continuous, implantable diagnostics.
Journal reference
Chen Y., Fu K.X., et al. (2025). A biochemical sensor with continuous extended stability in vivo. Nature Biomedical Engineering. DOI: 10.1038/s41551-025-01389-6, https://www.nature.com/articles/s41551-025-01389-6
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