Continuous Molecular Monitoring Biosensor to Enable Early Disease Detection

Continuous monitoring of the body's molecular state could unlock a variety of solutions, ranging from optimized drug delivery to the early detection of life-threatening diseases like cancer. Over the past two decades, research has focused on developing devices capable of measuring chemical or biological reactions in the body and transmitting their readings externally. These devices, known as biosensors, can now detect minute molecules such as drugs in real time, but they typically function for only short periods. Currently, there is no single reliable biosensor capable of monitoring multiple substances over extended periods. Now, researchers have developed a novel sensor inspired by the body’s natural protective mechanisms that can monitor substances continuously for up to a week after being implanted in live rats.

Researchers at Stanford University (Stanford, CA, USA) have engineered a modular biosensor system called the Stable Electrochemical Nanostructured Sensor for Blood In situ Tracking (SENSBIT). This system has been proven to remain fully operational for up to a week when implanted directly into the blood vessels of living rats. In a study published in Nature Biomedical Engineering, the team demonstrated that SENSBIT could track drug concentration profiles continuously. The system achieved optimal signal efficacy in both live rat models and human serum. Over the course of ten years, the Stanford team designed a molecular switch that could bind to specific molecules in the body, generating a readable signal to continuously monitor the concentration of those molecules. However, these switches alone were susceptible to degradation due to the body's natural immune responses.

To address this challenge, the team previously encased the switches in nanoporous electrodes. These electrodes successfully measured drug levels inside the tumor of a live rat for the first time. Despite these efforts, the technology still struggled to survive long-term within the body due to immune system interference. Drawing inspiration from the human gut’s protective mechanisms, the team developed the SENSBIT system to replicate these natural defenses. Similar to the microvilli in the intestinal wall, the system’s 3D nanoporous gold surface shields its sensitive components from interference, while a protective coating resembling gut mucosa helps prevent degradation. This bioinspired design allows SENSBIT to remain stable and sensitive even after extended exposure to flowing blood within living animals.

Upon testing, the team found that the SENSBIT system retained over 70% of its signal after one month in undiluted human serum and over 60% after one week of implantation in the blood vessels of living rats. Previously, the longest duration that similar devices could function intravenously was about 11 hours, whereas SENSBIT lasted up to seven days. This development means SENSBIT can deliver reliable, real-time molecular monitoring in complex biological fluids. The body’s intricate immune response is an effective defense mechanism against viruses, bacteria, and other invaders. By understanding how the body coordinates these responses using molecular signals, it may be possible to detect infections before symptoms appear. While SENSBIT is not the only approach for continuous molecular monitoring, it is a significant improvement over any other similar devices tested in blood. Continuous molecular monitoring could revolutionize medicine, offering the potential not only for earlier disease detection but also for real-time, personalized treatment adjustments.

“This work began more than a dozen years ago and we have been steadily advancing this technology,” said Tom Soh, senior author of the paper and a professor of electrical engineering, of bioengineering, and of radiology in the schools of Engineering and Medicine. “This order-of-magnitude improvement in whole-blood sensor longevity over existing technologies is a huge advancement toward next-generation biosensors.”