The ability to continuously monitor the molecular state of our body could be harnessed to help optimize drug delivery or enable early detection of deadly diseases like cancer. For the last two decades, research has aimed to achieve this by developing biosensors that measure chemical or biological reactions within the body and send measurements as a signal that is readable outside the body. While biosensors can now detect tiny molecules, such as drugs, in real time, they work only briefly. There is still no single reliable biosensor that can monitor many different substances in our bodies over long periods of time.
Drawing inspiration from the human gut, researchers at Stanford engineered a modular synthetic biosensor, which they’ve called the Stable Electrochemical Nanostructured Sensor for Blood In situ Tracking (SENSBIT) system. This system’s tests remained fully functional for up to a week when implanted directly into the blood vessels of live rats. Their studies showed that SENSBIT could continuously track drug concentration profiles, with maximum signal efficacy obtained in both live rat models and human serum.
“This work began more than a dozen years ago and we have been steadily advancing this technology,” said Tom Soh, PhD, 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.”
Soh is a senior author of the team’s published paper in Nature Biomedical Engineering, titled “A biochemical sensor with continuous extended stability in vivo,” in which the scientists suggest that their development provides “… a generalizable design foundation for biosensors that can continuously operate in vivo for extended durations…By drawing inspiration from intestinal mucosa that can protect host cell receptors in the presence of the gut microbiome, we develop a synthetic biosensor that can continuously detect specific target molecules in vivo.”
Blood tests represent what the authors describe as a “… cornerstone of clinical care and health monitoring …” but they point out that the vast majority of blood tests are only designed to provide instantaneous measurements at a single point in time. “Compact or wearable sensors that enable continuous measurement of circulating analytes could greatly extend the use of blood-based monitoring by tracking disease states, drug dosing, or metabolic and physiological activity in a wide range of clinical and non-clinical settings,” they suggested. However, they noted, “Many challenges have confounded past attempts at long-term in vivo detection in the bloodstream … The development of biosensors that can detect specific analytes continuously, in vivo, in real time has proven difficult due to biofouling, probe degradation and signal drift that often occur in vivo.”
Over the span of a decade, researchers in Soh’s lab designed a molecular switch that could bind to small molecules of interest in the body to give a readable signal output to continuously measure the molecules’ concentrations. These switches by themselves are prone to degradation due to the body’s natural immune responses, so, to help prevent this issue, in previous work, the team “hid” the switches in nanoporous electrodes. Signals from these electrodes could then measure the drug levels inside the tumor of a live rat for the first time. Despite the effort, this technology still could not last long enough inside an organism, due to immune system attacks.
“We needed a material system that could sense the target while protecting the molecular switches, and that’s when I thought, wait, how does biology solve this problem?” said first author Yihang Chen, who conducted this work while earning his PhD in materials science and engineering under Soh.
Chen and his team took inspiration from the intestinal mucosa, designing the SENSBIT system to mimic the gut’s natural defenses. Like microvilli lining the intestinal wall, the sensor’s 3D nanoporous gold surface shields its sensitive elements from interference while a protective coating modeled after gut mucosa helps prevent degradation. “SENSBIT features a three-dimensional (3D) nanoporous gold surface that emulates the complex structure of epithelial microvilli, sequestering electrochemically modified aptamer switch ‘receptors’ from interferents in the sample matrix,” they explained. “An additional coating of hyperbranched polymer molecules on the porous gold surface mimics the additional protection conferred by mucosal glycans, insulating the sensor against degradation and fouling.” This bioinspired design allows SENSBIT to remain stable and sensitive even after many days of continuous exposure to flowing blood inside living animals.
Tests with the SENSBIT system showed that it retained greater than 70% of its signal after one month in undiluted human serum (the part of the blood that remains after cells and clotting factors are removed) and more than 60% after a week implanted in the blood vessels of live rats. As far as the researchers know, the previous limit for intravenous exposure for this type of device is 11 hours, whereas SENSBIT lasted seven days. “Thus, SENSBIT’s week-long intravenous lifetime exceeds the clinical requirements of 4 days for peripheral intravenous (i.v.) device replacement,” the investigators stated. SENSBIT, they found, could deliver reliable, real-time molecular monitoring in complex biological fluids. “SENSBIT’s resilience and stability even after prolonged exposure to flowing blood and living tissue opens an exciting avenue for the development of biosensors that retain robust performance in vivo for extended periods of time,” they noted.
Our bodies have a very coordinated playbook of what to do when a virus, bacteria, or any other invader tries to disrupt our natural system. If we could understand how the body is coordinating using these molecules, we could potentially pick up infections before any symptoms arise. Using the SENSBIT system is not the only strategy for continuous molecular monitoring, but the researchers suggest it does seem to be significantly better than any similar devices that have been tested in blood. “Collectively, the results suggest that the simple multicomponent sensor design may serve as a general and robust platform for long-term monitoring of blood biomarkers, with durability and stability that exceeds those of previously reported sensors,” the authors concluded.
Continuous molecular monitoring could open the door to a new medical paradigm—one where it’s possible to detect disease earlier, and also, potentially to tailor treatments in real time. “I believe our work contributes to laying the foundation for this future,” Chen said, “and I’m motivated by the opportunity to help push those boundaries forward.” And while noting limitations of their study the team concluded, “Despite the challenges ahead, SENSBIT offers a potential foundation for implantable sensors that could aid precision medicine and health monitoring.”
The post Synthetic Biosensor Monitors Drugs <i>In Vivo</i> Over Time appeared first on GEN - Genetic Engineering and Biotechnology News.
Drawing inspiration from the human gut, researchers at Stanford engineered a modular synthetic biosensor, which they’ve called the Stable Electrochemical Nanostructured Sensor for Blood In situ Tracking (SENSBIT) system. This system’s tests remained fully functional for up to a week when implanted directly into the blood vessels of live rats. Their studies showed that SENSBIT could continuously track drug concentration profiles, with maximum signal efficacy obtained in both live rat models and human serum.
“This work began more than a dozen years ago and we have been steadily advancing this technology,” said Tom Soh, PhD, 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.”
Soh is a senior author of the team’s published paper in Nature Biomedical Engineering, titled “A biochemical sensor with continuous extended stability in vivo,” in which the scientists suggest that their development provides “… a generalizable design foundation for biosensors that can continuously operate in vivo for extended durations…By drawing inspiration from intestinal mucosa that can protect host cell receptors in the presence of the gut microbiome, we develop a synthetic biosensor that can continuously detect specific target molecules in vivo.”
Blood tests represent what the authors describe as a “… cornerstone of clinical care and health monitoring …” but they point out that the vast majority of blood tests are only designed to provide instantaneous measurements at a single point in time. “Compact or wearable sensors that enable continuous measurement of circulating analytes could greatly extend the use of blood-based monitoring by tracking disease states, drug dosing, or metabolic and physiological activity in a wide range of clinical and non-clinical settings,” they suggested. However, they noted, “Many challenges have confounded past attempts at long-term in vivo detection in the bloodstream … The development of biosensors that can detect specific analytes continuously, in vivo, in real time has proven difficult due to biofouling, probe degradation and signal drift that often occur in vivo.”
Over the span of a decade, researchers in Soh’s lab designed a molecular switch that could bind to small molecules of interest in the body to give a readable signal output to continuously measure the molecules’ concentrations. These switches by themselves are prone to degradation due to the body’s natural immune responses, so, to help prevent this issue, in previous work, the team “hid” the switches in nanoporous electrodes. Signals from these electrodes could then measure the drug levels inside the tumor of a live rat for the first time. Despite the effort, this technology still could not last long enough inside an organism, due to immune system attacks.
“We needed a material system that could sense the target while protecting the molecular switches, and that’s when I thought, wait, how does biology solve this problem?” said first author Yihang Chen, who conducted this work while earning his PhD in materials science and engineering under Soh.
Chen and his team took inspiration from the intestinal mucosa, designing the SENSBIT system to mimic the gut’s natural defenses. Like microvilli lining the intestinal wall, the sensor’s 3D nanoporous gold surface shields its sensitive elements from interference while a protective coating modeled after gut mucosa helps prevent degradation. “SENSBIT features a three-dimensional (3D) nanoporous gold surface that emulates the complex structure of epithelial microvilli, sequestering electrochemically modified aptamer switch ‘receptors’ from interferents in the sample matrix,” they explained. “An additional coating of hyperbranched polymer molecules on the porous gold surface mimics the additional protection conferred by mucosal glycans, insulating the sensor against degradation and fouling.” This bioinspired design allows SENSBIT to remain stable and sensitive even after many days of continuous exposure to flowing blood inside living animals.
Tests with the SENSBIT system showed that it retained greater than 70% of its signal after one month in undiluted human serum (the part of the blood that remains after cells and clotting factors are removed) and more than 60% after a week implanted in the blood vessels of live rats. As far as the researchers know, the previous limit for intravenous exposure for this type of device is 11 hours, whereas SENSBIT lasted seven days. “Thus, SENSBIT’s week-long intravenous lifetime exceeds the clinical requirements of 4 days for peripheral intravenous (i.v.) device replacement,” the investigators stated. SENSBIT, they found, could deliver reliable, real-time molecular monitoring in complex biological fluids. “SENSBIT’s resilience and stability even after prolonged exposure to flowing blood and living tissue opens an exciting avenue for the development of biosensors that retain robust performance in vivo for extended periods of time,” they noted.
Our bodies have a very coordinated playbook of what to do when a virus, bacteria, or any other invader tries to disrupt our natural system. If we could understand how the body is coordinating using these molecules, we could potentially pick up infections before any symptoms arise. Using the SENSBIT system is not the only strategy for continuous molecular monitoring, but the researchers suggest it does seem to be significantly better than any similar devices that have been tested in blood. “Collectively, the results suggest that the simple multicomponent sensor design may serve as a general and robust platform for long-term monitoring of blood biomarkers, with durability and stability that exceeds those of previously reported sensors,” the authors concluded.
Continuous molecular monitoring could open the door to a new medical paradigm—one where it’s possible to detect disease earlier, and also, potentially to tailor treatments in real time. “I believe our work contributes to laying the foundation for this future,” Chen said, “and I’m motivated by the opportunity to help push those boundaries forward.” And while noting limitations of their study the team concluded, “Despite the challenges ahead, SENSBIT offers a potential foundation for implantable sensors that could aid precision medicine and health monitoring.”
The post Synthetic Biosensor Monitors Drugs <i>In Vivo</i> Over Time appeared first on GEN - Genetic Engineering and Biotechnology News.