The idea of implantable sensors that continuously transmit information on vital values and concentrations of substances or drugs in the body has fascinated physicians and scientists for a long time. Such sensors enable the constant monitoring of disease progression and therapeutic success. However, until now implantable sensors have not been suitable to remain in the body permanently but had to be replaced after a few days or weeks. On the one hand, there is the problem of implant rejection because the body recognizes the sensor as a foreign object. On the other hand, the sensor’s color, which indicates concentration changes has been unstable so far and faded over time. Scientists at Johannes Gutenberg University Mainz (JGU) have developed a novel type of implantable sensor that can be operated in the body for several months. The sensor is based on color-stable gold nanoparticles that are modified with receptors for specific molecules. Embedded into an artificial polymeric tissue, the nanogold is implanted under the skin where it reports changes in drug concentrations by changing its color.
Professor Carsten Sӧnnichsen’s research group has been using gold nanoparticles as sensors to detect tiny amounts of proteins in microscopic flow cells for many years. Gold nanoparticles act as small antennas for light. They strongly absorb and scatter it and, therefore, appear colorful. They react to alterations in their surroundings by changing color. Sӧnnichsen’s team has exploited this concept for implanted medical sensing.
To prevent the tiny particles from swimming away or being degraded by immune cells, they are embedded in a porous hydrogel with a tissue-like consistency. Once implanted under the skin, small blood vessels and cells grow into the pores. The sensor is integrated in the tissue and is not rejected as a foreign body. “Our sensor is like an invisible tattoo, not much bigger than a penny and thinner than one millimeter,” said Sӧnnichsen. Since the gold nanoparticles are infrared, they are not visible to the eye. However, a special kind of measurement device can detect their color noninvasively through the skin.
In their study the researchers implanted their gold nanoparticle sensors under the skin of hairless rats. Color changes in these sensors were monitored following the administration of various doses of an antibiotic. The drug molecules are transported to the sensor via the bloodstream. By binding to specific receptors on the surface of the gold nanoparticles, they induce color change that is dependent on drug concentration. Thanks to the color-stable gold nanoparticles and the tissue-integrating hydrogel, the sensor was found to remain mechanically and optically stable over several months.
Colored objects bleach over time. Gold nanoparticles, however, do not bleach, but keep their color permanently. As they can be easily coated with different receptors, they are an ideal platform for implantable sensors.
This concept is generalizable and has the potential to extend the lifetime of implantable sensors. In the future, gold nanoparticle-based implantable sensors could be used to observe concentrations of different biomarkers or drugs in the body simultaneously. Such sensors could find application in drug development, medical research, or personalized medicine, such as the management of chronic diseases.