Printable Molecule-Selective Nanoparticles Enable Mass Production of Wearable Biosensors

The future of medicine is likely to focus on the personalization of healthcare—understanding exactly what an individual requires and delivering the appropriate combination of nutrients, metabolites, and medications, when necessary, to stabilize and enhance their condition. To make this vision a reality, doctors first need a reliable way to continuously measure and track specific biomarkers of health. Now, a team of scientists has developed a method for inkjet printing arrays of unique nanoparticles, which enables the mass production of durable wearable sweat sensors. These sensors could be used to track various biomarkers, such as vitamins, hormones, metabolites, and medications, in real-time, allowing both patients and their physicians to continuously monitor fluctuations in the levels of these molecules. The wearable biosensors incorporating the new nanoparticles have already been successfully used to track metabolites in individuals with long COVID and the levels of chemotherapy drugs in cancer patients.

Scientists from the California Institute of Technology (Pasadena, CA, USA) have termed these nanoparticles as core-shell cubic nanoparticles. The cubes are created in a solution that includes the molecule the researchers aim to track—such as vitamin C. As the monomers spontaneously form a polymer, the target molecule—like vitamin C—is trapped inside the cubic nanoparticles. A solvent is then used to selectively remove the vitamin C molecules, leaving behind a polymer shell with holes that match the shape of the vitamin C molecules, similar to artificial antibodies that specifically recognize the shape of certain molecules.

In the new study, the researchers combine these specially formed polymers with a nanoparticle core made of nickel hexacyanoferrate (NiHCF). This material can be oxidized or reduced under an electrical voltage when exposed to human sweat or other bodily fluids. For instance, in the case of vitamin C, the fluid will come into contact with the NiHCF core as long as the vitamin C-shaped holes are unoccupied, which will generate an electrical signal. However, when vitamin C molecules enter the polymer, they fit into these holes, preventing the sweat or bodily fluids from interacting with the core. This causes the electrical signal to weaken. The strength of the electrical signal, therefore, indicates the concentration of vitamin C present.

The core-shell nanoparticles are highly adaptable and are used in printing sensor arrays capable of measuring multiple amino acids, metabolites, hormones, or drugs in sweat or bodily fluids by utilizing various nanoparticle "inks" in a single array. For example, in the research discussed in the paper, the scientists printed nanoparticles that bind to vitamin C, along with others that bind to the amino acid tryptophan and creatinine, a biomarker commonly used to assess kidney function. All these nanoparticles were combined into a single sensor, which was then mass-produced. These three molecules are of particular interest in studies involving long COVID patients. Similarly, the researchers printed nanoparticles to create wearable sensors specific to three different antitumor drugs, which were then tested on cancer patients. In a paper published in the journal Nature Materials showcasing the new technique, the team also demonstrated that these nanoparticles could be used to print sensors that can be implanted just below the skin to accurately monitor drug levels within the body.

"There are many chronic conditions and their biomarkers that these sensors now give us the possibility to monitor continuously and noninvasively," said Professor Wei Gao, who is the corresponding author of the paper. "Demonstrating the potential of this technology, we were able to remotely monitor the amount of cancer drugs in the body at any given time. This is pointing the way to the goal of dose personalization not only for cancer but for many other conditions as well."

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