To that end, Caltech engineers have developed a technique for inkjet printing arrays of nanoparticles that enables the mass production of long-lasting wearable sweat sensors to monitor a variety of biomarkers - such as vitamins, hormones, metabolites, and medications in real time - providing patients and their doctors with the ability to continually follow changes in the levels of those molecules.
Wearable biosensors that incorporate the new nanoparticles have been used to monitor metabolites in patients suffering from long COVID and the levels of chemotherapy drugs in cancer patients at City of Hope in Duarte, California.
"These are just two examples of what is possible," said Wei Gao, a professor of medical engineering in Caltech’s Andrew and Peggy Cherng Department of Medical Engineering. "There are many chronic conditions and their biomarkers that these sensors now give us the possibility to monitor continuously and noninvasively."
In a paper published in Nature Materials, corresponding author Gao and his team describe the nanoparticles as core–shell cubic nanoparticles.
The cubes are formed in a solution that includes the molecule that the researchers want to track. As the monomers spontaneously assemble to form a polymer, the target molecule – such as vitamin C - is trapped inside the cubic nanoparticles.
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A solvent is then used to specifically remove the vitamin C molecules, leaving behind a molecularly imprinted polymer shell dotted with holes that have shapes exactly matching that of the vitamin C molecules.
For this study, the researchers combined those specially formed polymers with a nanoparticle core made of nickel hexacyanoferrate (NiHCF). This material can be oxidised or reduced under an applied electrical voltage when in contact with human sweat or other bodily fluids. Returning to the vitamin C example, fluid will encounter the NiHCF core as long as the vitamin C–shaped holes are unoccupied, and this will generate an electrical signal.
However, when vitamin C molecules come into contact with the polymer, they slip into those holes, which prevents sweat or other bodily fluids from making contact with the core. This weakens the electrical signal, the strength of which reveals how much vitamin C is present.
"This core is critical. The nickel hexacyanoferrate core is highly stable, even in biological fluids, making these sensors ideal for long-term measurement," Gao said in a statement.
The new core-shell nanoparticles are said to be highly versatile and are used in printing sensor arrays that measure levels of multiple amino acids, metabolites, hormones, or drugs in sweat or bodily fluids by using multiple nanoparticle "inks" in a single array.
In the work described in the paper, the researchers printed out nanoparticles that bind to vitamin C along with other nanoparticles that bind to the amino acid tryptophan and creatinine, a biomarker commonly measured for kidney health. All of the nanoparticles were combined into one sensor that was then mass produced. These three molecules are of interest in studies of patients with long COVID.
Similarly, the researchers printed out nanoparticles-based wearable sensors that were specific to three different antitumour drugs on individual sensors that were then tested on cancer patients at City of Hope.
"Demonstrating the potential of this technology, we were able to remotely monitor the amount of cancer drugs in the body at any given time," said Gao. "This is pointing the way to the goal of dose personalisation not only for cancer but for many other conditions as well."
The paper also describes how the nanoparticles can be used to print sensors that can be implanted just below the skin to precisely monitor drug levels in the body.
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