Caltech engineers look at personalisation of healthcare

These sensors have the potential to be applied to monitor biomarkers in human health, such as vitamins, hormones, metabolites, and medications in real time. This means patients and doctors could continually track changes in the levels of the molecules.

Wearable biosensors incorporating the new nanoparticles have been successfully demonstrated in monitoring metabolites in patients suffering from long Covid and for the levels of chemotherapy drugs in patients based in Duarte, California.

"These are just two examples of what is possible," explained Wei Gao, a professor of medical engineering in the Andrew and Peggy Cherng Department of Medical Engineering at Caltech. "There are many chronic conditions and their biomarkers that these sensors now give us the possibility to monitor continuously and noninvasively.”

Gao and his team refer to the nanoparticles as core-shell cubic nanoparticles. The cubes are formed in a solution that includes the molecule the researchers track, such as vitamin C. As the monomers spontaneously assemble to form a polymer, the target molecule, in this case vitamin C, is trapped inside the cubic nanoparticles. A solvent is then used to remove the vitamin C molecules which leaves a molecularly imprinted polymer shell dotted with holes that shape the molecules - much like artificial antibodies that selectively recognise the shape of particular modules.

In the new study, the researchers combined the specially formed polymers with a nanoparticle core made up of nickel hexacyanoferrate (NiHCF). NiHCF can be oxidised or reduced under an applied electrical voltage when it comes into contact with human sweat or other bodily fluids. With vitamin C, for example, fluid will come into contact with the NiHCF core provided the vitamin C-shaped holes are unoccupied, and this will generate an electrical signal.

When vitamin C molecules come into contact with the polymer they slip into those holes which prevents bodily fluids from making contact with the core, thereby weakening the electrical signal. With this method, the strength of the electrical signal indicates 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," said Gao, who is also a Heritage Medical Research Institute Investigator and a Ronald and JoAnne Willens Scholar.

The new core-shell nanoparticles are highly versatile and can be used in printing sensor arrays that measure levels of multiple amino acids, metabolites, hormones, or drugs in bodily fluids by using multiple nanoparticle links in a single array.

In the published paper detailing the research, 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 that is commonly used to understand how well the kidneys are working. All of the nanoparticles were then combined into one sensor that was mass produced.

The researchers also printed out nanoparticles-based wearable sensors specific to three different antitumour drugs on individual sensors that were then tested on cancer patients at City of Hope in California.

"Demonstrating the potential of this technology, we were able to remotely monitor the amount of cancer drugs in the body at any given time," added Gao. "This is pointing the way to the goal of dose personalisation not only for cancer but for many other conditions as well."

In the paper, the team showed that the nanoparticles can be used to print sensors that can be implanted just below the skin to precisely monitor drug levels in the body.