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To make that possible, healthcare professionals need a way to continuously monitor certain biomarkers. Wearable and implantable sensors offer a way to do that – but until now, scaling up production has been a challenge.
A team of researchers at the California Institute of Technology hope to change that with a new technique for inkjet printing arrays of special nanoparticles, which could be used in mass production of long-lasting wearable sweat sensors. These could monitor biomarkers such as vitamins, hormones and medications in real time, allowing patients and physicians to track changes.
Wearable biosensors that incorporate the new nanoparticles have already been used to monitor metabolites in patients suffering from long Covid, and the levels of chemotherapy drugs in cancer patients.
“These are just two examples of what is possible,” said Professor Wei Gao, corresponding author of a paper describing the new technique. “There are many chronic conditions… that these sensors now give us the possibility to monitor continuously and non-invasively.”
The printed nanoparticles are formed in a solution that includes the molecule that the researchers want to track – vitamin C, for example. As monomers assemble into polymers, the target molecule – vitamin C – is trapped inside the cubic nanoparticles. A solvent then removes the vitamin C, leaving behind a polymer shell dotted with holes that match vitamin C molecules.
In the new study, the researchers combined those polymers with a nanoparticle core of nickel hexacyanoferrate (NiHCF), which can be oxidised or reduced under an applied electrical voltage when in contact with human sweat or other bodily fluids.
In the vitamin C example, fluid comes into contact with the NiHCF core as long as the vitamin C-shaped holes are unoccupied, generating an electrical signal. When the holes are occupied by vitamin C molecules, however, they prevent sweat or other fluids from contacting the core, weakening the electrical signal. The strength of the electrical signal therefore 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,” said Professor Gao.
The new nanoparticles can be used in 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 nanoparticles that bind to vitamin C along with other nanoparticles that bind to the amino acid tryptophan and creatinine, a biomarker commonly measured to see how well the kidneys are working. All of the nanoparticles were combined into one sensor that was then produced at scale. The three molecules are all of interest in studies of patients with long Covid.
The researchers also printed nanoparticle-based wearable sensors that were specific to three anti-tumour drugs that were administered to cancer patients. “We were able to remotely monitor the amount of cancer drugs in the body at any given time,” Professor Gao said. “This is pointing the way to the goal of dose personalisation, not only for cancer but for many other conditions as well.”
The team also showed that the nanoparticles can be used to print sensors that can be implanted just below the skin, to monitor drug levels in the body.
The work was published in Nature Materials.
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