A “lab on a contact lens” can measure the neurotransmitter serotonin in tears, potentially offering a novel wearable method to noninvasively analyze levels of stress, a new study finds.

“Tears could become a practical, noninvasive source of biochemical information that can be measured repeatedly over time,” says Yangzhi Zhu, director of the biomedical device center at the Terasaki Institute for Biomedical Innovation in Los Angeles. “Most biomarker testing today still relies on blood draws or isolated laboratory measurements, which provide only snapshots. A wearable platform based on a contact lens could eventually make it possible to follow biochemical changes more continuously and in everyday settings.”

Stress is linked to the development of many disorders, such as depression and schizophrenia. Currently, doctors often measure stress using questionnaires or diaries, but these are highly subjective, complicating accurate evaluations. In the new study, researchers sought to create a device that measured serotonin for a potentially objective method to gauge stress.

Serotonin, often called a “feel-good” hormone, plays a central role in regulating mood. It’s found mostly in the digestive tract, blood, and nervous system, but small amounts can also be found in tears. As such, the scientists explored whether tears might offer a noninvasive, easily accessible route to analyze serotonin levels. However, because serotonin is only present at very low concentrations, Zhu says, “a sensor needs to be extremely sensitive while still distinguishing serotonin from other molecules in tears.”

Zhu and his team fabricated soft, reusable hydrogel lenses encapsulating flexible biocompatible graphene and silver electrodes printed in serpentine patterns designed to tolerate repeated deformation. A compound called ferrocene was bonded onto the graphene to help detect serotonin in a strong, repeatable manner.

The researchers tested these smart contact lenses in lab dishes with commercially available artificial tears that they laced with serotonin. The lenses could detect as little as 72-trillionths of a mole per liter of serotonin, well below the average serotonin concentration in human tears of roughly 15-billionths of a mole per liter. Experiments also showed the lenses could withstand more than 28 days of repeated flipping, folding, stretching, and twisting while staying functional.

The scientists also tested the lenses in lab dishes on tears collected from 10 volunteers five minutes before, immediately after, and roughly 30 minutes after they each performed a pair of stressful tasks—public speaking and math challenges. As expected, serotonin levels in tears fell with increased stress.

In addition, the researchers placed one of their lenses on the eye of an anesthetized live pig for about five minutes. The lens could detect serotonin when the eye was given artificial tears containing 50 and 100 nanomolar levels of the hormone. In addition, the lens caused no sign of infection or irritation.

“We were able to detect very low concentrations of serotonin in tears using a soft contact-lens platform while preserving the transparency, flexibility, and comfort-related properties of the lens,” Zhu says.

When the lenses were used to detect serotonin in the lab and with the pig, the scientists connected the lenses to readout equipment using soft flexible nickel wires. Zhu and his colleagues have developed a proof-of-concept wireless version of their lens incorporating a miniaturized near-field communications (NFC) chip and stretchable antenna for battery-free sensing and smartphone-based data transmission. However, they say further optimization, safety testing, and validation are needed. (Corrective versions of these lenses could also be made, Zhu says.)

Promise for noninvasive biosensing

All in all, “I think the work highlights an exciting direction in wearable biosensing—moving beyond physical signals such as heart rate and temperature toward continuous monitoring of molecular information,” says Wei Gao, a professor of medical engineering at the California Institute of Technology who did not take part in this research. “The eye and tear fluid provide an interesting interface for this because they may enable repeated biochemical measurements without blood sampling.”

In tests where the scientists limited the movements of mice for a few hours per day in order to increase their stress, the researchers found that serotonin levels dropped in both the rodents’ blood and tears to a similar degree. These findings suggest that tears may provide a noninvasive window into blood serotonin levels, but more testing is needed before doctors might use these lenses in medicine, Zhu says.

“We need to understand how tear serotonin varies across different individuals, times of day, stress conditions, ocular surface states, and disease conditions, and how those measurements relate to blood biomarkers and clinical assessments,” Zhu says.

The researchers also measured the stress hormone cortisol in the lab tests of the tears as they used the lenses to measure serotonin. A number of techniques are already being developed to monitor cortisol, such as patches measuring it in sweat or fluid under the skin. Zhu says measuring both serotonin and cortisol can provide complementary information—cortisol measures immediate, short-term responses to stress, while serotonin gives a picture of what a person faces in the long term. He adds that detecting serotonin is also more challenging and shows what they can do with their technology.

In the future, the scientists would like to move beyond measuring only serotonin using their lenses, and to analyzing multiple molecules at the same time for “a much richer picture of a person’s physiological state,” Zhu says. “The long-term goal is to develop a comfortable, wearable platform that can track biochemical changes over time in everyday life.”

The scientists detailed their findings 16 September in the journal Science Translational Medicine.