A new study has introduced a "lab on a contact lens" that can measure the neurotransmitter serotonin in tears, potentially providing a noninvasive method to analyze stress levels. Yangzhi Zhu, director of the biomedical device center at the Terasaki Institute for Biomedical Innovation in Los Angeles, stated, "Tears could become a practical, noninvasive source of biochemical information that can be measured repeatedly over time." Current biomarker testing often relies on blood draws or isolated laboratory measurements, which provide only snapshots of biochemical changes. This new wearable platform could allow for continuous monitoring in everyday settings.
Stress is associated with various disorders, including depression and schizophrenia. Traditionally, stress is measured through subjective questionnaires or diaries, which can complicate accurate evaluations. The researchers aimed to create a device that measures serotonin levels to provide a more objective method for gauging stress.
Serotonin, known as a "feel-good" hormone, is primarily found in the digestive tract, blood, and nervous system, with small amounts present in tears. The scientists investigated whether tears could serve as a noninvasive and accessible means to analyze serotonin levels. Zhu noted that due to the low concentrations of serotonin in tears, "a sensor needs to be extremely sensitive while still distinguishing serotonin from other molecules in tears."
The research team developed soft, reusable hydrogel lenses that incorporate flexible biocompatible graphene and silver electrodes arranged in serpentine patterns to withstand repeated deformation. A compound called ferrocene was bonded to the graphene to enhance serotonin detection.
In laboratory tests, the smart contact lenses detected serotonin concentrations as low as 72-trillionths of a mole per liter, significantly below the average concentration of serotonin in human tears, which is approximately 15-billionths of a mole per liter. The lenses also demonstrated durability, functioning effectively after more than 28 days of repeated manipulation.
The researchers conducted tests using tears from 10 volunteers before, during, and after performing stressful tasks, such as public speaking and math challenges. Results indicated that serotonin levels in tears decreased with increased stress.
Additionally, the lenses were tested on an anesthetized live pig, where they successfully detected serotonin in artificial tears containing 50 and 100 nanomolar levels of the hormone without causing infection or irritation. Zhu remarked, "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."
The lenses were connected to readout equipment via soft flexible nickel wires. The team has also developed a proof-of-concept wireless version of the lens that includes a miniaturized near-field communications (NFC) chip and stretchable antenna for battery-free sensing and smartphone data transmission. However, further optimization, safety testing, and validation are necessary.
Wei Gao, a professor of medical engineering at the California Institute of Technology who did not participate in the research, commented, "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."
In additional tests involving mice, the researchers observed that serotonin levels decreased in both the blood and tears when the animals were subjected to stress. This suggests that tears may provide a noninvasive method to assess blood serotonin levels, although more research is required before clinical applications can be realized.
Zhu emphasized the need to understand how tear serotonin varies across different individuals, times of day, stress conditions, ocular surface states, and disease conditions, and how these measurements correlate with blood biomarkers and clinical assessments.
The researchers also measured cortisol, a stress hormone, during their tests. Zhu noted that while cortisol reflects immediate stress responses, serotonin provides insight into long-term stress effects. He expressed interest in expanding the technology to analyze multiple molecules simultaneously for a more comprehensive understanding of a person's physiological state. The long-term goal is to create a comfortable, wearable platform that can continuously track biochemical changes in daily life.
The findings were published on 16 September in the journal Science Translational Medicine.