New framework aims to improve reliability of tear-based health sensors

Dr. Yangzhi Zhu of the Terasaki Institute for Biomedical Innovation (TIBI), with collaborators at UC San Diego and USC, published a Nature Sensors perspective on what it will take to turn tear-based wearable sensors into reliable, long-term health-tracking tools.

For people with dry eye disease, glaucoma, or other eye conditions, care often relies on occasional office visits and single-point measurements that can miss how symptoms change day to day. Tears are constantly renewed and carry chemical signals linked to eye and, in some cases, whole-body health, making them an appealing target for continuous, minimally invasive monitoring. But according to Zhu and colleagues, sensing devices placed on or near the eye have so far focused mainly on detecting more biomarkers and shrinking hardware, without fully accounting for the fact that tears are part of a constantly shifting physiological process shaped by blinking, evaporation, and fluid turnover.

In Nature Sensors, the team argues that the field needs to treat the tear film itself, not just the biomarkers within it, as central to device design. They propose matching each type of biological signal, such as pH and electrolytes versus larger proteins or inflammatory markers, to the sensing frequency and device format best suited to it. The authors also call for systems that pair chemical sensing with contextual data, including blink patterns and tear flow, to help separate true biological change from normal fluctuations.

The perspective lays out a framework spanning four areas: the biological interface, device performance under real-world wear, clinical translation, and the trust needed for adoption. It also points to smart contact lenses, punctal devices, and periocular patches as complementary formats, each suited to different monitoring needs rather than one design fitting every case.

"Tear film isn't just a source of biomarkers; it's a constantly moving physiological system," said Dr. Chia-Wei Liu, Postdoctoral Researcher at the Terasaki Institute for Biomedical Innovation. "If a sensor doesn't account for blinking, evaporation, and fluid turnover, it's very easy to mistake normal tear-film behavior for a biological signal."

"Our goal is to move the field past counting how many biomarkers a device can detect and toward asking whether the readings can actually be trusted over time," said Dr. Yangzhi Zhu, Principal Investigator and Assistant Professor at the Terasaki Institute. "That means designing sensors and interpretation methods together, not as separate problems."

The authors see dry-eye disease as a natural first proving ground for this approach, given its close ties to tear-film instability and symptom fluctuation, with glaucoma monitoring and metabolic tracking highlighted as additional potential applications. Realizing that potential will require moving beyond short-term wear tests toward longitudinal studies that compare tear-based readings against established clinical measures. The Terasaki Institute continues to invest in translational sensor research aimed at bringing longitudinal, patient-in-the-loop ocular monitoring closer to clinical care.