The Advanced Research Projects Agency for Health (ARPA-H), an agency within the U.S. Department of Health and Human Services (HHS), has awarded up to $75.8 million to four research teams through its Ocular Laboratory for Analysis of Biomarkers (OCULAB) program. Researchers from Penn State will develop biosensors for the Closed-Loop Sensing and Microdosing for Dry Eye and Systemic Disease Management (COSMIC) team led by Lacristat, a California-based ophthalmology company.
Dipanjan Pan, Dorothy Foehr Huck and J. Lloyd Huck Chair Professor in Nanomedicine and professor of nuclear engineering, of chemistry, of biomedical engineering and of materials science and engineering, will serve as the Penn State principal investigator on the COSMIC team and receive $1.3 million to fund his lab's work on the project for two years. Other institutions comprising the COSMIC team include the University of Miami and the University of Illinois Chicago.
The COSMIC team aims to create nanostructured electrodes that can analyze the biomolecules present in a person's tears to detect signs of dry eye and measure indicators of overall metabolic health as well as women's health. Pan's group will spearhead the development of a tiny biosensing platform that can be inserted into the tear duct to collect data for these electrodes, using molecular elements to detect tear biomarkers associated with inflammation, infection, disease progression and hormonal changes. The electrode system will be designed to work in tandem with an integrated drug delivery module that can supply the right type and dosage of medication in response to fluctuations in tear chemistry.
Research teams from Columbia University, the Massachusetts Institute of Technology (MIT) and the University of Southern California also received funding through OCULAB to "create systems that continuously measure biomarkers in tears and then respond with customized treatment. … The program brings together advances in tiny biosensors, long-lasting eye drug delivery devices, and [artificial intelligence (AI)] to decide how and when to adjust treatment," according to the ARPA-H press release.
"Our work within OCULAB is laying the foundation for a new class of autonomous, precision systems for eye and visual conditions, capable of both diagnosing and treating disease in a continuous, patient-specific manner," Pan said. "My lab's early pioneering works focused on detecting biomolecules in tears, and we are excited to apply our research to the development of a wearable sensing platform that can help manage ocular and systemic complications."
Doctors often determine medication schedules based on blood or urine tests, which provide a snapshot of a patient's health at a single moment in time. However, many cases require close monitoring to follow disease progression, and important changes can be missed if they occur between tests.
Tears could offer a promising avenue for continuous disease monitoring, Pan said. In addition to containing many of the same biomarkers found in blood, tears can be accessed readily, repeatedly and non-invasively without being removed from the eyes. On top of that, tears are clear and water-based, meaning they pose fewer risks to delicate medical equipment compared to blood, which can clot on some surfaces and affect sensor functionality.
The OCULAB teams will aim to develop a tiny closed-loop health system that resides in the tear duct and makes personalized real-time adjustments to a patient's medication.Miniaturized biosensors will detect changes in tear biomarkers and send that information to an integrated drug delivery module, which will release the appropriate therapeutics directly into the space surrounding the eye. This system aims to optimize dosing, minimize side effects and reduce excess drug delivery to irrelevant organ systems, according to Pan.
"With OCULAB, we are completely rethinking how we monitor and treat disease - using the eye as both a sensor and a delivery system," said ARPA-H Director Alicia Jackson in the ARPA-H press release. "That kind of leap, which cuts across biology, nanotechnology, devices and artificial intelligence (AI), all at once, is exactly the sort of challenge only an ARPA can take on. We're not looking for incremental improvements; we're building a new way to see and manage health in real time."
OCULAB will start with a focus on dry eye disease, a common chronic condition that causes pain, irritation and vision difficulty and predominantly affects women. With time, the goal is to use tears for the diagnosis and treatment of various eye, brain and whole-body conditions, providing patients and healthcare professionals with a more complete picture of overall health.
"Imagine the ultimate wearable, a minute sensor in your tear duct, which is unseen and could monitor your wellness, quietly track disease and adjust treatment for you throughout the day," said OCULAB Program Manager Calvin Roberts in the ARPA-H press release. "With OCULAB, we're designing systems that can continuously read the chemistry of your tears and respond with the right therapy at the right moment. This could transform life for people with dry eye disease and open the door to managing conditions like diabetes, depression and neurologic disease in a far more precise and less invasive way."
