A team of researchers from USC in collaboration with the California Institute of Technology (Caltech) have received approximately $7.8 million from the Advanced Research Projects Agency for Health (ARPA-H) Ocular Laboratory for Analysis of Biomarkers (OCULAB) program to build a medical device that could transform testing and treatment for a range of health conditions. The project, Personalized Automated Continuous Treatment for Eye Plus Systemic Disease (PACE+), aims to develop an implantable system, placed near the eye, that can measure biomarkers in tears to monitor dry eye disease (DED) and automatically deliver medication to treat the condition. The technology uses remote sensing capabilities and could be expanded for use in a range of other diseases, such as cancer, diabetes and neurological conditions.
ARPA-H, an agency within the U.S. Department of Health & Human Services, focuses on rapidly accelerating innovation to solve society’s most pressing health problems. OCULAB, which is led by ARPA-H program manager Calvin Roberts, MD , is focused on the development of a tear-based system that can measure biomarkers of DED and deliver medication for personalized treatment. ThePACE+ project is well positioned to meet this challenge, drawing on longstanding collaborations that unite clinical and biological expertise with advanced biomedical engineering.
The OCULAB approach centers on tears as a diagnostic fluid. Tears contain many of the same biomarkers as blood but are easier to collect. Compared to intermittent blood draws, continuous monitoring of tears can track disease states more chronically with less burden to patients.
“Many people don’t realize how much information is in our tears. Because we can collect this information non-invasively and in real time, it can help personalize the approach to managing and treating a number of health conditions,” said Mark S. Humayun, MD, PhD , director of the USC Dr. Allen and Charlotte Ginsburg Institute for Biomedical Therapeutics and co-director of the USC Roski Eye Institute at the Keck School of Medicine of USC , who is leading the PACE+ project team.
An implant for dry eye disease
In DED, which affects more than 20 million people in the United States, tears do not adequately lubricate the eyes, causing dryness, pain and inflammation. Diagnosing and treating DED involves periodic testing and daily eye drops, which many patients find uncomfortable, inconvenient or difficult to adjust when symptoms change.
Humayun and his team will work to develop a closed-loop system that keeps DED symptoms under control, similar to the way an insulin pump monitors blood sugar and automatically adjusts dosing to keep it stable.
They intend to build a tiny implant, the size of a grain of rice, that can be placed through a small existing opening in the eyelid (corner of the eye) during a quick, painless procedure. A chip inside the implant measures tear biomarkers linked to DED symptoms and sends the data to the patient’s smartphone. The phone then automatically dispatches medication as needed through a second small device, tucked between the eye and lower lid. This helps manage symptoms as they fluctuate without requiring any action from the patient.
The researchers face several technical challenges. Because biomarker levels in tears are typically lower than levels in blood, the system must be highly sensitive. Meanwhile, most existing biosensors can measure markers for days or weeks, but the PACE+ system’s goal is to work for up to six months.
Power and data transfer are also difficult with such a small device. The system may be powered using a biofuel cell, which uses an energy source from the human body, or near-field communication (NFC), which wirelessly supplies power from a nearby device, such as a smartphone. NFC may also be used to transfer data between the implant and the patient’s smartphone.
Building a tear-based device
Over the next 18 months, the researchers will focus on engineering and validating the system. This includes demonstrating in the lab that the sensor can accurately measure DED biomarkers, confirming that the system can be safely positioned around the eye and conducting early tests in preclinical models. If the team meets these milestones, the project is eligible for up to $9.3 million in additional funding.
Beyond DED, the team will also explore whether the system can reliably measure depression-related biomarkers, including serotonin. The technology could someday be used for detecting and monitoring breast cancer, prostate cancer, Alzheimer’s disease, multiple sclerosis, infertility and a number of other conditions with known tear-based biomarkers.
“This has never been done before, anywhere in the world,” said Humayun, who is also the inaugural holder of the Dennis and Michele Slivinski Chair in Macular Degeneration Research and University Professor of ophthalmology, biomedical engineering, and stem cell biology and regenerative medicine. “It’s a moonshot, but it could give us a far better way to monitor and manage some of the world’s most common and serious diseases.”
About this research
In addition to Humayun, the project’s other investigators include experts in dry eye Sarah Hamm-Alvarez and Maria C. Edman from the Keck School of Medicine of USC, University of Southern California; drug development expert Stan Louie from the Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California; and bioelectromagnetics expert Gianluca Lazzi from the Keck School of Medicine and the Viterbi School of Engineering, University of Southern California. California Institute of Technology (Caltech) collaborators include microelectromechanical systems (MEMS) expert Yu-Chong Tai; high-performance, low-power, mixed-mode integrated systems expert Azita Emami; biosensor design expert Wei Gao; and artificial intelligence and machine learning expert Yisong Yue. The project also includes biomanufacturing expert Andrew Urazaki from Urazaki Corp.
This research is funded, in part, by the Advanced Research Projects Agency for Health (ARPA-H). The views and conclusions contained in this document are those of the authors and should not be interpreted as representing the official policies, either expressed or implied, of the U.S. Government.