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A grant of $180 million has been allocated to advance equipment for detecting ultra-low levels of disease particles.

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A grant of $180 million has been allocated to advance equipment for detecting ultra-low levels of disease particles.

       In Judith Su’s (Judith Su) Little Sensor Lab (Little Sensor Lab), researchers are working to detect small quantities—even single molecules—of biomarkers ranging from dopants to cancer, Alzheimer's disease, Lyme disease, and even COVID-19.


"Everything we do in our lab revolves around ultrasensitive optical sensors that can be used for a variety of applications, such as environmental health monitoring, food and water quality monitoring, and detection of toxic industrial chemicals," said Su. "If it's worth sensing, we can sense it."


Su is a professor of biomedical engineering and optical sciences and a member of the BIO5 Institute. She has received a five-year Maximizing Investigators' Research Award grant of $182 million from the National Institutes of Health (National Institutes of Health) National Institute of General Medical Sciences (National Institute of General Medical Sciences).


Whispering Gallery Mode Optical Resonators

The core of the Su laboratory is a unique technology called Whispering Gallery Mode Optical Resonators, or FLOWER, which utilizes a phenomenon known as whispering gallery modes. The most famous example of these waves occurs in the form of sound: a whisper at one end of a room with specially curved walls, such as St. Paul's Cathedral in London, can be clearly heard by a friend at the other end. In the case of St. Paul's, the distance exceeds 100 feet.


To detect substances at levels as low as single molecules, FLOWER uses light waves instead of sound, on a much smaller scale (approximately 100 microns), with dimensions about the size of a grain of salt. The device consists of a ring or toroidal structure through which light propagates. Each time the light completes a loop, a small portion extends outside the sensor and interacts with a solution (such as urine, blood, sweat, or water). If the molecule under investigation (also known as an analyte) is present, even in small amounts, it will very slightly change the refractive index of the light. However, because the light interacts with the molecules many times as it circulates around the ring, the change becomes more pronounced, making FLOWER more sensitive than many existing sensing methods.


"Conventional sensors interact with a molecule only once. But in this case, it interacts with the molecule hundreds of thousands of times, so we get this signal accumulation, which enhances our sensitivity," said Su.


In just 40 nanoseconds, light travels around the toroid 240,000 times. This means it travels approximately 68 meters. FLOWER can determine the presence of an analyte within 30 seconds.


Compared to popular sensing methods, FLOWER has several other advantages. Many methods use fluorescent dyes or other chemicals to label analytes and make them visible under a microscope. However, labels that are often expensive and difficult to produce can interfere with particularly small analytes. Furthermore, FLOWER sensors are larger than other sensors, allowing them to cast a wider net to capture trace analytes.


COVID-19, Portable Detection and More

FLOWER can be adapted for various substances and used to address the most pressing issues in the medical community. For example, Su is collaborating with a group at the California Institute of Technology to study COVID-19 drugs. The research team is looking for compounds that bind to specific receptors in the lungs and can resist viruses.


"We are also launching a project to study smell, vapors, and breath," said Su. "There are many molecules in the air that can provide a non-invasive method for testing diseases. For example, a breath test for COVID-19, rather than using swabs or blood tests."


This funding will also help expand the capabilities of FLOWER. First, Su's laboratory intends to improve the sensitivity of the equipment to detect smaller and lighter molecules. In addition, researchers are working to adapt the device not only to detect the presence of molecules but also to detect molecular anomalies or shape changes. To give just one example, the device could help researchers study light-activated proteins in the eye and enhance the scientific understanding of vision. The research team is even integrating artificial intelligence so that the system can continuously improve itself.


Finally, laboratory members are working to miniaturize the system to make it portable and easy to use. Su envisions a smartphone attachment that would enable soldiers to detect contaminants in water, healthcare workers to identify trace diseases, and citizen scientists to test air quality.


"Dr. Su and her team's work is an incredible example of the increasing convergence of the digital, physical, and biological worlds, and why the University of Arizona is poised to lead the Fourth Industrial Revolution to create a bright future for us all," said Robert C. Robbins, President of the University of Arizona. "With the support of NIH, Dr. Su and her team have a tremendous opportunity to develop a portable technology that can be a game-changer in multiple fields."