Translating Light Across the Sciences

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• Xochitl Rojas-Rocha- [email protected]

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• Mika Ono- [email protected]

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As a boy, Zhaowei Liu entertained himself by stargazing, curious about how light could cross mind-boggling distances to reach Earth.

Today, Liu's interest in light remains, albeit traveling at smaller intervals. In his laboratory at the UC San Diego Jacobs School of Engineering's Department of Electrical and Computer Engineering, Liu manipulates the physics of light to create new optical materials for more powerful microscopes. His research is helping others surpass technology's current limits to drive discoveries in the biological sciences.

"My interest lies in building better tools," said Liu, an affiliate of the university's Qualcomm Institute (QI). "I think I can have a bigger impact that way."

How to Wield Your Curiosity

As an adult, Liu's curiosity has yielded honors such as a Young Investigator Award from the Office of Naval Research and, in 2023, a National Science Foundation award to create the materials for a groundbreaking microscope in the biological sciences.

As a child, Liu's curiosity led to some cautionary tales.

In elementary school, after learning how the lights in his home were powered by a current running through the thin filament in a light bulb, Liu returned home feeling like he needed more hands-on knowledge. Considering the ceiling light in his family's kitchen, he wondered if he might be able to increase its intensity by replacing the light bulb's filament with something bigger.

With his parents still at work, Liu found what he recalled as a "metal rod" and set a wooden stool on top of his family's kitchen table. He climbed up, unscrewed the lightbulb and touched the rod to the light socket.

The electricity passed through Liu and into the wood of the stool, which insulated him from the worst of the blowback. He woke up on the floor. Aside from the brief loss of consciousness, he was unharmed, if not rattled.

"You see, that curiosity, if you don't use it carefully, it might kill you," Liu said, laughing.

With a somewhat more cautious approach, in high school Liu gravitated toward physics. The field seemed to drive directly at what he found most interesting: the mechanics behind how we perceive and navigate the world around us. He won a competition in his physics class and, with encouragement from his teacher, decided to pursue a physics degree.

'The Basis of Understanding'

To Liu, physics was "the basis of understanding," which he wanted to use to build tools to make advances possible across the sciences. To do that, he also needed to understand why scientists wanted specific tools.

At the time he entered graduate school, Liu says, breaking something called the "diffraction limit" had been the "holy grail" of optics, a branch of physics, for more than a century. Diffraction is a phenomenon in which light waves bend as they pass through an opening like a pinhole. The diffraction limit meant that physicists could sharpen a microscope's resolution to a point, and then no further. The way light behaved simply wouldn't let them.

The problem lay in their materials-namely, glass. As a Ph.D. student in the lab of Xiang Zhang at UCLA Liu learned about artificial materials being engineered with specific patterns to manipulate and concentrate light. Pioneered in part by then-UC San Diego researcher Sheldon Schultz and David Smith, these "metamaterials" promised to change the subfield of optics and bring physicists closer to breaking the diffraction limit.

Liu sensed that the technology could be groundbreaking. By 2000, typical optical microscopes could resolve images as small as 300 nanometers, but anything smaller than that, including viruses, proteins, and individual parts of cells, would remain blurry. Researchers had the option of turning to a high-powered scanning electron microscope, but that required placing their samples in a vacuum, a death sentence for any live samples they wanted to study.

Something needed to be done. Liu devoted to explore optical metamaterials with a particular focus on imaging applications for biological sciences. Biology, he reasoned, was an area he could help others overcome technological barriers to make meaningful advances that would interest everyone.

"I wanted to make something useful," Liu said. "The biggest mystery on our planet is ourselves. If you can build a tool that can assist any discovery related to life, that sounds like a big deal to me."

Freedom to Explore

During his doctoral program, Liu met a high-profile member of the National Institutes of Health (NIH) interested in imaging brain's neural network, or neurons. Without a reliable means of imaging tools, neuroscientists were struggling to test their hypotheses.

Liu was offered a role of principal investigator, or lead researcher, on a study, so long as the NIH could train him for three years. He declined.

Liu declined offers of employment in industry as well. Academia offered the freedom to explore new fields of study in ways he believed he couldn't elsewhere.

Upon joining UC San Diego in 2008, Liu took advantage of that freedom to collaborate across disciplines to design new metamaterials for applications in biological and biomedical imaging, and more. With the 2013 Young Investigator Award from the Office of Naval Research, Liu applied his research to high-speed LED lights for underwater communication.

Previously, in a study published in early 2014 with "Nature Nanotechnology," Liu's team demonstrated that custom metamaterials could increase the blinking speed of an LED by up to 76 times, and increase its intensity by 80 times. Liu cites this research as pioneering work. In the future, he hopes to use this proof-of-concept study to advance LiFi, a WiFi alternative that replaces the radio waves of the wireless internet with light. Currently, LEDs blink too slowly to carry a signal as reliably as the wireless internet. It's a gap that Liu hopes to cover through the advances made by his team.

The Power of Collaboration

Liu's $1 million grant from the National Science Foundation furthers another pioneering angle: the metamaterial-enabled structured illumination microscope, or MESIM, a novel tool based at the UC San Diego Qualcomm Institute with the potential to contribute to interdisciplinary research and education. The MESIM, which unites Liu with researchers with expertise in microscopy, imaging, machine learning and the engineering and biological sciences, uses metamaterials to achieve 10 times the resolution and more than 100 times the measurement speed of current state-of-the-art microscopes. The microscope paves the way for imaging the bonds between molecules without the need for fluorescent markers that can weigh molecules down and skew behavior in live cells.

Liu looks forward to future collaborations. Although he views his research as intrinsically linked to light and microscopes continue to progress in resolution and technique, he sees a future that continues to provide new opportunities for growth and cross-disciplinary work.

"So far, we haven't done the job yet," said Liu. "There are an infinite number of topics I could explore."