Facilitators of Discovery

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Without Yuhwa Lo, traffic lights and car taillights might not have made the switch from incandescent to LEDs until a decade later, NASA’s deep-space communications efforts might have taken a different path, Illumina’s gene-sequencing technology might not have been developed yet, and flow cytometers and cell sorters, cornerstones of the biotech industry, might not have made it to the lab bench.

William S. C. Chang Distinguished Endowed Chair at UC San Diego Department of Electrical and Computer Engineering, Jacobs School of EngineeringDirector of the Qualcomm Institute Nano3 nanofabrication cleanroom facility and its director San Diego Nanotechnology Infrastructure (SDNI)Lo wears many hats.

With a career spanning over 30 years, over 500 published papers, and 55 issued patents (many of which have been commercialized), he is a highly sought-after expert in the electrical engineering and nanotechnology communities.

“I spend more time on other people’s research than I do on my own research, and I spend a lot of time on my own research,” Lo explained, adding that she enjoys learning about other researchers’ work to satisfy her curiosity and think about how their findings might impact her own. “I’m interested in taking the technology out of academia and into the marketplace to help commercialize and integrate science with industry and the local community.”

His career began in semiconductor materials and photonic devices; Lo, along with Raj Bhat, invented direct wafer fusion in 1989, which spurred the industrial adoption of LEDs. This work is now widely regarded as the first study of heterogeneous integration. In about five years, red and amber traffic lights and automotive taillights around the world switched from incandescent bulbs to LEDs, and the switch improved energy efficiency and reliability, Lo said.

A creative mind and an analytical eye

Lo approaches everything she does with a creative, curious mindset and scientific thought process, which is part of what makes her academic and professional career so significant.

This is also what makes him a great cook.

Lo explained that although she did not follow the recipes, she used her scientific knowledge to understand the philosophy of the dish and created a delicious dish.

“I use two basic principles to control the cooking process: optimizing the temperature gradient and optimizing the water gradient of the ingredients,” he said. “Although the spices and flavors will vary from dish to dish, if you properly control the water and temperature gradients of the dish, you will get a good result!”

And compared to research or business ideas that take years and large amounts of money to test, cooking has much lower risk.

“The cost of failure is minimal, and people can be really happy with the outcome,” Lo said. “I love using my creativity and imagination to create things. Cooking, science and engineering provide ample opportunities for this type of mental exercise.”

Transformative technologies

No matter what kind of problem Lo is facing—whether she’s preparing a feast or developing photodetectors that can process single photons for NASA—she starts with one fundamental question: What is the fundamental principle I need to grasp?

For flow cytometers, or devices that measure the qualities and quantities of cells moving through a liquid, their room-scale size in the early 2000s meant they were expensive, difficult to use, and out of reach for many labs. Lo wanted to democratize access to flow cytometry, which is now commonplace in the biotech industry and hospitals around the world.

In 2009, Lo Laboratory flow cytometers scaled down to the world’s first microfluidic benchtop systems. Lo helped commercialize this technology NanoCella San Diego startup he co-founded. A decade later, bioanalytical technology is used by nearly every major pharmaceutical company, some of which are relying on NanoCellect’s products to help develop COVID-19 vaccines.

“We were able to bring flow cytometry into the individual research lab,” Lo explained. “It’s now an extremely user-friendly tool that can be used by graduate students and professionals after just a few hours of training. It’s been truly transformative in the industry as a workhorse.”

Lo now combines NanoCellect’s liquid cytometers with another important biotechnology: microscopy.

Currently, cell observation and cell analysis must be done separately. If a particular cell needs to be isolated for study under a microscope, scientists must use microdissection, which separates the cell from the rest of the group. The slow and expensive process can cause cell damage and is not widely available.

Flow cytometers make it easy to isolate cells, but studying cell morphology and other characteristics is impossible without microscopy. Scientists must choose between cell observation without sorting or cell sorting without observation, Lo explained.

A discovery in his laboratory changed everything.

Lo’s lab has published the first paper showing that flow cytometry and microscopy can be integrated in a highly compact way, allowing scientists to access genomic information while isolating cells. Lo is “very excited” about expanding access to this combination technology, having played an instrumental role in NanoCellect’s launch of VERLO, the world’s first desktop image-guided cell sorter.

His laboratory also developed a new generation system that can produce 3D cell tomography at an unprecedented speed of 1,000 images per second.

Accelerating discovery

Lo also serves as director of the Nano3 facility and SDNI, one of 16 sites nationwide that host the NSF-funded National Nanotechnology Coordinated Infrastructure. He described the facility as “infrastructure providers for the STEM community,” where engineers and scientists help bring nanotechnology ideas to life through research, prototyping and commercialization.

“The measure of our success is the number of users we have helped and the projects we have enabled and supported,” Lo said. Last year, Nano3 helped more than 70 doctoral students complete their theses and was recognized in nearly 200 peer-reviewed publications.

By taking on a supporting role, the center aims to transform projects from the idea stage into the backbone of a successful company.

One of them is Illumina.

Next-generation gene sequencing tools from Illumina, a leader in genomics, have benefited greatly from Nano3, with the company transferring its nanoimprinting process to produce first-of-its-kind gene sequencing flow cells. The supportive, collaborative creative environment at Nano3 and the Qualcomm Institute reflects Lo’s desire to help others succeed in science and beyond.

This passion is also what drew him and Nano3 to be a part of this community. California DREAMS program.

Funded by CHIPS and Science Act 2022The California DREAMS coalition brings together more than 15 university and industry partners to accelerate American microelectronics development and manufacturing. Under Lo’s direction, Nano3 will become one of the Department of Defense’s “lab-to-factory” rapid development facilities that will help scale new technologies and deploy them at higher speeds.

Lo looks forward to the continued collaboration and the chance to reconnect with his semiconductor roots, but at the end of the day, he’s excited to see what new discoveries the alliance will bring.

“As an engineer, my research is not focused on discovery,” he said. “We are inventors and enablers; we build tools with unique capabilities to help scientists make discoveries and accelerate the discovery process.”