The engineer who speaks the language of medical doctors

In this series, NUS News profiles the University’s Presidential Young Professors who are at the forefront of their research fields, turning creative ideas into important innovations that make the world better.

When she was a PhD student, Assistant Professor Shao Huilin returned to her lab after a two-week holiday to find that her biology experiment no longer worked, although she did it exactly the same way as before. It was mystifying and frustrating. She was forced to troubleshoot it step by step.

Finally she found the problem. She had used a micropipette with a slightly different-sized tip. She could not even see the difference with her eyes, but that was enough to cause the experiment to fail. She learnt not to take seemingly unimportant details for granted.

Now an NUS Presidential Young Professor at NUS Biomedical Engineering under the NUS College of Design and Engineering as well as NUS Institute for Health Innovation & Technology, with a joint appointment at the Agency for Science, Technology and Research (A*STAR), no detail escapes Asst Prof Shao’s eye as she engineers nanoscale devices to detect early-warning signals of disease - so-called biomarkers - in blood samples.

Carving “jewelry” at the nanoscale

Asst Prof Shao’s nanodevices are often made of precious metals like gold and silver, but not because they look nice and shiny. These metals possess unique properties when they are patterned at the nanoscale.

She designs her “jewelry” using powerful computer simulations to find a particular surface pattern that will interact uniquely with specific disease biomarkers.

Then she uses precise lithography, to “print” the pattern, but the “ink” is a powerful electron beam from a sophisticated machine with steel pressure hatches at high vacuum. It can make fine patterns with nanoscale resolution.

A blood sample is pipetted onto the patterned device and a light shone on it - a smartphone LED will do. If biomarkers of the target disease are present, the device will produce light with a unique spectrum of wavelengths in a phenomenon called surface plasmon resonance. It shows not only that the disease is present but also contains lots of molecular information that can guide treatment decisions.

Asst Prof Shao’s work helps to advance biomedical science and translation medicine, one of the eight key focus areas of NUS’ research strategy. Her team’s successful research outcomes also contributes towards the Human Health and Potential domain of the Singapore Government’s Research, Innovation and Enterprise (RIE) 2025 plan.

The adventures of a budding scientist

As a junior college student, she split her time between a project on genes in living cells and another on signal transmission through fibre optics because she knew nothing about the topic and “it sounded cool”.

Soon after, she earned a National Science Scholarship from A*STAR that covered her studies all the way from undergraduate to PhD.

After receiving a double major in Biological Sciences and in Physics from Cornell University, she undertook dual PhD studies in Biophysics at Harvard University and Medical Engineering at Massachusetts Institute of Technology. The PhD training made engineers do full-time rotations in hospitals, as if they were medical students. She had to see patients and conduct medical examinations.

Asst Prof Shao said, “It gave us the right language to discuss medical problems with clinicians, while having the science and engineering background to find new ways to address them.”

She had a once-in-a-lifetime experience being in an operating theatre for six hours and holding a living heart that was undergoing a bypass. She also experienced first-hand the anxiety of patients and their loved ones while waiting for medical test results, which could take weeks. She realised the difference it would make, both medically and emotionally, if serious diseases could be diagnosed more quickly.

She decided to harness her knowledge of physics and engineering to help doctors make faster and better decisions that could mean the difference between life and death.

A “crime scene” at the molecular level

To Asst Prof Shao, biomarkers of disease are like clues at a crime scene. “The secrets to these diseases are already present in the blood. The trick is how to reveal them,” she said.

This approach enabled her lab to formulate the world’s first blood test that takes just an hour to determine how cancer is responding to treatments. The ExoSCOPE test can be conducted 24 hours after treatment initiation, so doctors could adjust the treatment plan to improve the patient’s chance of recovery.

She has also been using her spycraft on COVID-19. Her lab has engineered a molecular switch – a nanostructure comprising an enzyme coupled to a DNA sequence. This molecular switch is highly sensitive to the presence of COVID messenger RNA (mRNA).

When in contact with COVID-19 mRNA from a swab sample, the molecular switch is turned on to activate a cascade of intense reactions, thereby generating strong optical signals that can be detected using a smartphone camera. The procedure takes less than an hour. It is much faster and easier than the conventional polymerase chain reaction test, and just as accurate.

The researchers’ findings were published in the journal Science Advances in March 2021 and Advanced Science in July 2021.

Besides cancer and COVID-19, Asst Prof Shao’s team has also developed a blood test in 2019 to detect Alzheimer’s disease in its early stages. Recently, Asst Prof Shao has also set-up a spin-off company to commercialise the novel technology platforms developed by her team.

Her outstanding scientific achievements were also recognised through various awards, such as the NUS Young Researcher Award in 2021, the Young Scientist Award conferred by the Singapore National Academy of Science (2019) and the L’Oréal-UNESCO For Women in Science National Fellowship (2016).

New opportunities

Asst Prof Shao says the Presidential Young Professorship (PYP) programme encourages research in scientifically riskier but medically important areas, such as neurodegenerative diseases. “PYP brings a strong sense of responsibility to do something meaningful and impactful. It’s a new chapter,” she added.

Her favourite place for hanging out with her lab members and exploring new research opportunities is the NUS Science Canteen, where generations of budding scientists have gone through their rites of passage. And as she enjoys her favourite laksa and chicken rice, which she missed dearly when she was in the US, she is chewing on her next project, trying to figure out, in her own words, “new ways of hacking biology”.

More Proof of Passion stories here.

The NUS Presidential Young Professorship (PYP) scheme supports talented young academics with excellent research track records in advancing their cutting-edge research. More information about the PYP scheme is available here.