Chemist developing kaleidoscope of fluorescent sensors for everyday use.
Q: Your research focuses on fluorescent dyes, which seems like a rather niche area. Why did you decide to specialise in this field?
I actually started my academic career with research in chemical biology, and spent seven years at New York University researching this area.
I used a collection of chemicals to conduct screening in order to find biologically active compounds that potentially could be made into drugs to treat diseases. But I realised that I was competing directly with biologists and biochemists to study how these compounds worked.
Also, after academicians identified these compounds, big pharmaceutical companies would take over in developing the drugs and I realised that I did not have as much say in the end product as I wanted.
But during the course of my chemical biology research, I was fascinated by fluorescent dyes that were used to visualise live biological
systems and found that they can be extremely useful in identifying cell types or probing small molecules known as metabolites in the cells.
I also realised there are not enough fluorescent sensors or probes available to choose from, so I decided to venture into this field.
Q: So why are fluorescent compounds important?
Fluorescent compounds are widely used due to their high sensitivity. They also make things easy to find. Many fluorescent sensors have been developed so far for almost every possible specimen, from specific genes to small ion detection, but most of them are used only in the lab, with the help of professional machines.
I want to develop fluorescent sensors that can be used in our daily lives, without any machine.
When you shine a green laser light into a caffeine sensor mixed with a drop of your coffee, for instance, it can be used to identify caffeine in a drink by showing a strong orange colour, so that when you order decaffeinated coffee for an evening meal, you know you get the right thing and can go to sleep.
Such compounds can even be used to identify date rape drugs in drinks very discreetly.
In medical research, fluorescent compounds are used to identify, say, neural stem cells. Scientists hope to preserve such stem cells so that they can help repair the neural system in the event of a neurological disorder or accident.
Q: You have amassed a library of 10,000 fluorescent compounds in seven years, one of the world's largest. How did you manage to do that, why do you need so many colours, and do you have a favourite?
We adopted solid phase chemistry, which is more efficient than the usual method making fluorescent dyes involving chromatography. Solid phase chemistry has been used widely for the synthesis of drug candidates, but has not been fully optimised for fluorescent dye synthesis. We are the pioneer in this route to construct, arguably, the world's largest fluorescent dye library.
Personally, I love the deep orange colour of 590 nanometres wavelength.
Q: What are some key innovations you have made in fluorescent compounds?
Most of the known fluorescent sensors are made to home in on known targets or analytes. That means, if there is no information about the target, there is no way to develop sensors.
In our approach, we make fluorescent molecules without asking what the target is. This approach is uniquely powerful for complex systems, such as live cells or chemical mixtures. Different cells may have hundreds of different reasons why they are different. We use the whole cells for screening for differences, rather than asking why or how they are different.
Q: Out of your 10,000 compounds, how many are used now?
All of them have been tested against many targets, including DNA, RNA - a nucleic acid present in all living cells, antibodies, fructose sugar, caffeine and date rape compounds. Also, these compounds have been tested against many cell types, such as muscle cells and certain stem cells.
Q: You developed fluorescent compounds that can detect the date rape drug GHB and one which can be used to decipher the amount of fat in milk. Can they be used in real-life settings?
Yes, but all the fluorescent compounds could be potentially toxic. So, we do not recommend adding the sensor directly into your drink. Instead, you may put drops of your drink into the sensor to check it.
Sensor development usually ends as an academic publication or is for research purpose only. I want to make sensors that have applications in real-life settings. For this, the materials should be relatively inexpensive to create and the detection should be done within a short time.
The sensors for caffeine and date rape drugs created a lot of interest from all over the world. Fat content in milk is the primary quality indicator and, currently, heavy equipment is needed to test the amount of fat present in milk.
In India, milk is an important source of nutrients, and more than half of the milk business is owned by small-scale business people, who do not have proper equipment to test milk quality. We hope to develop a handy and affordable device to help small-scale farmers or dealers to check milk quality easily.
In principle, we could also develop a fluorescent compound to detect melamine, given the milk scandal in China in 2008.
Q: You came to Singapore in 2007 as you heard that it has a good academic environment. How does this compare with the United States, where you were based for seven years?
In the United States, research is led mainly by a sense of academic curiosity, and thus creativity and uniqueness are more valued. However, the research funding situation faced a downturn around the time I moved to Singapore and it seems the situation has not fully recovered yet.
In Singapore, research appears to be more driven by application and industry, with results being expected down the road. But this is also understandable, as Singapore has a smaller pool of researchers and you want to get a fair amount of usable discoveries from what you invest in. Each system has its pros and cons.
Q: What do you do in your spare time?
I enjoy traditional Korean farmers' drumming called Sa-mul-no-ri.
I started Korean drumming when I was a college student at Pohang University of Science and Technology in South Korea, and continued in a student cultural club in New York University.
Since I moved to Singapore, I have joined a Korean drumming club in Yio Chu Kang Community Club.
The former South Korean ambassador to Singapore Oh Joon invited me to dinner in my capacity as a scientist a few times and I was unable to attend. However, there was one time when I shook hands with him after I performed Korean drumming at an event. I wonder if he knew it was me.
I also hit the gym twice a week with my post-doctoral researchers. It's important to establish a sense of camaraderie with them, as better team spirit contributes to better research.
Q: What is the next big thing you are working on?
We are developing fluorescent probes which can visualise healthy neurons or nerve cells, pancreatic beta cells which make insulin, and inflammatory atherosclerosis, a vascular disease. Currently, we do not have a non-invasive way to detect them in the human body.
By converting the fluorescent probes into positron emission tomography (PET) probes, which use a radioactive substance to trace diseases in the body, my dream is that the specific cells can be easily detected and visualised accurately and non-invasively, without surgical procedure.
This article was first published on Jan 18, 2015.
Get a copy of The Straits Times or go to straitstimes.com for more stories.