Understanding a single molecule

5 million euro, from Dutch Organization for Scientific Research (NWO), for his outstanding work in biological nanoscience, an important scientific field that many people believe will ultimately fundamentally change the way we live.

“I like to understand things in some depth. And more than understanding how something works I want to understand exactly why it works,” Dr. Serge Lemay says, explaining his switch from applied to fundamental physics. Lemay is a humble man. In his overly tidy office he asserts that major scientific breakthroughs will not come from nanoscientists, but rather from people in other fields who will use the very scientific tools that nanoscientists like him will develop.

Dr. Lemay, a Canadian national, started his career at Nortel in the field of optoelectronics. In order to better understand the principles of this field (quantum mechanics), he decided to pursue a PhD in physics. Departing from this field in his quest to understand why things work as they do, Lemay now has the problem of naming his work: “I have the problem that some of the stuff I do doesn’t have a standard label yet, because it’s very new and very few people are doing it.”

With the Vici you were recently granted, you’re going to try to find ways to detect electrically single molecules. Why is it important to be able to detect single molecules?

“If you eat an entire box of paracetamol, for example, you will die within, say, 24 hours from liver failure. If you currently go to the hospital, a chemical test is done by a specialized analyst who detects the amount of paracetamol in your blood. And he may even not be working that night and has to come over to run a complicated machine. And in the meantime your liver is degrading. The reason that it’s so complicated to detect the amount of paracetamol in your blood is because there are many different compounds in body fluids like blood and urine. By enabling the detection of single molecules, and thus enabling more discrimination, we are trying to see if a quick and simple electrical measurement can be done that would allow quantifying the amount of a specific compound.”

And this is then done by a simple handheld device?

“That’s the dream! Such a device would take as an input urine or blood and display a number that indicates the concentration of paracetamol. We do this by working at the nanometer scale, in order to amplify certain types of electrochemical signals. Essentially, molecules interact at the scale of a few nanometers. Currently, it’s possible to electrochemically detect the level of glucose in blood for diabetes patients. But this is only possible because the concentration of glucose is very high. The idea is essentially to extend this type of analysis to a much broader range of things.”

This research is part of the development of a so-called ‘lab on chip’ technology?

“Indeed, this work ultimately entails miniaturizing chemical labs. The idea is to build silicon chips, but instead of having electronic circuits, we make water circuits. This is basically a small chip where you can have a tiny amount of sample with which you can do a lot of chemical processing very quickly and cheaply. We, the scientific community, have yet to prove how far we can push this, but it’s a technology that is called for in the water purification sector, for example. In some remote area in Northern Africa, say, there is a micro-water purification plant near a well, but there isn’t a lab handy. In such cases you want an easy-to-use technology that can constantly monitor the level of a certain contaminant and sends a warning wirelessly as soon as something abnormal happens.”

After you obtained your PhD in the USA you moved in 1999 to Delft. Are there differences between these two countries in terms of how research at universities is organized?

“In the US, when you start you get your own empty lab and you need to convince investors to finance your research by showing that you’re able to do something useful in that particular area. And this tends to make you conservative. Here, when you start your research is embedded in a larger group that has other scientists who are usually already established. The biggest advantage of the Dutch style compared to the US style is in my opinion that it allows you to take more risks. This depends of course on many things, such as the group you’re working with, but when all the pieces fall in the right place, then I think that it creates more possibilities for more creative ideas and major changes.”

Nanoscience is often heralded as the scientific field of the 21st century. Do you think that nanoscience will, for example, be able to provide a breakthrough in the fight against cancer?

“Often in the press nanoscience is presented as something completely new, which it’s not. It’s a refinement of what already existed. We’re now able to look very closely at matter in completely new ways, but nanoscience cannot do instant wonders. With respect to cancer, for example, nanoscience helps us to study the molecular machines that make our cells tick and to understand exactly how they work. And this may trigger somebody to realize: ‘Aha! Therefore if you want to kill it this is what you must do!’ Contrary to how drugs are currently developed, which is by massive trial and error tests to see if something works, understanding the molecule will ultimately enable us to purposefully design and construct a drug that attacks a particular site at a particular cell.”

For a listing of this week’s Study Breaks, go to: www.delta.tudelft.nl

“I like to understand things in some depth. And more than understanding how something works I want to understand exactly why it works,” Dr. Serge Lemay says, explaining his switch from applied to fundamental physics. Lemay is a humble man. In his overly tidy office he asserts that major scientific breakthroughs will not come from nanoscientists, but rather from people in other fields who will use the very scientific tools that nanoscientists like him will develop.

Dr. Lemay, a Canadian national, started his career at Nortel in the field of optoelectronics. In order to better understand the principles of this field (quantum mechanics), he decided to pursue a PhD in physics. Departing from this field in his quest to understand why things work as they do, Lemay now has the problem of naming his work: “I have the problem that some of the stuff I do doesn’t have a standard label yet, because it’s very new and very few people are doing it.”

With the Vici you were recently granted, you’re going to try to find ways to detect electrically single molecules. Why is it important to be able to detect single molecules?

“If you eat an entire box of paracetamol, for example, you will die within, say, 24 hours from liver failure. If you currently go to the hospital, a chemical test is done by a specialized analyst who detects the amount of paracetamol in your blood. And he may even not be working that night and has to come over to run a complicated machine. And in the meantime your liver is degrading. The reason that it’s so complicated to detect the amount of paracetamol in your blood is because there are many different compounds in body fluids like blood and urine. By enabling the detection of single molecules, and thus enabling more discrimination, we are trying to see if a quick and simple electrical measurement can be done that would allow quantifying the amount of a specific compound.”

And this is then done by a simple handheld device?

“That’s the dream! Such a device would take as an input urine or blood and display a number that indicates the concentration of paracetamol. We do this by working at the nanometer scale, in order to amplify certain types of electrochemical signals. Essentially, molecules interact at the scale of a few nanometers. Currently, it’s possible to electrochemically detect the level of glucose in blood for diabetes patients. But this is only possible because the concentration of glucose is very high. The idea is essentially to extend this type of analysis to a much broader range of things.”

This research is part of the development of a so-called ‘lab on chip’ technology?

“Indeed, this work ultimately entails miniaturizing chemical labs. The idea is to build silicon chips, but instead of having electronic circuits, we make water circuits. This is basically a small chip where you can have a tiny amount of sample with which you can do a lot of chemical processing very quickly and cheaply. We, the scientific community, have yet to prove how far we can push this, but it’s a technology that is called for in the water purification sector, for example. In some remote area in Northern Africa, say, there is a micro-water purification plant near a well, but there isn’t a lab handy. In such cases you want an easy-to-use technology that can constantly monitor the level of a certain contaminant and sends a warning wirelessly as soon as something abnormal happens.”

After you obtained your PhD in the USA you moved in 1999 to Delft. Are there differences between these two countries in terms of how research at universities is organized?

“In the US, when you start you get your own empty lab and you need to convince investors to finance your research by showing that you’re able to do something useful in that particular area. And this tends to make you conservative. Here, when you start your research is embedded in a larger group that has other scientists who are usually already established. The biggest advantage of the Dutch style compared to the US style is in my opinion that it allows you to take more risks. This depends of course on many things, such as the group you’re working with, but when all the pieces fall in the right place, then I think that it creates more possibilities for more creative ideas and major changes.”

Nanoscience is often heralded as the scientific field of the 21st century. Do you think that nanoscience will, for example, be able to provide a breakthrough in the fight against cancer?

“Often in the press nanoscience is presented as something completely new, which it’s not. It’s a refinement of what already existed. We’re now able to look very closely at matter in completely new ways, but nanoscience cannot do instant wonders. With respect to cancer, for example, nanoscience helps us to study the molecular machines that make our cells tick and to understand exactly how they work. And this may trigger somebody to realize: ‘Aha! Therefore if you want to kill it this is what you must do!’ Contrary to how drugs are currently developed, which is by massive trial and error tests to see if something works, understanding the molecule will ultimately enable us to purposefully design and construct a drug that attacks a particular site at a particular cell.”

For a listing of this week’s Study Breaks, go to: www.delta.tudelft.nl