An interview with Alexandre Persat

Microfluidics is the science and engineering of manipulating tiny amounts of fluids, in the order of femtolitres to microlitres, using networks of channels with dimensions of a single to hundreds of micrometres. It is a truly multidisciplinary field, overlapping between engineering, physics and chemistry. In the past 20 years, it has found application in anything from inkjet printers to DNA chips and micropropulsion.

“People think that it is a new field,” says Persat. “But microfluidics actually dates back to the 19th century, when French physician/physiologist Jean Léonard Marie Poiseuille studied blood flow through capillaries and veins. More recently, in the 1950’s, there were a number of studies in small-scale channels, but today we have the technology to build more complex systems — what we call ‘lab-on-a-chip’.”

But more recently, microfluidics has opened up new avenues in biology and biotechnology. The ability to build tiny networks of channels has allowed scientists to simulate and study the inner workings of single cells, which, we are learning, rely on mechanics for their biological functions more than we had previously suspected. Microfluidics enables the precise control of physico-chemical conditions in the study of a variety of organisms and expands our ability to test their response to different types of stress.

During his studies, Persat was struck at the lack of systmatic studies on how mechanics affect the biological functions of bacteria. The vast majority of studies had focused on the chemistry of their environment, so he now attempted to demonstrate that some of these micron-sized organisms have also evolved the ability to sense and respond to mechanical stimulation. Using a multidisciplinary approach that combines microfluidics, polymer physics and microbiology, Alexandre Persat’s research programme at EPFL will thus focus on the field of bacterial mechanics. This includes mechanotransduction in bacteria, where mechanical signals turn into biochemical signals that lead to cellular responses.

Racing cars, theory, and practice

Of French origin, Persat got his Bachelor degree at the École Polytechnique in Paris. “My background is originally in Physics and Engineering, but I really focused on fluid mechanics. As a teenager, I wanted to optimize Formula 1 cars. I was fascinated by their aerodynamics, the shape of streamlines around the car’s body that you can visualize in wind tunnels. But I quickly gave up on this when I went to engineering school because I got captivated by other things!”

Studying in France was heavy on theory. “There was a lot of math, theoretical physics, which was really a gift as it gave me a strong basis for understanding many problems both in fundamental and applied sciences. But when it came to fluid dynamics, everything was very theoretical. I found myself wanting to do more experimental work. There were many fun experiments to do in small-scale fluid dynamics, particularly in microfluidics and soft-matter physics.”

This is where going abroad helped. “During my final year I did a few months of research in Professor Howard Stone’s Complex Fluids lab at Harvard. There I was able to run a lot of experiments, and I used my background in theory to develop a model that helped us understand our observations. I really fell in love with lab-based work, which I’ve been doing ever since. I mean, theoretical work on a blackboard or on computer simulations is fantastic, but I want to get the thrill of discovery that a concrete experiment can give you. Building a theoretical model that explains your experiments gives you the satisfaction of having understood the underlying phenomena, and helps you design the next experiments. I found that this combination is very powerful and intellectually satisfying. I bet Einstein was frustrated that he could not test general relativity experimentally. It would drive me crazy, so I prefer starting from the experiment - and of course with much more humble problems than his!”

From microfluidics to microbiology

After his degree, Persat went to Stanford to pursued a Master in Chemical Engineering, which continued into a PhD there. “I chose a microfluidics lab. It was great; I started building little devices and I learned new techniques. But I quickly realized that the biggest potential for microfluidics applications lay in biology.”

“I didn’t use microfluidics to analyze biological molecules, which is what most people did with these systems. Instead, I used it to prepare and purify biological molecules, which was new at the time — it is actually still difficult to fish out specific biomolecules from e.g. blood samples, in particular since there is intense effort put into single-cell studies. So I used all my background in physics to design a new microfluidics technique that allows us to pull out DNA or RNA of different sizes from very complex samples — and all in a miniature experiment that uses fluid mechanics and electric fields to move molecules in those fields. Depending on the molecule you’re trying to isolate, you need to combine all these different factors.”

This focus on biology characterized his next steps as a postdoc at Princeton and a Research Fellow at Caltech before joining EPFL’s Global Health and Bioengineering Institutes. “In my research, I use microfluidics to develop new systems for growing biological organisms — much like what Matthias Lütolf is already doing at EPFL’s Institute of Bioengineering with stem cells. But instead, we are interested in bacteria, and particularly pathogens such as Pseudomonas aeruginosa, Vibrio cholerae and others.”

The ultimate aim is to simulate the bacterium’s natural environment. "What most people don’t realize is that when we grow bacteria in the lab, we fail to capture the full biological picture, namely the relationship of their physical environment to their genome. For example, bacteria experience the mechanics of our tissues and flow of fluids as they colonize our intestines. So the aim of my lab is to move away from the traditional agar plate and culture flask, and study bacteria in more realistic contexts — under flow, on different types of surfaces — and make them feel like they are at home. We can really learn a lot from this, and it is particularly critical to explore alternative approaches for studying pathogens since we are now helpless against the rise of antibiotic resistance. We need to examine how bacteria behave in realistic environments so we can develop new strategies to combat the harmful ones.”

Persat emphasizes that his lab is about microbiology, not microfluidics. “We are looking at using engineering to answer specific questions about bacterial behavior. So I want to build a strong, interdisciplinary team, with people from different backgrounds who are passionate and excited about their research, work as a team, and are happy to share and teach their skills. Ultimately, the lab will combine microbiologists, physicists interested in developing new microscopy techniques, materials scientists who will be developing different polymer hydrogels, and engineers who will design microfluidic devices.”

In short, Persat’s future looks as interdisciplinary as his past. “What we do here is kind of high-risk research,” he admits. “I’m open to a variety of collaborations with other groups and have already spoken with several groups across the campus. Overall, I am very excited about EPFL’s rich research community, which is exactly why I came here in the first place."