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Ana Valero (promotion date: 12 October 2006)

Single cell electroporation on a chip

Promotion Date: 12 October 2006

Ana Valero

Electroporation is a technique to change the permeability of the cell membrane to facilitate transport of drugs or chemicals for instance in and out of the cells. For this purpose, I applied an electric field of a high voltage but for a very short time in order not to kill the cell. The membrane opens up for a short time during which you can insert your chemical or other substance.

We have developed a microfluidic cell trap device to distinguish between various kinds of cells. We have a docking site for the individual cells and through the microscope you can select the cell you want.

What was your thesis about?

Electroporation is a technique to change the permeability of the cell membrane to facilitate transport of drugs or chemicals for instance in and out of the cells. For this purpose, I applied an electric field of a high voltage but for a very short time in order not to kill the cell.

The membrane opens up for a short time during which you can insert your chemical or other substance. We have developed a microfluidic cell trap device to distinguish between various kinds of cells. We have a docking site for the individual cells and through the microscope you can select the cell you want.

So this is not about cells in the body?

No, no. Everything is in a microstructure, a so called lab-on-a-chip.

But then it is a long way from an actual drug delivery application, or isn’t it?

Yes, we still have a long way to go to integrate this in the body. But for the pharmaceutical industry the lab-on-a-chip devices will become increasingly important.

Also in genetically modified organisms the research into electroporation, or rather bulk electroporation is important. But unfortunately the transfection rate, meaning the successful rate with which you transfer a substance (such as DNA) into groups of cells is very low.
This is because electroporation is very cell type specific and every cell responds in different way to the applied electric field.

So for successful gene transfection studies, single cell electroporation on a chip is a great tool and offers big advantages compared to conventional techniques.

What would you do with a cell after it is treated?

We have gone one step further. We did not only transfer DNA in single cells but we also follow the dynamics of the protein that was transferred. We performed this work in stem cells which is important for the differentiation of the cells.

Electroporation is a known technique, how would you describe your specific scientific contribution?

We have developed a chip with which you can address individual cells – you trap them individually and then you can manipulate them individually and study the difference in behaviour according to the modifications you have done.

Is there a lot of manipulation of cells going on in the Lab-on-a-chip group?

I was the first one!

And you are going to continue in this field?

Yes, I will do a post-doc for one more year and will work on electrofusion instead of electroporation. We will melt two cells to make in one. But it is not well defined as yet.

Was it difficult being the first in a group?

Yes, a lot. In the first place we did not have the cell biology people around to tell us how to work with cells, how to keep them alive etcetera. And my background is chemistry so everything was very new. But I still wanted to do it, because I really got very interested in the subject and it is a promising subject too. Compared to this chemistry is boring!! Fortunately within MESA+ I could find the people I needed to get anywhere with this research: the micro machining and that kind of thing that you need for integrating a living cell on a chip.

What did you like best about your research?

There were many options open for the line of research and I could go my own way. They trust you. Furthermore there are plenty facilities available and there is no obvious lack of money that hampers your research. I learned a lot – it was tough but it was a great learning experience.

I had the advantage of being the first in the group, but that at the same time was a disadvantage as well. I really had to find my own way and find the right contacts. To move between various scientific disciplines and to get what you want is not common practice as yet.

And I had to learn about optics, lasers, chemistry, biochemistry, electricity, connectors, micromachining, everything was new! The first two years I had the feeling that I was drowning and was desperate for results.

Did you have somebody to share your frustrations with?

About two years ago there was a great Spanish group within MESA+, and they together also with my colleagues at the BIOS-group have been a great support.

Did you (and do you, because you will stay for another year) enjoy living in the Netherlands?

It was a change, that’s for sure. I had to get used to the very direct way of the Dutch people. At first I found it difficult to get into a group. And also I missed the companionship of other women, there are so few in this university. That is very different in my country where you’ll find far more women in a technical university!

For the summary of the thesis, click here.