Interview with Dr. Jos Quist.
Dr. Jos Quist is an experienced FluidFM user and currently a postdoc at the Nanoionics group at the University of Twente, in the east of The Netherlands. His group is part of the MESA+ institute for nanotechnology, one of the largest nanotechnology institutes in the world. Since early 2014 he has been working with a Nanosurf FlexAFM based FluidFM system in the shared facility of the BioNanoLab, also part of MESA+.
Dr. Quist, can you tell us about your research interests?
In my research I want to interface single living cells with microfluidic probes and chips. This gives me a range of possibilities to perturb cells mechanically, chemically or electrically. Meanwhile changes in the physical and chemical properties of the cell can be monitored. One of my specific goals is to extract and analyze samples from individual cells while keeping the cells alive.
What challenges do you face there?
One major challenge is how to approach a cell with a probe in a very gentle and controlled manner? Of course you can use very precise micromanipulators, but they don’t provide any feedback. You don’t know what forces you apply to the cell.
Another challenge is integration of all the controls and measurements: positioning, fluidics, imaging, electric measurements, force measurements and more.
How does FluidFM help you overcoming these challenges?
The FluidFM technology combines very precise micromanipulation with fluidics and force control. So you have direct and precise feedback on the probes you want to interface with cells or other micro-objects. With FluidFM, you quite exactly know what you are doing to a cell, mechanically.
Also, the FluidFM setup integrates a lot of functionalities with very user-friendly software. I think FluidFM has a promising future regarding the integration of other modes of sensing and actuation, for example electrical probes, which could become relevant soon.
Could you give some examples?
There are so many research questions that remain to be explored with FluidFM. Consider the cell microenvironment. Cells are not isolated and static units, rather they have very dynamic interactions with their environment. With FluidFM, I can construct and modify these microenvironments. For example, it is easy to pick up and position single cells, and thus to create patterns of cells. Next, I can inject a non-fluorescent compound onto or into a single cell, and see it metabolized into a fluorescent compound. I imagine constructing a communication network of individual cells, and then intercepting and modulating the signals.
Single cell force spectroscopy is another application. Very recently I collaborated with John McGrath from the Heriot-Watt University in Edinburgh to measure the deformability of hundreds of Cryptosporidium Cryptosporidium pathogens with FluidFM. I was able to measure over 50 of those “bugs” per hour. We discovered that temperature-based inactivation methods increased the deformability of these pathogens, among other factors.
Do you think FluidFM is also interesting for other researchers? Why?
Sure. Here at the University of Twente the FluidFM system is at a shared facility, the BioNanoLab. One day I may use the instrument for cell microinjection. The next morning a colleague from a different group within MESA+ may use FluidFM for colloidal probe measurements. And an hour after lunch, the instrument may be ready again for spotting or lithography experiments by some external party. So it has very diverse applications and it is very flexible.
How is the situation for a researcher like you in the Netherlands? Where can you get funding for your research?
I enjoy the research culture in the Netherlands. Within a radius of 150 km, you have like 10-15 institutes that are among the 200 best universities in the world. On top of that, you have a lot of innovative biotech and high-tech companies. So I think it is safe to say that you have world-class research and technologies around the corner everywhere. On the other side, getting funding is as competitive as almost everywhere. I am in an early stage of my research career. For me, a “Veni” is the most important grant within the Netherlands. I just submitted an application to combine the FluidFM technology with mass spectrometry for real-time monitoring of many simultaneous biochemical reactions in individual cells. This could truly boost our understanding of the behavior of cancer and stem cells.
Thanks so much for your time, Dr. Quist!
(2016) J.S. McGrath, J. Quist, J.R.T. Seddon, S.C.S. Lai, S.G. Lemay & H.L. Bridle. Deformability Assessment of Waterborne Protozoa Using a Microfluidic-Enabled Force Microscopy Probe. PloS one, 11(3), e0150438. doi:10.1371/journal.pone.0150438