Murali Ghatkesar
No two human beings are alike, similarly, no two cells in our body are alike. To understand health and disease at high precision, we need to understand the functioning of every cell in our body. Just like a medical doctor taking a biopsy from a person to understand their health condition, Murali Ghatkesar is taking biopsies from single cells to understand their functional behaviour.
We have now reached the scale of fluid manipulation at which all the magic in biology happens – the cell and the inside of the cell
As a child, Murali certainly liked biology, but he absolutely fell in love with physics. Partly thanks to a PhD in Basel, Switzerland, he found his sweet spot of building tiny mechanical devices that can be used to investigate biological matter at a very small scale. ‘Carving devices out of silicon that are so small that you can only see them under an electron microscope, and then to see that it functions!’ he exclaims. ‘We have now reached the scale at which all the magic in biology happens – the cell and the inside of the cell. If I can contribute to demystify at least one inner workings among the many complex unknowns inside a cell, then I consider my scientific career a success.’
Essential fluids
Having specialised in bio-MEMS – microelectromechanical devices for characterising biomolecular interactions in liquid by mass change – he decided to take the next step: using such devices to directly peer inside single cells. “I am now developing precision probes for scooping out sub-cellular components, which can then be analysed to better understand how cells operate at the molecular level,” he says. “To achieve this, we must really push the precision of nano-engineered tools.” As biology happens inside liquid, he calls his lab the Precision Microfluidics Lab. And TU Delft is a perfect place for him to grow. “It has great facilities, and a big group of people working at the interface of biology and physics.”
Cancer and immunology
Biologists see all kind of breakthrough applications for the tool he is perfecting. Take Ronald Kanaar, radiation biologist at ErasmusMC, who wants to understand DNA repair mechanisms in radiation therapy for cancer patients. “He can fluorescently tag some of the proteins involved in that process, but there are many more unknown molecules involved,” Murali says. “We want to grab this symphony of molecules during the repair process and identify them, leaving the DNA behind. Apart from extracting an extremely tiny sample, there are many challenges, such as the adhesion of the molecules to the DNA.”
In another collaboration he aims to scoop out the ingested bacteria from immune cells, at various moments after they have started digesting these pathogens. “It may ultimately help in developing much needed new ways of immunotherapy. Important, given the growing concerns of antibiotic resistance.”
3D printing
As the channel for the uptake of sub-cellular material is so small, his micro mechanical probes are prone to clogging. “We used to make channels with standard chip technology,” he says. “But the high development costs and long wait times have significantly delayed experiments in pursuit of our scientific dreams. We therefore recently developed a new fabrication method based on multiscale 3D-printing. Instead of several weeks, we can now print a new probe in less than a day!”
Our devices may ultimately help in developing much needed new ways of immunotherapy given the growing concerns of antibiotic resistance.
Cooking up new ideas
His often spends his weekends jogging along farmlands and cooking, giving him the necessary relaxation to brew new ideas in science and take on the challenges of the society. His frontier work in nanofabrication has landed him several research grants, and he has a few more up his sleeve. In one of them, he will build a tiny lab on a chip for processing the minute cell samples, preparing them for further analysis. His research lab currently has a team of 2 Postdocs/2 PhDs/4 Master students/4 Bachelor students. “I spent a lot of my time supervising them, discussing their experimental results,” he says. “Unfortunately, that means I do only little hands-on work myself, nowadays.”
Using multi-scale 3D-printing, we can fabricate new probes in less than a day instead of weeks.