Using Microfluidic Devices for Gene Therapy

At Carnegie Mellon University, researchers are engineering cutting-edge micro- and nanoscale technologies that interact with living cells in unprecedented ways. Using microfluidic chips inspired by computer chip manufacturing, they manipulate viscoelastic, non-Newtonian fluids to stretch cells and create nanoscale openings—all without physical contact. This allows DNA and proteins to enter cells safely and efficiently, opening the door to faster, safer, and more affordable gene therapies like CAR-T. By blending complex fluid mechanics with biomolecular engineering, the team aims to democratize the future of medicine—and train the next generation of innovators along the way.


Topics:
Medical

Transcript

00:00:08 Our group is developing microscale and nanoscale  technologies that interact with living systems in   new ways. We develop microfluidic devices that  we make using technology that was originally   developed by the microelectronics industry  to make computer chips. And in those devices,   we take advantage of the surprising fluid  mechanics of viscoelastic flows and non-Newtonian   flows. One thing that's challenging about this  research is that we're interested in phenomena   that occur on timescales that are too short to see  with regular microscopes. So we're also developing   new optical techniques to understand what's  going on inside of our microfluidic devices.   One project that's going on in our lab right now  is that we're developing an approach to perform a   type of surgery on millions of individual cells  within seconds. We've developed a microfluidic   chip, which takes advantage of the non-Newtonian  fluid mechanics of viscoelastic solutions to  

00:01:11 stretch cells within a microfluidic device without  ever touching the cell with a solid surface. This   allows us to tear nanoscale holes in the membrane  of the cell, and those holes allow biomolecules   like DNA and proteins to diffuse into cells,  and then they reseal within a few seconds so   the cells can continue to survive. To paraphrase  William Gibson, "The future of medicine is already   here. It's just not evenly distributed." One of the major goals of our work is to improve   the safety and accessibility of gene therapies.  Gene therapies are a new type of medicine that   involves making changes to the DNA of some  particular cells in our bodies with the goal   of treating a disease. And they're tremendously  exciting because they have the potential to treat   disease at its source. However, they're also the  most expensive medicines ever produced. One of   the reasons these therapies are so expensive  is because they're also extremely complex to  

00:02:14 manufacture. One area that we're hoping to have  an impact in the near term is in the manufacturing   of a type of gene therapy called CAR-T. CAR-T is a therapy where the patient's T-cells,   a type of immune cell, are isolated  from their blood, and then genetically   modified to express a new gene that will  target those cells to treat a disease.   We want to have an impact on reducing the cost and  also increasing the safety of CAR T therapies. One really exciting thing about working on  these problems here at CMU is that we have   experts both in complex fluid mechanics  and also in biomolecular engineering.   So I think it's a really exciting time to be  working on these problems in this area, and I   think it's going to make for a really excellent  training environment for our students as well.