A chip laboratory for the screening and sorting of T cells

Currently, bringing two cells into contact with each other to study their binding properties is a difficult and tedious process. However, this is a necessary step in understanding how cells interact in hopes of finding new cancer treatments, especially cell-based cancer immunotherapies. EPFL researcher Clémentine Lipp's new technology brings a significant improvement in this area by combining two different trapping technologies in one chip-lab system, enabling high-throughput analysis of key cell-cell interactions. The results of their work were published in the journal Lab On A Chip and selected by the journal as a «hot article for 2023».

«When I tell people what I do, the easiest thing to explain is that I create a speed dating environment for cells», Lipp says. And while this may sound like a half-joke, the analogy is very apt. Understanding how cells interact is critical to many scientific endeavors, and accelerating this process will likely accelerate entire fields of study.

Specifically in cell therapy, cancer researchers are looking for T cells that can respond to and destroy tumor cells. For a T cell to trigger an immune system response, it must attach to the tumor cell via its specialized receptor, a parameter known as the adhesion state. Until now, individual cells or cell populations had to be manually brought into contact with each other in a microscopic environment that was difficult to manipulate. The new microfluidic device, on the other hand, allows independent monitoring of these two cell types and has the potential to revolutionize cell screening for T cells and other applications.

In a microfluidic device, also known as a lab-on-a-chip, cells are placed in a maze of microscopic channels and propelled through the pathways using fluid flow. These miniature laboratories, which first appeared in the 1980s, offer many advantages over traditional methods: they are faster, smaller, customizable, more precise, and allow for automation. To study the interaction of cells with fluids and other cells, the cell or cells must be held in a specific location. To screen T cells in such a device, researchers would need to capture both the T cell and the tumor cell without damaging the cell - a feat that has not been possible to date and has so far excluded T cell screening from the benefits of lab-on-a-chip technology.

What's new about Lipp's device is that it brings T-cell screening into the world of microfluidics by combining two trapping methods: one based on planar hydrodynamic trapping of cells and another based on dielectrophoretic (DEP) trapping. These hydrodynamic traps rely on microscopic holes that trap the cell by changing the pressure in the fluid environment - imagine gently sucking a baseball with a vacuum hose to hold it in place, only a thousand times smaller. DEP trapping, on the other hand, is a completely different technology that exploits the polarity of a cell to electrically trap it by switching electrodes on and off. Both capture techniques require microfabrication and are impressive examples of precision microengineering.

The combination of these two different capture systems allows independent manipulation of cells in the microfluidic device and provides spatial and temporal control over their contact. As a result, various adhesion studies can be performed on the chip, making it a versatile tool for various immunological studies. The new microfluidic chip is designed to maintain cell integrity and receptor functions, paving the way for the development of higher throughput devices through automation. Combining this technology with automation should lead to faster and more cost-effective screening and sorting of T cells, making cell-based immunotherapies more accessible and widely applicable.