Going Native with Microfluidics

If you think about how (bio)therapeutics work, you will immediately note that interactions – either between proteins or proteins and other molecules – are key. Those interactions are enabled by the protein’s conformation, which not only imbues each protein’s unique functionality but can also change depending on the conditions in which it exists. We now acknowledge that proteins do not function alone and, therefore, should not be considered as isolated entities, but as part of complex networks that ultimately drive biological systems.

Now, let’s think about how we analyze proteins. Does the protein typically exist in its native state when we study it? Are we getting a “true picture?” Techniques that rely on denaturation or digestion – or where the molecules must interact with a surface or matrix (or are fixed to a surface) – affect protein conformation (or the ensemble of conformations), which means that we are actually testing a proxy of the native solution-state protein. Indeed, the dominant techniques for measuring protein-protein interactions, such as surface plasmon resonance (SPR) or bio-layer interferometry (BLI), rely upon fixing a protein to a surface to detect binding to an interaction partner, and thus may not be an accurate representation of the interaction in the biological system.

This is the challenge we want to address at Fluidic Analytics. We want to study protein interactions with as little interference as possible. In the pursuit of this challenge we investigated the use of microfluidic technology. But first, a little background.