Microfluidic tools for the screening crystallization conditions of monoclonal antibodies*

In the framework of the European research project AMECRYS, we developed microfluidic chips for studying protein crystallization processes. The challenge is to combine membrane-assisted crystallization and mesoporous silica 3D-nanotemplates to enable the crystallization of structurally complex proteins, such as anti-CD20 mAbs (monoclonal antibodies), one of the most important advances in the treatment of lymphocytic leukemia and autoimmune disorders.

We developed original microfluidic devices making use of controlled pervaporation through thin PDMS membranes, to perform high-throughput screening experiments mimicking classical hanging drop experiments. Our devices make possible to control in time the concentration of solutes within multicomponent phase diagrams (protein/salt/crystallizing agent) and allow performing simultaneously analytical measurements. We determine the full phase diagram of crystallization experiments of anti-CD20 in a given aqueous two-phase system.

We also show that the integration of miniaturized Quake valves makes also possible to investigate the possible role of recirculating flows on the growth rate of mAbs crystals.