Coagulation On A Chip!

by Donna Castellone, MS, MT (ASCP) SH • June 07, 2018

Just when you think you have heard everything, technology comes up with something new. Engineering microvasculature-on-chip models as research-enabling systems for hemostasis and thrombosis was presented at the THSNA meeting by Dr. Wilbur Lam from Emory and Georgia Tech University.

The methodology is based on using microfluidic devices to conduct experiments. This model is similar to a computer chip but has a set of microchannels into which fluids can be perfused using either syringe pumps or hydrostatic pressure. Using this process enables the control of biological conditions to quantitatively analyze hematologic and vascular processes involved in thrombosis and hemostasis.

Studies have also used live culture of endothelial cells enabling this technology to accurately recapitulate and integrate the interactions that occur in vivo among blood cells, endothelial cells and factors in hemostasis. This system then allows the inclusion or exclusion of different cell populations such as platelets, red cells, white cells as well as coagulation proteins or inflammatory mediators. Conducted are mechanistic studies under controlled shear conditions in which cells are incorporated and clot formation can be visualized using brightfield and fluorescence videomicroscopy. Studies conducted using this methodology allow the technology to capture in vitro studies of bleeding and clotting. This can be applied to the discovery of platforms for novel antithrombotic therapeutics. 

The microfluidic technology has made devices hydrogel based or increase functionality by incorporating mechanical components. One example used an interpenetrating poly network with functionality of longer than one month allowing the monitoring of processes that require a longer resolution such as clotting and fibrinolysis. Or using a microchannel with endothelial cells and a micro engineered pneumatic valve that simulated a vascular injury allows for visulation of plug formation and measuring in vivo injury. Limitations of this “clot on a chip system” involve the material and geometric properties of the devices.

One study that used this technology used a microvascular whole blood flow model to determine the impact of the complement system on clot formation which closely interacts with the coagulation system. It is believed the interaction contributes to the proinflammatory and prothrombotic conditions that contribute to the complication of thrombosis in certain disease states. Complement MASP-1 (mannan-binding lectin-associated serine protease-1) activates coagulation factors and promotes clot formation. Previously this was only shown in plasma based systems, this simulation was conducted in a microfluidic system in which blood flows through micro vessels using physiological flow and shear rates, which a chip that allows real time evaluation of clot formation.  This closely resembles human physiology. Specific activators and inhibitors of MASP were added to test effects on clot formation. Results demonstrated that complement activator zymosan led to increased clot formation which was reversed by an anti-complement pathway inhibitor. 

Using this technology has many exciting possibilities in the field of coagulation by recreating what happens in vivo. By adding specific cell populations information can be obtained of their role in hemostasis.