2015-2016

Engineering Microsystems to Investigate Hematologic Processes and Disorders Towards Clinical Translation

Hematologic processes are frequently comprised of cellular and biomolecular interactions that are biophysical in nature and may involve blood cells (erythrocytes, leukocytes, and platelets), endothelial cells, soluble factors (coagulation proteins, von Willebrand factor, and cytokines), the hemodynamic environment, or all of the above. These phenomena are often pathologically altered in hematologic and thrombotic diseases and are difficult to study using standard in vitro and in vivo systems. With the capabilities to dissect cellular and biomolecular phenomena at the micro to nanoscales with tight control of the mechanical and fluidic parameters, micromechanical and microfluidic systems may provide new insight into key aspects of hematology. For example, the capability of using microsystems to study biology at the single cell level enables the quantitative investigation of how the mechanical and physical microenvironment affects platelet physiology and biophysics. Using micromechanical systems, we have characterized platelet contraction, a poorly understood biophysical aspect of clotting, at the single cell level and have demonstrated that platelet contraction force is not only dependent on microenvironmental mechanical and biochemical cues but may also function as a clinical biophysical biomarker to aid in the diagnosis of bleeding disorders. In addition, using single cell micropatterning techniques to study single platelets, we have demonstrated that platelets sense and physiologically respond to the geometry and physical properties of their microenvironment. Microfluidic systems also enable the quantitative study of hematologic and vascular phenomena under tightly controlled hemodynamic conditions. Using microfluidic techniques, we have developed “endothelialized” microvasculature models to probe the cellular mechanical mechanisms of sickle cell disease and thrombotic microangiopathies and to function as novel hemostasis assays. Finally, microfluidic experiments may lead to reductionist insights that could not be achieved with in vivo animal models alone. For instance, our lab has recently leveraged a microfluidic approach to deduce the multifaceted underlying mechanisms of the in vivo ferric chloride thrombosis model. By developing state-of-the art microdevices to answer hematologic questions, microsystems engineering has the potential to significantly advance our understanding of blood disorders and to develop novel diagnostics and therapeutic targets for patients afflicted with those potentially life-threatening diseases.