Deterministic Lateral Displacement as a Means to Enrich Cardiomyocytes for Tissue Engineering

Introduction Myocardial infarction is a condition that affects more than 7 million individuals in the United States. Conventional therapies are limited by the inability of the myocardium to regenerate after injury and the shortage of organs for transplantation. A novel alternative to conventional therapies is the in vitro cultivation of cell-based cardiac grafts that can be surgically attached to the myocardium. The native myocardium (cardiac muscle) is a highly differentiated tissue composed of cardiomyocytes and several other cell types (mostly fibroblasts) along with a dense supporting vasculature and a collagen-based extracellular matrix. Cardiomyocytes, when harvested from the myocardium, can be used to construct cardiac tissue. The state of the art method of cardiomyocyte enrichment involves starting with a heterogeneous suspension of digested donor tissue followed by sequential preplating in culture flasks to allow the more adhesive non-myocyte cells to be depleted from the supernatant. Other than carrying out additional cycles, there are no parameters in the pre-plating enrichment process that can be systematically varied to obtain more efficient and fast separation. Deterministic lateral displacement (DLD) is a microfluidic separation method in which an array of obstacles is created in a flow channel such that particles below a critical hydrodynamic diameter (Dc) flow along a straight path through the channel whereas particles with diameters larger than the Dc are horizontally displaced. A microfluidic DLD approach could be an effective way to isolate cardiomyocytes from non-myoctyes based on size as cardiomyocytes are 17.0 ± 4.0 μm and non-myocytes are 12.0 ± 3.0 μm.