S.S. Shevkoplyas
University of Houston,
United States
Keywords: microfluidic cell separation, size-based separation, blood, transfusion, cellular therapy
Summary:
Separation of blood cells from whole blood and blood products is fundamental to modern transfusion medicine and cellular therapies, from routine platelet transfusions to advanced CAR-T cell manufacturing. Centrifugation remains a widely used technology for blood cell separation because it is capable of processing clinically relevant volumes in a reasonable amount of time. However, centrifugation is far from benign and has significant limitations. Pelleting damages the cells and leads to substantial sample losses. Spinning makes ‘closed system’ processing needlessly complicated and scaling of the manufacturing workflows up and out difficult. The need for electricity and expert maintenance increases the cost and reduces availability in resource-limited settings. In contrast, microfluidic separation methods can operate in a continuous flow regime without pelleting, thereby minimizing cell damage and simplifying 'closed system' processing. Their inherently modular designs enable volumetric throughput to be readily scalable through multiplexing. With a compact footprint and low material costs, these devices become portable and disposable, making them ideal for austere environments and enabling straightforward scale-out. Passive microfluidic separation methods are particularly useful because they are typically easier to fabricate and integrate with standard tubing, bags and pumps currently being used in routine medical practice. The significant recent advances in the field suggest that microfluidic devices based on these methods can soon replace centrifugation for blood cell separation, with a potentially transformative impact on blood transfusion and cellular therapy applications. This talk will illustrate this anticipated paradigm shift using three recent examples of applying ‘controlled incremental filtration’ (CIF), a high-throughput microfluidic technology for separating cells by size, to (1) volume reduction and leukodepletion of platelets prior to transfusion, (2) rapid, label-free enrichment of lymphocytes from leukapheresis units in a ‘closed system’, and (3) high-efficiency separation of large leukocytes from undiluted whole blood in the recirculation regime (microfluidic leukapheresis).