Professor of Biomedical Engineering University of Houston Houston, Texas, United States
Background/Case Studies: Platelet (PLT) transfusion is a lifesaving therapy intended to prevent and treat bleeding. However, PLT units contain harmful contaminants which are responsible for virtually all adverse reactions associated with PLT transfusions. PLT leukoreduction (LR) removes leukocytes and large aggregates but is ineffective against smaller contaminants. Volume reduction (VR) of PLT units minimizes transfusion of proinflammatory cytokines, microparticles, and residual plasma proteins, but when performed via conventional centrifugation it activates and damages PLTs, has relatively low PLT recovery, and can be technically challenging to perform in routine practice. Our objective was to develop and validate a simple-to-use, disposable microfluidic device capable of performing both VR and LR simultaneously, while preserving the majority of functional PLTs, to ultimately enable lower-risk, higher-quality PLT transfusions.
Study
Design/Methods: The device utilized microfluidic size-based separation technology called ‘controlled incremental filtration’ (CIF). Two distinct CIF elements (one for VR and another for LR) were designed and optimized individually and then combined into a multiplexed device to enable both LR and VR at high throughput. VR and LR efficiency were evaluated using apheresis PLT units obtained from a local blood center. A complete blood count with 5-part differential was performed using a hematology analyzer on all samples, before and after processing.
Results/Findings: The optimized LR CIF element reduced the residual leukocyte count below the detection limit of the hematology analyzer while recovering 93.0 ± 0.8% of large ( >12 fL) and 91.5 ± 1.0% of all PLTs. The optimized CIF element for VR was able to remove 59 ± 6% of the volume while recovering 93.9 ± 4.2% of large ( >12 fL) and 81.5 ± 5.9% of all PLTs. The multiplexed device consisted of an LR section (comprising 20 LR CIF elements arranged in parallel) connected serially to a VR section (comprising 48 VR CIF elements arranged in parallel). The device prototype was able to process apheresis PLTs at a flow rate of 2.7 ± 0.2 mL/min when placed on a leukocyte reduction stand ~6ft below a suspended PLT unit, and significantly faster ( >5 mL/min) when driven by a peristaltic pump. Conclusions: This work demonstrates the feasibility of purifying PLTs for transfusion in one processing step by integrating both VR and LR functionalities into a single microfluidic device.The device prototype demonstrated performance on par with standard protocols employed clinically, while being significantly simpler. Because of its passive, scalable design, and continuous, flow-through operation, the CIF device could be used in hospital blood banks (driven by gravity) as well as potentially at bedside (using an infusion pump).
