Abstract
Leukocyte reduction of donated blood products substantially reduces the risk of a number of transfusion-related complications. Current ‘leukoreduction’ filters operate by trapping leukocytes within specialized filtration material, while allowing desired blood components to pass through. However, the continuous release of inflammatory cytokines from the retained leukocytes, as well as the potential for platelet activation and clogging, are significant drawbacks of conventional ‘dead end’ filtration. To address these limitations, here we demonstrate our newly-developed ‘controlled incremental filtration’ (CIF) approach to perform high-throughput microfluidic removal of leukocytes from platelet-rich plasma (PRP) in a continuous flow regime. Leukocytes are separated from platelets within the PRP by progressively syphoning clarified PRP away from the concentrated leukocyte flowstream. Filtrate PRP collected from an optimally-designed CIF device typically showed a ~1000-fold (i.e. 99.9%) reduction in leukocyte concentration, while recovering >80% of the original platelets, at volumetric throughputs of ~1 mL/min. These results suggest that the CIF approach will enable users in many fields to now apply the advantages of microfluidic devices to particle separation, even for applications requiring macroscale flowrates.
Highlights
A microfluidics-based approach could potentially circumvent these fundamental limitations of conventional LR filters by enabling continuous separation of leukocytes from a stream of whole blood (WB) or PRP, at the micro-scale[18,19]
Unlike other microfluidic separation techniques which utilize simple size-exclusion, the controlled incremental filtration (CIF) approach allows for the separation of particles that are substantially smaller than the minimum feature size of the device
The CIF approach uses a recursive calculation to generate the pattern of a ‘co-flow’ device in which a centre channel retains particles that are larger than the desired c.d., and two adjacent ‘side channels’ which progressively increase in width along the length of the device
Summary
A microfluidics-based approach could potentially circumvent these fundamental limitations of conventional LR filters by enabling continuous separation of leukocytes from a stream of WB or PRP, at the micro-scale[18,19]. Numerous microfluidic techniques for size-based particle separation have been developed, including deterministic lateral displacement (DLD)[20,21,22,23], cross flow filtration[24,25,26,27,28], biomimetic separation[29,30], inertial flow[31,32], and pinched flow fractionation[33] These techniques typically require complex fabrication processes and/or small device feature sizes, and cannot reliably separate blood cells with sufficient purity and throughput to enable practical leukoreduction of WB or diluted WB. We describe the development and validation of a CIF-based microdevice capable of high-throughput leukoreduction of platelet rich plasma, which overcomes the long-standing limitations of conventional filters and existing microfluidic methods alike
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call