Lee Lap Man, Bhatt Ketan H, Haithcock Dustin W, Prabhakarpandian Balabhaskar
CFD Research Corporation, Huntsville, Alabama 35806, USA.
Biomicrofluidics. 2023 Oct 16;17(5):054106. doi: 10.1063/5.0176457. eCollection 2023 Sep.
Separation of blood components is required in many diagnostic applications and blood processes. In laboratories, blood is usually fractionated by manual operation involving a bulk centrifugation equipment, which significantly increases logistic burden. Blood sample processing in the field and resource-limited settings cannot be readily implemented without the use of microfluidic technology. In this study, we developed a small footprint, rapid, and passive microfluidic channel device that relied on margination and inertial focusing effects for blood component separation. No blood dilution, lysis, or labeling step was needed as to preserve sample integrity. One main innovation of this work was the insertion of fluidic restrictors at outlet ports to divert the separation interface into designated outlet channels. Thus, separation efficiency was significantly improved in comparison to previous works. We demonstrated different operation modes ranging from platelet or plasma extraction from human whole blood to platelet concentration from platelet-rich plasma through the manipulation of outlet port fluidic resistance. Using straight microfluidic channels with a high aspect ratio rectangular cross section, we demonstrated 95.4% platelet purity extracted from human whole blood. In plasma extraction, 99.9% RBC removal rate was achieved. We also demonstrated 2.6× concentration of platelet-rich plasma solution to produce platelet concentrate. The extraction efficiency and throughput rate are scalable with continuous and clog-free recirculation operation, in contrast to other blood fractionation approaches using filtration membranes or affinity-based purification methods. Our microfluidic blood separation method is highly tunable and versatile, and easy to be integrated into multi-step blood processing and advanced sample preparation workflows.
在许多诊断应用和血液处理过程中,都需要进行血液成分分离。在实验室中,血液通常通过涉及大容量离心设备的手动操作进行分离,这显著增加了后勤负担。在现场和资源有限的环境中,如果不使用微流控技术,血液样本处理就无法轻易实现。在本研究中,我们开发了一种占地面积小、快速且被动的微流控通道装置,该装置依靠边缘效应和惯性聚焦效应进行血液成分分离。无需进行血液稀释、裂解或标记步骤,以保持样本完整性。这项工作的一个主要创新是在出口端口插入流体限制器,将分离界面转移到指定的出口通道。因此,与以前的工作相比,分离效率得到了显著提高。我们展示了不同的操作模式,从从人全血中提取血小板或血浆到通过控制出口端口流体阻力从富血小板血浆中浓缩血小板。使用具有高纵横比矩形横截面的直微流控通道,我们展示了从人全血中提取的血小板纯度为95.4%。在血浆提取中,红细胞去除率达到99.9%。我们还展示了将富血小板血浆溶液浓缩2.6倍以生产血小板浓缩物。与使用过滤膜或基于亲和力的纯化方法的其他血液分离方法相比,提取效率和通量率可通过连续且无堵塞的循环操作进行扩展。我们的微流控血液分离方法具有高度的可调性和通用性,并且易于集成到多步骤血液处理和先进的样本制备工作流程中。