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使用级联惯性微流控技术从全血中高效分离白细胞

High-efficient white blood cell separation from whole blood using cascaded inertial microfluidics.

作者信息

Cha Haotian, Kang Xiaoyue, Yuan Dan, de Villiers Belinda, Mak Johnson, Nguyen Nam-Trung, Zhang Jun

机构信息

Queensland Micro- and Nanotechnology Centre, Griffith University, Nathan, Queensland, 4111, Australia.

School of Mechanical and Mining Engineering, The University of Queensland, Brisbane, QLD, 4072, Australia.

出版信息

Talanta. 2025 Mar 1;284:127200. doi: 10.1016/j.talanta.2024.127200. Epub 2024 Nov 14.

Abstract

White blood cells (WBCs) are a crucial component of the human immune system. WBCs contain invaluable information about the health status of the human body. Therefore, separating WBCs is indispensable for the diagnosis of many diseases in clinical setting. The low ratio of WBCs to red blood cells in whole blood has made the isolation of WBCs challenging. As the conventional single-stage microfluidic technology cannot provide sufficient separation purity. We used a cascaded inertial microfluidic chip by consecutively connecting two sinusoidal channels to enhance the purity of WBCs after single processing. The improvement was in part due to the diversion of the sample at the end of the first stage separation, resulting in a lower flow rate in the second stage of processing within the cascaded device. We embedded concave micro-obstacles in sinusoidal channels to adjust their effective working flow rate range and enable the proper operation of both channels simultaneously. Using polystyrene beads mixture (5 and 10 μm) with a primary ratio of 1000 to 1, a single processing step through our cascaded chip improved the purity of 10-μm particles with more than three orders of magnitude of enrichment (from 0.08 % to 99.83 %) with a flow rate of 560 μL/min (Re = 77). Using diluted whole blood ( × 1/10), we achieved 307-fold enrichment of WBCs (0.14 %-43.017 %) in a single process which was accompanied with ∼3 orders of magnitude background removal of RBCs (from 4.8 × 10 to 5.7 × 10 counts/mL). This cascaded manner chip has the capacity to achieve high-efficiency separation of blood cells for clinical diagnosis.

摘要

白细胞(WBCs)是人体免疫系统的重要组成部分。白细胞包含有关人体健康状况的宝贵信息。因此,在临床环境中分离白细胞对于许多疾病的诊断至关重要。全血中白细胞与红细胞的比例较低,这使得白细胞的分离具有挑战性。由于传统的单级微流控技术无法提供足够的分离纯度。我们通过连续连接两个正弦通道使用了一种级联惯性微流控芯片,以提高单次处理后白细胞的纯度。这种改进部分归因于在第一阶段分离结束时样品的分流,导致级联装置第二阶段处理中的流速较低。我们在正弦通道中嵌入了凹形微障碍物,以调整其有效工作流速范围,并使两个通道能够同时正常运行。使用比例为1000比1的聚苯乙烯珠混合物(5和10μm),通过我们的级联芯片进行单个处理步骤,在流速为560μL/min(Re = 77)的情况下,将10μm颗粒的纯度提高了三个多数量级的富集(从0.08%提高到99.83%)。使用稀释的全血(×1/10),我们在单个过程中实现了白细胞307倍的富集(0.14%-43.017%),同时红细胞的背景去除约为三个数量级(从4.8×10到5.7×10个细胞/mL)。这种级联方式的芯片有能力实现用于临床诊断的血细胞高效分离。

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