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使用带有一对线性锥形错流过滤器阵列的微流控芯片,从血液中稳健且高效地分离白细胞。

Robust and efficient separation of white blood cells from blood using a microfluidic chip with a pair of linearly tapered crossflow filter arrays.

作者信息

Huang Yuanding, Chen Ping, Niu Meng, Peng Weng Kung

机构信息

Frontier Research Centre, Songshan Lake Materials Laboratory, Dongguan, 523830, Guangdong, China.

Department of Health Examination, Dongguan Songshan Lake Tungwah Hospital, Dongguan, 523820, Guangdong, China.

出版信息

Mikrochim Acta. 2024 Dec 30;192(1):41. doi: 10.1007/s00604-024-06913-0.

DOI:10.1007/s00604-024-06913-0
PMID:39738679
Abstract

Clinical and immunological assays of white blood cells (WBCs) in human peripheral blood are of significance for disease diagnosis and immunological studies. However, separating WBCs from blood with high recovery and high purity remains challenging. In this study, by incorporating a pair of linearly tapered filter arrays, a crossflow filtration-based microfluidic chip was designed and fabricated for separation of WBCs from blood. The implementation of the linearly tapered filter arrays not only ensures a minimal and consistent flow through each sieve, but also achieves a high filtration ratio (~ 19). The validity and robustness of this straightforward design were substantiated through theoretical analysis, simulations, and model microparticle tests. The microfluidic chip achieved an almost perfect (> 99.2%) recovery and a ~ 20-fold enrichment of the targeted 8 μm particles (as surrogates for WBCs) from undesired 2 μm particles (as substitutes for red blood cells, RBCs) at flow rates ranging from 50 to 200 μL/min, irrespective of the filter array length and particle concentration. When applied to a twenty times diluted blood sample, the chip achieved a 96.6% recovery and 19.7-fold enrichment of WBCs, as well as a 95.0% removal of RBCs, at the optimal flow rate of 100 μL/min. With its simple design, cost-effectiveness, high recovery, substantial enrichment ratio, and considerable throughput, this chip offers an alternative solution that is potentially applicable to scenarios involving the separation of WBCs as well as other particles/cells.

摘要

对人体外周血中的白细胞(WBC)进行临床和免疫分析对于疾病诊断和免疫研究具有重要意义。然而,以高回收率和高纯度从血液中分离白细胞仍然具有挑战性。在本研究中,通过结合一对线性渐变的过滤器阵列,设计并制造了一种基于错流过滤的微流控芯片,用于从血液中分离白细胞。线性渐变过滤器阵列的应用不仅确保了通过每个筛网的流量最小且一致,还实现了较高的过滤比(约19)。通过理论分析、模拟和模型微粒测试证实了这种简单设计的有效性和稳健性。该微流控芯片在50至200μL/min的流速范围内,无论过滤器阵列长度和颗粒浓度如何,都能从不需要的2μm颗粒(作为红细胞的替代物)中几乎完美地回收(>99.2%)目标8μm颗粒(作为白细胞的替代物),并实现约20倍的富集。当应用于稀释20倍的血液样本时,在100μL/min的最佳流速下,该芯片实现了96.6%的白细胞回收率和19.7倍的富集,以及95.0%的红细胞去除率。该芯片设计简单、成本效益高、回收率高、富集比大且通量可观,为涉及白细胞以及其他颗粒/细胞分离的场景提供了一种潜在适用的替代解决方案。

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本文引用的文献

1
Characterization of the phagocytic ability of white blood cells separated using a single curvature spiral microfluidic device.使用单曲率螺旋微流控装置分离的白细胞吞噬能力的表征。
Biomed Eng Lett. 2024 Aug 8;14(6):1409-1419. doi: 10.1007/s13534-024-00414-y. eCollection 2024 Nov.
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Red blood cell rosetting enables size-based separation of specific lymphocyte subsets from blood in a microfluidic device.红细胞缗钱状形成使我们能够在微流控装置中基于大小分离特定的淋巴细胞亚群。
Lab Chip. 2023 Mar 28;23(7):1804-1815. doi: 10.1039/d2lc00817c.
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无标记微流控细胞分选和检测用于快速血液分析。
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Engineered cellular immunotherapies in cancer and beyond.癌症及其他领域的工程化细胞免疫疗法。
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Multiphysics microfluidics for cell manipulation and separation: a review.多物理场微流控技术在细胞操控与分离中的应用:综述。
Lab Chip. 2022 Feb 1;22(3):423-444. doi: 10.1039/d1lc00869b.
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Fully-automated and field-deployable blood leukocyte separation platform using multi-dimensional double spiral (MDDS) inertial microfluidics.使用多维双螺旋(MDDS)惯性微流控技术的全自动且可现场部署的血液白细胞分离平台。
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A numbering-up strategy of hydrodynamic microfluidic filters for continuous-flow high-throughput cell sorting.基于流道式微流控滤器的编号策略用于连续流高通量细胞分选。
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