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大规模生产的表面声波(SAW)驱动微流控芯片中的血小板富集。

Blood platelet enrichment in mass-producible surface acoustic wave (SAW) driven microfluidic chips.

机构信息

Leibniz-IFW Dresden, Helmholtzstr. 20, 01069 Dresden, Germany.

Experimentelle Transfusionsmedizin, Medizinische Fakultät Carl Gustav Carus der Technischen Universität Dresden/DRK-Blutspendedienst Nord-Ost gGmbH, Blasewitzer str. 68/70, 01370 Dresden, Germany.

出版信息

Lab Chip. 2019 Dec 21;19(24):4043-4051. doi: 10.1039/c9lc00804g. Epub 2019 Nov 14.

Abstract

The ability to separate specific biological components from cell suspensions is indispensable for liquid biopsies, and for personalized diagnostics and therapy. This paper describes an advanced surface acoustic wave (SAW) based device designed for the enrichment of platelets (PLTs) from a dispersion of PLTs and red blood cells (RBCs) at whole blood concentrations, opening new possibilities for diverse applications involving cell manipulation with high throughput. The device is made of patterned SU-8 photoresist that is lithographically defined on the wafer scale with a new proposed methodology. The blood cells are initially focused and subsequently separated by an acoustic radiation force (ARF) applied through standing SAWs (SSAWs). By means of flow cytometric analysis, the PLT concentration factor was found to be 7.7, and it was proven that the PLTs maintain their initial state. A substantially higher cell throughput and considerably lower applied powers than comparable devices from literature were achieved. In addition, fully coupled 3D numerical simulations based on SAW wave field measurements were carried out to anticipate the coupling of the wave field into the fluid, and to obtain the resulting pressure field. A comparison to the acoustically simpler case of PDMS channel walls is given. The simulated results show an ideal match to the experimental observations and offer the first insights into the acoustic behavior of SU-8 as channel wall material. The proposed device is compatible with current (Lab-on-a-Chip) microfabrication techniques allowing for mass-scale, reproducible chip manufacturing which is crucial to push the technology from lab-based to real-world applications.

摘要

从细胞悬浮液中分离特定生物成分的能力对于液体活检以及个性化诊断和治疗是不可或缺的。本文介绍了一种先进的基于表面声波(SAW)的设备,该设备专为全血浓度下从血小板(PLTs)和红细胞(RBCs)的分散体中富集血小板而设计,为涉及高通量细胞操作的各种应用开辟了新的可能性。该设备由图案化的 SU-8 光刻胶制成,采用新提出的方法在晶圆级上进行光刻定义。最初通过施加在驻波(SSAW)上的声辐射力(ARF)聚焦血液细胞,然后进行分离。通过流式细胞术分析,发现 PLT 浓度因子为 7.7,并证明 PLT 保持其初始状态。与文献中类似的设备相比,该设备实现了更高的细胞吞吐量和更低的应用功率。此外,还进行了基于 SAW 波场测量的完全耦合 3D 数值模拟,以预测波场与流体的耦合,并获得相应的压力场。与 PDMS 通道壁更简单的声情况进行了比较。模拟结果与实验观察结果非常吻合,并首次深入了解 SU-8 作为通道壁材料的声行为。所提出的设备与当前(片上实验室)微制造技术兼容,允许大规模、可重复的芯片制造,这对于将技术从实验室应用推向实际应用至关重要。

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