3D-Stacked Multistage Inertial Microfluidic Chip for High-Throughput Enrichment of Circulating Tumor Cells

Whether for cancer diagnosis or single-cell analysis, it remains a major challenge to isolate the target sample cells from a large background cell for high-efficiency downstream detection and analysis in an integrated chip. Therefore, in this paper, we propose a 3D-stacked multistage inertial microf...

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Main Authors: X. Xu, X. Huang, J. Sun, J. Chen, G. Wu, Y. Yao, N. Zhou, S. Wang, L. Sun
Format: Article
Language:English
Published: American Association for the Advancement of Science (AAAS) 2022-01-01
Series:Cyborg and Bionic Systems
Online Access:http://dx.doi.org/10.34133/2022/9829287
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author X. Xu
X. Huang
J. Sun
J. Chen
G. Wu
Y. Yao
N. Zhou
S. Wang
L. Sun
author_facet X. Xu
X. Huang
J. Sun
J. Chen
G. Wu
Y. Yao
N. Zhou
S. Wang
L. Sun
author_sort X. Xu
collection DOAJ
description Whether for cancer diagnosis or single-cell analysis, it remains a major challenge to isolate the target sample cells from a large background cell for high-efficiency downstream detection and analysis in an integrated chip. Therefore, in this paper, we propose a 3D-stacked multistage inertial microfluidic sorting chip for high-throughput enrichment of circulating tumor cells (CTCs) and convenient downstream analysis. In this chip, the first stage is a spiral channel with a trapezoidal cross-section, which has better separation performance than a spiral channel with a rectangular cross-section. The second and third stages adopt symmetrical square serpentine channels with different rectangular cross-section widths for further separation and enrichment of sample cells reducing the outlet flow rate for easier downstream detection and analysis. The multistage channel can separate 5 μm and 15 μm particles with a separation efficiency of 92.37% and purity of 98.10% at a high inlet flow rate of 1.3 mL/min. Meanwhile, it can separate tumor cells (SW480, A549, and Caki-1) from massive red blood cells (RBCs) with a separation efficiency of >80%, separation purity of >90%, and a concentration fold of ~20. The proposed work is aimed at providing a high-throughput sample processing system that can be easily integrated with flowing sample detection methods for rapid CTC analysis.
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spelling doaj.art-0755bc28935642c3a54d6f6cd71b45812022-12-22T03:41:05ZengAmerican Association for the Advancement of Science (AAAS)Cyborg and Bionic Systems2692-76322022-01-01202210.34133/2022/98292873D-Stacked Multistage Inertial Microfluidic Chip for High-Throughput Enrichment of Circulating Tumor CellsX. Xu0X. Huang1J. Sun2J. Chen3G. Wu4Y. Yao5N. Zhou6S. Wang7L. Sun8Ministry of Education Key Laboratory of RF Circuits and Systems, Hangzhou Dianzi University, Hangzhou, 310018 Zhejiang, ChinaMinistry of Education Key Laboratory of RF Circuits and Systems, Hangzhou Dianzi University, Hangzhou, 310018 Zhejiang, ChinaMinistry of Education Key Laboratory of RF Circuits and Systems, Hangzhou Dianzi University, Hangzhou, 310018 Zhejiang, ChinaMinistry of Education Key Laboratory of RF Circuits and Systems, Hangzhou Dianzi University, Hangzhou, 310018 Zhejiang, ChinaInstitute for Translational Medicine, Zhejiang University, Hangzhou, 310029 Zhejiang, ChinaKey Laboratory of 3D Micro/Nano Fabrication and Characterization of Zhejiang Province, School of Engineering, Westlake University, Hangzhou, 310024 Zhejiang, ChinaKey Laboratory of 3D Micro/Nano Fabrication and Characterization of Zhejiang Province, School of Engineering, Westlake University, Hangzhou, 310024 Zhejiang, ChinaInstitute for Translational Medicine, Zhejiang University, Hangzhou, 310029 Zhejiang, China; National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610065, China; Clinical Research Center for Respiratory Disease, West China Hospital, Sichuan University, Chengdu 610065, China; Institute for Advanced Study, Chengdu University, Chengdu 610106, ChinaMinistry of Education Key Laboratory of RF Circuits and Systems, Hangzhou Dianzi University, Hangzhou, 310018 Zhejiang, ChinaWhether for cancer diagnosis or single-cell analysis, it remains a major challenge to isolate the target sample cells from a large background cell for high-efficiency downstream detection and analysis in an integrated chip. Therefore, in this paper, we propose a 3D-stacked multistage inertial microfluidic sorting chip for high-throughput enrichment of circulating tumor cells (CTCs) and convenient downstream analysis. In this chip, the first stage is a spiral channel with a trapezoidal cross-section, which has better separation performance than a spiral channel with a rectangular cross-section. The second and third stages adopt symmetrical square serpentine channels with different rectangular cross-section widths for further separation and enrichment of sample cells reducing the outlet flow rate for easier downstream detection and analysis. The multistage channel can separate 5 μm and 15 μm particles with a separation efficiency of 92.37% and purity of 98.10% at a high inlet flow rate of 1.3 mL/min. Meanwhile, it can separate tumor cells (SW480, A549, and Caki-1) from massive red blood cells (RBCs) with a separation efficiency of >80%, separation purity of >90%, and a concentration fold of ~20. The proposed work is aimed at providing a high-throughput sample processing system that can be easily integrated with flowing sample detection methods for rapid CTC analysis.http://dx.doi.org/10.34133/2022/9829287
spellingShingle X. Xu
X. Huang
J. Sun
J. Chen
G. Wu
Y. Yao
N. Zhou
S. Wang
L. Sun
3D-Stacked Multistage Inertial Microfluidic Chip for High-Throughput Enrichment of Circulating Tumor Cells
Cyborg and Bionic Systems
title 3D-Stacked Multistage Inertial Microfluidic Chip for High-Throughput Enrichment of Circulating Tumor Cells
title_full 3D-Stacked Multistage Inertial Microfluidic Chip for High-Throughput Enrichment of Circulating Tumor Cells
title_fullStr 3D-Stacked Multistage Inertial Microfluidic Chip for High-Throughput Enrichment of Circulating Tumor Cells
title_full_unstemmed 3D-Stacked Multistage Inertial Microfluidic Chip for High-Throughput Enrichment of Circulating Tumor Cells
title_short 3D-Stacked Multistage Inertial Microfluidic Chip for High-Throughput Enrichment of Circulating Tumor Cells
title_sort 3d stacked multistage inertial microfluidic chip for high throughput enrichment of circulating tumor cells
url http://dx.doi.org/10.34133/2022/9829287
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