Biomicrofluidics.2013 Jan;7(1): 011801

Rapid isolation of cancer cells using microfluidic deterministic lateral displacement structure.

Zongbin Liu, Fei Huang, Jinghui Du, Weiliang Shu, Hongtao Feng, Xiaoping Xu, and Yan Chen

Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, People’s Republic of China.

Abstract: Circulating tumor cells (CTCs) are isolated tumor cells disseminated from disease site in metastatic or primary cancers and can be used as a diagnostic tool for disease severity, monitoring the effectiveness of therapy, and serving as an independent prognostic factor. However, the isolation and detection of low concentration of CTCs in blood sample is technically challenging. We report a microfluidic device with deterministic lateral displacement (DLD) arrays allowing rapid and label-free cancer cell separation and enrichment from diluted peripheral whole blood, by exploiting the size-dependent hydrodynamic forces. Experiment data and theoretical simulation are presented to evaluate the isolation efficiency of various types of cancer cells in the microfluidic DLD structure. We also demonstrated the use of both circular and triangular post arrays for cancer cell separation in cell solution and blood samples. The device was able to achieve high cancer cell isolation efficiency and enrichment factor with our optimized design. Therefore, this platform with DLD structure shows great potential on fundamental and clinical studies of circulating tumor cells.

Keywords: microfluidics, deterministic lateral displacement, circulating tumor cell

PMID: 24396522

SUPPLEMENTS:

A microfluidic chip with DLD array for rapid isolation of CTCs is successfully demonstrated in this study. Circular and triangular DLD arrays were employed to achieve size based cell separation. Triangular DLD array has better performance than circular DLD array due to less cell deformation. As an application of this device, cancer cell isolation from spiked blood sample with high isolation efficiency (99% for MCF-7 and 80% for MDAMB231) and 2ml/min throughput was achieved. Compared to current technologies for CTC enrichment, such as microfluidic filtration, our device has significantly higher throughput. Meanwhile, our platform has distinct advantages, such as label-free and clogging-free, and maintains high cell viability after processing. More importantly, this high throughput microfluidic device has the potential to be combined with other techniques, such as antibody based immuno-binding methods for post-capture processing. Therefore, the microfluidic DLD array device may provide a promising platform for rapid isolation and detection of CTCs in tumor research and clinical diagnostics.

Yan Chen fig1

Acknowledgments: This work was supported by the National Natural Science Foundation of China (Grant 61106128), the Knowledge Innovation Project of the Chinese Academy of Science (Grant KGCX2-YW-904), and the Guangdong Innovation Research Team Fund for Low-cost Healthcare Technologies(GIRTF-LCHT).

Contact: Yan Chen, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Phone: +86-755-86392254; Email: yan.chen@siat.ac.cn

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