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Issue 14, 2014
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High-throughput rare cell separation from blood samples using steric hindrance and inertial microfluidics

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Abstract

The presence and quantity of rare cells in the bloodstream of cancer patients provide a potentially accessible source for the early detection of invasive cancer and for monitoring the treatment of advanced diseases. The separation of rare cells from peripheral blood, as a “virtual and real-time liquid biopsy”, is expected to replace conventional tissue biopsies of metastatic tumors for therapy guidance. However, technical obstacles, similar to looking for a needle in a haystack, have hindered the broad clinical utility of this method. In this study, we developed a multistage microfluidic device for continuous label-free separation and enrichment of rare cells from blood samples based on cell size and deformability. We successfully separated tumor cells (MCF-7 and HeLa cells) and leukemic (K562) cells spiked in diluted whole blood using a unique complementary combination of inertial microfluidics and steric hindrance in a microfluidic system. The processing parameters of the inertial focusing and steric hindrance regions were optimized to achieve high-throughput and high-efficiency separation, significant advantages compared with existing rare cell isolation technologies. The results from experiments with rare cells spiked in 1% hematocrit blood indicated >90% cell recovery at a throughput of 2.24 × 107 cells min−1. The enrichment of rare cells was >2.02 × 105-fold. Thus, this microfluidic system driven by purely hydrodynamic forces has practical potential to be applied either alone or as a sample preparation platform for fundamental studies and clinical applications.

Graphical abstract: High-throughput rare cell separation from blood samples using steric hindrance and inertial microfluidics

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Supplementary files

Article information


Submitted
13 Dec 2013
Accepted
21 Mar 2014
First published
21 Mar 2014

Lab Chip, 2014,14, 2525-2538
Article type
Paper
Author version available

High-throughput rare cell separation from blood samples using steric hindrance and inertial microfluidics

S. Shen, C. Ma, L. Zhao, Y. Wang, J. Wang, J. Xu, T. Li, L. Pang and J. Wang, Lab Chip, 2014, 14, 2525
DOI: 10.1039/C3LC51384J

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