Journal
LAB ON A CHIP
Volume 14, Issue 14, Pages 2525-2538Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c3lc51384j
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Funding
- National Natural Science Foundation of China [21175107, 21375106]
- Ministry of Education of the People's Republic of China [NCET-08-6020464]
- Fundamental Research Funds for the Central Universities [Z109021303]
- Scientific Research Foundation for the Returned Overseas Chinese Scholars
- State Education Ministry
- Northwest AF University
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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 x 10(7) cells min(-1). The enrichment of rare cells was >2.02 x 10(5)-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.
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