Research Article: Rare cell isolation and recovery on open-channel microfluidic chip

Date Published: April 20, 2017

Publisher: Public Library of Science

Author(s): Taisuke Masuda, Woneui Song, Hayao Nakanishi, Wu Lei, Anas Mohd Noor, Fumihito Arai, Jeffrey Chalmers.


The ability to accurately detect and analyze rare cells in a cell population is critical not only for the study of disease progression but also for next flow cytometry systems in clinical application. Here, we report the development of a prototype device, the ‘Rare cell sorter’, for isolating and recovering single rare cells from whole blood samples. On this device, we utilized an open-channel microfluidic chip for rare cell isolation. And the advantage of open-channel allows us to recover the isolated rare cell directly from the chip. We set the circulating tumor cell (CTC) as a target cell.

Partial Text

Isolation of rare cells (low-abundance cells), such as circulating tumor cells (CTCs) [1], fetal nucleated red blood cells (fNRBC) [2], and vascular epithelial cells (ECs) [3], from large population of background cells such as blood has a wide range of applications. Several studies have analyzed the genetic mutations carried by CTCs, comparing the mutations to those of primary tumors or correlating the findings to the severity or spread of the patient’s disease [4, 5]. Therefore, the leading applications of CTC analyses are real-time genetic analyses of tumor cells. This is a subject that has become critical in the new era of genetically targeted cancer therapies. Thus, peripheral blood might serve as a perfect alternative sample for cancer diagnoses, such that the analysis of CTCs has been termed ‘liquid biopsy’ [6, 7].

Analysis of CTCs is an active areas of cancer research because these cells can be used as biomarkers for liquid biopsy to estimate the risk of metastatic relapse or metastatic progression and for real-time monitoring of cancer therapies. A number of methods for isolating CTCs have been reported, including fluorescence-activated cell sorting and magnetic-activated cell sorting. Reports of microfluidic chips have increased recently because hydrodynamic methods based on inertial microfluidics are widely applicable and thus enable continuous high-throughput separation of a variety of particles [27–29].

The present paper discussed the development of a prototype device, the ‘Rare cell sorter’, for isolating and recovering single rare cells from the whole blood samples. This device had an open-channel microfluidic chip for rare cell isolation and a micropipette manipulation for single cell recovery. Even though our isolation method is size-based and the applicable target is limited, the new concept utilizing the combination of an open-channel microfluidic chip and micropipette manipulation to achieve cell recovery is meaningful. Therefore, making hybrid method for cell isolation, we hope that open-channel microfluidic chip expand the application area, such as pre-treatment for single cell analysis.




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