Microfluidic devices for size-dependent separation of liver cells

Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan.
Biomedical Microdevices (Impact Factor: 2.77). 11/2007; 9(5):637-45. DOI: 10.1007/s10544-007-9055-5
Source: PubMed

ABSTRACT Liver is composed of various kinds of cells, including hepatic parenchymal cells (hepatocytes) and nonparenchymal cells, and separation of these cells is essential for cellular therapies and pharmacological and metabolic studies. Here, we present microfluidic devices for purely hydrodynamic and size-dependent separation of liver cells, which utilize hydrodynamic filtration. By continuously introducing cell suspension into a microchannel with multiple side-branch channels, cells smaller than a specific size are removed from the mainstream, while large cells are focused onto a sidewall in the microchannel and then separated into two or three groups. Two types of PDMS-glass hybrid microdevices were fabricated, and rat liver cells were successfully separated. Also, cell size, morphology, viability and several cell functions were analyzed, and the separation performances of the microfluidic devices were compared to that of a conventional centrifugal technique. The results showed that the presented microfluidic devices are low-cost and suitable for clinical use, and capable of highly functional separation with relatively high-speed processing.

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    • "In each trap, single microbeads are trapped based on the dynamic change in the hydraulic resistance (i.e., before and after microbead trapping) as a function of the cross-sectional shape of a microchannel. Briefly, depending on the relationship between the center position of a microbead and the flow pattern [i.e., a virtual width (W v )], the path of the introduced microbeads is determined (Yamada et al. 2007). First, to regulate the position of microbeads and to ensure the trapping of single microbeads, all introduced microbeads are aligned along one side wall using the buffer flow. "
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    • "According to our theoretical method for predicting the virtual width, single cell trapping feasibility can be checked, depending on cell size and the variation thereof. In addition, a sizedependent particle separation method (Yamada et al. 2007) can be integrated upstream or outside of a device to minimize the effect of size variation on single-cell trapping. The undesirable effects of mechanical stress resulting from direct contact with elastomeric valves on cell function may be insignificant because the presented trapping method with a certain flow rate ratio can be operated regardless of flow velocities (Frimat et al. 2011). "
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