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. 2015 Jun 12;9(3):034109.
doi: 10.1063/1.4922488. eCollection 2015 May.

Quantitative impedimetric monitoring of cell migration under the stimulation of cytokine or anti-cancer drug in a microfluidic chip

Lu Liu  1 , Xia Xiao  1 , Kin Fong Lei, Chia-Hao Huang  2
Affiliations

Quantitative impedimetric monitoring of cell migration under the stimulation of cytokine or anti-cancer drug in a microfluidic chip

Lu Liu et al. Biomicrofluidics. .

Abstract

Cell migration is a cellular response and results in various biological processes such as cancer metastasis, that is, the primary cause of death for cancer patients. Quantitative investigation of the correlation between cell migration and extracellular stimulation is essential for developing effective therapeutic strategies for controlling invasive cancer cells. The conventional method to determine cell migration rate based on comparison of successive images may not be an objective approach. In this work, a microfluidic chip embedded with measurement electrodes has been developed to quantitatively monitor the cell migration activity based on the impedimetric measurement technique. A no-damage wound was constructed by microfluidic phenomenon and cell migration activity under the stimulation of cytokine and an anti-cancer drug, i.e., interleukin-6 and doxorubicin, were, respectively, investigated. Impedance measurement was concurrently performed during the cell migration process. The impedance change was directly correlated to the cell migration activity; therefore, the migration rate could be calculated. In addition, a good match was found between impedance measurement and conventional imaging analysis. But the impedimetric measurement technique provides an objective and quantitative measurement. Based on our technique, cell migration rates were calculated to be 8.5, 19.1, and 34.9 μm/h under the stimulation of cytokine at concentrations of 0 (control), 5, and 10 ng/ml. This technique has high potential to be developed into a powerful analytical platform for cancer research.

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Figures

FIG. 1.
FIG. 1.
Microfluidic chip for quantitative impedimetric monitoring of cell migration activity. (a) Photographic image of the microfluidic chip. (b) Schematic illustration of the experiment setup. (c) Illustration of the electrode structure inside the microchannel.
FIG. 2.
FIG. 2.
Relationship between impedance magnitude and cell concentration under different measurement frequencies of 5, 20, 50, and 100 kHz. Error bars represent the standard deviations of three repeated experiments.
FIG. 3.
FIG. 3.
Construction of a wound edge in the microchannel. (a) Schematic illustration of the procedures of constructing the wound edge based on the formation of two parallel laminar flows in the microchannel. (b) A sequence of photographic images showing the process of constructing the wound edge in the microchannel. The red dashed line represents the start line of the cell migration process. Images were captured under an upright microscope because the electrodes were not transparent. (c) Photographic image of the wound edge constructing in the microchannel without embedding electrodes. Images were captured under an inverted microscope. (d) Photographic image of the cell monolayer corresponding to the dashed line square in (c).
FIG. 4.
FIG. 4.
Analyses of cell migration activity. (a) Successive images of cell migration process. The red dashed line represents the start line of the cell migration process. The red arrow indicates the leading edge. (b) Relationship between the migration distance and time identified from the images is shown in (a). (c) Impedance measurements across six pairs of electrodes at distances of 200, 400, 600, 800, 1000, and 1200 μm at different successive time points. Error bars represent the standard deviations of three repeated experiments. (d) Relationship between the migration distance and time calculated from the impedance data is shown in (c).
FIG. 5.
FIG. 5.
Impedimetric monitoring of cell migration under the stimulation of IL-6 cytokine at concentrations of (a) 5 and (c) 10 ng/ml. Error bars represent the standard deviations of three repeated experiments. (b) and (d) Relationship between the migration distance and time for the calculation of cell migration rate.
FIG. 6.
FIG. 6.
Impedimetric monitoring of cell migration under the stimulation of doxorubicin at concentrations of (a) 0.5 and (b) 1 μg/ml. Error bars represent the standard deviations of three repeated experiments.
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