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. 2016 Aug 12;7(8):141.
doi: 10.3390/mi7080141.

Study of a Microfluidic Chip Integrating Single Cell Trap and 3D Stable Rotation Manipulation

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Free PMC article

Study of a Microfluidic Chip Integrating Single Cell Trap and 3D Stable Rotation Manipulation

Liang Huang et al. Micromachines (Basel). .
Free PMC article

Abstract

Single cell manipulation technology has been widely applied in biological fields, such as cell injection/enucleation, cell physiological measurement, and cell imaging. Recently, a biochip platform with a novel configuration of electrodes for cell 3D rotation has been successfully developed by generating rotating electric fields. However, the rotation platform still has two major shortcomings that need to be improved. The primary problem is that there is no on-chip module to facilitate the placement of a single cell into the rotation chamber, which causes very low efficiency in experiment to manually pipette single 10-micron-scale cells into rotation position. Secondly, the cell in the chamber may suffer from unstable rotation, which includes gravity-induced sinking down to the chamber bottom or electric-force-induced on-plane movement. To solve the two problems, in this paper we propose a new microfluidic chip with manipulation capabilities of single cell trap and single cell 3D stable rotation, both on one chip. The new microfluidic chip consists of two parts. The top capture part is based on the least flow resistance principle and is used to capture a single cell and to transport it to the rotation chamber. The bottom rotation part is based on dielectrophoresis (DEP) and is used to 3D rotate the single cell in the rotation chamber with enhanced stability. The two parts are aligned and bonded together to form closed channels for microfluidic handling. Using COMSOL simulation and preliminary experiments, we have verified, in principle, the concept of on-chip single cell traps and 3D stable rotation, and identified key parameters for chip structures, microfluidic handling, and electrode configurations. The work has laid a solid foundation for on-going chip fabrication and experiment validation.

Keywords: 3D cell rotation; cell trap; dielectrophoresis (DEP); microfluidics; single cell manipulation.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The design and theory of the integrated chip. (a) The separate view of the integrated model. (b) The schematic of the microchannel. (c) The top view of electrode chamber regarding dielectrophoresis (DEP) torque. (d) The side view of electrode chamber regarding DEP force.
Figure 2
Figure 2
The flow rate distribution of microchannel before and after one-unit single cell be captured. (a) The volume rate of the straight channel is greater than that of the curved channel (Q1/Q2 > 1). (b) The rate distribution changed after one-unit single cell is captured (Q1/Q2 < 1). As shown in the detail figure, a cell is considered as an uncompressible solid sphere. Thus, the trap site is not completely blocked after the cell is captured, and the volume rate, Q1, decreases sharply, but is not zero.
Figure 3
Figure 3
The streamline distributions of the A-A section view at different rates. As the rate increases, the streamline in the channel will be straighter, so a cell will more easily arrive at the trap site. (a) 5 mm/s (equivalent to the volume flow rate in microchannle 0.1875 μL/min), (b) 50 mm/s (equivalent to the volume flow rate in microchannle 1.875 μL/min), and (c) 500 mm/s (equivalent to the volume flow rate in microchannle 18.75 μL/min).
Figure 3
Figure 3
The streamline distributions of the A-A section view at different rates. As the rate increases, the streamline in the channel will be straighter, so a cell will more easily arrive at the trap site. (a) 5 mm/s (equivalent to the volume flow rate in microchannle 0.1875 μL/min), (b) 50 mm/s (equivalent to the volume flow rate in microchannle 1.875 μL/min), and (c) 500 mm/s (equivalent to the volume flow rate in microchannle 18.75 μL/min).
Figure 4
Figure 4
The electric field distribution in the electrode chamber. (a) The top view of the electric field distribution of the chamber. (b) The electric field strength of the center cutline, B–B, of the chamber. The red solid rectangular box indicates that the field distribution exhibits about 20% variation and the cell in the region can maintain a stable rotation.
Figure 5
Figure 5
Trapping a cell in the central region of the electrode chamber. (a) The top view of the electric field distribution of the electrode chamber and the cell is in a balanced state. (b) The cell deviates from the balanced position, and the resultant force is not zero. (c) The distribution of the gradient of the square of the electric field in the electrode chamber.
Figure 6
Figure 6
Levitation of cell to overcome the sinking problem. (a) Side view of electric field strength distribution of the chamber. (b) The value of |E2| for different heights of the cell and bottom electrode.
Figure 7
Figure 7
The electric field distribution of rotation about the X-axis. (a) The electric field distribution of the electrode chamber with one bottom electrode. (b) The average strength of the electrical field of one period within the 10-μm-square region at the center of the chamber.
Figure 8
Figure 8
The fabrication process of the biochip. (a) The fabrication process of the capture part, (b) The fabrication process of rotation part, (c) Bonding and injection liquid metal, and (d) Connecting the electrodes.
Figure 9
Figure 9
(a) The biochip platform. The biochip is connected to the cell buffer solution medium and electrical connections are wired from the electrodes to the external potential supply of AC signals. (b) Close-up view of the electrodes and channel. (c) Snapshot of one captured cell in the trap site.
Figure 10
Figure 10
Comparison between simulated and experimental rotation rates of HeLa cells. (a) The relationship between the cell rotation rate and the AC frequency at Vp-p = 7 V. (b) The relationship between the cell rotation rate and the voltage at f = 600 kHz.

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References

    1. Soffe R., Tang S., Baratchi S., Nahavandi S., Nasabi M., Cooper J.M., Mitchell A., Khoshmanesh K. Controlled rotation and vibration of patterned cell clusters using dielectrophoresis. Anal. Chem. 2015;87:2389–2395. doi: 10.1021/ac5043335. - DOI - PubMed
    1. Jo Y., Shen F., Hahn Y., Park J., Park J. Magnetophoretic sorting of single Cell-Containing microdroplets. Micromachines. 2016;7:56–65. doi: 10.3390/mi7040056. - DOI
    1. Gascoyne P., Shim S. Isolation of circulating tumor cells by dielectrophoresis. Cancers. 2014;6:545–579. doi: 10.3390/cancers6010545. - DOI - PMC - PubMed
    1. Rao L., Cai B., Wang J., Meng Q., Ma C., He Z., Xu J., Huang Q., Li S., Cen Y., et al. A microfluidic electrostatic separator based on pre-charged droplets. Sens. Actuators B Chem. 2015;210:328–335. doi: 10.1016/j.snb.2014.12.057. - DOI
    1. Yasukawa T., Yamada J., Shiku H., Mizutani F., Matsue T. Positioning of cells flowing in a fluidic channel by negative dielectrophoresis. Sens. Actuators B Chem. 2013;186:9–16. doi: 10.1016/j.snb.2013.05.048. - DOI
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