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Research Paper

Demonstration of Cancer Cell Migration Using a Novel Microfluidic Device

[+] Author and Article Information
Smitha M. N. Rao1

Department of Electrical Engineering, University of Texas at Arlington, Arlington, TX 76019smitha@uta.edu

Victor K. Lin, Ganesh V. Raj, Jer-Tsong Hsieh

Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX 75390

Uday Tata, J.-C. Chiao

Department of Electrical Engineering, University of Texas at Arlington, Arlington, TX 76019

Kytai Nguyen

Department of Bioengineering, University of Texas at Arlington, Arlington, TX 76019

1

Corresponding author.

J. Nanotechnol. Eng. Med 1(2), 021003 (May 05, 2010) (6 pages) doi:10.1115/1.4001280 History: Received January 18, 2010; Revised February 16, 2010; Published May 05, 2010; Online May 05, 2010

Migration of cancer cells from the primary organ site via the bloodstream to distant sites is critical to the development of malignant metastasis and is in part determined by soluble host factors in the serum. Conventional Boyden chamber assays to evaluate cell motility require high volumes of reagents and are impractical for high-throughput analysis. We have designed and evaluated a poly-dimethylsiloxane (PDMS) microfluidic device in order to systematically study cancer cell migration. Photolithography and soft lithography processes were used to fabricate the PDMS devices from a negative photoresist (SU-8) mold. The device provides two separate identical chambers that are interconnected by an array of identical narrow channels, 10μm high, 25μm wide, and 1000μm long. One chamber is seeded with cancer cells whose migration characteristics are to be evaluated, while the other chamber contains media with chemoattractants toward which the cancer cells migrate. In this microfluidic chamber model, the migration of cancer cells within and across the microfluidic channels over a prescribed time was quantified using time-lapse photographs. The microfluidic chamber is a cost-effective platform that uses small volumes of reagents, can maintain stable chemokine gradients, allow real-time quantitative study of cancer cell migration, and provide information about cellular dynamics and biomechanical analysis. This work demonstrated the utility of the microfluidic device as a platform to study cancer cell migration as well as the potential applications in the identification of specific chemokine agents and development of drugs targeting cell migration.

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Copyright © 2010 by American Society of Mechanical Engineers
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Figures

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Figure 1

Our PDMS microfluidic device bonded to a culture dish with schematic. Cancer cells are introduced into the chamber A through the wells (shaded solid gray), while the chemokines are introduced into the chamber B through the wells (shaded with dots). Cancer cells migrate from the chamber A to chamber B across the microfluidic channels (direction shown by the arrow), which can be quantified within the field of view in a microscope.

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Figure 2

HPV-7 cell migration in response to serum containing media on days 7, 9 and 12 demonstrating that this microfluidic design can be used to monitor cell migration. Cells in serum-free media were placed on the left and serum containing media was placed on the right side of the channels.

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Figure 3

PC-3 cells migrate in response to FBS stimulation in a concentration-dependent manner. The yellow dashed lines indicate the edge of migration channels. The magnification of these images is 100×.

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Figure 4

Effect of increasing concentration of FBS on the migration of PC-3 cells on days 4–7. The numbers of cells in the channels on a specific day after the fourth day increased with the concentrations of FBS.

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Figure 5

PC-3 cells migrate in response to EGF stimulation in a concentration-dependent manner

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Figure 6

Effects of concentrations of EGF on PC-3 cells on days 2–4

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Figure 7

Cell migration in response to the factor gradient on (a) day 4 and (b) day 5 shown in the bright-field images indicates cell deformation in order to enter the microfluidic channel. The arrows show the deformation of the cells as they enter the microchannels and within the channels as the cells migrate.

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