Microfluidic array chip for analysis of pairwise cell interaction by temporal stimulation of secreted factors using chamber isolation

Cellular processes like cancer metastasis and stem cell proliferation and differentiation are highly susceptible to cell-to-cell interaction. Cell-cell interaction analysis has been used to elucidate many cellular processes, but conventional methods are limited to averaged measurement of hundreds or even millions of cells, which is not always desirable and makes high-throughput testing problematic. To address this issue, we propose a new microfluidic device which can analyze pairwise cell interactions in isolated microchamber arrays, enabling hundreds of simultaneous tests and potential high-throughput screening of useful cell pairings. Soluble factors secreted by cells in each pair can quickly reach high physiological concentrations when trapped in a small chamber in proximity to each other, rather than being diluted in larger amounts of media as in conventional methods. Media exchange for cell viability is achieved by quick washes and media perfusion alternated with media isolation phases to expose cells to accumulated signals.

Figure 1: Left: Fabricated device with color dyes. (A) Fabricated device, (B) Isolation test results: red dye is added to the inlet, and trapped in the microchambers, and blue dye is then added to the inlet and flows around the closed microchambers, with no observable diffusion over 4 hour. Top-Right: Photograph of Pairwise cell loading using PC3 (Prostate Cancer, Green fluorescence) and C2C12 (Myoblast, red fluorescence) into microchamber: (A) mixed image and (B) fluorescence. Bottom-Right: Schematic diagram of cell capturing and isolation operation in the array chip: (A) 3-D view of microchamber (B) steps used to capture a single cell in a microchamber and (C) sequential operation to capture additional cells.

Related Publication
  1. Y.-J. Kim, T. Bersano-Begey, X. Lou, J. Chung, and E. Yoon, "Microfluidic Array Chip for Analysis of Pairwise Cell Interaction by Temporal Stimulation of Secreted Factors Using Chamber Isolation," International Conference on Miniaturized Systems for Chemistry and Life Sciences (mTAS'09), pp. 1772-1774, November 2009.