Clonal culture and chemodrug assay of heterogeneous cells (pc3 prostate carcinoma cells) using microfluidic single cell array chips
A major obstacle in cancer research and treatment is that cancer cells often mutate or differentiate into multiple different cell types during experiments. Even testing a drug in a petridish culture might only give information that is averaged across multiple subtypes with very different resistance mechanisms. Recently it was reported that even PC3 human prostate carcinoma cells, a cell line, give rise to a mixture of three clonal phenotypes: holoclones, meroclones, and paraclones. We report a microfluidic array chip that can separate PC3 cancer cells into single cells in each microwell, grow them separately side by side into small uniform clonal colonies and test drugs on them. Using this chip we can detect how many subtypes of clones are present and to see if they respond differently to cancer drug treatments.
Figure 1: Top-left: Conceptual diagram of PC3 cell line spontaneously generating three different cell sub phenotypes (holo-, mero-, and paraclones) over time, which are normally mixed in conventional cell culture. Bottom-left: Schematics of the single cell capture array chip. Top-right: Fluorescence photography of microwell array 1 hour after PC cell loading; green dots represent PC3 single cells. In the image, 39 microwells are occupied with single cells out of 42 microwells, only three microwells were not occupied. Bottom-right: Fabricated single cell culture array chip, showing its simple operation (simply add cells and media in the inlet) and small size.
- J. Chung, T. Bersano-Begey, K. Pienta, E. Yoon, "Clonal Culture and Chemodrug Assay of Heterogeneous Cells (PC3 Prostate Carcinoma Cells) Using Microfluidic Single Cell Array Chips," International Conference on Miniaturized Systems for Chemistry and Life Sciences (mTAS'09), pp. 21-23, November 2009.