Singapore - Nanoengineering: Targeting cancer stem cells

Patented droplet microarray technology allows medical researchers to come to grips with rare cells

A miniaturized microarray technology patented by the A*STAR Institute of Bioengineering and Nanotechnology (IBN) can be used to measure the resistance of cancer stem cells (CSCs) to chemotherapeutic drugs1. Jackie Y. Ying and IBN co-workers, who invented the DropArray™ technology (pictured), say recent studies show it can be used for developing more effective cancer drug screening, as well as saving time, cost and the amount of material needed for analysis.

Cancer stem cells are a sub-group of tumor cells that are particularly resistant to chemotherapy and are drivers of metastasis, the spread of cancer via the blood stream. But they are so scarce that it is difficult to study their drug responses with standard laboratory methods.

Using DropArray™, however, the IBN researchers were able to investigate drug resistance in CSCs with high-content screening methods — whereby fluorescent tags are attached to compounds which identify cells of interest, then sensed automatically using microscopes. These methods, which typically employ 96-well of 384-well plates, demand at least 5,000 or 2,500 fluorescing cells respectively per well for detection. This is more than the number of CSCs that would typically be present.

Instead of wells in conventional microplates, DropArray™ uses plates coated with water-repellent material except for an array of two-millimeter-diameter spots that hold samples in the form of droplets. The key to the DropArray™ technology is a layer of proprietary oil with which the plate is covered to prevent evaporation and cross contamination between the droplets. This enables the entire plate to be rinsed easily and precisely in a specially built automated apparatus. Using DropArray™ only 500 fluorescing cells are needed for detection.

The researchers studied the drug response of CSCs from liver, breast and colon tumors and, using DropArray™, compared them to typical tumor cells with respect to the impact of a range of doses of drugs used in the treatment of these cancers. In the liver tumor cells, for instance, they looked at sensitivity to doxorubicin which stimulates apoptosis or cell suicide. By testing for a protein synthesized during apoptosis, they found normal tumor cells were far more sensitive to the drug than CSCs. The results for the other tumors were similar. The researchers also showed in mice that the material containing CSCs was much more effective at generating new tumors.

“We are now able to apply DropArray™ to develop novel drug screening assays using rare CSCs and facilitate cancer therapy research,” says Ying.

The A*STAR-affiliated researchers contributing to this research are from the Institute of Bioengineering and Nanotechnology

References

1. Lee, Y. Y., Narayanan, K., Gao, S. J. and Ying, J. Y. Elucidating drug resistant properties in scarce cancer stem cells using droplet microarray. Nano Today 7, 29–34 (2012). | article