IBN Droplet Array sheds light on drug-resistant cancer stem cells

Researchers at the Institute of Bioengineering and Nanotechnology (IBN) in Singapore have developed a miniaturised biochip for investigating the effect of drugs on cancer stem cells (CSCs).

CSCs form a small and distinct class of cancer cells in a tumour that are more resistant to chemotherapy. Similar to stem cells found in human tissues, CSCs can produce and differentiate into different cell types. If they are not eradicated, they can repopulate the tumour and lead to the recurrence of cancer.

It is important therefore for researchers to understand the effectiveness of anti-cancer drugs against CSCs. However, since CSCs make up only around 1% of cancer cells, their study has been hampered by conventional drug screening methods, which require large sample volumes and are slow and expensive.

The team of researchers, led by IBN executive director, Professor Jackie Ying, has developed the Droplet Array, a flat, rectangular glass plate on which a series of spots, each 2mm in diameter, are arranged to perform cheaper and more convenient drug screening using limited samples.

The samples are pipetted into these tiny spots, making them appear like droplets. The plate is then coated with a layer of proprietary oil to prevent evaporation and cross contamination between the sample droplets during the rinsing process. An accompanying bench-top device to automate the rinsing process of the plate has also been developed.

Being one-fifth the size of a well in a standard microplate, each spot on IBN's Droplet Array requires only 500 cells for screening.

Using the Droplet Array, the researchers investigated the drug responses of CSCs extracted from breast, liver and colon cancer cells. It was found that chemotherapeutic drugs such as doxorubicin, which usually induce cell death in liver cancer cells, demonstrated poor efficacy in liver CSCs. The CSCs from the breast and colon tumours also showed much greater ability to survive the effects of anti-cancer drugs.

Animal studies were conducted to validate the findings of the Droplet Array. CSCs and non-CSCs from liver tumours were implanted into two different sets of mice at the same time. After six weeks, tumours were formed in the mice implanted with CSCs, whereas the mice without CSCs did not develop any tumours. Tumours extracted from the mice with CSCs also showed blood vessel formation, which confirmed the self-renewal property of these cells.

Professor Ying said: ‘The Droplet Array marks a significant breakthrough in nanotechnology and lab-on-a-chip concepts, and provides an efficient platform for accelerating drug screening and development.

‘We hope that this finding will facilitate the development of more effective cancer drugs. We also hope to leverage on the Droplet Array's capabilities to complement/replace animal models for drug toxicity testing, and develop new cancer diagnostics.’

The Droplet Array technology is currently being commercialised by IBN's first spin-off company, Curiox Biosystems, as DropArray.

The research is published in Nano Today.