Published on December 6, 2013 at 8:29 PM
Prior to the passage of ascites fluid through the MGH team's device - called the ATC chip - the sample is first labeled with magnetic nanoparticles that bind to noncancerous inflammatory cells. The sample is introduced into the three-inch-long ATC chip through a filter that screens out clumps of debris and then passes by a magnet that traps the magnetically labeled benign cells. Also added to the device is a mixture of antibodies to the ATCDX proteins, which label the markers for imaging detection. After the magnetic sorting, the sample passes over a series of microwells of successively smaller size, which collect ATCs while even smaller leukocytes pass through the device. The concentration of ATCs captured on the chip is 1,000 times greater than it was in the original fluid sample.
The investigators tested the device initially by analyzing ascites samples repeatedly collected from a single ovarian cancer patient over a 14-week course of treatment, first with standard chemotherapy and then with antiangiogenic therapy when disease progression resumed. The ATC chip revealed that the number of ATCs dropped during initial treatment response, rose with progression and fell again as antiangiogenesis relieved the patient's symptoms. They also found that analysis of the molecular properties of ATCs from 46 ovarian cancer patients could distinguish those whose tumors responded to treatment from nonresponders.
"This device far exceeded our expectations," says Ralph Weissleder, MD, PhD, director of the Center for Systems Biology and senior author of the PNAS report. "Coupled with our diagnostic panel, we were able to clearly distinguish between tumor cells and the extensive cellular debris commonly found in ascites. The ATC chip and the set of protein markers we uncovered, which reliably identified ovarian cancer cells floating in ascites, provide a novel platform for extending ATC analysis to settings where the expensive equipment and labor-intensive techniques that ATC isolation previously required would not be feasible."
The research team notes that large-scale production of the ATC chip is already being planned, and if future studies confirm their results, the device's low cost - estimated at less than $1 each - and ease of use would make ATC analysis a practical and valuable tool for both treatment of and research into ovarian cancer and possibly for other tumors that induce the formation of ascites, including pancreatic cancer.
Source: Massachusetts General Hospital