ISOLATING CIRCULATING TUMOR CELLS USING A CENTRIFUGE ON A CHIP


Year of Award:
2013
Award Type:
R33
Project Number:
CA177456
RFA Number:
RFA-CA-12-003
Technology Track:
Molecular & Cellular Analysis Technologies
PI/Project Leader:
DI CARLO, DINO
Other PI or Project Leader:
N/A
Institution:
UNIVERSITY OF CALIFORNIA LOS ANGELES
The coming generation of personalized anti-cancer treatments will increasingly require companion diagnostic tests to ascertain the presence of specific genetic mutations for which drug targets are available. Cancer tissue or disseminated cancer cells in the circulation or other bodily fluids will be required to carry out these assays. Tissue directly from the tumor is ideal because it is highly pure and can yield sensitive mutational analyses, but this is not available in certain cases as the primary tumor may have already been resected, micrometastases are too small to biopsy, or tumor is present near sensitive anatomical sites thus preventing safe surgical access. In such cases, disseminated tumor cells present in the blood can be highly useful as this is an easily accessible source. A major problem with using cells from blood in companion diagnostics is the presence of a large background of white blood cells within unprocessed samples; these cells prevent the counting and overpower the molecular signal from rare cancer cells and must therefore be removed for accurate diagnosis. We are developing the 'Centrifuge on a Chip' technology to address this challenge and enrich rare circulating cancer cells from blood samples to high purity. This device innovatively utilizes inertial fluid physics at high fluid flow rates to generate microscale vortics which size-selectively and passively isolate larger cells and releases them into a small volume of fluid off chip. We have conducted a pilot study with this device in which we have isolated putative tumor cells from patients with advanced malignancies of the prostate and bladder and these cells can be processed for downstream molecular assays. This technology is easy to use and an order of magnitude faster than current microfluidic cell separation technologies. We aim to validate the Centrifuge Chip technology to enumerate circulating tumor cells as a function of cancer stage and to evaluate whether cells purified with this approach yield higher quality genetic and mutational analyses. Ultimately, such a device may provide a cost-effective and rapid 'liquid biopsy' sample which can be utilized for downstream genetic analyses in order to more effectively personalize anti-cancer therapy.