Friday, September 23, 2016
Microfluidics to Isolate Single and Clusters of Rare Circulating Tumor Cells to Manage Cancer Patients
Viable tumor-derived circulating tumor cells (CTCs) have been identified in peripheral blood from cancer patients and are not only the origin of intractable metastatic disease but also markers for early cancer. However, the ability to isolate CTCs has proven to be difficult due to the exceedingly low frequency of CTCs in circulation. As a result their clinical use until recently has been limited to prognosis with limited clinical utility. More recently, we introduced several microfluidic methods to improve the sensitivity of rare event CTC isolation, a strategy that is particularly attractive because it can lead to efficient purification of viable CTCs from unprocessed whole blood. The micropost CTC-Chip (μpCTC-Chip) relies on laminar flow of blood cells through anti-EpCAM antibody-coated microposts, whereas the herringbone CTC-Chip (HbCTC-Chip) uses micro-vortices generated by herringboneshaped grooves to efficiently direct cells toward antibody-coated surfaces.
These antigen-dependent CTC isolation approaches, also called “positive selection,” led to the development of a third technology, which is tumor marker free (or antigen-independent) sorting of CTCs. We call this integrated microfluidic system the CTC-iChip, based on the inertial focusing strategy, which allows positioning of cells in a near-single file line, such that they can be precisely deflected using minimal magnetic force. The major advantage of the approach stems from the fact that it is based on “negative depletion” of blood cells and hence it is applicable to all solid tumors and does not require tagging or labeling the tumor cells. As a result the CTCs are isolated in pristine conditions and are amenable to analysis using imaging, molecular, and other approaches. We applied these three microfluidic platforms to blood samples obtained from lung, prostate, breast, colon, melanoma, and pancreatic cancer patients. This presentation will share our integrated strategy to simultaneously advance the engineering and microfluidics of CTC-Chip development, the biology of these rare cells, and the potential clinical applications of circulating tumor cells.
Dr. Toner received a BS from Istanbul Technical University and a MS from the Massachusetts Institute of Technology (MIT), both in Mechanical Engineering. Subsequently he completed his PhD degree in Medical Engineering at Harvard-MIT Division of Health Sciences and Technology in 1989. Currently, he is the Helen Andrus Benedict Professor of Biomedical Engineering at the Massachusetts General Hospital, Harvard Medical School. His research interests are at the interface of engineering and life sciences including micro/nanotechnology and applications in clinical medicine. In 1994, he was recognized by the “YC Fung Faculty Award.” In 1998, Dr Toner was selected to become a “Fellow of the American Institute of Medical and Biological Engineering.” In 2007, he became a “Fellow of the American Society of Mechanical Engineers."
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