We are motivated by the view that development of a reliable and robust technology for efficient detection, characterization, and direct assay of minimal residual disease (MRD), including circulating tumor cells (CTCs) from blood and disseminated tumor cells (DTCs) from bone marrow, will make a major contribution toward elucidating the biology of the metastatic process and developing new methods for the management and treatment of cancer. These cells are important actors in how cancer may spread and kill people. Cancer is a dismal disease - within five years, almost 30% of cancer patients die, not from the primary tumor, but from the metastases or spread of the cancer to other organs in the body. It is thought that some cells can slough off the primary or secondary tumor and circulate in the bloodstream or find safe harbor in the relatively hypoxic bone marrow, and that some of these rare tumor cells (CTCs and DTCs) can lead to metastatic growth, especially if they acquire stem-cell like characteristics. The end goal is to demonstrate a transformative ability to capture and especially to manipulate rare cells on the same platform used to capture them, and to individually process captured cells in droplets for molecular characterization on the same chip. The novel idea embodied in this research is to use many small droplets containing immunomagnetic beads that probe for rare cells as the capture beads containing antibodies are sequentially incubated and washed with fluid droplets, in both a parallel and pipelined fashion. Gently probing small volumes with suspensions of magnetic beads should be much more efficient at capturing rare cells than probing a large volume, at the expense of requiring many repeated (but rapid) steps to eventually sample the full volume. Moreover, multiple antibodies may be used to probe one sample.
Our aims are 1) to demonstrate that sub-populations of rare cells can be captured in a pipeline of separate, individual droplets;and 2) to show that droplets containing rare cell types can be manipulated and transported to a site for biochemical profiling, by implementing assays designed towards exploiting the full metabolic potential of these cells.

Public Health Relevance

The end goal is to develop a device with a transformative ability to capture and individually characterize at the molecular level rare cancer cells found in the blood or bone marrow that may be responsible for the metastatic spread of cancer. Capturing and characterizing cancer cells will be done on a single chip for eventual use in selecting tumor-specific therapies.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (ZCA1-SRLB-Q (M2))
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Ossandon, Miguel
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Stanford University
Schools of Medicine
United States
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Padovani, José I; Jeffrey, Stefanie S; Howe, Roger T (2016) Electropermanent magnet actuation for droplet ferromicrofluidics. Technology (Singap World Sci) 4:110-119
Ferreira, Meghaan M; Ramani, Vishnu C; Jeffrey, Stefanie S (2016) Circulating tumor cell technologies. Mol Oncol 10:374-94