Cell Sorting and Cancer Diagnosis

The research thrust of the Cell Sorting and Diagnosis Group at the Center for Engineering in Medicine & Surgery is to develop point-of-care devices for capturing circulating tumor cells from the peripheral blood of cancer patients.

We are developing point-of-care devices using microfluidic technologies for capturing circulating tumor cells from peripheral blood of cancer patients.

These cells, called circulating tumor cells (CTCs), provide a cellular link between the primary malignant tumor and the metastatic sites, and thus, the ability to non-invasively isolate CTCs from the blood of cancer patients has far-reaching diagnostic, prognostic, therapeutic and basic cancer biology implications.

The major challenge for such isolation stems from the fact that CTCs are very rare in patients with cancer, comprising as few as only 1 to 10 cells/mL of blood, beyond the limits of current cell separation technologies.

Recently, we have developed a novel microfluidic platform capable of selective separation of CTCs from the peripheral blood of cancer patients. Using this technology, we successfully demonstrated the capture of CTCs from patients with lung, prostate, colon or pancreatic tumors.

This technological advance has important clinical implications and ultimately could be applied as a point-of-care high-throughput diagnostic device, and for longitudinal follow-up of cancer patients for tailored targeted therapy.

Examples of ongoing projects include:

• Isolation of CTCs by utilizing inertial focusing and magnetic selection
• Capturing CTCs in microvortex generating herringbone chip
• Microfluidic system for monitoring infection by radio-labeling leukocytes
• Protein isolation from whole blood using microfluidics

Affiliated Faculty

• Mehmet Toner, PhD
• Shannon Stott, PhD
• Daniel Irimia, MD, PhD
• Martin Yarmush, MD, PhD
• N. Murat Karabacak, PhD
• Irit Adini, PhD

Representative Publications

1. Aceto, Nicola, Aditya Bardia, David T. Miyamoto, Maria C. Donaldson, Ben S. Wittner, Joel A. Spencer, Min Yu, Adam Pely, Amanda Engstrom, Huili Zhu, Brian W. Brannigan, Ravi Kapur, Shannon L. Stott, Toshi Shioda, Sridhar Ramaswamy, David T. Ting, Charles P. Lin, Mehmet Toner, Daniel A. Haber, and Shyamala Maheswaran. "Circulating tumor cell clusters are oligoclonal precursors of breast cancer metastasis." Cell 158, no. 5 (2014): 1110-1122.
2. Luo, Xi, Devarati Mitra, Ryan J. Sullivan, Ben S. Wittner, Anya M. Kimura, Shiwei Pan, Mai P. Hoang, Brian W. Brannigan, Donald P. Lawrence, Keith T. Flaherty, Lecia V. Sequist, Martin McMahon, Marcus W. Bosenberg, Shannon L. Stott, David T. Ting, Sridhar Ramaswamy, Mehmet Toner, David E. Fisher, Shyamala Maheswaran, and Daniel A. Haber. "Isolation and molecular characterization of circulating melanoma cells." Cell reports 7, no. 3 (2014): 645-653.
3.  Karabacak, N. M., Spuhler, P. S., Fachin, F., Lim, E. J., Pai, V., Ozkumur, E., Martel, J.M., Kojic, N., Smith, K., Chen, P., Yang, J., Hwang, H., Morgan, B., Trautwein, J., Barber, T. A., Stott, S. L., Maheswaran, S., Kapur, R., Haber, D. A., and Toner, M. (2014).Microfluidic, marker-free isolation of circulating tumor cells from blood samples. Nature protocols, 9(3), 694-710.
4. Sarioglu, A. Fatih, Nicola Aceto, Nikola Kojic, Maria C. Donaldson, Mahnaz Zeinali, Bashar Hamza, Amanda Engstrom, Huili Zhu, Tilak K Sundaresan, David T Miyamoto, Xi Luo, Aditya Bardia, Ben S Wittner, Sridhar Ramaswamy, Toshi Shioda, David T Ting, Shannon L Stott, Ravi Kapur, Shyamala Maheswaran, Daniel A Haber and Mehmet Toner. "A microfluidic device for label-free, physical capture of circulating tumor cell clusters." Nature methods(2015).
5. Reátegui, Eduardo, Nicola Aceto, Eugene J. Lim, James P. Sullivan, Anne E. Jensen, Mahnaz Zeinali, Joseph M. Martel, Alexander J. Aranyosi, Wei Li, Steven Castleberry, Aditya Bardia, Lecia V. Sequist, Daniel A. Haber, Shyamala Maheswaran, Paula T. Hammond, Mehmet Toner, and Shannon L. Stott. "Tunable Nanostructured Coating for the Capture and Selective Release of Viable Circulating Tumor Cells." Advanced Materials 27, no. 9 (2015): 1593-1599.