Circulating Tumor Cell Technologies
One of the major focuses of our research in collaboration with Drs. Ronald Tompkins and Daniel Haber is to develop a microchip to sort circulating tumor cells from peripheral blood. Because CTCs provide a cellular link between the primary malignant tumor and the metastatic sites, the ability to non-invasively isolate CTCs from the blood of cancer patients has far-reaching diagnostic, prognostic, therapeutic, and basic cancer biology implications that would otherwise require invasive serial biopsies.  Unfortunately, CTCs are very rare in patients with cancer, comprising as few as only 1 to 10 cells/mL of blood and present a tremendous challenge for any cell separation technology. Current strategies for isolating CTCs are limited by complex analytic approaches, with relatively low yield and purity. To address this unmet technological challenge, we have developed a microfluidic platform (the “CTC-chip”) capable of efficient and selective separation of viable CTCs from peripheral whole blood samples, mediated by the interaction of target CTCs with antibody (EpCAM)-coated microposts under precisely controlled laminar flow conditions, and without requisite sample pre-labeling or processing. Using this technology, we successfully captured circulating epithelial cells from various adenocarcinomas such as lung, prostate, colon and pancreas. Given the high sensitivity and specificity of the CTC-chip, we tested its potential utility in monitoring response to anti-cancer therapy. In a small cohort of patients with metastatic cancer undergoing systemic treatment, temporal changes in CTC numbers correlated reasonably well with the clinical course of disease as measured by standard radiographic methods. This technological advance has important clinical implications and ultimately could be applied as a point-of-care high-throughput diagnostic device as well as being used for longitudinal follow-up of cancer patients for tailored targeted therapy. Efforts are also underway to identify, propagate and molecularly characterize CTC subpopulations and expand the understanding of the biology of metastasis.  These efforts are in collaboration with many members of the Massachusetts General Hospital Cancer Center.

Selected Publications

Cheng X, Irimia, Dixon M, Sekine K, Demirci U, Zamir L, Tompkins RG, Rodriguez W, Toner M. Practical label-free CD4+ T cell counting of HIV-infected subjects: A Microchip approach. Lab on a Chip 2007; 10:1039.

Demirci U, Toner M. Direct etch method for microfluidic channel and nanoheight post-fabrication by picoliter droplets. Applied Physics Letters 2006; 88 (5), 053117.

Irimia D, Geba D, Toner M. Universal microfluidic gradient generator. Analytical Chemistry 2006; 78: 3472-3477. 

Irimia D, Toner M. Cell handling using microstructured membranes. Lab on a Chip 2006; 6: 345-352.

Pregibon DC, Toner M, Doyle PS. Multi-functional encoded particles for high-throughput biomolecule analysis. Science 2007; 315:1393-1396.

DiCarlo D, Irimia D, Tompkins RG, Toner M. Inertial self-sorting of cells and particles.  Proceedings of the National Academy of Sciences USA (in press).

Cheng X, Irimia D, Dixon M, Ziperstein JC, Demirci U, Zamir L, Tompkins RG, Toner M, Rodriguez W. A microchip approach for practical label-free CD4+ T cell counting of HIV-infected subjects in resource-poor settings. J AIDS 2007; 45(3): 257-261.

Nagrath S, Sequist LV, Maheswaran S, Bell DW, Irimia D, Ulkus L, Smith MR, Kwak EL, Digumarthy S, Muzikansky A, Ryan P, Balis UJ, Tompkins RG, Haber DA, and Toner M. Microchip-based isolation of rare circulating epithelial cells in cancer patients. Nature, 2007 (in press).