BEGIN:VCALENDAR VERSION:2.0 PRODID:-//Memento EPFL// BEGIN:VEVENT SUMMARY:Extreme Microfluidics for Rare Tumor Cell Sorting from Large-Volu mes of Blood DTSTART:20170313T121500 DTSTAMP:20260407T164021Z UID:2240a9e64d8f0a3e08fa4dfea1b11d555363c9f33f8629e6e2de2619 CATEGORIES:Conferences - Seminars DESCRIPTION:Prof. Mehmet Toner\, MD\, PhD\, Massachusetts Institute of Tec hnology\, Cambridge\, MA (USA)\nDISTINGUISHED LECTURE IN BIOLOGICAL ENGINE ERING\n(sandwiches served)\n\nAbstract:\nViable tumor-derived circulating tumor cells (CTCs) have been identified in peripheral blood from cancer pa tients and are not only the origin of intractable metastatic disease but a lso marker for early cancer. However\, the ability to isolate CTCs has pro ven to be difficult due to the exceedingly low frequency of CTCs in circul ation. As a result their clinical use until recently has been limited to p rognosis with limited clinical utility.  More recently\, we introduced se veral microfluidic methods to improve the sensitivity of rare event CTC is olation\, a strategy that is particularly attractive because it can lead t o efficient purification of viable CTCs from unprocessed whole blood. The micropost CTC-Chip (μpCTC-Chip) relies on laminar flow of blood cells thr ough anti-EpCAM antibody-coated microposts\, whereas the herringbone CTC-C hip (HbCTC-Chip) uses micro-vortices generated by herringbone-shaped groov es to efficiently direct cells toward antibody-coated surfaces. These anti gen-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 mi crofluidic 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 a dvantage of the approach stems from the fact that it is based on “negati ve depletion” of blood cells and hence it is applicable to all solid tum ors and does not require tagging or labeling the tumor cells.  As a resul t the CTCs are isolated in pristine conditions and are amenable to analysi s using imaging\, molecular\, and other approaches.  We applied these thr ee microfluidic platforms to blood samples obtained from lung\, prostate\, breast\, colon\, melanoma\, and pancreatic cancer patients. We isolated C TCs from patients with metastatic non-small-cell-lung cancer and identifie d the EGFR activating mutation in CTCs. We also detected the T790M mutatio n\, which confers drug resistance. We also applied microchip to isolate CT Cs from blood specimens of patients with either metastatic or localized pr ostate cancer\, and showed the presence of CTCs in early disease. Remarkab ly\, the low shear design of the HBCTC-chip revealed micro-clusters of CTC s in a subset of patient samples. Microscopic CTC aggregates may contribut e to the hematogenous dissemination of cancer.  More recently\, we used m icrofluidic capture of CTCs to measure androgen receptor (AR) signaling re adouts before and after therapeutic interventions using single-cell immuno fluorescence analysis of CTCs. The results support the relevance of CTCs a s dynamic tumor-derived biomarkers\, reflecting “real time” effects of cancer drugs on their therapeutic targets\, and the potential of CTC sign aling analysis to identify the early emergence of resistance to therapy. W e also characterized epithelial-to-mesenchymal transition (EMT) in CTCs fr om breast cancer patients. While a few primary tumor cells simultaneously expressed mesenchymal and epithelial markers\, mesenchymal cells were high ly enriched in CTCs\, and most importantly\, serial CTC monitoring suggest ed an association of mesenchymal CTCs with disease progression suggesting a role for EMT in the blood-borne dissemination of human breast cancer. We have also identified the presence of CTC clusters\, which led to the deve lopment of a microchip that is designed to sort clusters of cells from who le blood without any labeling.  The propensity of CTC clusters to lead to metastasis is significantly higher than single CTCs\, and underlies the i mportance these cells play in the metastatic cascade.  This presentation will share our integrated strategy to simultaneously advance the engineeri ng and microfluidics of CTC-Chip development\, the biology of these rare c ells\, and the potential clinical applications of circulating tumor cells. \n\nBio:\nMehmet Toner is Professor of Surgery (Biomedical Engineering) at the Massachusetts General Hospital\, Harvard Medical School\, and is the founding director of the NIH BioMEMS Resource Center.\nDr. Toner was born in Istanbul\, Turkey in July 1958.  Dr. Toner received a Bachelor of Scie nce degree from Istanbul Technical University in 1983 and an M.S. degree f rom the Massachusetts Institute of Technology (MIT) in 1985\, both in Mech anical Engineering.  He subsequently completed his Ph.D. in Medical Engin eering at the Harvard-MIT Division of Health Sciences and Technology (HST) in 1989.  He joined the faculty at the Massachusetts General Hospital (M GH) and Harvard Medical School as an Assistant Professor of Biomedical Eng ineering in 1989\, and was promoted to Associate Professor in 1996\, and t o Professor in 2002.  Dr. Toner has a joint appointment as a Professor of Health Sciences and Technology at the Harvard-MIT Division of HST. LOCATION:SV 1717 https://plan.epfl.ch/?room==SV%201717 STATUS:CONFIRMED END:VEVENT END:VCALENDAR