Isolation of Rare Circulating Tumor Cells Sunitha Nagrath et al. Presentation by: Keara Darragh, Matthew Faw, and Will Plautz Overview of Metastasis and CTCs • Circulating tumor cells (CTCs) • Likely the origin of intractable metastatic disease • 1 CTC : 10^9 haematologic cells in the blood of cancer patients CTC chip better than existing methods Immunomagnetic-bead purification • Gross prognostic tool (high/low risk) • Isolates fewer CTCs with very low purity (<1%) and yield • Multiple bulk semiautomated preparatory steps Circulating Tumor Cell (CTC) Chip • First microfluidic device that can successfully isolate viable cells from milliliter volumes of whole blood • High sensitivity, selectivity, and yield • Single step What is Microfluidics? • Deals with small volumes (fL, pL, nL, µL) of fluids • Generally processed in a way that moves, mixes, or separates the contents • Microfluids act differently • Surface tension and low Reynolds number become larger factors in the system • Different types of microfluidics • Dealing with continuous-flow today What is Microfluidics? • Deals with small volumes (fL, pL, nL, µL) of fluids • Generally processed in a way that moves, mixes, or separates the contents • Microfluids act differently • Surface tension and low Reynolds number become larger factors in the system • Different types of microfluidics • Dealing with continuous-flow today What is Microfluidics? • Deals with small volumes (fL, pL, nL, µL) of fluids • Generally processed in a way that moves, mixes, or separates the contents • Microfluids act differently • Surface tension and low Reynolds number become larger factors in the system • Different types of microfluidics • Dealing with continuous-flow today How Does the Chip Capture Circulating Tumor Cells? • 25 mm x 66 mm silicon chip • 78,000 microposts • epCAM antibodies CTC Isolating Microfluidic Device 25mm Staining to Assess Purity • Stains are used in order to identify malignant cells from healthy cells. • Malignant cells look different • • • Large cellular size Relatively large nuclei Visible nucleoli Results and Applications • Successfully identified CTCs in 115/116 samples • Approximately 50% purity • CTCs isolated (per ml): • • NSCLC: 5-1,281 Breast: 5-174 • Monitor cancer treatment response Results and Applications • Successfully identified CTCs in 115/116 samples • Approximately 50% purity • CTCs isolated (per ml): • • NSCLC: 5-1,281 Breast: 5-174 • Monitor cancer treatment response Conclusion • First microfluidic device that can successfully process milliliter volumes of whole blood • High sensitivity, selectivity, and yield • Single step • Isolation of viable cells • Allows for real time monitoring of cancer progression in a non-invasive manner