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 Circulating Tumor Cell (CTC) Chip • Gross prognostic tool (high/low risk) • Isolates fewer CTCs with very low purity (<1%) and yield • Multiple bulk semi automated preparatory steps • 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