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

• 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

Circulating TumorCell (CTC) Chip

Immunomagnetic-bead purification

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