Isolation of circulating tumor cells using a microvortex-generating herringbone-chip.

Area of Science:

• Biotechnology
• Oncology
• Microfluidics

Background:

• Circulating tumor cells (CTCs) are crucial biomarkers for nonhematological cancer detection and monitoring.
• Previous microfluidic devices, like the CTC-Chip, captured CTCs using EpCAM antibodies.
• A need exists for high-throughput platforms for efficient CTC isolation and analysis.

Purpose of the Study:

• To introduce and evaluate the herringbone-chip (HB-Chip) for high-throughput CTC isolation.
• To enhance the interaction between CTCs and antibody-coated surfaces for improved capture efficiency.
• To demonstrate the clinical utility of the HB-Chip in prostate cancer patient samples.

Main Methods:

• The HB-Chip utilizes passive microfluidic mixing via microvortices to increase CTC-surface interactions.
• Capture efficiency was validated by spiking known numbers of cancer cells into blood.
• Clinical samples from prostate cancer patients were analyzed using the HB-Chip.

Main Results:

• The HB-Chip detected CTCs in 93% of metastatic prostate cancer patients (median 63 CTCs/mL).
• Tumor-specific TMPRSS2-ERG translocation was identified in captured CTCs via RT-PCR.
• Transparent materials enabled imaging of CTCs using standard and immunofluorescence stains.
• The low shear design revealed microclusters of CTCs, suggesting a role in cancer dissemination.

Conclusions:

• The HB-Chip is an effective high-throughput platform for CTC isolation and characterization.
• HB-Chip technology facilitates the detection of CTCs and their genetic alterations in cancer patients.
• The identification of CTC microclusters offers new insights into cancer metastasis mechanisms.