Post-enrichment circulating tumor cell detection and enumeration via deformability impedance cytometry

Area of Science:

• Biomedical Engineering
• Oncology
• Microfluidics

Background:

• Circulating tumor cells (CTCs) are crucial biomarkers for cancer detection, diagnosis, and monitoring.
• Accurate enumeration and characterization of CTCs are essential for effective cancer management.
• Existing methods for CTC analysis often require cell labeling or enrichment, adding complexity and potential bias.

Purpose of the Study:

• To develop and validate a novel microfluidic biosensor system for label-free detection and enumeration of CTCs.
• To assess the performance of the biosensor in differentiating between cancer cells and blood cells.
• To evaluate two configurations of the microfluidic sensor for their efficacy in CTC analysis.

Main Methods:

• A constriction-based microfluidic sensor with embedded electrodes was designed to measure cell impedance.
• Differential impedance profiles were analyzed as cells transited the microfluidic channel, exploiting deformability differences between cancer and blood cells.
• Two sensor configurations were tested: integrated electrodes and externally fixed electrodes, using spiked breast and prostate cancer cells in murine blood.

Main Results:

• The microfluidic biosensor successfully detected and enumerated all spiked tumor cells in murine blood.
• The system demonstrated the ability to differentiate between breast and prostate cancer cell lines based on impedance profiles.
• Both sensor configurations achieved high accuracy in detecting CTCs, with a current throughput of 1 μL/min.

Conclusions:

• The developed microfluidic biosensor offers a promising label-free method for CTC detection and enumeration.
• The system's ability to differentiate cell types and its potential for scalability make it valuable for cancer monitoring.
• This technology supports post-enrichment, label-free analysis of CTCs for improved cancer diagnostics and prognostics.