Leukocyte Depletion and Size-Based Enrichment of Circulating Tumor Cells Using a Pressure-Sensing Microfiltration...

Area of Science:

• Biomedical Engineering
• Oncology
• Genomics

Background:

• Isolating circulating tumor cells (CTCs) for liquid biopsy presents challenges in maintaining cellular integrity and purity.
• Current methods often struggle with cellular stress and contamination from other blood components.

Purpose of the Study:

• To develop and validate an optimal microfiltration device for noninvasive isolation of CTCs from whole blood.
• To assess the device's efficiency in separating tumor cells from leukocytes and enabling downstream genomic analysis.
• To demonstrate the clinical utility of CTCs isolated via microfiltration for molecular profiling in lung cancer.

Main Methods:

• Experimental analysis of microfilter performance using pressure sensing for cell separation.
• Spiking whole blood with tumor cells and quantifying recovery rates and leukocyte depletion.
• Genomic profiling of isolated CTCs, including DNA amplification and mutation detection.
• Application of the microfiltration method in a clinical setting for lung cancer patient samples.

Main Results:

• The microfiltration device achieved an average recovery rate of >96% for spiked tumor cells.
• Demonstrated significant depletion of >99% for total leukocytes, ensuring high purity of CTCs.
• Successfully performed genomic profiling on microfiltered CTCs, detecting epidermal growth factor receptor mutations.
• Validated the method's efficacy in a clinical setting for characterizing targeted drug efficacy in lung cancer.

Conclusions:

• The developed blood microfiltration device offers an optimal approach for noninvasive liquid biopsy targeting CTCs.
• The method provides high CTC recovery and purity, facilitating accurate genomic analysis.
• This technique serves as a valuable tool for evaluating filtration parameters and concentrating CTCs for cancer research and diagnostics.