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A high-throughput liquid biopsy for rapid rare cell separation from large-volume samples.

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This study introduces a high-throughput liquid biopsy platform for rare tumor cell separation. The novel gravity-driven system achieves high recovery and cell viability, advancing cancer detection and monitoring in various body fluids.

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Area of Science:

  • Biomedical Engineering
  • Cancer Research
  • Analytical Chemistry

Background:

  • Liquid biopsy offers a minimally invasive approach for cancer detection and monitoring.
  • Current techniques for rare tumor cell separation face challenges in throughput, recovery rates, and cell viability.
  • Efficient separation of circulating tumor cells (CTCs) and exfoliated tumor cells (ETCs) is crucial for clinical applications.

Purpose of the Study:

  • To develop and validate a high-throughput liquid biopsy platform for efficient rare tumor cell separation.
  • To enhance cell viability and recovery rates in liquid biopsy applications.
  • To expand the utility of liquid biopsy to various body fluids beyond whole blood.

Main Methods:

  • Utilized a 2.5D micropore-arrayed filtration membrane with high porosity (>40.2%) and small edge-to-edge pore spacing (<4 μm).
  • Employed a gravity-driven filtration system, eliminating the need for external pressure.
  • Tested the platform with spiked lung tumor cells (A549s) in PBS, bronchoalveolar lavage fluid (BALF), and whole blood, as well as clinical samples from lung cancer patients.

Main Results:

  • Achieved high filtration throughputs: >110 mL/min for aqueous samples and >17 mL/min for undiluted whole blood.
  • Demonstrated high recovery rates for spiked tumor cells: 88.0% in PBS, 86.0% in BALF, and 83.2% in whole blood.
  • Successfully detected circulating tumor cells (CTCs) in whole blood samples from lung cancer patients and confirmed the importance of small pore spacing for cell viability and purity.

Conclusions:

  • The developed high-throughput liquid biopsy platform offers superior performance in rare tumor cell separation, characterized by high recovery rates and cell viability.
  • The gravity-driven filtration system is effective for processing large volumes of various body fluids, including BALF and whole blood.
  • This technology has the potential to broaden the application of liquid biopsy for detecting exfoliated tumor cells (ETCs) in diverse clinical samples, facilitating practical clinical applications.