EGFR mutation detection of lung circulating tumor cells using a multifunctional microfluidic chip

Area of Science:

• Biomedical Engineering
• Molecular Diagnostics
• Cancer Research

Background:

• Microfluidics offers advantages for circulating tumor cell (CTC) detection due to its integration, small size, and efficiency.
• Existing methods for CTC analysis can be complex and time-consuming.

Purpose of the Study:

• To develop a multifunctional microfluidic device for integrated CTC capture, lysis, and genetic analysis.
• To enable precise genetic characterization of CTCs on a single chip.

Main Methods:

• A novel microfluidic device integrating CTC capture, lysis, and digital polymerase chain reaction (dPCR) based nucleic acid detection was developed.
• The device utilizes membrane valves for controlled transfer of lysed CTCs to a microcavity array for dPCR analysis.
• EGFR-L858R mutation detection was performed on lung cancer cell lines (H1975, A549) and normal leukocytes.

Main Results:

• The microfluidic chip successfully captured and lysed CTCs, enabling subsequent nucleic acid detection.
• EGFR-L858R mutations were specifically detected in H1975 lung cancer cells, with no signal in A549 cells or leukocytes.
• A high linear relationship (R² = 0.9897) was observed between detected and expected values, demonstrating assay reliability.

Conclusions:

• The developed multifunctional microfluidic chip integrates key steps for CTC genetic analysis, from capture to mutation detection.
• This technology provides a promising platform for precise diagnosis and targeted therapy selection in cancer treatment.
• The chip's ability to detect gene mutations in CTCs offers valuable insights for personalized oncology.