Controlling fluid flow rate to separate leukocytes and cancer cells based on stiffness differences

Area of Science:

• Biomedical Engineering
• Cell Biology
• Microfluidics

Background:

• Label-free sorting of circulating tumor cells (CTCs) often relies on size differences.
• Leukocytes and CTCs can have overlapping size ranges, hindering accurate separation.
• Existing methods face challenges in achieving high purity of CTCs due to size overlap.

Purpose of the Study:

• To develop a microfluidic strategy for label-free CTC sorting based on cell stiffness.
• To overcome limitations of size-based sorting methods by utilizing mechanical property differences.
• To improve the purity of isolated CTCs for downstream analysis.

Main Methods:

• Implemented a microfluidic device controlling fluid flow rate for cell separation.
• Established a quantitative model relating critical flow rate, cell diameter, and Young's modulus.
• Validated the model using fluid dynamics simulations and experimental verification.

Main Results:

• Achieved efficient separation of cells with overlapping sizes by controlling fluid flow.
• Demonstrated that high-stiffness leukocytes were captured, while low-stiffness CTCs passed through.
• Reported a high separation resolution of 0.3 µm, distinguishing cells based on stiffness.

Conclusions:

• Cell stiffness differences can be effectively utilized for microfluidic sorting of CTCs.
• This method complements existing size-based techniques, enhancing CTC isolation purity.
• The developed strategy offers a promising approach for improved CTC enrichment in liquid biopsies.