High-Throughput Characterization of Cell Adhesion Strength Using Long-Channel Constriction-Based Microfluidics.

Area of Science:

• Biophysics
• Cancer Biology
• Microfluidics

Background:

• Cancer cell adhesion strength is a critical biophysical marker for metastatic potential.
• Existing high-throughput methods using microfluidics struggle to accurately assess cell adhesion due to cell size heterogeneity.
• Understanding cell adhesion is vital for studying cancer cell escape from primary tumors and circulating tumor cell (CTC) anchoring.

Purpose of the Study:

• To develop a high-throughput microfluidic approach for accurately assessing cancer cell adhesion strength.
• To overcome the limitations of cell size heterogeneity in adhesion strength measurements.
• To establish a reliable method for characterizing the mechanical phenotypes of cancer cells.

Main Methods:

• Proposed a novel high-throughput method using a long-channel constriction microfluidic device.
• Utilized a friction coefficient based on the constant velocity stage of cell transit.
• Employed a compressed spring model to account for cell deformation and reduce the influence of cell size heterogeneity.

Main Results:

• Demonstrated that cell size is independent of adhesion strength but significantly affects transit velocity.
• The proposed model effectively offsets the influence of cell size heterogeneity on adhesion measurements.
• A strong linear relationship was observed between the friction coefficient and the logarithm of adhesion strength.

Conclusions:

• The developed friction coefficient-based microfluidic approach enables accurate, high-throughput characterization of cancer cell adhesion strength.
• This method enriches the functionality of constriction-based microfluidics for mechanical phenotype analysis.
• The findings offer new insights into the biophysical properties of cancer cells relevant to metastasis.