Pinched-flow hydrodynamic stretching of single-cells

Area of Science:

• Biophysics
• Cell Biology
• Microfluidics

Background:

• Cellular structural changes, like cytoskeletal reorganization, correlate with cell state and disease.
• Cell mechanical properties (mechanophenotype) serve as label-free biomarkers for disease detection.
• Accurate characterization of heterogeneous clinical samples requires high-throughput, single-cell analysis.

Purpose of the Study:

• To develop an advanced hydrodynamic stretching method for high-throughput cell mechanical phenotyping.
• To enable label-free biomarker discovery for diseases using cell deformability.
• To improve the throughput of cell mechanical analysis for rare cell population identification.

Main Methods:

• Developed an alternative hydrodynamic stretching mode using pinched flows to squeeze cells.
• Utilized hydraulic circuit design to control stretching forces and enable multiple stretching modes (pinched-flow and extensional) within a single microfluidic channel.
• Achieved high-throughput analysis with an order of magnitude increase compared to previous methods.

Main Results:

• The pinched-flow stretching method successfully differentiated cell deformability in two model systems.
• The system demonstrated the ability to generate a self-sheathing flow from a single fluid input.
• Achieved a throughput of 65,000 cells per second, significantly enhancing previous capabilities.

Conclusions:

• The novel pinched-flow hydrodynamic stretching technique offers a powerful tool for label-free cell mechanical phenotyping.
• This high-throughput method is particularly valuable for identifying rare cell populations in clinical samples.
• The adaptable microfluidic design has broad utility for various cytometry applications.