Analyzing cell mechanics in hematologic diseases with microfluidic biophysical flow cytometry

Area of Science:

• Hematology
• Biophysics
• Microfluidics

Background:

• Single-cell analysis is crucial for understanding hematologic diseases.
• Conventional flow cytometry lacks cell mechanical property measurement capabilities.
• Altered cell mechanics contribute to microvascular obstruction in diseases like sepsis and leukemia.

Purpose of the Study:

• To develop a high-throughput microfluidics-based biophysical flow cytometry technique.
• To measure single-cell transit times through in vitro capillary networks.
• To demonstrate clinical relevance in sepsis and leukemia-associated leukostasis.

Main Methods:

• Utilized microfluidics for high-throughput single-cell analysis.
• Measured single-cell transit times through in vitro capillary networks.
• Analyzed patient samples from sepsis and acute leukemia cases.

Main Results:

• Increased cell transit times and microfluidic channel occlusion observed in sepsis and leukostasis.
• Mechanical heterogeneity of blood cells predicted microvascular obstruction better than average properties.
• Identified specific alterations in neutrophil and leukemia cell subpopulations impacting disease progression.

Conclusions:

• Biophysical flow cytometry effectively characterizes disease-specific cellular mechanical changes.
• This method offers a novel diagnostic and drug discovery platform for microcirculatory disorders.
• Findings provide new insights into sepsis pathophysiology and leukostasis, guiding potential therapies.