A Label-Free Dual-Mode Flow Cytometry for Single-Cell Physicochemical Property Analysis

Area of Science:

• Biophysics
• Cell Biology
• Analytical Chemistry

Background:

• Label-free flow cytometry is crucial for cellular characterization.
• Existing methods lack the ability to measure both physical and chemical properties simultaneously at the single-cell level.

Purpose of the Study:

• To develop and validate a label-free dual-mode flow cytometry system integrating impedance and mass cytometry.
• To characterize physicochemical properties of single cells for improved cell typing and molecular mechanism investigation.

Main Methods:

• Integration of impedance cytometry for electrical and mechanical properties with mass cytometry for chemical composition analysis.
• On-chip electrospray ionization for mass spectrometry analysis of metabolites and lipids.
• Pilot testing on three human leukemia cell lines (THP-1, Jurkat, HL-60).

Main Results:

• Dual-mode cytometry achieved ~11% higher accuracy in cell typing compared to single-mode methods.
• Identified potential correlations between specific lipids (e.g., PC(P-36:0), PE(P-36:4), PC(38:2)) and cellular electrical properties.
• Preliminary findings suggest lipid composition influences biophysical characteristics like conductivity and capacitance.

Conclusions:

• The proposed dual-mode flow cytometry enables comprehensive single-cell physicochemical characterization.
• This technique offers new perspectives for studying molecular underpinnings of cellular biophysics.
• The findings open avenues for multimodal cell characterization and molecular cell biology research.