SCO-ph: Microfluidic Dynamic Phenotyping Platform for High-Throughput Screening of Single Cell Acidification

Area of Science:

• Biotechnology
• Cell Biology
• Analytical Chemistry

Background:

• Quantitative high-throughput metabolism assays are crucial for single-cell phenotyping dynamics.
• Extracellular acidification is a key metabolic phenotype linked to cellular processes like tumorigenicity.

Purpose of the Study:

• To develop a versatile microfluidic system for single-cell optical pH analysis (SCO-pH).
• To enable high-throughput, temporal extracellular pH analysis for dynamic single-cell phenotyping.

Main Methods:

• Compartmentalization of single cells in 140-pL droplets within a microfluidic system.
• Immobilization of approximately 40,000 droplets in a 2D array for analysis.
• Encapsulation of a cell-impermeable pH probe for fluorescence-based pH quantification within each droplet.

Main Results:

• The SCO-pH system successfully distinguished cells undergoing hyperglycolysis from untreated cells by monitoring extracellular acidification.
• Single-cell heterogeneity in extracellular acidification dynamics was observed.
• The system demonstrated the ability to differentiate cells based on metabolic activity.

Conclusions:

• The developed SCO-pH system provides a high-throughput method for dynamic single-cell phenotyping.
• This technology is valuable for applications requiring the analysis of cellular metabolism and heterogeneity.
• SCO-pH facilitates the study of cellular metabolism and its implications in various biological contexts.