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Multiplexed Single-Cell Measurements of FDG Uptake and Lactate Release Using Droplet Microfluidics
Debanti Sengupta1, Amy Mongersun2, Tae Jin Kim1
11 Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USA.
Cancer cell metabolism is complex. A new microfluidic device shows that glucose uptake and lactate release are poorly correlated at the single-cell level, revealing metabolic heterogeneity.
Area of Science:
- Biochemistry
- Cancer Biology
- Microfluidics
Background:
- Cancer cells exhibit enhanced aerobic glycolysis, consuming glucose and releasing lactate.
- Aerobic glycolysis is a key indicator of cancer metabolism.
- Single-cell analysis of both glucose uptake and lactate release simultaneously is lacking.
Purpose of the Study:
- To develop and characterize a novel droplet microfluidic device.
- To enable multiplexed measurements of glucose uptake and lactate release in single live cells.
- To investigate the correlation between glucose utilization and lactate production at the single-cell level.
Main Methods:
- Development of a droplet microfluidic device for single-cell encapsulation.
- Utilized 18F-fluorodeoxyglucose (an analog of glucose) for uptake measurements.
- Measured lactate release from individual cells within droplets.
Main Results:
- 18F-fluorodeoxyglucose uptake and lactate release showed only marginal correlation at the single-cell level.
- Cells with high 18F-fluorodeoxyglucose uptake released substantial lactate.
- Many cells released high lactate levels without significant 18F-fluorodeoxyglucose uptake.
Conclusions:
- Cancer cell metabolism is heterogeneous and relies on pathways beyond aerobic glycolysis.
- Single-cell metabolic analysis reveals significant cell-to-cell variability.
- Positron emission tomography (PET) measurements of 18F-fluorodeoxyglucose uptake reflect aggregate metabolic flux, not individual cell metabolism.
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