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Capillary-assisted microfluidic biosensing platform captures single cell secretion dynamics in nanoliter

Amin Hassanzadeh-Barforoushi1, Majid Ebrahimi Warkiani2, David Gallego-Ortega3

  • 1School of Mechanical and Manufacturing Engineering, University of New South Wales, Sydney, NSW, 2052, Australia; Cancer Division, Garvan Institute of Medical Research/ the Kinghorn Cancer Centre, Sydney, NSW, 2010, Australia; Graduate School of Biomedical Engineering, ARC Centre of Excellence in Nanoscale BioPhotonics (CNBP), Faculty of Engineering, University of New South Wales, Sydney, NSW, 2052, Australia; Australian Centre for NanoMedicine, University of New South Wales, Sydney, 2052, Australia.

Biosensors & Bioelectronics
|March 29, 2020
PubMed
Summary

This study introduces a new microfluidic biosensing method to capture and monitor single cancer cell secretions over time. The approach reveals distinct cancer cell secretion dynamics, aiding in understanding disease progression.

Keywords:
BiosensingCancerCapillary microfluidicsCellular heterogeneityDynamic protease secretionSingle cell analysis

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Area of Science:

  • Biomedical Engineering
  • Cancer Biology
  • Microfluidics

Background:

  • Cancer cells secrete inflammatory biomolecules crucial for disease progression and metastasis.
  • Existing microfluidic methods face challenges in operational complexity and long-term, real-time single-cell secretion analysis.

Purpose of the Study:

  • To develop a user-friendly and reliable capillary-based microfluidic biosensing system for single cancer cell secretion analysis.
  • To quantify individual cancer cell secretion dynamics at high resolution over extended culture periods.

Main Methods:

  • Utilized a capillary-based microfluidic device with isolated nanoliter compartments for single-cell capture via pipette injection.
  • Investigated fluid mechanics for compartment formation and employed a Förster Resonance Energy Transfer (FRET)-based biosensor to monitor single-cell protease activity.
  • Quantified single-cell secretion dynamics over approximately 16 hours.

Main Results:

  • Successfully captured ~500 single cells in isolated compartments.
  • Identified distinct cancer cell secretion dynamics, including low secretion, sharp spikes, and slow progressive trends.
  • Demonstrated a feasible and reliable method for high-throughput measurement of cancer cell metabolic activities.

Conclusions:

  • The developed microfluidic biosensing approach overcomes existing barriers in single-cell secretion analysis.
  • This technique enables long-term, real-time monitoring of individual cancer cell secretion dynamics.
  • Provides a valuable tool for understanding cancer cell heterogeneity and behavior.