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Microcavity array (MCA)-based biosensor chip for functional drug screening of 3D tissue models.

Daniel Kloss1, Randy Kurz, Heinz-Georg Jahnke

  • 1Center for Biotechnology and Biomedicine (BBZ), University of Leipzig, Division of Molecular Biological-Biochemical Processing Technology, Deutscher Platz 5, 04103 Leipzig, Germany.

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Summary

A novel sensor chip enables real-time, non-destructive impedance spectroscopy and extracellular recording of 3D cell cultures, advancing drug development through high-content screening with reduced costs and assay times.

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Area of Science:

  • Biomedical Engineering
  • Cell Biology
  • Drug Discovery

Background:

  • Multicellular tumor spheroids are vital models for drug testing, mimicking native cellular environments.
  • Real-time monitoring of drug effects on 3D cultures is crucial for accurate assessment.
  • Existing methods often lack the speed, non-destructive nature, or comprehensive data required for advanced drug development.

Purpose of the Study:

  • To design and fabricate a novel sensor chip for fast, non-destructive impedance spectroscopy and extracellular recording of 3D cell cultures.
  • To evaluate the chip's efficacy in monitoring drug-induced changes in multicellular tumor spheroids and cardiomyocyte spheroids.
  • To establish a versatile platform for high-content drug screening with reduced costs and assay times.

Main Methods:

  • Fabrication of a novel sensor chip with a silicon-based electrode array and microcavities for spheroid positioning.
  • Utilizing impedance spectroscopy and extracellular potential recording for real-time monitoring of spheroid responses.
  • Application of the sensor chip to human melanoma spheroids treated with Camptothecin (CTT) and cardiomyocyte spheroids.

Main Results:

  • The sensor chip enabled non-destructive, real-time monitoring of drug effects on spheroids.
  • Camptothecin-treated melanoma spheroids showed increased impedance magnitudes due to altered cell morphology, not disintegration.
  • Extracellular potentials of cardiomyocyte spheroids were successfully monitored, demonstrating the chip's versatility.

Conclusions:

  • The developed multifunctional sensor chip is an effective acute test system for monitoring diverse 3D cell cultures.
  • This technology facilitates improved drug development through high-content screening, offering reduced costs and assay times.
  • The chip's design supports parallel testing of multiple substances, further enhancing screening efficiency.