Compressible Hollow Microlasers in Organoids for High-Throughput and Real-Time Mechanical Screening

Area of Science:

• Biophysics
• Bioengineering
• Cell Biology

Background:

• Mechanical stress in organoids is crucial for disease modeling and drug development.
• Existing methods for measuring organoid mechanics are slow, invasive, and lack dynamic capabilities.

Purpose of the Study:

• To introduce a novel all-optical method for rapid, dynamic, and non-invasive assessment of mechanical stress in organoids.
• To establish a high-throughput platform for screening mechano-responsive drugs and understanding organoid mechanobiology.

Main Methods:

• Development of biocompatible and compressible hollow microlasers for laser spectroscopy.
• Integration of microlasers with microwell arrays for high-throughput screening.
• Application of the technique to tumoroids and human embryonic stem cell-derived cardiac organoids.

Main Results:

• Achieved nanometer-scale identification of cellular deformation with tens of pascals stress sensitivity.
• Enabled investigation of the isotropic mechanical component of multicellular models.
• Demonstrated high-throughput screening of mechanical cues in tumoroids and mapped dynamic contractile stress in cardiac organoids, revealing internal mechanical inhomogeneity.

Conclusions:

• The developed hollow microlaser platform offers a powerful tool for organoid mechanobiology research.
• This method facilitates rapid, dynamic, and non-invasive mechanical stress assessment, crucial for disease modeling and drug discovery.
• Provides new insights into the mechanical properties and inhomogeneity of organoids.