Pheno-Morphological Screening and Acoustic Sorting of 3D Multicellular Aggregates Using Drop Millifluidics

Area of Science:

• Biomedical Engineering
• Cell Biology
• Cancer Research

Background:

• Three-dimensional multicellular aggregates (MCAs) like organoids and spheroids are crucial for studying disease mechanisms and drug testing in cancer research.
• Current manual analysis methods for MCAs are time-consuming, limiting their application in large-scale biological assays.

Purpose of the Study:

• To introduce a novel drop millifluidic approach, ImOCAS (Image-based Organoid Cytometry and Acoustic Sorting), for high-throughput screening and sorting of MCAs.
• To overcome the limitations of manual analysis and enable routine use of MCAs in large-scale biological assays.

Main Methods:

• Real-time image processing to detect pheno-morphological traits of MCAs.
• Encapsulation of MCAs in millimetric drops for on-demand actuation using acoustic radiation force.
• Development of ImOCAS for automated screening and sorting of over one thousand MCAs.

Main Results:

• Demonstrated successful sorting of spheroids with uniform sizes from heterogeneous populations.
• Showcased isolation of organoids from spheroids based on differing phenotypes.
• Validated the capability of ImOCAS for high-throughput analysis of MCAs.

Conclusions:

• ImOCAS provides a groundbreaking platform for high-throughput screening and high-content analysis of MCAs.
• This technology facilitates the analysis of MCAs with controlled morphological and phenotypical properties.
• The ImOCAS system promises to accelerate progress in biomedical research, particularly in drug discovery and disease mechanism studies.