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Published on: July 5, 2019
Novel Omniphobic Platform for Multicellular Spheroid Generation, Drug Screening, and On-Plate Analysis
Mathew Boban1,2, Pooja Mehta3, Alex Kate Halvey2
1Macromolecular Science and Engineering, University of Michigan, Ann Arbor, Michigan 48109, United States.
Abstract:
Multicellular spheroids are superior to other culture geometries in reproducing critical physiological conditions of tumors, such as the diffusion of oxygen, nutrients, waste, and drugs, leading to a more precise model of in vivo drug sensitivity and resistance. Previously reported spheroid culture platforms are often difficult to use, expensive, single-use, or mechanically unstable. Here, we report a facile, mechanically stable, high-throughput spheroid culture platform based on hierarchically textured omniphobic surfaces. The developed omniphobic surfaces display very high contact angles with a range of different liquids, including the cell-laden culture media, thereby minimizing the cell surface contact area. Additionally, these surfaces maintain these high contact angles for extended periods of time to ensure cell aggregation. Using this novel platform, we demonstrate the generation and maintenance of robust multicellular spheroids, as well as heterogeneous, multicell-type spheroids. The platform is extremely robust, resistant to mechanical shock, allows for on-plate imaging, and is also the first-ever spheroid generation platform that can be reused repeatedly. Finally, the platform is suitable for on-plate drug screening and enables the first-ever, on-plate immunofluorescence staining and imaging of spheroids.
Insights
This study introduces a reusable, stable, and high-throughput platform for creating multicellular spheroids, improving tumor modeling and drug screening accuracy. The novel omniphobic surfaces facilitate spheroid formation and on-plate analysis.
Area of Science:
- Biotechnology
- Materials Science
- Cancer Research
Background:
- Multicellular spheroids better mimic tumor physiology than other culture methods, improving drug sensitivity and resistance models.
- Existing spheroid culture platforms often suffer from usability, cost, single-use limitations, or mechanical instability.
- Omniphobic surfaces offer potential for advanced cell culture applications due to their liquid-repellent properties.
Purpose of the Study:
- To develop a facile, mechanically stable, and reusable platform for high-throughput spheroid generation and culture.
- To leverage hierarchically textured omniphobic surfaces to minimize cell-surface contact and promote spheroid formation.
- To enable on-plate drug screening and analysis, including immunofluorescence staining, using the novel platform.
Main Methods:
- Fabrication of hierarchically textured omniphobic surfaces with high contact angles for cell-laden media.
- Demonstration of spheroid generation and maintenance using the developed platform.
- Assessment of platform robustness, reusability, and suitability for on-plate imaging and drug screening.
Main Results:
- The omniphobic surfaces effectively minimized cell-surface contact, promoting robust multicellular and multicell-type spheroid formation.
- The platform demonstrated exceptional mechanical stability and reusability over multiple cycles.
- On-plate drug screening and immunofluorescence staining of spheroids were successfully performed, showcasing the platform's utility.
Conclusions:
- The novel omniphobic surface platform provides a robust, reusable, and high-throughput solution for spheroid culture.
- This technology enhances the precision of tumor modeling and facilitates advanced on-plate drug screening assays.
- The platform represents a significant advancement in spheroid-based research for drug discovery and cancer studies.
