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Microfluidically-generated Encapsulated Spheroids (μ-GELS): An All-Aqueous Droplet Microfluidics Platform for
Jennifer Kieda1,2,3, Sila Appak-Baskoy2,3,4, Morteza Jeyhani2,3,5
1Graduate Program in Biomedical Engineering, Toronto Metropolitan University, TorontoM5B 2K3, Canada.
ACS Biomaterials Science & Engineering
|January 10, 2023
Summary
This study introduces an all-aqueous droplet microfluidic platform for creating multicellular spheroids (MCSs) without cytotoxic solvents. The system enables on-chip gelation and demonstrates viability for cancer drug testing.
Area of Science:
- Biotechnology
- Cell Biology
- Microfluidics
Background:
- Spheroids are vital in vitro tumor models, but current methods often use toxic organic solvents.
- Existing all-aqueous methods struggle with complete on-chip hydrogel gelation.
Purpose of the Study:
- To develop an enhanced droplet microfluidic platform for all-aqueous hydrogel multicellular spheroid (MCS) formation.
- To enable on-chip gelation of MCSs without cytotoxic organic solvents.
- To validate the platform for cell viability and cancer drug testing.
Main Methods:
- Utilized a droplet microfluidic system to generate dextran-alginate droplets with MCF-7 breast cancer cells.
- Incorporated a polyethylene glycol continuous phase and a calcium chloride crosslinking solution.
- Employed an embedded capillary at a second junction to delay gelation and prevent channel clogging.
Main Results:
- Achieved on-chip gelation of all-aqueous hydrogel MCSs.
- Demonstrated MCS viability for up to 6 days in drug-free conditions.
- Confirmed the platform's utility for cancer drug screening with doxorubicin, showing dose-dependent cell death.
Conclusions:
- The enhanced droplet microfluidic platform successfully forms viable, all-aqueous hydrogel MCSs on-chip.
- This method offers a non-cytotoxic alternative for spheroid generation and cancer drug testing.
- The system holds promise for improved in vitro tumor modeling and pharmaceutical screening.

