Microfluidic device flow field characterization around tumor spheroids with tunable necrosis produced in an optimized...

Area of Science:

• Biomedical Engineering
• Cancer Research
• Microfluidics

Background:

• Tumor spheroids are advanced 3-D in vitro models for cancer research.
• Microfluidic devices offer precise control over spheroid microenvironments.
• Tailoring spheroid properties is crucial for accurate drug efficacy testing.

Purpose of the Study:

• To demonstrate controlled tumor spheroid growth and necrotic core formation.
• To investigate nanoparticle hydrodynamics and mass transport within tumor spheroids.
• To assess the impact of spheroid characteristics on therapy evaluation.

Main Methods:

• Controlled seeding of human colon cancer cells (HCT-116) in microwells.
• Manipulation of glucose concentration to control necrotic core presence.
• Micro-particle imaging velocimetry (micro-PIV) for hydrodynamic analysis.
• Fluorescent nanoparticle tracking to study mass transport.

Main Results:

• Tumor spheroid growth rates were controlled by initial cell seeding density.
• Necrotic core formation was modulated by glucose concentration without altering spheroid size or hypoxia.
• Microfluidic device geometry influenced flow velocity distribution across the spheroid.
• Nanoparticle accumulation and penetration depth were dependent on flow dynamics and particle size.

Conclusions:

• Controlled manipulation of tumor spheroid characteristics, specifically necrotic core presence, is achievable.
• Microfluidic platforms enable detailed analysis of nanoparticle transport within 3-D tumor models.
• This approach enhances the potential for in vitro cancer therapy assessment by isolating key biological factors.