Uniform Tumor Spheroids on Surface-Optimized Microfluidic Biochips for Reproducible Drug Screening and Personalized...

Area of Science:

• Biotechnology
• Cancer Research
• Microfluidics

Background:

• Spheroids mimic natural tumors but conventional methods lack control over size, shape, and density, hindering reproducibility.
• Accurate prediction of cellular drug responses is vital for developing new cancer therapies and personalized medicine.

Purpose of the Study:

• To develop a surface-optimized polydimethylsiloxane (PDMS) microfluidic biochip for reproducible production of uniform multicellular spheroids.
• To assess the utility of this platform for predicting in vivo-like cellular responses to chemotherapeutic drugs.

Main Methods:

• A PDMS microfluidic biochip was surface-optimized with bovine serum albumin (BSA) to create cell-repellent properties, promoting spheroid self-aggregation.
• Lung cancer cell lines (A549), co-cultures (A549 with osteoblasts), and patient-derived cells were cultured in the biochip.
• Cellular responses to Doxorubicin were compared between the 3D biochip platform and 2D cultures.

Main Results:

• The optimized biochip reproducibly generated uniform and homogenous multicellular spheroids.
• 3D spheroids in the biochip showed cellular responses to Doxorubicin that more closely mimicked in vivo conditions compared to 2D cultures.
• Co-culture and patient-derived spheroids demonstrated greater anti-cancer drug resistance than mono-culture spheroids.

Conclusions:

• The surface-optimized biochip provides a reliable platform for generating uniform spheroids, enhancing reproducibility in drug screening.
• This 3D spheroid model offers a more accurate prediction of drug efficacy, supporting the development of personalized cancer therapies.
• The platform is valuable for studying the tumor microenvironment and for high-throughput drug screening.