Related Experiment Video
Updated: Jun 3, 2025
Generation of Heterogeneous Drug Gradients Across Cancer Populations on a Microfluidic Evolution Accelerator for Real-Time Observation
Published on: September 19, 2019
A Novel Microfluidic Platform for Personalized Anticancer Drug Screening Through Image Analysis
Maria Veronica Lipreri1, Marilina Tamara Totaro2, Julia Alicia Boos3
1Biomedical Science, Technologies, and Nanobiotecnology Lab, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy.
Abstract:
The advancement of personalized treatments in oncology has garnered increasing attention, particularly for rare and aggressive cancer with low survival rates like the bone tumors osteosarcoma and chondrosarcoma. This study introduces a novel PDMS-agarose microfluidic device tailored for generating patient-derived tumor spheroids and serving as a reliable tool for personalized drug screening. Using this platform in tandem with a custom imaging index, we evaluated the impact of the anticancer agent doxorubicin on spheroids from both tumor types. The device produces 20 spheroids, each around 300 µm in diameter, within a 24 h timeframe, facilitating assessments of characteristics and reproducibility. Following spheroid generation, we measured patient-derived spheroid diameters in bright-field images, calcein AM-positive areas/volume, and the binary fraction area, a metric analyzing fluorescence intensity. By employing a specially developed equation that combines viability signal extension and intensity, we observed a substantial decrease in spheroid viability of around 75% for both sarcomas at the highest dosage (10 µM). Osteosarcoma spheroids exhibited greater sensitivity to doxorubicin than chondrosarcoma spheroids within 48 h. This approach provides a reliable in vitro model for aggressive sarcomas, representing a personalized approach for drug screening that could lead to more effective cancer treatments tailored to individual patients, despite some implementation challenges.
Insights
A new microfluidic device effectively generates patient-derived tumor spheroids for personalized drug screening in osteosarcoma and chondrosarcoma. Doxorubicin significantly reduced spheroid viability, highlighting potential for tailored cancer therapies.
Area of Science:
- Oncology
- Biomedical Engineering
- Cancer Research
Background:
- Personalized medicine is crucial for treating rare, aggressive cancers like osteosarcoma and chondrosarcoma.
- Existing drug screening methods may not fully capture patient-specific tumor responses.
- Need for reliable in vitro models for evaluating novel therapeutic strategies.
Purpose of the Study:
- To develop and validate a novel PDMS-agarose microfluidic device for generating patient-derived tumor spheroids.
- To utilize the device for personalized drug screening of anticancer agents.
- To assess the efficacy of doxorubicin against osteosarcoma and chondrosarcoma spheroids.
Main Methods:
- Fabrication of a PDMS-agarose microfluidic device for spheroid generation.
- Generation of patient-derived osteosarcoma and chondrosarcoma spheroids (approx. 300 µm diameter).
- Drug screening using doxorubicin and a custom imaging index measuring spheroid viability (diameter, calcein AM, binary fraction area).
Main Results:
- The microfluidic device reliably produced 20 spheroids within 24 hours, enabling reproducible assessments.
- Doxorubicin treatment (10 µM) decreased spheroid viability by approximately 75% in both osteosarcoma and chondrosarcoma.
- Osteosarcoma spheroids demonstrated higher sensitivity to doxorubicin compared to chondrosarcoma spheroids within 48 hours.
Conclusions:
- The developed microfluidic platform offers a reliable in vitro model for aggressive bone sarcomas.
- This patient-derived spheroid model facilitates personalized drug screening for tailored cancer treatments.
- The approach shows promise for improving therapeutic strategies despite some implementation challenges.
