Drug screening of biopsy-derived spheroids using a self-generated microfluidic concentration gradient

Area of Science:

• Oncology
• Biotechnology
• Microfluidics

Background:

• Drug screening for cancer using 3D tumor models from patient biopsies faces limitations due to scarce cellular material.
• Physiologically relevant 3D tumor models are crucial for effective anticancer drug development and personalized medicine.

Purpose of the Study:

• To develop and validate a microfluidic platform for extensive anticancer compound screening using patient-derived multicellular spheroids.
• To enable pre-treatment drug screening for personalized medicine applications in oncology.

Main Methods:

• A microfluidic platform was designed to create multicellular spheroids from tumor biopsy samples.
• The platform facilitated the formation of reproducible drug concentration gradients across spheroid arrays without external fluid actuation.
• Spheroids derived from primary human prostate cancer cells were screened with standard-of-care compounds, with drug efficacy assessed via image analysis.

Main Results:

• The microfluidic platform successfully enabled drug screening of patient-derived prostate cancer spheroids.
• Repeatable drug concentration gradients were achieved, allowing simultaneous testing of multiple concentrations on various spheroid sizes and replicates.
• Analysis of brightfield and fluorescence images provided quantitative readouts of spheroid response to anticancer compounds over time.

Conclusions:

• This microfluidic technology offers a viable solution for drug screening with limited patient biopsy material.
• The platform supports personalized medicine by allowing extensive pre-treatment screening of anticancer compounds on patient-specific tumor models.
• The developed system has the potential to reduce costs and time in drug development and healthcare delivery for cancer patients.