Microfluidic Tissue Array Platform for Personalized Drug Screening Using Tumor Explants or Biopsies

Area of Science:

• Oncology
• Biomedical Engineering
• Translational Medicine

Background:

• Current breast cancer biomarkers lack precision in predicting treatment efficacy.
• Ex-vivo interrogation of tumor tissue in its native state is crucial for personalized treatment but technically challenging.

Purpose of the Study:

• To develop and validate a microfluidic tissue array (μFTA) for ex-vivo analysis of breast cancer.
• To assess the therapeutic response of breast cancer xenografts within the μFTA.
• To establish the clinical relevance and potential of the μFTA as a theranostic tool.

Main Methods:

• Development of a microfluidic tissue array (μFTA) using small breast cancer biopsy samples (< 1mm3).
• Maintenance of xenograft tissues in the μFTA for 2 weeks, mimicking physiological flow and preserving native stroma.
• Interrogation of drug response (doxorubicin, neratinib) and assessment of cell viability and proliferation (EdU/Ki67 assays).

Main Results:

• The μFTA demonstrated over a 2-fold reduction in tumor cell viability upon drug treatment, correlating with in vivo tumor shrinkage.
• Drug treatment in the μFTA selectively retained cells with higher proliferative capacity, mirroring in vivo observations.
• A valved-μFTA was developed to enhance throughput and accommodate diverse treatment conditions.

Conclusions:

• The developed microfluidic tissue array (μFTA) serves as a powerful, low-cost benchtop tool for personalized cancer therapeutics.
• The μFTA accurately predicts ex-vivo drug responses, offering a viable alternative to traditional methods.
• This technology aligns with FDA's New Approach Methods for drug development and theranostics.