Automated microfluidic platform for dynamic and combinatorial drug screening of tumor organoids

Abstract

Three-dimensional (3D) cell culture technologies, such as organoids, are physiologically relevant models for basic and clinical applications. Automated microfluidics offers advantages in high-throughput and precision analysis of cells but is not yet compatible with organoids. Here, we present an automated, high-throughput, microfluidic 3D organoid culture and analysis system to facilitate preclinical research and personalized therapies. Our system provides combinatorial and dynamic drug treatments to hundreds of cultures and enables real-time analysis of organoids. We validate our system by performing individual, combinatorial, and sequential drug screens on human-derived pancreatic tumor organoids. We observe significant differences in the response of individual patient-based organoids to drug treatments and find that temporally-modified drug treatments can be more effective than constant-dose monotherapy or combination therapy in vitro. This integrated platform advances organoids models to screen and mirror real patient treatment courses with potential to facilitate treatment decisions for personalized therapy.

Patient-derived organoids as a predictive biomarker for treatment response in cancer patients

“…Organoid-based drug screens are developing rapidly, offering new techniques and materials which can improve the reproducibility, high throughput design and automation of PDO screening. A newly developed automated microfluidic platform for PDO drug screening enables the addition of drugs at different time points, allowing drug screens to more closely resemble combination treatment regimens given to patients 45 . Such automated platforms may be compatible with image-based analysis 46 , which in contrast to single end points such as cell viability, allows researchers to assess multiple end points, better resembling the full drug response in PDOs.…”

Microfluidic Organoids-on-a-Chip: Quantum Leap in Cancer Research

“…Microfluidic technology allows precise control of drug distribution, increases the cellular fidelity of organoids in a limited time, and improves the dose-response accuracy. Recently, Schuster et al have developed an automated high-throughput microfluidic platform that enables culturing tumor organoids for the continuous monitoring of 3D growth and biochemical analyses [ 229 ]. The platform consists of a 3D culture with a 200-well array chamber and an overlayed multiplexer fluid control device.…”

Mimicking and surpassing the xenograft model with cancer-on-chip technology

“…In general adding complexity reduces scalability, e.g. the use of microfluidic pumps for dynamic drug concentration control requires a separate technical solution to scale up [ 93 , 94 ]. Furthermore the preferred solution for one aspect might complicate control of another.…”