A Unidirectional 96-Well Fluidic Culture Platform for Upstream Cell Dosing with Subsequent Downstream Nonlinear and...

Area of Science:

• Biotechnology
• Drug Discovery
• Toxicology

Background:

• Developing in vitro screening tools that accurately mimic in vivo models is crucial for drug and toxicant exposure assessments.
• Reproducible and adaptable culture platforms are needed to replicate native human organ system functions.

Purpose of the Study:

• To investigate the utility of a microfluidic system for predicting drug efficacy and toxicity.
• To delineate the design, fabrication, and characterization of the Stairstep Waterfall (SsWaterfall) Fluidic Culture System.

Main Methods:

• The SsWaterfall system is a unidirectional, gravity-driven, multiwell culture system with micro-channels for controlled fluid flow.
• Device characterization included assessing nonspecific binding, wettability, biocompatibility, flow dynamics, and auto-mixing properties.
• The system was demonstrated using sequential testing for drug toxicity and efficacy across a range of exposures (0→IC100) with real-time assessments.

Main Results:

• The SsWaterfall system demonstrated low nonspecific binding, good wettability, and biocompatibility with multiple cell types.
• Efficient intra-well and inter-well flow with effective auto-mixing of compounds was confirmed.
• The system successfully performed sequential drug toxicity and efficacy screening with real-time assessments.

Conclusions:

• The SsWaterfall Fluidic Culture System provides an easy and quick alternative for evaluating broad-ranging compound toxicity.
• Its integrated auto-gradient technology and gravity flow offer advantages over traditional manual dilutions or robotic systems.
• This microfluidic platform can aid in the development of pharmaceuticals, environmental, agricultural, and cosmetic compounds.