System-Level Modeling of Surface-Immobilized Biomolecular Concentration Gradient Generation

This paper presents a system-level modeling methodology for microfluidic surface-immobilized biomolecular concentration gradient generators (CGGs). The generator is broken down into a system of elemental microfluidic components with relatively simple geometries and functionality. Parameterized models for such components are developed, which hold for general biomolecular concentration profiles and arbitrary flow ratios at the component interface; hence, they are valid for a broad category of CGGs that rely on various operating mechanisms. The component models are then linked through an appropriate set of parameters at the interfaces to construct a system-level, network representation of the entire generator for simulation. The system model is extensively verified against experimental data reported in the literature. The model results are found to be in excellent agreement, and can be applied to accurately capture the overall effects of network geometry, biomolecular properties, operating parameters (e.g., flow rates and initial biomolecular concentration) on the generation of biomolecular gradients on the surfaces. The model also demonstrates salient computational efficiency (seconds of execution time) and can be used to guide fast, reliable, system-level design of CGGs and associated bioassays.