Multi-scale modeling of geometric flow control in lateral flow assays

Lateral flow assays (LFAs), such as pregnancy tests, are gaining significant interest due to their cost-effectiveness and suitability for resource-limited settings. However, challenges exist in fully understanding the underlying phenomena governing LFA performance, particularly in enhancing test sensitivity. Conventional approaches rely primarily on macro-scale experiments, which can be limited in capturing key mechanisms that occur at different length scales. In contrast, this dissertation addresses these limitations by employing multi-scale investigations that encompass both micro and macro-scale phenomena to comprehensively understand the governing processes in LFAs.

At the micro-scale, various parameters affecting wetting in porous polymeric membranes are investigated. These parameters include porosity, mean and effective pore radius, mean ligament radius, permeability, and tortuosity. To evaluate these parameters, the reconstructed digital twins of real porous membranes in equidistant three-dimensional grids are analyzed.

At the macro-scale, three complementary approaches are adopted: i) Experimental investigation: The gravimetric method is utilized to determine the porosity of the membrane, and the macro-scale wetting experiments are conducted to measure the wetting time and then calculate the wetting velocity. ... mehrii) Single-phase modeling: This approach studies fluid flow at the macro-scale in porous membrane structures, with and without variations in cross-section. The focus is on the analysis of the effect of geometric changes on the wetting process. This includes the study of different membrane geometries, such as hexagonal and T-shaped profiles. This proposed approach, centered on geometry tuning, serves as a basis for the development of application-specific membranes. iii) Two-phase simulation: A macroscopic two-phase model is implemented to investigate fluid flow in LFAs. This model accounts for the displacement of an initial fluid by an invading fluid during imbibition. Microscopic properties are incorporated as input to the macroscopic numerical simulations, allowing the study of wetting behavior in different LFAs. This multi-scale approach investigates capillary-driven flows in bifurcated (Y-shaped) and multi-branch membranes that are integral components of multiplexed LFAs. The study includes various parameters such as length ratio, width ratio, branching angle, bifurcation point location, inlet width, asymmetry, and membrane type.

In addition, a convection-diffusion-reaction model is employed as a systematic tool to address the challenge of quantitatively assessing signal intensity in LFAs. By leveraging data-driven information and understanding structure-sensitivity linkages, this multi-scale approach significantly contributes to ongoing efforts to improve the sensitivity of diagnostic assays.

The approaches presented in this work provide a comprehensive understanding of LFAs and facilitate their development. The knowledge gained is used to optimize design parameters, including wetting time and velocity, for specific LFA applications and target analytes.