Improving Lateral Flow Assay Performance Using Computational Modeling

Abstract

The performance, field utility, and low cost of lateral flow assays (LFAs) have driven a tremendous shift in global health care practices by enabling diagnostic testing in previously unserved settings. This success has motivated the continued improvement of LFAs through increasingly sophisticated materials and reagents. However, our mechanistic understanding of the underlying processes that drive the informed design of these systems has not received commensurate attention. Here, we review the principles underpinning LFAs and the historical evolution of theory to predict their performance. As this theory is integrated into computational models and becomes testable, the criteria for quantifying performance and validating predictive power are critical. The integration of computational design with LFA development offers a promising and coherent framework to choose from an increasing number of novel materials, techniques, and reagents to deliver the low-cost, high-fidelity assays of the future.

Sensitivity enhancement in lateral flow assays: a systems perspective

“…Another approach to the systematic improvement of LFAs, including sensitivity enhancement, is the application of computational models to the LFA development process, which is an area recently reviewed in detail. 108 The diagram in Fig. 2 illustrates how LFAs are complex systems composed of many different biological and structural features.…”

“…Recently, we have developed and validated a mechanistic model in the FlowDx group at Intellectual Ventures Laboratory to broadly improve LFA sensitivity. 108 The model accepts input parameters that include kinetic binding constants for reactions, porosity of transport materials, and viscosity of fluids, which allows for in silico optimization of signal generation and/or reagent use. Furthermore, the model can identify certain types of non-specific binding, which allows for at least partial in silico optimization of noise reduction.…”

Progress Report on Phase Separation in Polymer Solutions

“…[2] The success story of PPM originates from the concept of introducing pores into a dense polymer matrix in a controlled fashion, is driven by a concentration gradient. [10] Additional applications comprise biomaterials and lab-on-a-chip technologies including lateral flow assays, such as blood glucose analyzer [11] and pregnancy tests, [12,13] respectively. Furthermore, thanks to alterable ultrahigh surface areas, PPM have been adopted for catalyst supports to increase the efficiency of chemical reactions [14,15] and for electrodes of lithium-ion battery to enhance the electrochemical performance.…”

Soft, skin-interfaced microfluidic systems with integrated immunoassays, fluorometric sensors, and impedance measurement capabilities

“…The absorbent pad confines the reaction system within the NC membrane to ensure rapid and accurate immunoassay reactions. Selection of the membrane material and pore size follow considerations based on the Lucas-Washburn model, according to the following (44,45):…”