Simulation Tool Coupling Nonlinear Electrophoresis and Reaction Kinetics for Design and Optimization of Biosensors

Abstract

We present the development, formulation, validation, and demonstration of a fast, generic, and open source simulation tool, which integrates nonlinear electromigration with multispecies nonequilibrium kinetic reactions. The code is particularly useful for the design and optimization of new electrophoresis-based bioanlaytical assays, in which electrophoretic transport, separation, or focusing control analyte spatial concentration and subsequent reactions. By decoupling the kinetics solver from the electric field solver, we demonstrate an order of magnitude improvement in total simulation time for a series of 100 reaction simulations using a shared background electric field. The code can efficiently handle complex electrophoretic setups coupling sharp electric field gradients with bulk reactions, surface reactions, and competing reactions. For example, we demonstrate the use of the code for investigating accelerated reactions using isotachophoresis (ITP), revealing new regimes of operation which in turn enable significant improvement of the signal-to-noise ratio of ITP-based genotypic assays. The user can define arbitrary initial conditions and reaction rules, and we believe it will be a valuable tool for the design of novel bioanalytical assays. We will offer the code as open source, and it will be available for free download at http://microfluidics.technion.ac.il.

Dynamic computer simulations of electrophoresis: 2010–2020

“…• Monovalent and multivalent components, incl. ampholytes; model for pressure driven flow with Taylor-Aris dispersion; electroosmosis; data base of components; options: four numerical schemes and moving frame [32,33] • Correction of mobilities for ionic strength [66] • Quasi 1D model for variable cross-section channels featuring a finite volume method based on a SLIP 6) scheme together with an adaptive grid algorithm [67] • Coupling of nonlinear electromigration with multispecies nonequilibrium kinetic reactions in bulk solution and surfaces [68] CESE models 1) Space-time CESE 4) CFL-insensitive CESE 5) • Monovalent components [69] • 1D reduced model for microchannels with uniform or variable cross-sectional area, monovalent components and simple ampholytes [70] • Combination of adaptive grid redistribution and CESE scheme for ITP and IEF, mono-and multivalent components [71] SIMUL6 2) Second order centered (finite difference)…”

Analytical capillary isotachophoresis after 50 years of development: Recent progress 2014–2016

“…Dagan and Bercovici developed a new 1D simulation tool, designed as an extension of the freeware software SPRESSO and combining electromigration with reaction kinetics by treating both processes separately. Decoupling of the kinetics solver from the electric field solver provides a more general concept and considerably decreases simulation time, allowing fast simulation of nonlinear systems such as ITP.…”

“…Computer simulations of the dynamics of suitably selected electrolyte systems are the main present theoretical tool that brought and still brings detailed pictures of brand new and sometimes even unexpected properties of ITP systems. [25] developed a new 1D simulation tool, designed as an extension of the freeware software SPRESSO and combining electromigration with reaction kinetics by treating both processes separately. Decoupling of the kinetics solver from the electric field solver provides a more general concept and considerably decreases simulation time, allowing fast simulation of nonlinear systems such as ITP.…”

Application Of Two Phase Multi-Objective Optimization To Design Of Biosensors Utilizing Cyclic Substrate Conversion

“…The efforts to design biocatalytical systems can be mightily reduced by the aid of computer tools (Dagan and Bercovici 2014). The multi-objective optimization has been successfully applied to design biochemical systems (Vera et al 2010;Taras and Woinaroschy 2012), to increase the productivity of multi-enzyme systems (Ardao and Zeng 2013) and for optimal design of synergistic amperometric biosensors (Baronas et al 2016).…”