Kisoo Yoo

Efficient algorithm for simulation of isoelectric focusing

IEF simulation is an effective tool to investigate the transport phenomena and separation performance as well as to design IEF microchip. However, multidimensional IEF simulations are computationally intensive as one has to solve a large number of mass conservation equations for ampholytes to simulate a realistic case. In this study, a parallel scheme for a 2D IEF simulation is developed to reduce the computational time. The calculation time for each equation is analyzed to identify which procedure is suitable for parallelization. As expected, simultaneous solution of mass conservation equations of ampholytes is identified as the computational hot spot, and the computational time can be significantly reduced by parallelizing the solution procedure for that. Moreover, to optimize the computing time, electric potential behavior during transient state is investigated. It is found that for a straight channel the transient variation of electric potential along the channel is negligible in a narrow pH range (5∼8) IEF. Thus the charge conservation equation is solved for the first time step only, and the electric potential obtain from that is used for subsequent calculations. IEF simulations are carried out using this algorithm for separation of cardiac troponin I from serum albumin in a pH range of 5–8 using 192 biprotic ampholytes. Significant reduction in simulation time is achieved using the parallel algorithm. We also study the effect of number of ampholytes to form the pH gradient and its effect in the focusing and separation behavior of cardiac troponin I and albumin. Our results show that, at the completion of separation phase, the pH profile is stepwise for lower number of ampholytes, but becomes smooth as the number of ampholytes increases. Numerical results also show that higher protein concentration can be obtained using higher number of ampholytes.

Mathematical and numerical model to study two-dimensional free flow isoelectric focusing

Even though isoelectric focusing (IEF) is a very useful technique for sample concentration and separation, it is challenging to extract separated samples for further processing. Moreover, the continuous sample concentration and separation are not possible in the conventional IEF. To overcome these challenges, free flow IEF (FFIEF) is introduced in which a flow field is applied in the direction perpendicular to the applied electric field. In this study, a mathematical model is developed for FFIEF to understand the roles of flow and electric fields for efficient design of microfluidic chip for continuous separation of proteins from an initial well mixed solution. A finite volume based numerical scheme is implemented to simulate two dimensional FFIEF in a microfluidic chip. Simulation results indicate that a pH gradient forms as samples flow downstream and this pH profile agrees well with experimental results validating our model. In addition, our simulation results predict the experimental behavior of pI markers in a FFIEF microchip. This numerical model is used to predict the separation behavior of two proteins (serum albumin and cardiac troponin I) in a two-dimensional straight microchip. The effect of electric field is investigated for continuous separation of proteins. Moreover, a new channel design is presented to increase the separation resolution by introducing cross-stream flow velocity. Numerical results indicate that the separation resolution can be improved by three folds in this new design compare to the conventional straight channel design.

Effect of Joule heating on isoelectric focusing of proteins in a microchannel

Electric field-driven separation and purification techniques, such as isoelectric focusing (IEF) and isotachophoresis, generate heat in the system that can affect the performance of the separation process. In this study, a new mathematical model is presented for IEF that considers the temperature rise due to Joule heating. We used the model to study focusing phenomena and separation performance in a microchannel. A finite volume-based numerical technique is developed to study temperature-dependent IEF. Numerical simulation for narrow range IEF (6 < pH < 10) is performed in a straight microchannel for 100 ampholytes and two model proteins: staphylococcal nuclease and pancreatic ribonuclease. Separation results of the two proteins are obtained with and without considering the temperature rise due to Joule heating in the system for a nominal electric field of 100 V/cm. For the no Joule heating case, constant properties are used, while for the Joule heating case, temperature-dependent titration curves and thermo-physical properties are used. Our numerical results show that the temperature change due to Joule heating has a significant impact on the final focusing points of proteins, which can lower the separation performance considerably. In the absence of advection and any active cooling mechanism, the temperature increase is the highest at the mid-section of a microchannel. We also found that the maximum temperature in the system is a strong function of the [Formula: see text] value of the carrier ampholytes. Simulation results are also obtained for different values of applied electric fields in order to find the optimum working range considering the simulation time and buffer temperature. Moreover, the model is extended to study IEF in a straight microchip where pH is formed by supplying H(+) and OH(-), and the thermal analysis shows that the heat generation is negligible in ion supplied IEF.

Electrochemical Model for Ionic Liquid Electrolytes in Lithium Batteries

A mathematical model is developed for transport of ionic components to study the performance of ionic liquid based lithium batteries. The mathematical model is based on a univalent ternary electrolyte frequently encountered in ionic liquid electrolytes used for lithium batteries. Owing to the very high concentration of components in ionic liquid, the transport of lithium ions are described by the mutual diffusion phenomena using Maxwell-Stefan diffusivity. The model is used to study a lithium ion battery where the cations and anions of ionic liquid are mppy+ and TFSI-. The electric performance results predicted by the model are in good agreement with experimental data. We also studied the effect of load current density on the performance of lithium ion battery using this model. Numerical results indicate that low rate of lithium ion transport causes lithium depleted zone in the porous cathode regions as the load current density increases. This lithium depleted region is responsible for lower specific capacity in lithium-ion cells. The model presented in this study can be used for optimum design of ionic liquid electrolytes for lithium-ion and lithium-air batteries.Copyright

A Mathematical Model for Li-Air Battery Considering Volume Change Phenomena

Li-air battery has the potential to be the next generation energy storage device because of its much higher energy density and power density. However, the development of Li-air battery has been hindered by a number of technical challenges such as passivation of cathode, change in effective reaction area, volume change during charge and discharge, etc. In a lithium-air cell, the volume change can take place due to Li metal oxidation in anode during charge as well as due to the solubility of reaction product (lithium peroxide) in the electrolyte at cathode. In this study, a mathematical model is developed to study the performance of lithium-air batteries considering the significant volume changes at the anode and cathode sides using moving boundary technique. A numerical method was introduced to solve moving boundary problem using finite volume method. Using this model, the electric performance of lithium-air battery is obtained for various load conditions. Numerical results indicate that cell voltage drops faster with increase in load which is consistent with experimental observations. Also, the volume changes significantly affect the electric performance of lithium-air cell.Copyright

Free Flow Isoelectric Focusing in a Microfluidic Device

In recent years, there are growing interests in the use of free flow isoelectric focusing (FFIEF). In FFIEF, a thin sheath of laminar flow is introduced perpendicular to the direction of the applied electric field for continuous separation of proteins and charged species. This technique is especially useful in microfluidic device since the electrophoretically separated bands do not have to be mobilized for detection or further analysis. In this study, a mathematical model is developed to simulate free flow isoelectric process in microfluidic devices considering electroneutrality and incompressibility of electrolytes. Our mathematical model is based on mass, momentum and charge conservation equations. A finite volume based numerical scheme is implemented to simulate two dimensional FFIEF in a microfluidic chip. Simulation results indicate that pH gradient forms as samples flow downstream and proteins can be separated effectively using this technique. A new design of microfluidic chip is proposed for separation for cardiac troponin I from serum albumin using FFIEF technique.Copyright

Segregated Parallel Computing for Isoelectric Focusing of Proteins

A parallel algorithm is introduced to simulate isoelectric focusing (IEF) in a microfluidic device. This new algorithm is based on segregated method for solving a large number of mass conservation equations in the system. An in house numerical code is developed to simulate the transient focusing behavior of cardiac troponin I (cTnI) protein in a pH field formed by ampholytes in presence of an applied electric field. The effectiveness of the parallel scheme is assessed by analyzing the CPU times for each process. Numerical results show that the electric potential distribution is nearly independent of time or concentration of amphoteric molecules. Thus, the charge conservation equation is not solved after the first time step to reduce the computational expenses. As expected, the solution of mass conservation equations for ampholytes is the computational hot spot, and solving them in parallel reduces the overall computing time. The proposed algorithm is very suitable for solving mass conservation equations of 100∼1000 components used to form continuous pH in IEF.Copyright