March 23, 2009Kaela Leonard
| Kaela Leonard - Electrodynamic Transport, Electroporation and Lysis of Cells in Pharmacological and Bioanalytical Microsystems
By: Andrzej Przekwas, Z.J. Chen and Mahesh Athavale
| | | | Overview
Paper presents multiphysics design tool in order to better design biochip. They modeled cell transport as well as the interaction with the external electric field. This was combined to make a 3D Eulerian-Lagrangian computational model. In the end they were able to demonstrate that at a low electric field there is minimal electroporation and very little change in pore density from the base value. However at a higher electric field, electroporation becomes much stronger and the pore density is great enough to cause cell lysis.
Abstract
• Biological information stored in cells of prime interest to biological professionals
• Cell membrane must be passed in order to get at internal contents
• Possible to do this via electroporation- disrupt cell membrane in a reversible way
• Or via cell lysis- destroy cell membrane permanently
• Paper presents computational modeling approach for cell transport and interaction with an external field
• Objective: develop multiphysics design tools for bioanalytical systems
• Aim:
o Present new technique for modeling cell transport
o Demonstrate technique on devices used for cell trapping, electroporation and lysis
Introduction
• Strong interest in miniaturization of biotechnology/drug discovery
• Tremendous competition to develop complete biochemical microsystem for DNA analysis
• Biosensors hold promise for many types of drug discovery, disease therapy (ie cancer, immunology)
• Computation modeling of this is daunting task due to cell physiology being so complex
• Paper presents 3D Eulerian-Lagrangian computation model
• Modeled biological cell and following components:
o Lipid bilayer
o Membrane pores/channels
o Cytoplasm
o Extracellular matrix
• Fundamental PDE’s describe:
o Diffusive transport
o Convective transport
o Electrokinetic transport
o Dynamics of membrane pores
o Chemical kinetics of metabolic reactions
o Electric field
o Etc.
• Cell geometry represented by: fine 3D mesh for membrane surfaces and single polyhedral element for tissue
• Paper presents details of math and assumptions used to model membranes, pores, transport, electrochemistry and interaction with external fields
Cell Transport in Fluidic Channels with Electrokinetics
• Low concentrations of small particles in fluid flows- treatment in CFD-ACE+ based on:
o Lagrangian particle tracking
o Eulerian solution for fluid flow
• Eulerian calculations use pressure based Navier-Stokes
• Flow solutions couple with particle mass, momentum and energy equations from Lagrangian
• Particles tracking using “efficient tracking algorithm” (What is this? It would be nice to know in case this could help with my 1MHz experiments)
• Present approach- equations solved in Lagrangian frame of reference that moves with the cells after starting with initial conditions
• Difference between classical and microchannel simulations comes in how particle size is treated
o Classical: particle much smaller than mesh, treated as sniggle point
o Microchannel: must represent details of cell shape because cell is on the same dimensional size as channel
• Figure 1 shows flow field- this could have been much better with more detail
• Figure 2 shows simulation results of electric field and cell distribution of cell trapping device – again would have been much better with more detail
Physiology of Cell Membrane Electroporation and Lysis
• Cell membrane comprised of lipid bilayer (receptors, proteins, aqueous pores)
• Pores allow transport of small neutral particles
• After application of external electric field- transmembrane potential develops
• Hydorphobic pores open up more- electroporation
• Electroporation used for: transfection (via introduction of DNA), electrochemotherapy or drug delivery
• Figure 3 very good picture of hydrophilic and hydrophobic pores
• Pores remain open after field removed- provide pathways for ions, drugs, macromolecules and DNA
• With increase of larger field pulses, pores enlarge to point of complete cell rupture (we do this without the large field pulses)
• Process known as cell lysis- interior cell contents released into fluid
• Computational modeling if cell lysis via electric fields has not been reported prior to this paper (opportunity here for us because we are doing a different type of cell lysis)
Model of Cell Membrane Electroporation and Lysis
• Cells contain cytoplasm filled with macromoleculars in polyelectrolyte fluid
• Exposed to electric field- charged particles move via electromigration
• Equations 4 and 5 describe this movement
• Figure 4 shows electric potential and current for 10Hz and 1kHz
• 10Hz: current flows around cell because non-conductor in conducting medium
• 1kHz: current passes through cell because now acts like a conductor
• For design- must predict minimum energy and impulse needed to get desire hole size, number density or membrane breakdown in order to have cell lysis
• Equations 6 and 7 give energy required when no electric field is present
• Equations 8 and 9 give energy required when transmembrane potential occurs
• Equations 10-15 explore the pore distribution by making assumptions on the Smoluchowski PDE
• After solving equation 11 for pore density, total cross-sectional area of pores is calculated using Ap=Nrm2
• Proposed model to simulate cell electroporation and lysis (would have been nice if they had shown what this full model was exactly)
• Cell modeled as 3D polyhedral element with membrane model used at faces of cell
• Model demonstrated in Figure 5 ( very difficult to tell the difference in the lines, even though some are supposedly dashed)
o Small currents- electroporation minimal with small changes in pore density
o Larger current- electroporation much stronger and pore density sufficient to lyse cell
Summary
• Presented “progress” in computational modeling of transport, electroporation and cell lysis
• Proposed Eulerian-Lagrangian transport model can be used to design biochips
• New 3D model of cell membrane presented
My Thoughts:
Well written paper, especially considering the topic of modeling is somewhat foreign to what we are currently interested in. Would accept paper with revisions, mostly the figures. However it could have been made better by giving more details on the exact calculations done. A lot is not explained in the text. Changing font size also got really frustrating to read.
For my research, I think it might be useful to revisit this paper once I get to the part of my project that is concerned with modeling the effect of the ABO antigens on red blood cell movement through an electric field.
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