Page 32 - ASME_NEMB_2016_Program

Technical Program TRACK 3

threshold value, pores are created on the membrane of the cells, allowing lowed to pass through. The collected fluid molecules are passed via the tu-
for transport of ions and macromolecules across the membrane. Associated bule to the bladder and excreted as urine from the body. Given the viscous
with the disruption of the cell membrane is the increase of permeability of nature of the blood, its multiple molecular compositions and the varying hy-
foreign molecules, including foreign DNA, that may be inserted through the drostatic blood pressure against the interior surface of the blood capillaries,
defects and into the cells. the diffusion is difficult to model. One possible tool for potentially designing
a similar optimized nanoscale semipermeable membrane for dialysis is to-
Flow-through electroporation methods have been developed by Geng et pology optimization. Topology optimization uses sets of boundary conditions
al. [1] for delivery of genes into cells and by Wang et al. for electrical lysis and loads to build a material layout that will meet desired performance cri-
of bacterial cells [2]. These flow-through electroporation platforms are teria. Use of such a tool could open the door to the possibility of a portable
based on a geometric constriction that has a uniform cross-sectional area. dialysis device option for small scale hemofiltration. The hope is to create a
Adjusting the DC voltage applied, the constriction length, and the flow-rate device much like the insulin pump for diabetics that can be used to replace
allows cell exposure to a uniform electric field that if selected carefully can extracorporeal dialysis devices in the future.
successfully transform cells genetically. However, in many cases the optimal
conditions for genetic transformation are unknown as for intractable or diffi- In this example of designing a flow optimized, semipermeable membrane,
cult-to-transfect cells. topology optimization provides a visualization and analysis tool. The bound-
ary conditions consist of the hydrostatic pressure on the walls of the device
We developed a flow-through electroporation platform that removes the along with the size and concentrations of the blood molecules and fluid
electric field as a variable in the genetic transformation process. Specifically, particles in the blood. Other inputs are the size constraints dictated by the
our device employs a constriction with a variable cross-sectional area that size of the renal arteries and influx of fluid, namely the mass flow and veloc-
results in a linear electric field gradient. In order to increase the throughput ity. Once the inputs are given, the topology optimization tool can generate
of the electroporated sample and increase the potential for transfection a material layout for the filter. Flow is then simulated against this filter to
efficiency, a computational model to optimize experimental conditions was find the flow output and effectiveness of the filter. Efficiency is derived in
used. The computational model numerically coupled the fluid flow, electric, comparison to kidney filtration rates and the results show that the improved
and thermal responses to determine the optimum flow rate that is required design has potential as an integrated system for diffusion of waste from the
to expose cells to a subset of the continuous spectrum of the pulsed electric blood. It is expected that the topology optimized design could help increase
fields while allowing for heat dissipation generated by resistive heating. the lifespan of the dialysis device, minimize its size to an acceptable level
for portability and perform at a better efficiency than other extracorporeal
Our results demonstrate that a flow rate of about 50 µL/min may be optimal dialysis devices.
for dissipating the heat entirely from the constriction region before the deliv-
ery of the subsequent pulse (t = 100 ms). Specifically, at t = 50 ms there may 10:40am Enhanced microfluidic mixing via a tricritical spiral vor-
not be sufficient time for dissipation of the thermal energy deposited within tex instability
the constriction region. However, numerical results corroborate the initial
simulation estimates, demonstrating that 100 ms is sufficient to transport the
cells outside the constriction region and remove the heat generated during Technical Presentation. NEMB2016-5956
the electroporation pulse before the onset of the following pulse. The com-
putational models were validated with experimental results in E. coli BL21 in Amy Shen, Simon Haward, Noa Burshtein, Kazumi Toda-Peters,
which successful transformation was achieved with plasmid DNA (K176011) Okinawa Institute of Science and Technology Graduate University,
encoding for green fluorescent protein (GFP) expression and ampicillin resis- Okinawa, Japan, Rob Poole, University of Liverpool, Liverpool, Unit-
tance. Future work will further optimize the channel geometry and test bac- ed Kingdom
terial strains that are considered difficult-to-transfect with promising impact
in biotechnology and drug discovery. The ability of fluids to mix is greatly enhanced by turbulence, which occurs
at large values of the Reynolds number Re= UL/mu, where U and L are char-
1. Geng, T., et al., Transfection of cells using flow-through electroporation acteristic velocity and length scales respectively and mu is the kinematic vis-
based on constant voltage. Nat. Protocols, 2011. 6(8): p. 1192-1208. cosity of the fluid. Small length scales tend to suppress Re, making it difficult
2. Wang, H.-Y., A.K. Bhunia, and C. Lu, A microfluidic flow-through device for to develop turbulent mixing in microfluidic devices. Improved understanding
high throughput electrical lysis of bacterial cells based on continuous dc and characterization of stability conditions for flows through intersecting
voltage. Biosensors and Bioelectronics, 2006. 22(5): p. 582-588. geometries is vital for the optimization of many laboratory microfluidic ex-
periments and also practical lab-on-a-chip designs, including for the specific
10:20am Nanoscale Semipermeable Membrane Design with To- goal of enhancing the mixing of fluids in channels with small dimensions
pology Optimization for Portable Dialysis Device operating at low Re.

Technical Presentation. NEMB2016-5928 The planar elongational flow field generated by the cross-slot geometry has
found applications in many research areas including for studies of macromo-
Paul Braden, Air Force, Salt Lake City, UT, United States, Stephen lecular dynamics, extensional rheometry and elastic instabilities of viscoelas-
tic fluids, hydrodynamic trapping, and imposing controlled deformations to
Braden, St. Mary’s University, San Antonio, TX, United States, Lau- complex biological structures.
ren Gainer, Texas A&M University Medical School, College Station,
TX, United States In this work, we report the results of detailed experimental studies of the
spiral vortex flow instability of Newtonian fluids and dilute polymer solutions
Medical devices are reaching a new level of sophistication through the intro- in cross-slots with a range of aspect ratios and over a wide range of Re.
duction of nanotechnology. A major possibility for research is hemodialysis In contrast to previous studies, we identify appropriate order parameters
for early renal failure patients by means of osmosis through a semiperme- that characterize the instability as a function of Re in each case. At small
able membrane. Currently, such hemofiltration is performed external to the Reynolds numbers, Re, the flow is two-dimensional and a sharp symmetric
body in large scale, counter-current flow diffusion to maximize efficiency boundary exists between fluid streams entering the cross-slot from opposite
and concentration coefficient according to Darcy-Stoke’s Law. The empirical directions. Above an a dependent critical value Rec(a) ~ 20-100, the flow
relationship defines the key contributors to osmosis as geometric features bifurcates to an asymmetric state (though remains steady and laminar), and a
such as input and output diameters, pressure gradient, viscosity, permeabil- single three-dimensional spiral vortex structure develops around the central
ity of the medium, shear friction, etc. Kidneys perform this function of blood axis of the outflow channel. Image analysis allows an assessment of the mix-
32 filtration by means of some one million nephrons which are composed of ing quality between the two incoming fluid streams (one stream fluorescent-
a glomerulus and tubule. As blood enters the glomerulus with smaller fluid ly-dyed with rhodamine b), which undergoes a significant increase following
molecules and waste, the larger blood molecules and proteins are not al- the onset of the instability. For Re >> Rec, the mixing parameter grows