16 research outputs found
Modeling electrochemical systems with weakly imposed Dirichlet boundary conditions
Finite element modeling of charged species transport has enabled analysis,
design, and optimization of a diverse array of electrochemical and
electrokinetic devices. These systems are represented by the
Poisson-Nernst-Planck equations coupled with the Navier-Stokes equation, with a
key quantity of interest being the current at the system boundaries. Accurately
computing the current flux is challenging due to the small critical dimension
of the boundary layers (small Debye layer) that require fine mesh resolution at
the boundaries. We resolve this challenge by using the
Dirichlet-to-Neumanntransformation to weakly impose the Dirichlet conditions
for the Poisson-Nernst-Planck equations. The results obtained with weakly
imposed Dirichlet boundary conditions showed excellent agreement with those
obtained when conventional boundary conditions with highly resolved mesh we
reemployed. Furthermore, the calculated current flux showed faster mesh
convergence using weakly imposed conditions compared to the conventionally
imposed Dirichlet boundary conditions. We illustrate the approach on canonical
3D problems that otherwise would have been computationally intractable to solve
accurately. This approach substantially reduces the computational cost of
model-ing electrochemical systems.Comment: 24 pages, 14 figure
Direct numerical simulation of electrokinetic transport phenomena: variational multi-scale stabilization and octree-based mesh refinement
Finite element modeling of charged species transport has enabled the
analysis, design, and optimization of a diverse array of electrochemical and
electrokinetic devices. These systems are represented by the
Poisson-Nernst-Planck (PNP) equations coupled with the Navier-Stokes (NS)
equation. Direct numerical simulation (DNS) to accurately capture the
spatio-temporal variation of ion concentration and current flux remains
challenging due to the (a) small critical dimension of the electric double
layer (EDL), (b) stiff coupling, large advective effects, and steep gradients
close to boundaries, and (c) complex geometries exhibited by electrochemical
devices.
In the current study, we address these challenges by presenting a direct
numerical simulation framework that incorporates: (a) a variational multiscale
(VMS) treatment, (b) a block-iterative strategy in conjunction with
semi-implicit (for NS) and implicit (for PNP) time integrators, and (c) octree
based adaptive mesh refinement. The VMS formulation provides numerical
stabilization critical for capturing the electro-convective instabilities often
observed in engineered devices. The block-iterative strategy decouples the
difficulty of non-linear coupling between the NS and PNP equations and allows
using tailored numerical schemes separately for NS and PNP equations. The
carefully designed second-order, hybrid implicit methods circumvent the harsh
timestep requirements of explicit time steppers, thus enabling simulations over
longer time horizons. Finally, the octree-based meshing allows efficient and
targeted spatial resolution of the EDL. These features are incorporated into a
massively parallel computational framework, enabling the simulation of
realistic engineering electrochemical devices. The numerical framework is
illustrated using several challenging canonical examples
An Electrokinetic Separation Route to Source Dialysate from Excess Fluid in Blood
To
improve the health of patients with end-stage renal disease,
there is a clear need for slow, continuous hemodialysis, and the primary
barrier to a wearable device is the requirement of a large reservoir
of dialysate. We describe an electrokinetic means of producing dialysate
from the excess fluid extant in the peripheral blood of patients undergoing
therapy. A critical feature of this process is the retention of essential
components of blood, especially serum albumin. In progress toward
this goal, we demonstrate the separation of charged from neutral species
in blood plasma at a branched microchannel junction by ion concentration
polarization (ICP). Further, we introduce a method that reduces the
opportunity for damage to proteins and prevents electrode biofouling.
The present approach results in as high as 99.7% retention of albumin
and successful separation of neutral metabolites and excess fluid
to be utilized as a precursor to dialysate
Dual-channel bipolar electrode focusing: simultaneous separation and enrichment of both anions and cations
In this paper we show that a microelectrochemical cell comprising two parallel microchannels spanned by a single bipolar electrode can be used to simultaneously enrich and separate both anions and cations within a single microchannel. This is possible because reduction and oxidation of water at the cathodic and anodic poles of the bipolar electrode, respectively, lead to ion depletion zones. Specifically, TrisH + is neutralized by OH 2 at the cathodic pole, while acetate buffer is neutralized by H + at the anodic pole. This action creates a local electric field gradient having both positive and negative components, and hence positive and negative ions follow their respective field gradients leading to separation. In the presence of an opposing counter-flow (pressure driven flow in this case), enrichment also occurs. In addition to separation and enrichment in a single channel, it is also possible to simultaneously enrich cations in one microchannel and anions in the other. Enrichment is achieved by controlling experimental parameters, including the type of buffer and the direction and magnitude of the opposing counter-flow
Array of Interdigitated Bipolar Electrodes for Selective Capture and Analysis of Melanoma Cells
Abstract We report a method for dielectrophoretic capture of melanoma cells and their electrochemical analysis for tumorâspecific markers, using a microfluidic device composed of microwells overlying an array of interdigitated bipolar electrodes (IDBPEs). In this device, cells are captured on each IDBPE by dielectrophoresis, and microfabricated wells allow for retention of the cells to enable their subsequent electrochemical analysis. This advancement is significant because it addresses a need for cancer diagnostics with fewâ to singleâcell resolution amenable to use in lowâresource settings. Specifically, this approach combines the selectivity of dielectrophoresis for cell phenotype, the low cost of electrochemical methods, and the ability of BPEs to be arrayed, with the sensitivity afforded by interdigitation. The IDBPE detects a redoxâactive species produced by an enzymeâlinked antibody targeted to a cell surface antigen, and reports the current by electrochemiluminescence. In this work, we first characterize cell capture by dielectrophoresis at the IDBPE array. Second, the retention of cells in the microwells and their viability is demonstrated. Then, the sensitivity of the IDBPE for the redoxâactive species is quantified. Finally, we demonstrate capture and analysis of melanoma cells at the IDBPE array, which underscores the ability of the IDBPE to achieve biologically relevant detection limits
Improved Detection by Ensemble-Decision Aliquot Ranking of Circulating Tumor Cells with Low Numbers of a Targeted Surface Antigen
Circulating tumor cells (CTCs) are
shed from a solid tumor into
the bloodstream and can seed new metastases. CTCs hold promise for
cancer diagnosis and prognosis and to increase our understanding of
the metastatic process. However, their low numbers in blood and varied
phenotypic characteristics make their detection and isolation difficult.
One source of heterogeneity among CTCs is molecular: When they leave
the primary tumor, these cells must undergo a molecular transition,
which increases their mobility and chance of survival in the blood.
During this molecular transition, the cells lose some of their epithelial
character, which is manifested by the expression of the cell surface
antigen known as epithelial cell adhesion molecule (EpCAM). Some tumors
shed CTCs that express high levels of EpCAM; others release cells
that have a low level of the antigen. Nevertheless, many CTC isolation
techniques rely on the detection of EpCAM to discriminate CTCs from
other cells in the blood. We previously reported a high-throughput
immunofluorescence-based technology that targets EpCAM to rank aliquots
of blood for the presence or absence of a CTC. This technology, termed
ensemble decision aliquot ranking (eDAR), recovered spiked-in cancer
cells (taken from a model EpCAM<sup>high</sup> cell line) from blood
at an efficiency of 95%. In this paper, we evaluated eDAR for recovery
of cells that have low EpCAM expression and developed an immunofluorescence
labeling strategy that significantly enhances the methodâs
performance. Specifically, we used a cocktail of primary antibodies
for both epithelial and mesenchymal antigens as well as a dye-linked
secondary antibody. The cocktail allowed us to reliably detect a model
EpCAM<sup>low</sup> cell line for triple negative breast cancer, MDA-MB-231,
with a recovery efficiency of 86%. Most significantly, we observed
an average of 6-fold increase in the number of CTCs isolated from
blood samples from breast cancer patients. These findings underscore
the importance of benchmarking CTC technologies with model cell lines
that express both high and low levels of EpCAM
Negative Dielectrophoretic Capture and Repulsion of Single Cells at a Bipolar Electrode: The Impact of Faradaic Ion Enrichment and Depletion
This
paper describes the dielectrophoretic (DEP) forces generated
by a bipolar electrode (BPE) in a microfluidic device and elucidates
the impact of faradaic ion enrichment and depletion (FIE and FID)
on electric field gradients. DEP technologies for manipulating biological
cells provide several distinct advantages over other cell-handling
techniques including label-free selectivity, inexpensive device components,
and amenability to single-cell and array-based applications. However,
extension to the array format is nontrivial, and DEP forces are notoriously
short-range, limiting device dimensions and throughput. BPEs present
an attractive option for DEP because of the ease with which they can
be arrayed. Here, we present experimental results demonstrating both
negative DEP (nDEP) attraction and repulsion of B-cells from each
a BPE cathode and anode. The direction of nDEP force in each case
was determined by whether the conditions for FIE or FID were chosen
in the experimental design. We conclude that FIE and FID zones generated
by BPEs can be exploited to shape and extend the electric field gradients
that are responsible for DEP force
Negative Dielectrophoretic Capture and Repulsion of Single Cells at a Bipolar Electrode: The Impact of Faradaic Ion Enrichment and Depletion
This
paper describes the dielectrophoretic (DEP) forces generated
by a bipolar electrode (BPE) in a microfluidic device and elucidates
the impact of faradaic ion enrichment and depletion (FIE and FID)
on electric field gradients. DEP technologies for manipulating biological
cells provide several distinct advantages over other cell-handling
techniques including label-free selectivity, inexpensive device components,
and amenability to single-cell and array-based applications. However,
extension to the array format is nontrivial, and DEP forces are notoriously
short-range, limiting device dimensions and throughput. BPEs present
an attractive option for DEP because of the ease with which they can
be arrayed. Here, we present experimental results demonstrating both
negative DEP (nDEP) attraction and repulsion of B-cells from each
a BPE cathode and anode. The direction of nDEP force in each case
was determined by whether the conditions for FIE or FID were chosen
in the experimental design. We conclude that FIE and FID zones generated
by BPEs can be exploited to shape and extend the electric field gradients
that are responsible for DEP force
New Generation of Ensemble-Decision Aliquot Ranking Based on Simplified Microfluidic Components for Large-Capacity Trapping of Circulating Tumor Cells
Ensemble-decision aliquot ranking
(eDAR) is a sensitive and high-throughput
method to analyze circulating tumor cells (CTCs) from peripheral blood.
Here, we report the next generation of eDAR, where we designed and
optimized a new hydrodynamic switching scheme for the active sorting
step in eDAR, which provided fast cell sorting with an improved reproducibility
and stability. The microfluidic chip was also simplified by incorporating
a functional area for subsequent purification using microslits fabricated
by standard lithography method. Using the reported second generation
of eDAR, we were able to analyze 1 mL of whole-blood samples in 12.5
min, with a 95% recovery and a zero false positive rate (<i>n</i> = 15)