A.J.H. Frijns

On-line monitoring of electrolytes in hemodialysis: on the road towards individualizing treatment

ABSTRACT Introduction: End-stage renal disease (ESRD) patients depend on dialysis for removal of toxic waste products, fluid overload relief and maintenance of electrolyte balance. Dialysis prolongs millions of lives. To some extent, ESRD has become a manageable disease with a steadily growing dialysis population of increasing average age and associated comorbidity. During 7 decades many technical refinements have been developed e.g. sodium profiling, blood volume, ultrafiltration variation based on blood pressure measurement, urea kinetics etc. Despite its large potentials, in-line electrolyte monitoring lags behind in dialysis treatment. Areas covered: In this paper, we review the state of technologies available for in-line monitoring of the electrolytes sodium, potassium and calcium during hemodialysis. Expert commentary: We concluded that individual optimization of dialysate composition should be able to improve hard medical outcomes, but practical clinical implementation stands/falls with reliable and affordable in-line ion-selective sensing technology. Optical ion-selective microsensors and microsystems form a promising pathway for individualizing the dialysis treatment.

Molecular Dynamics and Monte Carlo Simulations for Heat Transfer in Micro and Nano-channels

There is a tendency to cool mechanical and electrical components by microchannels. When the channel size decreases, the continuum approach starts to fail and particle based methods should be used. In this paper, a dense gas in micro and nano-channels is modelled by molecular dynamics and Monte Carlo simulations. It is shown that in the limit situation both methods yield the same solution. Molecular dynamics is an accurate but computational expensive method. The Monte Carlo method is more efficient, but is less accurate near the boundaries. Therefore a new coupling algorithm for molecular dynamics and Monte Carlo is introduced in which the advantages of both methods are used.

Properties of a Dense Hard-Sphere Gas Near the Walls of a Microchannel

A mathematical model has been developed to characterize the effect of packing of molecules of a hard-sphere dense gas near the hard walls of a microchannel. Analytical techniques, Monte Carlo (MC) methods and Molecular Dynamics (MD) simulation methods have been used to characterize the influence of the characteristic parameters such as number density, reduced density, length of the system and molecular diameter on the equilibrium properties of the gas near the hard walls of the microchannel. The height and the position of the density oscillation peaks near the wall are characterized. Comparisons between MD and MC results for particles having different diameter are presented. For the same size of the particles and moderately dense gas, MC and MD results are similar, differences in the density profiles being limited only to the oscillatory region. For different particle sizes, MD and MC results are limited to a short distance near the wall for long size systems and moderately dense fluids. The effect of the boundary (particle size) on the simulation results is increasing with η (reduced density) and it is very small in case of a dilute gas. For small η and small particle size (R) relative to length of the system L, the height of the oscillations peaks is slowly increasing with R/L, and for high densities is always decreasing with R/L. The position of these peaks depends only on the size of the particles and when R is much smaller than L, it shows a small dependence on L.Copyright

Density distribution for a dense hard-sphere gas in micro/nano-channels

We study the properties of a hard-sphere dense gas near the hard walls of micro and nano-channels. Analytical techniques, Monte Carlo (MC) methods and molecular dynamics (MD) simulation methods have been used to characterize the influence of the characteristic parameters such as number density, reduced density, width of the system and molecular diameter, on the equilibrium properties of the gas near the hard walls of micro and nano-channels. A mathematical model has been developed to characterize the density oscillations as the result of packing of molecules in case of a dense gas near the micro and nano-channels walls. The height and the position of the density oscillation peaks near the wall are characterized. These results are also confirmed by the MD and MC simulation results.Comparisons between MD and MC simulation results for particles having different diameter are also presented. For the same size of the particles and moderately dense gas, MC and MD results are similar, differences in the density profiles being limited only to the oscillatory region. For different particle sizes, MD and MC results are limited to a short distance near the wall for long size systems and moderately dense fluids. The effect of the boundary (particle size) on the simulation results is found to increase with ? (reduced density) and it is very small in case of a dilute gas. For small ? and small particle size (R) relative to the width of the system L, the height of the oscillation peaks is slowly increasing with R/L, and for high densities is always decreasing with R/L. The position of these peaks depends only on the size of the particles and when R is much smaller than L, it shows a small dependence on L. The deviations in the oscillatory region for the pure MC simulation results compared to pure MD simulation results are quantified, and more efficient hybrid MC-MD simulations are performed to reduce these deviations.

Molecular dynamics simulation on rarefied gas flow in different nanochannel geometries

A three dimensional Molecular Dynamics simulation method was used to study the effect of different geometries for rarefied gas flows in nanochannels. Argon molecules have been used. The velocity profiles in the channel were obtained and analyzed with three different channel geometries: a circular, a rectangular (square), and a slit channel. We found that when using the same driving force, the maximum velocity of the flow increases when the geometry changes in the order from circular geometry to rectangular geometry to slit geometry, where the latter becomes 2∼2.5 times as large compared with either the rectangular or circular channel. Rectangular channels showed a similar maximum and slip velocity as the circular channel while the velocity profile was qualitatively similar to the slit channel for Kn higher than 1.0. We also investigated the effect of different Knudsen numbers on the velocity profiles. A channel width of 50nm is used for the simulation. We found that for Kn higher than 2∼3, the Knudsen number has a comparably small influence on the slip velocity for circular channel and rectangular channel.

Novel Hybrid Simulations for Heat Transfer at Atomistic Level

Hybrid simulations are used to overcome length and time scale limitations of atomistic simulations for problems involving multi-fluid dynamics in the presence of multi-fluid interfaces. An overview of hybrid atomistic-continuum for the treatment of dense fluid problems with emphasis on the coupling of molecular dynamics (MD) with continuum methods is given. A new hybrid approach coupling MD with a stochastic particles simulation approach based on Monte Carlo (MC) simulation is further described. The coupling in the hybrid MD-MC method is presented and simulation results are validated by comparing with pure MD simulation results of a system consisting of dense gas molecules confined between the walls of a micro/nano-channel. In the end, comparisons between accuracy and computational costs of MD, MC and hybrid MD-MC simulations are outlined. Flow and no-flow regimes are considered for comparisons and the predictions for heat transfer in micro/nano-channel cooling applications are discussed.Copyright

Hybrid Molecular Dynamics-Monte Carlo Simulations for the Properties of a Dense and Dilute Hard-Sphere Gas in a Microchannel

We present a hybrid method to study the properties of hard‐sphere gas molecules confined between two hard walls of a microchannel. The coupling between Molecular Dynamics(MD) and Monte Carlo(MC) simulations is introduced in order to combine the advantages of the MD and MC simulations, by performing MD near the boundaries for the accuracy of the interactions with the wall, and MC in the bulk because of the low computational cost. The effect of different gas densities, starting from a rarefied gas (reduced density η=πna3/6=0.001, where n=number density, a=molecular diameter) to a dense hard‐sphere gas (η=0.25), is investigated. We characterize the influence of different η’s and size of molecules on the equilibrium properties of the gas in a microchannel. The effect of the particle size on the simulation results, which is very small in case of a dilute gas, is increasing with η. Comparisons between MD, MC and hybrid MD‐MC simulation results are done, and comparisons between MD, MC, and hybrid MD‐MC computati...

Ion-selective optical sensor for continuous on-line monitoring of dialysate sodium during dialysis

Patients with end stage renal disease are dependent on dialysis. In most outpatient centers, the dialysate is prepared with a fixed electrolyte concentration without taking into account the inter-individual differences of essential electrolytes (sodium, potassium and calcium). This one-size fits all approach can lead to acute and chronic cardiovascular complications in dialysis patients. On-line monitoring of these essential electrolytes is an important physiological step towards patient specific dialysate leading to individualized treatment. Currently, changes in electrolyte concentrations are indirectly measured by conductivity measurements, which are not ion- specific. In this paper, we present a novel optical sensor for on-line monitoring of sodium concentrations in dialysate. This sensor is ion-specific and can detect up to a single ion. The working principle is based on the selective fluorescence quenching of photo-induced electron transfer (PET) molecules. The PET molecules when complexed with sodium ions start fluorescing upon laser excitation. The emission intensity is directly correlated to the sodium concentration. To prove the working principle, a micro-optofluidic device has been fabricated in polydimethylsiloxane (PDMS) with integrated optical fibers for fluorescence light collection. The PET molecules are covalently grafted in the PDMS microchannel for continuous monitoring of the sodium dialysate concentrations. The experimental setup consists of a laser module (λ=450nm) operating at 4.5mW, a syringe pump to precisely control the sample flow and a spectrometer for fluorescence collection. The performance of the sensor has been evaluated for sodium ions ranging from 0-50mM. A clear signal and good response time was observed.

Mathematical Modeling of Human Thermoregulation: A Neurophysiological Approach to Vasoconstriction

Skin blood flow is of major importance in human thermoregulation. Classic thermoregulation models require an explicit set point to control temperature. Normally such a set point is defined in the unit of the controlled variable (i.e. Celsius). However, the human body does not sense temperature directly, instead temperature information is coded into neuron fire rates. Here we explored the neurophysiology of thermoregulation to develop a mathematical model of skin blood flow that does not require a set point. The model was developed on measurement data of skin temperature, core temperature and skin blood flow and was validated using k-fold cross validation. The model explained over 90% of the variance in the measurements (r2=0.91). Hence, the results are promising and indicate that emulation of thermoregulatory neurophysiology is able to capture the dynamics of skin blood flow control.

Heat-transfer enhancement in AC electro-osmotic micro-flows

Heat transfer in micro-flows is essential to emerging technologies as advanced microelectronics cooling systems and chemical processes in lab-on-a-chip applications. The present study explores the potential of AC electro-osmotic (ACEO) flow forcing, a promising technique for the actuation and manipulation of micro-flows, for heat-transfer enhancement. Subjects of investigation include the 3D flow structure due to ACEO forcing via an array of electrodes in a micro-channel by way of 3D velocity measurements. Presence and properties of vortical structures of the 3D flow are quantified in laboratory experiments. Typical outcomes of the experimental study result from a number of 3D particle trajectories obtained by using 3D micro-Particle-Tracking Velocimetry (3D μ-PTV). The steady nature of the flow enables combination of results from a series of measurements into one dense data set. This facilitates accurate evaluation of quantities relevant for heat transfer by data-processing methods. The primary circulation is given above one half of an electrode in terms of the spanwise component of vorticity. The outline of the vortex boundary is determined via the eigenvalues of the strain-rate tensor. To estimate convective heat transfer, wall shear rate above one half of an electrode is quantitatively analyzed as function of voltage amplitude and frequency. These results yield first insights into the characteristics of 3D ACEO flows and ways to exploit and manipulate them for heat-transfer enhancement.