Mass transport in nanofluidic devices

Nanofluidics is a recent appearing research field, introduced in 1995 as an analogue of the field of microfluidics, and has been becoming popular in the past few years. The proximity of the channel dimension, the Debye length, and the size of biomolecules such as DNA and proteins gives the unique features of nanofluidic devices. Of various unique properties of the nanofluidics, mass transport in nanochannel plays determining roles in fundamental reaches and practical applications of nanofluidic device. Thus, much work including numerical and experimental researches has been performed to investigate the mass transport behaviors in nanofluidic devices. This review summarizes the fabrication technologies for nanofluidic devices, the mass transport behaviors in nanochannel, and their applications in bioanalysis. The main focus will be laid on the effects of nanochannel size and surface charge on mass transport including electrokinetic transport of charged analytes, diffusion of electric neutral molecules, ionic current rectification, concentration polarization, nonlinear electrokinetic flow at the micro-nanofluidic interfaces.     

Electrokinetic transport through nanochannels

This article presents a numerical study of the electrokinetic transport phenomena (electroosmosis and electrophoresis) in a three-dimensional nanochannel with a circular cross-section. Due to the nanometer dimensions, the Boltzmann distribution of the ions is not valid in the nanochannels. Therefore, the conventional theories of electrokinetic flow through the microchannels such as Poisson-Boltzmann equation and Helmholtz-Smoluchowski slip velocity approach are no longer applicable. In the current study, a set of coupled partial differential equations including Poisson-Nernst-Plank equation, Navier-Stokes, and continuity equations is solved to find the electric potential field, ionic concentration field, and the velocity field in the three-dimensional nanochannel. The effects of surface electric charge and the radius of nanochannel on the electric potential, liquid flow, and ionic transport are investigated. Unlike the microchannels, the electric potential field, ionic concentration field, and velocity field are strongly size-dependent in nanochannels. The electric potential gradient along the nanochannel also depends on the surface electric charge of the nanochannel. More counter ions than the coions are transported through the nanochannel. The ionic concentration enrichment at the entrance and the exit of the nanochannel is completely evident from the simulation results. The study also shows that the flow velocity in the nanochannel is higher when the surface electric charge is stronger or the radius of the nanochannel is larger.     

Effect of gate length and dielectric thickness on ion and fluid transport in a fluidic nanochannel

We have simulated the effect of gate length and dielectric thickness on ion and fluid transport in a fluidic nanochannel with negative surface charge on its walls. A short gate is unable to induce significant cation enrichment in the nanochannel and ion current is controlled mostly by cation depletion at positive gate potentials. The cation enrichment increases with increasing gate length and/or decreasing dielectric thickness due to higher changes induced in the surface charge density and zeta-potential. Thus, long gates and thin dielectric layers are more effective in controlling ion current. The model without Navier-Stokes equations is unable to correctly predict phenomena such as cation enrichment, increase in channel conductivity, and decreasing electric field. Body force and induced fluid velocity decrease slowly and then rapidly with gate potentials. The effectiveness of ion current control by a gate reduces with increasing surface charge density due to reduced fractional change in zeta-potential.     

Design of an interface to allow microfluidic electrophoresis chips to drink from the fire hose of the external environment

An interface design is presented that facilitates automated sample introduction into an electrokinetic microchip, without perturbing the liquids within the microfluidic device. The design utilizes an interface flow channel with a volume flow resistance that is 0.54-4.1 x 10(6) times lower than the volume flow resistance of the electrokinetic fluid manifold used for mixing, reaction, separation, and analysis. A channel, 300 microm deep, 1 mm wide and 15-20 mm long, was etched in glass substrates to create the sample introduction channel (SIC) for a manifold of electrokinetic flow channels in the range of 10-13 microm depth and 36-275 microm width. Volume flow rates of up to 1 mL/min were pumped through the SIC without perturbing the solutions within the electrokinetic channel manifold. Calculations support this observation, suggesting a leakage flow to electroosmotic flow ratio of 0.1:1% in the electrokinetic channels, arising from 66-700 microL/min pressure-driven flow rates in the SIC. Peak heights for capillary electrophoresis separations in the electrokinetic flow manifold showed no dependence on whether the SIC pump was on or off. On-chip mixing, reaction and separation of anti-ovalbumin and ovalbumin could be performed with good quantitative results, independent of the SIC pump operation. Reproducibility of injection performance, estimated from peak height variations, ranged from 1.5-4%, depending upon the device design and the sample composition.     

Dual opposite injection electrokinetic chromatography: nonionic microemulsion pseudostationary phase and novel approach to electrokinetic sampling bias

Dual opposite injection capillary electrophoresis (DOI-CE) is a family of CE techniques in which the sample is introduced into both ends of the capillary. For the analysis of compounds with widely varying pKa values using a voltage-driven separation scheme, DOI-CE is superior to conventional CE with sample introduction at only one end of the capillary due to DOI-CE's broader elution window. To enhance the DOI-CE separation, a running buffer with a microemulsion system was developed. Since DOI-CE works best under conditions of low electroosmotic flow (EOF), the suppression of EOF via the addition of a multiply charged cation (e.g., Zn2+) to the buffer was investigated, and was found to suppress the EOF effectively at moderate concentrations (2.5-10 mM). Three different dual opposite injection modes were studied: simultaneous electrokinetic injection, sequential electrokinetic injection, and sequential hydrodynamic injection. The injection bias in the first two electrokinetic injection modes was compared with the sequential hydrodynamic injection. Corrections in the bias of the electrokinetic injections were discussed, and an improved approach was suggested. Finally, the effect of the relative concentration of the multiply charged cation in the sample plug and running buffer on the peak shape of co-electroosmotic and counter-electroosmotic ions was examined, and found to be much more influential on the latter.     

Sample transport and electrokinetic injection in a microchip device for chemical cytometry

Sample transport and electrokinetic injection bias are well characterized in capillary electrophoresis and simple microchips, but a thorough understanding of sample transport on devices combining electroosmosis, electrophoresis, and pressure-driven flow is lacking. In this work, we evaluate the effects of electric fields from 0 to 300 V/cm, electrophoretic mobilities from 10(-4) to 10(-6) cm(2)/Vs, and pressure-driven fluid velocities from 50 to 250 μm/s on sample injection in a microfluidic chemical cytometry device. By studying a continuous sample stream, we find that increasing electric field strength and electrophoretic mobility result in improved injection and that COMSOL simulations accurately predict sample transport. The effects of pressure-driven fluid velocity on injection are complex, and relative concentration values lie on a surface defined by pressure-driven flow rates. For high-mobility analytes, this surface is flat, and sample injection is robust despite fluctuations in flow rate. For lower mobility analytes, the surface becomes steeper, and injection depends strongly on pressure-driven flow. These results indicate generally that device design must account for analyte characteristics and specifically that this device is suited to high-mobility analytes. We demonstrate that for a suitable pair of peptides fluctuations in injection volume are correlated; electrokinetic injection bias is minimized; and electrophoretic separation is achieved.     

Theory of transport in nanofluidic channels with moderately thin electrical double layers: effect of the wall potential modulation on solutions of symmetric and asymmetric electrolytes

Electrokinetic phenomena play an important role for the transport in submicrometer-size channels since the electric double layers formed at the walls can occupy a substantial part of the channel volume. This presents a theoretical difficulty and specific problems are usually treated numerically or not comprehensively. In our work we present a theoretical model that allows one to obtain analytical expressions for the transport of fluid (electro-osmotic flow), ions (electric current), and dissolved charged molecules (analytes). The model is based on the weak double layer approximation and has a wide range of validity. An important feature of this theoretical approach is that it is applicable not only to symmetric but also to asymmetric 2:1 and 1:2 electrolytes which exhibit very interesting properties in nanoscale channels. The possibility of affecting the wall electrokinetic zeta potential by applying a transverse voltage bias is analyzed. This transverse bias is used in an attempt to control the transport in the channel and such devices are often called "fluidic field-effect transistors." Our model quantifies the effect of the voltage bias on the zeta potential of the channel wall and therefore can be used for prediction of transport and optimization of separations in such fluidic devices.     

Modeling electrokinetics in ionic liquids

Using direct numerical simulations, we provide a thorough study regarding the electrokinetics of ionic liquids. In particular, modified Poisson–Nernst–Planck equations are solved to capture the crowding and overscreening effects characteristic of an ionic liquid. For modeling electrokinetic flows in an ionic liquid, the modified Poisson‐Nernst‐Planck equations are coupled with Navier–Stokes equations to study the coupling of ion transport, hydrodynamics, and electrostatic forces. Specifically, we consider the ion transport between two parallel charged surfaces, charging dynamics in a nanopore, capacitance of electric double‐layer capacitors, electroosmotic flow in a nanochannel, electroconvective instability on a plane ion‐selective surface, and electroconvective flow on a curved ion‐selective surface. We also discuss how crowding and overscreening and their interplay affect the electrokinetic behaviors of ionic liquids in these application problems.     

Optimal configuration of capillary electrophoresis microchip with expansion chamber in separation channel

This study develops a novel capillary electrophoresis (CE) microfluidic device featuring a conventional cross-form injection system and an expansion chamber located at the inlet of the separation channel. The combined injection system/expansion chamber arrangement is designed to deliver a high-quality sample band into the separation channel such that the detection performance of the device is enhanced. Numerical simulations are performed to investigate the electrokinetic transport processes in the microfluidic device and to establish the optimal configuration of the expansion chamber. The results indicate that an expansion chamber with an expansion ratio of 2.5 and an expansion length of 500 microm delivers a sample plug with the correct shape and orientation. With this particular configuration, the peak intensities of the sample are sharp and clearly distinguishable in the detection region of the separation channel. Therefore, this configuration is well suited for capillary electrophoresis applications which require a highly sensitive resolution of the sample plug. The novel CE microfluidic device developed in this study has an exciting potential for use in high-performance, high-throughput chemical analysis applications and in many other applications throughout the field of micro-total-analysis-systems.     

Nanofluidic channels by anodic bonding of amorphous silicon to glass to study ion-accumulation and ion-depletion effect

A unique phenomenon, ion-enrichment and ion-depletion effect, exists in nanofluidic channels and is observed in amorphous silicon (α-Si) nanochannels as shallow as 50 nm. As a voltage is applied across a nanochannel, ions are rapidly enriched at one end and depleted at the other end of the nanochannel. α-Si is deposited on glass by plasma enhanced chemical vapor deposition and is selectively etched to form nanochannels. The depth of nanochannels is defined by the thickness of the α-Si layer. Low temperature anodic bonding of α-Si to glass was used to seal the channel with a second glass wafer. The strength of the anodic bond was optimized by the introduction of a silicon nitride adhesion promoting layer and double-sided bonding resulting from the electric field reversal. Completed channels, 50 nm in depth, 5 micron wide, and 1 mm long were completely and reliably sealed. Structures based on nanochannels 50-300 nm deep were successfully incorporated into nanofluidic devices to investigate ionic accumulation and depletion effect due to overlapping of electric double layer.     

Electrokinetic ion transport in confined micro‐nanochannel

In this paper, a confined micronanochannel is presented to concentrate ions in a restricted zone. A general model exploiting the Poisson–Nernst–Plank equations coupled with the Navier–Stokes equation is employed to simulate the electrokinetic ion transport. The influences of the micronanochannel dimension and the surface charge density on the potential distribution, the ion concentration, and the fluid flow are investigated. The numerical results show that the potential drop depends mainly on the nanochannel, instead of the confined channel. Both decreasing the width and increasing the length enhance the ion enrichment performance. For a given nanochannel, ultimate value of ion concentration may be determined by the potential at the center point of the nanochannel. The study also shows that the enrichment stability can be improved by increasing the micronanochannel width, decreasing the micronanochannel length and reducing the surface charge density.     

Influence of channel position on sample confinement in two-dimensional planar microfluidic devices

We report enhanced sample confinement on microfluidic devices using a combination of electrokinetic flow from adjacent control channels and electric field shaping with an array of channels perpendicular to the sample stream. The basic device design consisted of a single first dimension (1D) channel, intersecting an array of 32 or 96 parallel second dimension (2D) channels. To minimize sample dispersion and leakage into the parallel channels as the sample traversed the sample transfer region, control channels were placed to the left and right of the 1D and waste channels. The electrokinetic flow from the control channels confined the sample stream and acted as a buffer between the sample stream and the 2D channels. To further enhance sample confinement, the electric field was shaped parallel to the sample stream by placing the channel array in close proximity to the sample transfer region. Using COMSOL Multiphysics, initial work focused on simulating the electric fields and fluid flows in various device geometries, and the results guided device design. Following the design phase, we fabricated devices with 40, 80, and 120 microm wide control channels and evaluated the sample stream width as a function of the electric field strength ratio in the control and 1D channels (E(C)/E(1D)). For the 32 channel design, the 40 and 80 microm wide control channels produced the most effective sample confinement with stream widths as narrow as 75 microm, and for the 96 channel design, all three control channel widths generated comparable sample stream widths. Comparison of the 32 and 96 channel designs showed sample confinement scaled easily with the length of the sample transfer region.     

Transmembrane potential across single conical nanopores and resulting memristive and memcapacitive ion transport

Memristive and memcapacitive behaviors are observed from ion transport through single conical nanopores in SiO(2) substrate. In i-V measurements, current is found to depend on not just the applied bias potential but also previous conditions in the transport-limiting region inside the nanopore (history-dependent, or memory effect). At different scan rates, a constant cross-point potential separates normal and negative hysteresis loops at low and high conductivity states, respectively. Memory effects are attributed to the finite mobility of ions as they redistribute within the negatively charged nanopore under applied potentials. A quantative correlation between the cross-point potential and electrolyte concentration is established.     

A nanochannel array based device for determination of the isoelectric point of confined proteins

A nanochannel array based nanodevice can mimic the biological environments and thus unveil the natural properties, conformation and recognition information of biomolecules such as proteins and DNA in confined spaces. Here we report that porous anodic alumina (PAA) of a highly parallel nanochannel array covalently modified with proteins significantly modulates the transport of a negatively charged probe of ferricyanide due to the electrostatic interactions between the probes and modified nanochannel inner surface. Results show that such electrostatic interaction exists in a wide range of ionic strength from 1 mM to 100 mM in 20 nm nanochannels modified with proteins (hemoglobin, bovine serum albumin, and goat anti-rabbit IgG secondary antibody). In addition, the maximal steady-state flux of the charged probe through the modified nanochannel array is directly related to the ionic strength which determines the electric double layer thickness and solution pH which modulates the nanochannel surface charge. Thus, the modulated mass transport of the probe by solution pH can be used to study the charge properties of the immobilized proteins in nanochannel confined conditions, leading us to obtain the isoelectric point (pI) of the proteins confined in nanochannels. The determined pI values of two known proteins of hemoglobin and bovine serum albumin are close to the ones of the same proteins covalently modified on a 3-mercaptopropionic acid self-assembled monolayer/gold electrode. In addition, the pI of an unknown protein of goat anti-rabbit IgG secondary antibody confined in nanochannels was determined to be 6.3. Finally, the confinement effect of nanochannels on the charge properties of immobilized proteins has been discussed.     

Evaporation driven pumping for chromatography application

A continuous transport process for liquids in micro-channels is reported. Flow was generated by evaporation at the channel end plus capillary forces. The micro-channels integrated into a two-glass-layer device were 110 microm wide, 28 microm deep and 4 or 10 cm long. A continuous liquid transport velocity of up to 2.25 mm s(-1) was observed for aqueous solutions. The flow velocity is shown to increase when an air stream is guided over the evaporation zone.     

纳通道的物质传输特性及应用

近年来,随着材料科学、微纳加工技术和微纳尺度物质传输理论的发展,纳通道技术得到了越来越多的研究和关注。纳通道包括生物纳通道和人工纳通道,其孔径通常为1~100 nm。在这一尺度下,通道表面与通道内物质之间的作用概率大大增强,使得纳通道表现出许多与宏观体系不同的物质传输特性,例如通道表面电荷与通道内离子之间的静电作用产生了离子选择性,通道内电化学势的不对称分布产生了离子整流特性,物质传输过程中占据通道产生了阻塞脉冲特性等。纳通道中的这些物质传输特性在传感、分离、能源等领域具有广泛应用,例如通过对纳通道进行功能化修饰可以实现门控离子传输;利用亚纳米尺度的通道可以实现单分子传感;利用通道与传输物质之间的相互作用可以实现离子、分子、纳米粒子的分离;利用纳通道的离子选择性可以在通道内实现电荷分离,将不同形式的能量（如光、热、压力、盐差等）高效转化为电能。纳通道技术是化学、材料科学、纳米技术等多学科的交叉集合,在解决生物、环境、能源等基本问题方面具有良好的前景。该文综述了近10年来与纳通道物质传输理论以及纳通道技术应用相关的前沿研究,梳理了纳通道技术的发展过程,并对其在各个领域的应用进行了总结与展望。     

An improved hybrid continuum‐atomistic four‐way coupled model for electrokinetics in nanofluidics

In this study, an efficient hybrid continuum‐atomistic method is proposed to study electrokinetic transport of aqueous solutions in nanofluidics. The aqueous phase is considered as a continuous phase containing immersed ion particles. The behavior of the system is then simulated through utilization of an improved hybrid continuum‐atomistic four‐way coupled approach, including the MultiPhase Particle‐In‐Cell method for the short‐ranged interaction between the ion particles, the Brownian force for the collision between the aqueous phase molecules and the ion particles, and a wall force accounting for the short‐ranged interaction of ions and walls. The validation of the proposed model with the results of Molecular Dynamics simulations suggests that this model can be a promising approach for studying the electrokinetic phenomena in more complicated geometries where the Molecular Dynamics approach is computationally prohibitive. Finally, the effects of electrokinetic parameters, such as the height of the channel, the external electric field, and bulk ionic concentration, on the electroosmotic flow in a nanochannel are investigated and discussed.     

Factors influencing the electrokinetic injection of oligonucleotides in capillary gel electrophoresis when using laser‐induced fluorescence detection

Capillary gel electrophoresis (CGE) is a powerful tool for the analysis of oligonucleotides owing to its extraordinary resolving power. However, the only feasible injection mode for CGE, electrokinetic injection, can cause bias of the injected amount and thus reproducibility issues for CGE methods. Although the source of the bias in electrokinetic injection for analysis of small molecules by capillary zone electrophoresis has long been identified, there are very few studies on electrokinetic injection issues for biological molecules analyzed by CGE. In this study, we report three issues related to electrokinetic injection for oligonucleotides. First, the relationship between the injection amount and the sample solution resistance is not always linear for oligonucleotides, as has been observed for small molecules. Second, the injecting water prior to an oligonucleotide sample dramatically improves the reproducibility of both the injected amount and resolution through a ‘stacking‐like’ mechanism. Third, optimizing the gel concentration dramatically increases the amount of oligonucleotide that is injected into the column. Copyright © 2013 John Wiley & Sons, Ltd.     

Electrical interfacial layer at TiO2/poly(4-styrene sulfonate) aqueous interface

The interfacial properties of the system titanium(IV) oxide/poly(4-styrenesulfonate) (PSS) over a broad pH region in the presence of different alkali metal chlorides of different concentrations were investigated by means of electrokinetic, adsorption and surface potential measurements. Adsorption and electrokinetic data were obtained with colloid TiO₂ particles, while surface potential data were obtained using a single crystal rutile electrode with the 001 plane exposed to the liquid medium. The electrokinetic and surface potentials of TiO₂ were measured in the absence and presence of PSS. Since the presence of PSS did not significantly affect surface potentials, it was concluded that negative PSS molecules adsorbed at the surface by forming an outer-sphere surface complex rather than inner-sphere complex. The adsorption decreases significantly with pH, while the electrokinetic potential in the presence of PSS is negative in the whole investigated pH region. Amount of adsorbed PSS molecules is limited by the electrostatic repulsion which suppresses further adsorption, i.e. above critical potential of ?50 millivolts. In the acidic region, where the surface is originally positively charged the amount of adsorbed PSS molecules is high since negative PSS molecules should at first compensate original positive charge and in the second step reverse the charge to reach the critical potential. In the basic region the surface charge is already negative so that small amount of adsorbed PSS molecules creates critical potential that prevents further adsorption.     

External ion accumulation of low molecular weight poly(ethylene glycol) by electrospray ionization fourier transform mass spectrometry

The combination of electrospray ionization (ESI) with Fourier transform mass spectrometry (FTMS) is a powerful tool in characterizing synthetic polymers. ESI permits the generation of intact, multiply charged high mass ions, whereas FTMS provides high mass resolution and correspondingly improved mass accuracy. However, under “nonideal” empirically determined operating conditions, a mass discrimination effect occurs as a function of accumulation time that can result in significant differences for calculated average mass values (M_n, M_w) and polydispersities. A multidimensional tuning process to eliminate the deleterious effects of mass bias is demonstrated for several sodiated poly(ethylene glycol) samples containing oligomers with masses covering a 600–3350 Da mass regime. In addition, experiments are performed in order to elucidate the possible mechanism(s) that cause the mass discrimination effect. It is proposed that extended collisions (reactive and nonreactive) occur in the hexapole to alter the energy (and velocity) distributions of the ions before injection into the trap. By choosing higher skimmer potentials, ions over a narrower energy “window” are preselected in the hexapole and exhibit lower overall mass bias effects.