Nanofluidics: Systems and Applications

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IEEE SENSORS JOURNAL, VOL. 8, NO. 5, MAY 2008 441 Nanofluidics: Systems and Applications Shaurya Prakash, Aigars Piruska, Enid N. Gatimu, Paul W. Bohn, Jonathan V. Sweedler, and Mark A. Shannon Abstract—Nanofluidics presents growing and exciting oppor- tunities for conducting fundamental studies for processes and systems that govern molecular-scale operations in science and engineering. In addition, nanofluidics provides a rapidly growing platform for developing new systems and technologies for an ever-growing list of applications. This review presents a summary of the transport phenomena in nanofluidics with a focus on several systems and applications important to problems of public health and welfare. Special emphasis is afforded to the role of the electric double layer and the molecular-scale interactions that occur within confined nanoscale systems. Index Terms—Microfluidics, nanofluidics, nanomedicine, sur- faces, water purification. NOMENCLATURE Symbol Description Molar flux of th species. Diffusion coefficient of th species. Molar concentration of th species. Velocity of bulk flow. Mobility of th species. Valence of th species. Faraday’s constant. Electrical potential. Universal gas constant. Manuscript received June 25, 2007; accepted August 12, 2007. This work was supported in part by the National Science Foundation through the Center for Nano-Chemical-Electrical-Mechanical Manufacturing Systems (Nano-CEMMS) under DMI-0328162, in part by the Science and Technology Center of Advanced Materials for the Purification of Water with Systems (WaterCAMPWS) under Agreement CTS-0120978, in part by the Department of Energy under Grant DE FG02 07ER15851, and in part by the Strategic Environmental Research and Development Program (SERDP). The associate editor coordinating the review of this paper and approving it for publication was Dr. Richard Fair. S. Prakash was with the Department of Mechanical Science and Engineering, University of Illinois at Urbana–Champaign, Urbana, IL 61801 USA. He is now with the Department of Mechanical and Aerospace Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ 08854-8058 USA (e-mail: [email protected]). A. Piruska, E. N. Gatimu, and P. W. Bohn are with the Department of Chem- ical and Biomolecular Engineering, University of Notre Dame, Notre Dame, IN 46556 USA (e-mail: [email protected]; egatimu@nd. du; [email protected]). J. V. Sweedler is with the Department of Chemistry, University of Illinois at Urbana–Champaign, Urbana, IL 61801 USA (e-mail: [email protected]). M. A. Shannon is with the Department of Mechanical Science and Engi- neering, University of Illinois at Urbana–Champaign, Urbana, IL 61801 USA (e-mail: [email protected]). Color versions of one or more of the figures in this paper are available online at http://ieeexplore.ieee.org. Digital Object Identifier 10.1109/JSEN.2008.918758 Symbol Description Absolute temperature. Applied electric potential. Local electric potential. Current density. Total number of ionic species. Inverse Debye length. Debye length. Diameter of nanochannel/nanopore. Radius of th ionic species. Viscosity. Length of nanochannel/nanopore. Hydraulic diameter. Pressure drop. Body force. Density. Electric field. Bessel function of the first kind. Zeta potential. Volumetric flow rate. I. INTRODUCTION T HE DIGITAL AGE has seen tremendous advances in sci- ence and technology that have propelled human imagina- tion to new heights. The vision of developing massively parallel microscale systems for automating operations in the chemical and biological sciences now seems within reach, and the re- search community wants to move to the next level—building systems to probe, analyze, and use individual molecules to ad- dress issues in public health and welfare. Toward these goals, nanofluidics will play an important role as chemistry and bi- ology occur at molecular length scales. The defining feature of nanofluidics is that transport processes occur within systems with critical dimensions on the order of characteristic physical scaling lengths, typically 1–100 nm. In some nanofluidic appli- cations, the key length scales are determined by the shielding properties of aqueous solutions. For example, the Debye length, is nm for deionized (DI) water (limited by the autoprotolysis of water), and is less than 1 nm for concen- trated salt solutions. Therefore, in many systems and applica- tions the effects of shielding and the electric double layer (EDL) 1530-437X/$25.00 © 2008 IEEE

Transcript of Nanofluidics: Systems and Applications

IEEE SENSORS JOURNAL, VOL. 8, NO. 5, MAY 2008 441

Nanofluidics: Systems and ApplicationsShaurya Prakash, Aigars Piruska, Enid N. Gatimu, Paul W. Bohn, Jonathan V. Sweedler, and Mark A. Shannon

Abstract—Nanofluidics presents growing and exciting oppor-tunities for conducting fundamental studies for processes andsystems that govern molecular-scale operations in science andengineering. In addition, nanofluidics provides a rapidly growingplatform for developing new systems and technologies for anever-growing list of applications. This review presents a summaryof the transport phenomena in nanofluidics with a focus on severalsystems and applications important to problems of public healthand welfare. Special emphasis is afforded to the role of the electricdouble layer and the molecular-scale interactions that occurwithin confined nanoscale systems.

Index Terms—Microfluidics, nanofluidics, nanomedicine, sur-faces, water purification.

NOMENCLATURE

Symbol Description

Molar flux of th species.

Diffusion coefficient of th species.

Molar concentration of th species.

Velocity of bulk flow.

Mobility of th species.

Valence of th species.

Faraday’s constant.

Electrical potential.

Universal gas constant.

Manuscript received June 25, 2007; accepted August 12, 2007. Thiswork was supported in part by the National Science Foundation through theCenter for Nano-Chemical-Electrical-Mechanical Manufacturing Systems(Nano-CEMMS) under DMI-0328162, in part by the Science and TechnologyCenter of Advanced Materials for the Purification of Water with Systems(WaterCAMPWS) under Agreement CTS-0120978, in part by the Departmentof Energy under Grant DE FG02 07ER15851, and in part by the StrategicEnvironmental Research and Development Program (SERDP). The associateeditor coordinating the review of this paper and approving it for publicationwas Dr. Richard Fair.

S. Prakash was with the Department of Mechanical Science and Engineering,University of Illinois at Urbana–Champaign, Urbana, IL 61801 USA. He isnow with the Department of Mechanical and Aerospace Engineering, Rutgers,The State University of New Jersey, Piscataway, NJ 08854-8058 USA (e-mail:[email protected]).

A. Piruska, E. N. Gatimu, and P. W. Bohn are with the Department of Chem-ical and Biomolecular Engineering, University of Notre Dame, Notre Dame, IN46556 USA (e-mail: [email protected]; egatimu@nd. du; [email protected]).

J. V. Sweedler is with the Department of Chemistry, University of Illinois atUrbana–Champaign, Urbana, IL 61801 USA (e-mail: [email protected]).

M. A. Shannon is with the Department of Mechanical Science and Engi-neering, University of Illinois at Urbana–Champaign, Urbana, IL 61801 USA(e-mail: [email protected]).

Color versions of one or more of the figures in this paper are available onlineat http://ieeexplore.ieee.org.

Digital Object Identifier 10.1109/JSEN.2008.918758

Symbol Description

Absolute temperature.

Applied electric potential.

Local electric potential.

Current density.

Total number of ionic species.

Inverse Debye length.

Debye length.

Diameter of nanochannel/nanopore.

Radius of th ionic species.

Viscosity.

Length of nanochannel/nanopore.

Hydraulic diameter.

Pressure drop.

Body force.

Density.

Electric field.

Bessel function of the first kind.

Zeta potential.

Volumetric flow rate.

I. INTRODUCTION

THE DIGITAL AGE has seen tremendous advances in sci-ence and technology that have propelled human imagina-

tion to new heights. The vision of developing massively parallelmicroscale systems for automating operations in the chemicaland biological sciences now seems within reach, and the re-search community wants to move to the next level—buildingsystems to probe, analyze, and use individual molecules to ad-dress issues in public health and welfare. Toward these goals,nanofluidics will play an important role as chemistry and bi-ology occur at molecular length scales. The defining featureof nanofluidics is that transport processes occur within systemswith critical dimensions on the order of characteristic physicalscaling lengths, typically 1–100 nm. In some nanofluidic appli-cations, the key length scales are determined by the shieldingproperties of aqueous solutions. For example, the Debye length,

is nm for deionized (DI) water (limited bythe autoprotolysis of water), and is less than 1 nm for concen-trated salt solutions. Therefore, in many systems and applica-tions the effects of shielding and the electric double layer (EDL)

1530-437X/$25.00 © 2008 IEEE

442 IEEE SENSORS JOURNAL, VOL. 8, NO. 5, MAY 2008

Fig. 1. A schematic description of the length scales and lithographic techniques used in micro and nanosystems. Figure from [1] and [2].

govern transport and reactions in nanofluidic structures. Usingnanoscale systems and functional nanoscale components in mi-croscale devices provide exciting opportunities for building sys-tems that can probe or manipulate individual molecules. Fig. 1shows the length scales important for transport at the micro andnanoscales. The length scales are presented from three perspec-tives: those based on representative devices and applications, theobjects that are important for these devices and applications, andlithographic and fabrication techniques that can be used to fab-ricate the devices.

The advantages of microfluidics, such as limited reagentconsumption, high throughput, and development of disposablelow-cost devices, are well documented [1], [3]–[6]. In addition,transport physics at the microscale are also well-understood[1], [7]–[10]. However, the story for nanofluidics is quitedifferent. The walls, due to the large surface-area-to-volumeratios (as high as m ), dominate behavior giving rise tointeresting phenomena such as ion permselectivity, ion enrich-ment (or depletion), fast injection of small volumes of reagents,rapid mixing, and pH, charge and concentration gradientsstable for long periods of time. New experimental tools suchas scanning probe microscopy (SPM), confocal microscopy,and single-molecule fluorescence along with the advances innumerical calculations and atomic scale simulation methodsprovide an increased clarity of understanding of the principleson which new applications can be based [8], [10]–[14].

The purpose of this review is to summarize the transport phe-nomena in nanofluidics, with special emphasis on the distinctiverole of the EDL and the molecular-scale interactions that occurwithin confined nanoscale systems. The range of devices, howthey are fabricated, and the applications differ in many waysfrom their microscale constructs. Theoretical investigations ofnanofluidics, including numerical simulations, have focused onnanoscale transport and several excellent references exist [8],[10], [12], [13], [15]–[21]. Experimental studies, which con-stitute the majority of this review, may require special fabrica-tion approaches, with a recent review highlighting methods ofnanofabrication [22].

II. THEORETICAL BACKGROUND

In contrast to the recent explosion of interest in nanoflu-idics, the underlying concepts that govern nanofluidics havebeen known for some time and are discussed next. The theoryassumes that the continuum descriptions of fluid transport arevalid. Once the continuum assumption breaks down, advancednumerical techniques are generally needed for accurate descrip-tions of transport phenomena. A discussion of noncontinuummodels and some key advances can be found in several excel-lent references [13], [23]–[30].

Most transport phenomena at the nanoscale are driven eitherby electrokinetic flow or surface mediated transport. Pressuredriven flows, more common for macroscale systems, are rarelyemployed for nanoscale systems due to the large driving pres-sures required, as can be seen from the dependence of pres-sure drop, , on channel diameter in the Hagen–Poiseuilleequation [31]

(1)

where is the viscosity of the fluid, the volumetric flow rate,and the length of the channel. For instance, with water thepressure drop across a 100 m long channel 1 nm in diameter foronly an attoliter ( m ) per second incompressible laminarflow would need a pressure drop from (1) greater than 3 GPa,which is impractical for any device. Electrokinetic flows cansustain higher flow rates through nanometer channels withoutexcessive pressures. Thus, electrokinetic flows are a preferredmethod for driving fluid and ions through nanochannels.

A. Electrokinetic Flow

A charged surface in contact with a liquid forms an EDL.The concept of the EDL has been developed over the last cen-tury [16], [17], [32], [33], and several excellent reviews havebeen presented [18], [19], [34], [35]. A schematic diagram il-lustrating the classic EDL structure is shown in Fig. 2, showingthe positions to which different characteristic surface charge re-lated potentials are referenced within the EDL. Ionic transport

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Fig. 2. A schematic depiction of the classic double-layer structure with thelocations where key potentials are measured. Figure based on the work of [16],[23], [25], and [35].

is classically described by the Nernst–Planck equation and thevelocity profiles are often obtained by using the Navier–Stokesequations, which are the equations of motion. The potential dis-tribution in the nanostructure is critical because the dominanttransport mechanisms are electrokinetically driven. The ionicand potential distributions are obtained from the Poisson equa-tion. Frequently, a Boltzmann distribution of charged speciesis assumed yielding the Poisson–Boltzmann (P-B) equation. Inmost applications, these equations are coupled, and a numericalsolution is required [7], [8], [10], [13], [15], [20], [21], [36] [37].

The terms used in the equations to follow are defined in thenomenclature section. The molar flux of the th species isgiven by a form of 1-D Nernst–Planck equation such that

(2)

where is the molar concentration of the th species, is theelectrical potential, is a bulk fluid velocity, and is the va-lence of the th species. Einstein’s relation connects the ionicmobility to the diffusion coefficient such that

(3)

where is Faraday’s constant. The electrical potential is gen-erally considered the sum of two potentials

(4)

where is the applied and is the local potential. Summingfluxes over all the species and accounting for the valence of eachspecies provides the total current density within a fluidicchannel

(5)

Fig. 3. A simple form of the molecular gate construct. The NCAM acts asa fluidic bridge between microfluidic channels. The NCAM presents excitingnew possibilities in micro-nanoscale systems due to the interesting physics asdiscussed in this review. (a) shows some SEM images of the NCAM and im-ages of Au nanotubes that can be formed within these NCAMs. (b) depicts thenearly instantaneous mixing that can occur after injection through an NCAM.The mixing is complete within a few hundred microns after injection into theseparation channel. The fluorescence images are collected as a function of time.

which combined with (2) yields

(6)

Now, let us look at some important limiting cases as theseoften arise in the microfluidic and nanofluidic systems beingreviewed in this paper. In the case of a concentration gradientbeing the only driving force, an electrical current arises such that

(7)

This equation can also be obtained from Fick’s laws of diffu-sion. For purely electrokinetic flow, the diffusion and electroos-motic terms can be often neglected in comparison to the elec-trophoretic term, yielding

(8)

Consider a single, cylindrical nanocapillary with the appliedpotential across it being the only driver for transport of ionicspecies. In such a case, the velocity of the species in the axialdirection is given by

(9)

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for which the solution is

(10)

where is the radius of the channel, is the electrical permit-tivity, and is the hyperbolic Bessel function of the first kind.Equation (10) is valid for small zeta potentials, , i.e., typically

mV. The potential is a phenomenological measure ofthe electric potential at a “slip” plane near a surface, beyond thefixed Stern layer, where the first layer of molecules from thesurface are thought to have significant motion. As (10) implies,the transport velocity is proportional to the potential and thepermittivity of the solution, varies inversely with the viscosity,and is exponentially affected by the shielding length. One caveatfor transport in nanochannels is that the concept of the slip orshear plane (Fig. 2) becomes ill-defined when the EDLs fromopposed walls within nanopores begin to overlap, and/or struc-tural layering of molecules and charges are a significant portionof the molecules within the channel. In these circumstances ofnanoscale transport with interacting or overlapping EDLs, it ismore useful to consider the surface charge or the surface poten-tial [38]–[41].

B. Advanced Numerical Techniques

The theoretical background presented in the previous sectionassumes the validity of the continuum assumptions, i.e., thatthe ions are treated as hard spheres and point charges andwater is considered as a continuum in the P-B equation. Inorder to evaluate transport characteristics, the Navier–Stokesand Nernst–Planck equations are used that consider water asa continuous medium with a constant viscosity. Any inter-actions between the surface and the analytes are consideredthrough the boundary conditions. These assumptions neglection-ion, ion-wall, ion-water interactions, and effects of hy-drogen bonding between water molecules. Advanced numericaltechniques such as molecular dynamic simulations present anattractive method to answer some questions about the atomisticnature of the interactions in confined nanoscale transport. Oneof the major downsides to advanced numerical techniques is thehigh computational cost [42]. Therefore, most advanced simu-lations are limited in scope. Typically, for confined nanoscaletransport if the size of the species of interest is about tentimes smaller than the characteristic system dimension thecontinuum approach has been found to be approximately valid.For example, for simple hydrated ions such as Na :H O in ananochannel with critical dimensions on the order of 10 nm orgreater, the continuum assumptions hold for dilute solutions.However, contrasting criteria for the breakdown of the con-tinuum methods have also been presented [13], [37], [43]–[46].

Employing advanced numerical techniques to nanofluidicshas demonstrated several interesting phenomena spurringgreater interest in developing better systems. In addition, theunderstanding of atomistic behavior governing the transportcharacteristics has also been enhanced. Effects of finite ion sizeand hydration on ion distribution and velocity [24], [42], [47],charge inversion and flow reversal [23], density fluctuations[48], role of fluid density on particle transport [49], role ofsurface charge on transport of ions and water [50], layering and

orientation of fluids and ions with changes in fluid density nearsurfaces due to surface energy interactions [51]–[54], and effectof surface roughness [55] in nanochannels have been investi-gated. An overall conclusion from these studies is that waterand ions organize within a nanochannel that is reminiscent ofclassical P-B and N-P solutions for potential, but with signifi-cant departures in the details that can give rise to unexpectedresults in transport of species through nanochannels, as will behighlighted in the following discussions.

III. APPLICATIONS

A. Transport Phenomena

Several interesting phenomena based on the fundamental dif-ferences in physics at the nanoscale have been observed. For ex-ample, the channel diameter, , and the inverse Debye length, ,may be combined into the dimensionless parameter . This pa-rameter may be tuned to control the dominant form of nanoflu-idic transport between electroosmosis and electro-migration [56]. This tuning can be achieved bychanging the EDL thickness relative to the pore diameter ei-ther by altering the electrolyte concentration of the solution orby changing the surface charge density by changing the solu-tion pH [56], [57], and functionalizing or applying an electricalbias to the channel walls (as will be discussed later). An implicitassumption in altering the EDL thickness by changing the bulkconcentration is that the concentration within the nanopores alsochanges in concert with the bulk concentration. However, deter-mining the exact concentration within the nanopores can requiredetailed numerical calculations [13], [35], [58] to account forfactors such as ion-ion interactions, changes in hydration levelof aqueous species in confined nanoscale spaces, and the molec-ular nature of water. The role of the EDL in reducing electroos-motic flow (EOF) has also been investigated. It has been shownthat once the EDL is greater than approximately 10% of thecritical channel dimension, the effect of EDL on EOF can nolonger be neglected, and at EDL thickness greater than %of the channel dimension EOF is reduced [59]. In a related ef-fect, ion permselectivity occurs due to the excess charge densitypresent on the inner walls of the nanochannels. For example,Au-plated nanocapillary array membranes (NCAMs) reject ionsof the same charge (co-ions) and transport ions of the oppositesign (counter-ions). This charge-selective transport is only pos-sible when the EDLs within the nanopores overlap or interact.This permselectivity effect of the surface potential has beendemonstrated by biasing the membrane, so that by switchingpolarity of the applied bias leads to either preferential cation oranion transport [60]. The effect of changing length scales ontransport and separation of polyelectrolytes such as DNA hasalso been investigated [61]. One notable point about separationsis that often the need for selectivity and high permeability are inconflict. Few studies have discussed competing roles of selec-tivity versus permeability across nanofluidic structures.

One of the key factors that affect transport at the nanoscaleis the surface charge [39]–[41], [62]. Surface charge can becontrolled by either functionalizing the inner surfaces of thenanofluidic systems through physical or chemical modifica-tions or by applying potentials to metal-coated interior pore

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walls. Several different surface modification schemes havebeen developed to affect several parameters for microscaletransport [63]–[68]; however, the use of surface coatings toaffect transport at the nanoscale is relatively new. Using surfacecoatings, size-based separations have been demonstrated bycontrolling the plating time of Au within an NCAM template totune the internal nanopore diameter. In addition, by using thiolmonolayers, chemical transport selectivity can be achieved[69]. Thiol-based surface modifications of Au-NCAMs havebeen used to generate chemical transport selectivity for dif-ferent experimental conditions, including selective transportof hydrophilic or hydrophobic species [70], pH-dependenttransport [71], separation of proteins by exploiting changes inthe isoelectric point of a functionalized surface [72], or directmolecular recognition mediated by thiolated-DNA used todetect base-pair mismatches [73]. Most surface modificationschemes to control the surface properties including surfacecharge utilize either Au-thiol self-assembled monolayers orSi-based monolayers for glass-like systems. Modification ofconfined surfaces at the nanoscale with synthetic polymersremains a challenge to researchers, although recent advancesin derivatization strategies for biological macromolecules haveseen both enzymes [74] and antibodies [75] derivatized withinnanopores.

The transport phenomena through nanostructures can also beinfluenced by applying an electrical potential across or to thenanostructures. An early demonstration of controlling ionic per-meability through a nanoporous membrane was shown over twodecades ago by using an embedded electrode [76]. Using thisapproach, ion movement through membranes containing fixedionic sites was shown to depend on the nature and number ofcharged sites, and ionic resistance of the membrane was electro-chemically controlled via the oxidation state on the redox siteswithin the polymer [76]. Embedded electrode systems are alsobeing developed to probe potential distributions within singlenanopores [66].

Rapid progress in microfluidics has led to an increasingdemand for developing systems that can handle complex flu-idic manipulations in confined nanoscale systems. Integratingnanofluidic components allows for not only further reduction ofvolumes but also permits manipulation of fluidic samples basedon size and charge of analyte species using valves, moleculargates, and fluidic architectures similar to VLSI circuits [9], [66],[77]–[81]. Developing multilayer 3-D integrated microfluidicsystems [77] constitutes one viable method to enhance com-plexity in fluid handling operations, because disparate fluidicmanipulations such as preparation, concentration, tagging,separation, or affinity recognition may be accomplished indifferent planes. Optimal use of these capabilities requires athorough understanding of nanofluidic transport at its mostbasic level. To this end, single nanopores, microfabricated inPMMA films can be used as individual interconnects or asplatforms to study fundamental nanofluidics [82]. However,several open questions such as the role of surface charge,surface potentials, specific interactions between the wallsand the translocating species, mechanisms of transport acrossnanofluidic structures, and visualization of confined nanoscaleflows remain a challenge to the research community.

Three-dimensional systems using nanofluidic interconnects,which provide fluidic communication among microfluidicchannels in vertically separated layers, have been of interest forthe purpose of fluid handling in mass-transported limited sam-ples [83], [84]. In these micro-nano hybrid systems size-basedselectivity for various dextrans has been demonstrated [85],[86]. Size-based selectivity can be understood based on theStokes–Einstein relation. For a chemical species in bulk solu-tion the diffusion coefficient is governed by

(11)

As the size of a nanochannel, nanopore, or nanotube decreases,with increasing molecule size, one expects to observe the phys-ical effects of hindered diffusion. For a molecule of radiusdiffusing within a nanoscale channel of comparable radius ,the center of the molecule cannot approach the wall within adistance . The extent to which the diffusion coefficient ofa molecule in the confined nanoscale space is reduced in con-trast to its value in the bulk solution is given by the Renkinequation

(12)

where . A similar analysis has been presented byBayley and Martin in their review article on resistive-pulsesensing [87].

The transport characteristics of multilevel 3-D hybrid micro-nano structures are related to the electrical characteristics of thefluidic network. This fluidic network was initially modeled as asimple resistive network in order to explain the polarity reversalin the direction of electrokinetic transport of 200 nm pore di-ameter NCAMs compared with 15 nm pore diameter NCAMs[80], [85]. In a later study, the capacitance of the NCAM wasincluded [88] in the models. However, further development ofequivalent circuit models may be necessary for nanofluidic sys-tems, since it has been shown recently that simple RC circuits,under certain conditions, are not sufficient to explain the trans-port characteristics at the nanoscale [66]. These 3-D microflu-idic structures with nanofluidic interconnects exhibit a variety ofinteresting and useful electrical characteristics stemming fromtheir nanoscale architecture. For example, they have been shownto maintain large concentration gradients for extended periodsof time [89], [90], possess near-diode like behavior with controlover rapid injection, mixing, and to preconcentrate attomolarconcentration solutions [81], [91], [92] and other mass-limitedsamples [93], [94].

B. Chemical Analysis

Nanofluidics can add functionality for sample manipulationsin analytical chemistry, such as sample injections, separa-tion, purifications, and preconcentration for quantitative andqualitative identification. For example, NCAMs functioningas controllable molecular gates can mediate digital transfer[95] of fluid voxels from one microfluidic channel to another.In addition, NCAMs presenting different pore sizes [96] cantransfer analytes with disparate mass characteristics at differentrates to achieve intelligent fluidic control. This capability hasconsequently found use in a miniaturized lead sensor that uses

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DNAzyme [97] as a probe and for preparative post-separationprocessing for mass limited samples [93]. Control of fluidictransport in nanochannels is crucial to the development of inte-grated components nanofluidic-microfluidic chemo-electronicdevices. In this regard, Karnik et al. reported a metal oxidesolution-based system analogous to a metal oxide semicon-ductor field effect transistor [39] that achieves flow switchingvia active control of the surface potential in the interior of thenanochannel, thereby demonstrating the ability to control trans-port of charged species in a nanostructure that could potentiallylead to fluiditronics.

Another area in which nanofluidics can have a profound im-pact on chemical analysis is sample preparation. For example,an analyte may need to be isolated from a complex matrix andmade available for analysis in a suitable chemical environment.Iannacone et al. [98] demonstrated that NCAMs can be used toenhance the intensity of an insulin peak introduced into a massspectrometer from a microfluidic channel using electrospray ion-ization; this occurs by reducing the salt adducts inherent in thesample preparation process. Additionally, various receptors canbe incorporated into NCAMs. This strategy could be beneficialfor sample preconcentration and purification of biomoleculesin microfluidic devices. Both antibodies [75] and DNA probes[99] have been successfully incorporated in NCAMs for appli-cations in protein purification and preconcentration. Preconcen-tration factors of up to 300 have been achieved for single polarityspecies [100] in NCAMs and up to for proteins and peptides[101] in simple nanofluidic structures.

Beyond these demonstrated applications of micro-nanoflu-idic architectures have enormous potential for novel chemicalseparations by reducing required sample amount and improvingresolution. This issue has been addressed both theoretically[102], [103] and experimentally, and is mainly driven byinterest in DNA separation. Periodically constricted nanochan-nels [104] have shown successful DNA separations and closepacked beads with nanometer spacing [105] have been utilizedto accomplish both DNA and protein separations.

C. Nanomedicine

One of the reasons the scientific community is excited aboutadvances in nanofluidics and nanotechnology centers on thepossibility of manipulating processes, especially in biologicalsystems, at the molecular level. This possibility has led to rapiddevelopment of new materials, methods, and systems for appli-cations in biomedicine [106]–[110]. A recent review explainsthe concept of nanomedicine and some of the early advances inapplying the principles of nanotechnology to medicine [111].Nanomaterials, such as silica or gold nanoparticles, quantumdots, functionalized micro and nanocantilevers, and artificialnanopores are being increasingly used for detection of DNA [2],[112]–[115], RNA [116]–[118], and proteins [119]–[122]. Insome cases, the asymmetry within artificial nanostructures isbeing exploited to mimic the behavior of natural systems, suchas ion-channels [123]–[125]. Multiple fabrication techniques,for example, e-beam lithography, focused ion-beam milling, andnanoimprint lithography have been used to construct nanostruc-tures for trapping and transporting DNA and focusing of proteinsusing dielectrophoresis [126]. Using well-defined nanochannels

from 30–500 nm DNA and proteins have been separated usingsteric effects that exploit the principle of entropic minimizationin the transport of biomacromolecules within confined geome-tries [123]. Nanostructures and single nanopores have beenused to reduce the entropic contribution to the total free energyof DNA, thereby modulating entry into a separation channelaccording to the oligonucleotide length [127], [128].

Silicon has been extensively used as a material for buildingsystems for applications in biochemical systems at thenanoscale due to its versatility in microfabrication [129].However, chemical modification can impart novel propertiesof the solid-liquid interface that can be usefully exploited.Many materials and methods are currently being researched fordrug-delivery applications [130] including dendrimers, suchas poly(amido amine) or PAMAM [131]. Dendrimers haverecently been attached to confined surfaces within microflu-idic devices and show a possible method for attachment ofPAMAM dendrimers to nanofluidic devices [68]. Developmentof systems relying on bacteria as molecular motors for pumpingsmall volumes of liquids has also been investigated [132].

D. Water Purification

Recent reports have highlighted the growing challenge ofproviding clean, safe water for a variety of applications in-cluding potable water, energy generation, and agricultural use[133]–[135]. These problems are central to the general publichealth and welfare and, therefore, have led to a resurgence ofinterest in researching new materials, systems, and methodsfor water purification and detection of various chemical andbiological species in water supplies [90], [136]–[139]. Mem-branes, consisting of nanopores or nanocapillaries ranging from1 nm to 1 m, have historically played an important role in ap-plications related to water purification [10], [140]–[142]. Theyhave been studied extensively for their role in aqueous systemsincluding studies on the importance of chemical composition,surface charge and morphology [62], [143]–[145], fouling[146], [147], and desalination and filtration [90], [135], [139],[148], [149]. Structures based on the purposeful manipulationof nanofluidics present excellent opportunities for growth in thearea of detection and sensing for water purification as illustratedby the use of an integrated microsystem for injection analysisof ammonia in surface waters for environmental applications[150]. Detection of heavy metal ions has found a new pathwayin the development of DNA-based sensors for lead and uraniumions [151]–[154]. Nanoparticles have been used for removalof trace organic contaminants such as trichloroethylene andchloroform [155] and mesoporous materials with pores in thesub-10 nm range have been used for removal of polyelectrolytespecies such as humic acids from water [156].

IV. SUMMARY

Many applications and scientific advances in nanotech-nology have created an intense debate both in the scientificand socio-political forums about the implications and futuredirections of the multitude of new technologies. Nanofluidicsis a rapidly evolving discipline with wide and varied appli-cations. A few of these applications with direct relevance toproblems of public health and welfare such as nanomedicine

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and water purification have been discussed in this paper. Therole of the EDL in determining transport in confined nanoscalesystems has been conclusively demonstrated. The theoreticalframework to understand and answer fundamental questionsin confined nanoscale transport was outlined and severalexperimental studies that have illustrated many interesting phe-nomena were summarized. The field of nanofluidics is highlyinterdisciplinary taking inspiration from nature and biologywith applications in chemistry, materials science, physics,environmental, and engineering systems. It is hoped that thispaper will assist researchers from diverse fields by providing acollection of varied references.

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Shaurya Prakash received the B.S. degree inmechanical engineering from the University ofArkansas, Fayetteville, in 2001, the M.S. degree inmechanical engineering working on laser-inducedfluorescence measurements of hydroxyl radicalsover various inert surfaces from the University ofIllinois at Urbana–Champaign, Urbana, in 2003. Heis currently working towards the Ph.D. degree fromthe University of Illinois under the supervision ofProf. M. A. Shannon, where has worked extensivelywith surface modification, impedance spectroscopy,

micro and nanofluidics, and flame structure studies.He brings together a multidisciplinary skill set with his areas of interest and

expertise, which include micro and nanofabrication, microscale combustion,and transport in confined micro and nanosystems.

Aigars Piruska was born in Riga, Latvia, in 1979. Hereceived the B.S. degree in chemistry from the Uni-versity of Latvia, Riga, in 2001, and the Ph.D. degreefrom the University of Cincinnati, Cincinnati, OH, in2006.

Currently, he is a Postdoctoral Researcher with theDepartment of Chemical Engineering, University ofNotre Dame du Lac. His research interests includeenvironmental sensing and micro/nanofluidics.

Enid N. Gatimu was born in Nairobi, Kenya, in 1970. She received the B.S.and Ph.D. degrees in chemistry from Clark Atlanta University, Atlanta, GA, in1994 and 2003, respectively.

In 2004, she joined Prof. P.l Bohn’s group at the University of Illinois atUrbana–Champaign campus as a Postdoc and in 2006 moved to the Universityof Notre Dame in the same capacity. Her research is focused on studying thehindered transport characteristics of electrolytes flowing through nanocapillaryarray membranes and PMMA single pores incorporated in 3-D nanomicrofluidicdevices.

Paul W. Bohn received the B.S. degree in chemistryfrom the University of Notre Dame, Notre Dame, IN,in 1977 and the Ph.D. degree in chemistry from theUniversity of Wisconsin-Madison, in 1981.

After a two-year stint at Bell Laboratories, hejoined the faculty at the University of Illinois atUrbana–Champaign (UIUC). While at UIUC, heserved as Centennial Professor in Chemical Sci-ences, Professor of Chemistry, and Professor inthe Beckman Institute. He also served as InterimDirector of the School of Chemical Sciences from

1993 to 1994, and Head of the Chemistry Department from 1994 to 1999.From 2001 2002, he was Interim Vice Chancellor for Research, the SeniorResearch Officer of the UIUC campus. In August 2006, he left UIUC to jointhe faculty at the University of Notre Dame as the Arthur J. Schmitt Professorof Chemical and Biomolecular Engineering and Professor of Chemistry. Hehas authored/coauthored over 165 publications, 4 patents issued, and deliveredover 200 invited lectures throughout the world. His research interests includeunderstanding and control of molecular transport on the nanometer lengthscale, developing new optical spectroscopic measurement strategies for surfaceand interfacial structure-function studies, optoelectronic materials and devicesand chemical sensors, and molecular approaches to nanotechnology.

Dr. Bohn has received several awards.

Jonathan V. Sweedler is a Lycan Professor ofChemistry, the Director of the Carver BiotechnologyCenter, and has appointments in the Physiology,Neuroscience and Bioengineering Programs, all atthe University of Illinois at Urbana–Champaign.His research emphasizes analytical neurochemistry,and involves developing analytical methods forassaying complex microenvironments that includemicro/nanofluidic sampling, electrophoresis sep-aration methods, mass spectrometric detectiontechniques, and nanoliter volume NMR. The second

group theme is the application of these technologies to the study neuropeptidesand classical transmitters, as well as their metabolism in a cell-specific manner.

Mark A. Shannon received the B.S., M.S., andPh.D. degrees in mechanical engineering from theUniversity of California at Berkeley, in 1989, 1991,and 1993, respectively.

He is the James W. Bayne Professor of Me-chanical Engineering at the University of Illinoisat Urbana–Champaign. His goal is to advance thestate-of-knowledge in coupled phenomenon at themicro to nanoscale, with applications to high-tem-perature combustion reactors, water purification,microfabrication, nano and microelectromechanical

systems (NEMS and MEMS), micro and nanofluidic devices, and mesoscalemachines that bridge the nano and microscales to the normal scales. Studentsin his group conduct research related to microfabrication process development,experimental measurements, and computational research. Currently, he is theDirector of a NSF STC the WaterCAMPWS, which is a multiple universityand government laboratory center for advancing the science and technologyof materials and systems for revolutionary improvements in water purificationfor human use. He is also the Director of the Micro-Nano-Mechanical Systems(MNMS) Laboratory at the University of Illinois at Urbana–Champaign, a 2000sq. ft class 10 and 100 clean room laboratory devoted to research and educationin the design and fabrication of a variety of MEMS and NEMS. He also chairsthe Instrument Systems Development Study Session for the National Institutesof Health. He has published over 150 papers.

Dr. Shannon has received numerous awards for excellence in teaching andresearch.