Single-Molecule Sensing Using Nanopores inTwo-Dimensional Transition Metal Carbide(MXene) MembranesMehrnaz Mojtabavi,†,# Armin VahidMohammadi,‡,# Wentao Liang,§ Majid Beidaghi,*,‡

and Meni Wanunu*,∥,⊥

†Department of Bioengineering, Northeastern University, Boston, Massachusetts 02115, United States‡Department of Materials Engineering, Auburn University, Auburn, Alabama 36849, United States§Kostas Advanced Nano-Characterization Facility, Northeastern University, Burlington Campus, 141 South Bedford Street,Burlington, Massachusetts 01803, United States∥Department of Physics, Northeastern University, Boston, Massachusetts 02115, United States⊥Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts 02115, United States

*S Supporting Information

ABSTRACT: Label-free nanopore technology for sequencingbiopolymers such as DNA and RNA could potentially replaceexisting methods if improvements in cost, speed, and accuracyare achieved. Solid-state nanopores have been developed over thepast two decades as physically and chemically versatile sensorsthat mimic biological channels, through which transport andsequencing of biomolecules have already been demonstrated. Ofparticular interest is the use of two-dimensional (2D) materialsas nanopore substrates, since these can in theory provide thehighest resolution readout (<1 nm of a biopolymer segment) andopportunities for electronic multiplexed readout through theirinteresting electronic properties. In this work, we report onnanopores comprising atomically thin flakes of 2D transition metal carbides called MXenes. We demonstrate a high-yield(60%), contamination-free, and alignment-free transfer method that involves their self-assembly at a liquid−liquidinterface to large-scale (mm-sized) films composed of sheets, followed by nanopore fabrication using focused electronbeams. Our work demonstrates the feasibility of MXenes, a class of hydrophilic 2D materials with over 20 compositionsknown to date, as nanopore membranes for DNA translocation and single-molecule sensing applications.KEYWORDS: MXene, 2D titanium carbide, nanopore, DNA translocation, transfer

The discovery and isolation of monolayer graphene, atwo-dimensional (2D) material, enabled investigationsof atomically thin crystalline structures that exhibit

distinct physical and chemical properties as compared to theirbulk forms.1,2 Since then, graphene and other 2D materialshave received considerable attention as potential candidates forvarious applications where thin robust membranes areneeded.3−11

Currently, 2D materials are available with properties thatspan a wide range. For example, 2D materials with electronicproperties of conductors, semiconductors, and insulators are allavailable. A particularly compelling application for 2Dmaterials involves their use as atomically thin membranes innanopore-based sensing of molecules. In this method,individual biomolecules stochastically pass through a nanoporein an otherwise impermeable membrane, and molecular

passage is detected by electrically monitoring ion passagethrough the pore while voltage is applied across it. Nanopore-based DNA and RNA sequencing, in which a strand is seriallyfed through the pore constriction, has recently become a realityand is commercially available.12−14 A hallmark feature ofnanopore sensing is that the length of the narrowest nanoporeconstriction determines the ultimate detection resolution.Lipid-embedded protein channels, which evolved from thecylindrical (low-resolution) β-barrel protein channelα-hemolysin15−17 to the extremely sharp (high-resolution)MspA18,19 and CsgG20,21 proteins, exhibit well-definedstructures that are tunable and engineerable. Recently, DNA-

Received: October 19, 2018Accepted: March 7, 2019Published: March 7, 2019

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based pores have also gained interest for the same mainattribute, namely, the ability to precisely engineer the porestructure.22−24 However, while protein pores offer precisetunability and reproducibility, the search for mechanically andchemically robust membranes that exhibit durability undervarious experimental conditions (i.e., protein-denaturingchemical conditions,25−28 nonaqueous solvents29,30) hasprompted the exploration of a variety of synthetic materialssuch as SiNx,

31 HfO2,32 SiO2,

33 Al2O3,34 and others.35−39 Over

a decade of research on nanopores composed of thesematerials revealed that despite robustness, the sensingresolution is ultimately limited by how thin these pores canbe made.40

This search for high-resolution pores has prompted thedevelopment of 2D solid-state nanopores, in which acrystalline atomically thin material serves as the nanoporemembrane.40 Graphene,41−43 molybdenum disulfide(MoS2),

44−47 boron nitride (BN),48−50 and tungsten disulfide(WS2)

51 are among the 2D materials that have beeninvestigated as nanopore membranes. While grapheneprovided the foundation for 2D nanopores, it has since beensuggested that even in the limit of a single-atom-thicknanopore the sensing region is longer than the nanoporethickness because of the dominance of access resistance.52

Furthermore, the sub-nanometer thickness of graphene,despite being theoretically ideal for high-resolution DNAbase discrimination, exhibits noise and poor mechanicalstability due to contamination and mechanical fluctuation,respectively, which severely limit the usable device yield.53−55

Therefore, pores in compound 2D materials such as MoS2have gained interest due to the higher hydrophilicity of MoS2in contrast to graphene56 and have shown DNA basediscrimination toward DNA sequencing29,56 as well as osmoticpower generation for blue energy applications.57

Realization of 2D nanopores for practical applications inDNA sequencing requires materials and methods to obtainrobust membranes with tunable chemical properties forbiomolecular analysis at high yield. Two-dimensional transitionmetal carbides and nitrides called MXenes are an emergingfamily of 2D materials that possess metallic conductivity (dueto their metal-carbide core layers) combined with fullyfunctionalized surfaces (terminated with O, OH, and Ffunctional groups).58,59 The general formula for MXenes isMn+1XnTx, where M is a transition metal, X is carbon and/ornitrogen, n can be between 1 and 3, and Tx indicates differentfunctional groups on the MXene surfaces.59,60 MXenes areusually synthesized by liquid exfoliation techniques andthrough selective etching of A-layer atoms from MAX phases,a large group of layered ternary carbides and nitrides (forexample, Al is the A-layer in MAX phase Ti3AlC2).

59 Due totheir versatile compositions and highly tunable surfaces,60

MXenes have shown promise in various fields such as energystorage,61−64 gas sensors,65,66 water purification,67,68 cataly-sis,69,70 and hybrid nanocomposite fabrication71−74 amongothers. Established methods of MXene synthesis have largelybeen successful in synthesizing single-layer Ti3C2Tx, the firstobserved and most studied MXene,75,76 and there is verylimited knowledge77,78 on synthesis and delamination of other

Figure 1. MXene synthesis and characterization. (a) Thickness comparison of representative 2D materials used in nanopore experiments todate, including the present work. (b) Schematic illustration of the route to MXene 2D flake etching/dispersion from MAX phases and crystalstructure of Ti2CTx and Ti3C2Tx. (c) Ti2CTx flakes drop cast on a holey carbon film TEM grid. (d) Ti2CTx flakes drop cast on a Si chip. (e)AFM image of Ti2CTx flakes drop cast on a SiO2 substrate. (f) Corresponding height profiles for the flakes shown in the AFM image. (g)Ti3C2Tx flakes drop cast on a holey carbon film TEM grid. (h) Ti3C2Tx flakes drop cast on a Si chip. (i) AFM image and (j) correspondingheight profile of the Ti3C2Tx flakes.

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MXene compositions (i.e., Ti2CTx) that have been predictedto have superior properties.79,80 Further, the lack of robustmethods for transferring MXene flakes onto substrates haspushed back their integration into devices.Herein, we investigate the use of MXenes as 2D membranes

for nanopore-based biomolecule detection. We have developeda liquid−liquid interface approach to assemble Ti2CTx andTi3C2Tx MXene sheets to a macroscale size (1−10 mm),facilitating their transfer with virtually no contamination, noneed for prealignment, and a high yield (∼60%). We havefabricated nanometer-sized pores in freestanding MXenemembranes using electron beams and demonstrated ultrathinion-impermeable membranes with low noise comparable to thestate-of-the-art 2D nanopore membranes made from grapheneor MoS2.

29,54 Using high-bandwidth ion current measurementswe have detected the transport of double-stranded DNA

(dsDNA) molecules through MXene nanopores with sub-10nm diameters. Considering more than 20 different MXenecompositions that are experimentally synthesized, and manymore theoretically predicted,60 this work provides a pathwayfor investigating MXenes as a large family of 2D materials forsolid-state nanopore sensing applications.

RESULTS AND DISCUSSION

We synthesized both Ti2CTx and Ti3C2Tx MXenes throughselective etching of their corresponding MAX phases (Ti2AlCand Ti3AlC2, respectively) in a HCl−LiF etching solution (seeMaterials and Methods section for details). Figure 1a shows acomparison of different 2D materials that have been used asfreestanding membranes for nanopore devices and theirrespective single-layer thicknesses, with the MXenes used inthis study shown on the bottom for comparison. Figure 1b

Figure 2. MXene film formation at the liquid−liquid interface: assembly and transfer. (a) Schematic illustration of self-assembly of MXeneflakes at the water/methanol−chloroform interface, assisted by methanol partitioning into the chloroform phase (see dashed red arrows instep 3). (b) Snapshots of flake self-assembly at the liquid−liquid interface (see SI for movie); a dispersion with a higher concentration (0.05mg/mL) was used in this image for illustration purposes. (c) Transferred flake of Ti2CTx onto a prefabricated 200 nm hole in a SiNxmembrane. (d) AFM image of transferred Ti2CTx on a SiNx membrane. (e) Corresponding line profile of the AFM image showing athickness of about 2.4 nm for a single-layer membrane. (f) Transferred flake of Ti3C2Tx onto a prefabricated 200 nm hole in a SiNxmembrane. (g and h) HAADF STEM images of transferred Ti3C2Tx flakes at a folded region, showing six-layer-thick and three-layer-thickregions, respectively.

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schematically shows the chemical etching process in which Alatoms are selectively removed from MAX phase structures,leaving behind stacks of weakly bonded M−X (Ti2C or Ti3C2)layers. Manual shaking was then performed to delaminate theas-etched MXene multilayered powders after their washing,yielding a delaminated dispersion containing MXene flakeswith relatively large lateral sizes. While this worked for theTi3C2Tx MXene, for Ti2CTx we found that even sonication didnot result in high-yield delamination. Therefore, to facilitatedelamination of Ti2CTx, we used tetra n-butyl ammoniumhydroxide (TBAOH) as an intercalant,63,77 previously shownto weaken the interactions between individual layers byincreasing the interlayer spacing. Manual shaking of theTBAOH-intercalated Ti2CTx powders in water resulted indelamination, yielding a stable dispersion of single/few-layerTi2CTx flakes that appears as a dark red dispersion (see FigureS1). Crystal structures of both Ti2CTx and Ti3C2Tx MXenesare shown in Figure 1b. The structure of Ti2CTx MXene, athree-atom-thick material, consists of two layers of Ti atomssandwiching a layer of carbon (in octahedral sites). Its thickeranalogue is the Ti3C2Tx MXene, which is a five-atom-thickmaterial consisting of three layers of titanium and two layers ofcarbon.59 As illustrated in the figure, MXene exfoliation alwaysresults in highly functionalized basal planes that consist of O,OH, and F surface termination groups, which render the flakes’basal plane more hydrophilic than its graphene and MoS2analogues.59,60

Figure 1c and d show bright-field transmission electronmicroscopy (TEM) images of as-synthesized Ti2CTx flakesdrop cast on a holey carbon film TEM grid and a SiNxsubstrate, respectively. An atomic force microscopy (AFM)image of Ti2CTx flakes is shown in Figure 1e, which confirmsthe presence of large (several-μm) flakes in the dispersion. AnAFM height profile of the Ti2CTx flake, shown in Figure 1f,reveals an apparent Ti2CTx thickness of ∼2.3 nm, and theRMS surface roughness within a 2 × 2 μm2 area on the flake is0.57 nm. Based on this measured thickness, the flake is 1 to 2layers thick, since measured MXene thicknesses using AFM areknown to be exaggerated by an underlying water layer andbound functional groups.75,81,82 Bright-field TEM images ofdelaminated single-layer Ti3C2Tx flakes are shown in Figure1g,h, and AFM measurements on the synthesized Ti3C2Txflakes are shown in Figure 1i. In the case of Ti3C2Tx weobserved a baseline layer thickness of 3.5 nm (Figure 1j), andthe RMS roughness within a 2 × 2 μm2 area on the flake is0.16 nm, significantly smoother than the Ti2CTx flake.Interestingly, the thickness of a MXene sheet fold in thisimage shows a thickness of 1.4 nm, which is closer to thetheoretical value (0.98 nm) and in good agreement withpreviously reported single-layer Ti3C2Tx flake analysis.81,82

We developed a liquid−liquid interfacial transfer approachto assemble MXene layers into macroscale 2D films prior totransfer, as schematically illustrated in Figure 2a. To achievethis, we first diluted the initial MXene dispersion (0.1−0.5 mg/mL) 3−20-fold, depending on the initial concentration; thenwe added an equal amount of methanol to make a 1:1 water−methanol mixture and then cast a drop of that mixture onto achloroform bath in a PTFE Petri dish. Since water andchloroform are immiscible, the aqueous MXene dispersionphase forms a floating droplet on the chloroform bath, and asmethanol partitions into the chloroform phase, it drags with itMXene flakes to the water−chloroform interface (see dashedred arrows, Figure 2a, step 3). Snapshots during different

stages of the assembly are shown in Figure 2b (see alsoSupporting Information, Movie 1). The driving force for thisinterfacial film formation is a reduction in the surface energyupon partitioning of the 2D materials to the interface.83−85

However, since pinning the flakes or nanoparticles at theinterface reduces their entropy, mechanical work such assonication or manual shaking is usually required to drive theflakes to the interface.83,85 Instead, our methanol-drivenapproach efficiently and rapidly promotes interfacial filmformation. Indeed, in a control experiment without methanol,we found that films did not form. Once the film is formed atthe interface, electrostatic repulsion between the negativelycharged flakes’ edges is compensated by attractive capillaryforces due to distortion at the liquid−liquid interface.83,86 Theresulting assembly (mm-scale), which was stable for a longtime at the liquid−liquid interface, was cast onto a 5 mm ×5 mm Si chip having a 50-nm-thick SiNx membrane at itscenter with a 100 or 200 nm diameter hole drilled through themembrane using either a focused ion beam (FIB) or anelectron-beam lithography (EBL) tool. Casting was achievedby dipping the chip into the chloroform phase, slowly liftingthe chip through the droplet, and drying on a hot plate at 80°C for 5 min to complete the transfer process. Figure 2c and fshow TEM images of the transferred Ti2CTx and Ti3C2Txflakes on the hole. Also, Figure S2 shows more examples ofsuccessful and unsuccessful transfers, and Figure S3 shows low-magnification TEM images of the SiNx membrane withtransferred Ti3C2Tx and Ti2CTx flakes, demonstrating thecoverage of the SiNx membrane by MXene flakes. In total, 225devices were fabricated, of which 140 were Ti3C2Tx and 85were Ti2CTx. We obtained a high (>60%) yield of transferusing this method, defined as the ratio of SiNx chips with holescompletely covered with MXene flakes to the overall numberof transfers attempted. We also found that increasing theconcentration of flakes in the initial dispersion increases thefull-coverage yield; however, it also decreases the probability ofobtaining single-layer membranes. In Figure 2b and Supple-mentary Movie 1, for illustration and technique demonstration,we used a dispersion with a relatively higher concentration(0.05 mg/mL). Figure S4 shows snapshots of a 5-fold dilutedMXene dispersion (∼0.02 mg/mL) cast on chloroform duringflake self-assembly (top panel). To better represent the flakes,we have shown a higher contrast version of each image(bottom panel). In general, to obtain single-layer MXenemembranes, a 10−20× dilution from the initial dispersion isneeded. Figure S5 shows UV−Vis absorbance spectra of an as-synthesized Ti3C2Tx dispersion, a 3-fold diluted dispersion,and a 10-fold diluted dispersion. The inset shows photographsof all three dispersions. Apart from the high yield, this transfermethod has several advantages over other fabrication methodsused previously. First, yields obtained by directly drop castingfrom the MXene dispersion, our initial method of deposition,were very poor and resulted in partial coverage, as well as theformation of multilayer films by the piling up of sheets into thehole (see Figure S6), as also recently reported by Lipatov etal.82 In contrast to drop casting, we did not observe this effectfor our transfer method, instead obtaining flat sheets (FigureS2m−o). Moreover, the lack of a need of a sacrificial polymerfor transfer eliminates other materials from contaminating theresulting membrane, which is a plaguing problem in handlingMXenes82 and other 2D materials.42,44,48,51,87−89 As mentionedearlier, freestanding MXene membranes fabricated with thismethod could have different thicknesses depending on the

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initial flake concentration in the dispersion. Differenttechniques could be used to find the thickness of themembrane. Figure 2d shows an AFM image of Ti2CTx flakestransferred using the liquid−liquid interface method, andFigure 2e shows line height profiles from the image, where athickness of about 2.4 nm for one layer of Ti2CTx wasmeasured. To find the spacing between layers in the MXenesheets, we transferred flakes onto holey carbon film TEM gridsusing the same assembly method and characterized the filmusing atomic-resolution TEM. Areas where folding wasobserved (Figure S7) were used to estimate the overallthickness. Figure 2g,h and Figure S8 are representative high-angle annular dark-field scanning transmission electronmicroscopy (HAADF STEM) images of Ti3C2Tx that showmultilayer flake structure in a folded area. On the basis of theobserved structure, we derive an empirical formula for the

overall thickness as a function of the number of layers,= + −T N N( ) 1.0 1.8( 1) nm, where N represents the

number of layers and T the end-to-end thickness of thelayer. To confirm their composition, Figure S9 shows energy-dispersive X-ray spectroscopy (EDS) elemental mapping ofone of the folded regions.Unlike AFM imaging, which produces thickness artifacts

from water presence, contrast measurements from TEMimaging is a robust method for thickness estimation, althougha reduced stability of Ti2CTx flakes to electron beam exposurerequires careful imaging to avoid hole formation.To investigate the performance of MXene freestanding

membranes, we used a focused electron beam to fabricatenanopores with diameters ranging from 3 to 10 nm in bothTi2CTx and Ti3C2Tx membranes. Following nanoporefabrication, we assembled the devices in a fluidic cell that

Figure 3. Nanopore fabrication and ionic current detection through MXene nanopores. (a) Schematic illustration of the MXene nanoporeexperimental setup. (b) HAADF STEM image of a ∼4.2 nm diameter Ti3C2Tx nanopore fabricated using a STEM probe. (c) Current−voltage curve of a 6.2 nm diameter Ti2CTx (red) and a 5.1 nm diameter Ti3C2Tx (blue) pore (buffer: 400 mM KCl, 10 mM Tris, pH 7.5). (d)Current vs time traces for both pores (color-coded as in panel c) at 100 and 200 mV. (e) Power spectral density plots of Ti2CTx (red),Ti3C2Tx (blue), and 5.7 nm SiNx (gray) pores at 100 mV (taken from 1.5 s current traces). (f) Conductance vs TEM-based effective porediameter for 33 nanopores and their corresponding fit to eq 4, where the effective membrane thickness contour curves are shown (indicatedby text to the right of each curve). Each dashed line shows access resistance contribution to the total conductance through the pore (eq 3) ateach buffer condition shown by different colors. We estimate there is an error of ±1 nm for nanopore diameters measured by TEM. Datapoints at d = 0 nm show membrane conductance in the absence of a fabricated pore.

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hosts two electrolyte chambers, such that the nanopore is thesole liquid junction between the chambers. Figure 3a showsschematic of the MXene nanopore setup, in which two Ag/AgCl electrodes are each in contact with an electrolytechamber, and ion current through the pore that results fromvoltage application is measured using an electrometer. Figure3b shows a HAADF-STEM image of a 4.2 nm diameterTi3C2Tx nanopore that was fabricated using a STEM pointprobe. The image clearly shows the pore in black, a 1-layerregion that defines the 4.2 nm pore, and a larger (6−7 nm)ring that outlines a region that was thinned during the drillingprocess, which consists of a multilayer MXene film (3 or 4layers). Figure 3c shows I−V curves for a Ti2CTx nanoporewith a measured cross-sectional area of 36.4 nm2 (redmarkers), as well as a Ti3C2Tx nanopore with a cross-sectionalarea of 19.2 nm2 (blue markers). Insets show bright-field TEMimages of the pores, with the pores outlined in their respectivecolors. The triangular pore shape for the Ti3C2Tx pore is likelyto be caused by the shape of the slightly out-of-focus electronbeam. Other example TEM images and I−V curves are shownin Figure S10. Figure 3d shows current-vs-time traces for bothpores at 100 and 200 mV voltages, low-pass-filtered to 100kHz. Corresponding power spectral density plots for the tracesat 100 mV are shown in Figure 3e and for 200 mV in FigureS11. For comparison, a typical power spectral density plot of a5.7 nm diameter SiNx pore has been added to each figure(shown in gray). Noise characteristics for nanopores at low-frequency and high-frequency regimes have been studiedbefore and were shown to have f1/ noise in the low-frequencyregime, whose amplitude is voltage dependent.90 In alltransferred 2D nanopores studied so far, graphene,54

graphene−Al2O3,91 graphene−TiO2,

41 MoS2,29 and BN,49 the

dominant source of noise is in the low-frequency regime,known as f1/ noise, which is due to a number of factors thatinclude mechanical fluctuation, surface charge variation, andpore contamination. Our results for MXene pores suggest asimilarity in terms of noise characteristics to other nanoporesin transferred 2D membranes, although the noise performancestill lags behind transfer-free 2D membrane materials such asgraphene55 and MoS2.

45

The ion conductance ( =G I V/ ) through a pore isdependent on several pore characteristics such as its diameter,thickness, and surface charge, as described by eq 1.92

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ÑÑÑÑÑÑÑÑÑÑÑπ μ μ μ σ= + ++ − +G

d

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pore2

pore pore (1)

where dpore is the pore diameter, Lpore is the pore thickness, μ +iand μ −i are electrophoretic mobilities of the cations andanions, respectively, n is the number density of anions orcations, e is the elementary charge, and σ is the pore’s surfacecharge density. In the brackets of eq 1, the left term is theconductance through the pore as a result of ion flow in thebulk and is linearly dependent on the bulk salt concentration,whereas the right term shows the conductance through thepore as a result of electro-osmotic flow of counterions.Surface charge density is described by the Grahame

equation92 shown in eq 2:

ikjjjjj

y{zzzzzσ ζ

κ ξ=ϵϵ K T

eeK T

( )2

sinh2

o B

B (2)

where ζ is the zeta potential, εo is the absolute permittivity, ε isthe relative solution permittivity, KB is Boltzmann’s constant, Tis the temperature, κ−1 is the Debye length, and e is theelementary charge. We measured average zeta potentials of−40 mV for Ti3C2Tx at pH 5.5, −24 mV for Ti2CTx at pH 7.5,and −38 mV at pH 10 using a Malvern Zetasizer NanoZSP(Malvern, UK). This corresponds to surface charge densities of−13.2 and −8.7 mC m−2 for Ti3C2Tx at pH 5.5 and Ti2CTx atpH 7.5 in 400 mM KCl, respectively. In order forelectroosmotic flow to dominate the pore conductance, thecondition n ≫ σ d e2 / pore must be satisfied.92 For the smallestpore used here (dpore = 3 nm), the term σ d e2 / pore issignificantly smaller than n since our minimum experimentalsalt concentration was 400 mM. Therefore, we neglect theright term in eq 1 and reason that conductance is governed bythe bulk term of the equation. Aside from the dependence ofconductance on pore and buffer characteristics, another factorthat strongly influences conductance through the nanopore inthe case of very thin membranes is access resistance,93 shownby eq 3:

μ μ=

++ −R

ned1

( )i iaccess

pore (3)

Taking this into account, the total ion conductance throughthe pore is shown by eq 4:

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We have used eq 4 to calculate effective pore thicknessvalues based on measured conductance for 33 pores withTEM-measured effective diameters (approximated as discswith diameter d based on the TEM-measured pore areas), asshown in Figure 3f. Overlaid with the data points are contourlines that represent eq 4 for different labeled pore thicknessvalues in the range of 1−24 nm. Each dashed line shows theaccess resistance contribution (eq 3) to the total conductancethrough the pore for different pore diameters at different bufferconditions (shown by different colors). In general, we foundthat most of the pores we tested fall within the range of 1−10layers. For atomically thin pores, access resistance dominatestotal conductance through the pore, resulting in pore diameterbeing the only geometrical factor that affects the conductancethrough the pore. We predict that the data points in thevicinity of the access resistance lines belong to the pores withmonolayer-thick membranes. A few of the pores fell above theaccess resistance lines, suggesting pore expansion between thefabrication and the measurement steps or formation of smallholes during electron beam exposure to a monolayermembrane as shown in Figure S12 (see Materials and Methodssection for more information on pore drilling and imagingconditions). In general, by using this model, about 45% ofMXene membranes shown in Figure 3f are single layer. Wenote that in the absence of a fabricated pore, we obtained <0.3nS leakage values for both MXene types shown as d = 0 nmpoints in Figure 3f, which confirmed very low leakage at theMXene/SiNx interface. Recently, Perez et al.

94 have shown thateq 4 overestimates conductance through sub-5-nm SL-MoS2nanopores (more than 50% for sub-2-nm nanopores) due to

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different behavior of K+ and Cl− ions in nanopores and in bulk.In the current study, using this model instead of eq 4 givescomparable results since all the nanopores tested here haveeffective diameters of more than 3 nm.Following the characterization of pores using TEM and ion

current measurements, we tested the ability of our fabricatednanopores to electrically detect DNA transport. Figure 4a

shows a schematic of a dsDNA molecule transiting through aMXene nanopore (Ti2CTx). We highlight here that anattractive feature of the MXene membrane surface is itshydrophilicity, a result of the basal functional groups in thematerial. We have fabricated a ∼7 nm diameter nanopore in atransferred Ti2CTx membrane using a TEM, for which weobtained the current−voltage curve shown in Figure 4b (insetshows TEM image). At the top of Figure 4c, we show acontinuous current vs time trace in which we increased thevoltage in 100 mV increments from 300 mV to 500 mV. At thebottom of Figure 4c, we show a continuous current vs timetrace after the addition of 4 kbp dsDNA to a finalconcentration of 3 nM, when 250 mV was applied across thepore. The negatively pointing spikes are caused by temporaryocclusion of the nanopore by the DNA molecules, and a closer

look at the shape of these spikes is shown by Figure 4d, whichdisplays concatenated sets of these spike events at threedifferent voltages. Finally, in Figure 4e we plot the mean DNAcapture rate (left axis) and mean DNA translocation dwell time(right axis) as a function of the applied voltage (see dwell timedistributions in Figure S13). Our observation of increasingcapture rate with voltage, as well as decreasing mean dwell timewith increasing voltage, is supportive of DNA transportthrough the pore. Moreover, we have investigated translocationof dsDNA through a Ti2CTx nanopore using a 2 M LiCl bufferin order to decrease the translocation speed of DNA throughthe pore. It has been reported that LiCl results in improvedread-out resolution of DNA translocation in SiNx nanoporesdue to decreased translocation speed.95 Figure S14 showscurrent−voltage curve, current vs time traces, and mean DNAcapture rate and mean DNA translocation dwell time as afunction of voltage for a 6.4 nm diameter pore (panels a−d)and a 4.5 nm pore (panels e−g). Comparing these results withresults obtained for 400 mM KCl, Table 1 in SI, we show thatusing LiCl has resulted in a much higher mean dwell time: 1.18ms at 700 mV for pore 2 and 0.128 ms at 550 mV for pore 3.We note that for Ti3C2Tx the observation of DNA spikes

was very rare despite having produced more than 100 pores. Amuch higher success rate was obtained for the Ti2CTx MXenepores, which we hypothesize is due to their different synthesismethods. As explained in the Materials and Methods section,for Ti2CTx delamination to be complete, addition of TBAOHas intercalant is needed. This renders the Ti2CTx surfacefunctionality different from Ti3C2Tx, leading to less negativesurface charge for Ti2CTx as compared to Ti3C2Tx. The highlynegative surface charge of Ti3C2Tx could account forelectrostatic repulsion that hinders DNA transport throughthese pores, rendering Ti2CTx as superior for DNA trans-location experiments.To point out the advantages of Ti2CTx over other 2D

materials studied so far as nanopore membranes, we compareddifferent properties and biomolecule sensing performance ofgraphene, MoS2, BN, WS2, and Ti2CTx shown in Table 1. Webelieve that a potential advantage of Ti2CTx over other 2Dmaterials is their functionalized and hydrophilic surfaces, whichprovide the ability to easily and precisely tailor their propertiesfor specific applications through surface or compositionalmodification. Moreover, liquid exfoliation synthesis of MXenesfurther provides the ability to easily control the flakes’ qualityand size. As a nanopore membrane support, Ti2CTx nanoporesare stable in a wider range of voltages compared to other 2Dmaterials and have a high signal-to-noise ratio (>10)comparable to that reported for MoS2. Furthermore, we wereable to decrease the translocation speed of dsDNA through thepore considerably using 2 M LiCl. On the other hand, thesuccess rate of device fabrication with biomolecule sensingcapability is still a challenge. This could be overcome bytailoring the surface chemistry of MXenes to less negativelycharged surface groups. Moreover, formation of several poresduring electron beam exposure could be inhibited by using anSTEM probe, which also yields a pore with more precise sizeand geometry.

CONCLUSIONSWe have carried out here a series of ion and DNA transportstudies through MXene nanopores, produced by transferringsheets of TBAOH-exfoliated Ti2CTx MXene, as well asTi3C2Tx, onto hole-containing SiNx devices. To facilitate the

Figure 4. DNA translocation through Ti2CTx nanopores. (a)Schematic illustration of dsDNA translocation through a single-layer Ti2CTx nanopore. (b) Current−voltage curve of a 7.2 nmdiameter (by TEM) Ti2CTx pore measured in 400 mM KCl buffer(inset: TEM image of the pore). (c) Top: Current vs time traces atindicated voltages in the absence of DNA. Bottom: Current vs timetrace of 4 kbp dsDNA translocations through the pore, obtained at250 mV applied bias. (d) Concatenated set of spikes shown at 250mV (blue), 225 mV (black), and 200 mV (green). (e) Mean DNAcapture rates (black, left axis) and mean dwell times (green, rightaxis) as a function of voltage (lines = exponential fits to the data).All traces shown were acquired at a 250 kHz sampling rate andlow-pass filtered to 10 kHz.

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MXene transfer process, we have developed a method for flakeself-assembly at the liquid−liquid interface to mm-sized arraysof sheets, which results in high-yield (60%) and contami-nation-free transfer of flakes such that they completely seal thesupport hole. The key to this self-assembly process at thechloroform−water interface is the introduction of methanol tothe aqueous phase, which rapidly drives the sheets to theintersolution interface. Characterization of nanopores pro-duced in these suspended MXene membranes shows thicknessvalues that range from 1 to 15 MXene layers, the thickness ofwhich can be controlled by optimizing the assembly process.Furthermore, the MXene membranes exhibit low ion currentleakage, and nanopores in the MXene membranes show noisecharacteristics that are comparable to other two-dimensionalmembranes. Finally, we have demonstrated MXene nanopore-based sensing of DNA molecules in sub-10 nm pores, whichshow that DNA can transit through the Ti2CTx pores. Furtherrefinement of this class of 2D materials, which are hydrophilicin nature and electronically conductive, can lead to distinctapplications in biosensing and alternative sensing modalitiessuch as electrically gating the pores and sensing DNA usingtransverse readout, the subject of future studies.

MATERIALS AND METHODSMXene Synthesis. Large flakes of Ti3C2Tx and Ti2CTx MXenes

were synthesized according to the minimally intensive layerdelamination (MILD) method reported in the literature.81 First theetching solution was prepared by adding 1 g of LiF powder (98.5%,Alfa Aesar) to 20 mL of 6 M HCl solution (ACS grade, BDH). Themixture was then stirred for 15 min to completely dissolve the LiFpowder in the solution. Then, 1 g of MAX phase powder (Ti3AlC2 orTi2AlC, synthesized according to previous work69,74) was slowlyadded to the etching solution. The addition of MAX phases should bevery slow, and an ice bath should be used to avoid excessive heatgeneration due to the exothermic nature of the reaction. The etchingprocess was carried out for 24 h at 35 °C while stirring the solution at550 rpm using a Teflon-coated magnetic bar. After the etchingprocess was complete, the solution was divided into four differentcentrifuge vials, and DI water was added (45 mL) to dilute them. Thesolutions were then centrifuged at 3500 rpm for 3 min, and thesupernatant was poured out. To obtain delaminated Ti3C2Txdispersions, the washing process was continued by adding DI water,manual shaking of the solutions for 2 min, and then centrifuging themat 3500 rpm for 3 min until a dark green supernatant was observed(pH > 4.5). At this stage, the initial delaminated solution was pouredout and DI water was added to the sediments. The solutions wereshaken for another 2 min and this time centrifuged at 3500 rpm for 1h to collect the large flake size MXene solutions (pH ∼5). As forTi2CTx, the etching and washing process by manual shaking did notresult in proper delamination. Therefore, to delaminate Ti2CTx, thesynthesized multilayered powders after etching (pH of supernatant∼4.5) were collected and intercalated with tetra n-butyl ammoniumhydroxide (40% w/w aqueous solution in water, Alfa Aesar) by adding200 mg of Ti2CTx powder to 4 mL of TBAOH solution and stirringfor 2 h at room temperature. Then, the obtained solution was dilutedwith DI water and hand shaken for 2 min, followed by centrifugationat 2000 rpm for 10 min. Again, the first supernatant (slightly dark redcolor) was poured out, as it contained residual TBAOH. Then, DIwater was added to the sediments, and the solutions were shaken for 2min, followed by centrifugation at 2000 rpm for 30 min. The obtaineddark red supernatant was collected and used for device fabrication.

MXene Transfer. To fabricate free-standing MXene membranes,MXenes flakes dispersed in water were mixed with an equal volume ofmethanol (to obtain a MXene dispersion in 50:50 water−methanol).Then, a small amount of dispersion was added to the chloroform andflakes were self-assembled on the drop/chloroform interface. A ×5 5mm2 chip with a 50 nm thick SiNx membrane at the centerT

able

1.Com

parisonbetween2D

MaterialsStud

iedso

Faras

Nanop

oreMem

brane

biom

oleculedetection

type

of2D

material

materials

synthesismethod

nanopore

mem

brane

fabrication

surface

properties

appliedvoltage

window

successrate

ofdevice

fordetection

type

d/Lb

(nm)

buffer

V(m

V)

translocationspeed

(bp(nt)/μs)

capturerate

(s−1nM

−1 )

SNR(@

10kH

z)ref

graphene

CVD/exfoliatio

ndirect

CVD/transfer

hydrophobic

[−500,

500]

91∼10%

dsDNA

8/2

1M KCl

100

33a

1>2

a41

notreported

dsDNA

22/0.3

1M KCl

200

18a

notreported

>2a

42

MoS

2CVD/exfoliatio

ndirect

CVD/transfer

semi-

hydrophobic

[−400,

400]

44>7

0%dsDNA

20/0.7

2M KCl

200

50notreported

>10

44

notreported

ssDNA

2.3/1.6

0.4M

KCl

200

10a

0.95

not reported

45

WS 2

CVD/exfoliatio

ntransfer

semi-

hydrophobic

notreported

notreported

dsDNA

4.4/0.7

3M KCl

400

25a

notreported

>4a

51

h-BN

CVD/exfoliatio

ntransfer

hydrophobic

notreported

notreported

dsDNA

∼6/1.1

3M KCl

160

62a

notreported

>2a

48

Ti 2C

exfoliatio

ntransfer

hydrophilic

[−900,

900]

∼10%

dsDNA

4.5/8

2M LiCl

500

0.5

0.042

>10

this study

aValuescalculated

usingthedata

provided

intheoriginalmanuscript.bd=diam

eter,L

=pore

length.

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(previously cleaned with hot piranha (H2SO4−H2O2, 2:1) anddeionized water) was dipped into the chloroform and lifted upthrough the drop. Afterward, chips were left on the hot plate at 80 °Cfor about 5 min to dry (the process is shown in the supplementaryvideo). For TEM imaging, the same transfer method was used butinstead of using SiNx chips, a holey carbon film TEM grid was used.Device and Nanopore Fabrication. ×5 5 mm2 chips with a 50

nm thick SiNx membrane at the center and a prefabricated 100 or 200nm hole made with FIB or EBL were used as substrates for devicefabrication. The chips were cleaned prior to MXene transfer with hotpiranha (H2SO4−H2O2 with a 2:1 ratio) and deionized water. AfterMXene transfer onto the chips, nanopores were fabricated on thefreestanding part of the MXene flakes using a JEOL 2010FEG at1.5M× magnification and spot sizes in the range of 3−5. Pores wereformed within 1−5 s (for <10-nm-thick membranes) by focusing thebeam on a small part of the membrane with a beam current density of0.5−1 nA·nm−2. Afterward, magnification was reduced to 800k× forimaging. For some monolayer membranes, during imaging with abeam current density of ∼0.02−0.15 pA·nm−2, we have observedformation of several pores on the membrane.Characterization Techniques. TEM analysis was done directly

on MXene flakes transferred to TEM grids or devices. High-resolutionTEM imaging was done using a JEOL 2010FEG operating in bright-field mode at 200 kV, and a probe-corrected FEI Titan Themis 300STEM with ChemiSTEM technology was used for atomic resolutionimaging of MXene sheets. Scanning electron microscopy (SEM)analysis of MXenes was done using a JEOL JSM-7000F scanningelectron microscope. AFM measurements were carried out by ParkInstruments NX10 AFM using a noncontact mode cantilever.Nanopore Experiment Data Acquisition and Analysis. SiNx

chips with fabricated nanopores on freestanding MXene membraneswere assembled on a PTFE cell, and edges were sealed using a siliconelastomer. Afterward, buffer was added to both chambers of the celland Ag/AgCl electrodes were immersed on both chambers for voltageapplication. Current was measured with an Axopatch 200B amplifierat 250 kHz sampling rate and low-pass filtered at 100 kHz. Aftergetting a stable current and measuring conductance of the pore,dsDNA molecules were added to the ground chamber, and positivevoltage was applied for detection of the events. Data processing wasdone using OpenNanopore (https://lben.epfl.ch/page-79460-en.html) software and further analyzed using Igor Pro software.

ASSOCIATED CONTENT

*S Supporting InformationThe Supporting Information is available free of charge on theACS Publications website at DOI: 10.1021/acsnano.8b08017.

Characterization of the MXene samples and additionaldata sets (PDF)

Movie that depicts the liquid interface assembly (AVI)

AUTHOR INFORMATION

Corresponding Authors*E-mail (M. Beidaghi): mbeidaghi@auburn.edu.*E-mail (M. Wanunu): wanunu@neu.edu.

ORCIDArmin VahidMohammadi: 0000-0002-6284-7560Majid Beidaghi: 0000-0002-3150-9024Meni Wanunu: 0000-0002-9837-0004Author Contributions#M. Mojtabavi and A. VahidMohammadi contributed equallyto the work.

NotesThe authors declare no competing financial interest.

ACKNOWLEDGMENTS

Funding is provided by NSF EFMA-1542707 (M.W.). A.V.M.acknowledges the support from Alabama EPSCoR GraduateResearch Scholar Program (GRSP Round 11-13) doctoralfellowship. M.B. acknowledges support from Auburn Uni-versity’s intramural grants program (IGP). We acknowledgeMohammad Amin Alibakhshi for fabrication of silicon nitridemembrane chips and membrane chips with ∼100 nm diametere-beam fabricated holes. We acknowledge Northeastern’sKostas Advanced Nano-Characterization Facility (KANCF,Burlington MA, USA) for access to their TEM imaging facility.

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