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1Ministry of Education (MOE) Key Laboratory of Spectrochemical Analysis and In-strumentation, College of Chemistry and Chemical Engineering, Xiamen University,Xiamen 361005, China. 2State Key Laboratory of Marine Environmental Science,Xiamen University, Xiamen 361005, China. 3Department of Physics, Xiamen Univer-sity, Xiamen 361005, China. 4State Key Laboratory of Physical Chemistry of SolidSurfaces, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen361005, China.*Corresponding author. Email: weihang@xmu.edu.cn (W.H.); li@xmu.edu.cn (J.L.)

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Tip-enhanced ablation and ionization massspectrometry for nanoscale chemical analysisZhisen Liang,1 Shudi Zhang,1 Xiaoping Li,1 Tongtong Wang,1 Yaping Huang,1

Wei Hang,1,2* Zhilin Yang,3 Jianfeng Li,1,3,4* Zhongqun Tian4

Spectroscopic methods with nanoscale lateral resolution are becoming essential in the fields of physics, chemis-try, geology, biology, and materials science. However, the lateral resolution of laser-based mass spectrometryimaging (MSI) techniques has so far been limited to the microscale. This report presents the development oftip-enhanced ablation and ionization time-of-flight mass spectrometry (TEAI-TOFMS), using a shell-isolatedapertureless silver tip. The TEAI-TOFMS results indicate the capability and reproducibility of the system for gen-erating nanosized craters and for acquiring the corresponding mass spectral signals. Multi-elemental analysis ofnine inorganic salt residues and MSI of a potassium salt residue pattern at a 50-nm lateral resolution wereachieved. These results demonstrate the opportunity for the distribution of chemical compositions at the nano-scale to be visualized.

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INTRODUCTIONAmong current commercial mass spectrometric techniques, only sec-ondary ion mass spectrometry (SIMS) and atomic probe tomography(APT) can offer nanoscale lateral resolution of chemical imaging.However, SIMS suffers from severe spectral interference and matrixeffects (1, 2), and sample preparation is very cumbersome in highlyspecialized APT (3). Laser-based mass spectrometry imaging (MSI)technologies are a prominent choice because of their usability andreliability (4–7), but nanoscale analysis is still challenging due to thediffraction (8) and detection (9) limits. Unceasing efforts have beenmade to bring the lateral resolution of laser-based MSI from the mi-croscale to the nanoscale. Using novel optics, atmospheric pressurematrix-assisted laser desorption/ionization (MALDI) MSI achievedits best lateral resolution of 1.4 mm in tissue analysis (10). At the costof using an extreme ultraviolet laser and elaborate optics, a lateral res-olution of 75 nm was achieved by analyzing polymers (11). By intro-ducing near-field optics intoMS systems, nanoscale lateral resolutionswere achieved using an aperture-type near-field probe (12, 13). On thepremise of obtaining MS signals, the optimal crater size was approx-imately 200 nm (14, 15). Furthermore, submicrometer lateral resolu-tions have been obtained using a nanotip for thermal desorptionwhenanalyzingmolecules with lowmelting points, such as caffeine and pig-ment (16, 17). Alternatively, because of the localized surface plasmonresonance (18), the near-field effect locally amplifies and highly con-fines the incident optical field at the apex of apertureless tip or nano-particles, enabling the lateral resolution to go beyond the diffractionlimit in Raman (19–21), infrared (22), and fluorescence spectrometry(23). Moreover, the apertureless tip can also endure much higher ir-radiance than the aperture-type probe (24). Near-field ablations at thenanoscale have been performed using nanoparticles (25) and aperture-less tips (26–29), but the idea of using the near-field effect of aperturelesstips as a direct ionization source for MSI has not been fully explored.

To exploit the near-field enhancement of the apertureless tip, a tip-enhanced ablation and ionization time-of-flight MS (TEAI-TOFMS)system was developed by integrating a scanning tunneling micro-scope (STM) system into an in-house–built reflectron TOFMS (Fig. 1,A and B). The distance control system was based on a modified STM,which provided precise control of the distance between the tip and thesample. To improve the transportation efficiency of ions, the hybridsystem was operated in high vacuum. The irradiation of the femto-second laser (fs-laser) was kept below the damage threshold of thesample, and no post-ionization source was applied in our design, sosample materials can only be ablated and ionized by the near-field–enhanced optical field.

RESULTS AND DISCUSSIONTip-enhanced ablation and ionizationThe performance of TEAI is demonstrated in Fig. 1 (D to I). In thiscase, a 10-nm-thick Ti layer was coated on the Au (111) substrate(Au@Ti). The surface roughness of the sample remained at ±1 nm(fig. S4, A and C). The laser irradiation (1.7 × 1010 W cm−2) was un-der the damage threshold of the sample (30, 31). A shell-isolated sil-ver tip coated with 2 nm of SiO2 (fig. S1B) was used in the near-fieldexperiment. The shell-isolated tip had an apex diameter of 80 nm(fig. S1A). When the tip was lifted to a position of 30 mm above thesample surface (the retracted mode), no surface damage was observedafter 200 pulses of fs-laser were applied to the area of interest (Fig. 1D).Consistent with this result, noMS signal was detected (Fig. 1F). How-ever, when the tip was kept at 5 nm from the surface of the sample (theapproached mode), a crater with a diameter of approximately 50 nmwas generated by performing the same 200 pulses of fs-laser (Fig. 1E).The absence of an ablated rimaround the crater perimeter is in accord-ance with the typical mechanism of fs-laser ablation (32), in which thethermal effect is minimized. The MS signal of the ablated and ionizedmaterial from the nanosized craterwas simultaneously acquired. Peaksof Ti and its isotopes could be seen in the spectra, and no silver ionswere detected (Fig. 1G).

An experiment was performed on Au@Ti to demonstrate the re-producibility of the system. After 200 laser pulses were applied to thearea of interest in the approached mode, a 2 × 2 array of craters wasachieved with diameters ranging from 50 to 80 nm (Fig. 1H). Signals

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of Ti are shown in the corresponding mass spectra, with the inten-sities matching the sizes of the craters (Fig. 1I).

Electromagnetic simulations showed that the magnitude of thePoynting vector was localized and enhanced at both the tip apexand the surface due to the near-field enhancement (Fig. 1C). Thiscontributed to the small size of the crater in near-field ablation. Themaximum enhancement factors of electromagnetic power were 42 nearthe apex and 15.8 near the sample surface. The localized energy trig-gered the change of temperature and the generation of plasma, result-ing in ablation and ionization. The intensity of the mass spectra wasrelatively lowdue to the low experimental ablated atomnumber (~2.2 ×105; table S2).

The formation of craters by tip-enhanced ablationThe formation of near-field craters was studied on Au@Ti. Figure 2Awas acquired in the retracted mode after firing 1600 laser pulses onthe sample, revealing that the sample was not damaged by the inci-dent laser. Results of Fig. 2 (B to H) were obtained in the approachedmode after performing different numbers of laser pulses ranging from40 to 1600. The diameters of the ablated craters weremaintainedwith-in the range of 40 to 50 nm, with a growing number of pulses up to 800(Fig. 2, B to F). This is because the laser energy mainly heats the elec-trons to high temperatures and isweakly transferred to the lattice duringthe fs-laser–induced near-field ablation, reducing damage to adjacentsurfaces (33). By performingmore than 800 pulses of fs-laser, the diam-eters of the craters became slightly enlarged until it reached about 80 nm(Fig. 2, G and H). The corresponding MS signals of the craters wereacquired (Fig. 2I). The intensity of MS signals first increased and thenstabilized as the cumulative number of pulses increased.

Comparison of TEAI-TOFMS and SIMSA comparative study of TEAI-TOFMS and SIMS for multi-elementalanalysis was carried out by analyzing a residue mixture of nine in-organic salts (Fig. 3, A and B). The area of interest was the central

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region of the coffee ring, where the tunneling current can be detected(Fig. 3C). The inset in Fig. 3E suggests that no signals were obtainedin the retracted mode. In the near-field experiments, nine metal ele-ments and their isotopes were observed (Fig. 3, D and E). Comparedwith those obtained from SIMS (Fig. 3, F and G), the results of TEAI-TOFMS are more explicit with less interference from the substrate.

Fig. 1. Schematic diagram of the TEAI-TOFMS system and spectra of Ti using fs-laser–induced TEAI. (A) Experimental setup. (B) Enlarged view of the ion source.(C) Enhancement factor of electromagnetic power density of near-field enhancement by a shell-isolated apertureless tip. (D) Scanning electron microscopy (SEM)images after performing 200 pulses of fs-laser in the retracted mode. (E) SEM images after performing 200 pulses of fs-laser in the approached mode. (F) Spectracorresponding to the modes used in (D). (G) Spectra corresponding to the modes used in (E). (H) SEM image of the array fs-laser TEAI obtained after performing 200 pulsesat each spot. (I) Corresponding mass spectra of (H).

Fig. 2. Study of crater formation on the surface of Au@Ti and correspondingMS spectra. (A) SEM images in the retracted mode after 1600 laser pulses wereapplied. (B to H) SEM images in the approached mode after 40 to 1600 laser pulseswere applied. (I) Relevant spectra obtained at the same condition for (A) to (H).

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MSI with nanoscale lateral resolutionAproof-of-principleMSI experimentwith a nanoscale lateral resolutionwas achieved by scanning a 1 mm × 1 mm area of interest on a micro-patterned potassium iodine residue (Fig. 4A), which was prepared byelectrohydrodynamic jet printing (fig. S3A). Figure 4B was acquiredusing fs-laser–based TEAI-TOFMS. It exhibits the distribution of39K+ corresponding to the potassium iodide residue with a lateralresolution of 50 nm, which coincides with the morphological image(Fig. 4A). However, theMS signal of iodine was not detected becauseof its high ionization potential (Fig. 4C).

Simulation result of near-field enhancementThe simulationmodel, in accordancewith the experimental conditions,consists of an Ag tip above the Au@Ti. The finite-difference time-domain (FDTD) method is introduced to calculate the near-field en-hancement for the tip located above the Ti surface.

The magnitude of the Poynting vector was recorded and imagedin both the XZ (Fig. 5A) and XY (Fig. 5B) planes. The physical sig-nificance of the Poynting vector is the electromagnetic power density.Given an experimental fs-laser irradiance value of 1.7 × 1010 W cm−2

on the ellipse irradiated area of the surface and the relationship be-tween Poynting vector and electromagnetic fields, the correspondingelectric field amplitude was calculated to be 3 × 106 V cm−1 and set tothe model. After FDTD calculation, the power densities are 7.2 ×1011 W cm−2 near the apex and 2.7 × 1011 W cm−2 near the samplesurface, which are 42 and 15.8 times higher than the incident laserpower density, respectively.

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Simulation results of ablation process, plasma initiation,expansion, and ionizationUsing the enhanced laser power above as the energy input, a three-dimensional (3D) “two-temperature” model was used to simulatethe femtosecond pulsed laser–solid interaction process (34–36). Withthis model, the sample temperature distribution (Fig. 6A) and ablatedpit morphology (Fig. 6B) can be calculated. All the necessary data forthe calculationwere acquired fromprevious studies (37–40). Note thatthe time points are selected to be 3000 fs, when the bulk temperaturesreach their highest values from one laser shot. The high-temperaturearea, with its highest value of 9371 K, is highly confined to the centralpart of the sample surface and hardly penetrates downward, leavingthe inner part of the bulk almost unaffected.With the ongoing heatingof the sample surface, a material phase transition takes place. The ab-lation crater progressively evolves and finally becomes steadily formedwhen the surface cools down, as shown in Fig. 6B by one laser shot. Ithas been reported that fs-laser ablation is so fast that the irradiatedsolid directly turns into the gas phase (sublimation) hardly with theprocess of melting (41, 42). The diameter of the ablated crater is about50 nm, which is in accordance with the experimental observation inFig. 2B. The crater has a distinct boundary in the case of the fs-laser–induced near-field enhancement, with minimal thermal effect on thesurrounding area. The total ablated volume during one laser shot isfound to be 132 nm3, which corresponds to 7472 Ti atoms.

As for the plasma initiation, expansion, and ionization processes, amodel has been developed, which takes into account the vaporization/sublimation equations (43, 44), the 1Dplanar fluidmechanics equations

Fig. 3. Comparative study of TEAI-TOFMS and SIMS to analyze a residue mixture of nine inorganic salts. (A) Image of the residue deposited on a Cu substrate.(B) SEM image of the residue deposited on a Cu substrate. (C) SEM image of the center area of the coffee ring, where the surface was smoothed by ethanol. (D) TEAI-MSspectrum in the approachedmode by sampling 10 spots with 400 laser pulses per spot. (E) Enlarged spectrum of (D); the inset is the spectrum in the retractedmode. (F) SIMSspectrum of the residue obtained from 200 scans (128 × 128 spots per scan, 1 shot per spot). (G) Enlarged spectrum of (F).

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Fig. 5. FDTD-simulated distribution of Poynting vector. (A) Magnitude of Poynting vector in the vertical XZ panel (Y = 0 nm). (B) Magnitude of Poynting vector inthe horizontal XY panel (Z = 0 nm).

Fig. 4. Results of MSI with a lateral resolution of 50 nm. (A) SEM image of the KI residue on a Si substrate coated with a 10-nm layer of Au. The area inside the redsquare represents the area of interest. (B) Image of 39K+ distribution obtained by fs-laser–induced near-field MSI with a lateral resolution of 50 nm by scanning an arrayof 20 × 20 spots at 50-nm spot intervals with 40 shots per spot. The color scale shows the normalized intensity of 39K+. (C) Typical mass spectrum in an MSI experiment.

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Fig. 6. Simulation results of tip-enhanced ablation, plasma initiation, expansion, and ionization processes. (A) 3D bulk temperature (at 3000 fs) from one shot.(B) Final ablation crater by one shot. (C) Plasma temperature from one fs-laser shot at 3000 fs. (D) Total/ionized particle number density from one shot at 3000 fs.

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(concerning the conservation of mass, momentum, and energy)(45, 46), the conservation laws of matter and charge (47), and a se-ries of plasma state equations (43). After solving these equations, theplasma temperature (Fig. 6C) and particle number density (Fig. 6D)at the central point of the ablated area (at 3000 fs) can be calculated.Note that this time point is when the surface temperature reaches itsmaximum value during one laser shot and, correspondingly, whenthe highest plasma ionization efficiency occurs. The highest plasmatemperature is 15,900 K. Using the total/ionized particle numberdensities, the plasma ionization efficiency can be calculated by inte-grating the ionized particle data over the whole plasma length andthen dividing them by the corresponding value of the total numberof particles. The calculated ionization efficiency is 3.9%.

In summary,wehave developed aTEAI-TOFMS systemanddemon-strated its capability and reproducibility for ablation and ioniza-tion using near-field enhancement. The TEAI is capable of sampling ananoscale area of interest. The shell-isolated tip has desirable featuresof robustness, anti-contamination, and a long lifetime (fig. S7). Fur-thermore, salt mixture residues were analyzed, indicating the rapidmulti-elemental analysis capability and explicit spectral feature. MSIof potassium in an area of 1 mm2 demonstrated a lateral resolution of50 nm using TEAI-TOFMS, showing the advantage of integrating thenear-field optical technique with the MS system. Future work willfocus on exploring the possibility of analyzing chemical species withhigh ionization energies by introducing a post-ionization source intothe TEAI-TOFMS system, and MSI of the chemical composition ofnanodevices, single cells, and even cell organelles is expected to enlargethe scope of its applications.

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MATERIALS AND METHODSChemicalsPerchloric acid (70%), anhydrous ethanol, and 10 different inorganicsalts [NaCl, MgCl2, Al(NO3)3, KCl, CaCl2, CrCl3, FeCl3, CuCl2,CsCl, and KI] were purchased from Sinopharm Chemical ReagentCo. Ltd. (analytical grade) and used without further purification. Sil-ver wire (0.25 mm in diameter, 99.9985%) and two types of goldwires (1 mm in diameter, 99.99%; 0.25 mm in diameter, 99.999%)were purchased from Alfa Aesar. Copper foil (polycrystalline) waspurchased from Hefei Kejing Materials Technology Co. Ltd. The ul-trapure water was used throughout the experiment.

Experimental setupThe schematic diagramof the TEAI-TOFMS system is shown in Fig. 1.The system was designed and built in-house. A frequency-doubled(515 nm) laser (s-Pulse HP, Amplitude Systèmes) with a pulse widthof 500 fs and p-polarization was used. The laser beamwas focused bya plano-convex lens (f = 230 mm) onto a spot diameter of 400 mm.

The laser irradiation intensity was below the damage threshold ofsamples. The pulse-to-pulse energy stability of fs-laser was better than5% (relative SD). The TOF mass analyzer was designed according tothe previous experience in constructing MS instruments in our group(48–50). The mass analyzer and the ion source were kept in the samehigh-vacuum chamber to keep the loss of ions at minimum. To verifythe potential in ablation and ionization from the near-field enhance-ment, no post-ionization source was used in our experiments. Thetime-lag focusing technique and a dual-stage reflectron were intro-duced into the TOF system to improve the mass resolution (51). Adigital storage oscilloscope (42Xs, LeCroy) was used to acquire mass

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spectral signals. The data were processed by an in-house–compiledprogram written in LabVIEW (National Instruments Inc.). Thedetailed operating parameters were listed in table S1.

A silver tip fabricated by electrochemical etching was fixed andmounted on a tip holder. The tip holder was connected to two levelplates and a step motor. The step motor was controlled by the STMsystem (MicroNano STM-II, Shanghai Zhuolun MicroNano Equip-ment Co. Ltd.). A 2D closed-loop piezo scanner (SLC-17, SmarActGmbH) provided precise control ofmovement of the samplemountedon the XY plane. In the Z direction, the coarse adjustment of the sam-ple was controlled by a manipulator. A scanning tube was connectedto the STM system and mounted on the piezo scanner, enabling pre-cise movement of the sample in the Z direction. The distance be-tween the tip and the surface of the sample was kept by adjustingthe coordinated movements of the step motor and the scanning tube.The tunneling current between the sample and the tip was measuredautomatically by the STM detection system. All the movements of thetipwere controlled by computer software. An in-house–built vibrationdamping system was used to minimize the vibration. Observation ofthe coarse position between the tip and the sample was achieved by acharge-coupled device (CCD) camera (SN-300/130, Shenzen SannuoCo. Ltd.). All the atomic forcemicroscopy (AFM) images were obtainedfrom Cypher S AFM (Asylum Research) operated in tapping mode.Near-field enhancement simulations are performed using the com-mercial software of FDTD Solutions (Lumerical Solutions Inc.).

Secondary ionmass spectra were obtained using a TOF secondaryionmass spectrometer (TOF-SIMS5) from IONTOFGmbH.A30-keVBi+ analyzing gun combined with a 500-eV O2

+ sputtering gun wasapplied to analyze the metal salt solution on silicon wafer under in-terlaced mode with a target current of 68 nA. The analyzed area was100 × 100 mm for Bi+ gun, and the sputtered areawas 300 × 300 mm forO2

+ gun. The final spectrumwas the sum of 200 scans (128 × 128 pixelsper scan and 1 shot per pixel).

Procedure for controlling the distance between the tipand the surface of the sampleInitially, the tip was far from the surface of the sample with a distanceof approximately 30 mm. To attain the working position, the tip waskept near the surface of the sample, which was driven by a step mo-tor, until it reached a position of 1 mm from the surface. Then, thesample was moved toward the apex of the tip driven by a piezo scan-ning tube until the tunneling current was detected by the STM sys-tem. To avoid themechanical contact between the tip and the surfacecaused by thermal expansion (52), the sample was quickly withdrawnto 5 nm from the surface by the piezo scanning tube after reaching thetunneling position, and then the lasers were operated at low frequencyin the experiment. All the movements of the stepper motor and thepiezo scanning tube were controlled by the feedback loop of theSTM system. After performing pulses of laser to the gap betweenthe surface and the tip, the tip was removed 30 mm from the surface.Then, the sample was moved to the next location for sampling. Thelaser was turned off at the interval between two consecutive samplingactions.

Preparation of shell-isolated silver tipThe silver tip was fabricated from a 0.25-mm silver wire by electro-chemical etching (53, 54). A mixture of perchloric acid and ethanolwith a volume ratio of 1:4 was used as the electrolyte. A gold ring wasfabricated from a 1-mm gold wire and served as the counter electrode.

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The silver wire was placed vertically in the center of the gold ring, andan approximately 3-mm-long silver wire was immersed in the electro-lyte. An automatic cutoff etch circuit was introduced to the etchingsystem to control the cutoff time of the applied voltage as the lowerpart of the silver wire dropped off, preventing over-etching (55). A dcvoltage of 8.9 Vwas applied to the etch circuit as a starting voltage. Thetotal etching time of a single silver tip was within 2 min. After etching,the upper part of the tip was retracted. It was immersed in deionizedwater for 5 min and then rinsed three times in ethanol. The silver tipswith an apex diameter of 80 nm (fig. S1A) were easily acquired by ad-justing the starting voltage. The shell-isolated tips were fabricated bydepositing a 2-nm-thick layer of SiO2 on the silver tip apex (fig. S1B)using an atomic layer deposition system (R-200 Advanced, Picosun).The shell-isolated tips were characterized by a transmission electronmicroscope (JEM-2100, JEOL).

Preparation of the metal coating sampleThe single crystalline Au (111) substrate was fabricated by the Claviliermethod (56). Briefly, a single crystalline bead with a diameter of ap-proximately 3mmwas formed bymelting one end of a 0.25-mmgoldwire in a hydrogen-oxygen flame. The beadwasmounted on a gold disc,with one of the (111) facets facing upward, and served as the substrate.Then, the gold surface was cleaned by electrochemical polishing andflame annealing in sequence. A metal layer of Ti with a thickness of10 nmwas coated on the Au (111) (fig. S2) by a magnetron sputteringdevice (Explorer-14, Denton Vacuum) in the Pen-Tung Sah Instituteof Micro-Nano Science and Technology of Xiamen University.

Preparation of residues on copper substrateBymodifying a previous method (57), we prepared the inorganic saltresidues (Fig. 3, A and B). Briefly, nine different inorganic salts weredissolved in ultrapure water with an identical concentration of 1 mM.By evaporating 10 ml of the solution on a Cu substrate, residues wereprepared. Then, 10 ml of ethanol was added to the center of the resi-dues. After the ethanol was evaporated, the residue surface becamesmoother in the central region such that the bump on the residuecan be avoided during the tip lateral movement. The residues werecoated with a 2-nm-thick layer of gold before analysis.

Preparation of the micropatterned KI sampleThe micropatterned KI sample was prepared by the electrohydro-dynamic jet printing (58). Glass pipettes with an inner diameter of2 mmwere fabricated using a laser-based micropipette puller (P-2000,Sutter Instrument). The outer pipette wall was coated with a layer ofgold by a sputter coater (MCM-200m, SEC Co. Ltd.). The solution of1 mMKI was drawn to the pipette by capillary forces from the nozzle.The pipette and the substrate were separated at a distance of 5 mm.After applying a 300-V dc voltage between the pipette and the sub-strate, a Taylor cone was generated and droplets of ink were ejectedfrom the pipette apex. A single-crystal silicon plate coated with a Cr/Au layer was placed on a piezo motor–driven linear stage (Ag-LS25,Newport). By moving the stage, droplets of KI were deposited on thesubstrate (fig. S3, A and B). Themicropatterned KI sample was coatedwith a 2-nm-thick layer of gold before analysis.

Depth profile of near-field cratersBecause the height fluctuation remained within ±1 nm (fig. S4,A and C), the surface of Au@Ti was smooth enough to distinguishany modifications caused by the tip-enhanced ablation. The crater

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morphology induced by fs-laser near-field enhancement obtainedby performing 40 pulses was shown in fig. S4B, indicating thatits diameter was approximately 50 nm. The cross section of the cra-ter showed that its depth was approximately 3 nm (fig. S4D). Allthe AFM images were obtained from Cypher S (Asylum Research)operated in tapping mode.

Locating the area of interest in MSI experimentThe reference system was built to locate the area of interest. First, wechoose a dust particle as the reference object, which can be observedin the CCD of TEAI-TOFMS. A calibrated coordinate system wasbuilt to locate the reference object based on the measurement of theSEM image (fig. S5A). According to the calibrated coordinate sys-tem, the 2D piezo scanner in the TEAI-TOFMS system was alignedcarefully. Thus, the area of interest forMSI was precisely positioned(fig. S5, B and C).

Lateral resolution analysisTo determine the lateral resolution of MSI based on the 16 to 84%criterion (59, 60), three scanning lines were selected in fig. S6A. FigureS6B shows the normalized MS signals extracted from three scanninglines of fig. S6A. Therefore, we believed that the lateral resolution ofthe MSI image was ~50 nm. It took ~6 hours for the elemental imagefollowing the previously reported procedure (61, 62). The correspond-ing mass spectral data were processed to construct the elemental imageusing a self-developed LabVIEWprogram.The results ofMSI presentedin Fig. 4B and fig. S6A were reconstructed with automatic interpolationusing Surfer 9 (Golden Surfer Inc.).

SUPPLEMENTARY MATERIALSSupplementary material for this article is available at http://advances.sciencemag.org/cgi/content/full/3/12/eaaq1059/DC1table S1. Operating parameters of the TEAI source.table S2. Experimental and theoretical ablated Ti particle numbers with 40 laser shots.fig. S1. Images of the shell-isolated tip.fig. S2. Picture of Au (111) with a 10-nm layer of Ti taken by a metallurgical microscope.fig. S3. Preparation progress of the micropatterned KI sample.fig. S4. AFM images of the surface of Au@Ti.fig. S5. SEM images of the area of interest.fig. S6. Demonstration of lateral resolution analysis.fig. S7. Morphologic comparison of tips used in TEAI experiment.

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SC I ENCE ADVANCES | R E S EARCH ART I C L E

Acknowledgments: We thank F. Wang for providing SIMS results. Funding: This work wassupported by the National Natural Science Foundation of China (grants 21427813, 21522508,and 21521004), the Fundamental Research Funds for the Central Universities (grants20720140539 and 20720150039), and the National Fund for Fostering Talents of Basic Science(grant J1310024). Author contributions: W.H. and J.L. supervised the project. W.H., J.L.,and Z.T. collectively conceived the ideas. Z.L. and X.L. performed the experiments. S.Z. and Z.Y.performed near-field enhancement simulations and thermodynamic calculations of theablation and plasma-related processes. Y.H. and T.W. prepared and characterized theshell-isolated silver tips and also helped with the experiments. All authors contributed to datainterpretation and writing of the manuscript. Competing interests: The authors declarethat they have no competing interests. Data and materials availability: All data needed to

Liang et al., Sci. Adv. 2017;3 : eaaq1059 8 December 2017

evaluate the conclusions in the paper are present in the paper and/or the SupplementaryMaterials. Additional data related to this paper may be requested from the authors.

Submitted 3 October 2017Accepted 10 November 2017Published 8 December 201710.1126/sciadv.aaq1059

Citation: Z. Liang, S. Zhang, X. Li, T. Wang, Y. Huang, W. Hang, Z. Yang, J. Li, Z. Tian,Tip-enhanced ablation and ionization mass spectrometry for nanoscale chemical analysis. Sci.Adv. 3, eaaq1059 (2017).

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Tip-enhanced ablation and ionization mass spectrometry for nanoscale chemical analysis

TianZhisen Liang, Shudi Zhang, Xiaoping Li, Tongtong Wang, Yaping Huang, Wei Hang, Zhilin Yang, Jianfeng Li and Zhongqun

DOI: 10.1126/sciadv.aaq1059 (12), eaaq1059.3Sci Adv 

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