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1.  Digging gold: keV He+ ion interaction with Au 
Helium ion microscopy (HIM) was used to investigate the interaction of a focused He+ ion beam with energies of several tens of kiloelectronvolts with metals. HIM is usually applied for the visualization of materials with extreme surface sensitivity and resolution. However, the use of high ion fluences can lead to significant sample modifications. We have characterized the changes caused by a focused He+ ion beam at normal incidence to the Au{111} surface as a function of ion fluence and energy. Under the influence of the beam a periodic surface nanopattern develops. The periodicity of the pattern shows a power-law dependence on the ion fluence. Simultaneously, helium implantation occurs. Depending on the fluence and primary energy, porous nanostructures or large blisters form on the sample surface. The growth of the helium bubbles responsible for this effect is discussed.
PMCID: PMC3740815  PMID: 23946914
formation and healing of defects in crystals; helium ion microscopy; ion beam/solid interactions; vacancies in crystals
2.  Channeling in helium ion microscopy: Mapping of crystal orientation 
Background: The unique surface sensitivity and the high resolution that can be achieved with helium ion microscopy make it a competitive technique for modern materials characterization. As in other techniques that make use of a charged particle beam, channeling through the crystal structure of the bulk of the material can occur.
Results: Here, we demonstrate how this bulk phenomenon affects secondary electron images that predominantly contain surface information. In addition, we will show how it can be used to obtain crystallographic information. We will discuss the origin of channeling contrast in secondary electron images, illustrate this with experiments, and develop a simple geometric model to predict channeling maxima.
Conclusion: Channeling plays an important role in helium ion microscopy and has to be taken into account when trying to achieve maximum image quality in backscattered helium images as well as secondary electron images. Secondary electron images can be used to extract crystallographic information from bulk samples as well as from thin surface layers, in a straightforward manner.
PMCID: PMC3458594  PMID: 23019544
channeling; crystallography; helium ion microscopy; ion scattering
3.  High Resolution Helium Ion Scanning Microscopy of the Rat Kidney 
PLoS ONE  2013;8(3):e57051.
Helium ion scanning microscopy is a novel imaging technology with the potential to provide sub-nanometer resolution images of uncoated biological tissues. So far, however, it has been used mainly in materials science applications. Here, we took advantage of helium ion microscopy to explore the epithelium of the rat kidney with unsurpassed image quality and detail. In addition, we evaluated different tissue preparation methods for their ability to preserve tissue architecture. We found that high contrast, high resolution imaging of the renal tubule surface is possible with a relatively simple processing procedure that consists of transcardial perfusion with aldehyde fixatives, vibratome tissue sectioning, tissue dehydration with graded methanol solutions and careful critical point drying. Coupled with the helium ion system, fine details such as membrane texture and membranous nanoprojections on the glomerular podocytes were visualized, and pores within the filtration slit diaphragm could be seen in much greater detail than in previous scanning EM studies. In the collecting duct, the extensive and striking apical microplicae of the intercalated cells were imaged without the shrunken or distorted appearance that is typical with conventional sample processing and scanning electron microscopy. Membrane depressions visible on principal cells suggest possible endo- or exocytotic events, and central cilia on these cells were imaged with remarkable preservation and clarity. We also demonstrate the use of colloidal gold probes for highlighting specific cell-surface proteins and find that 15 nm gold labels are practical and easily distinguishable, indicating that external labels of various sizes can be used to detect multiple targets in the same tissue. We conclude that this technology represents a technical breakthrough in imaging the topographical ultrastructure of animal tissues. Its use in future studies should allow the study of fine cellular details and provide significant advances in our understanding of cell surface structures and membrane organization.
PMCID: PMC3591388  PMID: 23505418
4.  Fabrication of carbon nanomembranes by helium ion beam lithography 
The irradiation-induced cross-linking of aromatic self-assembled monolayers (SAMs) is a universal method for the fabrication of ultrathin carbon nanomembranes (CNMs). Here we demonstrate the cross-linking of aromatic SAMs due to exposure to helium ions. The distinction of cross-linked from non-cross-linked regions in the SAM was facilitated by transferring the irradiated SAM to a new substrate, which allowed for an ex situ observation of the cross-linking process by helium ion microscopy (HIM). In this way, three growth regimes of cross-linked areas were identified: formation of nuclei, one-dimensional (1D) and two-dimensional (2D) growth. The evaluation of the corresponding HIM images revealed the dose-dependent coverage, i.e., the relative monolayer area, whose density of cross-links surpassed a certain threshold value, as a function of the exposure dose. A complete cross-linking of aromatic SAMs by He+ ion irradiation requires an exposure dose of about 850 µC/cm2, which is roughly 60 times smaller than the corresponding electron irradiation dose. Most likely, this is due to the energy distribution of secondary electrons shifted to lower energies, which results in a more efficient dissociative electron attachment (DEA) process.
PMCID: PMC3943867  PMID: 24605285
carbon nanomembranes; dissociative electron attachment; helium ion microscopy; ion beam-organic molecules interactions; self-assembled monolayers
5.  Shrinking of Solid-state Nanopores by Direct Thermal Heating 
Nanoscale Research Letters  2011;6(1):372.
Solid-state nanopores have emerged as useful single-molecule sensors for DNA and proteins. A novel and simple technique for solid-state nanopore fabrication is reported here. The process involves direct thermal heating of 100 to 300 nm nanopores, made by focused ion beam (FIB) milling in free-standing membranes. Direct heating results in shrinking of the silicon dioxide nanopores. The free-standing silicon dioxide membrane is softened and adatoms diffuse to a lower surface free energy. The model predicts the dynamics of the shrinking process as validated by experiments. The method described herein, can process many samples at one time. The inbuilt stress in the oxide film is also reduced due to annealing. The surface composition of the pore walls remains the same during the shrinking process. The linear shrinkage rate gives a reproducible way to control the diameter of a pore with nanometer precision.
PMCID: PMC3211463  PMID: 21711885
6.  Influence of helium-ion bombardment on the optical properties of ZnO nanorods/p-GaN light-emitting diodes 
Nanoscale Research Letters  2011;6(1):628.
Light-emitting diodes (LEDs) based on zinc oxide (ZnO) nanorods grown by vapor-liquid-solid catalytic growth method were irradiated with 2-MeV helium (He+) ions. The fabricated LEDs were irradiated with fluencies of approximately 2 × 1013 ions/cm2 and approximately 4 × 1013 ions/cm2. Scanning electron microscopy images showed that the morphology of the irradiated samples is not changed. The as-grown and He+-irradiated LEDs showed rectifying behavior with the same I-V characteristics. Photoluminescence (PL) measurements showed that there is a blue shift of approximately 0.0347 and 0.082 eV in the near-band emission (free exciton) and green emission of the irradiated ZnO nanorods, respectively. It was also observed that the PL intensity of the near-band emission was decreased after irradiation of the samples. The electroluminescence (EL) measurements of the fabricated LEDs showed that there is a blue shift of 0.125 eV in the broad green emission after irradiation and the EL intensity of violet emission approximately centered at 398 nm nearly disappeared after irradiations. The color-rendering properties show a small decrease in the color-rendering indices of 3% after 2 MeV He+ ions irradiation.
PMCID: PMC3274553  PMID: 22152066
7.  Three-dimensional micro/nano-scale structure fabricated by combination of non-volatile polymerizable RTIL and FIB irradiation 
Scientific Reports  2014;4:3722.
Room-temperature ionic liquid (RTIL) has been widely investigated as a nonvolatile solvent as well as a unique liquid material because of its interesting features, e.g., negligible vapor pressure and high thermal stability. Here we report that a non-volatile polymerizable RTIL is a useful starting material for the fabrication of micro/nano-scale polymer structures with a focused-ion-beam (FIB) system operated under high-vacuum condition. Gallium-ion beam irradiation to the polymerizable 1-allyl-3-ethylimidazolium bis((trifluoromethane)sulfonyl)amide RTIL layer spread on a Si wafer induced a polymerization reaction without difficulty. What is interesting to note is that we have succeeded in provoking the polymerization reaction anywhere on the Si wafer substrate by using FIB irradiation with a raster scanning mode. By this finding, two- and three-dimensional micro/nano-scale polymer structure fabrications were possible at the resolution of 500,000 dpi. Even intricate three-dimensional micro/nano-figures with overhang and hollow moieties could be constructed at the resolution of approximately 100 nm.
PMCID: PMC3893655  PMID: 24430465
8.  Helium Ion Microscopy (HIM) for the imaging of biological samples at sub-nanometer resolution 
Scientific Reports  2013;3:3514.
Scanning Electron Microscopy (SEM) has long been the standard in imaging the sub-micrometer surface ultrastructure of both hard and soft materials. In the case of biological samples, it has provided great insights into their physical architecture. However, three of the fundamental challenges in the SEM imaging of soft materials are that of limited imaging resolution at high magnification, charging caused by the insulating properties of most biological samples and the loss of subtle surface features by heavy metal coating. These challenges have recently been overcome with the development of the Helium Ion Microscope (HIM), which boasts advances in charge reduction, minimized sample damage, high surface contrast without the need for metal coating, increased depth of field, and 5 angstrom imaging resolution. We demonstrate the advantages of HIM for imaging biological surfaces as well as compare and contrast the effects of sample preparation techniques and their consequences on sub-nanometer ultrastructure.
PMCID: PMC3865489  PMID: 24343236
9.  Ice-assisted electron beam lithography of graphene 
Nanotechnology  2012;23(18):185302.
We demonstrate that a low energy focused electron beam can locally pattern graphene coated with a thin ice layer. The irradiated ice plays a crucial role in the process by providing activated species that locally remove graphene from a silicon dioxide substrate. After patterning the graphene, the ice resist is easily removed by sublimation to leave behind a clean surface with no further processing. More generally, our findings demonstrate that ice-assisted e-beam lithography can be used to pattern very thin materials deposited on substrate surfaces. The procedure is performed in situ in a modified scanning electron microscope. Desirable structures such as nanoribbons are created using the method. Defects in graphene from electrons backscattered from the bulk substrate are identified. They extend several microns from the e-beam writing location. We demonstrate that these defects can be greatly reduced and localised by using thinner substrates and/or gentle thermal annealing.
PMCID: PMC3350975  PMID: 22498712
10.  Silicon-based photonic crystals fabricated using proton beam writing combined with electrochemical etching method 
Nanoscale Research Letters  2012;7(1):416.
A method for fabrication of three-dimensional (3D) silicon nanostructures based on selective formation of porous silicon using ion beam irradiation of bulk p-type silicon followed by electrochemical etching is shown. It opens a route towards the fabrication of two-dimensional (2D) and 3D silicon-based photonic crystals with high flexibility and industrial compatibility. In this work, we present the fabrication of 2D photonic lattice and photonic slab structures and propose a process for the fabrication of 3D woodpile photonic crystals based on this approach. Simulated results of photonic band structures for the fabricated 2D photonic crystals show the presence of TE or TM gap in mid-infrared range.
PMCID: PMC3420235  PMID: 22824206
Proton beam writing; Defect density; Photonic band structure
11.  High-Throughput Top-Down Fabrication of Uniform Magnetic Particles 
PLoS ONE  2012;7(5):e37440.
Ion Beam Aperture Array Lithography was applied to top-down fabrication of large dense (108–109 particles/cm2) arrays of uniform micron-scale particles at rates hundreds of times faster than electron beam lithography. In this process, a large array of helium ion beamlets is formed when a stencil mask containing an array of circular openings is illuminated by a broad beam of energetic (5–8 keV) ions, and is used to write arrays of specific repetitive patterns. A commercial 5-micrometer metal mesh was used as a stencil mask; the mesh size was adjusted by shrinking the stencil openings using conformal sputter-deposition of copper. Thermal evaporation from multiple sources was utilized to form magnetic particles of varied size and thickness, including alternating layers of gold and permalloy. Evaporation of permalloy layers in the presence of a magnetic field allowed creation of particles with uniform magnetic properties and pre-determined magnetization direction. The magnetic properties of the resulting particles were characterized by Vibrating Sample Magnetometry. Since the orientation of the particles on the substrate before release into suspension is known, the orientation-dependent magnetic properties of the particles could be determined.
PMCID: PMC3365077  PMID: 22693574
12.  Revelation of graphene-Au for direct write deposition and characterization 
Nanoscale Research Letters  2011;6(1):424.
Graphene nanosheets were prepared using a modified Hummer's method, and Au-graphene nanocomposites were fabricated by in situ reduction of a gold salt. The as-produced graphene was characterized by X-ray photoelectron spectroscopy, ultraviolet-visible spectroscopy, scanning electron microscopy, and high-resolution transmission electron microscopy (HR-TEM). In particular, the HR-TEM demonstrated the layered crystallites of graphene with fringe spacing of about 0.32 nm in individual sheets and the ultrafine facetted structure of about 20 to 50 nm of Au particles in graphene composite. Scanning helium ion microscopy (HIM) technique was employed to demonstrate direct write deposition on graphene by lettering with gaps down to 7 nm within the chamber of the microscope. Bare graphene and graphene-gold nanocomposites were further characterized in terms of their composition and optical and electrical properties.
PMCID: PMC3211841  PMID: 21711490
13.  Nonlinear optical effects of ultrahigh-Q silicon photonic nanocavities immersed in superfluid helium 
Scientific Reports  2013;3:1436.
Photonic nanocavities are a key component in many applications because of their capability of trapping and storing photons and enhancing interactions of light with various functional materials and structures. The maximal number of photons that can be stored in silicon photonic cavities is limited by the free-carrier and thermo-optic effects at room temperature. To reduce such effects, we performed the first experimental study of optical nonlinearities in ultrahigh-Q silicon disk nanocavities at cryogenic temperatures in a superfluid helium environment. At elevated input power, the cavity transmission spectra exhibit distinct blue-shifted bistability behavior when temperature crosses the liquid helium lambda point. At even lower temperatures, the spectra restore to symmetric Lorentzian shapes. Under this condition, we obtain a large intracavity photon number of about 40,000, which is limited ultimately by the local helium phase transition. These new discoveries are explained by theoretical calculations and numerical simulations.
PMCID: PMC3595694  PMID: 23486445
14.  Ion-Selective Permeability of Ultrathin Nanoporous Silicon Membrane as Probed by Scanning Electrochemical Microscopy Using Micropipet-Supported ITIES Tips 
Analytical chemistry  2010;82(17):7127-7134.
We report on the application of scanning electrochemical microscopy (SECM) for the measurement of the ion-selective permeability of porous nanocrystalline silicon membrane as a new type of nanoporous material with potential applications in analytical, biomedical, and biotechnology device development. The reliable measurement of high permeability in the molecularly thin nanoporous membrane to various ions is important for greater understanding of its structure–permeability relationship and also for its successful applications. In this work, this challenging measurement is enabled by introducing two novel features into amperometric SECM tips based on the micropipet-supported interface between two immiscible electrolyte solutions (ITIES) to reveal the important ion-transport properties of the ultrathin nanopore membrane. The tip of a conventional heat-pulled micropipet is milled using focused ion beam (FIB) technique to be smoother, better aligned, and subsequently, approach closer to the membrane surface, which allows for more precise and accurate permeability measurement. The high membrane permeability to small monovalent ions is determined using FIB-milled micropipet tips to establish a theoretical formula for the membrane permeability that is controlled by free ion diffusion across water-filled nanopores. Moreover, the ITIES tips are rendered selective for larger polyions with biomedical importance, i.e., polyanionic pentasaccharide Arixtra and polycationic peptide protamine, to yield the membrane permeability that is lower than the corresponding diffusion-limited permeability. The hindered transport of the respective polyions is unequivocally ascribed to electrostatic and steric repulsions from the wall of the nanopores, i.e., the charge and size effects.
PMCID: PMC2932823  PMID: 20690617
15.  Long-term follow-up after uveal melanoma charged particle therapy. 
PURPOSE: To examine the results of helium ion irradiation in 218 uveal melanoma patients treated more than 10 years ago. METHODS: Retrospective review of 218 eyes treated with helium ion radiation for uveal melanoma between 1978 and 1984. Several parametric and non-parametric statistical analysis techniques were used. RESULTS: In 218 eyes treated with helium ion radiation for uveal melanoma, the mean dimension for largest basal diameter was 11.9 mm (range 5 mm to 24 mm). The mean tumor thickness was 6.7 mm (range 1.3 mm to 14.2 mm). Following helium ion radiation 208 (95.4%) of 218 eyes had local tumor control. At 10 years after radiation 46 (22.4%) of 218 eyes were enucleated; the majority (37 of 46) of enucleations were due to anterior ocular segment complications. At 10 years after radiation 102 (46.8%) of the 218 patients were dead; half had non-tumor related deaths and 51 died from metastatic melanoma. Best corrected visual acuity after radiation was > or = 20/40 in 21 of 93 eyes of patients that were alive and retained their eyes 10 or more years after treatment. In patients with tumors that were less than 6 mm in height and more than 3 mm away from the nerve or the fovea, 13 of 18 (72%) retained > or = 20/40. In contrast, only 11% of the patients with either thicker tumors or those close to the nerve or fovea retained that level of acuity. The actuarial enucleation rate at 5 years was 17.2% (2.7% S.E.) and at 10 years this was 22.4% (3.1% S.E). The recurrence tumor control rate at both 5 and 10 years was 5.3% (S.E 1.7%). CONCLUSIONS: Helium ion radiation of uveal melanoma is associated with good local tumor control and reasonable retention of the treated eye 10 years after treatment. In tumors that are less than 6 mm in thickness and greater than 3 mm from the optic nerve and fovea, many retain excellent vision. Approximately one-half of the deaths 10 years after treatment were due to non-tumor-related causes.
PMCID: PMC1298357  PMID: 9440169
16.  Collision Energetics in a Tandem Time-of-Flight (TOF/TOF) Mass Spectrometer with a Curved-Field Reflectron 
Collisions of fullerene ions (C60+) with helium and neon were carried out over a range of laboratory energies (3–20 keV) on a unique tandem time-of-flight (TOF/TOF) mass spectrometer equipped with a curved-field reflectron (CFR). The CFR enables focusing of product ions over a wide kinetic energy range. Thus, ions extracted from a laser desorption/ionization (LDI) source are not decelerated prior to collision, and collision energies in the laboratory frame are determined by the source extraction voltages. Comparison of product ion mass spectra obtained following collisions with inert gases show a time (and apparent mass) shift for product ions relative to those observed in spectra obtained by metastable dissociation (unimolecular decay), consistent with impulse collision models, in which interactions of helium with fullerene in the high energy range are primarily with a single carbon atom. In addition, within a narrow range of kinetic energies an additional peak corresponding to the capture of helium is observed for fragment ions C50+, C52+, C54+, C56+ and C58+.
PMCID: PMC3124870  PMID: 21731425
17.  Role of surface composition in morphological evolution of GaAs nano-dots with low-energy ion irradiation 
Nanoscale Research Letters  2012;7(1):552.
The surface chemistry of GaAs (100) with 50-keV Ar+ ion beam irradiation at off-normal incidence has been investigated in order to elucidate the surface nano-structuring mechanism(s). Core level and valence band studies of the surface composition were carried out as a function of fluences, which varied from 1 × 1017 to 7 × 1017 ions/cm2. Core-level spectra of samples analyzed by X-ray photoelectron spectroscopy confirmed the Ga enrichment of the surface resulting in bigger sized nano-dots. Formation of such nano-dots is attributed to be due to the interplay between preferential sputtering and surface diffusion processes. Valence band measurement shows that the shift in the Fermi edge is higher for Ga- rich, bigger sized nano-dots due to the partial oxide formation of Ga. ‘One-dimensional power spectral density’ extracted from atomic force micrographs also confirms the significant role of surface diffusion in observed nano-structuring.
PMCID: PMC3489695  PMID: 23035733
Ion irradiation; Nano-dots; XPS; AFM
18.  Imaging ultra thin layers with helium ion microscopy: Utilizing the channeling contrast mechanism 
Background: Helium ion microscopy is a new high-performance alternative to classical scanning electron microscopy. It provides superior resolution and high surface sensitivity by using secondary electrons.
Results: We report on a new contrast mechanism that extends the high surface sensitivity that is usually achieved in secondary electron images, to backscattered helium images. We demonstrate how thin organic and inorganic layers as well as self-assembled monolayers can be visualized on heavier element substrates by changes in the backscatter yield. Thin layers of light elements on heavy substrates should have a negligible direct influence on backscatter yields. However, using simple geometric calculations of the opaque crystal fraction, the contrast that is observed in the images can be interpreted in terms of changes in the channeling probability.
Conclusion: The suppression of ion channeling into crystalline matter by adsorbed thin films provides a new contrast mechanism for HIM. This dechanneling contrast is particularly well suited for the visualization of ultrathin layers of light elements on heavier substrates. Our results also highlight the importance of proper vacuum conditions for channeling-based experimental methods.
PMCID: PMC3458595  PMID: 23019545
channeling; contrast mechanism; helium ion microscopy; ion scattering; thin layers
19.  High-Resolution, High-Throughput, Positive-Tone Patterning of Poly(ethylene glycol) by Helium Beam Exposure through Stencil Masks 
PLoS ONE  2013;8(5):e56835.
In this work, a collimated helium beam was used to activate a thiol-poly(ethylene glycol) (SH-PEG) monolayer on gold to selectively capture proteins in the exposed regions. Protein patterns were formed at high throughput by exposing a stencil mask placed in proximity to the PEG-coated surface to a broad beam of helium particles, followed by incubation in a protein solution. Attenuated Total Reflectance–Fourier Transform Infrared Spectroscopy (ATR–FTIR) spectra showed that SH-PEG molecules remain attached to gold after exposure to beam doses of 1.5–60 µC/cm2 and incubation in PBS buffer for one hour, as evidenced by the presence of characteristic ether and methoxy peaks at 1120 cm−1 and 2870 cm−1, respectively. X-ray Photoelectron Spectroscopy (XPS) spectra showed that increasing beam doses destroy ether (C–O) bonds in PEG molecules as evidenced by the decrease in carbon C1s peak at 286.6 eV and increased alkyl (C–C) signal at 284.6 eV. XPS spectra also demonstrated protein capture on beam-exposed PEG regions through the appearance of a nitrogen N1s peak at 400 eV and carbon C1s peak at 288 eV binding energies, while the unexposed PEG areas remained protein-free. The characteristic activities of avidin and horseradish peroxidase were preserved after attachment on beam-exposed regions. Protein patterns created using a 35 µm mesh mask were visualized by localized formation of insoluble diformazan precipitates by alkaline phosphatase conversion of its substrate bromochloroindoyl phosphate-nitroblue tetrazolium (BCIP-NBT) and by avidin binding of biotinylated antibodies conjugated on 100 nm gold nanoparticles (AuNP). Patterns created using a mask with smaller 300 nm openings were detected by specific binding of 40 nm AuNP probes and by localized HRP-mediated deposition of silver nanoparticles. Corresponding BSA-passivated negative controls showed very few bound AuNP probes and little to no enzymatic formation of diformazan precipitates or silver nanoparticles.
PMCID: PMC3663801  PMID: 23717382
20.  Beam-assisted large elongation of in situ formed Li2O nanowires 
Scientific Reports  2012;2:542.
As an important component of the solid electrolyte interface in lithium ion batteries and an effective blanket breeding material in fusion reactor, the mechanical property of Li2O is of great interest but is not well understood. Here we show that the polycrystalline Li2O nanowires were formed in situ by touching and pulling lithium hydroxide under electron beam (e-beam) illumination. The Li2O nanowires sustained an enhanced elongation (from 80% to 176%) under low dose e-beam irradiation near room temperature as compared with that (from 51% to 57%) without e-beam irradiation. The extremely high deformability could be understood by the fast Li2O diffusion under e-beam irradiation and tensile stress condition. The large elongation without e-beam irradiation implies that nano-structured Li2O is ductile near room temperature.
PMCID: PMC3408129  PMID: 22848788
21.  Focused ion beam induced deflections of freestanding thin films 
Journal of applied physics  2006;100(10):104322-104330.
Prominent deflections are shown to occur in freestanding silicon nitride thin membranes when exposed to a 50 keV gallium focused ion beam for ion doses between 1014 and 1017 ions/cm2. Atomic force microscope topographs were used to quantify elevations on the irradiated side and corresponding depressions of comparable magnitude on the back side, thus indicating that what at first appeared to be protrusions are actually the result of membrane deflections. The shape in high-stress silicon nitride is remarkably flattopped and differs from that in low-stress silicon nitride. Ion beam induced biaxial compressive stress generation, which is a known deformation mechanism for other amorphous materials at higher ion energies, is hypothesized to be the origin of the deflection. A continuum mechanical model based on this assumption convincingly reproduces the profiles for both low-stress and high-stress membranes and provides a family of unusual shapes that can be created by deflection of freestanding thin films under beam irradiation.
PMCID: PMC3319714  PMID: 22485053
22.  The Fabrication of Sub-5-nm Nanochannels in Insulating Substrates using Focused Ion Beam Milling 
Nano letters  2010;11(2):512-517.
The use of focused ion beam (FIB) milling to fabricate nanochannels with critical dimensions extending below 5 nm is described. FIB milled lines have narrowing widths as they are milled deeper into a substrate. This focusing characteristic is coupled with a two-layered architecture consisting of a relatively thick (>100 nm) metal film deposited onto a substrate. A channel is milled through the metal layer until it penetrates a prescribed depth into the substrate material. The metal is then removed, leaving a nanochannel with smooth surfaces and lateral dimensions as small as sub-5 nm. These open nanochannels can be sealed with a cover plate and the resulting devices are well-suited for single-molecule DNA transport studies. This methodology is used with quartz, single-crystal silicon, and polydimethylsiloxane substrates to demonstrate its general utility.
PMCID: PMC3125600  PMID: 21171628
Nanochannels; nanofluidics; focused ion beam; FIB milling; DNA translocation
23.  Pulmonary Kinematics From Tagged Hyperpolarized Helium-3 MRI 
To propose and test the feasibility of a novel method for quantifying 3-D regional pulmonary kinematics from hyperpolarized helium-3 tagged MRI in human subjects using a tailored image processing pipeline and a recently developed nonrigid registration framework.
Materials and Methods
Following image acquisition, inspiratory and expiratory tagged helium-3 MR images were preprocessed using various image filtering techniques to enhance the tag surfaces. Segmentation of the three orthogonal sets of tag planes in each lung produced distinct point-set representations of the tag surfaces. Using these labeled point-sets, deformation fields and corresponding strain maps were obtained via nonrigid point-set registration. Kinematic analysis was performed on three volunteers.
Tag lines in inspiratory and expiratory images were co-registered producing a continuous 3-D correspondence mapping. Average displacement and directional strains were calculated in three subjects in the inferior, mid, and superior portions of the right and left lungs. As expected, the predominant direction of displacements with expiration is from inferior to superior.
Kinematic quantitation of pulmonary motion using tagged helium-3 MRI is feasible using the applied image preprocessing filtering techniques and nonrigid point-set registration. Potential benefits from regional pulmonary kinematic quantitation include the facilitation of diagnosis and local assessment of disease progression.
PMCID: PMC2997045  PMID: 20432362
helium-3; registration; pulmonary kinematics; tagging
24.  Water equivalent thickness values of materials used in beams of protons, helium, carbon and iron ions 
Physics in medicine and biology  2010;55(9):2481-2493.
Heavy charged particle beam radiotherapy for cancer is of increasing interest because it delivers a highly conformal radiation dose to the target volume. Accurate knowledge of the range of a heavy charged particle beam after it penetrates a patient’s body or other materials in the beam line is very important and is usually stated in terms of the water equivalent thickness (WET). However, methods of calculating WET for heavy charged particle beams are lacking. Our objective was to test several simple analytical formulas previously developed for proton beams for their ability to calculate WET values for materials exposed to beams of protons, helium, carbon and iron ions. Experimentally measured heavy charged particle beam ranges and WET values from an iterative numerical method were compared with the WET values calculated by the analytical formulas. Inmost cases, the deviations were within 1 mm. We conclude that the analytical formulas originally developed for proton beams can also be used to calculate WET values for helium, carbon and iron ion beams with good accuracy.
PMCID: PMC2977971  PMID: 20371908
25.  Collective Autoionization in Multiply-Excited Systems: A novel ionization process observed in Helium Nanodroplets 
Scientific Reports  2014;4:3621.
Free electron lasers (FELs) offer the unprecedented capability to study reaction dynamics and image the structure of complex systems. When multiple photons are absorbed in complex systems, a plasma-like state is formed where many atoms are ionized on a femtosecond timescale. If multiphoton absorption is resonantly-enhanced, the system becomes electronically-excited prior to plasma formation, with subsequent decay paths which have been scarcely investigated to date. Here, we show using helium nanodroplets as an example that these systems can decay by a new type of process, named collective autoionization. In addition, we show that this process is surprisingly efficient, leading to ion abundances much greater than that of direct single-photon ionization. This novel collective ionization process is expected to be important in many other complex systems, e.g. macromolecules and nanoparticles, exposed to high intensity radiation fields.
PMCID: PMC3887374  PMID: 24406316

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