Biomedical subjects

Nicholas Winograd

Publications and source records attributed to Nicholas Winograd.

At least 19 recordsLinked to original sources

PubMed2007

Effect of cluster size in kiloelectronvolt cluster bombardment of solid benzene.

Emission of benzene molecules by 5-keV cluster bombardment of a range of carbon projectiles from C6H6 to C180 is studied by a coarse-grained molecular dynamics (MD) technique. This approach permits calculations that are not feasible using more complicated potential energy functions, particularly as the interesting physics associated with the ion impact event approaches the mesoscale. These calculations show that the highest ejection yields are associated with clusters that deposit their incident energy 15-20 A below the surface. The highest yield for the projectiles is produced by the C20 and C60 projectiles. The results from the MD simulations are also compared favorably to an analytical model based on fluid dynamics to describe the energy deposition. The analytical model is then utilized to extend the range of the calculations to higher incident energies. The issue of the relative amount of chemical fragmentation and intact molecular desorption is also examined for the benzene crystal. These results show that damage accumulation at high-incident fluence should not be problematic and that it should be possible to perform molecular depth profiling via secondary ion mass spectrometry experiments. In general, the approach presented here illustrates the power of combining a simplified MD method with analytical strategies for describing a length scale that is difficult to achieve with traditional MD calculations.

Benzene↗

PubMed2006

The regulation of integrin-mediated osteoblast focal adhesion and focal adhesion kinase expression by nanoscale topography.

An important consideration in developing physical biomimetic cell-stimulating cues is that the in vivo extracellular milieu includes nanoscale topographic interfaces. We investigated nanoscale topography regulation of cell functions using human fetal osteoblastic (hFOB) cell culture on poly(l-lactic acid) and polystyrene (50/50 w/w) demixed nanoscale pit textures (14, 29, and 45nm deep pits). Secondary ion mass spectroscopy revealed that these nanotopographic surfaces had similar surface chemistries to that of pure PLLA because of PLLA component surface segregation during spin casting. We observed that 14 and 29nm deep pit surfaces increased hFOB cell attachment, spreading, selective integrin subunit expression (e.g., alphav relative to alpha5, beta1, or beta3), focal adhesive paxillin protein synthesis and paxillin colocalization with cytoskeletal actin stress fibers, and focal adhesion kinase (FAK) and phosphorylated FAK (pY397) expression to a greater degree than did 45nm deep pits or flat PLLA surfaces. Considering the important role of integrin-mediated focal adhesion and intracellular signaling in anchorage-dependent cell function, our results suggest a mechanism by which nanostructured physical signals regulate cell function. Modulation of integrin-mediated focal adhesion and related cell signaling by altering nanoscale substrate topography will have powerful applications in biomaterials science and tissue engineering.

Biocompatible Materials↗

PubMed2006

Surface and depth profiling investigation of a drug-loaded copolymer utilized to coat taxus express2 stents.

The surface of a styrene-b-isobutylene-b-styrene triblock copolymer, containing a solid-phase drug, was studied by time-of-flight secondary ion mass spectrometry employing 15-keV Ga+ and 20-keV C60+ ion sources. This polymer/drug system has direct application in the cardiac stent arena, where it has been used to treat restenosis or renarrowing of arterial walls after stent or angioplasty procedures. Overall, the results illustrate the successful use of a cluster ion beam for greatly enhancing the high-mass fragment ion and molecular ion intensities from the surface and bulk of the polymer system. The use of C60+ also established the ability to remove common overlayers like poly(dimethylsiloxane), which was not possible using a Ga+ ion source. Furthermore, the use of C60+ allowed depth profiles to be obtained using primary ion dose densities in excess of 6 x 1014 C60+/cm2. Resultant sputter craters reached depths of approximately 2 microm and possessed relatively flat bottoms without the need for sample rotation. AFM and profilometry studies support the relatively gentile removal of surface species via phase contrast and topographic imaging. In addition, the findings suggest that relatively high ion doses do not significantly alter the phase distribution or surface topography of the polymer surface; however, a slight increase in surface roughness was detected.

Cardiovascular Diseases↗

PubMed2006

Direct comparison of Au(3)(+) and C(60)(+) cluster projectiles in SIMS molecular depth profiling.

The sputtering properties of two representative cluster ion beams in secondary ion mass spectrometry (SIMS), C(60)(+) and Au(3)(+), have been directly compared. Organic thin films consisting of trehalose and dipalmitoylphosphatidylcholine (DPPC) are employed as prototypical targets. The strategy is to make direct comparison of the response of a molecular solid to each type of the bombarding cluster by overlapping the two ion beams onto the same area of the sample surface. The ion beams alternately erode the sample while keeping the same projectile for spectral acquisition. The results from these experiments are important to further optimize the use of cluster projectiles for SIMS molecular depth profiling experiments. For example, Au(3)(+) bombardment is found to induce more chemical damage as well as Au implantation when compared with C(60)(+). Moreover, C(60)(+) is found to be able to remove the damage and the implanted Au effectively. Discussions are also presented on strategies of enhancing sensitivity for imaging applications with cluster SIMS.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed2006

Controlling gold atom penetration through alkanethiolate self-assembled monolayers on Au{111} by adjusting terminal group intermolecular interactions.

The penetration behavior of thermally evaporated Au on S(CH(2))(15)CH(3), S(CH(2))(15)CO(2)CH(3), S(CH(2))(15)CO(2)H, K-modified S(CH(2))(15)CO(2)CH(3), and K-modified S(CH(2))(15)CO(2)H self-assembled monolayers (SAM) on Au substrates is investigated. Gold is a particularly interesting metal since vapor-deposited Au atoms are known to pass through alkanethiolate SAMs on Au{111} substrates at room temperature. Here we show that it is possible to control Au penetration by adjusting the interactions between terminal groups. It is found that Au atoms evenly penetrate into the CH(3) and CO(2)CH(3) films, forming smooth buried layers below the organic thin films. For the CO(2)H film, although Au atoms can still penetrate through it, filaments and mushroomlike clusters form due to H-bonding between film molecules. In the case of the K-modified CO(2)CH(3) or CO(2)H films, however, most Au atoms form islands at the vacuum interface. These results suggest that van der Waals forces and H-bonds are not strong enough to block Au from going through but that ionic interactions are able to block Au penetration. The measurements were performed primarily using time-of-flight secondary ion mass spectrometry (ToF-SIMS) and atomic force microscopy (AFM). The combination of these highly complementary probes provides a very useful strategy for the study of metal atom behavior on SAMs.

Journal Article↗

PubMed2006

Surface sensitivity in cluster-ion-induced sputtering.

The ion beam-induced removal of thin water ice films condensed onto Ag and bombarded by energetic Au, Au2, Au3, and C60 projectiles is examined both experimentally and with molecular dynamics computer simulations. For water overlayers of thicknesses greater than 10 A, the yields of sputtered Ag+ secondary ions decay exponentially with increasing ice thickness, revealing characteristic decay lengths of 24, 20, 18, and 7.0 A, respectively. It is shown that these values manifest the characteristic depths of projectile energy loss, rather than escape depths of the sputtered Ag atoms through the water ice overlayer. Computer simulations show that the mechanism of ejection involves the sweeping away of overlayer water molecules, allowing for an unimpeded escape of ejected Ag atoms. The relevance of these data with respect to surface sensitivity in secondary ion mass spectrometry is discussed.

Computer Simulation↗

PubMed2006

Molecular depth profiling with cluster ion beams.

Peptide-doped trehalose thin films have been characterized by bombardment with energetic cluster ion beams of C60+ and Aux+ (x = 1, 2, 3). The aim of these studies is to acquire information about the molecular sputtering process of the peptide and trehalose by measurement of secondary ion mass spectra during erosion. This system is important since uniform thin films of approximately 300 nm thickness can be reproducibly prepared on a Si substrate, allowing detailed characterization of the resulting depth profile with different projectiles. The basic form of the molecular ion intensity as a function of ion dose is described by a simple analytical model. The model includes parameters such as the molecular sputtering yield, the damage cross section of the trehalose or the peptide, and the thickness of a surface layer altered by the projectile. The results show that favorable conditions for successful molecular depth profiling are achieved when the total sputtering yield is high and the altered layer thickness is low. Successful molecular depth profiles are achieved with all of the cluster projectiles, although the degree of chemical damage accumulation was slightly lower with C60. With C60 bombardment, the altered layer thickness of about 20 nm and the damage cross section of about 5 nm2 are physically consistent with predictions of molecular dynamics calculations available for similar chemical systems. In general, the model presented should provide guidance in optimizing experimental parameters for maximizing the information content of molecular depth profiling experiments with complex molecular thin film substrates.

Algorithms↗

PubMed2006

TOF-SIMS evidence of intercalated molecular gases and diffusion-limited reaction kinetics in an alpha particle-irradiated PTFE matrix.

The chemical evolution of poly(tetrafluoroethylene) (PTFE) that is brought about by increasing levels of irradiation with alpha particles is accompanied by the emergence and proliferation of functionalized moieties. Families of reaction products specifically identified in the alpha-irradiated polymer matrix include hydride-, hydroxide-, and oxide-functionalized fluorocarbons. The data also indicate the emergence of hydrogen peroxide (H2O2) and hydrazine (N2H4), but no distinct evidence suggesting the formation of perfluorinated amines, amides, or cyanogens is found. In this article we substantiate the speciation of emergent species and reveal evidence of intercalated molecular gases with which alpha particle-generated radicals may react to form the observed products. Furthermore, we present evidence to suggest that the kinetics of alpha particle-induced reaction is limited by the diffusion of radicals within the polymer matrix. That is to say, chemical additives in the polymer matrix are shown to be scavengers of H*, O*, and F* radicals and limit the rates of reaction that produce functionalized fluorocarbon moieties. Above a threshold dose of alpha particles, the concentration of radicals exceeds that of the scavenger species, and free radical diffusion commences as evidenced by a sudden increase in the yield of reaction products. Samples of PTFE were irradiated to alpha doses in the range of 10(7) to 5 x 10(10) rad with 5.5 MeV 4He2+ ions from a tandem accelerator. Residual gas analysis (RGA) was utilized to monitor the liberation of molecular gases from PTFE during alpha particle irradiation of samples in vacuum. Static time-of-flight SIMS (TOF-SIMS), equipped with a 20 keV C60+ source, was employed to probe chemical changes as a function of alpha particle irradiation. Chemical images and high-resolution mass spectra were collected in both the positive and negative polarities.

Journal Article↗

PubMed2006

Metal nanoparticle deposition for TOF-SIMS signal enhancement of polymers.

A novel technique for improved time-of-flight secondary ion mass spectra of polymer ions is presented. This technique is a simple preparatory method, which involves deposition of a submonolayer coverage of metal nanoparticles on the surface of a polymer sample enabling an overall increase in characteristic polymer ions. This procedure gives spectra with enhanced intensity, a larger number of characteristic polymer peaks, and peaks of higher mass. Both Au and Ag nanoparticles were employed to facilitate the ionization of the polymer characteristic secondary ions. Moreover, these experiments demonstrate that the nanoparticles allow localization of high-mass fragment ions during imaging experiments utilizing focused ion beams. In general, we show that the metal nanoparticle deposition method is effective for time-of-flight secondary ion mass spectrometry examination of polymers.

Gold↗

PubMed2005

High-resolution TOF-SIMS imaging of eukaryotic cells preserved in a trehalose matrix.

A novel, trehalose-glycerol matrix was utilized to generate high-resolution, TOF-SIMS images of macrophages and glial cells. Viable cells incubated in 50 mM trehalose, then lyophilized in a 50 mM trehalose, 10-15% (w/w) glycerol rinse, are preserved and chemically profiled. These experiments demonstrate the utility of the disaccharide matrix as an efficient, cost-effective alternative to cryogenics for SIMS and other ultrahigh-vacuum (UHV) analyses of biological species. Cellular processes on oligodendrocytes and astrocytes, 1-3 mum in width, were well resolved for cells in the trehalose-glycerol matrix. The viscous cell matrixes were fractured and analyzed at room temperature and maintained their three-dimensional integrity under UHV. Images have been generated with a Au primary ion source near the static limit of 10(12) ions/cm2. Though these nucleated cells do not remain viable after desiccation, TOF-SIMS imaging and subsequent rehydration reveals structural and morphological preservation. Eliminating the inherent obstacles associated with cryogenic analysis opens the door to greater utility of SIMS as a bioanalytical tool, such as lipid mapping of single cells in the nervous system.

Animals↗

PubMed2005

Evolution of the interface and metal film morphology in the vapor deposition of Ti on hexadecanethiolate hydrocarbon monolayers on Au.

The combination of in situ X-ray photoelectron spectroscopy, infrared reflection spectroscopy, atomic force microscopy, and time-of-flight secondary ion mass spectrometry are used to probe the nature of the evolving interface chemistry and metal morphology arising from Ti vapor deposition onto the surface of a CH(3)(CH(2))(15)S/Au{111} self-assembled monolayer (SAM) at ambient temperature. The results show that for a deposition rate of approximately 0.15 Ti atom.nm(-2).s(-1) a highly nonuniform Ti overlayer is produced via a process in which a large fraction of impinging Ti atoms do not stick to the bare SAM surface. The adsorbed atoms form isolated Ti clusters and react with CH(3) groups to form carbide products at the cluster-SAM interfaces. Further growth of Ti clusters appears to be concentrated at these scattered reaction centers. The SAM molecules in the local vicinity are subsequently degraded to inorganic products, progressing deeper into the monolayer as the deposition proceeds to give an inorganic/organic nanocomposite. A continuous overlayer does not form until metal coverage approaches approximately 50 Ti atoms per SAM molecule. These data indicate that for applications such as molecular device contacts the use of Ti may be highly problematic, suffering from both a highly nonuniform contact area and the presence of extensive inorganic products such as nonstoichiometric carbides and hydrides.

Journal Article↗

PubMed2005

Secondary ion MS imaging of lipids in picoliter vials with a buckminsterfullerene ion source.

Investigation of the spatial distribution of lipids in cell membranes can lead to an improved understanding of the role of lipids in biological function and disease. Time-of-flight secondary ion mass spectrometry is capable of molecule-specific imaging of biological molecules across single cells and has demonstrated potential for examining the functional segregation of lipids in cell membranes. In this paper, standard SIMS spectra are analyzed for phosphatidylethanolamine, phosphatidylglycerol, phosphatidylserine, phosphatidylinositol, cholesterol, and sulfatide. Importantly, each of the lipids result in signature mass spectral peaks that allow them to be identified. These signature peaks are also useful for imaging experiments and are utilized here to simultaneously image lipids on a micrometer scale in picoliter vials. Because the low secondary ion signal achieved for lipids from an atomic primary ion source makes cell-imaging experiments challenging, improving signal with cluster primary ion sources is of interest. Here, we compare the secondary ion yield for seven lipids using atomic (Ga+ or In+) ion sources and a buckminsterfullerene (C60+) primary ion source. A 40-1000-fold improvement in signal is found with C60+ relative to the other two ion sources, indicating great promise for future cellular imaging applications using the C60+ probe.

Fullerenes↗

PubMed2005

Microscopic insights into the sputtering of thin organic films on Ag{111} induced by C60 and Ga bombardment.

Molecular dynamics computer simulations have been employed to model the bombardment of Ag{111} covered with three layers of C6H6 by 15 keV Ga and C60 projectiles. The study is aimed toward examining the mechanism by which molecules are desorbed from surfaces by energetic cluster ion beams and toward elucidating the differences between cluster bombardment and atom bombardment. The results show that the impact of the cluster on the benzene-covered surface leads to molecular desorption during the formation of a mesoscopic scale impact crater via a catapulting mechanism. Because of the high yield of C6H6 with both Ga and C60, the yield enhancement is observed to be consistent with related experimental observations. Specific energy and angle distributions are shown to be associated with the catapult mechanism.

Journal Article↗

PubMed2005

Depth profiling of peptide films with TOF-SIMS and a C60 probe.

A buckminsterfullerene ion source is employed to characterize peptide-doped trehalose thin films. The experiments are designed to utilize the unique sputtering properties of cluster ion beams for molecular depth profiling. The results show that trehalose films with high uniformity can be prepared on Si by a spin-coating technique. Bombardment of the film with C60+ results in high quality time-of-flight secondary ion mass spectrometry spectra, even during ion doses of up to 3 x 10(14) ions/cm2. This result is in contrast to atomic bombardment experiments in which the dose of incident ions must be kept below 10(12) ions/cm2 so as to retain mass spectral information. Moreover, since the films are of uniform thickness, it is possible to depth-profile through the film and into the Si substrate. This experimental protocol allows the yield of trehalose molecular equivalents and the degree of interface mixing to be evaluated in detail. When doped with a variety of small peptides up to a molecular weight of m/z 500, we find that the peptide molecular ion intensity remains stable under continuous C60+ bombardment, although some decrease in intensity is observed. The results are interpreted in terms of a model whereby the high trehalose yield and low damage depth of the C60 projectile combine to prevent damage accumulation. In general, the peptide-trehalose system provides a valuable model for evaluating the parameters that lead to effective 3-dimensional characterization of biomaterials.

Fullerenes↗

PubMed2005

Lateral heterogeneity of dipalmitoylphosphatidylethanolamine-cholesterol Langmuir-Blodgett films investigated with imaging time-of-flight secondary ion mass spectrometry and atomic force microscopy.

To better understand the influence of cholesterol (CH) on dipalmitoylphosphatidylethanolamine (DPPE), Langmuir-Blodgett (LB) model membranes of DPPE with varying amounts of cholesterol were imaged by time-of-flight secondary ion mass spectrometry (ToF-SIMS) and atomic force microscopy (AFM). Cholesterol has a condensing effect on DPPE that at low cholesterol concentrations results in lateral heterogeneity of the LB monolayer. At 4:1 DPPE/CH, islands of DPPE/CH phase exist with a connected DPPE phase. As the concentration of cholesterol is increased, the percolation threshold is crossed and the DPPE/CH phase islands connect to separate the DPPE phase (2:1 DPPE/CH). Finally, at 50 mol % cholesterol a single homogeneous DPPE/CH phase LB monolayer exists. ToF-SIMS of the DPPE/CH phase provides a lower ion signal for the characteristic lipid fragments and substrate apparently owing to the higher molecular density induced by cholesterol. AFM data indicate that the DPPE/CH phase is lower in height than the DPPE phase. As phosphatidylethanolamine is predominant in the inner lipid leaflet of cellular membranes, this work has implications for the understanding of cholesterol domains in the inner leaflet of cells.

Cholesterol↗

PubMed2005

Energetic ion bombardment of Ag surfaces by C60+ and Ga+ projectiles.

The ion bombardment-induced release of particles from a metal surface is investigated using energetic fullerene cluster ions as projectiles. The total sputter yield as well as partial yields of neutral and charged monomers and clusters leaving the surface are measured and compared with corresponding data obtained with atomic projectile ions of similar impact kinetic energy. It is found that all yields are enhanced by about one order of magnitude under bombardment with the C60+ cluster projectiles compared with Ga+ ions. In contrast, the electronic excitation processes determining the secondary ion formation probability are unaffected. The kinetic energy spectra of sputtered particles exhibit characteristic differences which reflect the largely different nature of the sputtering process for both types of projectiles. In particular, it is found that under C60+ impact (1) the energy spectrum of sputtered atoms peaks at significantly lower kinetic energies than for Ga+ bombardment and (2) the velocity spectra of monomers and dimers are virtually identical, a finding which is in pronounced contrast to all published data obtained for atomic projectiles. The experimental findings are in reasonable agreement with recent molecular dynamics simulations.

Carbon↗

PubMed2004

Molecular depth profiling of histamine in ice using a buckminsterfullerene probe.

We employ a buckminsterfullerene ion source to probe the distribution of histamine molecules at the water-ice/vacuum interface. The experiments utilize secondary ion mass spectrometry to detect molecular ions that are desorbed from a frozen aqueous histamine solution. The results show that this cluster ion probe induces an extraordinarily high sputter yield of 2400 ice molecules per impact event as determined by a quartz crystal microbalance. As a consequence of this high yield, we show that it is possible to produce molecular depth profiles of the top several hundred nanometers below the ice surface without destruction of the molecular ion signal by accumulation of beam-induced chemical damage. Similar profiles are reported for desorbed neutral molecular fragments by utilizing a high-power femtosecond-pulsed laser for photoionization. While this type of information could not be achieved using atomic projectiles, it is possible to remove the damage induced by such projectiles by subsequent cluster bombardment. These experiments are particularly important for organic surface analysis since they suggest that cluster ion probes may successfully be employed to remove overlayers that may mask the desired molecular information in static secondary ion mass spectral analysis.

Combinatorial Chemistry Techniques↗

PubMed2004

Depth profiling of Langmuir-Blodgett films with a buckminsterfullerene probe.

Bombardment with C60+ primary ions of monolayer and multilayer barium arachidate Langmuir-Blodgett (LB) films is investigated. The behavior of cluster versus atomic (Ga+) bombardment is monitored by the barium-cationized arachidate ion (mass-to-charge ratio (m/z) 449) and a characteristic fragment ion (m/z 209) using 1-, 7-, and 15-layer model systems. The removal rate of material from the films is shown to be on the order of several hundred molecules per C60 impact, a value 100-fold larger than Ga+ impact. The enhancement in secondary ion yield is also shown to be larger for the 15-layer film (400x) than for the monolayer film (100x). Moreover, most of the increase in yield is shown to be associated with ejection of sputtered species rather than an increase in ionization probability. High yields associated with cluster bombardment are also shown to be amenable to depth profiling experiments in which the two ions can be monitored as the film is being removed. In this modality, chemical damage associated with bombardment is removed before it can accumulate on the surface. Due to the similarity of fatty acid LB films to cellular membranes, these results suggest that C60+ primary ion beams may improve the prospects for TOF-SIMS studies of biological systems.

Fullerenes↗