From Top-Down to Bottom-Up to Hybrid Nanotechnologies: Road to Nanodevices

The current development and future prospects of nanotechnology are discussed with special emphasis on the pros and cons of the “bottom-up” and “top-down” approaches to nanotechnology, and the eventual merging of the two, at the scale of about 30 nm in feature size, to form a new “hybrid” technology. At the scale of about 3 nm in feature size, this “hybrid” technology will be challenged by the emerging “supramolecular” and “molecular” technologies epitomized by large-scale integration of single-molecule devices. Ultimately the “supramolecular” and “molecular” technologies will yield to “atomic” or “nuclear” technologies at the dimension of below 0.3 nm whereby single-atom, single-electron, single-spin, single-photon devices become realities.     

Applicability of a cut-off reflector for grazing incidence X-ray fluorescence analysis

The applicability of a cut-off reflector, instead of the commonly used multilayer reflector, for grazing incidence X-ray fluorescence (GI-XRF) analysis is demonstrated. Owing to the precise angular adjustment possible in the total reflection X-ray fluorescence (TXRF) spectrometer developed in house, it is possible to adjust the cut-off reflector so as to pass all X-ray energies up to Cu-K_α, eliminating Cu-K_β and higher X-ray energies emitted from a Cu target X-ray generator. The advantage of this technique is that one gets a higher flux of Cu-K_α radiation (>98%) compared to 80–90% from a good quality multilayer optics. Moreover, the same cut-off reflector, used at different grazing angles, serves the purpose for different primary beam energies. The suitability of such an arrangement for GI-XRF analysis for surface characterization has been demonstrated by analyzing a 50 ng aqueous residue of Fe on top of a float glass substrate. The GI-XRF results thus obtained are compared with those obtained using a multilayer monochromator in the primary beam as well as with theoretical calculations.     

Urine dry reagent strip “error” rates using different reading methods

 The need for “quality” in near patient testing (NPT) has been acknowledged since the mid 1980s. The commonest biochemical NPT device is the dry reagent strip or “dipstick” for urinalysis. Dipsticks may be read in three ways, against the color chart printed along the side of the bottle, using a benchreader (the color chart printed on a flat card) or using an electronic reader. This report uses the results of a urinalysis quality assurance (QA) program, over 1998, to evaluate the “error” rates which occur using the three different reading methods. The QA samples are buffered aqueous solutions which are “spiked” to give concentrations midway between two color blocks for each analyte. Results are scored as ±1 if a color block adjacent to the target value, ±2 for results two color blocks (defined as “error”) and ±3 for results three color blocks (defined as “gross error”) from the target value. Analysis of the results show that the error rates are similar reading visually by either method, but greatly reduced when read electronically. Some persisting errors when using the electronic reader are explained by observation studies. The study highlights the value of a urinalysis QA program for NPT urinalysis in understanding the error rates of this simple but ubiquitous test. Received: 10 July 2000 / Accepted: 10 July 2000     

The electrophoresis of poly(N-isopropylacrylamide) microgel particles

 The electrophoretic mobility of a poly(N-isopropylacrylamide) microgel containing carboxylic groups has been measured as a function of the ionic strength, between 0.1 and 100 mM NaCl, over the temperature range 2545 ^∘C. The mobility data obtained have been evaluated using different models, including the porous-sphere, the soft-plate and the soft-sphere models as well as the hard-sphere model developed by Henry and later refined by O'Brien and White. The “porous” or “soft” behaviour is evident at lower temperatures, whereas at higher temperatures none of the models can fully explain the observed behaviour. It is suggested that the discrepancies at higher temperatures can be partly ascribed to the neglect of the relaxation effect in the “soft” models. Received: 30 June 1999/Accepted in revised form: 12 October 1999     

Scanning electron microscopic observation of porous glass fibers with immobilized glucoamylase

Porous glass fibers with silane-glutaraldehyde immobilized glucoamylase have been examined by Scanning Electron Microscopy (SEM). Partial multilayer coating (“sheeting”) on the fibers’ surfaces has been observed even on gold uncoated samples by using a high resolution SEM. This “sheeting” is attributed to the fiber chemical activation treatment prior to enzyme loading. A 40% reduction of free pore area as a consequence of enzyme attachment is also observed.     

The Si-doped planar tetracoordinate carbon (ptC) unit CAl<Subscript>3</Subscript>Si<Superscript>−</Superscript> could be used as a building block or inorganic ligand during cluster-assembly

Currently, the molecular assembly and growth from a small building block to the bulk compounds have become a focus in various fields. Ever being chemical curiosities, the “anti-van’t Hoff/Le Bel” realm that is associated with tetracoordinate or hypercoordiate planar centers has made vast progress. Being important in the fundamental research areas, the ptC species have potential applications in materials science. The existence of ptC in a divanadium complex and a large number of organometallic compounds have since been reported to possess ptC and these provide us with great hope that many more compounds with ptC building blocks may be synthesized in future. Herein, we report the assembly and stabilization of CAl₃Si⁻ in both the “homo-decked sandwich” and “hetero-decked sandwich” schemes at the B3LYP/6-311+G(d) level. We show that while the Si-doped indeed introduces much complexity during assembly, the electronic and structural integrity feature of CAl₃Si⁻ is well conserved during cluster-assembly, characteristic of a “superatom”. This study should be helpful in understanding the hetero-doped assembly mechanism of the ptC chemistry. Moreover, the present results are expected to enrich the flat carbon chemistry, superatom chemistry, metallocenes and combinational chemistry. Electronic Supplementary Material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Characterization of peak purity by fast multiscan circular dichroism detection

Summary A method has been developed to detect inhomogeneity of apparently homogeneous peaks of very similar analytes. The method utilizes the rapid scan feature of state-of-the-art spectrometers/detectors that allow the recording of up to 30 spectra in a single chromatographic peak. Sensitivity and selectivity are enhanced by chiroptical/optical detection. Thus, identification of “front” and “rear” components of the peak can be carried out. The method is exemplified by mixtures of codeine, hydrocodone and oxycodone as analytes. Presented at: Balaton Symposium on High-Performance Separation Methods, Siófok, Hungary, September 3–5, 1997     

Distances and volumina for graphs

It has long been realized that connected graphs have some sort of geometric structure, in that there is a natural distance function (or metric), namely, the shortest-path distance function. In fact, there are several other natural yet intrinsic distance functions, including: the resistance distance, correspondent “square-rooted” distance functions, and a so‐called “quasi‐Euclidean” distance function. Some of these distance functions are introduced here, and some are noted not only to satisfy the usual triangle inequality but also other relations such as the “tetrahedron inequality”. Granted some (intrinsic) distance function, there are different consequent graph-invariants. Here attention is directed to a sequence of graph invariants which may be interpreted as: the sum of a power of the distances between pairs of vertices of G, the sum of a power of the “areas” between triples of vertices of G, the sum of a power of the “volumes” between quartets of vertices of G, etc. The Cayley–Menger formula for n-volumes in Euclidean space is taken as the defining relation for so-called “n-volumina” in terms of graph distances, and several theorems are here established for the volumina-sum invariants (when the mentioned power is 2). This revised version was published online in July 2006 with corrections to the Cover Date.     

A comparison of location estimators for interlaboratory data contaminated with value and uncertainty outliers

While estimation of measurement uncertainty (MU) is increasingly acknowledged as an essential component of the chemical measurement process, there is little agreement on how best to use even nominally well-estimated MU. There are philosophical and practical issues involved in defining what is “best” for a given data set; however, there is remarkably little guidance on how well different MU-using estimators perform with imperfect data. This report characterizes the bias, efficiency, and robustness properties for several commonly used or recently proposed estimators of true location, μ, using “Monte Carlo” (MC) evaluation of “measurement” data sets drawn from well-defined distributions. These synthetic models address a number of issues pertinent to interlaboratory comparisons studies. While the MC results do not provide specific guidance on “which estimator is best” for any given set of real data, they do provide broad insight into the expected relative performance within broadly defined scenarios. Perhaps the broadest and most emphatic guidance from the present study is that (1) well-estimated measurement uncertainties can be used to improve the reliability of location determination and (2) some approaches to using measurement uncertainties are better than others. The traditional inverse squared uncertainty-weighted estimators perform well only in the absence of unrepresentative values (value outliers) or underestimated uncertainties (uncertainty outliers); even modest contamination by such outliers may result in relatively inaccurate estimates. In contrast, some inverse total variance-weighted-estimators and probability density function area-based estimators perform well for all scenarios evaluated, including underestimated uncertainties, extreme value outliers, and asymmetric contamination.     

Linearly polarized white fluorescence from shish-kebab type liquid crystalline poly(P-phenylenevinvlene)s with (P-phenylene)s as kebab

Liquid crystalline(LC) polymers with a shish-kebab-type moiety on their cross-conjugated(p-phenylene)s-poly(p-phenylenevinylene) s main chains were synthesized through Gilch polymerization in order to develop a kind of polymers available for linearly polarized white-light-emitting from single chain.In this system,the 2,5-bis(4’-alkoxyphenyl)benzene as the "kebabs" connects with poly(p-phenylenevinylene)(PPV) main chain backbone using its molecular gravity center and the PPV as the "shish" or "skewer"(the "shish-kebab").The polymers possess desirable properties such as excellent solubility and liquid crystalline properties.To drop the "kebabs" of the 2,5-bis(4’-alkoxyphenyl)benzene into the orientation microgroove of aligned polyimide film,not only the "shish" of polymer main chain can be aligned by the virtue of orientation of "kebabs" but also the uniform cross-conjugated structure between the "kebabs" and "shish" can be broken. Then,the alignment of the polymer main chain showed yellow light emission and was also accompanied by orientation of the LC side chains showing blue light emission,this gave rise to a notable linearly polarized white fluorescence.     

Study on molecular interactions between proteins on live cell membranes using quantum dot-based fluorescence resonance energy transfer

Mouse anti-human CD71 monoclonal antibody (anti-CD71) was conjugated with red quantum dots (QDs; 5.3 nm, emission wavelength λ _em = 614 nm) and used to label HeLa cells successfully. Then green QD-labeled goat anti-mouse immunoglobulin G (IgG; the size of the green QDs was 2.2 nm; λ _em = 544 nm) was added to bind the red-QD-conjugated anti-CD71 on the cell surface by immunoreactions. Such interaction between anti-CD71 and IgG lasted 4 min and was observed from the fluorescence spectra: the fluorescence intensity of the “red” peak at 614 nm increased by 32%; meanwhile that of the “green” one at 544 nm decreased by 55%. The ratio of the fluorescence intensities (I _544 nm/I _614 nm) decreased from 0.5 to 0.2. The fluorescence spectra as well as cell imaging showed that fluorescence resonance energy transfer took place between these two kinds of QDs on the HeLa cells through interactions between the primary antibody and the secondary antibody.     

Organic electronics—Silicon device design without semiconductor band theory

Before the invention of the transistor in the 1940s, semiconductors were used as detectors in radios in a device called a “cat’s whisker”. At that time their operation was completely mysterious. Only after the introduction of semiconductor band theory did it become clear that the “cat’s whisker” is a primitive example of a metal-semiconductor Schottky diode. Today organic materials are being investigated for their electronic properties. Such materials are especially attractive for lightweight, flexible, and low-cost solar cells and light emitting devices, as well as transistors and electrophotographic photoreceptors. Yet, even after 40 years of work and a large database, the physics and chemistry that determines the electronic properties of organic materials are not well understood. Practicing organic electronics is like attempting to do silicon device design without semiconductor band theory. It is the purpose of this paper to briefly summarize what is known about the electronic properties of organic materials from charge transport data. It will be shown that our understanding of the charge transport mechanism and the electronic properties of organic materials is at a rudimentary phase which is a limiting factor in applying these materials to practical devices, very similar to the “cat’s whisker” phase of inorganic semiconductor research.     

Calibration of activity readings from radiopharmaceuticals with impurities

Accurately determining the amount of a radionuclide actually administered to a patient is an important aspect of quality control in nuclear medicine. In this study, in order to accurately assess the “apparent” radioactivities of radionuclides with impurities by a dose calibrator, two methods, (1) curve fitting, and (2) relative sensitivities calculation, have been employed to determine the parameter, M (relative response). From the comparisons between the measurement and re-calculated radioactivity using the M values, each method was found to have its own advantage and disadvantage, depending upon the fraction ratio of the impurity as well as the energy level of the impurity’s photons. This study might be helpful for improving the assessment of radiopharmaceuticals’ “true” activity and its “apparent” activity measured by a dose calibrator.     

Introduction of a 20 kHz Nd:YVO4 laser into a hybrid quadrupole time-of-flight mass spectrometer for MALDI-MS imaging

A commercial hybrid quadrupole time–of–flight mass spectrometer has been modified for high-speed matrix-assisted laser desorption ionisation (MALDI) imaging using a short-pulse optical technology Nd:YVO₄ laser. The laser operating in frequency-tripled mode (λ = 355 nm) is capable of delivering 1.5-ns pulses of energy at up to 8 μJ at 5–10 kHz and 3 μJ at 20 kHz. Experiments to improve beam homogeneity and reduce laser speckle by mechanical vibration of the fibre-optic laser delivery system are reported along with data from trial and tissue imaging experiments using the modified instrument. The laser appeared to yield best results for MALDI-MS imaging experiments when operating at repetition rates 5–10 kHz. Combining this with raster imaging allowed images of rat brain sections to be recorded in 37 min. Similarly, images of the distribution of peptides in “on-tissue” digest experiments from tumour tissues were recorded in 1 h and 30 min rather than the 8-h acquisition time previously used. A brief investigation of targeted protein analysis/imaging by multiple reaction monitoring experiments “on-tissue” is reported. A total of 26 transitions were recorded over a 3-s cycle time and images of abundant proteins were successfully recorded.     

Multivariate analysis of HT/GC-(IT)MS chromatographic profiles of triacylglycerol for classification of olive oil varieties

The ability of multivariate analysis methods such as hierarchical cluster analysis, principal component analysis and partial least squares-discriminant analysis (PLS-DA) to achieve olive oil classification based on the olive fruit varieties from their triacylglycerols profile, have been investigated. The variations in the raw chromatographic data sets of 56 olive oil samples were studied by high-temperature gas chromatography with (ion trap) mass spectrometry detection. The olive oil samples were of four different categories (“extra-virgin olive oil”, “virgin olive oil”, “olive oil” and “olive-pomace” oil), and for the “extra-virgin” category, six different well-identified olive oil varieties (“hojiblanca”, “manzanilla”, “picual”, “cornicabra”, “arbequina” and “frantoio”) and some blends of unidentified varieties. Moreover, by pre-processing methods of chemometric (to linearise the response of the variables) such as peak-shifting, baseline (weighted least squares) and mean centering, it was possible to improve the model and grouping between different varieties of olive oils. By using the first three principal components, it was possible to account for 79.50% of the information on the original data. The fitted PLS-DA model succeeded in classifying the samples. Correct classification rates were assessed by cross-validation.     

Tunable single-photon ionization TOF mass spectrometry using laser-produced plasma as the table-top VUV light source

Here we report on a laser plasma-based tunable VUV photoionization time-of-flight (TOF) mass spectrometer conceived mainly to study complex gaseous mixtures. Ionizing photons at tunable vacuum UV (VUV) wavelengths are generated by a gas-target laser-produced plasma, spectrally dispersed in the range 100–160 nm and efficiently focused onto a sample molecular beam. As a test case, we studied the exhaust gas of a four-stroke moped, a typical example of a complex gaseous mixture. Due to the VUV “soft” ionization, the mass spectra are less congested and more easily interpretable. Substituted benzene derivatives are found to give the most intense signals. Several aliphatic hydrocarbons are also detected. The use of tunable VUV radiation allowed the investigation of the contribution of isomers in the mass spectrum from the onset and shape of the photoionization efficiency spectra. Semiquantitative analysis was performed using known literature data detailing the photoionization cross sections. Our findings suggest that using combined data on the mass/photoionization efficiency spectra may be very helpful for a comprehensive analysis of complex gaseous mixtures.     

“Osmiophilic particles”—a fungal agent with characteristic distribution in white-and brown-rotted wood

When pine wood decayed by white- and brown-rot fungi was observed in TEM after fixation and staining with glutaraldehyde/osmium tetroxide/ uranylacetate and embedding in Spurr’s ultralow viscosity resin electron dense particles, called “osmiophilic particles,” a typical distribution for the two decay types could be observed: in white-rotted wood the particles could be found in and around the hyphae and on the lumen surface of the wood cell wall, mostly aggregated to thick clusters. During the whole course of decay the wood cell walls were free of the particles, but they were present on the corroded surfaces. In brown-rotted wood the “osmiophilic particles” also could be found in and around the hyphae, but in contrast the particles were distributed over all the wood cell wall layers from the early to late stages of decay. The distribution of the “osmiophilic particles” coincides with the place where the major cell wall degradation takes place: in white-rot the cell walls are degraded from the lumen to the middle lamella; in brown-rot a depolymerization and degradation of the carbohydrates takes place all over the wood cell wall. Since the “osmiophilic particles” can be found where the degradation takes place, it can be concluded that they are causally connected with wood decay. The fact that they also were found in, and some of them also around, hyphae grown on malt-agar or Sabouraud-dextrose-agar proves that they are produced by the fungi and cannot be degradation products. The possibility that they could be preparative artifacts can be excluded because uncolonized wood was free of “osmiophilic particles.” Since the “osmiophilic particles” are produced by the fungi and can be found in places where wood is decaying, it can be further concluded that they are a fungal agent that is involved in wood degradation, probably fungal enzymes. The observation that the large “osmiophilic particles,” which may have a size of up to 20 nm, are composed of globular subunits of a diameter of 2—3 nm also speaks for their enzymatic nature. To find out which type of enzyme they might be, the white-rot fungusTrametes hirsuta was grown on wood pulp with 7% lignin, on delignified wood pulp containing cellulose and hemicellulose, and on filterpaper (pure cellulose). The hyphae on wood pulp containing 7% lignin were surrounded by thick sheaths of “osmiophilic particles,” whereas with the hyphae grown on delignified wood pulp and pure cellulose only a few particles could be found. This makes it clear that the production of the “osmiophilic particles” is induced by lignin.     

Protein–Protein Binding Affinities in Solution Determined by Electrospray Mass Spectrometry

Electrospray ionization (ESI) allows the transfer of multi-protein complexes into the gas phase, thereby providing a simple approach for monitoring the stoichiometry of these noncovalent assemblies by mass spectrometry (MS). It remains unclear, however, whether the measured ion abundance ratios of free and bound species are suitable for determining solution-phase binding affinities (K _d values). Many types of mass spectrometers employ rf-only quadrupoles as ion guides. This work demonstrates that the settings used for these devices are a key factor for ensuring uniform transmission behavior, which is a prerequisite for meaningful affinity measurements. Using bovine β-lactoglobulin and hemoglobin as model systems, it is demonstrated that under carefully adjusted conditions the “direct” ESI-MS approach is capable of providing K _d values that are in good agreement with previously published solution-phase data. Of the several ion sources tested, a regular ESI emitter operated with pressure-driven flow at 1 μL min^–1 provided the most favorable results. Potential problems in these experiments include conformationally-induced differences in ionization efficiencies, inadvertent collision-induced dissociation, and ESI-induced clustering artifacts. A number of simple tests can be conducted to assess whether or not these factors are prevalent under the conditions used. In addition, the fidelity of the method can be scrutinized by performing measurements over a wide concentration range. Overall, this work supports the viability of the direct ESI-MS approach for determining binding affinities of protein–protein complexes in solution.     

Synchrotron radiation induced total reflection X-ray fluorescence of low Z elements on Si wafer surfaces at SSRL — comparison of excitation geometries and conditions

The analysis of low Z elements, like Na and Al at ultra trace levels (<10¹⁰ atoms/cm²) on Si wafer surfaces is required by the semiconductor industry. Synchrotron radiation induced total reflection X-ray fluorescence analysis (SR-TXRF) is a promising method to fulfill this task, if a special energy dispersive detector with an ultra thin window is used. Synchrotron radiation is the ideal excitation source for TXRF of low Z elements due to its intense, naturally collimated and linearly polarized radiation with a wide spectral range down to low energies even below 1 keV. TXRF offers some advantages for wafer surface analysis such as non-destructive analysis and mapping capabilities. Experiments have been performed at the Stanford Synchrotron Radiation Lab (SSRL) using Beamline 3-4 (BL 3-4), a bending magnet beamline using white (<3 keV) and monochromatic radiation, as well as Beamline 3-3 (BL 3-3), using a crystal monochromator as well as a multilayer monochromator. A comparison of excitation–detection geometry was performed, using a side-looking detector with a vertically positioned wafer as well as a down-looking detector with a horizontally arranged wafer. The advantages and disadvantages of the various geometrical and excitation conditions are presented and the results compared. Detection limits are in the 100-fg range for Na, as determined with droplet samples on Si wafer surfaces.     

Comparability of measurement results for pesticide residues in foodstuffs: an open issue?

The dispersion of results from proficiency tests for the analysis of pesticide residues in foodstuffs suggests that improvements in the compatibility of measurement results are needed. Currently observed divergences can make the evaluation conclusion on foodstuffs compliance with certain legislation dependent on the consulted laboratory. This work discusses the origin and impact of this lack of compatibility, following the metrological concepts presented at the latest version of the “International Vocabulary of Metrology” (VIM3), thus allowing for a clear diagnostic of the problem. The reporting of results from different measurement methods uncorrected for the observed analyte recovery makes them traceable to different “operationally defined measurement procedures” (VIM3) and, therefore, not comparable. When results from different measurement methods are reported corrected for analyte recovery, R, and R is different for spiked and incurred residues, measurement results may be not compatible if this effect is not considered on the uncertainty budget. This discussion is illustrated with metrological models for any possible combination of “measurement performance” and “maximum residue level”. These models are complemented with experimental data of the analysis of pesticide residues in a sample of ginseng powder from a proficiency test. The adopted experimental design allowed the identification of additional threats to metrological compatibility in this field. Solutions to the faced problem are discussed for practicability and impact on regulatory issues. The use of a universal “reference measurement procedure” proves to be the most feasible way of ensuring comparability of measurements in this field.