Ion beam-induced magnetic patterning at the sub-0.1 μm level

We present a method that allows magnetic patterning of a continuous magnetic film without significant modification of the surface roughness or of the film's optical indices. It involves ion irradiation of Co/Pt multilayers, using either a standard ion implantation technology combined with high resolution masking, or a focussed ion beam. We fabricated arrays of lines or dots whose magnetic properties differ on a sub-100 nm scale. We describe the ion collision physics on which the techniques are based, as well as some of the observed consequences on the micromagnetic properties of the arrays and on the ultimate resolution. Possible applications to high-density information storage are briefly discussed.     

Kinetic investigation of narrow-bore columns packed with prototype sub-2 μm superficially porous particles with various shell thickness

The recent successful breakthrough of sub-3 μm shell particles in HPLC has triggered considerable research efforts toward the design of new brands of core-shell particles. We investigated the mass transfer mechanism of a few analytes in narrow-bore columns packed with prototype 1.7 μm shell particles, made of 1.0, 1.2, and 1.4 μm solid nonporous cores surrounded by porous shells 350, 250, and 150 nm thick, respectively. Three probe solutes, uracil, naphthalene, and insulin, were chosen to assess the kinetic performance of these columns. Inverse size exclusion chromatography, peak parking experiments, and the numerical integration of the experimental peak profiles were carried out in order to measure the external, internal, and total column porosities, the true bulk diffusion coefficients of these analytes, the height equivalent to a theoretical plate, the longitudinal diffusion term, and the trans-particle mass transfer resistance term. The residual eddy diffusion term was measured by difference. The results show the existence of important trans-column velocity biases (7%) possibly due to the presence of particle multiplets in the slurry mixture used during the packing process. Our results illustrates some of the difficulties encountered by scientists preparing and packing shell particles into narrow-bore columns.     

Some practical comparisons of the efficiency and overloading behaviour of sub-2 μm porous and sub-3 μm shell particles in reversed-phase liquid chromatography

At their optimum flow, sub-3 μm superficially porous or "shell" particles demonstrate similar efficiency to sub-2 μm totally porous particles. The performance of 0.21 cm i.d shell columns is however inferior to those of 0.46 cm i.d., presumably due to packing difficulties. At high flow, shell columns can give flatter Knox curves due to lower operating pressure (half or less of that of the totally porous particles) producing less frictional heating, which combined with the increased thermal conductivity of their non-porous core, gives more efficient heat dissipation. However, the effects of frictional heating for sub-2 μm columns are considerably exaggerated when using pure ACN as mobile phase, as it has a thermal conductivity 3 times less than that of pure water, leading to poorer heat dissipation. Overloading is already problematic for ionised solutes, a group which contains many pharmaceuticals and compounds of clinical relevance, on conventional columns (5 μm porous particles). However, it becomes a more serious issue for both new column types, partially as a result of their very high efficiency, which concentrates the sample as a very narrow band. The sample capacity of one type of shell particle was estimated to be 60% of that of the small totally porous particles, in line with the fraction of the particle volume that is porous. Due to overloading, it is barely possible to achieve perfect peak symmetry for ionised acids or bases with either of these new column types, even by injecting the lowest amounts of sample detectable by UV. While ammonium formate and potassium phosphate buffers gave similar results in overloading studies, use of formic acid as sole mobile phase additive is not recommended for these solutes, as its ionic strength is too low, leading to a catastrophic deterioration in efficiency when sample concentrations of even a few mg/L are injected.     

Histamine determination in human urine using sub-2 μm C18 column with fluorescence and mass spectrometric detection

A fast, sensitive, and selective method for the determination of histamine in human urine samples by ultrahigh pressure liquid chromatography (LC) with fluorescence and mass spectrometry (MS) detection is investigated. A fluorescent reagent, 4-(1-pyrene) butyric acid N-hydroxysuccinimide ester was conjugated to the primary and secondary amino moieties of histamine. The structure of dipyrene-labeled histamine in human urine was determined by quadrupole time-of-flight MS with electospray ionization interface. The determination of the dipyrene derivative of histamine in urine samples was achieved within 3.9 min on an ultrahigh pressure LC Eclipse Zorbax XDB-C(18) column with 1.8 μm particle diameter. In this work, histamine separation was achieved significantly faster (3.9 min) with improved detection limit (signal-to-noise = 3) of 0.04 nM than 19.5 min with a detection limit of 0.183 nM as reported in a previous method.     

Analysis of peptides and proteins using sub-2 μm fully porous and sub 3-μm shell particles

The objective of this study was to evaluate the potential of sub-2 μm totally porous particles and sub-3 μm shell particles for peptide and protein analysis. Specific analytical strategies must be developed for these biomolecules as their importance in the pharmaceutical industry increases and as their structural complexity involves some issues when classical LC conditions are employed. Attention was paid on comparing these different columns in various LC conditions (different temperatures, gradient times, and mobile phase flow rates). The comparison of the different supports was assessed considering columns characteristics (quality of packing, silanol activity, pore size, totally porous or shell particles). In this article, peptides were first analyzed with both column technologies. Similar results to those achieved with low molecular weight compounds were obtained (peak capacity >100 for t_grad around 3 min and columns dimensions of 2.1 mm id × 50 mm), but specific conditions were required (elevated temperature and the use of a volatile ion-pairing reagent, namely TFA). For peptide analysis following tryptic digestion, the goal was to improve peak capacity and resolution because of the large number of generated peptides. For this purpose, longer columns packed with porous sub-2 μm or shell sub-3 μm particles (i.e., 150 mm) and gradient times (i.e., up to 30 min) were tested. On the other hand, proteins in their intact forms have higher molecular weights (MW > 5000 Da) and a tertiary structure, thus requiring different conditions in terms of stationary phase hydrophobicity (C₄vs. C₁₈) and pore size (300 vs. 120 Å). In addition, there were issues with adsorption onto the LC system and/or the column itself. This study showed that proteins with MWs lower than 40,000 Da required chromatographic conditions close to those employed for peptide analysis. For larger proteins, a C₄ 300 Å stationary phase gave the best results, confirming theoretical predictions.     

On the extra-column band-broadening contributions of modern, very high pressure liquid chromatographs using 2.1 mm I.D. columns packed with sub-2 μm particles

The efficiencies of two narrow bore columns (100 mm and 50 mm × 2.1 mm) packed with 1.7 μm totally porous BEH-C₁₈ particles were measured on two very high pressure liquid chromatographs (Acquity from Waters and 1290 Infinity HPLC System from Agilent) operating at maximum pressures of 1034 and 1200 bar, respectively. The probe compounds were a mixture of uracil, acetophenone, toluene, and naphthalene eluted in a 50/50 (v/v) solution of acetonitrile and water at 303 K with a flow rate of 0.40 mL/min. The apparent efficiencies of columns, which lumps the consequences of band broadening due to the column and the system contributions, may depend much on the extra-column volumes of the instruments used. Actually, it is known for a long time that the apparent column performance is strongly affected by the instrument characteristics, including the diameter of the connecting tubes, the injection technique (with or without needle seat capillary), and the detection cell volume. When the 1290 Infinity HPLC System is equipped with a needle seat, an inlet and an outlet connecting capillary tube with inner diameters around 115 μm, its extra-column variance for a 0.1 μL injection volume is 9.2 μL² while that of the Acquity instrument is 6.9 μL². Minor modifications suggested by their respective manufacturers allowed significant reductions of these variances, to 6.2 and 3.9 μL², respectively. Yet, in their optimized configurations and for weakly retained compounds (k ? 1), these modern, sophisticated instruments cannot provide more than 75% (1290 Infinity) and 85% (Acquity) of the maximum efficiency of a 2.1 mm × 50 mm BEH column. For more strongly retained compounds (k > 4), in contrast, they are both able to provide more than 95% of the maximum expected efficiency.     

Modern analytical supercritical fluid chromatography using columns packed with sub-2 μm particles: A tutorial

This tutorial provides an overview of the possibilities, limitations and analytical conditions of modern analytical supercritical fluid chromatography (SFC) using columns packed with sub-2 μm particles. In particular, it gives a detailed overview of commercially available modern SFC instrumentation and the detectors that can be employed (UV, MS, ELSD, FID, etc.). Some advice on the choice of the stationary phase dimensions and chemistries, the nature of the mobile phase (choice of organic modifier and additives) and its flow rate as well as the backpressure and temperature are also provided. Finally, several groups of potentially problematic compounds, including lipophilic compounds, hydrophilic substances and basic drugs, are discussed in detail. All these families of analytes can be resolved with SFC but require specific analytical conditions.     

Characterization of a 2.6 μm Kinetex porous shell hydrophilic interaction liquid chromatography column in supercritical fluid chromatography with a comparison to 3 μm totally porous silica

The first systematic study of the performance of a porous shell, hydrophylic interaction liquid chromatography (HILIC) column in supercritical fluid chromatography (SFC) is presented. Observed efficiency on 2.6-μm porous shell particles exceeded all reports using UHPLC on 100-mm long columns packed with <2-μm totally porous particles. A Kinetex 4.6 × 150 mm, 2.6 μm HILIC column significantly outperformed a 3 μm Luna totally porous silica of the same length and diameter. A 17 component, low molecular weight test mix, consisting of a range of small drug-like molecules was separated isocratically on each column, with similar selectivity, but the porous shell column required ½ the time (≈2 min vs. 4 min), with almost 50% higher efficiency. Even little retained compounds (k < 0.5) exhibited more than 30,000 plates under some conditions. Reduced plate heights were higher than previously reported on porous shell particles in both HILIC and rHPLC, with the lowest value of 1.62. Significant fronting was sometimes observed. The cause of the fronting was not determined. The least symmetrical peaks showed the highest apparent efficiency. Pressure drop at optimum velocity (2.5 ml/min) and low modifier concentrations was <60 bar, and only exceeded 250 bar at near double optimum flow and 65% modifier. Peak widths were mostly just over 0.01 min (20 Hz) wide. There was a loss of efficiency when the injection volume was increased. The chromatograph was shown to have extremely low extra-column dispersion, on the order of 5–10 μL², which is also the lowest reported in an SFC, in spite of using standard components. This is likely due to turbulent flow in the tubing and fittings.     

Hydrophilic interaction chromatography of seized drugs and related compounds with sub 2 μm particle columns

The use of hydrophilic interaction chromatography (HILIC) with sub 2 μm particle columns for the analysis of drugs and related compounds of forensic interest is described. This technique uses a high organic/low aqueous buffered mobile phase with a polar stationary phase, and is excellent for the separation of many of the charged solutes that are found in forensic drug exhibits. In this study, HILIC is investigated for 11 solutes of forensic interest, including weak bases, weak acids, and a neutral solute. In addition, for columns containing either ethylene bridged hybrid particles with or without an amide bonded phase, the effects of acetonitrile concentration, buffer type, buffer concentration, linear velocity, and sample concentration were studied. Based on these studies, HILIC with sub 2 μm particle columns can offer highly efficient, selective, and rapid isocratic separations of drugs and related compounds of forensic interest, with excellent peak shapes and low back pressures. This is in contrast to reverse phase chromatography (RPLC), where gradient elution is usually required, which can result in extensive overlap between acidic, neutral, and basic solutes. In addition, since HILIC exhibits a much greater loading capacity than RPLC, it could be a preferred technique for drug profiling. Furthermore, because high organic content mobile phases are highly amenable to mass spectrometric detection, the use of HILIC with tandem mass spectrometric detection for the analysis of seized drugs is described.     

Hydrothermal Tm3+-Lu2O3 nanorods with highly efficient 2 μm emission

Cubic Ia3Tm-Lu(2)O(3) porous nanorods of ～45 μm length and 90 nm diameter have been prepared with precise compositions through a soft hydrothermal route (i.e., autogenic pressure, neutral pH, and 185 °C for 24 h) by using chloride reagents. For these nanorods, room temperature excitation and photoluminescence spectra of Tm(3+) multiplets related to the eye-safe (3)F(4)→(3)H(6) laser transition at ～1.85-2.05 μm are similar to those of bulk crystals. Room-temperature luminescence decays of (3)H(4) and (3)F(4) exhibit nonexponential dynamics analytically reproduced by the sum of two exponential regimes, which are ascribed to the different rates of nonradiative relaxations in defects at the surface and in the body of the nanocrystals, respectively. Measured fluorescence lifetimes τ ～ 200-260 μs and τ ～ 2.3-2.9 ms for (3)H(4) and (3)F(4), respectively, in 0.2% mol Tm-Lu(2)O(3) nanorods, are considerably larger than in previous nanocrystalline Tm-doped sesquioxides, and they are close to values of bulk sesquioxide crystals with equivalent Tm(3+) content.     

Progress of 1.5～1.6 μm Laser Crystals

Eye-safe 1.5～1.6 μm lasers have important applications in optical fiber communication, medicine, laser-range-finding, lidar, etc. Er^3＋ and Yb^3＋ co-doped crystal pumped by diode laser around 976 nm is an attractive method for obtaining 1.5～1.6 μm laser in compact device with high output beam quality. In this paper, the recent research and progress of several important Er^3＋ and Yb^3＋ co-doped laser crystals at 1.5～1.6 μm in authors’ lab are reported.     

Fast capillary electrophoresis-time-of-flight mass spectrometry using capillaries with inner diameters ranging from 75 to 5 μm

Fast electrophoretic separations in fused silica capillaries (CE) coupled to time-of-flight mass spectrometry (TOF-MS) are presented. CE separations of the model analytes (epinephrine, norepinephrine, dopamine, histidine, and isoproterenol) under conditions of high electric field strengths of up to 1.25 kV cm⁻¹ are completed in 20 s. Coupling of CE with TOF-MS is accomplished using a coaxial sheath liquid electrospray ionization interface. The influence of parameters inherent to the interface and their effects, including suction pressure and dilution, are discussed. In addition to standard capillaries of 75 and 50 μm inner diameter (ID), separations in capillaries with IDs of 25, 15, and 5 μm have been successfully applied to this setup. The analytical performance is compared over this range of capillary dimensions, and both advantages and disadvantages are discussed.     

High temperature-high efficiency liquid chromatography using sub-2 μm coupled columns for the analysis of selected non-steroidal anti-inflammatory drugs and veterinary antibiotics in environmental samples

A high efficiency HPLC method was developed by coupling three sub-2 μm columns in series and operating them at high temperature for the separation of selected non-steroidal anti-inflammatory drugs and veterinary antibiotics in environmental samples. The separation was performed at 80 °C to reduce the solvent viscosity, thus reducing the column backpressure. The chromatographic performance of high temperature-extended column length HPLC method was used to determine the most widely used non-steroidal anti-inflammatory drugs and veterinary antibiotics such as sulphonamides in wastewater samples. The method could simultaneously determine 24 pharmaceuticals in short analysis time with high efficiency. The method involved pre-concentration and clean-up by solid phase extraction (SPE) using Oasis HLB extraction cartridges. It was validated based on linearity, precision, detection and quantification limits, selectivity and accuracy. Good recoveries were obtained for all analytes ranging from 72.7% to 98.2% with standard deviations not higher than 6%, except for acetaminophen and acetyl salicylic acid, for which low recovery was obtained. The detection limits of the studied pharmaceuticals ranged from 2 to 16 μg L⁻¹, while limits of quantification were in the range from 7 to 54 μg L⁻¹ with UV detection.     

CuLn complexes with a single μ-oximato bridge

Two original dinuclear (LnYb, 3 and LnEr, 4) and one trinuclear Cu^IILn^IIICu^II (LnGd, 5) complexes derived from a polydentate non symmetrical Schiff base ligand H₂L have been prepared. The ligand possesses two functions (phenol and oxime) able to coordinate the Ln ions, but structural studies (X-ray diffraction and powder X-ray diffraction) show that the Cu^II and Ln^III ions are only bridged by the oximato (NO) pair. The missing phenoxo bridge is replaced by a surprising pseudo-bridge involving one oxygen atom of the nitrato anion linked to the Cu and Ln ions according to a η²: η¹: μ mode. Although this latter contact has no role from the magnetic point of view, it introduces a large deformation of the unique bridging network. The CuYb complex 3 and the trinuclear CuGdCu complex 5 present antiferromagnetic interactions, with a J_CuGd interaction equal to ?1.25 cm^?1 in 5. The genuine single bridge can be considered as responsible for the antiferromagnetic character of the interaction.     

Metabolic profiling of amino acids in cellular samples via zwitterionic sub-2 μm particle size HILIC-MS/MS and a uniformly 13C labeled internal standard

A novel analytical method using hydrophilic interaction liquid chromatography combined with electrospray tandem mass spectrometry for metabolic profiling of free, underivatized amino acids is presented. The separation uses a zwitterionic modified silica-based stationary phase with 1.8-μm particle size functionalized with ammonium sulfonic acid groups. Quantification is based on external standard calibration using a Pichia pastoris cell extract grown on uniformly ¹³C labeled glucose as an internal standard. The absolute limits of detection in the cellular matrix were in the subpicomolar range. Measurement accuracy was assessed by analyzing NIST Standard Reference Material 2389a, which provides certified values for 17 amino acids. The recovery of the amino acids ranged between 65 % (proline) and 120 % (lysine), with excellent repeatability precision below 2.5 % (n?=?5). Only, cystine showed poor recovery (29 %) and repeatability precision (13 %). Generally, the long-term precision obtained by hydrophilic interaction liquid chromatography–tandem mass spectrometry was excellent, being on average less than 9 % over 20 h of measurement time. Moreover, the novel separation method had average repeatability and reproducibility of the chromatographic peak width over time periods of 20 h and 6 months of 8 and 15 %, respectively, demonstrating its high robustness in routine analysis of cellular samples. Large concentration differences depending on the amino acid were found in the cell extracts, typically ranging from 0.002 nmol per milligram of cell dry weight (cystine) to 56 nmol per milligram of cell dry weight (arginine and glutamic acid).     

Theoretical Investigation of Transparent (3–5 μm) and High Reflective (1.3 μm) Filter by Sol-Gel Process

When designing a cut-off interference filter, extra layers are needed to add on each side of periodic symmetrical multilayer to match the incident medium and the substrate. In this paper, we use sol-gel film with adjustable refractive index as the match layer. The influence of the refractive index and thickness of the match layer on the film system is discussed in detail. As an example, a special filter which is transparent (>80%) at the wavelength 3–5 m and high reflective (>90%) at the wavelength 1.3 m is designed. Finally a series of optimized film parameters are presented. The whole design process is a good reference to the other multilayer special filter made by sol-gel process.     

Single-cell recording and stimulation with a 16k micro-nail electrode array integrated on a 0.18 μm CMOS chip

To cope with the growing needs in research towards the understanding of cellular function and network dynamics, advanced micro-electrode arrays (MEAs) based on integrated complementary metal oxide semiconductor (CMOS) circuits have been increasingly reported. Although such arrays contain a large number of sensors for recording and/or stimulation, the size of the electrodes on these chips are often larger than a typical mammalian cell. Therefore, true single-cell recording and stimulation remains challenging. Single-cell resolution can be obtained by decreasing the size of the electrodes, which inherently increases the characteristic impedance and noise. Here, we present an array of 16,384 active sensors monolithically integrated on chip, realized in 0.18 μm CMOS technology for recording and stimulation of individual cells. Successful recording of electrical activity of cardiac cells with the chip, validated with intracellular whole-cell patch clamp recordings are presented, illustrating single-cell readout capability. Further, by applying a single-electrode stimulation protocol, we could pace individual cardiac cells, demonstrating single-cell addressability. This novel electrode array could help pave the way towards solving complex interactions of mammalian cellular networks.     

Kinetic behaviour in supercritical fluid chromatography with modified mobile phase for 5 μm particle size and varied flow rates

After much development of stationary phase chemistry, in recent years the focus of many studies in HPLC has shifted to increase the efficiency and analysis speed. Ultra high pressure liquid chromatography (UHPLC) using sub-2 μm particles, and high temperature liquid chromatography (HTLC), using temperatures above 100°C have received much attention. These new approaches allow the use of flow rates higher than those classically used in HPLC, reducing the analysis duration. Due to the low viscosity of supercritical fluids, high velocities, i.e. high flow rates, can be achieved with classical pumping systems typically used in supercritical fluid chromatography (SFC). The effects of the flow rate increase with CO(2)/methanol mobile phase was studied on the inlet pressure, t(0), the retention factor of the compounds, and on the efficiency. Simple comparisons of efficiencies obtained at varied temperature between SFC and HPLC, with a packed column containing 5 μm particles, show the greater kinetic performances achieved with the CO(2)/methanol fluid, and underline specific behaviours of SFC, occurring for high flow rates and sub-ambient temperature. Some values (N/t(0)) are also compared to UHPLC data, showing that good performance can be achieved in SFC without applying drastic analytical conditions. Finally, simple kinetic plots (t(0) vs N) at constant column length are used to select combinations of temperature and flow rate necessary to achieve a required theoretical plate number.     

Two new dinuclear complexes with flexible bipyrazole ligand bridged via μ-Cl or μ1,1-N3

Two dinuclear complexes, {[Cd(bdpp)Cl₂](CH₃OH)}₂ (1) and [Cd(bdpp)(N₃)(NO₃)]₂ (2), have been synthesized by reactions of bdpp with cadmium salts (bdpp?=?1,3-bis(3′,5′-dimethylpyrazol-1′-yl)propane), and characterized by IR, element analysis, fluorescence properties and single crystal structural analysis. Cd in 1 has a trigonal bipyramidal coordination geometry and two such units form a dimer through two μ-Cl bridges. Each Cd in 2 has a distorted octahedral coordination geometry and two Cd units form a dimer through μ_1,1-N₃ bridges. The emission spectra show λ_em?=?413?nm for 1 and λ_em?=?338?nm for 2.     

Stage-frit: A straightforward sub-2 μm nano-liquid chromatography column fabrication for proteomic analysis

In this work we demonstrated a facile method for the fabrication of C18 coordination polymer gel in a capillary, called stage-frit, which was efficiently applied to pack sub-2 μm C18 beads into the capillary by a high pressure bomb for the online separation of proteolytic peptides. The back pressure of the column with 10 cm × 75 μm i.d. is regularly lower than 170 bar at a flow rate of 300 nl/min, which could be operated on a common nanoLC system instead of nanoUPLC system due to the good permeability, low back pressure and high mechanical stress of the frit that will totally reduce the cost for the purchase of instrument. The stage-frit allows long-term continuous flow of the solvent and no significant beads loss or pressure instability was observed during the period. The repeatability of retention time for fifteen BSA tryptic peaks was found to be less than 1.08% (RSD) in six time nanoLC-ESI-MS/MS experiments. The average full width at half maximum (FWHM) of peptide peaks is 5.87 s. The sub-2 μm stage-frit nanoLC column showed better sensitivity than the commercial available for large scale proteomic analysis of total tissue proteins from human spleen. The number of identified peptides is approximately 0.4-fold and 0.2-fold higher than that obtained by utilizing commercial columns packed with 3 μm and 1.8 μm C18 materials, respectively. In the field of analytical chemistry, particularly the use of nanoLC systems, stage-frit nanoLC column offers a great potential for the separation of complex mixtures.