H. B. Lim

Cerium oxide-deposited mesoporous silica nanoparticles for the determination of carcinoembryonic antigen in serum using inductively coupled plasma-mass spectrometry.

CeO2-deposited mesoporous silica nanoparticles were synthesized as a probe to determine carcinoembryonic antigen (CEA) in serum by inductively coupled plasma-mass spectrometry (ICP-MS). The prepared mesoporous nanoparticles were modified and tagged to the target for sandwich-type immunoassay. Fe3O4 magnetic nanoparticles (MNPs) were also synthesized and immobilized with antibody to extract the target biomarker. The calibration curve of the synthesized CeO2-deposited silica nanoparticles, which was plotted by the signal ratio of (140)Ce/(57)Fe measured by ICP-MS vs. the concentration of CEA, showed excellent linearity and sensitivity owing to the signal amplification and low spectral interference. Under optimal conditions, the sandwich-type analytical method was applied to determine CEA in serum spiked in the range of 0.001-5 ng mL(-1) and showed a limit of detection of 0.36 ng mL(-1). Since the deposited CeO2 in the mesoporous silica layer can be substituted by other metal compounds, various kinds of metal-deposited nanoparticles can be prepared as probe materials for multiplex detection in bioanalysis.

Determination of prostate-specific antigen (PSA) tagged with TiO2 nanoparticles using ICP-MS

An ultrasensitive analytical method was developed to determine prostate specific antigen (PSA) tagged with TiO2 nanoparticles (NPs) using inductively coupled plasma mass spectrometry (ICP-MS). The synthesized TiO2 NPs (19.8 nm) were modified with monoclonal antibody, IgG, for tagging on the PSA through the antigen–antibody reaction. For the sample pretreatment, magnetic NPs (MNPs) were also synthesized and modified for the collection of PSA in a serum sample. The sandwiched complexes thereby obtained were collected using a permanent magnet in order to remove any remaining unbound particles. The MNPs were then eliminated after the cleavage of antigen–antibody bindings by treatment with 0.33 M nitric acid. The concentration of the TiO2 NPs remaining in the solution was determined by ICP-MS with a flow injection system and a 10 μL injection loop. The PSA concentration was determined by measuring the 49Ti signal of the tagged TiO2 NPs. The obtained limit of detection for PSA in serum was 1.16 fg mL−1, which was more than 3.44 × 106 times lower than the current PSA levels for cancer diagnosis.

Double membrane desolvator for direct analysis of isopropyl alcohol in inductively coupled plasma atomic emission spectrometry (ICP-AES) and inductively coupled plasma mass spectrometry (ICP-MS)

Abstract A double membrane desolvator (DMD) with an MCN was built and tested for the analysis of isopropyl alcohol using ICP-AES and ICP-MS. Unlike a conventional membrane desolvator, two different concentric membrane tubes were used for the DMD. Additionally, the length of the membrane was reduced in half and the total area was increased. Influence of sweep gas flow on analyte intensities in ICP-AES was studied. Approximately 70–90% of C(I) signal was reduced by using the DMD and this reduction was the largest among the emission lines measured, for example Cr(II), Ca(II), and Mn(II) showed the reduction in the range of 30–50%. The use of DMD also reduced the background level, and heating the spray chamber enhanced the signal intensity of Cr(II) significantly in ICP-AES. For ICP-MS, the reduction of molecular interference was demonstrated when MCN-DMD was used. The ratio of CeO+/Ce+ was approximately 0.16 at the sample uptake rate of 210 μl/min and it was reduced by a factor of 3 for 110 μl/min.

Diagnostic studies of a low-pressure inductively coupled plasma in argon using a double Langmuir probe

The electron temperature and electron number density of a laboratory-built low-pressure inductively coupled plasma (LP-ICP) were measured using a double Langmuir probe. The probe was composed of two 0.5 mm diameter tungsten wires and a magnesia sleeve shielding the wires that could be linearly moved in the central channel of the plasma by a vacuum linear-motion feedthrough. The role of parameters was studied at a height of 25 mm above the load coil, which yielded an electron temperature of 3–6 eV and an electron number density of 2.5–5 × 1013 cm−3. Less dependence on operating factors was noticed at higher observation heights, and when water loaded on the low-pressure plasma was increased, the electron temperature and electron number density were reduced, unlike with an atmospheric ICP.

Metal/dye-doped core-shell silica nanoparticles for potential use in bioassay

Nanoparticles (NPs) have become an important material used to detect bio-targets at the molecular level with accurate quantification and multiplex detection, in conjunction with inductively coupled plasma-mass spectrometry (ICP-MS). Various types of NPs have been developed so far for selective tagging of a wide range of bio targets. In this work, metal and dye, both doped silica core-shell NPs with the combination of Cs and Cy5, Cd and RhBITC, and Pb and FITC were synthesized for particle tagging and characterized by ICP-MS. For the metal and dye doping, metal salts and dyes were seeded together during the core formation, and then the surface was covered with silica shell. The developed synthesis method will provide an important opportunity to produce silica NPs (SNPs) bearing various metal ions for multiplex detection. In addition, fluorescence from the doped dye offers a tool to monitor the particle loss during the treatment procedures. No leaching of doped Cd into 2% nitric acid was observed for 18 days. The estimated average numbers of Pb, Cs and Cd atoms in each NP were in the range of 3.3 × 104 to 2.7 × 106 atoms, and the limit of detection was about 64.6 particles for Pb, 7.7 particles for Cs, and 11.8 particles for Cd. For demonstration of potential bio application, the synthesized Cs/Cy5-doped core-shell SNPs were used to monitor ss-DNA cleavage through Fenton-type reaction.

Plasma temperature measurement of a low-pressure inductively coupled plasma using spectroscopic methods

Direct nebulization of an aqueous sample was successfully carried out in our laboratory in a lab-built low pressure-inductively coupled plasma (LP-ICP) using a double membrane desolvator (DMD). For the particular LP-ICP used, rotational temperatures of selected diatomic molecules and excitation temperatures of Fe II and Fe I were measured. The OH radical showed two rotational temperatures, low and high. The former were obtained in the range 800 to 1100 K, while the latter were obtained between 1850 and 2800 K. The molecular nitrogen ion consistently obtained the same temperatures as those of the high rotational temperatures of the OH radical. This result suggests that the high density of rotational states of these molecules, N+2 and OH radical, allows collisional energy exchange between molecular rotational and argon translational degrees of freedom in the plasma. An increase of plasma gas flow from 0.3 to 1.1 L min−1 produced a decrease of excitation temperatures of Fe II from 10400 to 9200 K. The excitation temperature of Fe I was measured to be about 6000 K. Noticeably, the excitation temperature of Fe ion was high, and even higher than that reported in an atmospheric ICP. This experiment provides proof that the mechanism of ionization and excitation was influenced mainly by the character of electrons in the low-pressure plasma.

Short-term Effect of Fine Particulate Matter on Children’s Hospital Admissions and Emergency Department Visits for Asthma: A Systematic Review and Meta-analysis

Objectives: No children-specified review and meta-analysis paper about the short-term effect of fine particulate matter (PM2.5) on hospital admissions and emergency department visits for asthma has been published. We calculated more precise pooled effect estimates on this topic and evaluated the variation in effect size according to the differences in study characteristics not considered in previous studies. Methods: Two authors each independently searched PubMed and EMBASE for relevant studies in March, 2016. We conducted random effect meta-analyses and mixed-effect meta-regression analyses using retrieved summary effect estimates and 95% confidence intervals (CIs) and some characteristics of selected studies. The Egger’s test and funnel plot were used to check publication bias. All analyses were done using R version 3.1.3. Results: We ultimately retrieved 26 time-series and case-crossover design studies about the short-term effect of PM2.5 on children’s hospital admissions and emergency department visits for asthma. In the primary meta-analysis, children’s hospital admissions and emergency department visits for asthma were positively associated with a short-term 10 μg/m3 increase in PM2.5 (relative risk, 1.048; 95% CI, 1.028 to 1.067; I2=95.7%). We also found different effect coefficients by region; the value in Asia was estimated to be lower than in North America or Europe. Conclusions: We strengthened the evidence on the short-term effect of PM2.5 on children’s hospital admissions and emergency department visits for asthma. Further studies from other regions outside North America and Europe regions are needed for more generalizable evidence.

LA-ICP-MS with microarray chip sampling to determine holoceruloplasmin in serum

An analytical method was developed to determine holoceruloplasmin (holo-CP) concentration in serum using laser ablation inductively coupled plasma-mass spectrometry (LA-ICP-MS). Since each holo-CP in serum contains six Cu ions, the concentration was estimated quantitatively by determining the Cu concentration. For small sample consumption, polydimethylsiloxane (PDMS) microarray chips with 150 μm diameter pillars were manufactured. The surface of each pillar was immobilized by a ceruloplasmin (CP) antibody (IgG) for an antigen–antibody reaction to afford high selectivity for the sampling of total CP in the serum matrix. A calibration curve with a linear regression coefficient of 0.992 was obtained by standard addition methods. For demonstration, 126 pL of human serum was loaded on each pillar of the microarray chips and analyzed by LA-ICP-MS in single-shot mode. The determined concentration of holo-CP was compared with that of the total CP estimated by competitive enzyme linked immunosorbent assay (ELISA), from which the concentration of apoceruloplasmin (apo-CP) was deduced. In conclusion, this analytical method for determining holo-CP concentration with high selectivity and small sample volume can be used in the confirmative diagnosis of diseases related to copper deficiency in clinical samples.

Maternal cell phone use during pregnancy and child behavioral problems in five birth cohorts

INTRODUCTION Previous studies have reported associations between prenatal cell phone use and child behavioral problems, but findings have been inconsistent and based on retrospective assessment of cell phone use. This study aimed to assess this association in a multi-national analysis, using data from three cohorts with prospective data on prenatal cell phone use, together with previously published data from two cohorts with retrospectively collected cell phone use data. METHODS We used individual participant data from 83,884 mother-child pairs in the five cohorts from Denmark (1996-2002), Korea (2006-2011), the Netherlands (2003-2004), Norway (2004-2008), and Spain (2003-2008). We categorized cell phone use into none, low, medium, and high, based on frequency of calls during pregnancy reported by the mothers. Child behavioral problems (reported by mothers using the Strengths and Difficulties Questionnaire or Child Behavior Checklist) were classified in the borderline/clinical and clinical ranges using validated cut-offs in children aged 5-7years. Cohort specific risk estimates were meta-analyzed. RESULTS Overall, 38.8% of mothers, mostly from the Danish cohort, reported no cell phone use during pregnancy and these mothers were less likely to have a child with overall behavioral, hyperactivity/inattention or emotional problems. Evidence for a trend of increasing risk of child behavioral problems through the maternal cell phone use categories was observed for hyperactivity/inattention problems (OR for problems in the clinical range: 1.11, 95%CI 1.01, 1.22; 1.28, 95%CI 1.12, 1.48, among children of medium and high users, respectively). This association was fairly consistent across cohorts and between cohorts with retrospectively and prospectively collected cell phone use data. CONCLUSIONS Maternal cell phone use during pregnancy may be associated with an increased risk for behavioral problems, particularly hyperactivity/inattention problems, in the offspring. The interpretation of these results is unclear as uncontrolled confounding may influence both maternal cell phone use and child behavioral problems.

Laser ablation ICP-MS to determine Cu on a Si wafer prepared by ion sputtering

This work describes an analytical method using laser ablation (LA)-ICP-MS to determine the Cu metal deposited on a silicon wafer by ion sputtering, which can be applied to control the manufacturing process of semiconductors and silicon-based solar cells. The number of Cu atoms on a layer with thickness of 1.0 µm was determined to be 1.1 × 1013 (±2%) atoms per cm2 by ICP-MS with chemical vapour deposition followed by radial scanning. Since LA-ICP-MS lacks proper standards for silicon wafer analysis, a glass NIST SRM 616 was used as a reference material. For the calculation of Cu level, the concentration ratio of Cu on the silicon wafer to the glass SRM was determined by a non-matrix matched standard addition using a desolvation nebulizer. Due to the internal standard effect of the nebulized aerosols, this method minimized experimental errors caused by possible fluctuations in particle generation, transportation and ionization. In order to quantify the Cu on a silicon wafer, the weight of particles transported to the plasma was estimated to be approximately 15 ng per single laser shot. The number of Cu atoms on the wafer was determined to be 9.3 × 1011 (±28.7%) atoms per cm2. The most significant error occurred during the ablation process resulted from the interaction of the laser beam with the surface material, which produced irregular craters and particles due to their unique physical properties of reflective index and hardness.