Mass Detection Limit Research Articles

Voltammetric microwell array for oxidized guanosine in intact ds-DNA.

Oxidative stress in humans causes damage to biomolecules by generating reactive oxygen species (ROS). DNA can be oxidatively damaged by ROS, which may lead to carcinogenesis. Here we report a microfluidic electrochemical array designed to rapidly detect oxidation in intact DNA in replicate measurements. Sensor arrays were fabricated by wet-chemistry patterning of gold compact discs. The eight-sensor array is incorporated into a 60 μL microfluidic channel connected to a pump and sample valve. The array features 7 nm thick osmium bipyridyl poly(vinylpyridine) chloride [Os(bpy)2(PVP)10Cl](+) films assembled layer-by-layer with polyions onto the gold sensors. 8-Hydroxy-7,8-hydro-2'-deoxyguanosine (8-oxodG) is selectively oxidized by [Os(bpy)2(PVP)10Cl](+) in intact ds-DNA to provide catalytic square wave voltammograms (SWV). The device is easy-to-use, fast, inexpensive, reusable, and can detect one 8-oxodG per 6600 nucleobases. The mass detection limit is 150-fold lower than a previously reported dip-and-read voltammetric sensor for oxidized DNA. Fast assays (<1 min) and moderate sample consumption (15 pmol DNA) suggest potential for research and clinical applications. Practical use is illustrated by detecting DNA oxidation from cigarette smoke and ash extracts in dispersions with NADPH and Cu(2+).

Development of Orthogonal Acceleration Time-of-Flight Mass Spectrometer for Detection of Ions with Wide Energies Distribution

Abstract A time-of-flight mass spectrometer was developed for the detection of ions with wide energies distribution. The instrument associated with an electron impact source. The ions flow was effectively modulated by a lens system and then introduced into the time-of-flight mass analyzer which included a dual field of acceleration region, a reflection region, and a large-size micro channel plate (MCP) detection device. The characteristics of the spectrometer were as follows: half-peak width of single ion signal was about 2 ns, resolution of the instrument was better than 1600 FWHM, mass range of actual samples was 1–127 amu in comparison with the theoretical mass detection limit of higher than 800 amu, and ion energy detection range was better than two orders of magnitude (3–140 eV). If coupled with short-instantaneous pulse discharge ion source, the TOF mass analyzer would be used in the field of rapid detection of high-energy ion beam, such as vacuum cathode discharge preparation of thin films, ion injection material characterization, ion charge state distribution of conductive material and determination of ion diffusion speed.

Tapered silicon nanowires for enhanced nanomechanical sensing

We investigate the effect of controllably induced tapering on the resonant vibrations and sensing performance of silicon nanowires. Simple analytical expressions for the resonance frequencies of the first two flexural modes as a function of the tapering degree are presented. Experimental measurements of the resonance frequencies of singly clamped nanowires are compared with the theory. Our model is valid for any nanostructure with tapered geometry, and it predicts a reduction beyond two orders of magnitude of the mass detection limit for conical resonators as compared to uniform beams with the same length and diameter at the clamp.

A nano-TiO2 supported AuAg alloy nanocluster functionalized electrode for sensitizing the electrochemiluminescent analysis

A nano-hybrid of nano-titania supported AuAg alloy nanocluster was synthesized. It was then modified onto the surface of indium tin oxide (ITO) coated glass to act as a working electrode for exciting the electrochemiluminescence (ECL) of luminol. The properties of the nano-hybrid and the functionalized electrode were characterized by X-ray diffraction spectroscopy (XRD), electrochemistry, spectroscopy, transmission electron microscopy (TEM), scanning electron microscopy (SEM) and atomic force microscopy (AFM). Coupled with microemulsion as a carrying matrix with the flow-injection analysis (FIA) mode, the ECL emission of luminol is greatly intensified on this functionalized electrode. Till to pH 6.0, needless any added co-reactant, the synergic sensitizing effect of nano-hybrid and microemulsion increased the ECL signal of luminol to a recordable level for the first time. The ECL response for H2O2 on this functionalized electrode gains a descended mass detection limit (LODM) for 1/230 than before. This research very significantly extended the area of ECL applications due to the extended practicable pH range which was suitable for environmental or biological targets etc. As an example, this intensified ECL was successfully applied to evaluate the gross antioxidant activity of some fruits with satisfactory results.

Forensic Analysis of Laser Printed Ink by X-ray Fluorescence and Laser-Excited Plume Fluorescence

We demonstrated a minimally destructive two-tier approach for multielement forensic analysis of laser-printed ink. The printed document was first screened using a portable-X-ray fluorescence (XRF) probe. If the results were not conclusive, a laser microprobe was then deployed. The laser probe was based on a two-pulse scheme: the first laser pulse ablated a thin layer of the printed ink; the second laser pulse at 193 nm induced multianalytes in the desorbed ink to fluoresce. We analyzed four brands of black toners. The toners were printed on paper in the form of patches or letters or overprinted on another ink. The XRF probe could sort the four brands if the printed letters were larger than font 20. It could not tell the printing sequence in the case of overprints. The laser probe was more discriminatory; it could sort the toner brands and reveal the overprint sequence regardless of font size while the sampled area was not visibly different from neighboring areas even under the microscope. In terms of general analytical performance, the laser probe featured tens of micrometer lateral resolution and tens to hundreds of nm depth resolution and atto-mole mass detection limits. It could handle samples of arbitrary size and shape and was air compatible, and no sample pretreatment was necessary. It will prove useful whenever high-resolution and high sensitivity 3D elemental mapping is required.

DARK MATTER SUBSTRUCTURE DETECTION USING SPATIALLY RESOLVED SPECTROSCOPY OF LENSED DUSTY GALAXIES

We investigate how strong lensing of dusty, star-forming galaxies by foreground galaxies can be used as a probe of dark matter halo substructure. We find that spatially resolved spectroscopy of lensed sources allows dramatic improvements to measurements of lens parameters. In particular we find that modeling of the full, three-dimensional (angular position and radial velocity) data can significantly facilitate substructure detection, increasing the sensitivity of observables to lower mass subhalos. We carry out simulations of lensed dusty sources observed by early ALMA (Cycle 1) and use a Fisher matrix analysis to study the parameter degeneracies and mass detection limits of this method. We find that, even with conservative assumptions, it is possible to detect galactic dark matter subhalos of ~ 10^8 M_{\odot} with high significance in most lensed DSFGs. Specifically, we find that in typical DSFG lenses, there is a ~ 55 % probability of detecting a substructure with M>10^8 M_{\odot} with more than 5 sigma detection significance in each lens, if the abundance of substructure is consistent with previous lensing results. The full ALMA array, with its significantly enhanced sensitivity and resolution, should improve these estimates considerably. Given the sample of ~100 lenses provided by surveys like the South Pole Telescope, our understanding of dark matter substructure in typical galaxy halos is poised to improve dramatically over the next few years.

Neuronal metabolomics by ion mobility mass spectrometry: cocaine effects on glucose and selected biogenic amine metabolites in the frontal cortex, striatum, and thalamus of the rat

We report results of studies of global and targeted neuronal metabolomes by ambient pressure ion mobility mass spectrometry. The rat frontal cortex, striatum, and thalamus were sampled from control nontreated rats and those treated with acute cocaine or pargyline. Quantitative evaluations were made by standard additions or isotopic dilution. The mass detection limit was ~100 pmol varying with the analyte. Targeted metabolites of dopamine, serotonin, and glucose followed the rank order of distribution expected between the anatomical areas. Data was evaluated by principal component analysis on 764 common metabolites (identified by m/z and reduced mobility). Differences between anatomical areas and treatment groups were observed for 53 % of these metabolites using principal component analysis. Global and targeted metabolic differences were observed between the three anatomical areas with contralateral differences between some areas. Following drug treatments, global and targeted metabolomes were found to shift relative to controls and still maintained anatomical differences. Pargyline reduced 3,4-dihydroxyphenylacetic acid below detection limits, and 5-HIAA varied between anatomical regions. Notable findings were: (1) global metabolomes were different between anatomical areas and were altered by acute cocaine providing a broad but targeted window of discovery for metabolic changes produced by drugs of abuse; (2) quantitative analysis was demonstrated using isotope dilution and standard addition; (3) cocaine changed glucose and biogenic amine metabolism in the anatomical areas tested; and (4) the largest effect of cocaine was on the glycolysis metabolome in the thalamus confirming inferences from previous positron emission tomography studies using 2-deoxyglucose.

Capillary zone electrophoresis-multiple reaction monitoring from 100 pg of RAW 264.7 cell lysate digest

Capillary zone electrophoresis-multiple/single reaction monitoring (CZE-MRM/SRM), which employed an electrokinetically driven sheath-flow electrospray interface, was used for the rapid and highly sensitive detection of protein analytes in complex tryptic digests. MRM channels were developed against a commercial exponential mixture of bovine proteins. Five proteins spanning four orders of magnitude concentration range were confidently detected from only 2.5 ng of the digest mixture; the mass detection limits (S/N = 3) of two detected proteins, alpha-casein and glutamate dehydrogenase were about 600 zmol and 30 amol, respectively. This technique was then applied to a RAW 264.7 cell lysate digest. Three proteins were confidently and reproducibly detected from 100 pg of this digest. The sample amount corresponds to the approximate protein content from a single cell, which suggests that CZE-MRM may be a useful analytical tool in chemical cytometry. In addition to providing highly sensitive detection of proteins in complex mixtures, this system is highly rapid; migration time of the protein digests was less than 10 min.

A mobile instrument for in situ scanning macro-XRF investigation of historical paintings

Scanning macro-X-ray fluorescence analysis (MA-XRF) is rapidly being established as a technique for the investigation of historical paintings. The elemental distribution images acquired by this method allow for the visualization of hidden paint layers and thus provide insight into the artist's creative process and the painting's conservation history. Due to the lack of a dedicated, commercially available instrument the application of the technique was limited to a few groups that constructed their own instruments. We present the first commercially available XRF scanner for paintings, consisting of an X-ray tube mounted with a Silicon-Drift (SD) detector on a motorized stage to be moved in front of a painting. The scanner is capable of imaging the distribution of the main constituents of surface and sub-surface paint layers in an area of 80 by 60 square centimeters with dwell times below 10 ms and a lateral resolution below 100 μm. The scanner features for a broad range of elements between Ti (Z = 22) and Mo (Z = 42) a count rate of more than 1000 counts per second (cps)/mass percent and detection limits of 100 ppm for measurements of 1 s duration. Next to a presentation of spectrometric figures of merit, the value of the technique is illustrated through a case study of a painting by Rembrandt's student Govert Flinck (1615–1660).

Development of Orthogonal Acceleration Time-of-Flight Mass Spectrometer for Detection of Ions with Wide Energies Distribution

A wide detection range of ion energy time-of-flight(TOF) mass spectrometer was developed successfully.The instrument coupled associated with electron impact source,ions flow was modulated effectively by a lens system,and then introduced into time-of-flight mass analyzer,which had dual field of acceleration region and reflection region,and a large-size microchannel plate(MCP) detection device.Half-peak width of single ion signal is about 2 ns,resolution of the instrument is better than 1600 FWHM,mass range of actual samples is 1-127amu(theoretical mass detection limit could be higher than 800 amu),ion energy detection range is better than two orders of magnitude(3-140 eV).If couple associated with short-instantaneous pulse discharge ion source,the TOF mass analyzer could be used in the field of rapid detection of high-energy ion beam,such as vacuum cathode discharge preparation of thin films,ion injection material characterization,the ion charge state distribution of conductive material and determination of ion diffusion speed.

Comparison of different exoplanet mass detection limit methods using a sample of main-sequence intermediate-type stars

The radial velocity (RV) technique is a powerful tool for detecting extrasolar planets and deriving mass detection limits that are useful for constraining planet pulsations and formation models. Detection limit methods must take into account the temporal distribution of power of various origins in the stellar signal. These methods must also be able to be applied to large samples of stellar RV time series We describe new methods for providing detection limits. We compute the detection limits for a sample of ten main sequence stars, which are of G-F-A type, in general active, and/or with detected planets, and various properties. We use them to compare the performances of these methods with those of two other methods used in the litterature. We obtained detection limits in the 2-1000 day period range for ten stars. Two of the proposed methods, based on the correlation between periodograms and the power in the periodogram of the RV time series in specific period ranges, are robust and represent a significant improvement compared to a method based on the root mean square of the RV signal. We conclude that two of the new methods (correlation-based method and local power analysis, i.e. LPA, method) provide robust detection limits, which are better than those provided by methods that do not take into account the temporal sampling.

On-line amino acid-based capillary isoelectric focusing-ESI-MS/MS for protein digests analysis

Six amino acids with pIs that ranged from 3.2 to 9.7 were used as ampholytes to establish a pH gradient in capillary isoelectric focusing. This amino acid-based capillary isoelectric focusing (cIEF) was coupled with ESI-MS/MS using an electrokinetically pumped sheath-flow interface for peptide analysis. Amino acid-based isoelectric focusing generates a two-order of magnitude lower background signal than commercial ampholytes in the important m/z range of 300–1800. Good focusing was achieved for insulin receptor, which produced ∼10s peak width. For 0.1mgmL−1 bovine serum albumin (BSA) digests, 24±1 peptides (sequence coverage 47±4%) were identified in triplicate analysis. As expected, the BSA peptides were separated according to their pI. The concentration detection limit for the BSA digests is 7nM and the mass detection limit is 7fmole. A solution of six bovine protein tryptic digests spanning 5 orders of magnitude in concentration was analyzed by amino acid based cIEF-ESI-MS/MS. Five proteins with a concentration range spanning 4 orders of magnitude were identified in triplicate runs. Using amino acid based cIEF-ESI-MS/MS, 112 protein groups and 303 unique peptides were identified in triplicate runs of a RAW 264.7 cell homogenate protein digest. In comparison with ampholyte based cIEF-ESI-MS/MS, amino acid based cIEF-ESI-MS/MS produces higher resolution of five acidic peptides, much cleaner mass spectra, and higher protein spectral counts.

High-speed cryo-focusing injection for gas chromatography: Reduction of injection band broadening with concentration enrichment

In order to maximize peak capacity and detection sensitivity of fast gas chromatography (GC) separations, it is necessary to minimize band broadening, and in particular due to injection since this is often a major contributor. A high-speed cryo-focusing injection (HSCFI) system was constructed to first cryogenically focus analyte compounds in a 6cm long section of metal MXT column, and second, reinject the focused analytes by rapidly resistively heating the metal column via an in-house built electronic circuit. Since the cryogenically cooled section of column is small (∼750nl) and the direct resistive heating is fast (∼6000°C/s), HSCFI is demonstrated to produce an analyte peak with a 6.3ms width at half height, w1/2. This was achieved using a 1m long column with a 180μm inner diameter (i.d.) operated at an absolute head pressure of 55psi and an oven temperature of 60°C, with a 10V pulse applied to the metal column for 50ms. HSCFI was also used to demonstrate the head space sampling and fast GC analysis of an aqueous solution containing six test analytes (acetone, methanol, ethanol, toluene, chlorobenzene, pentanol). Using Henry’s law constants for each of the analytes, injected mass limits of detection (LODs) were typically in the low pg levels (e.g., 1.2pg for acetone) for the high speed separation. Finally, to demonstrate the use of HSCFI with a complex sample, a gasoline was separated using a 20m×100μm i.d. column and the stock GC oven for temperature programming, which provided a separation time of 200s and an average peak width at the base of 440ms resulting in a total peak capacity of 460 peaks (at unit resolution).

Resonantly excited AlN-based microcantilevers for immunosensing

The purpose of this work is to study the performance of resonantly driven microcantilevers excited with a piezoelectric aluminium nitride thin film as a mass sensor for the detection of interactions in the field of immunosensing. Two cantilevers with different width (i.e. 300 and 200 μm), but constant length and thickness of 300 and 20 μm were considered. The figures of merit of these structures, such as the mass sensitivity and the limit of mass detection, were determined. According to the results obtained, a cantilever being 300 × 200 μm2 in size and a high frequency mode was the best combination to detect antibody/antigen interactions. The previous combination was applied to detect the affinity between rabbit immunoglobulin G (IgG) and the complementary anti-rabbit IgG produced in goat. The binding was registered as a shift of the resonance frequency of the mode under investigation and the correlation between the added mass and the measured shift is analysed.

Dried blood spot (DBS) sample collection for determination of the oxidative stress biomarker 8‐epi‐PGF2α in humans using liquid chromatography/tandem mass spectrometry

F2-isoprostanes are a series of prostaglandin F2-like compounds that are formed by free-radical-catalyzed peroxidation of arachidonic acid (ARA). Several F2-isoprostanes, but in particular 8-epi-PGF(2α), are widely used as oxidative stress biomarkers. In this study we have developed an analytical tool for finger-tip blood sampling and analysis of 8-epi-PGF(2α) from dried blood spots (DBS). We have applied solid-phase extraction (SPE) and liquid chromatography/tandem mass spectrometry (LC/MS/MS) for the extraction, separation and detection of 8-epi-PGF(2α) in DBS and have studied the stability of this marker using the DBS collection platform. The mass limit of detection (mLOD) for 8-epi-PGF(2α) extracted from DBS samples was 1.5 pg while the concentration limit of detection (cLOD) and concentration limit of quantitation (cLOQ) were 6 pg/mL and 18 pg/mL, respectively. All values based on triplicate analysis. Sufficient stability of 8-epi-PGF(2α) in DBS was achieved by preconditioning DBS paper with vitamin E and BHT. The developed method is sensitive, specific, robust, efficient, and can accurately measure endogenous concentrations of 8-epi-PGF(2α) in DBS. Thus, it offers an analytical approach to measure 8-epi-PGF(2α) by a novel sample collection technique that is less invasive and costly than conventional techniques.

Measurement of elemental concentration of aerosols using spark emission spectroscopy.

A coaxial microelectrode system has been used to collect and analyse the elemental composition of aerosol particles in near real-time using spark emission spectroscopy. The technique involves focused electrostatic deposition of charged aerosol particles onto the flat tip of a microelectrode, followed by introduction of spark discharge. A pulsed spark discharge was generated across the electrodes with input energy ranging from 50 to 300 mJ per pulse, resulting in the formation of controlled pulsed plasma. The particulate matter on the cathode tip is ablated and atomized by the spark plasma, resulting in atomic emissions which are subsequently recorded using a broadband optical spectrometer for element identification and quantification. The plasma characteristics were found to be very consistent and reproducible even after several thousands of spark discharges using the same electrode system. The spark plasma was characterized by measuring the excitation temperature (~7000 to 10 000 K), electron density (~1016 cm-3), and evolution of spectral responses as a function of time. The system was calibrated using particles containing Pb, Si, Na and Cr. Absolute mass detection limits in the range 11 pg to 1.75 ng were obtained. Repeatability of spectral measurements varied from 2 to 15%. The technique offers key advantages over similar microplasma-based techniques such as laser-induced breakdown spectroscopy, as: (i) it does not require any laser beam optics and eliminates any need for beam alignment, (ii) pulse energy from dc power supply in SIBS system can be much higher compared to that from laser source of the same physical size, and (iii) it is quite conducive to compact, field-portable instrumentation.

Simplified sheath flow cuvette design for ultrasensitive laser induced fluorescence detection in capillary electrophoresis.

We present a design for a sheath-flow cuvette that uses a relatively inexpensive quartz cuvette. The cuvette has a high optical quality square flow chamber that is fused to quartz tubes at each end. PEEK/TEFZEL fittings hold and seal the quartz flow chamber without putting strain on the cuvette. The performance of the cuvette is evaluated as a laser-induced fluorescence detector for capillary electrophoresis. The cuvette produces mass detection limits of 50 yoctomoles (30 copies) for 5-carboxyl tetramethylrhodamine (5 TAMRA SE) with a separation efficiency of 400,000 theoretical plates.

New Approach for Near-Real-Time Measurement of Elemental Composition of Aerosol Using Laser-Induced Breakdown Spectroscopy.

A new approach has been developed for making near-real-time measurement of elemental composition of aerosols using plasma spectroscopy. The method allows preconcentration of miniscule particle mass (pg to ng) directly from the sampled aerosol stream through electrostatic deposition of charged particles (30-900 nm) onto a flat-tip microneedle electrode. The collected material is subsequently ablated from the electrode and monitored by laser-induced breakdown spectroscopy. Atomic emission spectra were collected using a broadband spectrometer with a wavelength range of 200-980 nm. A single-sensor delay time of 1.3 μs was used in the spectrometer for all elements to allow simultaneous measurement of multiple elements. The system was calibrated for various elements including Cd, Cr, Cu, Mn, Na, and Ti. The absolute mass detection limits for these elements were experimentally determined and found to be in the range of 0.018-5 ng. The electrostatic collection technique has many advantages over other substrate-based methods involving aerosol collection on a filter or its focused deposition using an aerodynamic lens. Because the particle mass is collected over a very small area that is smaller than the spatial extent of the laser-induced plasma, the entire mass is available for analysis. This considerably improves reliability of the calibration and enhances measurement accuracy and precision. Further, the aerosol collection technique involves very low pressure drop, thereby allowing higher sample flow rates with much smaller pumps-a desirable feature for portable instrumentation. Higher flow rates also make it feasible to measure trace element concentrations at part per trillion levels. Detection limits in the range of 18-670 ng m-3 can be achieved for most of the elements studied at a flow rate of 1.5 L min-1 with sampling times of 5 min.

Capillary Action-Supported Contactless Atmospheric Pressure Ionization for the Combined Sampling and Mass Spectrometric Analysis of Biomolecules

It is proposed that a short tapered capillary can be utilized as a nanoliter-volume sampling tool and sample emitter for generation of gas-phase ions in front of the mass spectrometer, without the need for using an additional electric power supply, a gas supply, or a syringe pump. A wide range of molecules can be analyzed in pure solutions and complex matrixes (cell extract, urine, and plant tissue) with no or minimum sample preparation. Singly and multiply charged ions can be detected in either positive or negative-ion mode. Because of the nanoliter-volume sampling and low spectral background, the mass detection limit for bradykinin is in the low attomole range. Other advantages include simplicity, disposability, and low cost. The putative mechanism of the ion formation in this capillary-action supported contactless spray emitter is discussed.

Nine orders of magnitude dynamic range: picomolar to millimolar concentration measurement in capillary electrophoresis with laser induced fluorescence detection employing cascaded avalanche photodiode photon counters.

The dynamic range of capillary electrophoresis analysis is ultimately limited by molecular shot noise at low concentrations and by concentration-induced band broadening at high concentrations. We report a system that approaches these fundamental limits. A laser-induced fluorescence detector is reported that employs a cascade of four fiber-optic beam splitters connected in series to generate a primary signal and four attenuated signals, each monitored by a single-photon counting avalanche photodiode. Appropriate scaling of the signals from the five photodiodes produces a linear optical calibration curve for 5-carboxyl-tetramethylrhodamine from the concentration detection limit of 1 pM to the upper limit of 1 mM. Mass detection limits are 120 yoctomoles (70 molecules) injected into the instrument. The very-wide dynamic range instrument was used to study the metabolic products of the fluorescently labeled glycosphingolipid tetramethylrhodamine labeled GM1 (GM1-TMR) produced by single cells isolated from the rat cerebellum.